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title: "ADEM"
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docid: "a3fafeb7-5861-4364-beb8-c0e30220564e"
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authors:
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- key: "99e1aff7-f42c-43a0-95ae-d89c8551aa01"
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value: "Kevin R. Moore, MD"
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- key: "a25c450b-3d34-4f64-bba3-cc0834813df6"
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value: "Miral D. Jhaveri, MD, MBA"
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- key: "b2e6dabb-ee1c-42a4-a332-9f0814c1c607"
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value: "Surjith Vattoth, MD, FRCR"
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breadcrumbs:
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-
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name: "Brain"
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slug: "brain"
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treeNodeId: "6d8829f1-14d7-45af-8675-255189aa526a"
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-
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name: "Diagnosis"
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slug: "diagnosis"
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treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
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name: "Pathology-Based Diagnoses"
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slug: "pathology-based-diagnoses"
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treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
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-
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name: "Infectious, Inflammatory, and Demyelinating Disease"
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slug: "infectious-inflammatory-and-demyel-"
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treeNodeId: "7210f860-fe5f-4a2d-81cc-4fe06c769607"
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-
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name: "Inflammatory and Demyelinating Disease"
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slug: "inflammatory-and-demyelinating-dis-"
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treeNodeId: "62ab4dc3-dbf6-45a9-8532-f0e962aa62dc"
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-
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name: "ADEM"
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slug: "adem"
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treeNodeId: null
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category: "Brain"
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documentVersionId: "c2a39730-fd89-4f20-9447-d7fb297710c6"
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imageCount: 22
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lastUpdated: "08/07/20"
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pageDescription: "ADEM"
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pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Infectious, Inflammatory, and Demyelinating Disease, Inflammatory and Demyelinating Disease, ADEM"
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pageTitle: "ADEM | STATdx"
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enhancedTitle: "ADEM"
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type: "DX"
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references: true
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breadcrumbs:
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- "Brain"
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- "Diagnosis"
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- "Pathology-Based Diagnoses"
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- "Infectious, Inflammatory, and Demyelinating Disease"
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- "Inflammatory and Demyelinating Disease"
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- "ADEM"
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---
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# KEY FACTS
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- ## Terminology
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- Autoimmune-mediated white matter (WM) demyelination of brain &/or spinal cord, usually with remyelination
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- ## Imaging
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- Best diagnostic clue: Multifocal WM and deep gray lesions days to weeks following infection/vaccination
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- May involve both brain and spinal cord; WM > gray matter, but usually both affected
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- Both supratentorial and infratentorial lesions
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- Multifocal punctate to large flocculent FLAIR hyperintensities
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- Deep/juxtacortical WM > periventricular WM
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- Do not usually involve callososeptal interface
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- Most lesions show increased signal on DWI (T2 shine-through)
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- Punctate, ring, incomplete ring, peripheral enhancement
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- Absence of enhancement does not exclude diagnosis
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- MRS: ↓ NAA within lesions; may see ↑ Cho, ↑ lactate
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- ## Top Differential Diagnoses
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- Multiple sclerosis
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- Autoimmune-mediated vasculitis
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- Acute hypertensive encephalopathy, PRES
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- Fabry disease
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- Behçet disease
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- ## Pathology
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- > 30 different infectious agents and immunizations reported
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- Anti-MOG (myelin oligodendrocyte glycoprotein) IgG antibodies found more commonly in younger patients
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- ## Clinical Issues
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- Mean age 5-8 years, but can occur at any age
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- Male predominance (M:F = 1:0.6-0.8), unlike MS
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- Usually monophasic, self-limited
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- Complete recovery within 1 month: 50-60%
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- Mortality: 10-30%
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- ## Diagnostic Checklist
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- Imaging findings often lag behind symptom onset, resolution
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# TERMINOLOGY
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- ## Abbreviations
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- Acute disseminated encephalomyelitis (ADEM)
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- ## Definitions
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- Autoimmune-mediated white matter (WM) demyelination of brain &/or spinal cord, usually with remyelination
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# IMAGING
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- ## General Features
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- ### Best diagnostic clue
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- Multifocal WM/basal ganglia lesions days to weeks following infection/vaccination
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- 93% within 3 weeks of infection, 5% within 1 month of vaccination
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- ### Location
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- May involve both brain and spinal cord; WM > gray matter, but usually both affected
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- Deep/juxtacortical WM > periventricular WM
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- Both supratentorial and infratentorial lesions
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- ### Size
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- Tumefactive lesions may be large, but with less mass effect than expected from tumor size
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- ### Morphology
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- Punctate to flocculent
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- Tumefactive, mass-like lesions possible
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- ## CT Findings
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- ### NECT
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- Initial CT normal in 40%
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- ### CECT
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- Multifocal punctate or ring-enhancing lesions
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- ## MR Findings
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- ### T2WI
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- Hyperintensities may be better visualized in brainstem and posterior fossa on T2
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- ### FLAIR
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- Multifocal punctate to large, flocculent FLAIR hyperintensities
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- Bilateral but asymmetric
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- Involve peripheral WM-gray matter junction subcortical WM
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- Thalami and basal ganglia frequently involved, typically symmetric
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- Can involve brainstem and posterior fossa
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- Do not usually involve callososeptal interface
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- ### DWI
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- Variably hyperintense lesions on DWI (trace) images
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- Apparent diffusion coefficient (ADC) may be increased or decreased
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- Most lesions show increased signal (T2 shine-through)
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- Diffusion restriction uncommon, suggests worse prognosis
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- Diffusivity normal within normal-appearing WM (NAWM), unlike MS
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- ### T1WI C+
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- Punctate, ring, incomplete ring, peripheral enhancement
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- Cranial nerve(s) may enhance
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- Absence does not exclude diagnosis
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- ### MRS
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- NAA low within lesions; lactate may be elevated
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- Choline often elevated in acute lesions
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- NAA normalizes with resolution of symptoms/MR abnormalities
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- Magnetization transfer ratio (MTR)
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- ADEM MTR normal within NAWM, unlike MS
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- ## Imaging Recommendations
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- ### Best imaging tool
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- Contrast-enhanced MR
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- Initial imaging often normal but more sensitive than CT
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- May appear identical to MS; repeat MR necessary to distinguish with certainty
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- ### Protocol advice
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- Limited rapid interval follow-up may be provided by FLAIR alone
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- ## Nuclear Medicine Findings
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- Tc-99m-HMPAO SPECT shows more extensive hypoperfusion than T2 lesions
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# DIFFERENTIAL DIAGNOSIS
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- [Multiple Sclerosis](/document/pediatric-multiple-sclerosis-brain/f2592b04-f800-4235-9eea-a43f2bf4adfe)
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- Predilection for periventricular WM (callososeptal interface), involves subcortical U fibers, commonly in posterior fossa
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- Lesions often more symmetric than ADEM
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- Relapsing-remitting course common
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- [Autoimmune-Mediated Vasculitis](/document/miscellaneous-vasculitis/5a4d4cbd-67e3-4722-8a44-8d411cbb98f0)
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- Multifocal gray matter-WM lesions
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- Bilateral, usually cortical/subcortical, basal ganglia/thalami
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- Ring-enhancing lesions may mimic infection
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- [Acute Hypertensive Encephalopathy, PRES](/document/acute-hypertensive-encephalopathy--/efc6f9c2-dad9-4eb8-bad2-421bfaf1ec57)
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- Typically posterior circulation in cortex/subcortical WM
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- May affect deep gray nuclei
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- [Aging Brain With Hyperintense WM Lesions](/document/normal-aging-brain/2a315550-b2ea-4afe-a2ef-f93a2209f276)
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- Atherosclerotic brain changes in 50% patients > 50 years old
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- Found in normotensive patients; more common in hypertensives patients
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- Present in 10-30% of cognitively normal elderly patients
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- MR: Scattered, asymmetric WM lesions, without enhancement
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- Often periatrial; posterior fossa uncommon
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- Spares callososeptal interface, subcortical U fibers
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- [Fabry Disease](/document/fabry-disease/83fd222a-9b37-4087-afab-34ba74525887)
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- Synonym: Angiokeratoma corporis diffusum universalis
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- X-linked recessive; incidence 1/40,000
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- Deficiency α-galactosidase A; overaccumulation of glycosphingolipids within lysosomes
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- MR: Scattered, asymmetric WM lesions without enhancement
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- May involve brainstem and posterior fossa
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- Spares callososeptal interface and subcortical U fibers
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- Cranial MR sensitive to identify neurologic involvement in asymptomatic patients
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- Present with renal failure/heart disease
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- [Behçet Disease](/document/behet-disease/4e447bb6-0f14-40e1-929a-4c1465feec0a)
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- MR: Scattered, asymmetric, subcortical WM lesions without cortical involvement
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- Nodular enhancement in acute phase
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- Predilection for midbrain
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- ADC ↑, similar to ADEM
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- Classic triad: Oral and genital ulcerations with uveitis
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# PATHOLOGY
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- ## General Features
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- ### Etiology
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- Autoimmune-mediated severe acute demyelination
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- Following nonspecific upper respiratory tract infection, often viral
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- > 30 different infectious agents and immunizations reported
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- After specific viral illness: Epstein-Barr, influenza A, mumps, coronavirus
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- Especially after exanthematous diseases of childhood (chickenpox, measles)
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- After vaccination: Diphtheria, influenza, rabies, smallpox, tetanus, typhoid
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- Spontaneous (no known cause)
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- ### Genetics
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- ADEM associated with DRB1*01 and DRB1*017(03) in Russian population
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- ### Associated abnormalities
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- Acute hemorrhagic leukoencephalopathy variant associated with ulcerative colitis and asthma
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- Anti-MOG (myelin oligodendrocyte glycoprotein) IgG antibodies found more commonly in younger patients
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- ## Gross Pathologic & Surgical Features
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- None, unless hemorrhage (rare) or tumefactive edema
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- ## Microscopic Features
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- Acute myelin breakdown
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- Perivenous inflammation; lymphocytic infiltrates
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- Relative axonal preservation; atypical astrogliosis
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- Virus generally not found, unlike viral encephalitides
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- Similar to experimental allergic encephalomyelitis, supporting autoimmune-related etiology
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# CLINICAL ISSUES
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- ## Presentation
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- ### Most common signs/symptoms
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- Usually preceded by prodromal phase: Fever, malaise, myalgia
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- Multifocal neurologic symptoms, 2 days to 4 weeks after viral illness/immunization
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- Initial symptoms: Headache, fever, drowsiness
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- Cranial nerve palsies, seizures, hemiparesis
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- Decreased consciousness (from lethargy to coma)
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- Behavioral changes
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- ### Other signs/symptoms
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- Seizures in 10-35%
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- ### Clinical profile
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- Cerebrospinal fluid (CSF) normal in 60%
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- If abnormal (lymphocyte pleocytosis, elevated protein)
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- Usually lacks CSF oligoclonal bands
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- ## Demographics
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- ### Age
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- Children > adults
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- Mean age 5-8 years, but can occur at any age
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- ### Sex
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- Male predominance (M:F = 1.0:0.6-0.8), unlike MS
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- ### Epidemiology
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- Rare, yet most common para-/postinfectious disorder
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- Most common in winter and spring
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- Exact epidemiology unknown, but increasingly reported
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- ## Natural History & Prognosis
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- Usually monophasic, self-limited
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- Variable prognosis
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- Complete recovery within 1 month (50-60%)
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- Neurologic sequelae (most commonly seizures) (20-30%)
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- Mortality (10-30%)
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- Relapses are rare
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- "Relapsing disseminated encephalomyelitis"
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- May not be separate entity from relapsing-remitting MS
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- Typically delay between symptom onset and imaging findings
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- Varicella and rubella ADEM have preferential patterns
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- Varicella ADEM characterized by cerebellar ataxia and mild pyramidal dysfunction
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- Rubella ADEM characterized by acute explosive onset, seizures, coma, and moderate pyramidal signs
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- Rare manifestations of ADEM
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- Acute hemorrhagic leukoencephalopathy (2%)
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- Young patients with abrupt symptom onset
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- Fulminant, often ending in death
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- Bilateral striatal necrosis (usually in infants, may be reversible)
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- ## Treatment
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- Immunosuppressive/immunomodulatory therapy
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- MR may show prompt improvement after therapy
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- Plasma exchange therapy
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- 40% of patients failing steroid treatment may show marked improvement
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# DIAGNOSTIC CHECKLIST
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- ## Image Interpretation Pearls
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- Imaging findings often lag behind symptom onset, resolution
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3aec74c8-de53-4430-a00a-d8165ad210c7
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## References
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# Selected References
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1. [Carvalho K et al: Acute disseminated encephalomyelitis (ADEM) associated with mosquito-borne diseases: Chikungunya virus X yellow fever immunization. Rev Soc Bras Med Trop. 53:e20190160, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=31994659%5Bpmid%5D)
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1. [Molero-Senosiain M et al: Neuro-ophthalmological manifestations as complication of an infection with Mycoplasma pneumoniae and subsequent development of disseminated acute encephalitis. Arch Soc Esp Oftalmol. 95(5(:254-8, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32147128%5Bpmid%5D)
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1. [Stokes Brackett AC et al: Multiphasic acute disseminated encephalomyelitis and differential with early onset multiple sclerosis. Intractable Rare Dis Res. 9(1):61-3, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32201679%5Bpmid%5D)
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1. [Baumann M et al: MRI of the first event in pediatric acquired demyelinating syndromes with antibodies to myelin oligodendrocyte glycoprotein. J Neurol. 265(4):845-55, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29423614%5Bpmid%5D)
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1. [Aubert-Broche B et al: Monophasic demyelination reduces brain growth in children. Neurology. 88(18):1744-50, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28381515%5Bpmid%5D)
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1. [Bester M et al: Neuroimaging of multiple sclerosis, acute disseminated encephalomyelitis, and other demyelinating diseases. Semin Roentgenol. 49(1):76-85, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24342677%5Bpmid%5D)
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1. [Longoni G et al: White matter changes in paediatric multiple sclerosis and monophasic demyelinating disorders. Brain. 140(5):1300-15, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28334875%5Bpmid%5D)
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1. [Koelman DLH et al: Acute disseminated encephalomyelitis: prognostic value of early follow-up brain MRI. J Neurol. 264(8):1754-62, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28695361%5Bpmid%5D)
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1. [Marziali S et al: Acute disseminated encephalomyelitis following Campylobacter jejuni gastroenteritis: Case report and review of the literature. Neuroradiol J. 30(1):65-70, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=27888275%5Bpmid%5D)
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1. [Kanekar S et al: A pattern approach to focal white matter hyperintensities on magnetic resonance imaging. Radiol Clin North Am. 52(2):241-61, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24582339%5Bpmid%5D)
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1. [Daida K et al: Cytomegalovirus-associated encephalomyelitis in an immunocompetent adult: a two-stage attack of direct viral and delayed immune-mediated invasions. case report. BMC Neurol. 16(1):223, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=27855658%5Bpmid%5D)
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1. [Pohl D et al: Acute disseminated encephalomyelitis: updates on an inflammatory CNS syndrome. Neurology. 87(9 Suppl 2):S38-45, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=27572859%5Bpmid%5D)
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1. [Yuan JL et al: Acute Disseminated Encephalomyelitis following Vaccination against Hepatitis B in a Child: A Case Report and Literature Review. Case Rep Neurol Med. 2016:2401809, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=27478662%5Bpmid%5D)
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1. [Baumann M et al: Clinical and neuroradiological differences of paediatric acute disseminating encephalomyelitis with and without antibodies to the myelin oligodendrocyte glycoprotein. J Neurol Neurosurg Psychiatry. 86(3):265-72, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25121570%5Bpmid%5D)
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1. [Karussis D: The diagnosis of multiple sclerosis and the various related demyelinating syndromes: a critical review. J Autoimmun. 48-49:134-42, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24524923%5Bpmid%5D)
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1. [Mariotto S et al: Clinical spectrum and IgG subclass analysis of anti-myelin oligodendrocyte glycoprotein antibody-associated syndromes: a multicenter study. J Neurol. 264(12):2420-30, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=29063242%5Bpmid%5D)
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1. [Nakamura Y et al: Anti-MOG antibody-positive ADEM following infectious mononucleosis due to a primary EBV infection: a case report. BMC Neurol. 17(1):76, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28420330%5Bpmid%5D)
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1. [Tenembaum SN: Acute disseminated encephalomyelitis. Handb Clin Neurol. 112:1253-62, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23622336%5Bpmid%5D)
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1. [Wingerchuk DM et al: Acute disseminated encephalomyelitis, transverse myelitis, and neuromyelitis optica. Continuum (Minneap Minn). 19(4 Multiple Sclerosis):944-67, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23917095%5Bpmid%5D)
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1. [Callen DJ et al: Role of MRI in the differentiation of ADEM from MS in children. Neurology. 72(11):968-73, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19038851%5Bpmid%5D)
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1. [Noorbakhsh F et al: Acute disseminated encephalomyelitis: clinical and pathogenesis features. Neurol Clin. 26(3):759-80, ix, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18657725%5Bpmid%5D)
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1. [Rossi A: Imaging of acute disseminated encephalomyelitis. Neuroimaging Clin N Am. 18(1):149-61; ix, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18319160%5Bpmid%5D)
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1. [Tenembaum S et al: Acute disseminated encephalomyelitis. Neurology. 68(16 Suppl 2):S23-36, 2007](http://www.ncbi.nlm.nih.gov/pubmed/?term=17438235%5Bpmid%5D)
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1. [Menge T et al: Acute disseminated encephalomyelitis: an update. Arch Neurol. 62(11):1673-80, 2005](http://www.ncbi.nlm.nih.gov/pubmed/?term=16286539%5Bpmid%5D)
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1. [Yeh EA et al: Detection of coronavirus in the central nervous system of a child with acute disseminated encephalomyelitis. Pediatrics. 113(1 Pt 1):e73-6, 2004](http://www.ncbi.nlm.nih.gov/pubmed/?term=14702500%5Bpmid%5D)
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1. [Dale RC: Acute disseminated encephalomyelitis. Semin Pediatr Infect Dis. 14(2):90-5, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12881796%5Bpmid%5D)
|
||||
1. [Garg RK: Acute disseminated encephalomyelitis. Postgrad Med J. 79(927):11-17, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12566545%5Bpmid%5D)
|
||||
1. [Idrissova ZhR et al: Acute disseminated encephalomyelitis in children: clinical features and HLA-DR linkage. Eur J Neurol. 10(5):537-46, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12940836%5Bpmid%5D)
|
||||
1. [Okamoto K et al: MR features of diseases involving bilateral middle cerebellar peduncles. AJNR Am J Neuroradiol. 24(10):1946-54, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=14625215%5Bpmid%5D)
|
||||
1. [Sener RN: Neuro-Behcet's disease: diffusion MR imaging and proton MR spectroscopy. AJNR Am J Neuroradiol. 24(8):1612-4, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=13679280%5Bpmid%5D)
|
||||
1. [Stonehouse M et al: Acute disseminated encephalomyelitis: recognition in the hands of general paediatricians. Arch Dis Child. 88(2):122-4, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12538312%5Bpmid%5D)
|
||||
1. [Inglese M et al: Magnetization transfer and diffusion tensor MR imaging of acute disseminated encephalomyelitis. AJNR Am J Neuroradiol. 23(2):267-72, 2002](http://www.ncbi.nlm.nih.gov/pubmed/?term=11847052%5Bpmid%5D)
|
||||
1. [Murthy JM: Acute disseminated encephalomyelitis. Neurol India. 50(3):238-43, 2002](http://www.ncbi.nlm.nih.gov/pubmed/?term=12391446%5Bpmid%5D)
|
||||
1. [Tenembaum S et al: Acute disseminated encephalomyelitis: a long-term follow-up study of 84 pediatric patients. Neurology. 59(8):1224-31, 2002](http://www.ncbi.nlm.nih.gov/pubmed/?term=12391351%5Bpmid%5D)
|
||||
1. [Bizzi A et al: Quantitative proton MR spectroscopic imaging in acute disseminated encephalomyelitis. AJNR Am J Neuroradiol. 22(6):1125-30, 2001](http://www.ncbi.nlm.nih.gov/pubmed/?term=11415908%5Bpmid%5D)
|
||||
1. [Honkaniemi J et al: Delayed MR imaging changes in acute disseminated encephalomyelitis. AJNR Am J Neuroradiol. 22(6):1117-24, 2001](http://www.ncbi.nlm.nih.gov/pubmed/?term=11415907%5Bpmid%5D)
|
||||
1. [Straussberg R et al: Improvement of atypical acute disseminated encephalomyelitis with steroids and intravenous immunoglobulins. Pediatr Neurol. 24(2):139-43, 2001](http://www.ncbi.nlm.nih.gov/pubmed/?term=11275464%5Bpmid%5D)
|
||||
1. [Dale RC et al: Acute disseminated encephalomyelitis, multiphasic disseminated encephalomyelitis and multiple sclerosis in children. Brain. 123 Pt 12:2407-22, 2000](http://www.ncbi.nlm.nih.gov/pubmed/?term=11099444%5Bpmid%5D)
|
||||
1. [Rust RS: Multiple sclerosis, acute disseminated encephalomyelitis, and related conditions. Semin Pediatr Neurol. 7(2):66-90, 2000](http://www.ncbi.nlm.nih.gov/pubmed/?term=10914409%5Bpmid%5D)
|
||||
1. [Schaefer PW et al: Diffusion-weighted MR imaging of the brain. Radiology. 217(2):331-45, 2000](http://www.ncbi.nlm.nih.gov/pubmed/?term=11058626%5Bpmid%5D)
|
||||
1. [Kocer N et al: CNS involvement in neuro-Behcet syndrome: an MR study. AJNR Am J Neuroradiol. 20(6):1015-24, 1999](http://www.ncbi.nlm.nih.gov/pubmed/?term=10445437%5Bpmid%5D)
|
||||
|
||||
|
||||
## Images
|
||||
|
||||
|
||||
### Selected Images
|
||||
|
||||
|
||||
*Axial FLAIR MR shows peripheral, confluent areas of hyperintensity predominantly involving the subcortical white matter (WM) in this child with ADEM. The bilateral but asymmetric pattern is typical of ADEM.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows peripheral, confluent areas of hyperintensity predominantly involving the subcortical white matter (WM) in this child with ADEM. The bilateral but asymmetric pattern is typical of ADEM.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows peripheral, confluent areas of hyperintensity predominantly involving the subcortical white matter (WM) in this child with ADEM. The bilateral but asymmetric pattern is typical of ADEM.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows marked, irregular enhancement of nearly all lesions. As ADEM is a monophasic illness, enhancement of the majority of lesions is typical; all lesions have a similar time course. Enhancement of multiple sclerosis (MS) lesions is more variable.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows marked, irregular enhancement of nearly all lesions. As ADEM is a monophasic illness, enhancement of the majority of lesions is typical; all lesions have a similar time course. Enhancement of multiple sclerosis (MS) lesions is more variable.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR shows an incomplete ring of peripheral enhancement, typical of a demyelinating process. Other contrast enhancement patterns include ovoid or punctate homogeneous enhancement.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR shows an incomplete ring of peripheral enhancement, typical of a demyelinating process. Other contrast enhancement patterns include ovoid or punctate homogeneous enhancement.*
|
||||
|
||||
|
||||
*Axial DWI MR shows increased signal in areas of FLAIR hyperintensity. The foci were hypointense on ADC images, indicating diffusion restriction. Both WM and gray matter involvement is present. Diffusion restriction is an uncommon imaging finding and is associated with a worse prognosis.*
|
||||
|
||||
|
||||
*Axial DWI MR shows increased signal in areas of FLAIR hyperintensity. The foci were hypointense on ADC images, indicating diffusion restriction. Both WM and gray matter involvement is present. Diffusion restriction is an uncommon imaging finding and is associated with a worse prognosis.*
|
||||
|
||||
|
||||
*Axial T2 MR shows hyperintense lesions in the brachium pontis bilaterally, typical for demyelination. The right-sided lesion shows a targetoid <img src='/img/arrows/WS.png'/> appearance. Enhancement of several lesions was present on postcontrast T1 images (not shown).*
|
||||
|
||||
|
||||
*Axial T2 MR shows hyperintense lesions in the brachium pontis bilaterally, typical for demyelination. The right-sided lesion shows a targetoid <img src='/img/arrows/WS.png'/> appearance. Enhancement of several lesions was present on postcontrast T1 images (not shown).*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows large, confluent regions of hyperintense signal <img src='/img/arrows/CC.png'/> in the periventricular and subcortical WM in a 14 year old who presented with neck stiffness, fatigue, and seizures.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows large, confluent regions of hyperintense signal <img src='/img/arrows/CC.png'/> in the periventricular and subcortical WM in a 14 year old who presented with neck stiffness, fatigue, and seizures.*
|
||||
|
||||
|
||||
*Axial SWI MR in the same patient shows petechial hemorrhages <img src='/img/arrows/CS.png'/> in regions of FLAIR signal abnormality.*
|
||||
|
||||
|
||||
*Axial SWI MR in the same patient shows petechial hemorrhages <img src='/img/arrows/CS.png'/> in regions of FLAIR signal abnormality.*
|
||||
|
||||
|
||||
*Sagittal T1 C+ MR in the same patient shows extensive irregular ring enhancement <img src='/img/arrows/CC.png'/> in multiple subcortical WM lesions. Acute hemorrhagic leukoencephalopathy (AHL) is a rare manifestation of ADEM occurring in 2% of cases. AHL is associated with a very poor prognosis. Aggressive therapeutic management is a prerequisite to avoid usual disease course with fatal outcome.*
|
||||
|
||||
|
||||
*Sagittal T1 C+ MR in the same patient shows extensive irregular ring enhancement <img src='/img/arrows/CC.png'/> in multiple subcortical WM lesions. Acute hemorrhagic leukoencephalopathy (AHL) is a rare manifestation of ADEM occurring in 2% of cases. AHL is associated with a very poor prognosis. Aggressive therapeutic management is a prerequisite to avoid usual disease course with fatal outcome.*
|
||||
|
||||
|
||||
*Coronal T2 MR shows large, confluent regions of hyperintense signal in the WM <img src='/img/arrows/WO.png'/> and deep gray nuclei <img src='/img/arrows/WS.png'/> of a child with ADEM. Although ADEM predominantly involves WM, gray matter is often affected.*
|
||||
|
||||
|
||||
*Coronal T2 MR shows large, confluent regions of hyperintense signal in the WM <img src='/img/arrows/WO.png'/> and deep gray nuclei <img src='/img/arrows/WS.png'/> of a child with ADEM. Although ADEM predominantly involves WM, gray matter is often affected.*
|
||||
|
||||
|
||||
*MRS at long TE in a patient with acute lesions in ADEM demonstrates ↑ choline <img src='/img/arrows/CC.png'/>, ↓ NAA <img src='/img/arrows/CS.png'/>, and the presence of a lactate doublet <img src='/img/arrows/WS.png'/>. Increase in choline with corresponding reductions in NAA normalize as the clinical and conventional neuroimaging abnormalities resolve.*
|
||||
|
||||
|
||||
*MRS at long TE in a patient with acute lesions in ADEM demonstrates ↑ choline <img src='/img/arrows/CC.png'/>, ↓ NAA <img src='/img/arrows/CS.png'/>, and the presence of a lactate doublet <img src='/img/arrows/WS.png'/>. Increase in choline with corresponding reductions in NAA normalize as the clinical and conventional neuroimaging abnormalities resolve.*
|
||||
|
||||
|
||||
### Additional Images
|
||||
|
||||
|
||||
*Axial FLAIR MR shows multiple bilateral, asymmetric, flocculent, hyperintense lesions of acute disseminated encephalomyelitis.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows multiple bilateral, asymmetric, flocculent, hyperintense lesions of acute disseminated encephalomyelitis.*
|
||||
|
||||
|
||||
*Coronal T1 C+ MR demonstrates partial peripheral enhancement around multiple asymmetric, flocculent lesions of acute disseminated encephalomyelitis. Note the supra- and infratentorial lesions.*
|
||||
|
||||
|
||||
*Coronal T1 C+ MR demonstrates partial peripheral enhancement around multiple asymmetric, flocculent lesions of acute disseminated encephalomyelitis. Note the supra- and infratentorial lesions.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows asymmetric, flocculent, nearly confluent, hyperintense lesions of acute disseminated encephalomyelitis within posterior fossa structures.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows asymmetric, flocculent, nearly confluent, hyperintense lesions of acute disseminated encephalomyelitis within posterior fossa structures.*
|
||||
|
||||
|
||||
*Axial FLAIR MR reveals multiple asymmetric, primarily punctate, hyperintense lesions of acute disseminated encephalomyelitis.*
|
||||
|
||||
|
||||
*Axial FLAIR MR reveals multiple asymmetric, primarily punctate, hyperintense lesions of acute disseminated encephalomyelitis.*
|
||||
|
||||
|
||||
*Axial FLAIR MR demonstrates a large, tumefactive, hyperintense lesion. Less mass effect is present than expected for lesion size. Smaller lesions were also present at other locations.*
|
||||
|
||||
|
||||
*Axial FLAIR MR demonstrates a large, tumefactive, hyperintense lesion. Less mass effect is present than expected for lesion size. Smaller lesions were also present at other locations.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR demonstrates a large, tumefactive, hypointense lesion with minimal partial peripheral enhancement. Less mass effect is present than expected for lesion size. More lesions were seen elsewhere.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR demonstrates a large, tumefactive, hypointense lesion with minimal partial peripheral enhancement. Less mass effect is present than expected for lesion size. More lesions were seen elsewhere.*
|
||||
|
||||
|
||||
*Axial FLAIR MR demonstrates a rare manifestation of ADEM: Bilateral striatal necrosis, evidenced by asymmetric confluent hyperintensity involving the gray and white matter of bilateral corpus striatum.*
|
||||
|
||||
|
||||
*Axial FLAIR MR demonstrates a rare manifestation of ADEM: Bilateral striatal necrosis, evidenced by asymmetric confluent hyperintensity involving the gray and white matter of bilateral corpus striatum.*
|
||||
|
||||
|
||||
*Axial DWI MR confirms the rare manifestation of ADEM, displaying bilateral striatal necrosis, as evidenced by asymmetric confluent restricted diffusion involving gray and white matter of bilateral corpus striatum.*
|
||||
|
||||
|
||||
*Axial DWI MR confirms the rare manifestation of ADEM, displaying bilateral striatal necrosis, as evidenced by asymmetric confluent restricted diffusion involving gray and white matter of bilateral corpus striatum.*
|
||||
|
||||
|
||||
*Axial T2 MR shows multiple bilateral, but asymmetric, T2-hyperintense foci <img src='/img/arrows/WS.png'/>. None of the lesions demonstrate significant mass effect in this adult patient with ADEM. Imaging mimics multiple sclerosis, vasculitis, and microvascular ischemia.*
|
||||
|
||||
|
||||
*Axial T2 MR shows multiple bilateral, but asymmetric, T2-hyperintense foci <img src='/img/arrows/WS.png'/>. None of the lesions demonstrate significant mass effect in this adult patient with ADEM. Imaging mimics multiple sclerosis, vasculitis, and microvascular ischemia.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows a large, tumefactive, hyperintense ADEM lesion <img src='/img/arrows/WS.png'/> with mass effect less than expected for the size of the lesion. Another clue to its nonneoplastic nature is the right-sided lesion <img src='/img/arrows/WC.png'/>.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows a large, tumefactive, hyperintense ADEM lesion <img src='/img/arrows/WS.png'/> with mass effect less than expected for the size of the lesion. Another clue to its nonneoplastic nature is the right-sided lesion <img src='/img/arrows/WC.png'/>.*
|
||||
|
||||
|
||||
*MRS at a long TE in the same patient shows the tumefactive lesion has a depressed choline <img src='/img/arrows/WC.png'/> and NAA <img src='/img/arrows/WO.png'/> metabolites in the presence of a large lactate doublet <img src='/img/arrows/WS.png'/>. This MRS helps distinguish this lesion from a neoplasm. MRS of ADEM may show elevated choline acutely.*
|
||||
|
||||
|
||||
*MRS at a long TE in the same patient shows the tumefactive lesion has a depressed choline <img src='/img/arrows/WC.png'/> and NAA <img src='/img/arrows/WO.png'/> metabolites in the presence of a large lactate doublet <img src='/img/arrows/WS.png'/>. This MRS helps distinguish this lesion from a neoplasm. MRS of ADEM may show elevated choline acutely.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows typical findings of ADEM with peripheral, subcortical hyperintense foci <img src='/img/arrows/WC.png'/>. Bilateral insular involvement is seen <img src='/img/arrows/WS.png'/>. Periventricular and callososeptal lesions, which are typical of multiple sclerosis, are not commonly seen in ADEM.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows typical findings of ADEM with peripheral, subcortical hyperintense foci <img src='/img/arrows/WC.png'/>. Bilateral insular involvement is seen <img src='/img/arrows/WS.png'/>. Periventricular and callososeptal lesions, which are typical of multiple sclerosis, are not commonly seen in ADEM.*
|
||||
|
||||
@@ -0,0 +1,326 @@
|
||||
---
|
||||
title: "AHLE"
|
||||
docid: "0ec0bca6-abee-4931-a6ed-43541b626261"
|
||||
authors:
|
||||
- key: "5cff4116-3654-4b3a-bb75-5ebe0b8c9850"
|
||||
value: "Anne G. Osborn, MD, FACR"
|
||||
breadcrumbs:
|
||||
-
|
||||
name: "Brain"
|
||||
slug: "brain"
|
||||
treeNodeId: "6d8829f1-14d7-45af-8675-255189aa526a"
|
||||
-
|
||||
name: "Diagnosis"
|
||||
slug: "diagnosis"
|
||||
treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
|
||||
-
|
||||
name: "Pathology-Based Diagnoses"
|
||||
slug: "pathology-based-diagnoses"
|
||||
treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
|
||||
-
|
||||
name: "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
slug: "infectious-inflammatory-and-demyel-"
|
||||
treeNodeId: "7210f860-fe5f-4a2d-81cc-4fe06c769607"
|
||||
-
|
||||
name: "Inflammatory and Demyelinating Disease"
|
||||
slug: "inflammatory-and-demyelinating-dis-"
|
||||
treeNodeId: "62ab4dc3-dbf6-45a9-8532-f0e962aa62dc"
|
||||
-
|
||||
name: "AHLE"
|
||||
slug: "ahle"
|
||||
treeNodeId: null
|
||||
category: "Brain"
|
||||
documentVersionId: "05d076c7-6110-4f03-952a-c22726d85e4d"
|
||||
imageCount: 12
|
||||
lastUpdated: "08/05/20"
|
||||
pageDescription: "AHLE"
|
||||
pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Infectious, Inflammatory, and Demyelinating Disease, Inflammatory and Demyelinating Disease, AHLE"
|
||||
pageTitle: "AHLE | STATdx"
|
||||
enhancedTitle: "AHLE"
|
||||
type: "DX"
|
||||
references: true
|
||||
breadcrumbs:
|
||||
- "Brain"
|
||||
- "Diagnosis"
|
||||
- "Pathology-Based Diagnoses"
|
||||
- "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
- "Inflammatory and Demyelinating Disease"
|
||||
- "AHLE"
|
||||
---
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Hyperacute, fulminant hemorrhagic perivascular demyelinating disorder
|
||||
- Usually viral or immunization related
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Best imaging: MR with T2* GRE, SWI
|
||||
- CT: May be normal if only microbleeds present
|
||||
- MR
|
||||
- Multifocal scattered or confluent WM hyperintensities on T2/FLAIR
|
||||
- T2* shows multifocal blooming microbleeds in WM (often striking sparing of cortex)
|
||||
- Most striking in corpus callosum
|
||||
- Less common: Large, lobar, confluent hemorrhages
|
||||
- SWI significantly more sensitive than GRE
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Acute disseminated encephalomyelitis (ADEM)
|
||||
- Multiple sclerosis
|
||||
- Acute necrotizing encephalopathy
|
||||
- Other brain "microbleeds"
|
||||
- Critical illness associated (e.g., ARDS ± on ECMO)
|
||||
- Trauma (DAI), fat emboli, HUS/TTP
|
||||
- Sepsis, vasculitis, hemorrhagic viral fevers
|
||||
- High-altitude cerebral edema
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Demographics
|
||||
- AHLE represents ~ 2% of ADEM cases
|
||||
- All ages but children, young adults most common
|
||||
- Presentation and course
|
||||
- Fever, then rapid neurologic deterioration
|
||||
- 60-80% mortality without treatment
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- T2* (GRE or SWI) MR in all febrile CNS illnesses with rapid clinical deterioration
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Acute hemorrhagic leukoencephalitis (AHLE)
|
||||
- Acute disseminated encephalomyelopathy (ADEM)
|
||||
- ## Synonyms
|
||||
|
||||
|
||||
- Acute hemorrhagic encephalomyelitis (AHEM)
|
||||
- Weston-Hurst disease
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Hyperacute, fulminant, hemorrhagic perivascular demyelinating disorder
|
||||
- Usually post viral or immunization related
|
||||
- May be exceptionally severe, fulminant form of ADEM
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- T2* shows multifocal petechial white matter (WM) microhemorrhages with striking sparing of cortex
|
||||
- Less common: Large, lobar, confluent hemorrhages
|
||||
- ### Location
|
||||
|
||||
|
||||
- WM
|
||||
- Corpus callosum, subcortical WM (U fibers)
|
||||
- Less common: Basal ganglia, midbrain, pons, cerebellum
|
||||
- ### Size
|
||||
|
||||
|
||||
- Punctate microbleeds > large, lobar hemorrhages
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- ### NECT
|
||||
|
||||
|
||||
- May be normal if only microbleeds present
|
||||
- ± WM edema with hypodensity
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- Often normal
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- Multifocal scattered or confluent WM hyperintensities
|
||||
- Most striking in corpus callosum
|
||||
- May have reversible corpus callosum splenium lesion
|
||||
- ### T2* GRE
|
||||
|
||||
|
||||
- Multifocal blooming microbleeds
|
||||
- SWI significantly more sensitive than GRE
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MR with T2* GRE, SWI
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Acute Disseminated Encephalomyelitis](/document/adem/a3fafeb7-5861-4364-beb8-c0e30220564e)
|
||||
- AHLE may be most severe form of ADEM
|
||||
- ADEM usually less fulminant
|
||||
- ADEM lacks lobar or perivascular hemorrhages of AHLE
|
||||
- [Multiple Sclerosis](/document/multiple-sclerosis/7892b2a2-f52a-4d7f-9858-a326f2b7ab04)
|
||||
- Acute fulminant multiple sclerosis
|
||||
- Lacks hemorrhage, high fever, marked leukocytosis
|
||||
- ## Acute Necrotizing Encephalopathy
|
||||
|
||||
|
||||
- Rare complication of acute viral infection, such as influenza A
|
||||
- Children < 4 years most common
|
||||
- Bilateral, symmetric lesions in thalami typical
|
||||
- WM predominance rare
|
||||
- ## Other Etiologies of Brain Microbleeds
|
||||
|
||||
|
||||
- Diffuse, traumatic vascular injury
|
||||
- Critical illness-associated (e.g., ARDS ± on ECMO)
|
||||
- Sepsis, vasculitis
|
||||
- Fat emboli
|
||||
- HUS/TTP
|
||||
- Hemorrhagic infections
|
||||
- Viral (H1N1, coronavirus), malaria, rickettsia
|
||||
- High-altitude cerebral edema
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Predominantly involves WM of brain ± spinal cord
|
||||
- May affect basal ganglia but usually spares cortical gray matter
|
||||
- Focal confluent &/or multifocal petechial WM hemorrhages
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- Fibrinoid necrosis of vessel walls
|
||||
- Perivascular demyelination, hemorrhages
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Fever, then rapid neurologic deterioration
|
||||
- Somnolence, impaired consciousness
|
||||
- ### Other signs/symptoms
|
||||
|
||||
|
||||
- Long-tract signs
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- AHLE represents ~ 2% of ADEM cases
|
||||
- All ages but children, young adults most common
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Rapid clinical deterioration; death within days typical course
|
||||
- Mortality: 60-80%
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- Aggressive IV steroids, immunoglobulin, plasmapheresis
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- T2* (GRE or SWI) MR in all febrile CNS illnesses with rapid clinical deterioration
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- Corpus callosum, subcortical WM microbleeds with striking sparing of overlying cortex typical for AHLE
|
||||
|
||||
8f325204-5ce7-4da8-b816-cb545fa5b054
|
||||
|
||||
## References
|
||||
|
||||
# Selected References
|
||||
|
||||
1. [Mondia MWL et al: Acute hemorrhagic leukoencephalitis of Weston Hurst secondary to herpes encephalitis presenting as status epilepticus: a case report and review of literature. J Clin Neurosci. 67:265-70, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31239199%5Bpmid%5D)
|
||||
1. [Yae Y et al: Fulminant acute disseminated encephalomyelitis in children. Brain Dev. 41(4):373-7, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30522797%5Bpmid%5D)
|
||||
1. [Bonduelle T et al: Weston-Hurst syndrome with acute hemorrhagic cerebellitis. Clin Neurol Neurosurg. 173:118-9, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=30121019%5Bpmid%5D)
|
||||
1. [Fanou EM et al: Critical illness-associated cerebral microbleeds. Stroke. 48(4):1085-7, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28235962%5Bpmid%5D)
|
||||
1. [Nabi S et al: Weston-Hurst syndrome: a rare fulminant form of acute disseminated encephalomyelitis (ADEM). BMJ Case Rep. 2016, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=27797801%5Bpmid%5D)
|
||||
1. [Jeganathan N et al: Acute hemorrhagic leukoencephalopathy associated with influenza A (H1N1) virus. Neurocrit Care. 19(2):218-21, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23943349%5Bpmid%5D)
|
||||
|
||||
|
||||
## Images
|
||||
|
||||
|
||||
### Selected Images
|
||||
|
||||
|
||||
*Close-up view of autopsied brain in a patient with acute hemorrhagic leukoencephalitis (AHLE) shows innumerable tiny microbleeds in the subcortical and deep white matter (WM) <img src='/img/arrows/BO.png'/> and corpus callosum <img src='/img/arrows/BS.png'/>. Note the overlying cortex is almost completely spared <img src='/img/arrows/BC.png'/>. (Courtesy E. Rushing, MD.)*
|
||||
|
||||
|
||||
*Close-up view of autopsied brain in a patient with acute hemorrhagic leukoencephalitis (AHLE) shows innumerable tiny microbleeds in the subcortical and deep white matter (WM) <img src='/img/arrows/BO.png'/> and corpus callosum <img src='/img/arrows/BS.png'/>. Note the overlying cortex is almost completely spared <img src='/img/arrows/BC.png'/>. (Courtesy E. Rushing, MD.)*
|
||||
|
||||
|
||||
*Close-up view of autopsied brain in a patient with acute hemorrhagic leukoencephalitis (AHLE) shows innumerable tiny microbleeds in the subcortical and deep white matter (WM) <img src='/img/arrows/BO.png'/> and corpus callosum <img src='/img/arrows/BS.png'/>. Note the overlying cortex is almost completely spared <img src='/img/arrows/BC.png'/>. (Courtesy E. Rushing, MD.)*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a 28-year-old man with rapidly declining mental status after a flu-like illness shows patchy hyperintensities in the corpus callosum <img src='/img/arrows/WC.png'/> and deep/subcortical WM <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a 28-year-old man with rapidly declining mental status after a flu-like illness shows patchy hyperintensities in the corpus callosum <img src='/img/arrows/WC.png'/> and deep/subcortical WM <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Axial T2* GRE MR in the same patient shows multiple tiny hypointensities in the corpus callosum <img src='/img/arrows/BC.png'/> and deep/subcortical WM <img src='/img/arrows/BS.png'/>. The cortex is largely spared.*
|
||||
|
||||
|
||||
*Axial T2* GRE MR in the same patient shows multiple tiny hypointensities in the corpus callosum <img src='/img/arrows/BC.png'/> and deep/subcortical WM <img src='/img/arrows/BS.png'/>. The cortex is largely spared.*
|
||||
|
||||
|
||||
*Axial T2* SWI MR MIP shows the innumerable microbleeds in the corpus callosum <img src='/img/arrows/CC.png'/> with diffuse involvement of the hemispheric WM <img src='/img/arrows/CS.png'/> in this patient with AHLE.*
|
||||
|
||||
|
||||
*Axial T2* SWI MR MIP shows the innumerable microbleeds in the corpus callosum <img src='/img/arrows/CC.png'/> with diffuse involvement of the hemispheric WM <img src='/img/arrows/CS.png'/> in this patient with AHLE.*
|
||||
|
||||
|
||||
### Additional Images
|
||||
|
||||
|
||||
*Axial FLAIR MR in a 25-year-old man with fever and rapidly decreasing mental status shows no definite abnormalities.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a 25-year-old man with fever and rapidly decreasing mental status shows no definite abnormalities.*
|
||||
|
||||
|
||||
*Axial T2* GRE MR in the same patient shows a few punctate "blooming" foci in the corpus callosum genu <img src='/img/arrows/WO.png'/> and splenium <img src='/img/arrows/WS.png'/>. The remainder of the WM appears normal.*
|
||||
|
||||
|
||||
*Axial T2* GRE MR in the same patient shows a few punctate "blooming" foci in the corpus callosum genu <img src='/img/arrows/WO.png'/> and splenium <img src='/img/arrows/WS.png'/>. The remainder of the WM appears normal.*
|
||||
|
||||
|
||||
*Axial SWI MR n the same patient shows innumerable tiny "blooming" microbleeds in the corpus callosum <img src='/img/arrows/BO.png'/> and subcortical and deep WM <img src='/img/arrows/BS.png'/>. The cortex is largely spared.*
|
||||
|
||||
|
||||
*More cephalad axial T2* SWI MR shows innumerable tiny "blooming" foci in the WM, especially in the corpus callosum <img src='/img/arrows/BC.png'/>. These imaging findings are characteristic of AHLE.*
|
||||
|
||||
|
||||
*Autopsy shows 2 areas of gross hemorrhagic necrosis <img src='/img/arrows/BS.png'/>. These findings and clinical history of prior flu-like illness with rapidly progressive fatal clinical course are characteristic of AHLE. (Courtesy R. Hewlett, MD).*
|
||||
|
||||
|
||||
*Axial T2* GRE MR in a patient with rapid decline after a flu-like illness shows a large left frontal hemorrhage <img src='/img/arrows/WO.png'/> with numerous "blooming" foci in multiple WM lesions <img src='/img/arrows/BS.png'/>. Diagnosis was AHLE. (Courtesy R. Ramakantan, MD).*
|
||||
|
||||
|
||||
*Axial NECT in a patient with AHLE shows patchy hemorrhages in the corpus callosum splenium <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Axial T2* SWI MR MIP in the same patient shows the microbleeds are heavily concentrated in the corpus callosum <img src='/img/arrows/BC.png'/> and hemispheric WM <img src='/img/arrows/BS.png'/>. Note involvement of the internal capsules and relative sparing of the basal ganglia and cortex.*
|
||||
|
||||
@@ -0,0 +1,516 @@
|
||||
---
|
||||
title: "Autoimmune Encephalitis"
|
||||
docid: "6eb3d5d6-7f6a-4367-a792-b5d4b19675da"
|
||||
authors:
|
||||
- key: "8d5254e9-8dda-478b-8f08-bdee97a32c79"
|
||||
value: "Karen L. Salzman, MD, FACR"
|
||||
breadcrumbs:
|
||||
-
|
||||
name: "Brain"
|
||||
slug: "brain"
|
||||
treeNodeId: "6d8829f1-14d7-45af-8675-255189aa526a"
|
||||
-
|
||||
name: "Diagnosis"
|
||||
slug: "diagnosis"
|
||||
treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
|
||||
-
|
||||
name: "Pathology-Based Diagnoses"
|
||||
slug: "pathology-based-diagnoses"
|
||||
treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
|
||||
-
|
||||
name: "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
slug: "infectious-inflammatory-and-demyel-"
|
||||
treeNodeId: "7210f860-fe5f-4a2d-81cc-4fe06c769607"
|
||||
-
|
||||
name: "Inflammatory and Demyelinating Disease"
|
||||
slug: "inflammatory-and-demyelinating-dis-"
|
||||
treeNodeId: "62ab4dc3-dbf6-45a9-8532-f0e962aa62dc"
|
||||
-
|
||||
name: "Autoimmune Encephalitis"
|
||||
slug: "autoimmune-encephalitis"
|
||||
treeNodeId: null
|
||||
category: "Brain"
|
||||
documentVersionId: "cc8c3891-88b7-44bb-9e2a-3a321d092f4c"
|
||||
imageCount: 22
|
||||
lastUpdated: "08/05/20"
|
||||
pageDescription: "Autoimmune Encephalitis"
|
||||
pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Infectious, Inflammatory, and Demyelinating Disease, Inflammatory and Demyelinating Disease, Autoimmune Encephalitis"
|
||||
pageTitle: "Autoimmune Encephalitis | STATdx"
|
||||
enhancedTitle: "Autoimmune Encephalitis"
|
||||
type: "DX"
|
||||
references: true
|
||||
breadcrumbs:
|
||||
- "Brain"
|
||||
- "Diagnosis"
|
||||
- "Pathology-Based Diagnoses"
|
||||
- "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
- "Inflammatory and Demyelinating Disease"
|
||||
- "Autoimmune Encephalitis"
|
||||
---
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Autoimmune encephalitis (AE): Immune-mediated disease with antibody-mediated inflammation of brain
|
||||
- May be immune mediated or paraneoplastic
|
||||
- Paraneoplastic: Remote neurologic effects of cancer, associated with extra-CNS tumors
|
||||
- Most common tumor: Small cell lung carcinoma
|
||||
- Limbic encephalitis (LE) is most common clinical paraneoplastic syndrome
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- AE: T2/FLAIR hyperintensities in cortex/subcortical white matter, basal ganglia (BG), thalami, brainstem
|
||||
- AE: May have no associated imaging findings
|
||||
- LE: Hyperintensity in mesial temporal lobes/limbic system
|
||||
- Mimics herpes encephalitis but subacute/chronic
|
||||
- Paraneoplastic cerebellar degeneration (PCD): Cerebellar atrophy
|
||||
- Brainstem encephalitis: T2 hyperintensity in midbrain, pons, cerebellar peduncles, BG
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- AE: Viral encephalitis, ADEM, vasculitis
|
||||
- LE: Herpes encephalitis, diffuse astrocytoma, status epilepticus, gliomatosis cerebri imaging pattern
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- AE: 2 distinct groups (group I and group II) have overlapping clinical and imaging features
|
||||
- Group I (intracellular) or group II (cell surface) antigens
|
||||
- < 1% of patients with systemic cancers develop paraneoplastic syndrome
|
||||
- LE: Memory loss, cognitive dysfunction, dementia, psychological features, seizures
|
||||
- PCD: Ataxia, incoordination, dysarthria, nystagmus
|
||||
- Brainstem encephalitis: Brainstem dysfunction
|
||||
- Treatment of primary tumor may improve symptoms
|
||||
- AE treated with immunosuppressive therapy
|
||||
- AE may occur as complication of cancer treatment (immune checkpoint inhibitors)
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Synonyms
|
||||
|
||||
|
||||
- Paraneoplastic syndromes (PS), paraneoplastic disease
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Autoimmune encephalitis (AE): Immune-mediated disease with antibody-mediated inflammation of brain
|
||||
- Includes autoimmune and paraneoplastic encephalitis
|
||||
- Paraneoplastic: Remote neurologic effects of cancer, associated with extra-CNS tumors
|
||||
- Most common tumor: Small cell lung carcinoma
|
||||
- Limbic encephalitis (LE) is most common clinical paraneoplastic syndrome
|
||||
- Only PS with clearly defined imaging features
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- AE: Hyperintensity in mesial temporal lobes, limbic system
|
||||
- Often mimics herpes encephalitis but has different clinical course (subacute vs. chronic)
|
||||
- Initial study normal in 20-40%
|
||||
- Most PS do not have associated imaging findings
|
||||
- ### Location
|
||||
|
||||
|
||||
- AE: Limbic structures, deep gray nuclei, brainstem, cortex and subcortical white matter (WM)
|
||||
- LE: Hippocampus, amygdala, cingulate gyrus, pyriform cortex, subfrontal cortex, insula
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- NECT: Initial CT scan normal in > 95%
|
||||
- Rare: Low density within mesial temporal lobes
|
||||
- CECT: Usually no visible enhancement
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- AE: Hypointensity in cortex, WM, deep gray, or brainstem
|
||||
- LE: Hypointensity in mesial temporal lobes (hippocampus, amygdala), insula, cingulate gyrus, subfrontal cortex, inferior frontal WM
|
||||
- May see minimal mass effect
|
||||
- May see atrophy in chronic cases
|
||||
- No hemorrhage
|
||||
- ### DWI
|
||||
|
||||
|
||||
- Diffusion restriction rare
|
||||
- T2WI: Hyperintensity in mesial temporal lobes &/or cortex, WM, deep gray, or brainstem
|
||||
- May see minimal mass effect
|
||||
- FLAIR: Hyperintensity
|
||||
- T2* GRE: No hemorrhage
|
||||
- If blood products seen, consider herpes encephalitis
|
||||
- T1WI C+: Patchy enhancement may be seen
|
||||
- Brainstem encephalitis: T2 hyperintensity in midbrain, pons, cerebellar peduncles, basal ganglia
|
||||
- Paraneoplastic cerebellar degeneration (PCD): Cerebellar atrophy
|
||||
- ## Nuclear Medicine Findings
|
||||
|
||||
|
||||
- FDG PET: Increased glucose metabolism in medial temporal lobes in LE patients
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MR is most sensitive
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- Contrast-enhanced MR with coronal T2 or FLAIR
|
||||
- Consider repeat MR if initial scan normal with high clinical suspicion
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Herpes Encephalitis](/document/herpes-encephalitis/6bbe5645-2178-411e-871e-8878d244f482)
|
||||
- T2 hyperintensity in temporal lobes, limbic system
|
||||
- Mass effect common; restricted DWI common
|
||||
- Rapid onset, febrile illness
|
||||
- HSV titers (CSF, serum) may be negative early
|
||||
- Late acute/subacute may hemorrhage
|
||||
- May be indistinguishable from LE
|
||||
- ## Diffuse Astrocytoma (WHO Grade 2)
|
||||
|
||||
|
||||
- Unilateral T2-hyperintense mass
|
||||
- May involve medial temporal lobe
|
||||
- No enhancement typical
|
||||
- [Status Epilepticus](/document/status-epilepticus/a058b733-4b80-46a1-8097-d68685ecf921)
|
||||
- Seizures related to abnormal T2/FLAIR of mesial temporal lobes
|
||||
- Cortical enhancement with DWI is typical
|
||||
- Clinical history of seizures
|
||||
- Follow-up imaging may be necessary
|
||||
- ## Gliomatosis Cerebri Imaging Pattern
|
||||
|
||||
|
||||
- Diffuse process; no predilection for limbic system
|
||||
- T2 hyperintensity in multiple contiguous lobes
|
||||
- Enlarges affected area
|
||||
- ## Vasculitis
|
||||
|
||||
|
||||
- Multiple T2/FLAIR hyperintensities
|
||||
- Blood products common
|
||||
- Small infarcts common
|
||||
- ## Acute Disseminated Encephalomyelitis
|
||||
|
||||
|
||||
- T2/FLAIR hyperintensities in WM and deep gray nuclei
|
||||
- Enhancement typical
|
||||
- Often 1-2 weeks following infection/vaccination
|
||||
- ## Parenchymal Metastases
|
||||
|
||||
|
||||
- Typically multifocal, enhancing lesions
|
||||
- Primary tumor often known
|
||||
- No predilection for limbic system
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- AE may be characterized as either **group I**or **group II** according to location of their neuronal antigens
|
||||
- **Group I**antibodies targeting **intracellular antigens**
|
||||
- **Group II**antibodies targeting **antigens on cell surface**:1, 2, 6, 7, 9, 27
|
||||
- Distinction clinically relevant: Implications for treatment response, association with underlying malignancy, and prognosis
|
||||
- **Group I**antibodies are more closely associated with underlying malignancy
|
||||
- Immune mediated by **autoantibodies** or cytotoxic T cell-related mechanisms
|
||||
- 60% of patients have circulating serum **autoantibodies**
|
||||
- **Anti-Hu** (75% small cell lung cancer): LE pattern
|
||||
- **Anti-Ma/Ta** (testicular germ cell tumors > > lung cancer > breast cancer): LE, brainstem encephalitis
|
||||
- **Anti-Yo** (breast and ovarian): PCD pattern
|
||||
- **Anti-Tr** (Hodgkin disease): PCD pattern
|
||||
- **Anti-Ri**(lung, breast, ovarian): Opsoclonus myoclonus, brainstem encephalitis
|
||||
- **Anti-CV2**(small-cell lung cancer, malignant thymoma): T2/FLAIR-hyperintense lesions in striatum
|
||||
- **Anti-glutamic acid decarboxylase (GAD65)**(not typically associated with malignancy): LE pattern
|
||||
- Stiff man syndrome, cerebellar ataxia, seizures
|
||||
- Reversible extralimbic paraneoplastic encephalopathy
|
||||
- Associated with breast cancer and lung cancer
|
||||
- Reversible when primary tumors controlled
|
||||
- **Group II**cell surface antigens
|
||||
- **Voltage-gated potassium channels (VGKC)** and N-methyl-D-aspartate receptor (**NMDAR**)
|
||||
- Appear to be antibody mediated and respond better to immunotherapy (90%)
|
||||
- Associated with other tumors (thymoma, teratoma, Hodgkin lymphoma)
|
||||
- Patients may present with LE; more frequently manifest severe psychiatric symptoms, seizures, dyskinesias, autonomic instability, or hypoventilation
|
||||
- Antibody to α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (**AMPAr**)
|
||||
- Associated with LE pattern, T2 hyperintensities in hippocampus
|
||||
- May occur with other antibodies
|
||||
- Often associated with lung, breast, or thymic tumors
|
||||
- γ aminobutyric acid encephalitis (**GABAr**)
|
||||
- LE pattern ± other MR findings, seizures
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- 2 distinct groups (group I and group II) have overlapping clinical and imaging features
|
||||
- PSs divided into disorders of CNS, peripheral NS (PNS), CNS/PNS, neuromuscular junction
|
||||
- CNS: PCD, opsoclonus myoclonus, retinopathy
|
||||
- PNS: Sensory-motor neuropathy, autonomic neuropathy
|
||||
- Both CNS/PNS: Encephalomyelitis (LE, brainstem encephalitis, myelitis, motor neuron disease)
|
||||
- Neuromuscular junction: Lambert-Eaton myasthenic syndrome
|
||||
- LE is most common AE (paraneoplastic, group I)
|
||||
- Nonparaneoplastic LE reported
|
||||
- PCD is 2nd most common PS
|
||||
- Multiple PSs may occur in same patient
|
||||
- NMDAR and VGKC encephalitis are most common group II subtypes of AE
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- AE: Ill-defined softening, discoloration of gray matter
|
||||
- LE: Hippocampus, cingulate gyrus, pyriform cortex, frontal orbital surface of temporal lobe, insula, amygdala; typically bilateral
|
||||
- PCD: Cerebellar atrophy, gyral thinning
|
||||
- Brainstem encephalitis: Brainstem softening
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- AE: Neuronal loss, reactive gliosis, perivascular infiltration of lymphocytes, microglial nodules
|
||||
- No neoplasm and no viral inclusions
|
||||
- PCD: Purkinje cell loss, microglial proliferation, Bergmann glia hyperplasia, decrease in granule cells
|
||||
- Brainstem encephalitis: Perivascular inflammatory infiltrates, glial nodules, neuronophagia
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- AE: Memory loss, cognitive dysfunction, dementia, psychological features (anxiety, depression, hallucinations), seizures; subacute presentation
|
||||
- PCD: Ataxia, incoordination, dysarthria, nystagmus
|
||||
- In patients > 50 years, cerebellar degeneration is paraneoplastic in 50% of cases, often precedes remote malignancy
|
||||
- Brainstem encephalitis: Brainstem dysfunction including cranial nerve palsies, visual changes
|
||||
- PSs represent spectrum of neurologic manifestations
|
||||
- In patients with known primary tumor, must exclude other complications
|
||||
- Metastases, infection, metabolic disorder, chemotherapy effects
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- Up to 60% of LE patients have no known primary tumor at presentation, many have no tumor found at work-up
|
||||
- Identification of antineuronal antibodies in serum or cerebrospinal fluid (CSF) facilitates diagnosis of PS and primary cancer
|
||||
- AE may occur as complication of cancer treatment (immune checkpoint inhibitors)
|
||||
- Primary neoplasms
|
||||
- LE
|
||||
- Most common: Small cell lung carcinoma
|
||||
- Other: Gastrointestinal, genitourinary (ovary > renal > uterus), lymphoma, breast, testicular, thymus, neuroblastoma (pediatric)
|
||||
- 90% have positive CSF (pleocytosis, increased protein, oligoclonal bands)
|
||||
- EEG reveals involvement of temporal lobes
|
||||
- PCD
|
||||
- Genitourinary (ovary), breast, lung, lymphoma
|
||||
- Opsoclonus myoclonus
|
||||
- Neuroblastoma, lung cancer
|
||||
- Lambert-Eaton myasthenic syndrome
|
||||
- Small cell lung cancer
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Sex
|
||||
|
||||
|
||||
- No sex predominance
|
||||
- Age: Occurs at all ages, most commonly adults
|
||||
- Epidemiology: < 1% of patients with systemic cancers develop paraneoplastic syndrome
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- AE has variable prognosis
|
||||
- Prognosis of PS may relate to primary neoplasm
|
||||
- Relates to type of paraneoplastic syndrome
|
||||
- Slow, long-term cognitive decline (LE)
|
||||
- Progressive ataxia, weakness (PCD, spinal cord degeneration)
|
||||
- Some reports suggest patients with PSs have more indolent primary tumor growth than those without
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- AE often treated with immunotherapy (IV steroids, plasma exchange, IVIg) ± rituximab or cyclophosphamide
|
||||
- Treatment of primary malignancy may improve neurologic symptoms of PS
|
||||
- Primary neoplasm resected, ± chemoradiation
|
||||
- Treatment of PS is variable
|
||||
- Treatment of primary tumor is best therapy
|
||||
- ± steroids, immunoglobulins, plasmapheresis
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- LE is only PS with defined imaging features
|
||||
- PS are often clinically evident before diagnosis of primary tumor
|
||||
- Repeat MR if initial scan normal and high clinical suspicion, as initial MR often normal in LE
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- Herpes encephalitis mimics LE on imaging but has acute presentation
|
||||
- Patients often initially treated with antiviral therapy until HSV titers final
|
||||
- Hemorrhage suggests herpes rather than LE
|
||||
|
||||
89d11c00-03ef-4d5a-aea9-2d9c2669fa58
|
||||
|
||||
## References
|
||||
|
||||
# Selected References
|
||||
|
||||
1. [Iorio R et al: Clinical characteristics and outcome of patients with autoimmune encephalitis: clues for paraneoplastic etiology. Eur J Neurol. ePub, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32412135%5Bpmid%5D)
|
||||
1. [Mongay-Ochoa N et al: Anti-Hu-associated paraneoplastic syndromes triggered by immune-checkpoint inhibitor treatment. J Neurol. ePub, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32451614%5Bpmid%5D)
|
||||
1. [Vogrig A et al: Central nervous system complications associated with immune checkpoint inhibitors. J Neurol Neurosurg Psychiatry. ePub, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32312871%5Bpmid%5D)
|
||||
1. [Bradshaw MJ et al: An overview of autoimmune and paraneoplastic encephalitides. Semin Neurol. 38(3):330-43, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=30011413%5Bpmid%5D)
|
||||
1. [Long JM et al: Autoimmune dementia. Semin Neurol. 38(3):303-15, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=30011411%5Bpmid%5D)
|
||||
1. [Kelley BP et al: Autoimmune encephalitis: pathophysiology and imaging review of an overlooked diagnosis. AJNR Am J Neuroradiol. 38(6):1070-8, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28183838%5Bpmid%5D)
|
||||
1. [da Rocha AJ et al: Recognizing Autoimmune-Mediated Encephalitis in the Differential Diagnosis of Limbic Disorders. AJNR Am J Neuroradiol. 36(12):2196-205, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=26381566%5Bpmid%5D)
|
||||
1. [Höftberger R et al: Encephalitis and AMPA receptor antibodies: novel findings in a case series of 22 patients. Neurology. 84(24):2403-12, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25979696%5Bpmid%5D)
|
||||
1. [Thomas AC et al: Autoimmune limbic encephalitis detected on FDG brain scan performed for the evaluation of dementia. Clin Nucl Med. 40(4):358-9, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25608163%5Bpmid%5D)
|
||||
1. [Zekeridou A et al: Treatment and outcome of children and adolescents with N-methyl-D-aspartate receptor encephalitis. J Neurol. 262(8):1859-66, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25987208%5Bpmid%5D)
|
||||
1. [Kotsenas AL et al: MRI findings in autoimmune voltage-gated potassium channel complex encephalitis with seizures: one potential etiology for mesial temporal sclerosis. AJNR Am J Neuroradiol. 35(1):84-9, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=23868165%5Bpmid%5D)
|
||||
1. [Masangkay N et al: Brain 18F-FDG-PET characteristics in patients with paraneoplastic neurological syndrome and its correlation with clinical and MRI findings. Nucl Med Commun. 35(10):1038-46, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=25023997%5Bpmid%5D)
|
||||
1. [Sarria-Estrada S et al: Neuroimaging in status epilepticus secondary to paraneoplastic autoimmune encephalitis. Clin Radiol. 69(8):795-803, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24824979%5Bpmid%5D)
|
||||
1. [Baumgartner A et al: Cerebral FDG-PET and MRI findings in autoimmune limbic encephalitis: correlation with autoantibody types. J Neurol. 260(11):2744-53, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23900756%5Bpmid%5D)
|
||||
1. [Aye MM et al: CD8 positive T-cell infiltration in the dentate nucleus of paraneoplastic cerebellar degeneration. J Neuroimmunol. 208(1-2):136-40, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19217169%5Bpmid%5D)
|
||||
1. [Berger JR et al: A brainstem paraneoplastic syndrome associated with prostate cancer. J Neurol Neurosurg Psychiatry. 80(8):934-5, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19608787%5Bpmid%5D)
|
||||
1. [Damek DM: Cerebral edema, altered mental status, seizures, acute stroke, leptomeningeal metastases, and paraneoplastic syndrome. Emerg Med Clin North Am. 27(2):209-29, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19447307%5Bpmid%5D)
|
||||
1. [Honnorat J et al: Onco-neural antibodies and tumour type determine survival and neurological symptoms in paraneoplastic neurological syndromes with Hu or CV2/CRMP5 antibodies. J Neurol Neurosurg Psychiatry. 80(4):412-6, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=18931014%5Bpmid%5D)
|
||||
1. [Jaster JH: Reversible autoimmune encephalopathy spectrum. Arch Neurol. 66(7):916, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19597101%5Bpmid%5D)
|
||||
1. [Khan NL et al: Histopathology of VGKC antibody-associated limbic encephalitis. Neurology. 72(19):1703-5, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19433746%5Bpmid%5D)
|
||||
1. [Kröll-Seger J et al: Non-paraneoplastic limbic encephalitis associated with antibodies to potassium channels leading to bilateral hippocampal sclerosis in a pre-pubertal girl. Epileptic Disord. 11(1):54-9, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19251579%5Bpmid%5D)
|
||||
1. [McKeon A et al: Reversible extralimbic paraneoplastic encephalopathies with large abnormalities on magnetic resonance images. Arch Neurol. 66(2):268-71, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19204167%5Bpmid%5D)
|
||||
1. [Modoni A et al: Successful treatment of acute autoimmune limbic encephalitis with negative VGKC and NMDAR antibodies. Cogn Behav Neurol. 22(1):63-6, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19372772%5Bpmid%5D)
|
||||
1. [Saiz A et al: Anti-Hu-associated brainstem encephalitis. J Neurol Neurosurg Psychiatry. 80(4):404-7, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19015226%5Bpmid%5D)
|
||||
1. [Uribe-Uribe NO et al: Paraneoplastic sensory neuropathy associated with small cell carcinoma of the gallbladder. Ann Diagn Pathol. 13(2):124-6, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19302962%5Bpmid%5D)
|
||||
1. [Anderson NE et al: Limbic encephalitis - a review. J Clin Neurosci. 15(9):961-71, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18411052%5Bpmid%5D)
|
||||
1. [Basu S et al: Role of FDG-PET in the clinical management of paraneoplastic neurological syndrome: detection of the underlying malignancy and the brain PET-MRI correlates. Mol Imaging Biol. 10(3):131-7, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18297363%5Bpmid%5D)
|
||||
1. [Blaes F et al: Autoantibodies in childhood opsoclonus-myoclonus syndrome. J Neuroimmunol. 201-202:221-6, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18687475%5Bpmid%5D)
|
||||
1. [Corapcioglu F et al: Response to rituximab and prednisolone for opsoclonus-myoclonus-ataxia syndrome in a child with ganglioneuroblastoma. Pediatr Hematol Oncol. 25(8):756-61, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=19065442%5Bpmid%5D)
|
||||
1. [Dalakas MC: Invited article: inhibition of B cell functions: implications for neurology. Neurology. 70(23):2252-60, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18519875%5Bpmid%5D)
|
||||
1. [Eker A et al: Testicular teratoma and anti-N-methyl-D-aspartate receptor-associated encephalitis. J Neurol Neurosurg Psychiatry. 79(9):1082-3, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18708569%5Bpmid%5D)
|
||||
1. [Fitzpatrick AS et al: Opsoclonus-myoclonus syndrome associated with benign ovarian teratoma. Neurology. 70(15):1292-3, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18391162%5Bpmid%5D)
|
||||
1. [Geschwind MD et al: Voltage-gated potassium channel autoimmunity mimicking creutzfeldt-jakob disease. Arch Neurol. 65(10):1341-6, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18852349%5Bpmid%5D)
|
||||
1. [Hassan KA et al: Long-term survival in paraneoplastic opsoclonus-myoclonus syndrome associated with small cell lung cancer. J Neuroophthalmol. 28(1):27-30, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18347455%5Bpmid%5D)
|
||||
1. [Jarius S et al: Relative frequency of VGKC and 'classical' paraneoplastic antibodies in patients with limbic encephalitis. J Neurol. 255(7):1100-1, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18574619%5Bpmid%5D)
|
||||
1. [Johnson V et al: Immune mediated neurologic dysfunction as a paraneoplastic syndrome in renal cell carcinoma. J Neurooncol. 90(3):279-81, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18726185%5Bpmid%5D)
|
||||
1. [Ko MW et al: Neuro-ophthalmologic manifestations of paraneoplastic syndromes. J Neuroophthalmol. 28(1):58-68, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18347462%5Bpmid%5D)
|
||||
1. [Musunuru K et al: Paraneoplastic opsoclonus-myoclonus ataxia associated with non-small-cell lung carcinoma. J Neurooncol. 90(2):213-6, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18618225%5Bpmid%5D)
|
||||
1. [Novillo-López ME et al: Treatment-responsive subacute limbic encephalitis and NMDA receptor antibodies in a man. Neurology. 70(9):728-9, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18299525%5Bpmid%5D)
|
||||
1. [Pellkofer HL et al: Lambert-eaton myasthenic syndrome differential reactivity of tumor versus non-tumor patients to subunits of the voltage-gated calcium channel. J Neuroimmunol. 204(1-2):136-9, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18809213%5Bpmid%5D)
|
||||
1. [Sabater L et al: SOX1 antibodies are markers of paraneoplastic Lambert-Eaton myasthenic syndrome. Neurology. 70(12):924-8, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18032743%5Bpmid%5D)
|
||||
1. [Sekiguchi Y et al: Potassium channel antibody-associated encephalitis with hypothalamic lesions and intestinal pseudo-obstruction. J Neurol Sci. 269(1-2):176-9, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18378260%5Bpmid%5D)
|
||||
1. [Tan KM et al: Clinical spectrum of voltage-gated potassium channel autoimmunity. Neurology. 70(20):1883-90, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18474843%5Bpmid%5D)
|
||||
1. [Darnell RB et al: Paraneoplastic syndromes affecting the nervous system. Semin Oncol. 33(3):270-98, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16769417%5Bpmid%5D)
|
||||
1. [Dropcho EJ: Update on paraneoplastic syndromes. Curr Opin Neurol. 18(3):331-6, 2005](http://www.ncbi.nlm.nih.gov/pubmed/?term=15891421%5Bpmid%5D)
|
||||
1. [Dadparvar S et al: Paraneoplastic encephalitis associated with cystic teratoma is detected by fluorodeoxyglucose positron emission tomography with negative magnetic resonance image findings. Clin Nucl Med. 28(11):893-6, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=14578703%5Bpmid%5D)
|
||||
1. [Messori A et al: Resolution of limbic encephalitis with detection and treatment of lung cancer: clinical-radiological correlation. Eur J Radiol. 45(1): 78-80, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12499067%5Bpmid%5D)
|
||||
1. [Barnett M et al: Paraneoplastic brain stem encephalitis in a woman with anti-Ma2 antibody. J Neurol Neurosurg Psychiatry. 70(2):222-5, 2001](http://www.ncbi.nlm.nih.gov/pubmed/?term=11160472%5Bpmid%5D)
|
||||
1. [Gultekin SH et al: Paraneoplastic limbic encephalitis: neurological symptoms, immunological findings and tumour association in 50 patients. Brain. 123 ( Pt 7):1481-94, 2000](http://www.ncbi.nlm.nih.gov/pubmed/?term=10869059%5Bpmid%5D)
|
||||
1. [Dalmau J et al: Paraneoplastic neurologic syndromes: pathogenesis and physiopathology. Brain Pathol. 9(2):275-84, 1999](http://www.ncbi.nlm.nih.gov/pubmed/?term=10219745%5Bpmid%5D)
|
||||
1. [Scaravilli F et al: The neuropathology of paraneoplastic syndromes. Brain Pathol. 9(2):251-60, 1999](http://www.ncbi.nlm.nih.gov/pubmed/?term=10219743%5Bpmid%5D)
|
||||
1. [Voltz R et al: A serologic marker of paraneoplastic limbic and brain-stem encephalitis in patients with testicular cancer. N Engl J Med. 340(23): 1788-95, 1999](http://www.ncbi.nlm.nih.gov/pubmed/?term=10362822%5Bpmid%5D)
|
||||
|
||||
|
||||
## Images
|
||||
|
||||
|
||||
### Selected Images
|
||||
|
||||
|
||||
*Axial FLAIR MR shows abnormal hyperintensity in the bilateral medial temporal lobes <img src='/img/arrows/CS.png'/>, characteristic of limbic encephalitis (LE), the most common paraneoplastic syndrome. Bilateral involvement is typical of limbic encephalitis.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows abnormal hyperintensity in the bilateral medial temporal lobes <img src='/img/arrows/CS.png'/>, characteristic of limbic encephalitis (LE), the most common paraneoplastic syndrome. Bilateral involvement is typical of limbic encephalitis.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows abnormal hyperintensity in the bilateral medial temporal lobes <img src='/img/arrows/CS.png'/>, characteristic of limbic encephalitis (LE), the most common paraneoplastic syndrome. Bilateral involvement is typical of limbic encephalitis.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows no significant enhancement in the medial temporal lobes. Enhancement is often present in limbic encephalitis. The patient's symptoms often improve after treatment of the primary tumor.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows no significant enhancement in the medial temporal lobes. Enhancement is often present in limbic encephalitis. The patient's symptoms often improve after treatment of the primary tumor.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a 61 year old with multiple myeloma who presented with seizures shows abnormal hyperintensity <img src='/img/arrows/CS.png'/> in the cortex and subcortical white matter of the temporal lobes.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a 61 year old with multiple myeloma who presented with seizures shows abnormal hyperintensity <img src='/img/arrows/CS.png'/> in the cortex and subcortical white matter of the temporal lobes.*
|
||||
|
||||
|
||||
*Axial T1 C+ FS MR in the same patient shows no enhancement. Differential considerations include autoimmune encephalitis (AE), acute demyelinating encephalomyelitis (ADEM), viral encephalitis, and vasculitis in this case. AE related to GABAr was diagnosed by CSF and serum markers.*
|
||||
|
||||
|
||||
*Axial T1 C+ FS MR in the same patient shows no enhancement. Differential considerations include autoimmune encephalitis (AE), acute demyelinating encephalomyelitis (ADEM), viral encephalitis, and vasculitis in this case. AE related to GABAr was diagnosed by CSF and serum markers.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a 71 year old with altered mental status shows abnormal hyperintensity in the left temporal lobe <img src='/img/arrows/CS.png'/>. Differential considerations include infectious, inflammatory, and neoplastic etiologies. GAD65 AE was diagnosed at brain biopsy.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a 71 year old with altered mental status shows abnormal hyperintensity in the left temporal lobe <img src='/img/arrows/CS.png'/>. Differential considerations include infectious, inflammatory, and neoplastic etiologies. GAD65 AE was diagnosed at brain biopsy.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows hyperintensity in the medial temporal lobes <img src='/img/arrows/CS.png'/> in this patient with subacute dementia and voltage-gated potassium channel (VGKC) autoimmunity. VGKC may occur with or without a primary neoplasm and may have an LE pattern.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows hyperintensity in the medial temporal lobes <img src='/img/arrows/CS.png'/> in this patient with subacute dementia and voltage-gated potassium channel (VGKC) autoimmunity. VGKC may occur with or without a primary neoplasm and may have an LE pattern.*
|
||||
|
||||
|
||||
*Axial T2 MR shows midbrain hyperintensity <img src='/img/arrows/CS.png'/> related to brainstem encephalitis, which is characterized by hyperintensity in the midbrain, pons, cerebellar peduncle, and basal ganglia.*
|
||||
|
||||
|
||||
*Axial T2 MR shows midbrain hyperintensity <img src='/img/arrows/CS.png'/> related to brainstem encephalitis, which is characterized by hyperintensity in the midbrain, pons, cerebellar peduncle, and basal ganglia.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows patchy enhancement of the midbrain lesions <img src='/img/arrows/CS.png'/> and the medial temporal lobe <img src='/img/arrows/CO.png'/>. This patient was diagnosed with LE with new brainstem symptoms. Multiple paraneoplastic syndromes may occur in the same patient.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows patchy enhancement of the midbrain lesions <img src='/img/arrows/CS.png'/> and the medial temporal lobe <img src='/img/arrows/CO.png'/>. This patient was diagnosed with LE with new brainstem symptoms. Multiple paraneoplastic syndromes may occur in the same patient.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows abnormal hyperintensity in the medial temporal lobes bilaterally, related to LE. As imaging mimics herpes encephalitis, most patients are initially treated with antiviral therapy until HSV titers are found to be negative. < 1% of cancer patients develop a paraneoplastic syndrome.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows abnormal hyperintensity in the medial temporal lobes bilaterally, related to LE. As imaging mimics herpes encephalitis, most patients are initially treated with antiviral therapy until HSV titers are found to be negative. < 1% of cancer patients develop a paraneoplastic syndrome.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows patchy enhancement <img src='/img/arrows/CO.png'/> of the medial temporal lobes. LE is the only paraneoplastic syndrome with defined imaging features.*
|
||||
|
||||
|
||||
### Additional Images
|
||||
|
||||
|
||||
*Axial T2 MR shows abnormal hyperintensity in the right medial temporal lobe <img src='/img/arrows/CO.png'/>, typical of limbic encephalitis. Note the abnormal hyperintensity in the midbrain <img src='/img/arrows/CS.png'/>, indicative of brainstem encephalitis. Brainstem encephalitis is a very uncommon paraneoplastic syndrome. Multiple paraneoplastic syndromes can occur in the same patient.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with subacute dementia and lung cancer shows hyperintensity within the medial temporal lobes, classic for limbic encephalitis. Imaging mimics herpes encephalitis.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR shows subtle patchy enhancement of the medial temporal lobes bilaterally <img src='/img/arrows/CS.png'/>, which is a typical enhancement pattern for limbic encephalitis. Bilateral involvement is common.*
|
||||
|
||||
|
||||
*Coronal T2 MR in a patient with limbic encephalitis shows abnormal hyperintensity in the medial temporal lobes and right insula <img src='/img/arrows/CS.png'/> in this patient with severe memory loss and dementia. Symptoms improved after the removal of the primary tumor.*
|
||||
|
||||
|
||||
*Coronal T1 C+ MR shows abnormal gyriform enhancement in the medial temporal lobes and left insula <img src='/img/arrows/CS.png'/>. The more typical patchy enhancement pattern of limbic encephalitis is seen in the hippocampi bilaterally.*
|
||||
|
||||
|
||||
*Axial T1 MR shows hyperintensity representing blood products in the medial temporal lobes in this patient with treated lung cancer and limbic encephalitis. Blood products are rare in limbic encephalitis, in which imaging mimics herpes encephalitis.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows abnormal hyperintensity in the right medial temporal lobe and midbrain in this patient with a history of limbic encephalitis and new brainstem symptoms positive for anti-Hu autoantibody.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR shows enhancement in the medial temporal lobes and left anterior temporal lobe related to limbic encephalitis. As imaging mimics herpes encephalitis, most patients are initially treated with antiviral therapy until HSV titers are found to be negative.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows abnormal hyperintensity in the medial temporal lobes bilaterally, characteristic of limbic encephalitis, the most common paraneoplastic syndrome. Bilateral involvement is typical of limbic encephalitis.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in an older adult with small cell lung cancer and subacute dementia shows striking hyperintensity in the right insula <img src='/img/arrows/WO.png'/>.*
|
||||
|
||||
|
||||
*Coronal T2 MR in the same patient shows abnormal hyperintensity in both medial temporal lobes <img src='/img/arrows/WS.png'/> and right insular cortex <img src='/img/arrows/WO.png'/>. Imaging of limbic encephalitis mimics that of herpes encephalitis; however, patients with limbic encephalitis have a subacute presentation. Hemorrhage suggests herpes rather than limbic encephalitis.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows abnormal hyperintensity in the medial temporal lobes bilaterally, characteristic of limbic encephalitis, the most common paraneoplastic syndrome. Bilateral involvement is typical of limbic encephalitis.*
|
||||
|
||||
@@ -0,0 +1,395 @@
|
||||
---
|
||||
title: "CIDP"
|
||||
docid: "12e4033c-edc8-46ff-8081-3acc433cda78"
|
||||
authors:
|
||||
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name: "CIDP"
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imageCount: 12
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lastUpdated: "06/08/20"
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pageDescription: "CIDP"
|
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pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Infectious, Inflammatory, and Demyelinating Disease, Inflammatory and Demyelinating Disease, CIDP"
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pageTitle: "CIDP | STATdx"
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- "Infectious, Inflammatory, and Demyelinating Disease"
|
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- "Inflammatory and Demyelinating Disease"
|
||||
- "CIDP"
|
||||
---
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Clinically heterogeneous, grossly symmetric, sensory & motor neuropathy evolving as monophasic, relapsing, or progressive disorder
|
||||
- Develops over > 8 weeks
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Sagittal FLAIR may reveal hyperintense brain lesions similar to multiple sclerosis
|
||||
- Enlargement & abnormal T2 hyperintensity of nerve roots, plexi, or peripheral nerves
|
||||
- ↑ nerve root diameter, cross-sectional area (CSA), & volume
|
||||
- Spinal nerve roots & peripheral nerves (extraforaminal > intradural)
|
||||
- Lumbar > cervical, brachial plexus, thoracic/intercostal > cranial nerve
|
||||
- Fair degree of CSA correlation between high-resonance nerve ultrasound (HRUS) & MR neurography (MRN)
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Guillain-Barré (AIDP)
|
||||
- Inherited demyelinating neuropathy (Charcot-Marie-Tooth)
|
||||
- Neurofibromatosis type 1, schwannomatosis
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- Autoimmune disease of cellular & humoral immunity
|
||||
- Hallmarks of CIDP: Enlarged nerves with onion bulb formations, demyelination
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Usually **clinical**diagnosis based on progressive weakness/sensory loss & response to steroids
|
||||
- Typical: Symmetric proximal & distal weakness, sensory loss
|
||||
- Abnormal EMG/NCV: Key electrophysiologic features → nerve conduction block, slowed conduction velocities suggestive of demyelination
|
||||
- Diagnosis relies primarily on clinical, electrophysiologic examination supplemented by nerve biopsy
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Chronic inflammatory demyelinating polyneuropathy (CIDP)
|
||||
- ## Synonyms
|
||||
|
||||
|
||||
- Chronic inflammatory demyelinating polyradiculoneuropathy
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Chronic acquired, immune-mediated demyelinating neuropathy characterized by relapsing or progressive muscle weakness ± sensory loss
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Enlargement & abnormal T2 hyperintensity of nerve roots, plexi, or peripheral nerves
|
||||
- Spinal nerve roots & peripheral nerves (extraforaminal > intradural)
|
||||
- Lumbar > cervical, brachial plexus, thoracic/intercostal > cranial nerves (CNs)
|
||||
- ### Size
|
||||
|
||||
|
||||
- Nerve size varies; small → very large
|
||||
- Mean diameter of spinal nerve roots in CIDP: Cervical 6-6.8 mm; lumbosacral 7.3-10.4 mm
|
||||
- 5-mm best cut-off value of C6, C7, C8 nerve root diameters to distinguish CIDP patients from controls
|
||||
- CIDP nerves larger volumes, which positively correlate with disease duration
|
||||
- Recent MR neurography (MRN) of L3-S1 nerve roots of lumbosacral plexus using 3D multiple echo recalled gradient-echo (3D MERGE) sequence showed
|
||||
- ↑ mean cross-sectional area (CSA): 28.04 ± 8.55 mm² in CIDP (14.91 ± 2.36 square mm² in normal); optimal cut-off value 19.20 mm²
|
||||
- ### Morphology
|
||||
|
||||
|
||||
- Focal or diffuse fusiform enlargement of cauda equina, nerve roots/plexi, & peripheral nerves
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- ### NECT
|
||||
|
||||
|
||||
- Isodense nerve enlargement
|
||||
- ### CECT
|
||||
|
||||
|
||||
- Mild to moderate nerve enhancement
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- Enlargement, abnormal hyperintensity of intradural & extradural spinal nerves/branches
|
||||
- ### FLAIR
|
||||
|
||||
|
||||
- Sagittal FLAIR may reveal hyperintense brain lesions similar to multiple sclerosis (MS)
|
||||
- ### DWI
|
||||
|
||||
|
||||
- Diffusion-weighted MRN
|
||||
- DTI: ↓ nerve fractional anisotropy (FA) (mean 0.42 ± 0.08) in CIDP compared to healthy controls (0.52 ± 0.04)
|
||||
- ↓ FA due to ↑ radial diffusivity (RD); axial diffusivity (AD) not significant
|
||||
- FA & RD correlate strongly with electrophysiological markers of demyelination
|
||||
- ### T1WI C+
|
||||
|
||||
|
||||
- Mild to moderate nerve enhancement
|
||||
- ## Ultrasonographic Findings
|
||||
|
||||
|
||||
- ### Grayscale ultrasound
|
||||
|
||||
|
||||
- Hypoechoic, hypertrophic nerves
|
||||
- Fair degree of CSA correlation in high resonance nerve US (HRUS) & MRN of cervical plexus, & peripheral nerves in CIDP
|
||||
- CSA in HRUS correlate well with markers of nerve integrity, such as ↓ FA in DTI & with ↑ T2 signal
|
||||
- HRUS-CSA of interscalene brachial plexus correlated significantly with MRN-CSA & T2 signal of L5 & S1 lumbar plexus roots
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MRN, T2WI, enhanced coronal & axial T1WI sequences with fat suppression best delineate nerve lesions
|
||||
- Brain MR to detect subclinical CNS demyelination
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- ## Conditions Recently Proposed to be Included Under CIDP Syndrome
|
||||
|
||||
|
||||
- Antimyelin associated glycoprotein (MAG) neuropathy
|
||||
- Chronic neuropathies associated with IgG4 antibodies against paranodal/nodal proteins; chronic immune sensory polyradiculopathy (CISP); multifocal motor neuropathy
|
||||
- [Guillain-Barré (Acute Inflammatory Demyelinating Polyneuropathy)](/document/guillain-barr-spectrum-disorders/c1f52a65-920e-4e28-8a75-07dfa208f290)
|
||||
- Pial, nerve root enhancement similar to CIDP
|
||||
- Differs from CIDP in onset duration, clinical course
|
||||
- Acute onset of ascending paralysis with relative sensory preservation
|
||||
- [Hereditary Motor and Sensory Neuropathy](/document/hypertrophic-neuropathy/e246f4d1-0262-4ca7-b8e1-6f2a4bd67c06)
|
||||
- Also called Charcot-Marie-Tooth (CMT) disease
|
||||
- CMT1, CMT 3 (Dejerine-Sottas disease) CMT4, CMTX1
|
||||
- Genetic testing, clinical phenotype distinguish from CIDP
|
||||
- [Neurofibromatosis Type 1](/document/neurofibromatosis-type-1-spine/89236653-e750-4fa7-b2b1-0a3c4ed31a87)
|
||||
- Diffuse nerve root enlargement, enhancement
|
||||
- Genetic testing & distinctive clinical stigmata to distinguish
|
||||
- ## Lateral Meningocele
|
||||
|
||||
|
||||
- CSF density/signal intensity (not solid) ± foraminal enlargement, dural ectasia
|
||||
- Usually coexisting NF1 or connective tissue disorder (Marfan syndrome)
|
||||
- ## Schwannomatosis
|
||||
|
||||
|
||||
- Multiple schwannomas of peripheral nerves & CNs [nonvestibular schwannomas (nVS)]
|
||||
- However, unilateral VS described with germline mutations of Schwannomatosis in SMARCB1 & LZTR1
|
||||
- ## Other Clinical Differential Diagnosis
|
||||
|
||||
|
||||
- Diabetic neuropathy, amyloid neuropathy due to TTR mutations, vasculitic neuropathy, POEMS syndrome
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Exact pathogenesis of CIDP unclear; involves both cellular & humoral immune factors
|
||||
- Polyneuropathies co-occurring with MS: Underdiagnosed; extra disability burden; includes CIDP
|
||||
- 1/3 of MS-CIDP cases with serum testing show IgG4 autoantibodies to neurofascin-155
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Extensive fusiform nerve enlargement ± gross onion bulb formations
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- Large nerve, onion bulb formations, demyelination
|
||||
- Macrophage, T-cell infiltration → perivascular inflammatory infiltrates, nerve demyelination & remyelination
|
||||
- Onion bulb formation: Excessive Schwann cell process proliferation → repetitive demyelination/remyelination
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Mixed sensorimotor neuropathy; typical form: Symmetric proximal & distal weakness, sensory loss
|
||||
- Rarer atypical form (Lewis-Sumner syndrome)
|
||||
- Predominantly uni- or multifocal as well as distal
|
||||
- CNs are occasionally affected, with particular tropism for CNVII, but ophthalmoplegia or bulbar weakness can be present
|
||||
- ### Other signs/symptoms
|
||||
|
||||
|
||||
- Chronic progressive: Progressively deteriorate until treatment is given
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Sex
|
||||
|
||||
|
||||
- M = F
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Average disease duration: 7.5 years
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- European Federation of Neurological Societies/Peripheral Nerve Society Guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy; immunomodulation or immunosuppression therapy
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- Consider CIDP in differential of nerve root/peripheral nerve enlargement
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- MR findings imperfectly correlate with clinical disease activity/severity, laboratory findings
|
||||
|
||||
0f953548-b230-4137-9147-51d6ed147c6c
|
||||
|
||||
## References
|
||||
|
||||
# Selected References
|
||||
|
||||
1. [Campagnolo M et al: Sporadic hereditary neuropathies misdiagnosed as chronic inflammatory demyelinating polyradiculoneuropathy: Pitfalls and red flags. J Peripher Nerv Syst. 25(1):19-26, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=31919945%5Bpmid%5D)
|
||||
1. [Van den Bergh PYK et al: Boundaries of chronic inflammatory demyelinating polyradiculoneuropathy. J Peripher Nerv Syst. 25(1):4-8, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=31981273%5Bpmid%5D)
|
||||
1. [Wu F et al: MR neurography of lumbosacral nerve roots: diagnostic value in chronic inflammatory demyelinating polyradiculoneuropathy and correlation with electrophysiological parameters. Eur J Radiol. 124:108816, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=31923808%5Bpmid%5D)
|
||||
1. [Suanprasert N et al: Polyneuropathies and chronic inflammatory demyelinating polyradiculoneuropathy in multiple sclerosis. Mult Scler Relat Disord. 30:284-90, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30870805%5Bpmid%5D)
|
||||
1. [Pitarokoili K et al: High-resolution nerve ultrasound and magnetic resonance neurography as complementary neuroimaging tools for chronic inflammatory demyelinating polyneuropathy. Ther Adv Neurol Disord. 11:1756286418759974, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29552093%5Bpmid%5D)
|
||||
1. [Ishikawa T et al: MR neurography for the evaluation of CIDP. Muscle Nerve. 55(4):483-9, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=27500391%5Bpmid%5D)
|
||||
1. [Kronlage M et al: Large coverage MR neurography in CIDP: diagnostic accuracy and electrophysiological correlation. J Neurol. 264(7):1434-43, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28620719%5Bpmid%5D)
|
||||
1. [Kronlage M et al: Diffusion tensor imaging in chronic inflammatory demyelinating polyneuropathy: diagnostic accuracy and correlation with electrophysiology. Invest Radiol. 52(11):701-7, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28574858%5Bpmid%5D)
|
||||
1. [Said G et al: Chronic inflammatory demyelinative polyneuropathy. Handb Clin Neurol. 115:403-13, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23931792%5Bpmid%5D)
|
||||
1. [Mahdi-Rogers M et al: Overview of the pathogenesis and treatment of chronic inflammatory demyelinating polyneuropathy with intravenous immunoglobulins. Biologics. 4:45-9, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=20376173%5Bpmid%5D)
|
||||
1. [Tracy JA et al: Investigations and treatment of chronic inflammatory demyelinating polyradiculoneuropathy and other inflammatory demyelinating polyneuropathies. Curr Opin Neurol. 23(3):242-8, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=20389243%5Bpmid%5D)
|
||||
1. [Vallat JM et al: Chronic inflammatory demyelinating polyradiculoneuropathy: diagnostic and therapeutic challenges for a treatable condition. Lancet Neurol. 9(4):402-12, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=20298964%5Bpmid%5D)
|
||||
1. [Van den Bergh PY et al: European Federation of Neurological Societies/Peripheral Nerve Society guideline on management of chronic inflammatory demyelinating polyradiculoneuropathy: report of a joint task force of the European Federation of Neurological Societies and the Peripheral Nerve Society - first revision. Eur J Neurol. 17(3):356-63, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=20456730%5Bpmid%5D)
|
||||
1. [Brannagan TH 3rd: Current treatments of chronic immune-mediated demyelinating polyneuropathies. Muscle Nerve. 39(5):563-78, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19301378%5Bpmid%5D)
|
||||
1. [Laughlin RS et al: Incidence and prevalence of CIDP and the association of diabetes mellitus. Neurology. 73(1):39-45, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19564582%5Bpmid%5D)
|
||||
1. [Tazawa K et al: Spinal nerve root hypertrophy on MRI: clinical significance in the diagnosis of chronic inflammatory demyelinating polyradiculoneuropathy. Intern Med. 47(23):2019-24, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=19043253%5Bpmid%5D)
|
||||
1. [Tsuchiya K et al: Demonstration of spinal cord and nerve root abnormalities by diffusion neurography. J Comput Assist Tomogr. 32(2):286-90, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18379319%5Bpmid%5D)
|
||||
1. [Said G: Chronic inflammatory demyelinating polyneuropathy. Neuromuscul Disord. 16(5):293-303, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16631367%5Bpmid%5D)
|
||||
1. [Köller H et al: Chronic inflammatory demyelinating polyneuropathy--update on pathogenesis, diagnostic criteria and therapy. Curr Opin Neurol. 18(3):273-8, 2005](http://www.ncbi.nlm.nih.gov/pubmed/?term=15891411%5Bpmid%5D)
|
||||
1. [Matsuoka N et al: Detection of cervical nerve root hypertrophy by ultrasonography in chronic inflammatory demyelinating polyradiculoneuropathy. J Neurol Sci. 219(1-2):15-21, 2004](http://www.ncbi.nlm.nih.gov/pubmed/?term=15050432%5Bpmid%5D)
|
||||
1. [Cocito D et al: Different clinical, electrophysiological and immunological features of CIDP associated with paraproteinaemia. Acta Neurol Scand. 108(4):274-80, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12956862%5Bpmid%5D)
|
||||
1. [Fee DB et al: Resolution of chronic inflammatory demyelinating polyneuropathy-associated central nervous system lesions after treatment with intravenous immunoglobulin. J Peripher Nerv Syst. 8(3):155-8, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12904236%5Bpmid%5D)
|
||||
1. [Haq RU et al: Chronic inflammatory demyelinating polyradiculoneuropathy in diabetic patients. Muscle Nerve. 27(4):465-70, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12661048%5Bpmid%5D)
|
||||
1. [Magda P et al: Comparison of electrodiagnostic abnormalities and criteria in a cohort of patients with chronic inflammatory demyelinating polyneuropathy. Arch Neurol. 60(12):1755-9, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=14676052%5Bpmid%5D)
|
||||
1. [Odaka M et al: Patients with chronic inflammatory demyelinating polyneuropathy initially diagnosed as Guillain-Barre syndrome. J Neurol. 250(8):913-6, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12928908%5Bpmid%5D)
|
||||
1. [Oguz B et al: Diffuse spinal and intercostal nerve involvement in chronic inflammatory demyelinating polyradiculoneuropathy: MRI findings. Eur Radiol. 13 Suppl 4:L230-4, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=15018192%5Bpmid%5D)
|
||||
1. [Press R et al: Aberrated levels of cerebrospinal fluid chemokines in Guillain-Barre syndrome and chronic inflammatory demyelinating polyradiculoneuropathy. J Clin Immunol. 23(4):259-67, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12959218%5Bpmid%5D)
|
||||
1. [Rodriguez-Casero MV et al: Childhood chronic inflammatory demyelinating polyneuropathy with central nervous system demyelination resembling multiple sclerosis. Neuromuscul Disord. 13(2):158-61, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12565914%5Bpmid%5D)
|
||||
1. [Ropper AH: Current treatments for CIDP. Neurology. 60(8 Suppl 3):S16-22, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12707418%5Bpmid%5D)
|
||||
1. [Saperstein DS et al: Current concepts and controversy in chronic inflammatory demyelinating polyneuropathy. Curr Neurol Neurosci Rep. 3(1):57-63, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12507413%5Bpmid%5D)
|
||||
1. [Toyka KV et al: The pathogenesis of CIDP: rationale for treatment with immunomodulatory agents. Neurology. 60(8 Suppl 3):S2-7, 2003](http://www.ncbi.nlm.nih.gov/pubmed/?term=12707416%5Bpmid%5D)
|
||||
1. [Costello F et al: Childhood-onset chronic inflammatory demyelinating polyradiculoneuropathy with cranial nerve involvement. J Child Neurol. 17(11):819-23, 2002](http://www.ncbi.nlm.nih.gov/pubmed/?term=12585721%5Bpmid%5D)
|
||||
1. Cros D: Peripheral Neuropathy. 1st ed. Philadelphia: Lippincott Williams & Wilkins: 432, 2001
|
||||
1. [Sabatelli M et al: Pure motor chronic inflammatory demyelinating polyneuropathy. J Neurol. 248(9):772-7, 2001](http://www.ncbi.nlm.nih.gov/pubmed/?term=11596782%5Bpmid%5D)
|
||||
1. [Saperstein DS et al: Clinical spectrum of chronic acquired demyelinating polyneuropathies. Muscle Nerve. 24(3):311-24, 2001](http://www.ncbi.nlm.nih.gov/pubmed/?term=11353415%5Bpmid%5D)
|
||||
1. [Taniguchi N et al: Sonographic detection of diffuse peripheral nerve hypertrophy in chronic inflammatory demyelinating polyradiculoneuropathy. J Clin Ultrasound. 28(9):488-91, 2000](http://www.ncbi.nlm.nih.gov/pubmed/?term=11056027%5Bpmid%5D)
|
||||
1. [Van den Bergh PY et al: Chronic demyelinating hypertrophic brachial plexus neuropathy. Muscle Nerve. 23(2):283-8, 2000](http://www.ncbi.nlm.nih.gov/pubmed/?term=10639625%5Bpmid%5D)
|
||||
1. [Duarte J et al: Hypertrophy of multiple cranial nerves and spinal roots in chronic inflammatory demyelinating neuropathy. J Neurol Neurosurg Psychiatry. 67(5):685-7, 1999](http://www.ncbi.nlm.nih.gov/pubmed/?term=10519883%5Bpmid%5D)
|
||||
1. [Midroni G et al: MRI of the cauda equina in CIDP: clinical correlations. J Neurol Sci. 170(1):36-44, 1999](http://www.ncbi.nlm.nih.gov/pubmed/?term=10540034%5Bpmid%5D)
|
||||
1. [Mizuno K et al: Chronic inflammatory demyelinating polyradiculoneuropathy with diffuse and massive peripheral nerve hypertrophy: distinctive clinical and magnetic resonance imaging features. Muscle Nerve. 21(6):805-8, 1998](http://www.ncbi.nlm.nih.gov/pubmed/?term=9585338%5Bpmid%5D)
|
||||
1. [Kuwabara S et al: Magnetic resonance imaging at the demyelinative foci in chronic inflammatory demyelinating polyneuropathy. Neurology. 48(4):874-7, 1997](http://www.ncbi.nlm.nih.gov/pubmed/?term=9109870%5Bpmid%5D)
|
||||
1. [Simmons Z et al: Chronic inflammatory demyelinating polyradiculoneuropathy in children: I. Presentation, electrodiagnostic studies, and initial clinical course, with comparison to adults. 20(12):1569-75, 1997](http://www.ncbi.nlm.nih.gov/pubmed/?term=9390670%5Bpmid%5D)
|
||||
1. [Van Es HW et al: Magnetic resonance imaging of the brachial plexus in patients with multifocal motor neuropathy. Neurology. 48(5):1218-24, 1997](http://www.ncbi.nlm.nih.gov/pubmed/?term=9153446%5Bpmid%5D)
|
||||
|
||||
|
||||
## Images
|
||||
|
||||
|
||||
### Selected Images
|
||||
|
||||
|
||||
*Sagittal T1 C+ MR of the cervical spine shows marked hypertrophy and enhancement of all exiting cervical nerve roots <img src='/img/arrows/CS.png'/>. 5 mm is considered an adequate cut-off value of cervical spinal nerve root diameter, discriminating CIDP from controls. Mean diameter of spinal nerve roots in CIDP: Cervical 6-6.8 mm; lumbosacral 7.3-10.4 mm.*
|
||||
|
||||
|
||||
*Sagittal T1 C+ MR of the cervical spine shows marked hypertrophy and enhancement of all exiting cervical nerve roots <img src='/img/arrows/CS.png'/>. 5 mm is considered an adequate cut-off value of cervical spinal nerve root diameter, discriminating CIDP from controls. Mean diameter of spinal nerve roots in CIDP: Cervical 6-6.8 mm; lumbosacral 7.3-10.4 mm.*
|
||||
|
||||
|
||||
*Sagittal T1 C+ MR of the cervical spine shows marked hypertrophy and enhancement of all exiting cervical nerve roots <img src='/img/arrows/CS.png'/>. 5 mm is considered an adequate cut-off value of cervical spinal nerve root diameter, discriminating CIDP from controls. Mean diameter of spinal nerve roots in CIDP: Cervical 6-6.8 mm; lumbosacral 7.3-10.4 mm.*
|
||||
|
||||
|
||||
*Sagittal T2WI MR reveals enlargement and T2 hyperintensity of exiting extradural lumbosacral nerves <img src='/img/arrows/CS.png'/>. High signal of CSF should be excluded while measuring nerve root size/area in T2 MR.*
|
||||
|
||||
|
||||
*Sagittal T2WI MR reveals enlargement and T2 hyperintensity of exiting extradural lumbosacral nerves <img src='/img/arrows/CS.png'/>. High signal of CSF should be excluded while measuring nerve root size/area in T2 MR.*
|
||||
|
||||
|
||||
*Axial T1WI C+ MR depicts enlargement and abnormal enhancement of exiting extradural lumbosacral nerves <img src='/img/arrows/CS.png'/>. Blood-nerve barrier breakdown can cause contrast enhancement. Axon loss associated with demyelination is the most important factor of disability and resistance to treatment. Root hypertrophy also may cause stenosis symptoms.*
|
||||
|
||||
|
||||
*Axial T1WI C+ MR depicts enlargement and abnormal enhancement of exiting extradural lumbosacral nerves <img src='/img/arrows/CS.png'/>. Blood-nerve barrier breakdown can cause contrast enhancement. Axon loss associated with demyelination is the most important factor of disability and resistance to treatment. Root hypertrophy also may cause stenosis symptoms.*
|
||||
|
||||
|
||||
*Sagittal FLAIR MR demonstrates periventricular ovoid hyperintensities <img src='/img/arrows/CO.png'/> in a typical case of marked fusiform CIDP nerve enlargement with brain demyelination.*
|
||||
|
||||
|
||||
*Sagittal FLAIR MR demonstrates periventricular ovoid hyperintensities <img src='/img/arrows/CO.png'/> in a typical case of marked fusiform CIDP nerve enlargement with brain demyelination.*
|
||||
|
||||
|
||||
### Additional Images
|
||||
|
||||
|
||||
*Axial T1WI C+ MR shows thickening and enhancement of ventral and dorsal cauda equina nerve roots <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Axial T1WI C+ MR shows thickening and enhancement of ventral and dorsal cauda equina nerve roots <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Sagittal T2WI MR demonstrates diffuse thickening of the intradural cauda equina nerve roots.*
|
||||
|
||||
|
||||
*Sagittal T2WI MR demonstrates diffuse thickening of the intradural cauda equina nerve roots.*
|
||||
|
||||
|
||||
*Sagittal FLAIR MR of the brain in a CIDP patient shows a typical paraventricular demyelinating lesion <img src='/img/arrows/WS.png'/> similar to those seen in multiple sclerosis patients.*
|
||||
|
||||
|
||||
*Sagittal FLAIR MR of the brain in a CIDP patient shows a typical paraventricular demyelinating lesion <img src='/img/arrows/WS.png'/> similar to those seen in multiple sclerosis patients.*
|
||||
|
||||
|
||||
*Sagittal T2WI MR depicts enlarged lumbar nerve roots extending into extraforaminal ventral primary rami <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Sagittal T2WI MR depicts enlarged lumbar nerve roots extending into extraforaminal ventral primary rami <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Axial T2WI MR shows diffuse thickening and hyperintensity of thoracic nerve roots and paraspinal intercostal nerves.*
|
||||
|
||||
|
||||
*Axial T2WI MR reveals bilateral symmetric enlargement, hyperintensity of cervical nerve roots and brachial plexus <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Sagittal T1WI C+ MR demonstrates diffuse pial thickening and enhancement extending into the cauda equina nerve roots. Clinical course distinguished from Guillain-Barré (AIDP).*
|
||||
|
||||
|
||||
*Axial T2WI MR shows marked enlargement of the lumbar/sacral nerve roots <img src='/img/arrows/BS.png'/> and lumbosacral trunk <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
@@ -0,0 +1,346 @@
|
||||
---
|
||||
title: "CLIPPERS"
|
||||
docid: "ba394f3b-bbff-4128-90b5-3e1c07564c5f"
|
||||
authors:
|
||||
- key: "5cff4116-3654-4b3a-bb75-5ebe0b8c9850"
|
||||
value: "Anne G. Osborn, MD, FACR"
|
||||
breadcrumbs:
|
||||
-
|
||||
name: "Brain"
|
||||
slug: "brain"
|
||||
treeNodeId: "6d8829f1-14d7-45af-8675-255189aa526a"
|
||||
-
|
||||
name: "Diagnosis"
|
||||
slug: "diagnosis"
|
||||
treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
|
||||
-
|
||||
name: "Pathology-Based Diagnoses"
|
||||
slug: "pathology-based-diagnoses"
|
||||
treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
|
||||
-
|
||||
name: "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
slug: "infectious-inflammatory-and-demyel-"
|
||||
treeNodeId: "7210f860-fe5f-4a2d-81cc-4fe06c769607"
|
||||
-
|
||||
name: "Inflammatory and Demyelinating Disease"
|
||||
slug: "inflammatory-and-demyelinating-dis-"
|
||||
treeNodeId: "62ab4dc3-dbf6-45a9-8532-f0e962aa62dc"
|
||||
-
|
||||
name: "CLIPPERS"
|
||||
slug: "clippers"
|
||||
treeNodeId: null
|
||||
category: "Brain"
|
||||
documentVersionId: "259b8c88-93cc-45d6-93d8-75d279e9ead2"
|
||||
imageCount: 12
|
||||
lastUpdated: "08/05/20"
|
||||
pageDescription: "CLIPPERS"
|
||||
pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Infectious, Inflammatory, and Demyelinating Disease, Inflammatory and Demyelinating Disease, CLIPPERS"
|
||||
pageTitle: "CLIPPERS | STATdx"
|
||||
enhancedTitle: "CLIPPERS"
|
||||
type: "DX"
|
||||
references: true
|
||||
breadcrumbs:
|
||||
- "Brain"
|
||||
- "Diagnosis"
|
||||
- "Pathology-Based Diagnoses"
|
||||
- "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
- "Inflammatory and Demyelinating Disease"
|
||||
- "CLIPPERS"
|
||||
---
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- **C**hronic **l**ymphocytic **i**nflammation with**p**ontine **p**erivascular **e**nhancement **r**esponsive to **s**teroids (CLIPPERS)
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Location predominantly pons/cerebellum **but****may extend
|
||||
- Laterally into cerebellar peduncles or hemispheres
|
||||
- Rostrally into midbrain
|
||||
- Caudally into medulla, spinal cord
|
||||
- ≈ 60% have CNS lesions **outside**pontocerebellar region
|
||||
- Basal ganglia, hemispheric white matter, cortex
|
||||
- MR
|
||||
- Punctate/curvilinear enhancing foci "peppering" pons
|
||||
- May exhibit subtle radiating pattern
|
||||
- No ring or patchy enhancement
|
||||
- Patchy/"speckled" punctate hyperintensities on T2/FLAIR
|
||||
- Does not significantly exceed areas of T1 C+ enhancement
|
||||
- Caution: May begin as isolated, enhancing mass in pons/cerebellar peduncle before exhibiting typical pattern of multifocal punctate pontine lesions
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Angiocentric (intravascular) lymphoma
|
||||
- Neurosarcoidosis
|
||||
- Demyelinating disease (multiple sclerosis, MOG spectrum)
|
||||
- Vasculitis (primary, secondary, Behçet)
|
||||
- Lymphomatoid granulomatosis
|
||||
- Histiocytosis (e.g., hemophagocytic lymphohistiocytosis)
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- Perivascular predominance lymphohistiocytic infiltrates + diffuse adjacent parenchymal inflammatory infiltrate
|
||||
- May be type of macrophage activation syndrome (secondary hemophagocytic lymphohistiocytosis)
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Mean age at onset 50 years (range: 13-86 years)
|
||||
- Subacute pontocerebeller dysfunction
|
||||
- Often relapsing-remitting course (without treatment)
|
||||
- Keep in mind: CLIPPERS is diagnosis of exclusion!
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- **C**hronic **l**ymphocytic **i**nflammation with**p**ontine **p**erivascular **e**nhancement responsive to **s**teroids (CLIPPERS)
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Recently described inflammatory CNS disorder
|
||||
- Distinct form of nonneoplastic encephalitis with predominant T-cell pathology
|
||||
- Predominantly involves brainstem, adjacent rhombencephalic structures
|
||||
- Striking clinical, imaging response to glucocorticosteroids
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Enhancing punctate/curvilinear lesions "peppering" pons
|
||||
- ### Location
|
||||
|
||||
|
||||
- Predominantly pons/cerebellum **but**may extend
|
||||
- Caudally into medulla, spinal cord
|
||||
- Rostrally into midbrain
|
||||
- ≈ 60% have CNS lesions **outside** pontocerebellar region
|
||||
- Basal ganglia, hemispheric white matter, cortex
|
||||
- Meningeal inflammation
|
||||
- Caution: May begin as isolated, enhancing mass in pons/cerebellar peduncle before exhibiting typical pattern of multifocal punctate pontine lesions
|
||||
- ### Size
|
||||
|
||||
|
||||
- Usually (but not always) ≤ 3mm
|
||||
- ### Morphology
|
||||
|
||||
|
||||
- Typically small, punctate or curvilinear
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- Usually normal
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- Usually normal
|
||||
- Pontocerebellar/cerebellar, cord, cerebral atrophy may be late changes
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- ± faint, patchy or "speckled" punctate hyperintensities on T2/FLAIR
|
||||
- Minimal or no mass effect, vasogenic edema
|
||||
- Homogeneous hyperintensity; does not significantly exceed T1 C+ enhancement
|
||||
- ### T2* GRE
|
||||
|
||||
|
||||
- Usually negative
|
||||
- ### DWI
|
||||
|
||||
|
||||
- Usually absent
|
||||
- ### T1WI C+
|
||||
|
||||
|
||||
- Punctate &/or curvilinear enhancing foci ("peppering" pons)
|
||||
- No ring or patchy enhancement
|
||||
- ↓ to absence of enhancement following steroids
|
||||
- ## Angiographic Findings
|
||||
|
||||
|
||||
- DSA normal without evidence for vasculitis
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MR ± contrast (include coronal T1C+), DWI, T2*
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- ## Lymphoma, Angiocentric (Intravascular)
|
||||
|
||||
|
||||
- Stroke-like symptoms, dementia
|
||||
- Hemorrhage, foci of restricted diffusion common
|
||||
- [Neurosarcoidosis](/document/neurosarcoid/fef69139-0019-4be3-9bdc-e26bc3644251)
|
||||
- Dura, leptomeningeal lesions common
|
||||
- Pituitary-hypothalamus often affected
|
||||
- [Vasculitis](/document/miscellaneous-vasculitis/5a4d4cbd-67e3-4722-8a44-8d411cbb98f0)
|
||||
- Primary angiitis of CNS (PACNS), systemic vasculitides
|
||||
- Neuro-Behçet
|
||||
- [Demyelinating Disease](/document/multiple-sclerosis/7892b2a2-f52a-4d7f-9858-a326f2b7ab04)
|
||||
- Multiple sclerosis (MS), MOG antibody-associated disease
|
||||
- Seropositive autoimmune encephalitides
|
||||
- ## Lymphomatoid Granulomatosis
|
||||
|
||||
|
||||
- Brain often more diffusely involved
|
||||
- [CNS Histiocytosis](/document/langerhans-cell-histiocytosis-skul-/6515bdbb-ce3d-47ef-9930-2dbb1949f807)
|
||||
- Hemophagocytic lymphohistiocytosis (HLH) resembles CLIPPERS on brain biopsy
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- May be type of macrophage activation syndrome (secondary HLH)
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- Perivascular predominance lymphohistiocytic infiltrates + diffuse adjacent parenchymal inflammatory infiltrate
|
||||
- Marked CD3-positive T lymphocytes, variable macrophage components
|
||||
- Variable tissue destruction, astrogliosis, myelin loss
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Subacute pontocerebeller dysfunction
|
||||
- ± other CNS symptoms (e.g., cognitive dysfunction, myelopathy)
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- Mean age at onset 50 years (range: 13-86 years)
|
||||
- ### Sex
|
||||
|
||||
|
||||
- M:F = 3:1
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Generally subacute presentation
|
||||
- Often relapsing-remitting course (without treatment)
|
||||
- Relapse rare when daily glucocorticoids ≥ 30 mg
|
||||
- Diagnosis of exclusion
|
||||
- Requires careful exclusion of alternative diagnoses
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- Corticosteroids (marked clinical, imaging response key to diagnosis)
|
||||
- Corticosteroid responsiveness also common but not universal in non-CLIPPERS diagnoses
|
||||
- Relapse off treatment common
|
||||
- Hydroxychloroquine has been reported to induce, maintain remission of symptoms
|
||||
|
||||
0e17b374-1564-4020-a6e2-552480332e98
|
||||
|
||||
## References
|
||||
|
||||
# Selected References
|
||||
|
||||
1. [Li Z et al: CLIPPERS, a syndrome of lymphohistiocytic disorders. Mult Scler Relat Disord. 42:102063, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32234602%5Bpmid%5D)
|
||||
1. [Turnquist C et al: CLIPPERS: a case report with radiology, three serial biopsies and a literature review. Clin Neuropathol. 39(1):19-24, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=31661071%5Bpmid%5D)
|
||||
1. [Taieb G et al: CLIPPERS and its mimics: evaluation of new criteria for the diagnosis of CLIPPERS. J Neurol Neurosurg Psychiatry. 90(9):1027-38, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31072955%5Bpmid%5D)
|
||||
1. [Berzero G et al: CLIPPERS mimickers: relapsing brainstem encephalitis associated with anti-MOG antibodies. Eur J Neurol. 25(2):e16-7, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29356261%5Bpmid%5D)
|
||||
1. [Tian D et al: Case 259: Primary central nervous system lymphomatoid granulomatosis mimicking chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Radiology. 289(2):572-7, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=30332362%5Bpmid%5D)
|
||||
1. [Tobin WO et al: Diagnostic criteria for chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain. 140(9):2415-25, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=29050399%5Bpmid%5D)
|
||||
1. [Taieb G et al: Punctate and curvilinear gadolinium enhancing lesions in the brain: a practical approach. Neuroradiology. 58(3):221-35, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=26700824%5Bpmid%5D)
|
||||
1. [Gul M et al: Atypical presentation of CLIPPERS syndrome: a new entity in the differential diagnosis of central nervous system rheumatologic diseases. J Clin Rheumatol. 21(3):144-8, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25807094%5Bpmid%5D)
|
||||
1. [Dudesek A et al: CLIPPERS: chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids. Review of an increasingly recognized entity within the spectrum of inflammatory central nervous system disorders. Clin Exp Immunol. 175(3):385-96, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24028073%5Bpmid%5D)
|
||||
1. [Pittock SJ et al: Chronic lymphocytic inflammation with pontine perivascular enhancement responsive to steroids (CLIPPERS). Brain. 133(9):2626-34, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=20639547%5Bpmid%5D)
|
||||
|
||||
|
||||
## Images
|
||||
|
||||
|
||||
### Selected Images
|
||||
|
||||
|
||||
*Sagittal FLAIR MR in a 56-year-old woman with weight loss and a 3-week history of diplopia and disequilibrium shows confluent and punctate hyperintensities in the pons <img src='/img/arrows/WO.png'/> and medulla <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Sagittal FLAIR MR in a 56-year-old woman with weight loss and a 3-week history of diplopia and disequilibrium shows confluent and punctate hyperintensities in the pons <img src='/img/arrows/WO.png'/> and medulla <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Sagittal FLAIR MR in a 56-year-old woman with weight loss and a 3-week history of diplopia and disequilibrium shows confluent and punctate hyperintensities in the pons <img src='/img/arrows/WO.png'/> and medulla <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows multiple punctate and curvilinear enhancing foci "peppering" the pons <img src='/img/arrows/WS.png'/>. Additional lesions are present in both cerebellar peduncles, vermis, and the left cerebellar hemisphere.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows multiple punctate and curvilinear enhancing foci "peppering" the pons <img src='/img/arrows/WS.png'/>. Additional lesions are present in both cerebellar peduncles, vermis, and the left cerebellar hemisphere.*
|
||||
|
||||
|
||||
*More cephalad T1 C+ MR scan in the same patient shows the punctate <img src='/img/arrows/WS.png'/> and curvilinear <img src='/img/arrows/WC.png'/> lesions involving the upper pons.*
|
||||
|
||||
|
||||
*More cephalad T1 C+ MR scan in the same patient shows the punctate <img src='/img/arrows/WS.png'/> and curvilinear <img src='/img/arrows/WC.png'/> lesions involving the upper pons.*
|
||||
|
||||
|
||||
*Coronal T1 C+ FS MR in the same patient shows the lesions "peppering" the pons. Note cephalad extension into the cerebral peduncles <img src='/img/arrows/WO.png'/> and inferior extension into the medulla <img src='/img/arrows/WC.png'/> and upper cervical cord <img src='/img/arrows/WS.png'/>. DSA (not shown) was negative. The lesions resolved with corticosteroids, so this is a presumed case of CLIPPERS.*
|
||||
|
||||
|
||||
*Coronal T1 C+ FS MR in the same patient shows the lesions "peppering" the pons. Note cephalad extension into the cerebral peduncles <img src='/img/arrows/WO.png'/> and inferior extension into the medulla <img src='/img/arrows/WC.png'/> and upper cervical cord <img src='/img/arrows/WS.png'/>. DSA (not shown) was negative. The lesions resolved with corticosteroids, so this is a presumed case of CLIPPERS.*
|
||||
|
||||
|
||||
### Additional Images
|
||||
|
||||
|
||||
*Sagittal FLAIR in a 52-year-old man with diplopia, dysarthria, and facial numbness shows confluent hyperintensity in the pons <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Sagittal FLAIR in a 52-year-old man with diplopia, dysarthria, and facial numbness shows confluent hyperintensity in the pons <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR shows scattered, faint, punctate enhancing foci <img src='/img/arrows/WS.png'/> as well as larger confluent, nodular <img src='/img/arrows/WO.png'/>, and partial ring-enhancing <img src='/img/arrows/WC.png'/> lesions in the pons.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR shows scattered, faint, punctate enhancing foci <img src='/img/arrows/WS.png'/> as well as larger confluent, nodular <img src='/img/arrows/WO.png'/>, and partial ring-enhancing <img src='/img/arrows/WC.png'/> lesions in the pons.*
|
||||
|
||||
|
||||
*Coronal T1 C+ MR in the same patient shows large, confluent, patchy enhancing lesions <img src='/img/arrows/WS.png'/> in the pons. Differential diagnosis included lymphoma, lymphomatoid granulomatosis, vasculitis, and CLIPPERS. The patient improved on steroids.*
|
||||
|
||||
|
||||
*Coronal T1 C+ MR in the same patient shows large, confluent, patchy enhancing lesions <img src='/img/arrows/WS.png'/> in the pons. Differential diagnosis included lymphoma, lymphomatoid granulomatosis, vasculitis, and CLIPPERS. The patient improved on steroids.*
|
||||
|
||||
|
||||
*Sagittal FLAIR in the same patient obtained a year later when symptoms relapsed off steroids shows multiple punctate hyperintensities "peppering" the pons <img src='/img/arrows/WS.png'/> and medulla <img src='/img/arrows/WC.png'/>. Note extension into upper spinal cord <img src='/img/arrows/WO.png'/>.*
|
||||
|
||||
|
||||
*Sagittal FLAIR in the same patient obtained a year later when symptoms relapsed off steroids shows multiple punctate hyperintensities "peppering" the pons <img src='/img/arrows/WS.png'/> and medulla <img src='/img/arrows/WC.png'/>. Note extension into upper spinal cord <img src='/img/arrows/WO.png'/>.*
|
||||
|
||||
|
||||
*Axial T1 C + FS MR in the same patient shows small, punctate foci of enhancement <img src='/img/arrows/WS.png'/> "peppering" the pons, cerebellar peduncles.*
|
||||
|
||||
|
||||
*Axial T1 C + FS MR in the same patient shows small, punctate foci of enhancement <img src='/img/arrows/WS.png'/> "peppering" the pons, cerebellar peduncles.*
|
||||
|
||||
|
||||
*More inferior T1 C+ FS MR in the same patient shows additional small enhancing foci in the medulla <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*More cephalad T1 C+ FS MR in the same patient shows additional lesions in the midbrain <img src='/img/arrows/WS.png'/> and medial temporal lobe <img src='/img/arrows/WC.png'/>.*
|
||||
|
||||
|
||||
*More cephalad T1 C+ FS MR in the same patient shows a solitary enhancing lesion <img src='/img/arrows/WS.png'/> in the subcortical white matter of the "hand knob." One of the cerebellar lesions was biopsied and disclosed CD4+ T-cell perivascular infiltrates, consistent with CLIPPERS. In rare cases, CLIPPERS initially manifests as a more mass-like confluent pontine lesion before the typical peppering pattern emerges.*
|
||||
|
||||
@@ -0,0 +1,320 @@
|
||||
---
|
||||
title: "Guillain-Barr\u00e9 Spectrum Disorders"
|
||||
docid: "c1f52a65-920e-4e28-8a75-07dfa208f290"
|
||||
authors:
|
||||
- key: "b2e6dabb-ee1c-42a4-a332-9f0814c1c607"
|
||||
value: "Surjith Vattoth, MD, FRCR"
|
||||
breadcrumbs:
|
||||
-
|
||||
name: "Brain"
|
||||
slug: "brain"
|
||||
treeNodeId: "6d8829f1-14d7-45af-8675-255189aa526a"
|
||||
-
|
||||
name: "Diagnosis"
|
||||
slug: "diagnosis"
|
||||
treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
|
||||
-
|
||||
name: "Pathology-Based Diagnoses"
|
||||
slug: "pathology-based-diagnoses"
|
||||
treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
|
||||
-
|
||||
name: "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
slug: "infectious-inflammatory-and-demyel-"
|
||||
treeNodeId: "7210f860-fe5f-4a2d-81cc-4fe06c769607"
|
||||
-
|
||||
name: "Inflammatory and Demyelinating Disease"
|
||||
slug: "inflammatory-and-demyelinating-dis-"
|
||||
treeNodeId: "62ab4dc3-dbf6-45a9-8532-f0e962aa62dc"
|
||||
-
|
||||
name: "Guillain-Barr\u00e9 Spectrum Disorders"
|
||||
slug: "guillain-barr-spectrum-disorders"
|
||||
treeNodeId: null
|
||||
category: "Brain"
|
||||
documentVersionId: "52016b28-7710-43a4-8cca-e659ab8227cf"
|
||||
imageCount: 5
|
||||
lastUpdated: "06/12/20"
|
||||
pageDescription: "Guillain-Barr\u00e9 Spectrum Disorders"
|
||||
pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Infectious, Inflammatory, and Demyelinating Disease, Inflammatory and Demyelinating Disease, Guillain-Barr\u00e9 Spectrum Disorders"
|
||||
pageTitle: "Guillain-Barr\u00e9 Spectrum Disorders | STATdx"
|
||||
enhancedTitle: "Guillain-Barr\u00e9 Spectrum Disorders"
|
||||
type: "DX"
|
||||
references: true
|
||||
breadcrumbs:
|
||||
- "Brain"
|
||||
- "Diagnosis"
|
||||
- "Pathology-Based Diagnoses"
|
||||
- "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
- "Inflammatory and Demyelinating Disease"
|
||||
- "Guillain-Barr\u00e9 Spectrum Disorders"
|
||||
---
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS), Bickerstaff brainstem encephalitis (BBE)
|
||||
- **Classic GBS**: Acute-onset, rapidly progressive, ascending sensorimotor neuropathy; absent or ↓ tendon reflexes
|
||||
- **Clinical variants of GBS**: Pure motor, paraparetic, bilateral facial palsy with paraesthesias, pharyngeal-cervical-brachial (PCB) variants and MFS
|
||||
- **Other disorders often included in GBS spectrum** (controversial): Pure sensory variant, pure sensory ataxia, BBE
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Cauda equina (CE) nerve root enhancement in > 80%
|
||||
- Isolated ventral CE in 17%, both ventral and dorsal in 65%
|
||||
- Enhancement intensity of ventral CE ≥ dorsal CE
|
||||
- Pial surface of distal cord/conus variable enhancement
|
||||
- Pediatric GBS and MFS: CN enhancement in > 80%
|
||||
- CNIII, CNVI, CNVII most common; others like CNII (and optic chiasm), CNV, CNXI, CNXII
|
||||
- BBE: Brainstem T2 hyperintensities, may involve cerebellar peduncles and cerebellum
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Subacute or chronic demyelinating polyneuropathies (SIDP/CIDP)
|
||||
- CSF metastatic seeding, infections, arachnoiditis
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- 6 temporally associated pathogens: *Campylobacter jejuni*, Cytomegalovirus (CMV), Hepatitis E virus, *Mycoplasma pneumoniae*, Epstein Barr virus (EBV), and Zika virus
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Motor weakness and sensory signs in legs progressing to upper limbs and cranial muscles
|
||||
- GBS spectrum/clinical variants with various findings
|
||||
- Serum anti-GQ1b antibodies in up to 90% of MFS, 70% of BBE, and 8% of classic GBS
|
||||
- Anti-GM1 antibodies more characteristic of classic GBS
|
||||
- Intravenous immunoglobulins and plasma exchange therapy
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Consider GBS, variants or overlap syndromes in MR with ventral > dorsal cauda equina nerve root enhancement
|
||||
- Look for cranial nerve root enhancement in MFS
|
||||
- Look for brainstem signal abnormalities in BBE
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Guillain-Barré syndrome (GBS), Miller Fisher syndrome (MFS), Bickerstaff brainstem encephalitis (BBE)
|
||||
- Acute inflammatory demyelinating polyradiculoneuropathy (AIDP), acute motor axonal neuropathy (AMAN), acute motor sensory axonal neuropathy (AMSAN)
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Immune-mediated peripheral nerves and nerve roots disorder, usually triggered by infections
|
||||
- **Classic GBS**: Acute-onset, rapidly progressive, ascending sensorimotor neuropathy; absent or ↓ tendon reflexes
|
||||
- Initially in legs, progressing to arms and cranial muscles
|
||||
- Usually reach maximum disability within 2 weeks
|
||||
- **Electrophysiological subtypes**: **AIDP, AMAN, AMSAN**
|
||||
- **Clinical variants of GBS**: Do not characteristically progress to classic GBS pattern of sensory loss and weakness
|
||||
- Usually not "pure"; often partial overlap with classic GBS or other variants
|
||||
- **Pure motor variant**: Motor weakness; no sensory signs
|
||||
- **Paraparetic variant**: Paresis in lower limbs only
|
||||
- **Bilateral facial palsy with paraesthesias variant**: Weakness limited to cranial nerves; ↓ reflexes
|
||||
- **Pharyngeal-cervical-brachial (PCB) variant**: PCB muscle weakness, no lower limb weakness
|
||||
- **MFS**: Ophthalmoplegia, areflexia, ataxia
|
||||
- 15% overlap classic GBS
|
||||
- Incomplete forms: **Acute ataxic neuropathy** (isolated ataxia); **acute ophthalmoplegia**
|
||||
- **Other disorders often included in GBS spectrum**:****Due to similar clinical or pathophysiological features
|
||||
- Inclusion in GBS spectrum debatable as these do not fulfil GBS diagnostic criteria
|
||||
- **Pure sensory variant**: Overlapping clinical features of classic GBS, except motor signs and symptoms
|
||||
- **Pure sensory ataxia**: Overlap with MFS
|
||||
- **BBE**: Initially ophthalmoplegia, ataxia, areflexia (like MFS), later brainstem dysfunction, e.g., ↓ consciousness and pyramidal tract signs; often overlap classic GBS
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Cauda equina (CE) nerve root enhancement > 80%
|
||||
- Isolated ventral CE 17%, both ventral and dorsal 65%
|
||||
- Enhancement intensity of ventral CE ≥ dorsal CE
|
||||
- Pial surface of distal cord/conus variable enhancement
|
||||
- Pediatric GBS and MFS: Cranial nerve enhancement > 80%
|
||||
- CNIII, CNVI, CNVII most common; others like CNII (and optic chiasm), CNV, CNXI, CNXII
|
||||
- Entire spinal cord T2-hyperintense posterior column described as delayed-onset finding in MFS case
|
||||
- BBE: Brainstem T2 hyperintensities, may involve cerebellar peduncles and cerebellum
|
||||
- Enhance only rarely; extremely rare, patchy spinal cord involvement described
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- May see slight nerve root thickening
|
||||
- Brainstem hyperintensities in BBE
|
||||
- ### T1WI C+
|
||||
|
||||
|
||||
- Ventral > dorsal nerve root enhancement
|
||||
- Cranial nerve enhancement
|
||||
- ## Ultrasonographic Findings
|
||||
|
||||
|
||||
- Enlarged nerves/roots during first 3 weeks, improve later
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MR of lumbar spine with contrast
|
||||
- MR of brain with contrast if MFS or BBE suspected
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- ## Infections
|
||||
|
||||
|
||||
- Bacterial or granulomatous meningitis
|
||||
- Nerve root enhancement in minority of enterovirus D68 acute flaccid myelitis
|
||||
- ## CSF Metastatic Seeding
|
||||
|
||||
|
||||
- Nodular nerve root thickening and enhancement
|
||||
- ## Subacute or Chronic Demyelinating Polyneuropathies
|
||||
|
||||
|
||||
- Slower onset, protracted course
|
||||
- CIDP: Nadir 2 months; SIDP: 4-8 weeks
|
||||
- ## Arachnoiditis
|
||||
|
||||
|
||||
- Secondary to hemorrhage, surgery, chemicals, chemotherapy (like vincristine), radiation
|
||||
- ## Vasculitic Neuropathy
|
||||
|
||||
|
||||
- Polyarteritis nodosa, Churg-Strauss syndrome
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- Infection in 6 weeks prior to onset in 2/3; triggering immune response causing GBS
|
||||
- 6 temporally associated pathogens: *Campylobacter jejuni*, Cytomegalovirus (CMV), Hepatitis E virus, *Mycoplasma pneumoniae*, Epstein Barr virus (EBV), and Zika virus
|
||||
- Absence of preceding illness does not exclude GBS
|
||||
- Infections and other immunological stimuli (immunobiologicals like tumour necrosis factor antagonists, immune checkpoint inhibitors or type I interferons, surgery, amlgnancy) may be subclinical
|
||||
- Serum antibodies against gangliosides in axolemma and other peripheral nerve components
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Peripheral nerve and nerve root complement activation, macrophage infiltration, and edema
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Motor weakness and sensory signs in legs progressing to upper limbs and cranial muscles
|
||||
- Low back pain common symptom
|
||||
- GBS spectrum/clinical variants with various findings
|
||||
- Respiratory failure and mechanical ventilation in 20%
|
||||
- Autonomic nervous system involvement with cardiac arrhythmias and unstable blood pressure
|
||||
- ### Other signs/symptoms
|
||||
|
||||
|
||||
- Serum **anti-GQ1b** antibodies in up to 90% of MFS, 70% of BBE, and 8% of classic GBS
|
||||
- **Anti-GM1** antibodies more characteristic of classic GBS
|
||||
- Should not wait for antibody test results to start treatment when GBS is suspected
|
||||
- Albumino-cytological dissociation: Classic GBS finding
|
||||
- ↑ CSF protein and normal CSF cell count
|
||||
- Protein levels normal in 30-50% during 1st week and 10-30% during 2nd week
|
||||
- Mild CSF pleocytosis (10-50 cells/μl) can be seen in GBS, but should exclude infectious polyradiculitis
|
||||
- Electrodiagnostic studies not required to diagnose GBS; might be normal during 1st week, mild or variant disease, initial proximal weakness, or slow progression
|
||||
- GBS: Sensorimotor polyradiculoneuropathy or polyneuropathy: ↓ conduction velocities, sensory and motor evoked amplitudes, abnormal temporal dispersion &/or partial motor conduction blocks
|
||||
- GBS: Typical "sural sparing" pattern: Normal sural sensory nerve action potential, but abnormal or absent median and ulnar sensory nerve action potentials
|
||||
- MFS: Normal or only ↓ amplitude of sensory nerve action potentials
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- 1-2 per 100,000 person-years; M > F; ↑ with age
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Rapid progression, nadir within 2 weeks; mortality 3-10%
|
||||
- GBS plateau phase (days to weeks or months); then recovery
|
||||
- 60-80% walk independently after 6 months
|
||||
- GBS typically monophasic illness, but relapses in 2-5%
|
||||
- Treatment-related fluctuation (TRF): Deterioration after intial stability/improvement on therapy
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- Intravenous immunoglobulin for 5 days (0.4 g/kg daily)
|
||||
- Plasma exchange for 5 sessions (200-250 mL/kg)
|
||||
- If TRF, repeat same treatment
|
||||
- If no initial response or incomplete recovery, currently no evidence to support repeat treatment
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- GBS, variants or overlap syndromes in MR showing ventral > dorsal cauda equina nerve root enhancement
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- Look for cranial nerve root enhancement in MFS
|
||||
- Look for brainstem signal abnormalities in BBE
|
||||
|
||||
5e867f2a-de7e-44dd-83cf-67453b9125d2
|
||||
|
||||
## References
|
||||
|
||||
# Selected References
|
||||
|
||||
1. [Al Othman B et al: Update: the Miller Fisher variants of Guillain-Barré syndrome. Curr Opin Ophthalmol. 30(6):462-6, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31567467%5Bpmid%5D)
|
||||
1. [Leonhard SE et al: Diagnosis and management of Guillain-Barré syndrome in ten steps. Nat Rev Neurol. 15(11):671-83, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31541214%5Bpmid%5D)
|
||||
1. [Malhotra A et al: MRI findings of optic pathway involvement in Miller Fisher syndrome in 3 pediatric patients and a review of the literature. J Clin Neurosci. 39:63-7, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28209311%5Bpmid%5D)
|
||||
1. [Cuneo GL et al: An atypical Bickerstaff's brainstem encephalitis with involvement of spinal cord. Neuroradiol J. 29(5):396-9, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=27540012%5Bpmid%5D)
|
||||
1. [Tyrakowska Z et al: Relapsing-Remitting Severe Bickerstaff's Brainstem Encephalitis - Case Report and Literature Review. Pol J Radiol. 81:622-628, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=28096906%5Bpmid%5D)
|
||||
1. [Zuccoli G et al: Redefining the Guillain-Barré spectrum in children: neuroimaging findings of cranial nerve involvement. AJNR Am J Neuroradiol. 32(4):639-42, 2011](http://www.ncbi.nlm.nih.gov/pubmed/?term=21292802%5Bpmid%5D)
|
||||
1. [Inoue N et al: MR imaging findings of spinal posterior column involvement in a case of Miller Fisher syndrome. AJNR Am J Neuroradiol. 25(4):645-8, 2004](http://www.ncbi.nlm.nih.gov/pubmed/?term=15090361%5Bpmid%5D)
|
||||
|
||||
|
||||
## Images
|
||||
|
||||
|
||||
### Selected Images
|
||||
|
||||
|
||||
*Axial T1 C+ MR of the lumbar spine in a patient with Guillain-Barré syndrome (GBS) shows the characteristic ventral cauda equina (CE) nerve root enhancement <img src='/img/arrows/CS.png'/> and slight thickening.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR of the lumbar spine in a patient with Guillain-Barré syndrome (GBS) shows the characteristic ventral cauda equina (CE) nerve root enhancement <img src='/img/arrows/CS.png'/> and slight thickening.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR of the lumbar spine in a patient with Guillain-Barré syndrome (GBS) shows the characteristic ventral cauda equina (CE) nerve root enhancement <img src='/img/arrows/CS.png'/> and slight thickening.*
|
||||
|
||||
|
||||
*Sagittal T1 C+ FS MR of the lumbar spine in a patient with GBS shows CE nerve root enhancement, more intense in ventral <img src='/img/arrows/CS.png'/> than dorsal <img src='/img/arrows/CC.png'/> CE. Also note enhancement of the pial surface of the distal cord/conus <img src='/img/arrows/CO.png'/>. GBS is an immune-mediated peripheral nerves and nerve roots disorder, usually triggered by infections.*
|
||||
|
||||
|
||||
*Sagittal T1 C+ FS MR of the lumbar spine in a patient with GBS shows CE nerve root enhancement, more intense in ventral <img src='/img/arrows/CS.png'/> than dorsal <img src='/img/arrows/CC.png'/> CE. Also note enhancement of the pial surface of the distal cord/conus <img src='/img/arrows/CO.png'/>. GBS is an immune-mediated peripheral nerves and nerve roots disorder, usually triggered by infections.*
|
||||
|
||||
|
||||
*Coronal angled T1 C+ MPRAGE MR reformat in a patient with Miller Fisher syndrome (MFS) shows mild thickening and enhancement of right facial (CNVII) <img src='/img/arrows/CC.png'/> and bilateral trigeminal (CNV) <img src='/img/arrows/CS.png'/> nerves.*
|
||||
|
||||
|
||||
*Coronal angled T1 C+ MPRAGE MR reformat in a patient with Miller Fisher syndrome (MFS) shows mild thickening and enhancement of right facial (CNVII) <img src='/img/arrows/CC.png'/> and bilateral trigeminal (CNV) <img src='/img/arrows/CS.png'/> nerves.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with BBE shows hyperintense signal in the pons <img src='/img/arrows/CS.png'/>, middle cerebellar peduncles <img src='/img/arrows/CC.png'/>, and cerebellum <img src='/img/arrows/CO.png'/>. Both MFS and BBE may initially show ophthalmoplegia, ataxia, and areflexia, the differentiating feature being reduced consciousness and other brainstem signs in BBE later.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with BBE shows hyperintense signal in the pons <img src='/img/arrows/CS.png'/>, middle cerebellar peduncles <img src='/img/arrows/CC.png'/>, and cerebellum <img src='/img/arrows/CO.png'/>. Both MFS and BBE may initially show ophthalmoplegia, ataxia, and areflexia, the differentiating feature being reduced consciousness and other brainstem signs in BBE later.*
|
||||
|
||||
|
||||
### Additional Images
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with Bickerstaff brainstem encephalitis (BBE) shows abnormal hyperintense signal in the pons <img src='/img/arrows/CS.png'/>. Both MFS and BBE initially present with ophthalmoplegia, ataxia and areflexia; the differentiating feature being development of brainstem dysfunction in BBE later (reduced consciousness and pyramidal tract signs).*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with Bickerstaff brainstem encephalitis (BBE) shows abnormal hyperintense signal in the pons <img src='/img/arrows/CS.png'/>. Both MFS and BBE initially present with ophthalmoplegia, ataxia and areflexia; the differentiating feature being development of brainstem dysfunction in BBE later (reduced consciousness and pyramidal tract signs).*
|
||||
|
||||
@@ -0,0 +1,497 @@
|
||||
---
|
||||
title: "Multiple Sclerosis"
|
||||
docid: "7892b2a2-f52a-4d7f-9858-a326f2b7ab04"
|
||||
authors:
|
||||
- key: "a25c450b-3d34-4f64-bba3-cc0834813df6"
|
||||
value: "Miral D. Jhaveri, MD, MBA"
|
||||
breadcrumbs:
|
||||
-
|
||||
name: "Brain"
|
||||
slug: "brain"
|
||||
treeNodeId: "6d8829f1-14d7-45af-8675-255189aa526a"
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-
|
||||
name: "Diagnosis"
|
||||
slug: "diagnosis"
|
||||
treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
|
||||
-
|
||||
name: "Pathology-Based Diagnoses"
|
||||
slug: "pathology-based-diagnoses"
|
||||
treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
|
||||
-
|
||||
name: "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
slug: "infectious-inflammatory-and-demyel-"
|
||||
treeNodeId: "7210f860-fe5f-4a2d-81cc-4fe06c769607"
|
||||
-
|
||||
name: "Inflammatory and Demyelinating Disease"
|
||||
slug: "inflammatory-and-demyelinating-dis-"
|
||||
treeNodeId: "62ab4dc3-dbf6-45a9-8532-f0e962aa62dc"
|
||||
-
|
||||
name: "Multiple Sclerosis"
|
||||
slug: "multiple-sclerosis"
|
||||
treeNodeId: null
|
||||
category: "Brain"
|
||||
documentVersionId: "7ced4781-f9a4-4a48-a5ed-954fa6ea87cf"
|
||||
imageCount: 27
|
||||
lastUpdated: "10/08/20"
|
||||
pageDescription: "Multiple Sclerosis"
|
||||
pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Infectious, Inflammatory, and Demyelinating Disease, Inflammatory and Demyelinating Disease, Multiple Sclerosis"
|
||||
pageTitle: "Multiple Sclerosis | STATdx"
|
||||
enhancedTitle: "Multiple Sclerosis"
|
||||
type: "DX"
|
||||
references: true
|
||||
breadcrumbs:
|
||||
- "Brain"
|
||||
- "Diagnosis"
|
||||
- "Pathology-Based Diagnoses"
|
||||
- "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
- "Inflammatory and Demyelinating Disease"
|
||||
- "Multiple Sclerosis"
|
||||
---
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Idiopathic chronic inflammatory demyelinating disease of CNS
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Multiple perpendicular callososeptal T2 hyperintensities characteristic of multiple sclerosis (MS)
|
||||
- Perivenular extension: "Dawson fingers"
|
||||
- Bilateral, asymmetric linear/ovoid FLAIR hyperintensities
|
||||
- Periventricular/perivenular, callososeptal interface
|
||||
- May also commonly involve brachium pontis, brainstem, spinal cord, cortex/juxtacortical
|
||||
- SWI central vein sign
|
||||
- Transient enhancement during active demyelination
|
||||
- Rare: Large tumefactive enhancing rings
|
||||
- Advanced imaging techniques show disease in normal-appearing white matter
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- **Multifocal T2/FLAIR hyperintensities**
|
||||
- Arteriolosclerosis, ADEM, NMOSD, vasculitis, Susac syndrome, Lyme disease
|
||||
- **Mass-like ("tumefactive") lesion(s)**
|
||||
- Neoplasms, PML/PML-IRIS
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- Major clinical subtypes from least to most severe
|
||||
- Radiologically isolated syndrome, clinically isolated syndrome, relapsing-remitting, relapsing-progressive, a.k.a. secondary progressive & primary progressive MS
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- ~ 2.5 million people in world have MS
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Requires dissemination in time & space in CNS for diagnosis
|
||||
- McDonald criteria: Consensus statement for diagnostic criteria, last revised in 2017
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Multiple sclerosis (MS)
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Idiopathic chronic inflammatory demyelinating disease of CNS
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Multiple perpendicular callososeptal T2 hyperintensities
|
||||
- ### Location
|
||||
|
||||
|
||||
- > 85% periventricular/perivenular, callososeptal interface
|
||||
- Brachium pontis, brainstem, spinal cord
|
||||
- Infratentorial (< 10% in adults, more common in children)
|
||||
- Gray matter [cortex & basal ganglia (BG) ~ 10%]
|
||||
- Juxtacortical: Lesion in cerebral white matter (WM) abutting cortex
|
||||
- Cortical: Lesion within cerebral cortex
|
||||
- Leukocortical (inner aspect ± involvement of juxtacortical WM)
|
||||
- Intracortical (purely within cortex)
|
||||
- Subpial (at its outer aspect)
|
||||
- ### Size
|
||||
|
||||
|
||||
- Small (5-10 mm); tumefactive lesions several cm
|
||||
- ### Morphology
|
||||
|
||||
|
||||
- Linear, round, or ovoid; beveled, target
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- NECT often normal early in disease course
|
||||
- Solitary/multiple ill-defined WM hypodensities
|
||||
- Mild/moderate punctate, patchy, ring enhancement in acute/subacute lesions
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- Typically hypo- or isointense
|
||||
- Hypointensity correlates with axonal destruction ("black holes"), faint mildly hyperintense rim
|
||||
- Chronic/severe: Volume loss, thin corpus callosum
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- Hyperintense, linear foci radiating from ventricles
|
||||
- ### FLAIR
|
||||
|
||||
|
||||
- Early: Alternating linear hyperintensity along ependyma on sagittal FLAIR: Ependymal dot-dash sign
|
||||
- Bilateral, asymmetric, linear/ovoid hyperintensities
|
||||
- Perivenular extension; "Dawson fingers"
|
||||
- Hyperintensities become confluent with severity
|
||||
- Cortical lesions may precede classic WM lesions
|
||||
- ### T2* GRE
|
||||
|
||||
|
||||
- SWI central vein sign (CVS) = vein located centrally within MS lesion
|
||||
- Magnetic resonance imaging in multiple sclerosis (MAGNIMS) study
|
||||
- CVS sensitivity of 68.1% & specificity of 82.9% in distinguishing MS from radiologic mimics using 35% CVS proportion threshold
|
||||
- Chronic lesions: Paramagnetic rims at lesion edge
|
||||
- Iron accumulation in deep gray matter structures
|
||||
- SWI C+ to better detect BBB dysfunction in MS plaques
|
||||
- Natalizumab-associated progressive multifocal leukoencephalopathy (PML): Juxtacortical low signal
|
||||
- ### DWI
|
||||
|
||||
|
||||
- Majority of acute plaques: Normal or ↑ diffusivity
|
||||
- May show restricted diffusion at plaque margins
|
||||
- Subacute/chronic plaques show ↑ diffusivity
|
||||
- DTI: Reduced longitudinal diffusivity due to axonal injury
|
||||
- ### T1WI C+
|
||||
|
||||
|
||||
- Transient enhancement during active demyelination
|
||||
- Punctate, nodular, linear, incomplete ring
|
||||
- Semilunar, "open" nonenhancing segment facing cortex
|
||||
- ± leptomeningeal enhancement on delayed FLAIR MR, marker for cortical demyelination
|
||||
- ### MRS
|
||||
|
||||
|
||||
- ↓ NAA , ↑ choline (Cho/Cr), ↑ myoinositol
|
||||
- Abnormalities found in normal-appearing WM (NAWM)
|
||||
- Secondary progressive MS may show ↓ NAA in normal-appearing gray matter (NAGM)
|
||||
- May allow early distinction between relapsing-remitting & secondary progressive
|
||||
- 3D double inversion recovery (DIR) sequence
|
||||
- ↑ intracortical lesion detection
|
||||
- Perfusion MR: Low rCBV, can help differentiate tumefactive MS from neoplasm
|
||||
- Magnetization transfer (MT)
|
||||
- ↓ MT ratio (MTR) in lesions/NAWM
|
||||
- Functional connectivity MR (fcMR)
|
||||
- ↓ functional connectivity between right/left hemisphere primary visual & motor cortices
|
||||
- 3T vs. 1.5T: ↑ number of contrast-enhancing lesions, enhancing lesion volume, total lesion volume
|
||||
- 7T: Improved detection of cortical lesions
|
||||
- ## PET With Translocator Protein Radioligands
|
||||
|
||||
|
||||
- In vivo quantification of microglial activation
|
||||
- Presence of widespread inflammation in NAWM
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MR
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- Contrast-enhanced MR with sagittal FLAIR
|
||||
- Fat saturation to assess for optic neuritis
|
||||
- **Consortium of Multiple Sclerosis Centers (CMSC) 2018 guidelines**
|
||||
- Brain MR C+ recommended for diagnosis of MS
|
||||
- Spinal cord MR if brain MR nondiagnostic or presenting symptoms referable to cord
|
||||
- Follow-up brain MR recommended
|
||||
- Demonstrate dissemination in time
|
||||
- Detect clinically silent disease activity on Rx
|
||||
- **PML**surveillance while on Rx
|
||||
- Evaluate unexpected clinical worsening
|
||||
- New baseline MR before starting/modifying Rx
|
||||
- Every 6 months to 2 years for relapsing MS
|
||||
- MR brain core sequences
|
||||
- 2D/3D sagittal & axial FLAIR, 2D/3D axial T2, 2D axial DWI, 3D IR-prep GE T1 ± 2D/3D axial T1 C+
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- ## Multifocal T2/FLAIR Hyperintensities
|
||||
|
||||
|
||||
- [Arter io lo sc lerosis](/document/arteriolosclerosis/ce5a75ed-3a88-42a4-a0e8-4f339375c062)
|
||||
- Patchy confluent & focal lesions; subcortical/deep WM & BG involved; ± cortical infarcts, vascular risk factors
|
||||
- [Acute disseminated encephalomyelitis](/document/adem/a3fafeb7-5861-4364-beb8-c0e30220564e)
|
||||
- Viral prodrome, monophasic, more common in children
|
||||
- Can mimic MS; gray matter often involved
|
||||
- Lesions tend to be larger & often symmetric
|
||||
- [Neuromyelitis optica spectrum disorders](/document/neuromyelitis-optica-spectrum-diso-/54d4a8bc-9267-4df6-98c1-f22aae051d01)
|
||||
- Optic neuritis & spinal cord lesions
|
||||
- Tend to border midline CSF spaces
|
||||
- [Vasculitis](/document/miscellaneous-vasculitis/5a4d4cbd-67e3-4722-8a44-8d411cbb98f0)
|
||||
- Enhancing lesions spare callososeptal interface
|
||||
- Beaded angiogram appearance
|
||||
- [Susac syndrome](/document/susac-syndrome/af240d31-5918-4981-971f-c6780f7b405f)
|
||||
- Classic triad: Encephalopathy, branch retinal artery occlusions, hearing loss
|
||||
- [Lyme Disease](/document/lyme-disease/ca3da7a8-0f21-4e06-9961-a43e6af1b0cc)
|
||||
- Can be identical to MS (skin rash common)
|
||||
- ## Mass-Like ("Tumefactive") Lesion(s)
|
||||
|
||||
|
||||
- **Neoplasms**:****Glioblastoma, metastasis
|
||||
- [PML/PML-IRIS : HIV/AIDS, Natalizumab-treated MS](/document/progressive-multifocal-leukoenceph-/fc94bcd6-17a1-4966-8e27-51f5c7df6537)
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Multifactorial disease, precise pathogenesis unknown
|
||||
- Autoimmune, environmental, & genetic factors
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- Multifactorial; ↑ incidence in 1st-order relatives
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- **Major clinical subtypes from least to most severe**
|
||||
- **Radiologically isolated syndrome****(RIS)**
|
||||
- Asymptomatic with routine MR findings highly suggestive of MS
|
||||
- **Clinically isolated syndrome (CIS)**
|
||||
- Single episode of neurologic symptoms suggestive of MS, chance of developing MS → CIS(+) MR(-) (20%) & if CIS(+) MR(+) (60-80%)
|
||||
- **Relapsing-remitting** **(RR-MS)**85% initial presentation
|
||||
- Relapses alternating with remission phases
|
||||
- **Relapsing-progressive** **(RP-MS)**
|
||||
- Secondary progressive MS, progressive worsening of neurologic function over time
|
||||
- **Primary progressive (PP-MS)**
|
||||
- 5-10% of patients progressive from start
|
||||
- **MS variants/subtypes**
|
||||
- **Malignant/Marburg disease**: Younger patients, febrile prodrome, clinically fulminant, death in months
|
||||
- **Schilder** type ("diffuse sclerosis"): Extensive, confluent, asymmetric demyelination in bilateral supra-/infratentorial parenchyma
|
||||
- **Baló**type ("concentric sclerosis"): Large lesions with alternating zones of demyelinated/myelinated WM
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Acute: Poorly delineated, yellowish-white, periventricular plaques
|
||||
- Chronic: Gray, granular, well-demarcated plaques ± generalized volume loss
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- Relatively sharp borders, macrophage infiltration (interstitial & perivascular), perivascular inflammation
|
||||
- Acute: Foamy macrophages, perivascular T-cell lymphocytic cuffing, microglial activation
|
||||
- Chronic: Marked loss of myelin, oligodendrocytes; dense astrogliosis; minimal/no perivascular inflammation
|
||||
- CSF positive for oligoclonal bands
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Weakness, numbness, tingling, gait disturbances, impaired vision, diplopia
|
||||
- ↓ sphincter control, paralysis, dementia
|
||||
- Cranial nerve palsy; usually multiple
|
||||
- Spinal cord symptoms
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- 20-40 years; median: 30 years
|
||||
- ### Sex
|
||||
|
||||
|
||||
- Adults: M:F = 1:1.77; adolescents: M:F = 1:3-5
|
||||
- ### Ethnicity
|
||||
|
||||
|
||||
- All groups but most common in white patients
|
||||
- ### Epidemiology
|
||||
|
||||
|
||||
- ~ 2.5 million people worldwide
|
||||
- Most often occurs in temperate zones
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- 1/3 have initial episode followed by near-normal function
|
||||
- Majority: Protracted course with progression of deficits
|
||||
- Late: Severe disability, cognitive impairment
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- Immunomodulators &/or immunosuppressants
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- 95% with clinically definite MS have positive MR
|
||||
|
||||
b58b4061-1b92-4b32-abf6-1debb49d180c
|
||||
|
||||
## References
|
||||
|
||||
# Selected References
|
||||
|
||||
1. [Gaitán MI et al: SWAN-Venule: an optimized MRI technique to detect the central vein sign in MS plaques. AJNR Am J Neuroradiol. 41(3):456-60, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32054616%5Bpmid%5D)
|
||||
1. [Sastre-Garriga J et al: MAGNIMS consensus recommendations on the use of brain and spinal cord atrophy measures in clinical practice. Nat Rev Neurol. 16(3):171-82, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=32094485%5Bpmid%5D)
|
||||
1. [do Amaral LLF et al: Gadolinium-enhanced susceptibility-weighted imaging in multiple sclerosis: optimizing the recognition of active plaques for different mr imaging sequences. AJNR Am J Neuroradiol. 40(4):614-9, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30846435%5Bpmid%5D)
|
||||
1. [Filippi M et al: Association between pathological and MRI findings in multiple sclerosis. Lancet Neurol. 18(2):198-210, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30663609%5Bpmid%5D)
|
||||
1. [Hartung HP et al: Diagnosis of multiple sclerosis: revisions of the McDonald criteria 2017 - continuity and change. Curr Opin Neurol. 32(3):327-37, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30985371%5Bpmid%5D)
|
||||
1. [Maranzano J et al: Comparison of multiple sclerosis cortical lesion types detected by multicontrast 3T and 7T MRI. AJNR Am J Neuroradiol. 40(7):1162-9, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31221631%5Bpmid%5D)
|
||||
1. [Suthiphosuwan S et al: The central vein sign in radiologically isolated syndrome. AJNR Am J Neuroradiol. 40(5):776-83, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31000526%5Bpmid%5D)
|
||||
1. [Zipp F et al: Implementing the 2017 McDonald criteria for the diagnosis of multiple sclerosis. Nat Rev Neurol. 15(8):441-5, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=31086264%5Bpmid%5D)
|
||||
1. [Filippi M et al: MRI in multiple sclerosis: what is changing? Curr Opin Neurol. 31(4):386-95, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29952834%5Bpmid%5D)
|
||||
1. [Inglese M et al: MRI in multiple sclerosis: clinical and research update. Curr Opin Neurol. 31(3):249-55, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29561520%5Bpmid%5D)
|
||||
1. [Thompson AJ et al: Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 17(2):162-73, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29275977%5Bpmid%5D)
|
||||
1. [Castellaro M et al: Heterogeneity of cortical lesion susceptibility mapping in multiple sclerosis. AJNR Am J Neuroradiol. 38(6):1087-95, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28408633%5Bpmid%5D)
|
||||
1. [Filippi M et al: MRI criteria for the diagnosis of multiple sclerosis: MAGNIMS consensus guidelines. Lancet Neurol. 15(3):292-303, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=26822746%5Bpmid%5D)
|
||||
1. [Roosendaal SD et al: Imaging phenotypes in multiple sclerosis. Neuroimaging Clin N Am. 25(1):83-96, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25476514%5Bpmid%5D)
|
||||
1. [Aliaga ES et al: MRI mimics of multiple sclerosis. Handb Clin Neurol. 122:291-316, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24507523%5Bpmid%5D)
|
||||
1. [Ciccarelli O et al: Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging. Lancet Neurol. 13(8):807-22, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=25008549%5Bpmid%5D)
|
||||
1. [Fernandez O et al: Biomarkers in multiple sclerosis: an update for 2014. Rev Neurol. 58(12):553-70, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24915032%5Bpmid%5D)
|
||||
1. [Hardy TA et al: Baló's concentric sclerosis. Lancet Neurol. 13(7):740-6, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24943346%5Bpmid%5D)
|
||||
1. [Miller TR et al: Advances in multiple sclerosis and its variants: conventional and newer imaging techniques. Radiol Clin North Am. 52(2):321-36, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24582342%5Bpmid%5D)
|
||||
1. [Steenwijk MD et al: What explains gray matter atrophy in long-standing multiple sclerosis? Radiology. 272(3):832-42, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24761837%5Bpmid%5D)
|
||||
1. [Klawiter EC: Current and new directions in MRI in multiple sclerosis. Continuum (Minneap Minn). 19(4 Multiple Sclerosis):1058-73, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23917101%5Bpmid%5D)
|
||||
1. [Polman CH et al: Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 69(2):292-302, 2011](http://www.ncbi.nlm.nih.gov/pubmed/?term=21387374%5Bpmid%5D)
|
||||
|
||||
|
||||
## Images
|
||||
|
||||
|
||||
### Selected Images
|
||||
|
||||
|
||||
*Sagittal graphic illustrates multiple sclerosis (MS) plaques involving the corpus callosum, pons, and spinal cord. Note the characteristic perpendicular orientation of the lesions <img src='/img/arrows/BS.png'/> at the callososeptal interface along penetrating venules.*
|
||||
|
||||
|
||||
*Sagittal graphic illustrates multiple sclerosis (MS) plaques involving the corpus callosum, pons, and spinal cord. Note the characteristic perpendicular orientation of the lesions <img src='/img/arrows/BS.png'/> at the callososeptal interface along penetrating venules.*
|
||||
|
||||
|
||||
*Sagittal FLAIR demonstrates numerous well-defined and ill-defined callososeptal hyperintensities <img src='/img/arrows/CC.png'/> radiating from the lateral ventricular margin with a typical perpendicular orientation, characteristic of MS.*
|
||||
|
||||
|
||||
*Sagittal FLAIR demonstrates numerous well-defined and ill-defined callososeptal hyperintensities <img src='/img/arrows/CC.png'/> radiating from the lateral ventricular margin with a typical perpendicular orientation, characteristic of MS.*
|
||||
|
||||
![Axial FLAIR MR shows subcortical <img src='/img/arrows/CC.png'/> and cortical <img src='/img/arrows/CS.png'/> demyelinating MS plaques. Cortical lesions are better seen at higher field strength MR and are classified as leukocortical [inner aspect of cortex ± involvement of juxtacortical white matter (WM)], intracortical (purely within cortex), and subpial (involving outer aspect of cortex).](images/app.statdx.com_image_thumbnail_8e1b38d3-c2c0-4128-80a1-f2e3640c3b91_annotated_true_size_900_quality_90_d73c35bf_20251018T122505Z.jpg)
|
||||
*Axial FLAIR MR shows subcortical <img src='/img/arrows/CC.png'/> and cortical <img src='/img/arrows/CS.png'/> demyelinating MS plaques. Cortical lesions are better seen at higher field strength MR and are classified as leukocortical [inner aspect of cortex ± involvement of juxtacortical white matter (WM)], intracortical (purely within cortex), and subpial (involving outer aspect of cortex).*
|
||||
|
||||
![Axial FLAIR MR shows subcortical <img src='/img/arrows/CC.png'/> and cortical <img src='/img/arrows/CS.png'/> demyelinating MS plaques. Cortical lesions are better seen at higher field strength MR and are classified as leukocortical [inner aspect of cortex ± involvement of juxtacortical white matter (WM)], intracortical (purely within cortex), and subpial (involving outer aspect of cortex).](images/app.statdx.com_image_thumbnail_8e1b38d3-c2c0-4128-80a1-f2e3640c3b91_size_168_quality_85_9844f252_20251018T095337Z.jpg)
|
||||
*Axial FLAIR MR shows subcortical <img src='/img/arrows/CC.png'/> and cortical <img src='/img/arrows/CS.png'/> demyelinating MS plaques. Cortical lesions are better seen at higher field strength MR and are classified as leukocortical [inner aspect of cortex ± involvement of juxtacortical white matter (WM)], intracortical (purely within cortex), and subpial (involving outer aspect of cortex).*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in a patient with MS demonstrate multiple enhancing plaques due to active demyelination. Punctate <img src='/img/arrows/CS.png'/>, nodular <img src='/img/arrows/CC.png'/>, and rim patterns <img src='/img/arrows/CO.png'/> are seen.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in a patient with MS demonstrate multiple enhancing plaques due to active demyelination. Punctate <img src='/img/arrows/CS.png'/>, nodular <img src='/img/arrows/CC.png'/>, and rim patterns <img src='/img/arrows/CO.png'/> are seen.*
|
||||
|
||||
|
||||
*Sagittal T1 MR in a patient with longstanding MS shows ovoid lesions in the periventricular WM with ill-defined hyperintense rims <img src='/img/arrows/CC.png'/> surrounding the plaques, giving the distinct lesion within a lesion appearance.*
|
||||
|
||||
|
||||
*Sagittal T1 MR in a patient with longstanding MS shows ovoid lesions in the periventricular WM with ill-defined hyperintense rims <img src='/img/arrows/CC.png'/> surrounding the plaques, giving the distinct lesion within a lesion appearance.*
|
||||
|
||||
|
||||
*Axial SWI (R) demonstrates characteristic perivenular location of a demyelinating plaque <img src='/img/arrows/CC.png'/> with the medullary vein <img src='/img/arrows/CS.png'/> coursing through it. Axial SWI (L) in the same patient shows findings related to Natalizumab-associated PML <img src='/img/arrows/WC.png'/> with juxtacortical hypointense rim <img src='/img/arrows/CO.png'/>.*
|
||||
|
||||
|
||||
*Axial SWI (R) demonstrates characteristic perivenular location of a demyelinating plaque <img src='/img/arrows/CC.png'/> with the medullary vein <img src='/img/arrows/CS.png'/> coursing through it. Axial SWI (L) in the same patient shows findings related to Natalizumab-associated PML <img src='/img/arrows/WC.png'/> with juxtacortical hypointense rim <img src='/img/arrows/CO.png'/>.*
|
||||
|
||||
|
||||
*Sagittal T1WI C+ MR shows a large hypointense mass <img src='/img/arrows/CC.png'/> with a peripheral crescent of incomplete or "open ring" enhancement <img src='/img/arrows/CS.png'/>. This enhancement pattern is classic for a tumefactive demyelinating disease, most commonly MS.*
|
||||
|
||||
|
||||
*Sagittal T1WI C+ MR shows a large hypointense mass <img src='/img/arrows/CC.png'/> with a peripheral crescent of incomplete or "open ring" enhancement <img src='/img/arrows/CS.png'/>. This enhancement pattern is classic for a tumefactive demyelinating disease, most commonly MS.*
|
||||
|
||||
|
||||
*MRS at 144 TE in the same patient demonstrates a large choline peak <img src='/img/arrows/CC.png'/> with ↓ in NAA <img src='/img/arrows/CS.png'/>. MRS in a tumefactive demyelinating lesion is not specific and can mimic a tumor profile. MR DSC perfusion (insert) shows marked ↓ rCBV <img src='/img/arrows/WO.png'/>, which goes more in favor of a demyelinating lesion.*
|
||||
|
||||
|
||||
*MRS at 144 TE in the same patient demonstrates a large choline peak <img src='/img/arrows/CC.png'/> with ↓ in NAA <img src='/img/arrows/CS.png'/>. MRS in a tumefactive demyelinating lesion is not specific and can mimic a tumor profile. MR DSC perfusion (insert) shows marked ↓ rCBV <img src='/img/arrows/WO.png'/>, which goes more in favor of a demyelinating lesion.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR demonstrates concentric laminated "onion bulb" enhancement <img src='/img/arrows/CC.png'/>, characteristic of acute Baló concentric sclerosis. Baló concentric sclerosis is a rare aggressive MS variant characterized by acute onset and rapid deterioration.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR demonstrates concentric laminated "onion bulb" enhancement <img src='/img/arrows/CC.png'/>, characteristic of acute Baló concentric sclerosis. Baló concentric sclerosis is a rare aggressive MS variant characterized by acute onset and rapid deterioration.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in a young male with rapid onset of visual disturbance demonstrates large enhancing demyelinating lesions <img src='/img/arrows/CS.png'/> in the deep and periventricular WM. Marburg disease is an acute fulminant MS variant.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in a young male with rapid onset of visual disturbance demonstrates large enhancing demyelinating lesions <img src='/img/arrows/CS.png'/> in the deep and periventricular WM. Marburg disease is an acute fulminant MS variant.*
|
||||
|
||||
|
||||
### Additional Images
|
||||
|
||||
|
||||
*Sagittal FLAIR MR shows MS plaques with typical perpendicular orientation at the callososeptal interface along penetrating venules ("Dawson fingers"), as well as involving subcortical WM.*
|
||||
|
||||
|
||||
*Sagittal FLAIR MR shows MS plaques with hyperintense rim and central hypointensity (latter also hypointense on T1WI; not shown). Note the characteristic posterior fossa lesion <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Axial T1WI C+ MR demonstrates nodular, enhancing MS plaques. Note the common periventricular location with perpendicular orientation, as well as the involvement of subcortical WM.*
|
||||
|
||||
|
||||
*Axial T2WI MR demonstrates very hypointense bilateral basal ganglia, atrophy (evidenced by ventricular prominence), and confluent periventricular/subcortical hyperintense plaques in this patient with advanced MS.*
|
||||
|
||||
|
||||
*Axial T1WI C+ MR shows irregular, thick, partial ring enhancement around a mass-like lesion in a patient not previously diagnosed with MS. This was biopsy-proven tumefactive MS. (Courtesy M. Mirfakharee, MD.)*
|
||||
|
||||
|
||||
*Sagittal FLAIR shows callososeptal hyperintensities radiating from the lateral ventricles with a typical perpendicular orientation, characteristic of MS.*
|
||||
|
||||
|
||||
*Axial FLAIR MR 3T shows multiple nonenhancing, periventricular, hyperintense MS lesions oriented perpendicular to the callosomarginal interface. These lesions are perivenular, along the path of the deep medullary veins, and represent "Dawson fingers." Confluent lesions are also seen along the right periventricular margin.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows confluent periventricular WM hyperintensity typical of advanced, longstanding MS with loss of discrete, linear, periventricular lesions.*
|
||||
|
||||
|
||||
*Sagittal T1WI MR shows multiple hypointense lesions ("black holes") in the deep WM <img src='/img/arrows/BS.png'/> related to axonal destruction. Note the associated moderate ventricular and sulcal enlargement.*
|
||||
|
||||
|
||||
*Coronal T1WI C+ MR shows a hypointense mass in the left posterior frontal region with a peripheral crescent of incomplete or "horseshoe" enhancement <img src='/img/arrows/WS.png'/>. This enhancement pattern is classic for tumefactive demyelinating disease, most commonly MS.*
|
||||
|
||||
|
||||
*Axial T1WI C+ FS shows bright enhancement of the optic nerves <img src='/img/arrows/WS.png'/>, similar to the extraocular muscles, in a patient with MS and acute bilateral optic neuritis.*
|
||||
|
||||
|
||||
*Axial FLAIR MR shows numerous peripheral WM and cortical lesions that exhibited robust contrast enhancement in an 18-year-old woman with malignant (Marburg) MS. The patient presented with a 2-week history of behavioral changes and leg pain and died 3 weeks after presentation. Autopsy showed typical demyelinating pathology.*
|
||||
|
||||
|
||||
*Axial T1WI C+ MR shows numerous enhancing MS plaques that were present throughout the infratentorial and supratentorial brain. Lesions may show homogeneous enhancement but may also exhibit ring or an incomplete ring pattern of enhancement.*
|
||||
|
||||
|
||||
*Sagittal FLAIR shows callososeptal hyperintensities <img src='/img/arrows/CC.png'/> radiating from the lateral ventricles with a typical perpendicular orientation, characteristic of MS.*
|
||||
|
||||
|
||||
*Axial FLAIR in a 35-year-old woman with MS shows extensive confluent periventricular hyperintense lesions <img src='/img/arrows/CS.png'/>, typical of advanced, longstanding MS with loss of discrete, linear, periventricular lesions. Note prominence of the ventricles and cortical sulci due to diffuse atrophy.*
|
||||
|
||||
|
||||
*Sagittal T1WI MR shows multiple hypointense lesions ("black holes") in the periventricular WM <img src='/img/arrows/CS.png'/> related to axonal destruction. Note the associated moderate ventricular and sulcal enlargement. T1 "back holes" are correlated with greater tissue damage and ↑ axonal destruction on histopathology.*
|
||||
|
||||
|
||||
*Axial SWI demonstrates characteristic perivenular location of a demyelinating plaque <img src='/img/arrows/CC.png'/> with the medullary vein <img src='/img/arrows/CS.png'/> coursing through it.*
|
||||
|
||||
@@ -0,0 +1,445 @@
|
||||
---
|
||||
title: "Neuromyelitis Optica Spectrum Disorders"
|
||||
docid: "54d4a8bc-9267-4df6-98c1-f22aae051d01"
|
||||
authors:
|
||||
- key: "a25c450b-3d34-4f64-bba3-cc0834813df6"
|
||||
value: "Miral D. Jhaveri, MD, MBA"
|
||||
breadcrumbs:
|
||||
-
|
||||
name: "Brain"
|
||||
slug: "brain"
|
||||
treeNodeId: "6d8829f1-14d7-45af-8675-255189aa526a"
|
||||
-
|
||||
name: "Diagnosis"
|
||||
slug: "diagnosis"
|
||||
treeNodeId: "51c00394-446e-4a38-94af-d3b1d14d34e8"
|
||||
-
|
||||
name: "Pathology-Based Diagnoses"
|
||||
slug: "pathology-based-diagnoses"
|
||||
treeNodeId: "d9d3a8ed-f21b-4831-8c77-591a3500ef77"
|
||||
-
|
||||
name: "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
slug: "infectious-inflammatory-and-demyel-"
|
||||
treeNodeId: "7210f860-fe5f-4a2d-81cc-4fe06c769607"
|
||||
-
|
||||
name: "Inflammatory and Demyelinating Disease"
|
||||
slug: "inflammatory-and-demyelinating-dis-"
|
||||
treeNodeId: "62ab4dc3-dbf6-45a9-8532-f0e962aa62dc"
|
||||
-
|
||||
name: "Neuromyelitis Optica Spectrum Disorders"
|
||||
slug: "neuromyelitis-optica-spectrum-diso-"
|
||||
treeNodeId: null
|
||||
category: "Brain"
|
||||
documentVersionId: "e640534a-1c8b-4d12-970e-c0994fbfc239"
|
||||
imageCount: 22
|
||||
lastUpdated: "07/28/20"
|
||||
pageDescription: "Neuromyelitis Optica Spectrum Disorders"
|
||||
pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Infectious, Inflammatory, and Demyelinating Disease, Inflammatory and Demyelinating Disease, Neuromyelitis Optica Spectrum Disorders"
|
||||
pageTitle: "Neuromyelitis Optica Spectrum Disorders | STATdx"
|
||||
enhancedTitle: "Neuromyelitis Optica Spectrum Disorders"
|
||||
type: "DX"
|
||||
references: true
|
||||
breadcrumbs:
|
||||
- "Brain"
|
||||
- "Diagnosis"
|
||||
- "Pathology-Based Diagnoses"
|
||||
- "Infectious, Inflammatory, and Demyelinating Disease"
|
||||
- "Inflammatory and Demyelinating Disease"
|
||||
- "Neuromyelitis Optica Spectrum Disorders"
|
||||
---
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Neuromyelitis optica spectrum disorders (NMOSDs)
|
||||
- MOG antibody-associated disease (MOG-AAD)
|
||||
- Autoimmune inflammatory demyelinating disease of CNS with preferential involvement of optic nerves and spinal cord, AQP4 antibody (+/-)
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Hyperintense, mildly enlarged optic nerves + enhancement
|
||||
- **AQP4 antibody (+)**:****More posterior involvement, including chiasm
|
||||
- **MOG-AAD**:****More anterior optic nerve involvement
|
||||
- Expansile, hyperintense cord signal, ≥ 3 segments
|
||||
- Brain lesions in NMOSD are distinct from multiple sclerosis (MS)
|
||||
- Acute cord lesions show patchy enhancement
|
||||
- Patchy enhancement with blurred margins (cloud-like enhancement) in cerebral lesions
|
||||
- "Pencil-thin" ependymal enhancement
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- MS, acute disseminated encephalomyelitis (ADEM)
|
||||
- Optic neuritis, transverse myelitis
|
||||
- Spinal cord neoplasm, neurosarcoid
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- NMO antibody: IgG autoantibody that binds to AQP4
|
||||
- **AQP4-IgG** is 90% specific and 70-75% sensitive for NMOSD
|
||||
- **AQP4-IgG (-) NMOSD** less common (10-25%)
|
||||
- Minority of AQP4-IgG (-) patients with phenotype of NMOSD are MOG-IgG (+)
|
||||
- 2015 International Panel for NMO Diagnosis (IPND) developed revised diagnostic criteria for NMOSD stratified by serologic testing (NMOSD with or without AQP4-IgG)
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Impaired vision, myelopathy, brainstem syndrome
|
||||
- Relapsing course in 85-90% of patients
|
||||
- Acute exacerbation: Steroids, plasmapheresis
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Neuromyelitis optica spectrum disorders (NMOSDs)
|
||||
- Aquaporin-4 (AQP4)
|
||||
- Myelin oligodendrocyte glycoprotein (MOG)
|
||||
- MOG antibody-associated disease (MOG-AAD)
|
||||
- ## Synonyms
|
||||
|
||||
|
||||
- Devic syndrome
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Autoimmune inflammatory demyelinating disease of CNS with preferential involvement of optic nerves and spinal cord, AQP4 antibody (+/-)
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Optic neuritis and myelitis
|
||||
- Spectrum of lesions atypical for multiple sclerosis (MS)
|
||||
- ### Location
|
||||
|
||||
|
||||
- **AQP4 antibody (+)**
|
||||
- Spinal cord: More common cervicomedullary junction
|
||||
- Optic nerves: More posterior involvement of optic nerve, including chiasm, bilateral disease
|
||||
- Brain lesions: Deep white matter, periependymal regions, corpus callosum, corticospinal tracts, brainstem, and cerebellum
|
||||
- **MOG-AAD**
|
||||
- Spinal cord: More likely thoracolumbar and conus
|
||||
- Optic nerves: Long, bilateral, anterior optic nerve
|
||||
- Brain lesions: Basal ganglia, thalamus, infratentorial (brainstem, cerebellar peduncles, around 4th ventricle)
|
||||
- ### Size
|
||||
|
||||
|
||||
- Spinal lesions typically expansile, multisegment
|
||||
- Brain lesions punctate or small (< 3 mm) to large, confluent in cerebral white matter
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- Hyperintense, mildly enlarged optic nerves
|
||||
- **AQP4 antibody (+)**:****More posterior involvement, including chiasm
|
||||
- **MOG-AAD**: More anterior optic nerve involvement
|
||||
- Expansile, hyperintense cord signal, ≥ 3 segments → longitudinally extensive transverse myelitis (LETM)
|
||||
- May have heterogeneous areas of brighter T2 signal
|
||||
- Central/central and peripheral, > 50% cord area
|
||||
- ### STIR
|
||||
|
||||
|
||||
- Hyperintense optic nerve
|
||||
- LETM: Central gray matter/central and peripheral, > 50% cord area
|
||||
- ### FLAIR
|
||||
|
||||
|
||||
- Brain lesions are quite characteristic and distinct from lesions in MS
|
||||
- Hyperintense brain lesions in AQP4 antibody (+) NMOSD correspond to sites of high AQP4 expression
|
||||
- Adjacent to ventricular system at any level
|
||||
- **Periependymal surrounding 3rd ventricle and cerebral aqueduct**
|
||||
- Thalamus, hypothalamus, ventral midbrain
|
||||
- **Dorsal brainstem adjacent to 4th ventricle**
|
||||
- Including area postrema and nucleus tracts solitarius
|
||||
- **Periventricular surrounding lateral ventricles**
|
||||
- Follow ependymal lining in disseminated pattern
|
||||
- Often edematous and heterogeneous, creating marbled pattern unlike MS
|
||||
- Complete thickness of splenium in unique arch bridge pattern
|
||||
- Chronic lesions reduce in size and intensity; may even disappear
|
||||
- Cystic changes and atrophy of corpus callosum
|
||||
- **Lesions involving corticospinal tracts**
|
||||
- Unilateral or bilateral, posterior limb internal capsule, cerebral peduncle
|
||||
- Contiguous, often longitudinally extensive
|
||||
- **Extensive hemispheric lesions**
|
||||
- Tumefactive (> 3 cm), long spindle-like, or radial
|
||||
- Occasionally mimicking posterior reversible encephalopathy syndrome (PRES)
|
||||
- **Nonspecific lesions: Not unique, but most common**
|
||||
- Nonspecific punctate or small (< 3 mm) dots or patches of hyperintensities in subcortical or deep white matter
|
||||
- **MOG-AAD** lesions tend to involve deep gray matter and infratentorial parenchyma
|
||||
- ### DWI
|
||||
|
||||
|
||||
- ↑ diffusivity, ↓ fractional anisotropy than MS patients or controls
|
||||
- Patient with NMOSD and normal brain MR
|
||||
- DTI shows ↑ mean diffusivity in corticospinal tract and optic radiation, but not in cingulum or corpus callosum
|
||||
- ### T1WI C+
|
||||
|
||||
|
||||
- Long-segment optic nerve enhancement unilateral or bilateral, often extending posterior to optic chiasm
|
||||
- Acute lesions in cord show patchy enhancement
|
||||
- Most brain lesions do not show enhancement
|
||||
- Patchy enhancement with blurred margins (cloud-like enhancement) in cerebral lesions
|
||||
- Relatively specific for NMOSD
|
||||
- "Pencil-thin" ependymal enhancement
|
||||
- Rarely, well-marginated nodular enhancement, leptomeningeal enhancement
|
||||
- ### MRS
|
||||
|
||||
|
||||
- In NMOSD, metabolites are normal in normal-appearing white matter (NAWM) and normal-appearing gray matter (NAGM) compared to patients with MS
|
||||
- In MS, NAA ↓ and choline ↑ in NAWM
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- Contrast-enhanced MR of brain, spine, and orbits
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- Orbits: Axial and coronal STIR/T2 FS and T1 C+ FS
|
||||
- Spine: Sagittal STIR/T2, T1WI C+
|
||||
- Brain: Axial and sagittal FLAIR, T1WI C+
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Multiple Sclerosis](/document/multiple-sclerosis/7892b2a2-f52a-4d7f-9858-a326f2b7ab04)
|
||||
- Radially oriented, perivenular lesions (Dawson fingers)
|
||||
- Optic neuritis, typically unilateral, shorter segment
|
||||
- Myelitis, usually smaller longitudinal extension, peripheral
|
||||
- [Acute Disseminated Encephalomyelitis](/document/adem/a3fafeb7-5861-4364-beb8-c0e30220564e)
|
||||
- Bilateral, asymmetric involvement of supratentorial and infratentorial, white matter and gray matter lesions
|
||||
- Common in children and young adults
|
||||
- LETM similar to NMOSD
|
||||
- [Optic Neuritis](/document/optic-neuritis/ac9c8fc9-33cd-4716-a509-2542ec5579ca)
|
||||
- 1 component of NMOSD
|
||||
- Consider NMOSD in case of 1st optic neuritis, but otherwise normal brain MR
|
||||
- [Transverse Myelitis](/document/idiopathic-acute-transverse-myelit-/6e774628-d7ad-48f1-9847-e09a4fad168b)
|
||||
- 1 component of NMOSD
|
||||
- Idiopathic inflammatory or postinfectious myelitis
|
||||
- Differentiation from other immune-mediated myelitis like Sjögren disease or SLE difficult
|
||||
- [Spinal Cord Neoplasm](/document/spinal-cord-astrocytoma/43d5efa2-7a6d-4972-bfc6-c300cc31f9af)
|
||||
- Astrocytoma or ependymoma can show similar multisegment cord T2 hyperintensity and enhancement
|
||||
- [Neurosarcoid](/document/neurosarcoid/fef69139-0019-4be3-9bdc-e26bc3644251)
|
||||
- Parenchymal granulomas near hypothalamus, visual pathway
|
||||
- Optic nerve involvement bilateral, extensive, resemble NMOSD
|
||||
- Nodular leptomeningeal, dural, and cranial nerve enhancement
|
||||
- Systemic manifestations, (+) chest x-ray
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- NMO antibody: IgG autoantibody that binds to AQP4
|
||||
- AQP4 channel is most abundant water channel in CNS
|
||||
- Located in foot processes of astrocytes
|
||||
- Highly expressed in optic nerve, spinal cord, periventricular areas, hypothalamus, subpial regions, brainstem, area postrema
|
||||
- **AQP4-IgG** can be identified in other autoimmune disorders, myasthenia gravis, SLE, Sjögren syndrome, RA
|
||||
- Rare clinical coexistence of anti-*n*-methyl-*d*-aspartate (NMDA) receptor encephalitis and NMOSD
|
||||
- **AQP4-IgG** is 90% specific and 70-75% sensitive for NMOSD
|
||||
- **AQP4-IgG (-) NMOSD** less common (10-25%)
|
||||
- Minority of AQP4-IgG (-) patients with phenotype of NMOSD are MOG-IgG (+)
|
||||
- MOG antibody targets oligodendrocytes
|
||||
- MOG-IgG also found in association with other demyelinating disorders, such as MS, acute disseminated encephalomyelitis (ADEM), optic neuritis, LETM
|
||||
- Controversial if MOG-AAD distinct entity or part of NMOSD
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- Selective AQP4 immunoreactivity loss, vasculocentric complement, immunoglobulin deposition characteristic
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Optic neuritis: Impaired or double vision
|
||||
- Myelitis: Myelopathy
|
||||
- Brainstem symptoms: Nystagmus, dysarthria, dysphagia, ataxia, ophthalmoplegia
|
||||
- Area postrema syndrome: Hiccups, nausea, vomiting
|
||||
- Symptomatic narcolepsy or acute diencephalic syndrome
|
||||
- ### Clinical profile
|
||||
|
||||
|
||||
- CSF: Pleocytosis, ↑ protein, (-) oligoclonal bands
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- 1st symptoms commonly between 32-45 years of age
|
||||
- 15-20% of patients over age 60 at onset
|
||||
- NMOSD worldwide disease
|
||||
- AQP4(+) NMOSD, F:M ratio is 8-9:1
|
||||
- MOG-AAD usually younger age at onset, F:M ratio is ~ 1:1
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Relapsing course in 85-90% of patients
|
||||
- Worse prognosis with more severe disability than MS
|
||||
- Anti-AQP4 antibody (+): High risk of further relapses
|
||||
- MOG-AAD: More likely to be monophasic, fewer relapses
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- Acute exacerbation: Steroids
|
||||
- Plasma exchange in relapses not responding to steroids
|
||||
- Prevention of relapses: Immunosuppression, eculizumab
|
||||
- Symptom management and rehabilitation
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Consider
|
||||
|
||||
|
||||
- NMOSD in patient with optic neuritis and myelitis
|
||||
- Characteristic brain lesions involving periependymal regions, corpus callosum, corticospinal tracts, brainstem
|
||||
|
||||
9e0e24a9-6707-4e55-9895-fe13a49f7c8e
|
||||
|
||||
## References
|
||||
|
||||
# Selected References
|
||||
|
||||
1. [Rosenthal JF et al: CNS inflammatory demyelinating disorders: MS, NMOSD and MOG antibody associated disease. J Investig Med. 68(2):321-30, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=31582425%5Bpmid%5D)
|
||||
1. [Salama S et al: MRI differences between MOG antibody disease and AQP4 NMOSD. Mult Scler. 1352458519893093, 2020](http://www.ncbi.nlm.nih.gov/pubmed/?term=31937191%5Bpmid%5D)
|
||||
1. [Fujihara K: Neuromyelitis optica spectrum disorders: still evolving and broadening. Curr Opin Neurol. 32(3):385-94, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30893099%5Bpmid%5D)
|
||||
1. [Huda S et al: Neuromyelitis optica spectrum disorders. Clin Med (Lond). 19(2):169-76, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30872305%5Bpmid%5D)
|
||||
1. [Wynford-Thomas R et al: Neurological update: MOG antibody disease. J Neurol. 266(5):1280-6, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30569382%5Bpmid%5D)
|
||||
1. [Dutra BG et al: Neuromyelitis optica spectrum disorders: spectrum of MR imaging findings and their differential diagnosis. Radiographics. 38(1):169-93, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29320331%5Bpmid%5D)
|
||||
1. [Narayan R et al: MOG antibody disease: a review of MOG antibody seropositive neuromyelitis optica spectrum disorder. Mult Scler Relat Disord. 25:66-72, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=30048919%5Bpmid%5D)
|
||||
1. [Kim HJ et al: MRI characteristics of neuromyelitis optica spectrum disorder: an international update. Neurology. 84(11):1165-73, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25695963%5Bpmid%5D)
|
||||
1. [Wingerchuk DM et al: International consensus diagnostic criteria for neuromyelitis optica spectrum disorders. Neurology. 85(2):177-89, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=26092914%5Bpmid%5D)
|
||||
1. [Barnett Y et al: Conventional and advanced imaging in neuromyelitis optica. AJNR Am J Neuroradiol. 35(8):1458-66, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=23764723%5Bpmid%5D)
|
||||
1. [Kawachi I et al: [Characteristic features of radiological findings in multiple sclerosis and neuromyelitis optica.] Nihon Rinsho. 72(11):1976-82, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=25518380%5Bpmid%5D)
|
||||
1. [Uzawa A et al: Neuromyelitis optica: concept, immunology and treatment. J Clin Neurosci. 21(1):12-21, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=23916471%5Bpmid%5D)
|
||||
1. [Jacob A et al: Current concept of neuromyelitis optica (NMO) and NMO spectrum disorders. J Neurol Neurosurg Psychiatry. 84(8):922-30, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23142960%5Bpmid%5D)
|
||||
1. [Sato DK et al: Clinical spectrum and treatment of neuromyelitis optica spectrum disorders: evolution and current status. Brain Pathol. 23(6):647-60, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=24118482%5Bpmid%5D)
|
||||
1. [Kim W et al: Brain abnormalities in neuromyelitis optica spectrum disorder. Mult Scler Int. 2012:735486, 2012](http://www.ncbi.nlm.nih.gov/pubmed/?term=23259063%5Bpmid%5D)
|
||||
1. [Lana-Peixoto MA et al: The expanded spectrum of neuromyelitis optica: evidences for a new definition. Arq Neuropsiquiatr. 70(10):807-13, 2012](http://www.ncbi.nlm.nih.gov/pubmed/?term=23060108%5Bpmid%5D)
|
||||
1. [Benavente E et al: Neuromyelitis optica-AQP4: an update. Curr Rheumatol Rep. 13(6):496-505, 2011](http://www.ncbi.nlm.nih.gov/pubmed/?term=21922173%5Bpmid%5D)
|
||||
1. [Cree B: Neuromyelitis optica: diagnosis, pathogenesis, and treatment. Curr Neurol Neurosci Rep. 8(5):427-33, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18713580%5Bpmid%5D)
|
||||
1. [Jacob A et al: Treatment of neuromyelitis optica with rituximab: retrospective analysis of 25 patients. Arch Neurol. 65(11):1443-8, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18779415%5Bpmid%5D)
|
||||
1. [Li Y et al: Brain magnetic resonance imaging abnormalities in neuromyelitis optica. Acta Neurol Scand. 118(4):218-25, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18384459%5Bpmid%5D)
|
||||
1. [Jarius S et al: NMO-IgG in the diagnosis of neuromyelitis optica. Neurology. 68(13):1076-7, 2007](http://www.ncbi.nlm.nih.gov/pubmed/?term=17287449%5Bpmid%5D)
|
||||
1. [Matiello M et al: Neuromyelitis optica. Curr Opin Neurol. 20(3):255-60, 2007](http://www.ncbi.nlm.nih.gov/pubmed/?term=17495617%5Bpmid%5D)
|
||||
1. [Benedetti B et al: Grading cervical cord damage in neuromyelitis optica and MS by diffusion tensor MRI. Neurology. 67(1):161-3, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16832101%5Bpmid%5D)
|
||||
1. [Pittock SJ et al: Brain abnormalities in neuromyelitis optica. Arch Neurol. 63(3):390-6, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16533966%5Bpmid%5D)
|
||||
1. [Wingerchuk DM et al: Revised diagnostic criteria for neuromyelitis optica. Neurology. 66(10):1485-9, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16717206%5Bpmid%5D)
|
||||
|
||||
|
||||
## Images
|
||||
|
||||
|
||||
### Selected Images
|
||||
|
||||
|
||||
*Axial T1 C+ MR in a 22-year-old woman with right vision loss demonstrates swelling with enhancement <img src='/img/arrows/CC.png'/> of the intraorbital segment of the right optic nerve.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in a 22-year-old woman with right vision loss demonstrates swelling with enhancement <img src='/img/arrows/CC.png'/> of the intraorbital segment of the right optic nerve.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in a 22-year-old woman with right vision loss demonstrates swelling with enhancement <img src='/img/arrows/CC.png'/> of the intraorbital segment of the right optic nerve.*
|
||||
|
||||
|
||||
*Axial FLAIR MR (top) and T1 C+ MR (bottom) images in the same patient show hyperintense enhancing lesions <img src='/img/arrows/CS.png'/> along the cerebral peduncles. AQP4 antibody was positive in this patient with NMOSD. Brain lesions in NMOSD typically involve the deep white matter, periependymal regions, corpus callosum, corticospinal tracts, brainstem, and cerebellum.*
|
||||
|
||||
|
||||
*Axial FLAIR MR (top) and T1 C+ MR (bottom) images in the same patient show hyperintense enhancing lesions <img src='/img/arrows/CS.png'/> along the cerebral peduncles. AQP4 antibody was positive in this patient with NMOSD. Brain lesions in NMOSD typically involve the deep white matter, periependymal regions, corpus callosum, corticospinal tracts, brainstem, and cerebellum.*
|
||||
|
||||
|
||||
*Coronal T1 C+ MR images in a patient with AQP4 antibody (+) NMOSD show enhancement along the prechiasmatic right optic nerve <img src='/img/arrows/CC.png'/> and the optic chiasm <img src='/img/arrows/CO.png'/>.*
|
||||
|
||||
|
||||
*Coronal T1 C+ MR images in a patient with AQP4 antibody (+) NMOSD show enhancement along the prechiasmatic right optic nerve <img src='/img/arrows/CC.png'/> and the optic chiasm <img src='/img/arrows/CO.png'/>.*
|
||||
|
||||
|
||||
*Axial FLAIR MR (top) and T1 C+ MR (bottom) in the same patient show hyperintense lesions with patchy enhancement in the periependymal region surrounding the 3rd ventricle <img src='/img/arrows/CS.png'/>, and the hypothalamus <img src='/img/arrows/CO.png'/>. Brain lesions in NMOSD are typically localized in the periependymal regions where AQP4 is highly expressed.*
|
||||
|
||||
|
||||
*Axial FLAIR MR (top) and T1 C+ MR (bottom) in the same patient show hyperintense lesions with patchy enhancement in the periependymal region surrounding the 3rd ventricle <img src='/img/arrows/CS.png'/>, and the hypothalamus <img src='/img/arrows/CO.png'/>. Brain lesions in NMOSD are typically localized in the periependymal regions where AQP4 is highly expressed.*
|
||||
|
||||
|
||||
*Sagittal STIR MR in a patient presenting with myelopathy demonstrates a long segment of cord enlargement with hyperintensity <img src='/img/arrows/CC.png'/>.*
|
||||
|
||||
|
||||
*Sagittal STIR MR in a patient presenting with myelopathy demonstrates a long segment of cord enlargement with hyperintensity <img src='/img/arrows/CC.png'/>.*
|
||||
|
||||
|
||||
*Sagittal T1 C+ FS MR in the same patient demonstrates patchy enhancement <img src='/img/arrows/CS.png'/> in the cervical and upper thoracic cord. Cord lesions in NMOSD typically extend over 3 or more contiguous vertebral segments. There is involvement of the central gray matter or central and peripheral regions of the cord with > 50% cord area in the axial plane.*
|
||||
|
||||
|
||||
*Sagittal T1 C+ FS MR in the same patient demonstrates patchy enhancement <img src='/img/arrows/CS.png'/> in the cervical and upper thoracic cord. Cord lesions in NMOSD typically extend over 3 or more contiguous vertebral segments. There is involvement of the central gray matter or central and peripheral regions of the cord with > 50% cord area in the axial plane.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with AQP4-IgG (+) NMOSD demonstrates large confluent lesions in the right temporal and occipital regions <img src='/img/arrows/CC.png'/> with involvement of the splenium <img src='/img/arrows/CS.png'/> of the corpus callosum.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with AQP4-IgG (+) NMOSD demonstrates large confluent lesions in the right temporal and occipital regions <img src='/img/arrows/CC.png'/> with involvement of the splenium <img src='/img/arrows/CS.png'/> of the corpus callosum.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows large patchy areas of enhancement <img src='/img/arrows/CC.png'/>, often called "cloud-like" enhancement. This is one of the most common patterns of enhancement in NMOSD. Other patterns of enhancement include "pencil-thin" periependymal, nodular, and leptomeningeal.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows large patchy areas of enhancement <img src='/img/arrows/CC.png'/>, often called "cloud-like" enhancement. This is one of the most common patterns of enhancement in NMOSD. Other patterns of enhancement include "pencil-thin" periependymal, nodular, and leptomeningeal.*
|
||||
|
||||
|
||||
*Sagittal T2 MR (right) and T1 C+ MR (left) in a patient with NMOSD presenting with nausea and myelopathy demonstrate patchy enhancing lesion involving the dorsal medulla <img src='/img/arrows/CC.png'/> (area postrema region) and the upper cervical cord <img src='/img/arrows/CO.png'/>.*
|
||||
|
||||
|
||||
*Sagittal T2 MR (right) and T1 C+ MR (left) in a patient with NMOSD presenting with nausea and myelopathy demonstrate patchy enhancing lesion involving the dorsal medulla <img src='/img/arrows/CC.png'/> (area postrema region) and the upper cervical cord <img src='/img/arrows/CO.png'/>.*
|
||||
|
||||
|
||||
*Axial FLAIR (top) and T1 C+ MR (bottom) show patchy hyperintensity involving the cortex <img src='/img/arrows/CC.png'/>, cingulate gyrus, and corpus callosum <img src='/img/arrows/CO.png'/> with leptomeningeal <img src='/img/arrows/CS.png'/> and nodular <img src='/img/arrows/WC.png'/> enhancement. MOG was (+) and AQP4-IgG was (-).*
|
||||
|
||||
|
||||
*Axial FLAIR (top) and T1 C+ MR (bottom) show patchy hyperintensity involving the cortex <img src='/img/arrows/CC.png'/>, cingulate gyrus, and corpus callosum <img src='/img/arrows/CO.png'/> with leptomeningeal <img src='/img/arrows/CS.png'/> and nodular <img src='/img/arrows/WC.png'/> enhancement. MOG was (+) and AQP4-IgG was (-).*
|
||||
|
||||
|
||||
### Additional Images
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with NMO demonstrates an ill-defined hyperintense lesion involving the right cerebral peduncle and midbrain <img src='/img/arrows/CC.png'/>.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows a well-defined nodular area of enhancement <img src='/img/arrows/CS.png'/> in the region of FLAIR signal abnormality. Most reported NMO brain lesions do not show enhancement. The enhancement patterns reported include patchy enhancement with blurred margins ("cloud-like" enhancement), "pencil-thin" ependymal enhancement, and solid enhancement.*
|
||||
|
||||
|
||||
*Axial T1WI C+ FS MR shows a markedly enhancing prechiasmatic right optic nerve and chiasm <img src='/img/arrows/WS.png'/>, consistent with acute optic neuritis.*
|
||||
|
||||
|
||||
*Sagittal T2 DP FSE MR in the same patient shows a long segment of cord enlargement with hyperintensity. Ill-defined enhancement was also present in the cervical cord in this patient with myelopathy and vision loss. Patients with NMO have a worse prognosis with more severe disability than multiple sclerosis, despite lack of brain involvement.*
|
||||
|
||||
|
||||
*Sagittal T2 (left) and T1WI C+ FS (right) images show multilevel T2 hyperintensity with irregular posterior enhancement <img src='/img/arrows/WS.png'/> in the cervical cord in a patient with a previous history of optic neuritis.*
|
||||
|
||||
|
||||
*Sagittal T2WI MR in the same patient 1 year after treatment shows near-complete resolution of the T2 signal abnormality. Enhancement was no longer seen in the cervical cord. The cord lesions seen in NMO typically extend over 3 or more segments.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient who presented with altered sensorium demonstrates a large hyperintense lesion in the left medial temporal lobe <img src='/img/arrows/CC.png'/>.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows patchy enhancement <img src='/img/arrows/CC.png'/> with blurred margins ("cloud-like" enhancement). NMO- IgG antibody in serum was positive in this patient. This pattern of enhancement has been reported as relatively specific for NMO.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient 4 days after IV steroid therapy shows almost complete resolution of the enhancement <img src='/img/arrows/CS.png'/>.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with NMO shows multiple characteristic brain lesions. A large tumefactive lesion with ill-defined borders is seen in the left frontal lobe <img src='/img/arrows/CC.png'/>. An ill-defined hyperintense lesion is seen involving the posterior limb of right internal capsule <img src='/img/arrows/CS.png'/>, and there is involvement of the splenium of corpus callosum <img src='/img/arrows/WO.png'/> in a unique "arch bridge" pattern.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a patient with NMOSD shows characteristic periependymal lesions surrounding the 3rd ventricle, involving the thalamus <img src='/img/arrows/CC.png'/> and hypothalamus <img src='/img/arrows/CS.png'/>.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient shows subtle rim enhancement in the lesion in the right thalamus <img src='/img/arrows/CS.png'/>. Brain lesions in NMO/NMOSD are typically localized in the periependymal regions where AQP4 is highly expressed.*
|
||||
|
||||
@@ -0,0 +1,504 @@
|
||||
---
|
||||
title: "Pediatric Multiple Sclerosis, Brain"
|
||||
docid: "f2592b04-f800-4235-9eea-a43f2bf4adfe"
|
||||
authors:
|
||||
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|
||||
value: "Kevin R. Moore, MD"
|
||||
breadcrumbs:
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|
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|
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slug: "pediatrics"
|
||||
treeNodeId: "a915965c-d436-44cf-ae65-2f22e7246ea4"
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|
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|
||||
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|
||||
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treeNodeId: "feaaadba-649b-4f0a-9aad-9188a8f9926a"
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|
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name: "Pathology-Based Diagnoses"
|
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slug: "pathology-based-diagnoses"
|
||||
treeNodeId: "2d26053f-23a7-4062-bf35-a93775ae1209"
|
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-
|
||||
name: "Inflammatory and Demyelinating Disease"
|
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slug: "inflammatory-and-demyelinating-dis-"
|
||||
treeNodeId: "cb319228-da96-4d29-8276-c72388a57656"
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name: "Pediatric Multiple Sclerosis, Brain"
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slug: "pediatric-multiple-sclerosis-brain"
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category: "Pediatrics"
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|
||||
imageCount: 27
|
||||
lastUpdated: "02/14/24"
|
||||
pageDescription: "Pediatric Multiple Sclerosis, Brain"
|
||||
pageKeywords: "Pediatrics, Diagnosis, Pediatric Neuroradiology, Brain, Pathology-Based Diagnoses, Inflammatory and Demyelinating Disease, Pediatric Multiple Sclerosis, Brain"
|
||||
pageTitle: "Pediatric Multiple Sclerosis, Brain | STATdx"
|
||||
enhancedTitle: "Pediatric Multiple Sclerosis, Brain"
|
||||
type: "DX"
|
||||
references: true
|
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breadcrumbs:
|
||||
- "Pediatrics"
|
||||
- "Diagnosis"
|
||||
- "Pediatric Neuroradiology"
|
||||
- "Brain"
|
||||
- "Pathology-Based Diagnoses"
|
||||
- "Inflammatory and Demyelinating Disease"
|
||||
- "Pediatric Multiple Sclerosis, Brain"
|
||||
---
|
||||
# KEY FACTS
|
||||
|
||||
- ## Terminology
|
||||
|
||||
|
||||
- Probable autoimmune-mediated demyelination in which environmental factors act upon genetically susceptible individuals
|
||||
- ## Imaging
|
||||
|
||||
|
||||
- Multiple perpendicular callososeptal T2 hyperintensities characteristic of multiple sclerosis (MS)
|
||||
- Perivenular extension: Dawson fingers
|
||||
- Bilateral, asymmetric, linear/ovoid FLAIR hyperintensities
|
||||
- > 85% periventricular/perivenular
|
||||
- 50-90% callososeptal interface
|
||||
- May also commonly involve subcortical U fibers, brachium pontis, brainstem, spinal cord
|
||||
- Transient enhancement during active demyelination
|
||||
- > 90% disappear within 6 months
|
||||
- Rare: Large, tumefactive enhancing rings
|
||||
- T1-hypointense lesions suggest worse prognosis
|
||||
- Correlate with disability, atrophy, progressive disease
|
||||
- Advanced imaging techniques show disease in normal-appearing white matter
|
||||
- ## Top Differential Diagnoses
|
||||
|
||||
|
||||
- Acute disseminated encephalomyelitis
|
||||
- Neuromyelitis optica
|
||||
- Autoimmune-mediated vasculitis
|
||||
- Leukodystrophies and mitochondrial diseases
|
||||
- Lyme disease
|
||||
- Susac syndrome
|
||||
- ## Pathology
|
||||
|
||||
|
||||
- Probable autoimmune-mediated demyelination in which environmental factors act upon genetically susceptible individuals
|
||||
- Pathogenesis requires combination of genetically susceptible individual and specific environmental trigger
|
||||
- ## Clinical Issues
|
||||
|
||||
|
||||
- Estimated 2.5 million people in world have MS
|
||||
- Pediatric MS defined as onset < 18 years
|
||||
- ≈ 5% of MS patients
|
||||
- < 1% of MS patients have onset < 10 years
|
||||
- Most common disabling CNS disease of young adults; 1:1,000 in Western world
|
||||
- Adults: M:F = 1:2; adolescents: M:F = 1:3
|
||||
- ## Diagnostic Checklist
|
||||
|
||||
|
||||
- Requires dissemination in time and space within CNS for diagnosis
|
||||
- McDonald criteria: Consensus statement for diagnostic criteria; last revised in 2010
|
||||
|
||||
# TERMINOLOGY
|
||||
|
||||
- ## Abbreviations
|
||||
|
||||
|
||||
- Multiple sclerosis (MS)
|
||||
- ## Synonyms
|
||||
|
||||
|
||||
- Previously known as early-onset MS (EOMS) or juvenile MS
|
||||
- ## Definitions
|
||||
|
||||
|
||||
- Chronic demyelinating disease characterized by recurrent episodes of CNS demyelination separated in space and time
|
||||
- Pediatric MS defined as onset < 18 years
|
||||
- ≈ 5% of MS patients
|
||||
- < 1% of MS patients have onset < 10 years
|
||||
|
||||
# IMAGING
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Best diagnostic clue
|
||||
|
||||
|
||||
- Multiple perpendicular callososeptal T2 hyperintensities
|
||||
- ### Location
|
||||
|
||||
|
||||
- > 85% periventricular/perivenular
|
||||
- 50-90% callososeptal interface
|
||||
- Subcortical U fibers, brachium pontis, brainstem, spinal cord
|
||||
- Infratentorial (< 10% in adults, more common in children)
|
||||
- ### Size
|
||||
|
||||
|
||||
- Small (5-10 mm); tumefactive lesions several cm
|
||||
- ### Morphology
|
||||
|
||||
|
||||
- Linear, round, or ovoid; beveled, target, lesion-in-lesion appearance
|
||||
- Some children present with large, tumor-like demyelinating lesions [tumefactive demyelinating lesions (TDLs)]
|
||||
- ## CT Findings
|
||||
|
||||
|
||||
- ### CECT
|
||||
|
||||
|
||||
- Iso-/hypodense ± mild/moderate enhancement
|
||||
- Both solid and ring enhancement patterns
|
||||
- ## MR Findings
|
||||
|
||||
|
||||
- ### T1WI
|
||||
|
||||
|
||||
- Typically hypo- or isointense
|
||||
- Hypointensity correlates with axonal destruction (black holes)
|
||||
- Complete tissue loss following inflammatory injury
|
||||
- T1-hypointense lesions suggest worse prognosis
|
||||
- Correlated with disability, atrophy, progressive disease
|
||||
- Hyperintense dentate nuclei seen in secondary progressive form
|
||||
- ### T2WI
|
||||
|
||||
|
||||
- Hyperintense, linear foci radiating from ventricles
|
||||
- Also prevalent in subcortical U fibers, brachium pontis, brainstem, and spinal cord
|
||||
- Lesions tend to be well demarcated
|
||||
- High cortical disease burden can be predictor of PPMS
|
||||
- Hypointense basal ganglia 10-20% of chronic MS
|
||||
- ### FLAIR
|
||||
|
||||
|
||||
- Most sensitive sequence for brain lesions but relatively unhelpful in spinal cord
|
||||
- Earliest finding: Alternating linear hyperintensity along ependyma on sagittal FLAIR
|
||||
- Ependymal dot-dash sign
|
||||
- Bilateral, asymmetric, linear/ovoid hyperintensities
|
||||
- Perivenular extension; Dawson fingers
|
||||
- Along path of deep medullary veins
|
||||
- Hyperintensities become confluent with ↑ severity
|
||||
- ### DWI
|
||||
|
||||
|
||||
- Majority of acute plaques: Normal or ↑ diffusivity
|
||||
- Few acute MS plaques may show restricted diffusion
|
||||
- Often at margins of acute plaque
|
||||
- Subacute/chronic plaques: ↑ diffusivity
|
||||
- DTI: Reduced longitudinal diffusivity in areas of axonal injury
|
||||
- ### T1WI C+
|
||||
|
||||
|
||||
- Transient enhancement during active demyelination (> 90% disappear within 6 months)
|
||||
- Nodular (68%) or ring (23%)
|
||||
- Semilunar, incomplete, horseshoe-shaped (9%)
|
||||
- Rare: Large, tumefactive enhancing rings
|
||||
- ### MRS
|
||||
|
||||
|
||||
- ↓ NAA (NAA/Cr), ↑ choline (Cho/Cr), ↑ myoinositol
|
||||
- MRS abnormalities found in normal-appearing white matter
|
||||
- Only secondary progressive MS shows ↓ NAA in normal-appearing gray matter
|
||||
- May allow early distinction between relapsing-remitting and secondary-progressive
|
||||
- Perfusion MR (contrast-enhanced T2*): Low rCBV
|
||||
- Can separate tumefactive MS from neoplasm
|
||||
- Magnetization transfer (MT)
|
||||
- ↓ MT ratio (MTR) in lesions/normal-appearing white matter
|
||||
- Functional connectivity MR (fcMR)
|
||||
- ↓ functional connectivity between right/left hemisphere primary visual and motor cortices
|
||||
- 3.0 T vs. 1.5 T: 21% ↑ number of contrast-enhancing lesions, 30% ↑ enhancing lesion volume, 10% ↑ total lesion volume
|
||||
- ## Imaging Recommendations
|
||||
|
||||
|
||||
- ### Best imaging tool
|
||||
|
||||
|
||||
- MR
|
||||
- ### Protocol advice
|
||||
|
||||
|
||||
- Contrast-enhanced brain MR with FLAIR
|
||||
- Sagittal thin T2 FLAIR sequence in midline
|
||||
- To identify callosal-septal interface demyelinating lesions
|
||||
- Fat saturation to assess for optic neuritis (ON)
|
||||
|
||||
# DIFFERENTIAL DIAGNOSIS
|
||||
|
||||
- [Acute Disseminated Encephalomyelitis](/document/adem-brain/ed94b660-cf20-4ebb-8d6f-2b93505f2928)
|
||||
- Viral prodrome, monophasic illness; more common in children
|
||||
- Can mimic MS; gray matter often involved
|
||||
- Lesions tend to be larger, more edematous, and often symmetric compared to MS
|
||||
- [Neuromyelitis Optica](/document/neuromyelitis-optica-spectrum-diso-/54d4a8bc-9267-4df6-98c1-f22aae051d01)
|
||||
- ON and spinal cord lesions
|
||||
- Brain lesions look atypical for MS, tend to border midline CSF spaces
|
||||
- [Autoimmune-Mediated Vasculitis](/document/miscellaneous-vasculitis/5a4d4cbd-67e3-4722-8a44-8d411cbb98f0)
|
||||
- Enhancing lesions spare callososeptal interface
|
||||
- Beaded angiogram appearance
|
||||
- ## Leukodystrophies and Mitochondrial Diseases
|
||||
|
||||
|
||||
- Consider in younger patients and atypical presentations
|
||||
- Genetic &/or laboratory confirmation
|
||||
- [Lyme Disease](/document/lyme-disease/ca3da7a8-0f21-4e06-9961-a43e6af1b0cc)
|
||||
- Can be identical to MS (skin rash common)
|
||||
- [Susac Syndrome](/document/susac-syndrome/af240d31-5918-4981-971f-c6780f7b405f)
|
||||
- Classic triad: Encephalopathy, branch retinal artery occlusions, hearing loss
|
||||
|
||||
# PATHOLOGY
|
||||
|
||||
- ## General Features
|
||||
|
||||
|
||||
- ### Etiology
|
||||
|
||||
|
||||
- Unknown; probably virus &/or autoimmune mediated in genetically susceptible individuals
|
||||
- Proposed environmental triggers for MS include exposure to infectious agents (Epstein-Barr virus in particular), low serum vitamin D levels
|
||||
- Higher MS prevalence in northern latitudes has prompted theories about role of vitamin D metabolites in MS pathogenesis
|
||||
- Activated T cells attack myelinated axons
|
||||
- Cox-2, iNOS may cause excitotoxic death of oligodendrocytes
|
||||
- To date, causation has not been proved for any of proposed pathogenic etiologies
|
||||
- ### Genetics
|
||||
|
||||
|
||||
- Multifactorial; ↑ incidence in 1st-order relatives
|
||||
- ## Staging, Grading, & Classification
|
||||
|
||||
|
||||
- Major clinical subtypes
|
||||
- **Relapsing-remitting** (RR) 85% initial presentation
|
||||
- **Secondary-progressive** (SP), a.k.a. relapsing progressive
|
||||
- By 10 years 50%; by 25 years 90% of RR patients enter SP phase
|
||||
- **Primary-progressive** (PP), a.k.a. chronic progressive
|
||||
- 5-10% of MS population progressive from start
|
||||
- **Progressive-relapsing** (PR)
|
||||
- Rare; defined as progressive disease with clear acute relapses ± full recovery
|
||||
- Periods between relapses characterized by continuing disease progression
|
||||
- **Radiologically isolated syndrome**(RIS)
|
||||
- MR findings satisfy criteria for dissemination in space, but with no attributable MS signs and symptoms
|
||||
- Increasingly recognized in pediatric population
|
||||
- Presumed that some will transition to formal MS diagnosis over time
|
||||
- MS variants/subtypes
|
||||
- **Malignant/Marburg disease**: Younger patients, febrile prodrome, clinically fulminant, death in months
|
||||
- **Schilder** type (diffuse sclerosis): Extensive, confluent, asymmetric demyelination in bilateral supra-/infratentorial parenchyma
|
||||
- **Baló**type (concentric sclerosis): Large lesions with alternating zones of demyelinated/myelinated white matter
|
||||
- **2017 revised McDonald criteria for MS diagnosis**
|
||||
- **Dissemination in space**
|
||||
- ≥ 1 T2-hyperintense lesion(s) characteristic of MS
|
||||
- In at least 2 of following 4 areas
|
||||
- Periventricular, juxtacortical, infratentorial, spinal cord
|
||||
- **Dissemination in time**
|
||||
- Simultaneous presence of gadolinium-enhancing and nonenhancing lesions at any time **or**by new T2-hyperintense or gadolinium-enhancing lesion on follow-up MR with reference to baseline scan, irrespective of timing of baseline MR
|
||||
- Unlike 2010 McDonald criteria, no distinction between symptomatic and asymptomatic MR lesions is required
|
||||
- ## Gross Pathologic & Surgical Features
|
||||
|
||||
|
||||
- Acute: Poorly delineated, yellowish-white, periventricular plaques
|
||||
- Chronic: Gray, granular, well-demarcated plaques ± generalized volume loss
|
||||
- ## Microscopic Features
|
||||
|
||||
|
||||
- Perivenous demyelination, oligodendrocyte loss
|
||||
- Active: Foamy macrophages with myelin fragments, lipids; reactive astrocytes + perivascular inflammation; atypical reactive astrocytes, mitoses (mimic tumor)
|
||||
- Chronic: Marked loss of myelin, oligodendrocytes; dense astrogliosis; minimal/no perivascular inflammation
|
||||
- Axonal transection
|
||||
- CSF positive for oligoclonal bands
|
||||
|
||||
# CLINICAL ISSUES
|
||||
|
||||
- ## Presentation
|
||||
|
||||
|
||||
- ### Most common signs/symptoms
|
||||
|
||||
|
||||
- Variable; initially impaired/double vision of acute ON
|
||||
- ≈ 50% with positive MR develop MS
|
||||
- Weakness, numbness, tingling, gait disturbances
|
||||
- ↓ sphincter control, blindness, paralysis, dementia
|
||||
- Cranial nerve palsy; usually multiple, 1-5% isolated (CNV, CNVI most common)
|
||||
- Spinal cord symptoms in 80%
|
||||
- Children may have similar clinical presentation to adults
|
||||
- Clinically distinct episodes of ON, brainstem or cerebellar syndrome, or transverse myelitis followed by at least partial resolution
|
||||
- More likely (than adults) to present with isolated ON, brainstem syndrome, or encephalitic symptoms, such as headache, vomiting, seizure, or altered consciousness
|
||||
- ## Demographics
|
||||
|
||||
|
||||
- ### Age
|
||||
|
||||
|
||||
- 20-40 years; peak onset: 30 years, 3-5% < 15 years, 9% > 50 years
|
||||
- ### Sex
|
||||
|
||||
|
||||
- Adults: M:F = 1:2
|
||||
- Adolescents: M:F = 1:3
|
||||
- ### Ethnicity
|
||||
|
||||
|
||||
- All groups, but White populations most common
|
||||
- Most often occurs in temperate zones
|
||||
- ### Epidemiology
|
||||
|
||||
|
||||
- Estimated 2.5 million people in world have MS
|
||||
- Rare disease; estimated frequency ~ 2.5 per 100,000 children
|
||||
- Most common disabling CNS disease of young adults; 1:1,000 in Western world
|
||||
- ## Natural History & Prognosis
|
||||
|
||||
|
||||
- Prognostically, pediatric-onset MS (POMS) portends more inflammatory course and higher relapse rate compared with adult-onset MS (AOMS)
|
||||
- Relapse recovery is faster and more complete compared to adults, disability progression is slower, and longer time elapses before transitioning to secondary progression
|
||||
- 34% of patients have initial episode followed by normal or near-normal function
|
||||
- Unfortunately, given younger age at diagnosis, POMS patients reach comparable level of handicap 10 years earlier than patients with AOMS
|
||||
- Moreover, POMS can impact children's cognitive function and development
|
||||
- > 50% of MS pediatric patients continue to accrue cognitive deficits within first 5 years after disease onset
|
||||
- > 80% with probable MS, positive MR progress to clinically definite MS
|
||||
- Majority: Protracted course with progression of deficits
|
||||
- Late: Severe disability, cognitive impairment
|
||||
- ## Treatment
|
||||
|
||||
|
||||
- Immunomodulators &/or immunosuppressants
|
||||
- Emerging trend toward earlier use of disease modifying therapies to achieve prompt immunomodulatory disease control
|
||||
- Newer, more specific and effective treatments rapidly entering clinical realm
|
||||
|
||||
# DIAGNOSTIC CHECKLIST
|
||||
|
||||
- ## Image Interpretation Pearls
|
||||
|
||||
|
||||
- 95% with clinically definite MS have positive MR findings
|
||||
|
||||
a5089f2b-fbb1-4100-b013-c093925fe15e
|
||||
|
||||
## References
|
||||
|
||||
# Selected References
|
||||
|
||||
1. [Bower A et al: Radiologically isolated syndrome and the multiple sclerosis prodrome in pediatrics: early features of the spectrum of demyelination. Semin Pediatr Neurol. 46:101053, 2023](http://www.ncbi.nlm.nih.gov/pubmed/?term=37451751%5Bpmid%5D)
|
||||
1. [Kornbluh AB et al: Pediatric multiple sclerosis. Semin Pediatr Neurol. 46:101054, 2023](http://www.ncbi.nlm.nih.gov/pubmed/?term=37451754%5Bpmid%5D)
|
||||
1. [Malani Shukla N et al: Demographic features and clinical course of patients with pediatric-onset multiple sclerosis on newer disease-modifying treatments. Pediatr Neurol. 145:125-31, 2023](http://www.ncbi.nlm.nih.gov/pubmed/?term=37348193%5Bpmid%5D)
|
||||
1. [Teleanu RI et al: The state of the art of pediatric multiple sclerosis. Int J Mol Sci. 24(9), 2023](http://www.ncbi.nlm.nih.gov/pubmed/?term=37175954%5Bpmid%5D)
|
||||
1. [De Meo E et al: Dynamic gray matter volume changes in pediatric multiple sclerosis: a 3.5 year MRI study. Neurology. 92(15):e1709-23, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30867274%5Bpmid%5D)
|
||||
1. [Makhani N et al: Oligoclonal bands increase the specificity of MRI criteria to predict multiple sclerosis in children with radiologically isolated syndrome. Mult Scler J Exp Transl Clin. 5(1):2055217319836664, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30915227%5Bpmid%5D)
|
||||
1. [Fadda G et al: MRI and laboratory features and the performance of international criteria in the diagnosis of multiple sclerosis in children and adolescents: a prospective cohort study. Lancet Child Adolesc Health. 2(3):191-204, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=30169254%5Bpmid%5D)
|
||||
1. [Otallah S et al: Pediatric multiple sclerosis: an update. Curr Neurol Neurosci Rep. 18(11):76, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=30229541%5Bpmid%5D)
|
||||
1. [Ruet A: Update on pediatric-onset multiple sclerosis. Rev Neurol (Paris). 174(6):398-407, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29784250%5Bpmid%5D)
|
||||
1. [Thompson AJ et al: Diagnosis of multiple sclerosis: 2017 revisions of the McDonald criteria. Lancet Neurol. 17(2):162-73, 2018](http://www.ncbi.nlm.nih.gov/pubmed/?term=29275977%5Bpmid%5D)
|
||||
1. [Yeshokumar AK et al: Pediatric multiple sclerosis. Curr Opin Neurol. 30(3):216-21, 2017](http://www.ncbi.nlm.nih.gov/pubmed/?term=28323645%5Bpmid%5D)
|
||||
1. [Waldman A et al: Pediatric multiple sclerosis: clinical features and outcome. Neurology. 87(9 Suppl 2):S74-81, 2016](http://www.ncbi.nlm.nih.gov/pubmed/?term=27572865%5Bpmid%5D)
|
||||
1. [Roosendaal SD et al: Imaging phenotypes in multiple sclerosis. Neuroimaging Clin N Am. 25(1):83-96, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25476514%5Bpmid%5D)
|
||||
1. [Aliaga ES et al: MRI mimics of multiple sclerosis. Handb Clin Neurol. 122:291-316, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24507523%5Bpmid%5D)
|
||||
1. [Ciccarelli O et al: Pathogenesis of multiple sclerosis: insights from molecular and metabolic imaging. Lancet Neurol. 13(8):807-22, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=25008549%5Bpmid%5D)
|
||||
1. [Fernandez O et al: Biomarkers in multiple sclerosis: an update for 2014. Rev Neurol. 58(12):553-70, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24915032%5Bpmid%5D)
|
||||
1. [Hardy TA et al: Baló's concentric sclerosis. Lancet Neurol. 13(7):740-6, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24943346%5Bpmid%5D)
|
||||
1. [Miller TR et al: Advances in multiple sclerosis and its variants: conventional and newer imaging techniques. Radiol Clin North Am. 52(2):321-36, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24582342%5Bpmid%5D)
|
||||
1. [Steenwijk MD et al: What explains gray matter atrophy in long-standing multiple sclerosis? Radiology. 272(3):832-42, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=24761837%5Bpmid%5D)
|
||||
1. [Klawiter EC: Current and new directions in MRI in multiple sclerosis. Continuum (Minneap Minn). 19(4 Multiple Sclerosis):1058-73, 2013](http://www.ncbi.nlm.nih.gov/pubmed/?term=23917101%5Bpmid%5D)
|
||||
1. [Filippi M et al: MR imaging of multiple sclerosis. Radiology. 259(3):659-81, 2011](http://www.ncbi.nlm.nih.gov/pubmed/?term=21602503%5Bpmid%5D)
|
||||
1. [Polman CH et al: Diagnostic criteria for multiple sclerosis: 2010 revisions to the McDonald criteria. Ann Neurol. 69(2):292-302, 2011](http://www.ncbi.nlm.nih.gov/pubmed/?term=21387374%5Bpmid%5D)
|
||||
1. [Calabrese M et al: Cortical lesions in primary progressive multiple sclerosis: a 2-year longitudinal MR study. Neurology. 72(15):1330-6, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19365054%5Bpmid%5D)
|
||||
1. [Filippi M et al: Conventional MRI in multiple sclerosis. J Neuroimaging. 17 Suppl 1:3S-9S, 2007](http://www.ncbi.nlm.nih.gov/pubmed/?term=17425730%5Bpmid%5D)
|
||||
1. [Janardhan V et al: Multiple sclerosis: hyperintense lesions in the brain on nonenhanced T1-weighted MR images evidenced as areas of T1 shortening. Radiology. 244(3):823-31, 2007](http://www.ncbi.nlm.nih.gov/pubmed/?term=17690319%5Bpmid%5D)
|
||||
1. [Traboulsee AL et al: The role of MRI in the diagnosis of multiple sclerosis. Adv Neurol. 98:125-46, 2006](http://www.ncbi.nlm.nih.gov/pubmed/?term=16400831%5Bpmid%5D)
|
||||
|
||||
|
||||
## Images
|
||||
|
||||
|
||||
### Selected Images
|
||||
|
||||
|
||||
*Sagittal graphic illustrates multiple sclerosis (MS) plaques involving the corpus callosum, pons, and spinal cord. Note the characteristic perpendicular orientation of the lesions <img src='/img/arrows/BS.png'/> at the callososeptal interface along penetrating venules.*
|
||||
|
||||
|
||||
*Sagittal graphic illustrates multiple sclerosis (MS) plaques involving the corpus callosum, pons, and spinal cord. Note the characteristic perpendicular orientation of the lesions <img src='/img/arrows/BS.png'/> at the callososeptal interface along penetrating venules.*
|
||||
|
||||
|
||||
*Sagittal T1 MR in a 14-year-old presenting with gait instability and facial numbness demonstrates T1-hypointense corpus callosum lesions <img src='/img/arrows/WS.png'/> that represent "black holes" of chronic demyelination. This was the initial clinical MS presentation for this patient.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in the same patient reveals larger lesions <img src='/img/arrows/WS.png'/> in the right frontal lobe and left periventricular white matter. Note surrounding edema in these more acute lesions.*
|
||||
|
||||
|
||||
*Axial T1 C+ FS MR in the same patient reveals the characteristic heterogeneous enhancement pattern for a demyelinating process in these more recent lesions <img src='/img/arrows/WS.png'/>, meeting McDonald criteria for dissemination in space and time.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a teen patient with acute extremity sensory changes and visual disturbance shows a focal periventricular T2-hyperintense lesion <img src='/img/arrows/WS.png'/>. Imaging also showed additional periventricular and callosal-septal lesions (not shown).*
|
||||
|
||||
|
||||
*Axial T1 C+ FS MR in the same patient confirms abnormal peripheral lesion enhancement with an incomplete ring pattern <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Sagittal T2 MR in a teenager presenting with acute ataxia demonstrates numerous hyperintense corpus callosum lesions <img src='/img/arrows/WS.png'/> extending to the callosal-septal interface as well as brainstem, cervicomedullary <img src='/img/arrows/WO.png'/>, and cord lesions <img src='/img/arrows/WC.png'/>.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in the same patient confirms ring- and solid-enhancing demyelinating lesions, including a characteristic perpendicular periventricular lesion <img src='/img/arrows/WS.png'/>.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in a teen patient with acute left body weakness and sensory disturbance shows a tumefactive lesion <img src='/img/arrows/WO.png'/> with surrounding T2 hyperintensity extending into the corpus callosum. Differential considerations include neoplasm and abscess in addition to demyelinating disease.*
|
||||
|
||||
|
||||
*Coronal T1 C+ MR in the same patient reveals an incomplete ring of enhancement surrounding the mildly hypointense lesion <img src='/img/arrows/WO.png'/>, permitting a diagnosis of tumefactive MS.*
|
||||
|
||||
|
||||
### Additional Images
|
||||
|
||||
|
||||
*Sagittal FLAIR MR in a patient with chronic MS demonstrates diffuse thinning of the corpus callosum <img src='/img/arrows/WS.png'/> with extensive abnormal T2 hyperintensity along the callosal-septal interface, reflecting chronic demyelinating disease.*
|
||||
|
||||
|
||||
*Axial FLAIR MR in the same patient reveals extensive bilateral white matter demyelinating lesions, predominately periventricular but also within more peripheral white matter. Mild diffuse white matter volume loss with passive ventricular enlargement is present.*
|
||||
|
||||
|
||||
*Axial T1 MR in the same patient reveals fairly extensive hypointensity within the demyelinating lesions, implying chronic disease with white matter axonal destruction (black holes).*
|
||||
|
||||
|
||||
*Axial SWI demonstrates the characteristic perivenular location of a demyelinating plaque <img src='/img/arrows/CC.png'/> with the medullary vein <img src='/img/arrows/CS.png'/> coursing through it.*
|
||||
|
||||
|
||||
*Sagittal T1 C+ MR shows a large, hypointense mass <img src='/img/arrows/CC.png'/> with a peripheral crescent of incomplete or open ring enhancement <img src='/img/arrows/CS.png'/>. This enhancement pattern is classic for a tumefactive demyelinating disease, most commonly MS.*
|
||||
|
||||
|
||||
*Axial T1 C+ MR in a young male patient with rapid onset of visual disturbance demonstrates large enhancing demyelinating lesions <img src='/img/arrows/CS.png'/> in the deep and periventricular white matter. Marburg disease is an acute fulminant MS variant.*
|
||||
|
||||
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*Axial T1 C+ MR demonstrates concentric laminated "onion bulb" enhancement <img src='/img/arrows/CC.png'/> characteristic of acute Baló concentric sclerosis. Baló concentric sclerosis is a rare, aggressive MS variant characterized by acute onset and rapid deterioration.*
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*Sagittal FLAIR MR shows MS plaques with typical perpendicular orientation at the callososeptal interface along penetrating venules (Dawson fingers) as well as involving subcortical white matter.*
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*Sagittal FLAIR MR shows MS plaques with a hyperintense rim and central hypointensity (latter also hypointense on T1WI; not shown). Note the characteristic posterior fossa lesion <img src='/img/arrows/WS.png'/>.*
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*Axial T1 C+ MR demonstrates nodular enhancing MS plaques. Note the common periventricular location with perpendicular orientation as well as involvement of subcortical white matter.*
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*Axial T1 C+ MR shows irregular, thick partial ring enhancement around a mass-like lesion in a patient not previously diagnosed with MS. This was biopsy-proven tumefactive MS. (Courtesy M. Mirfakharee, MD.)*
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*Sagittal FLAIR MR shows callososeptal hyperintensities radiating from the lateral ventricles with a typical perpendicular orientation, characteristic of MS.*
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*Axial FLAIR MR 3T shows multiple nonenhancing, periventricular, hyperintense MS lesions oriented perpendicular to the callosomarginal interface. These lesions are perivenular along the path of the deep medullary veins and represent Dawson fingers. Confluent lesions are also seen along the right periventricular margin.*
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*Axial FLAIR MR shows confluent periventricular white matter hyperintensity typical of advanced, longstanding MS with loss of discrete, linear, periventricular lesions.*
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*Sagittal T1 MR shows multiple hypointense lesions ("black holes") in the deep white matter <img src='/img/arrows/BS.png'/> related to axonal destruction. Note the associated moderate ventricular and sulcal enlargement.*
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*Coronal T1 C+ MR shows a hypointense mass in the left posterior frontal region with a peripheral crescent of incomplete or "horseshoe" enhancement <img src='/img/arrows/WS.png'/>. This enhancement pattern is classic for tumefactive demyelinating disease, most commonly MS.*
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*Axial T1 C+ FS MR shows bright enhancement of the optic nerves <img src='/img/arrows/WS.png'/> similar to the extraocular muscles in a patient with MS with acute bilateral optic neuritis.*
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Reference in New Issue
Block a user