526 lines
34 KiB
Markdown
526 lines
34 KiB
Markdown
---
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title: "Pediatric Multiple Sclerosis, Spine"
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docid: "59786b97-2a4d-4706-a6fe-fe2dcd476b5e"
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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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breadcrumbs:
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-
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name: "Pediatrics"
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slug: "pediatrics"
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treeNodeId: "a915965c-d436-44cf-ae65-2f22e7246ea4"
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name: "Diagnosis"
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slug: "diagnosis"
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treeNodeId: "2b5cea64-a083-489e-ac0c-ec14ba059026"
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name: "Pediatric Neuroradiology"
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slug: "pediatric-neuroradiology"
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treeNodeId: "d0eb8f4a-e769-43dd-896c-8c9c27ce8759"
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-
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name: "Spine"
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slug: "spine"
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treeNodeId: "b9e72e11-010d-4dd1-a609-2072db6047b2"
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-
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name: "Infection and Inflammatory Disorders"
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slug: "infection-and-inflammatory-disorde-"
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treeNodeId: "f2c25be2-4696-46d8-be79-383a6f15e826"
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-
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name: "Inflammatory and Autoimmune Disorders"
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slug: "inflammatory-and-autoimmune-disord-"
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treeNodeId: "dbd53cba-1e54-40fc-b62f-f7a8e8e78b53"
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-
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name: "Pediatric Multiple Sclerosis, Spine"
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slug: "pediatric-multiple-sclerosis-spine"
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treeNodeId: null
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category: "Pediatrics"
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cmeTopicId: "54a46ea3-7b26-4525-964c-6aa99ac50564"
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documentVersionId: "28aeb597-125a-4f17-91b9-738a90cdd336"
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imageCount: 19
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lastUpdated: "02/09/24"
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pageDescription: "Pediatric Multiple Sclerosis, Spine"
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pageKeywords: "Pediatrics, Diagnosis, Pediatric Neuroradiology, Spine, Infection and Inflammatory Disorders, Inflammatory and Autoimmune Disorders, Pediatric Multiple Sclerosis, Spine"
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pageTitle: "Pediatric Multiple Sclerosis, Spine | STATdx"
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enhancedTitle: "Pediatric Multiple Sclerosis, Spine"
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type: "DX"
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references: true
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breadcrumbs:
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- "Pediatrics"
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- "Diagnosis"
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||
- "Pediatric Neuroradiology"
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- "Spine"
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- "Infection and Inflammatory Disorders"
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- "Inflammatory and Autoimmune Disorders"
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- "Pediatric Multiple Sclerosis, Spine"
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---
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# KEY FACTS
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- ## Terminology
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- Primary demyelinating disease of CNS with multiple lesions disseminated over time & space
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- Concomitant intracranial lesions in periventricular, subcallosal, brainstem, or cerebellar white matter
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- ## Imaging
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- Isolated spinal cord disease (10-20%)
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- Cervical segment is most commonly affected
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- Dorsolateral aspect of cord
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- < 1/2 of cross-sectional area of spinal cord
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- < 2 vertebral segments in length
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- Sagittal & axial T1WI/T2WI sequences with gadolinium
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- Lesions typically oval, peripheral, & asymmetric
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- Discrete vs. vague hyperintense lesions
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- Enhancement lasts 1-2 months but does not reflect disease progression
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- ## Top Differential Diagnoses
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- Acute disseminated encephalomyelitis
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- Neuromyelitis optica spectrum disorders
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- Myelin oligodendrocyte glycoprotein antibody disorder
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- Idiopathic transverse myelitis
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- Intramedullary neoplasm
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- Spinal cord infarct
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- ## Pathology
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- Autoimmune, cell-mediated inflammatory process focused on CNS myelin
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- ## Clinical Issues
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- Peak onset: 20-40 years
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- Adult females more susceptible than males (1.7:1)
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- Multiple clinical presentations
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- Relapsing remitting (RR)
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- Secondary progressive (SP)
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- Primary progressive (PP)
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- Progressive relapsing (PR)
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- ## Diagnostic Checklist
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- Imaging findings must be correlated with clinical & laboratory features to confirm diagnosis
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# TERMINOLOGY
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- ## Abbreviations
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- Spinal cord multiple sclerosis (MS)
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- ## Definitions
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- Primary demyelinating disease of CNS with multiple lesions disseminated over time & space
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# IMAGING
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- ## General Features
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- ### Best diagnostic clue
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- Concomitant T2-hyperintense lesions in ≥ 2 of 4 areas of CNS: Periventricular, cortical or juxtacortical, infratentorial, & spinal cord
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- ### Location
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- Lesions solitary or multifocal
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- Isolated spinal cord disease in 10-20%
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- Cervical segment is most commonly affected (2/3 of cord lesions)
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- Lesions frequently in dorsolateral cord
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- Does not respect gray-white boundary
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- ### Size
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- < 1/2 of cross-sectional area of spinal cord
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- < 2 vertebral segments in length
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- ### Morphology
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- Wedge-shaped on axial MR
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- Apex directed centrally
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- ## MR Findings
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- ### T1WI
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- Iso- to hypointense lesions
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- In cord (unlike brain), rarely visible as hypointense
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- 30% of brain lesions are dark, "black holes"
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- Normal or mild focal cord expansion
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- Cord edema
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- Resolves after 6-8 weeks
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- ### T2WI
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- Discrete or ill-defined hyperintense lesions
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- May be related to extent of demyelination
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- Lesions ↑ in size due to edema associated with inflammatory infiltrates → reach max size at 4 weeks
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- Slow ↓ in size over 6-8 weeks as edema resolves ± remyelination
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- Lesions typically oval, peripheral, & asymmetric
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- ### PD/intermediate
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- Hyperintense lesions
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- ### STIR
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- Improved lesion detection, more artifact
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- ### FLAIR
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- Lower lesion sensitivity compared to STIR
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- ### DWI
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- ↑ mean diffusivity, ↓ fractional anisotropy in plaques & areas without T2 abnormality
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- ### T1WI C+
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- Variable
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- Homogeneous, nodular, or ring enhancement during acute or subacute phase
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- Enhancement lasts 1-2 months
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- Does not reflect disease progression
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- No enhancement during chronic phase
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- ### MRS
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- ↓ N-acetylaspartate level
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- ↑ choline levels, even in normal-appearing white matter
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- Cord atrophy
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- Usually in late stage
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- May be seen in early disease course
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- Useful for monitoring disease progression & therapeutic efficacy
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- Correlates with clinical disability
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- fMRI
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- Tactile-associated cervical cord fMRI activity ↑ in relapse-onset MS patients
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- Overactivation more prominent in patients with more severe locomotor disability
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- Suggests abnormality of cord functional properties may be among factors associated with clinical status of MS patient
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- ## Nonvascular Interventions
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- ### Myelography
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- Nonspecific mild cord expansion
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- ## Other Modality Findings
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- Magnetization transfer (MT) imaging
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- ↓ MT ratio in spinal cord
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- Better correlation with disability & axonal loss
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- ↓ MT ratios in enhancement patterns in which myelin known to be ↓ histopathologically
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- ## Imaging Recommendations
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- ### Best imaging tool
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- T1WI/T2WI spinal cord MR in sagittal & axial planes with gadolinium
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# DIFFERENTIAL DIAGNOSIS
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- [Acute Disseminated Encephalomyelitis](/document/adem-spine/d2226d10-f582-4cdf-8f32-71718e6c494d)
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- Para-/postinfectious immune-mediated inflammatory disorder of spinal cord white matter
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- Frequently preceding infection 4-12 days before onset
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- Usually monophasic
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- [Syringohydromyelia](/document/syringomyelia/fb362df4-5033-4f7c-9f4d-01d701ebab84)
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- Central cystic lesion
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- CSF intensity on all sequences
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- No abnormal enhancement
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- [Neuromyelitis Optica Spectrum Disorders](/document/neuromyelitis-optica/11d42d8d-e7bb-4ecf-85ce-d96f0afeb076)
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- Autoimmune inflammatory disorder involving myelin of neurons of optic nerves & spinal cord
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- Longitudinally extensive cord T2 hyperintensity + optic nerve enhancement
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- T2 abnormality involves entire cross section of cord
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- Limited brain involvement
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- ## Myelin Oligodendrocyte Glycoprotein Antibody Disease
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- Autoimmune inflammatory disorder involving neuronal myelin of brain, optic nerves, &/or spinal cord
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- Often longitudinally extensive
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- Predilection for conus
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- [Idiopathic Transverse Myelitis](/document/idiopathic-acute-transverse-myelit-/6e82fa47-19b7-45ac-b195-3c21687fa648)
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- Longitudinally extensive, > 2/3 of cord cross-sectional area
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- Lesion centrally located, variable enhancement
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- No associated intracranial lesions
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- Diagnosis of exclusion
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- [Intramedullary Neoplasm](/document/spinal-cord-astrocytoma/43d5efa2-7a6d-4972-bfc6-c300cc31f9af)
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- Cord expansion, peritumoral edema, cystic ± hemorrhagic components
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- Entire cross section of spinal cord
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- Diffuse or partial enhancement
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- [Spinal Cord Infarction](/document/spinal-cord-infarction/5afcaea7-09a0-49b7-8f23-f93734d627fb)
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- Sudden onset of symptoms
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- Positive diffusion restriction
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- Posterior columns typically spared in anterior spinal infarct
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# PATHOLOGY
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- ## General Features
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- ### Etiology
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- Autoimmune, cell-mediated inflammatory process focused on CNS myelin
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- Infectious agents may play primary or secondary role
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- Humoral mechanism: Cross reactivity between infectious & self-epitopes
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- May be association between MS & altered venous return due to multiple extracranial venous strictures
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- Hampered cerebrospinal venous drainage in patients with MS determines complex hemodynamic picture → chronic cerebrospinal venous insufficiency (CCSVI)
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- Multiple substitute circles with very high incidence of reflux in both intra-/extracranial venous segments
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- Loss of postural regulation of cerebral venous outflow
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- Primary progressive (PP) course related to CCSVI pattern differs significantly from relapsing remitting (RR) & secondary progressive (SP) → location of venous obstruction plays role in clinical course
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- Obstruction at several levels of azygous vein & of lumbar plexuses
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- → venous blood of cord can be drained only in upward direction & is shunted toward venous plexuses inside spine
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- ↑ cerebral blood flow/volume & ↓ mean transit time (compared with baseline values before relapse) precede development of plaques
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- Susceptibility-weighted imaging → venous blood in cerebral veins of patients with MS is less deoxygenated compared with healthy controls
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- Previously, these findings interpreted as sign of local flow disturbances mediated by inflammatory & neurodegenerative processes
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- However, may be attributable to recent findings of significant stenoses in extracranial veins draining brain & spinal cord
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- ### Genetics
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- May be inherited as complex multifactorial disorder resulting from interaction of genetic & environmental factors
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- Estimated risk to siblings of proband ~ 3.0-5.0%, ↑ to 29.5% if 1 or both parents have MS
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- Risk to offspring of person with MS is 2.0-3.0% & higher if both parents have MS
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- ### Associated abnormalities
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- 90% incidence of associated intracranial lesions
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- Neurofibromatosis type 1
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- Different serum thyroid hormone & complement C3, C4, & CH50 levels in neuromyelitis optica vs. MS
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- Thyroid hormones may play different role in modulating complement activation in MS & neuromyelitis optica
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- Focal regions of demyelination of varying size & age scattered throughout CNS white matter
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- ## Staging, Grading, & Classification
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- McDonald criteria (2001, revised in 2005 & 2017) widely used for adult MS diagnosis
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- Has also been shown to be useful for pediatric MS diagnosis
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- Relies on lesion dissemination in both time & space
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- Dissemination in space
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- Demonstrated by ≥ 1 T2-hyperintense lesions that are characteristic of MS in ≥ 2 of 4 areas of CNS
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- Periventricular, cortical or juxtacortical, infratentorial brain regions, & spinal cord
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- Dissemination in time
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- Simultaneous presence of gadolinium-enhancing & nonenhancing lesions at any time
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- New T2-hyperintense or gadolinium-enhancing lesion on follow-up MR with reference to baseline scan, irrespective of timing of baseline MR
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- ## Microscopic Features
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- Discrete lesions of myelin destruction
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- Active lesions with macrophages & lymphocytes
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- Chronic lesions with gliosis & cavitation
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- Perivascular cuffs of lymphocytes & mononuclear cells
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- Involvement of dorsal horns common
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# CLINICAL ISSUES
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- ## Presentation
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- ### Most common signs/symptoms
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- Cord lesions asymptomatic
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- Paresthesia
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- ### Other signs/symptoms
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- Muscle weakness, hyperreflexia, gait disturbance
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- Bladder/bowel dysfunction
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- Surveillance includes periodic neurologic examination to track disease progression & periodic brain & spinal cord MRs to monitor disease activity
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- Additional examination techniques → ambulation index, 25-foot timed walk, & 25-foot walk combined with 9-hole peg test & paced serial auditory addition test
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- ## Demographics
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- ### Age
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- Peak onset: 20-40 years
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- Onset < 18 years in 3-5% of MS cases
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- ### Sex
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- Women more susceptible than men (1.7:1)
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- Men more likely to have progressive relapsing (PR) & SP MS
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- Women more likely to have RR MS
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- Both sexes equally affected in PP MS
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- ### Ethnicity
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- Western Europeans have higher risk
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- ### Epidemiology
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- ↑ prevalence farther north from equator
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- 30-80 per 100,000 in northern USA & Europe
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- 6-14 per 100,000 in southern USA & Europe
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- 1 per 100,000 in equatorial regions
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- ## Natural History & Prognosis
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- Benign: 20%
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- Complete recovery after 1-2 attacks
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- Some may experience progressive MS after 10-15 years
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- RR: 25%
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- Distinct periods of new or worsening symptoms alternating with complete or partial recovery
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- 90% will evolve into progressive MS after 25 years
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- SP: 40%
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- From RR MS
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- Worsening deficits & disabilities
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- Incomplete & infrequent remission
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- PP: 12%
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- Steady progression of symptoms
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- Motor dysfunction common
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- Primary cord involvement; no distinct attacks
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- PR: 3%
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- Similar to PP MS
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- Distinct periods of exacerbation but without recovery
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- High mortality rate
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- ## Treatment
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- Multiple approved medications include interferon, chemotherapy agents, monoclonal antibodies
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- Several preparations available of interferon β (interferon β-1b, interferon β-1a)
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- Inhibition of immune cells
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- Glatiramer acetate
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- Synthetic protein similar to myelin protein
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- Serves as substrate for T cells
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- Mitoxantrone (chemotherapeutic agent)
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- Suppression of T lymphocytes & B lymphocytes
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- Monoclonal antibodies
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- Natalizumab, alemtuzumab, daclizumab, ocrelizumab
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- Small-molecule oral agents
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- Fingolimod, dimethyl fumarate, teriflunomide
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- Supportive therapy
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- Symptomatic treatment of pain, muscle spasms, fatigue, depression, sexual/bladder/bowel dysfunction
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- Anticholinergics, smooth muscle relaxants
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- Physical therapy
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# DIAGNOSTIC CHECKLIST
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- ## Consider
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- Multiplanar spine contrast MR ± contrast, including STIR MR
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- Brain MR, including high-resolution fast spin-echo T2 through corpus callosum
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- Gray matter atrophy correlates with disability
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- Periventricular, subcallosal, brainstem, or cerebellar white matter lesions suggest MS
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- ## Image Interpretation Pearls
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- Imaging findings must be correlated with clinical & laboratory features to confirm diagnosis
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- Acute MS can mimic cord neoplasm
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ec82b351-fbdc-43cf-8899-7d0ffed659d4
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## References
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# Selected References
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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)
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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)
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1. [Fadda G et al: Comparison of spinal cord magnetic resonance imaging features among children with acquired demyelinating syndromes. JAMA Netw Open. 4(10):e2128871, 2021](http://www.ncbi.nlm.nih.gov/pubmed/?term=34643718%5Bpmid%5D)
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1. [Ciccarelli O et al: Spinal cord involvement in multiple sclerosis and neuromyelitis optica spectrum disorders. Lancet Neurol. 18(2):185-97, 2019](http://www.ncbi.nlm.nih.gov/pubmed/?term=30663608%5Bpmid%5D)
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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)
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1. [Bigi S et al: Outcomes after early administration of plasma exchange in pediatric central nervous system inflammatory demyelination. J Child Neurol. 30(7):874-80, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25246301%5Bpmid%5D)
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1. [Kearney H et al: Spinal cord grey matter abnormalities are associated with secondary progression and physical disability in multiple sclerosis. J Neurol Neurosurg Psychiatry. 86(6):608-14, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25097217%5Bpmid%5D)
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1. [Riederer I et al: Double inversion recovery sequence of the cervical spinal cord in multiple sclerosis and related inflammatory diseases. AJNR Am J Neuroradiol. 36(1):219-25, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25169924%5Bpmid%5D)
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1. [Russi AE et al: The meninges: new therapeutic targets for multiple sclerosis. Transl Res. 165(2):255-69, 2015](http://www.ncbi.nlm.nih.gov/pubmed/?term=25241937%5Bpmid%5D)
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1. [De Stefano N et al: Spinal cord imaging in multiple sclerosis: filling the gap with the brain. Neurology. 83(15):1306-7, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=25186859%5Bpmid%5D)
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1. [Makary MS et al: Tumefactive demyelinating disease with isolated spinal cord involvement. Acta Radiol Short Rep. 3(5):2047981614539324, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=25298871%5Bpmid%5D)
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1. [Schlaeger R et al: Spinal cord gray matter atrophy correlates with multiple sclerosis disability. Ann Neurol. 76(4):568-80, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=25087920%5Bpmid%5D)
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1. [Toosy AT et al: Voxel-based cervical spinal cord mapping of diffusion abnormalities in MS-related myelitis. Neurology. 83(15):1321-5, 2014](http://www.ncbi.nlm.nih.gov/pubmed/?term=25186861%5Bpmid%5D)
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1. [Simka M et al: Reinterpreting the magnetic resonance signs of hemodynamic impairment in the brains of multiple sclerosis patients from the perspective of a recent discovery of outflow block in the extracranial veins. J Neurosci Res. 88(9):1841-5, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=20127806%5Bpmid%5D)
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1. [Tallantyre EC et al: Clinico-pathological evidence that axonal loss underlies disability in progressive multiple sclerosis. Mult Scler. 16(4):406-11, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=20215480%5Bpmid%5D)
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1. [Valsasina P et al: Cervical cord functional MRI changes in relapse-onset MS patients. J Neurol Neurosurg Psychiatry. 81(4):405-8, 2010](http://www.ncbi.nlm.nih.gov/pubmed/?term=19965858%5Bpmid%5D)
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1. [Zamboni P et al: Chronic cerebrospinal venous insufficiency in patients with multiple sclerosis. J Neurol Neurosurg Psychiatry. 80(4):392-9, 2009](http://www.ncbi.nlm.nih.gov/pubmed/?term=19060024%5Bpmid%5D)
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1. [Zhang B et al: Correlation between serum thyroxine and complements in patients with multiple sclerosis and neuromyelitis optica. Neuro Endocrinol Lett. 29(2):256-60, 2008](http://www.ncbi.nlm.nih.gov/pubmed/?term=18404143%5Bpmid%5D)
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1. [Yukawa Y et al: MR T2 image classification in cervical compression myelopathy: predictor of surgical outcomes. Spine (Phila Pa 1976). 32(15):1675-8; discussion 1679, 2007](http://www.ncbi.nlm.nih.gov/pubmed/?term=17621217%5Bpmid%5D)
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1. [Maravilla KR et al: Magnetic resonance demonstration of multiple sclerosis plaques in the cervical cord. AJR Am J Roentgenol. 144(2):381-5, 1985](http://www.ncbi.nlm.nih.gov/pubmed/?term=3871287%5Bpmid%5D)
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## Images
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### Selected Images
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*Sagittal graphic depicts multiple sclerosis (MS) demyelinating plaques within the cervical spinal cord. Lesions are focal and < 2 vertebral bodies in length, typical of MS.*
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*Sagittal graphic depicts multiple sclerosis (MS) demyelinating plaques within the cervical spinal cord. Lesions are focal and < 2 vertebral bodies in length, typical of MS.*
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*Sagittal T2WI MR (left) demonstrates a solitary active MS plaque <img src='img/arrows/WS.png'/> at the C6-C7 level with focal T2 hyperintensity but without significant cord enlargement. Sagittal T1WI C+ FS MR (right) confirms ring enhancement of the focal lesion, consistent with an active MS plaque.*
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*Sagittal T2WI (left), PD (middle), and STIR (right) MR images show multiple short-segment MS plaques within the thoracic spinal cord <img src='img/arrows/CS.png'/>. Note the relatively improved conspicuity of the plaques on PD and STIR relative to the routine T2 sequence.*
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*Sagittal STIR (left), T2WI (middle), and T1WI C+ FS (right) MR images of the thoracic spine show multiple short-segment foci of T2 hyperintensity <img src='img/arrows/WS.png'/> in a different patient with MS. Multiple lesions <img src='img/arrows/CS.png'/> show solid enhancement.*
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### Additional Images
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*Sagittal T2WI MR in a patient with MS and characteristic brain lesions (not shown) reveals a focal lesion <img src='img/arrows/WS.png'/> centered at C7 with minimal if any cord enlargement.*
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*Axial T2WI MR in the same patient reveals a lesion in the left hemicord that is focal and does not involve the entire cord diameter, features favoring MS.*
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*Sagittal T2WI (left) and T1WI C+ FS (right) MR images show several T2-hyperintense foci in the cervical cord in this patient with MS. Two of the lesions enhance, reflecting active demyelination <img src='img/arrows/WS.png'/>.*
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*Sagittal T2WI (left) and T1WI C+ (right) MR images show active enhancing plaque at the C2 level with both focal, well-defined (enhancing) T2 focus <img src='img/arrows/WS.png'/> and a small amount of surrounding nonenhancing edema <img src='img/arrows/WO.png'/>.*
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*Sagittal T2WI MR of the cervical cord shows a more discrete demyelinating focus at C3-C4.*
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*Axial T2WI MR of the cervical cord in a different patient shows a poorly defined, wedge-shaped, mildly hyperintense plaque within the right lateral aspect of the cord.*
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*Axial T1WI C+ MR with fat suppression of the cervical cord in a different patient shows right peripheral nodular enhancement.*
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*Sagittal T2WI MR of the cervical cord shows an ill-defined, hyperintense intramedullary lesion at C5-C6.*
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*Sagittal T2WI MR of the cervical spinal cord demonstrates multiple T2-hyperintense foci <img src='img/arrows/WS.png'/>, some well defined and others ill defined. The multiplicity of lesions and lack of edema or significant cord expansion is typical for demyelinating disease.*
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*Sagittal T1WI C+ MR shows multiple enhancing demyelinating lesions within the cervical spinal cord. Enhancement varies from focal <img src='img/arrows/WC.png'/> to ill defined <img src='img/arrows/WO.png'/>. The enhancement pattern changes with evolution of inflammation.*
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*T1WI C+ MR (sagittal on top, axial on bottom) illustrates an incomplete rim-enhancing lesion <img src='img/arrows/WS.png'/> in the dorsal cervical cord at the C3-C4 level. A 2nd small enhancing focus is noted in the ventral cord at the C6 level <img src='img/arrows/WC.png'/>.*
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*Sagittal PD FSE MR of the cervical spinal cord demonstrates characteristic ovoid hyperintense intramedullary demyelinating lesions <img src='img/arrows/WO.png'/> without significant cord expansion.*
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*Axial T1WI C+ MR of the cervical spinal cord depicts focal ring enhancement <img src='img/arrows/WS.png'/> within an active MS demyelinating lesion.*
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*Sagittal STIR MR shows a focal hyperintense demyelinating plaque <img src='img/arrows/WS.png'/> within the thoracic cord without significant cord expansion. STIR MR is more sensitive for lesion depiction than T2WI MR at the price of more artifacts.*
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*Sagittal high-resolution GRE MR of the thoracic cord shows multiple areas of ↑ signal <img src='img/arrows/WS.png'/> in this patient with MS. All lesions are ≤ 2 vertebral bodies in length, typical for MS.*
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