--- title: "CIDP" docid: "12e4033c-edc8-46ff-8081-3acc433cda78" 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: "CIDP" slug: "cidp" treeNodeId: null category: "Brain" documentVersionId: "96729e13-6c4b-4fd3-be3e-4e1a940566fd" imageCount: 12 lastUpdated: "06/08/20" pageDescription: "CIDP" pageKeywords: "Brain, Diagnosis, Pathology-Based Diagnoses, Infectious, Inflammatory, and Demyelinating Disease, Inflammatory and Demyelinating Disease, CIDP" pageTitle: "CIDP | STATdx" enhancedTitle: "CIDP" type: "DX" references: true breadcrumbs: - "Brain" - "Diagnosis" - "Pathology-Based Diagnoses" - "Infectious, Inflammatory, and Demyelinating Disease" - "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. 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[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 . 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.](images/app.statdx.com_image_thumbnail_e0d1598d-4a92-4d78-9124-87f27a196230_annotated_true_size_900_quality_90_8ebe0b28_20251018T122453Z.jpg) *Sagittal T1 C+ MR of the cervical spine shows marked hypertrophy and enhancement of all exiting cervical nerve roots . 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 . 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.](images/app.statdx.com_image_thumbnail_e0d1598d-4a92-4d78-9124-87f27a196230_size_168_quality_85_41f53f54_20251018T095234Z.jpg) *Sagittal T1 C+ MR of the cervical spine shows marked hypertrophy and enhancement of all exiting cervical nerve roots . 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 . 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.](images/app.statdx.com_image_thumbnail_e0d1598d-4a92-4d78-9124-87f27a196230_size_174_quality_85_90acc783_20251018T122441Z.jpg) *Sagittal T1 C+ MR of the cervical spine shows marked hypertrophy and enhancement of all exiting cervical nerve roots . 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 . High signal of CSF should be excluded while measuring nerve root size/area in T2 MR.](images/app.statdx.com_image_thumbnail_c27b3469-6c6e-4d3c-8cc8-a93671c5bf09_annotated_true_size_900_quality_90_ac6a09e4_20251018T122453Z.jpg) *Sagittal T2WI MR reveals enlargement and T2 hyperintensity of exiting extradural lumbosacral nerves . 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 . High signal of CSF should be excluded while measuring nerve root size/area in T2 MR.](images/app.statdx.com_image_thumbnail_c27b3469-6c6e-4d3c-8cc8-a93671c5bf09_size_168_quality_85_8455ce81_20251018T095234Z.jpg) *Sagittal T2WI MR reveals enlargement and T2 hyperintensity of exiting extradural lumbosacral nerves . 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 . 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.](images/app.statdx.com_image_thumbnail_f40f3c68-4a6c-4e61-a1d0-818ea614c071_annotated_true_size_900_quality_90_d99899db_20251018T122453Z.jpg) *Axial T1WI C+ MR depicts enlargement and abnormal enhancement of exiting extradural lumbosacral nerves . 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 . 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.](images/app.statdx.com_image_thumbnail_f40f3c68-4a6c-4e61-a1d0-818ea614c071_size_168_quality_85_b4a51382_20251018T095234Z.jpg) *Axial T1WI C+ MR depicts enlargement and abnormal enhancement of exiting extradural lumbosacral nerves . 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 in a typical case of marked fusiform CIDP nerve enlargement with brain demyelination.](images/app.statdx.com_image_thumbnail_8ef8ec72-8984-4f90-8380-953114da6604_annotated_true_size_900_quality_90_c59fe9eb_20251018T122453Z.jpg) *Sagittal FLAIR MR demonstrates periventricular ovoid hyperintensities in a typical case of marked fusiform CIDP nerve enlargement with brain demyelination.* ![Sagittal FLAIR MR demonstrates periventricular ovoid hyperintensities in a typical case of marked fusiform CIDP nerve enlargement with brain demyelination.](images/app.statdx.com_image_thumbnail_8ef8ec72-8984-4f90-8380-953114da6604_size_168_quality_85_e847b484_20251018T095234Z.jpg) *Sagittal FLAIR MR demonstrates periventricular ovoid hyperintensities 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 .](images/app.statdx.com_image_thumbnail_385d96c2-5ef1-466a-bbf7-bcfbf8fb9433_annotated_true_size_900_quality_90_b76815ce_20251018T122453Z.jpg) *Axial T1WI C+ MR shows thickening and enhancement of ventral and dorsal cauda equina nerve roots .* ![Axial T1WI C+ MR shows thickening and enhancement of ventral and dorsal cauda equina nerve roots .](images/app.statdx.com_image_thumbnail_385d96c2-5ef1-466a-bbf7-bcfbf8fb9433_size_168_quality_85_3828ef00_20251018T095234Z.jpg) *Axial T1WI C+ MR shows thickening and enhancement of ventral and dorsal cauda equina nerve roots .* ![Sagittal T2WI MR demonstrates diffuse thickening of the intradural cauda equina nerve roots.](images/app.statdx.com_image_thumbnail_e85adcc5-c5d2-4c04-b676-83773765bd8e_annotated_true_size_900_quality_90_6f96bf2d_20251018T122453Z.jpg) *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.](images/app.statdx.com_image_thumbnail_e85adcc5-c5d2-4c04-b676-83773765bd8e_size_168_quality_85_0a98e931_20251018T095234Z.jpg) *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 similar to those seen in multiple sclerosis patients.](images/app.statdx.com_image_thumbnail_4161f150-8dc2-4c83-94b9-4ee9d01c70f7_annotated_true_size_900_quality_90_b058499e_20251018T122453Z.jpg) *Sagittal FLAIR MR of the brain in a CIDP patient shows a typical paraventricular demyelinating lesion similar to those seen in multiple sclerosis patients.* ![Sagittal FLAIR MR of the brain in a CIDP patient shows a typical paraventricular demyelinating lesion similar to those seen in multiple sclerosis patients.](images/app.statdx.com_image_thumbnail_4161f150-8dc2-4c83-94b9-4ee9d01c70f7_size_168_quality_85_efb486ac_20251018T095234Z.jpg) *Sagittal FLAIR MR of the brain in a CIDP patient shows a typical paraventricular demyelinating lesion similar to those seen in multiple sclerosis patients.* ![Sagittal T2WI MR depicts enlarged lumbar nerve roots extending into extraforaminal ventral primary rami .](images/app.statdx.com_image_thumbnail_4683fb7b-747f-4882-8f72-0a9b82b28723_annotated_true_size_900_quality_90_af319ef1_20251018T122453Z.jpg) *Sagittal T2WI MR depicts enlarged lumbar nerve roots extending into extraforaminal ventral primary rami .* ![Sagittal T2WI MR depicts enlarged lumbar nerve roots extending into extraforaminal ventral primary rami .](images/app.statdx.com_image_thumbnail_4683fb7b-747f-4882-8f72-0a9b82b28723_size_168_quality_85_b2a08acd_20251018T095234Z.jpg) *Sagittal T2WI MR depicts enlarged lumbar nerve roots extending into extraforaminal ventral primary rami .* ![Axial T2WI MR shows diffuse thickening and hyperintensity of thoracic nerve roots and paraspinal intercostal nerves.](images/app.statdx.com_image_thumbnail_7443f593-4ded-4c77-b1e2-b2d61ecea64a_size_168_quality_85_52da947b_20251018T095234Z.jpg) *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 .](images/app.statdx.com_image_thumbnail_d53c481c-3aa4-4771-8aa3-b7081202b269_size_168_quality_85_93e086b6_20251018T095234Z.jpg) *Axial T2WI MR reveals bilateral symmetric enlargement, hyperintensity of cervical nerve roots and brachial plexus .* ![Sagittal T1WI C+ MR demonstrates diffuse pial thickening and enhancement extending into the cauda equina nerve roots. Clinical course distinguished from Guillain-Barré (AIDP).](images/app.statdx.com_image_thumbnail_f2bfe031-78d4-4f16-baa0-c95a54f6e565_size_168_quality_85_0fab86e2_20251018T095234Z.jpg) *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 and lumbosacral trunk .](images/app.statdx.com_image_thumbnail_7776240a-5af6-404a-bc66-83b9ee89150e_size_168_quality_85_e3313250_20251018T095234Z.jpg) *Axial T2WI MR shows marked enlargement of the lumbar/sacral nerve roots and lumbosacral trunk .*