How to diagnose and differentiate between multiple sclerosis (MS) and Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) in a patient with neurological symptoms?

Diagnosing and Differentiating MS from CIDP

Multiple sclerosis (MS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are distinguished primarily by their anatomical location—MS affects the central nervous system (CNS) while CIDP affects the peripheral nervous system (PNS)—and this differentiation is established through a combination of clinical presentation, MRI findings, nerve conduction studies, and cerebrospinal fluid analysis. 1, 2

Key Clinical Distinctions

Symptom Patterns

• MS typically presents with: optic neuritis, diplopia, paresthesias, paraparesis, myelopathy, and retrochiasmal visual deficits with acute onset over hours to days 1
• CIDP typically presents with: progressive symmetric or asymmetric weakness, sensory loss in a length-dependent pattern, and areflexia developing over at least 8 weeks 2, 3
• Critical timing difference: MS symptoms evolve acutely and may stabilize or resolve spontaneously, while CIDP symptoms progress subacutely over weeks to months 1

Neurological Examination Findings

• MS shows: upper motor neuron signs, optic nerve involvement, internuclear ophthalmoplegia, and cerebellar signs 1
• CIDP shows: hyporeflexia or areflexia, distal and proximal weakness, and sensory deficits without upper motor neuron signs 2, 3
• Red flag for overlap syndrome: Presence of both central and peripheral signs should raise suspicion for the rare combined central-peripheral demyelinating syndrome 4, 5

Diagnostic Imaging

MRI Characteristics for MS

• Brain lesions: Focal periventricular lesions (especially perpendicular to corpus callosum), juxtacortical lesions, infratentorial lesions, and involvement of U-fibers 1
• Lesion morphology: Sharp edges, round or flame-shaped, typically <3 cm, with characteristic periventricular distribution 1
• Spinal cord lesions: Short segment lesions (<2 vertebral segments), peripherally located in the cord, and often asymptomatic 1
• Gadolinium enhancement: Variable enhancement indicating active inflammation, with simultaneous enhancing and non-enhancing lesions demonstrating dissemination in time 1

MRI Characteristics for CIDP

• Nerve root enhancement: Thickening and enhancement of spinal nerve roots and cauda equina on MRI 5, 3
• Cranial nerve involvement: Possible hypertrophy of cranial nerves on imaging 5
• Absence of brain parenchymal lesions: Normal brain MRI or only nonspecific white matter changes that do not meet MS criteria 4

Critical MRI Protocol Requirements

• For MS diagnosis: T2-weighted, FLAIR, pre- and post-gadolinium T1-weighted sequences of brain and spinal cord 1, 6
• Slice thickness: Thin slices (≤3mm for brain) to detect small lesions 1
• Field strength: 3.0 Tesla preferred over 1.5 Tesla for improved lesion detection 1

Electrodiagnostic Studies

Nerve Conduction Studies

• CIDP findings: Demyelinating features including prolonged distal latencies, conduction velocity slowing (<70-80% of lower limit of normal), conduction block, temporal dispersion, and prolonged F-wave latencies 2, 3
• MS findings: Generally normal peripheral nerve conduction studies, though subclinical peripheral demyelination may occasionally occur 4
• Deep tendon reflex latencies: Prolonged at multiple sites in CIDP patients, useful for assessing proximal nerve segments 3

Cerebrospinal Fluid Analysis

MS Pattern

• Oligoclonal bands: Present in >95% of MS patients, indicating intrathecal IgG synthesis 1
• Protein elevation: Mild elevation (typically <100 mg/dL) 1
• Cell count: Usually <50 cells/μL, predominantly lymphocytes 1

CIDP Pattern

• Protein elevation: Marked elevation (often >70 mg/dL, can exceed 100-145 mg/dL) without pleocytosis 3
• Oligoclonal bands: Typically absent 2
• Albuminocytologic dissociation: Elevated protein with normal cell count is characteristic 2, 3

Diagnostic Criteria Application

MS Diagnosis (2010 McDonald Criteria)

• Dissemination in space (DIS): ≥1 T2 lesion in at least 2 of 4 CNS regions (periventricular, juxtacortical, infratentorial, spinal cord) 1
• Dissemination in time (DIT): Simultaneous presence of gadolinium-enhancing and non-enhancing lesions, OR new T2 or gadolinium-enhancing lesion on follow-up MRI, OR clinical relapse 1
• Exclusion requirement: Must exclude alternative diagnoses that better explain the presentation 1

CIDP Diagnosis

• Clinical criteria: Progressive or relapsing symmetric or asymmetric weakness and sensory dysfunction in proximal and distal muscles developing over ≥8 weeks 2
• Electrodiagnostic criteria: Demyelinating features on nerve conduction studies in ≥2 nerves 2, 3
• Supportive criteria: Elevated CSF protein without pleocytosis, nerve biopsy showing demyelination 2

Overlap Syndrome Recognition

When to Suspect Combined Disease

• Clinical red flags: Patient with established MS developing progressive weakness, areflexia, and distal sensory loss over weeks to months 4, 5, 3
• Imaging clues: MS patient with new nerve root or cranial nerve enhancement without corresponding intraparenchymal lesions 5, 3
• Temporal pattern: CIDP typically develops 4-22 years after MS diagnosis in overlap cases 3
• MRI findings: Approximately 38% of CIDP patients may have periventricular and subcortical white matter lesions resembling MS 4

Diagnostic Approach for Suspected Overlap

• Perform both: Complete brain and spinal cord MRI AND nerve conduction studies in all patients with mixed central and peripheral signs 4, 5
• CSF analysis: Protein levels increase significantly (from ~70 mg/dL to ~145 mg/dL) when CIDP develops in MS patients 3
• Consider nerve biopsy: May show demyelination, axonal loss, and onion-bulb formation, though proximal involvement may be more severe than distal 5

Common Diagnostic Pitfalls

Avoiding Misdiagnosis

• Do not diagnose MS if symptoms are purely peripheral (weakness, areflexia, length-dependent sensory loss) without CNS signs 2
• Do not diagnose CIDP if MRI shows typical MS lesions and nerve conduction studies are normal 1, 2
• Beware of pseudoflares: Temporary worsening of MS symptoms from fever or infection without new inflammatory activity should not be mistaken for true relapse 6
• Exclude NMO spectrum disorders: Longitudinally extensive transverse myelitis (≥3 vertebral segments) and optic neuritis with normal brain MRI suggest NMO, not MS 1

Atypical Presentations Requiring Caution

• Bilateral sudden hearing loss: Extremely rare in MS (<1% with isolated eighth nerve palsy); consider alternative diagnoses 1
• Recurrent or fluctuating symptoms: May suggest autoimmune inner ear disease, Ménière's disease, or Cogan's syndrome rather than MS 1
• Massive nerve hypertrophy: Suggests CIDP with atypical features; may show minimal response to standard therapies 5

Treatment Response as Diagnostic Clue

Differential Treatment Response

• CIDP responds to: Intravenous immunoglobulin (IVIG), corticosteroids, and plasma exchange 2, 3
• MS does not respond to: IVIG (ineffective in MS despite efficacy in CIDP) 2
• Overlap syndrome: May respond to IVIG for both central and peripheral manifestations, suggesting common antigenic targets 3
• Poor response indicator: Minimal improvement with standard therapies in overlap cases may indicate different disease mechanism requiring combination immunotherapy 5