How do you differentiate between multiple sclerosis (MS), Guillain-Barré Syndrome (GBS), and transverse myelitis?

Differentiating Multiple Sclerosis, Guillain-Barré Syndrome, and Transverse Myelitis

Use a systematic approach based on reflexes, symmetry, sensory level, and MRI patterns to distinguish these three conditions: GBS presents with ascending areflexia and peripheral nerve findings, transverse myelitis shows a sharp sensory level with symmetric cord involvement, and MS demonstrates asymmetric symptoms with disseminated CNS lesions in space and time.

Clinical Features That Distinguish These Conditions

Reflexes and Motor Patterns

• GBS shows absent or decreased reflexes in affected limbs as a required diagnostic feature, with progressive bilateral weakness ascending from legs to arms over days to 4 weeks 1
• Transverse myelitis presents with hyperreflexia or clonus below the lesion level, which should raise doubt about GBS diagnosis 1
• MS typically shows asymmetric motor weakness with hyperreflexia and extensor plantar responses, whereas transverse myelitis exhibits symmetric weakness uniformly 2

Sensory Distribution

• A sharp sensory level indicates spinal cord injury (transverse myelitis or MS myelitis) and casts doubt on GBS diagnosis 1
• GBS demonstrates a "sural sparing pattern" on nerve conduction studies where sural sensory nerve action potential remains normal while median and ulnar potentials are abnormal 1
• Symmetric sensory loss occurs in all but one transverse myelitis patient, while MS myelitis shows asymmetric sensory symptoms in all but one patient 2

Bladder and Bowel Function

• Bladder or bowel dysfunction at onset or persistent during disease course casts doubt on GBS and strongly suggests spinal cord pathology 1
• Sphincter involvement is more pronounced in MS myelitis (40.4%) compared to other causes of myelitis (27.3%) 3

MRI Patterns: The Critical Differentiator

Spinal Cord Imaging

• MS myelitis shows multifocal spinal cord involvement (77.2% vs 26.5% in other myelitis), shorter lesion extension (1.4 vs 2.4 vertebral segments), and posterior cord location (89.5% vs 41.2%) 3
• Transverse myelitis typically presents with longitudinally extensive lesions affecting ≥3 contiguous vertebral segments, central cord involvement (47.1% vs 14.1% in MS), and anterior location (47.1% vs 24.6% in MS) 4, 3
• GBS may show nerve root enhancement on gadolinium-enhanced MRI, but this is nonspecific and MRI is not part of routine diagnostic evaluation 1

Brain Imaging

• MS requires dissemination in space with at least one lesion in two or more locations: periventricular, juxtacortical, infratentorial, or spinal cord 5
• Transverse myelitis patients typically have normal brain MRI or non-specific findings, distinguishing it from MS 4
• GBS does not require brain MRI unless excluding differential diagnoses like brainstem stroke or infection 1

Cerebrospinal Fluid Analysis

Protein and Cell Count

• GBS shows albumino-cytological dissociation (elevated protein with normal cell count), though protein may be normal in 30-50% during the first week 1
• Marked pleocytosis (>50 cells/μl) suggests transverse myelitis from infectious or inflammatory causes rather than GBS 1
• MS demonstrates CSF oligoclonal bands specific to CSF in most cases, supporting the diagnosis 5

Electrodiagnostic Studies

Nerve Conduction Patterns

• GBS reveals sensorimotor polyradiculoneuropathy with reduced conduction velocities, reduced amplitudes, temporal dispersion, and/or partial motor conduction blocks 1
• Transverse myelitis and MS show normal peripheral nerve conduction studies since the pathology is in the CNS, not peripheral nerves 1
• Electrophysiology may be normal early in GBS (within 1 week), requiring repeat studies 2-3 weeks later 1

Time Course and Progression

Disease Evolution

• GBS progresses over days to 4 weeks (usually <2 weeks), then plateaus and improves 1
• Continued progression beyond 4 weeks casts doubt on GBS and suggests alternative diagnoses 1
• MS demonstrates dissemination in time requiring evidence of lesions occurring at different times, such as simultaneous gadolinium-enhancing and non-enhancing lesions 5
• Transverse myelitis typically reaches nadir within days to weeks and does not show the relapsing-remitting pattern of MS 4

Critical Pitfalls to Avoid

Red Flags Against GBS

• Fever at onset, hyper-reflexia, extensor plantar responses, or sharp sensory level all argue strongly against GBS 1
• Severe respiratory dysfunction with limited limb weakness at onset is atypical for GBS 1
• Marked asymmetry of weakness should prompt consideration of MS or focal spinal cord lesions 1

Distinguishing MS from Isolated Transverse Myelitis

• Multifocal spinal cord involvement (OR 9.38) and posterior cord involvement (OR 2.16) are independently associated with MS diagnosis rather than isolated transverse myelitis 3
• MS patients had asymmetric motor or sensory symptoms in all but one patient, whereas transverse myelitis patients exhibited symmetric findings 2
• None of the transverse myelitis patients developed MS over 4.5 years follow-up when strict clinical criteria were applied at presentation 2

GBS/Transverse Myelitis Overlap Syndrome

• Abnormal pyramidal signs in a patient with areflexia (29.4% with positive pyramidal signs or negative plantar reflex) suggests rare GBS/ATM overlap syndrome 6
• This overlap requires both electrophysiology confirming GBS and spinal MRI demonstrating cord lesions, most commonly involving cervical (69.6%) and thoracic (69.6%) segments 6
• Combined IVIG and steroids is the most frequent treatment for overlap syndrome, though less than half respond positively 6

Practical Diagnostic Algorithm

1. Check reflexes first: Areflexia → consider GBS; hyperreflexia → consider transverse myelitis or MS 1, 2
2. Assess symmetry: Symmetric weakness → transverse myelitis; asymmetric → MS 2, 3
3. Look for sensory level: Sharp level → spinal cord pathology (not GBS) 1
4. Order spinal MRI: Multifocal short lesions posteriorly → MS; longitudinally extensive central lesions → transverse myelitis; nerve root enhancement → GBS 1, 3
5. Perform nerve conduction studies: Abnormal → GBS; normal → CNS pathology 1
6. Check brain MRI: Periventricular/juxtacortical lesions → MS; normal → isolated transverse myelitis 5, 3