What are the diagnostic approaches and treatment options for Transverse Myelitis (TM) versus Guillain-Barré Syndrome (GBS)?

Distinguishing Transverse Myelitis from Guillain-Barré Syndrome

The key to differentiating transverse myelitis (TM) from Guillain-Barré syndrome (GBS) lies in identifying pyramidal signs, a sensory level, and bladder/bowel dysfunction (which point to TM), versus ascending areflexic weakness with preserved sphincter function (which points to GBS)—but recognize that these conditions can rarely coexist as an overlap syndrome requiring combined diagnostic approaches. 1, 2

Critical Distinguishing Clinical Features

Features That Favor GBS Over TM:

• Ascending bilateral weakness starting in legs, progressing to arms and cranial muscles over days to 2 weeks 1, 3
• Absent or decreased reflexes (areflexia or hyporeflexia) in affected limbs—this is a hallmark feature 1, 4
• Preserved sphincter function at onset and throughout disease course 1
• No sensory level—instead, distal paresthesias or "glove-and-stocking" sensory loss may occur 3, 4
• Bilateral facial palsy and other cranial nerve involvement 1, 4
• Dysautonomia (blood pressure/heart rate instability, pupillary dysfunction) without spinal shock 3, 4
• Preceding infection in approximately two-thirds of patients within 6 weeks 3, 4

Features That Favor TM Over GBS:

• Sharp sensory level indicating spinal cord injury 1
• Bladder or bowel dysfunction at onset or persistent during disease course 1
• Hyperreflexia, clonus, or extensor plantar responses (positive pyramidal signs) 1, 2
• Severe respiratory dysfunction with limited limb weakness at onset 1
• Sensory signs with limited weakness at onset 1

Red Flags for GBS/TM Overlap Syndrome:

• Areflexia or hyporeflexia combined with positive pyramidal signs—this paradoxical finding occurred in 17.6% of overlap cases 2
• Positive pyramidal signs or negative plantar reflex in 29.4% of overlap patients 2
• High rates of pain (43.5% at onset) and respiratory failure (47.8%) 2
• Recovery slower than anticipated with standard GBS treatment 5

Diagnostic Algorithm

Step 1: Initial Clinical Assessment

• Assess pattern of weakness: ascending (GBS) vs. level-dependent (TM) 1, 3
• Check reflexes carefully: absent/decreased (GBS) vs. increased with Babinski sign (TM) 1
• Test for sensory level: present (TM) vs. absent (GBS) 1
• Evaluate sphincter function: preserved (GBS) vs. impaired (TM) 1
• Document timing: GBS progresses over days to 4 weeks (usually <2 weeks), while TM typically reaches nadir within hours to days 1, 4

Step 2: Cerebrospinal Fluid Analysis

• Albumino-cytological dissociation (elevated protein with normal cell count) supports GBS, though protein may be normal in 30-50% during the first week 1, 4
• Marked pleocytosis (>50 cells/μl) argues against GBS and suggests TM or other inflammatory/infectious causes 1
• Mild pleocytosis (10-50 cells/μl) is compatible with GBS but should prompt consideration of infectious polyradiculitis 1

Step 3: Electrodiagnostic Studies

• Perform nerve conduction studies and EMG to identify sensorimotor polyradiculoneuropathy with reduced conduction velocities, reduced amplitudes, temporal dispersion, or conduction blocks 3, 4
• Look for "sural sparing pattern" (normal sural sensory nerve action potential with abnormal median/ulnar responses)—typical for GBS 3, 4
• Normal electrophysiology early (within 1 week) does not rule out GBS; repeat in 2-3 weeks if suspicion remains high 1
• In overlap syndrome, electrophysiology confirms peripheral nerve involvement even when spinal cord lesions are present 2, 5

Step 4: MRI Imaging

• Spinal MRI with gadolinium is essential when TM is suspected or when clinical features are atypical 3
• Nerve root enhancement on gadolinium-enhanced MRI supports GBS but is nonspecific 3
• Spinal cord signal abnormalities on T2-weighted sequences confirm TM—most commonly involving cervical (69.6%) and thoracic (69.6%) segments in overlap cases 2
• Brain MRI is recommended in suspected overlap syndrome to detect subclinical lesions (found in 3 patients in one series) 2
• MRI abnormalities were detected in all patients with GBS/TM overlap syndrome 2

Step 5: Additional Testing

• Serum antiganglioside antibodies (including anti-GQ1b for Miller Fisher variant) may be present in GBS subgroups 3
• Initial laboratory tests: CBC, glucose, electrolytes, kidney/liver function, creatine kinase to exclude metabolic causes 4

Treatment Approach

For Confirmed GBS:

• IVIg 0.4 g/kg/day for 5 days (total 2 g/kg) OR plasma exchange (200-250 ml/kg for 5 sessions) for patients unable to walk unaided 1, 4
• Do not use corticosteroids alone for idiopathic GBS (not effective) 1
• Admit to monitored setting with capability for rapid ICU transfer 1
• Monitor respiratory function closely—approximately one-third require mechanical ventilation 6

For Confirmed TM:

• High-dose IV methylprednisolone 1 g/day for 3-5 days followed by oral prednisone taper 2, 5
• Consider plasma exchange or IVIg if steroid-refractory 5

For GBS/TM Overlap Syndrome:

• Combined therapy with IVIg and corticosteroids is the most frequent treatment approach 2, 7
• Specifically: IVIg 0.4 g/kg/day for 5 days PLUS methylprednisolone 1 g/day for 3-5 days followed by 6-week oral prednisone course 2
• Warning: Only 46.2% of overlap patients who received combined IVIg and steroids responded well, and less than half had favorable outcomes overall 2
• Acute axonal polyneuropathy on electrodiagnostic studies is associated with poor prognosis (OR=3.00,95% CI 1.35-6.68) 2

Critical Pitfalls to Avoid

• Do not dismiss GBS based on normal CSF protein in the first week—it's normal in 30-50% of early cases 1, 4
• Do not rule out overlap syndrome simply because initial diagnosis was GBS—if recovery is slower than expected, obtain spinal MRI 5
• Do not delay treatment waiting for antibody results if GBS is clinically suspected 4
• Do not assume single pathology—while rare, GBS/TM overlap occurs and requires both electrophysiology AND spinal MRI for diagnosis 2, 5
• Marked persistent asymmetry, bladder dysfunction at onset, or marked CSF pleocytosis should prompt reconsideration of pure GBS diagnosis 4
• Only 29.4% of overlap patients were correctly diagnosed initially, highlighting the difficulty of early recognition 2