What is the approach to diagnosing and treating demyelinating neuropathies, such as Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) and Guillain-Barré Syndrome?

Diagnosis of Demyelinating Neuropathies

The diagnosis of demyelinating neuropathies requires a systematic integration of clinical features, electrophysiological studies showing demyelination, and cerebrospinal fluid analysis demonstrating cytoalbuminologic dissociation, with the critical distinction being the time course: progression over days to 4 weeks suggests Guillain-Barré syndrome (GBS), while progression beyond 2 months indicates Chronic Inflammatory Demyelinating Polyneuropathy (CIDP). 1, 2

Clinical Assessment

Guillain-Barré Syndrome (GBS)

Required diagnostic features:

• Progressive bilateral weakness of arms and legs (legs may be initially involved alone) 1
• Absent or decreased tendon reflexes in affected limbs at some point during the clinical course 1

Strongly supportive features:

• Progressive phase lasting days to 4 weeks (typically <2 weeks) 1
• Relative symmetry of symptoms and signs 1
• Mild sensory symptoms (absent in pure motor variant) 1
• Bilateral facial palsy or other cranial nerve involvement 1
• Autonomic dysfunction 1
• Muscular or radicular back/limb pain 1

Red flags that cast doubt on GBS diagnosis:

• CSF pleocytosis (>50 × 10⁶/L mononuclear or polymorphonuclear cells) 1
• Marked persistent asymmetry of weakness 1
• Bladder or bowel dysfunction at onset or persistent during disease course 1
• Continued progression for >4 weeks after symptom onset 1
• Sharp sensory level indicating spinal cord injury 1
• Hyperreflexia, clonus, or extensor plantar responses 1

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Key distinguishing features:

• Progression over more than 2 months (versus days to weeks in GBS) 2
• Symmetrical, motor-predominant peripheral neuropathy producing both distal and proximal weakness 3
• Large-fiber abnormalities (weakness and ataxia) predominate over small-fiber abnormalities (autonomic and pain) 3

CIDP variants to recognize:

• Multifocal Acquired Demyelinating Sensory and Motor Neuropathy (MADSAM/Lewis-Sumner Syndrome): asymmetric involvement with preserved reflexes in unaffected areas 2
• Chronic neurovisceral variants with slower progression 2

Diagnostic Testing

Cerebrospinal Fluid Analysis

Perform lumbar puncture looking for:

• Cytoalbuminologic dissociation: elevated protein with normal cell count 2, 3
• Critical caveat: Normal protein levels do not rule out GBS, especially early in disease course 1
• CSF pleocytosis (>50 cells) should prompt consideration of alternative diagnoses 1

Electrophysiological Studies

Nerve conduction studies demonstrate:

• Evidence of demyelination: slowed conduction velocities, temporal dispersion, and conduction block 3
• Differentiation between GBS subtypes: AIDP (acute inflammatory demyelinating polyradiculoneuropathy), AMAN (acute motor axonal neuropathy), and AMSAN (acute motor sensory axonal neuropathy) 1
• Important limitation: Normal electrophysiology in early stages does not rule out diagnosis 1
• Consider repeating studies 3-8 weeks after disease onset for better classification 1

Additional Diagnostic Workup for CIDP

Mandatory testing to exclude mimics:

• Metastatic bone surveys to rule out osteosclerotic myeloma 3
• Serum electrophoresis with immunofixation for monoclonal gammopathies 3
• HIV testing 3

Imaging studies:

• MRI of brachial or lumbosacral plexus can identify focal or diffuse peripheral nerve abnormalities 2
• MRI is not part of routine GBS diagnosis 1

Nerve biopsy:

• May be useful in evaluating atypical forms of CIDP 2
• Shows segmental demyelination, onion-bulb formation, and endoneurial inflammatory infiltrates 3

Critical Differential Diagnoses

CNS Disorders to Exclude

• Brainstem or spinal cord inflammation/infection (sarcoidosis, Sjögren syndrome, neuromyelitis optica) 1
• Leptomeningeal metastases or neurolymphomatosis 1, 2
• Brainstem or spinal cord compression 1
• Brainstem stroke 1
• Vitamin B1 deficiency (Wernicke encephalopathy) or B12 deficiency (subacute combined degeneration) 1

Neuromuscular Junction and Muscle Disorders

• Electrolyte disorders: hypokalemia, thyrotoxic hypokalemic periodic paralysis, hypomagnesemia, hypophosphatemia 1
• Inflammatory myositis 1
• Acute rhabdomyolysis 1
• Drug-induced toxic myopathy (colchicine, chloroquine, statins) 1

Other Neuropathies

• Diabetic polyradiculoneuropathy 2
• Infectious causes 2
• Systemic inflammatory disorders like lupus 2
• Metabolic disorders, toxins, or nutritional deficiencies 2

Diagnostic Algorithm

Step 1: Establish time course of progression

• Days to 4 weeks → Consider GBS 1
• Beyond 2 months → Consider CIDP 2

Step 2: Confirm clinical features

• Progressive bilateral weakness with areflexia 1
• Assess for red flags that suggest alternative diagnoses 1

Step 3: Obtain CSF analysis

• Look for cytoalbuminologic dissociation 2, 3
• Pleocytosis suggests alternative diagnosis 1

Step 4: Perform nerve conduction studies

• Document demyelinating features 3
• Classify electrophysiological subtype 1

Step 5: For CIDP, complete additional workup

• Serum electrophoresis with immunofixation 3
• Metastatic bone survey 3
• HIV testing 3
• Consider MRI of plexus 2

Step 6: Consider nerve biopsy only for atypical presentations of CIDP 2