10.6 Motor Neuron Disease & Acute Peripheral Neuropathy

1. Motor Neuron Disease: Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic lateral sclerosis (ALS / Lou Gehrig disease) is a fatal, progressive neurodegenerative disorder characterized by selective degeneration of both upper motor neurons (UMNs) in the primary motor cortex / corticospinal tract and lower motor neurons (LMNs) in the brainstem motor nuclei and anterior horns of the spinal cord.

Clinical Hallmark: Combined UMN and LMN Signs

Diagnosis requires the objective coexistence of UMN and LMN signs within the same body region / segment (bulbar, cervical, thoracic, or lumbosacral):

• Upper Motor Neuron Signs: Spasticity, hyperreflexia, clonus, extensor plantar response (positive Babinski sign), pseudobulbar affect (inappropriate, involuntary laughing or crying episodes), and brisk preserved deep tendon reflexes in an otherwise severely atrophic, wasted limb.
• Lower Motor Neuron Signs: Flaccid weakness, muscle atrophy, prominent fasciculations (visible twitching in tongue, arms, and legs), foot drop, hand intrinsic muscle wasting (preferential thenar wasting = "split-hand sign"), and muscle cramps.
• Systemic Sparing (What is NOT Affected in ALS):
  • Sensory function is completely normal (no numbness, paresthesias, or sensory loss).
  • Bowel and bladder sphincter control is preserved (Onuf's nucleus in S2-S4 is spared).
  • Extraocular eye movements are preserved (cranial nerves III, IV, VI spared).
  • Autonomic function is normal.

Diagnostic & Electrodiagnostic Workup

• Electromyography and Nerve Conduction Studies (EMG/NCS): Demonstrates widespread active denervation (fibrillation potentials, positive sharp waves, fasciculation potentials) and chronic reinnervation (giant, polyphasic, long-duration motor unit action potentials [MUAPs]) across >=3 body segments.
• Spine & Brain MRI: Essential to exclude compressive cervical spondylotic myelopathy, multiple sclerosis, or spinal cord tumors.

Evidence-Based Management of ALS

1. Disease-Modifying Pharmacotherapies:
   • Riluzole (50 mg PO BID): Glutamate antagonist that blocks voltage-gated sodium channels and inhibits glutamate release, reducing excitotoxicity. Prolongs survival or time to tracheostomy by 2 to 3 months; monitor liver enzymes (ALT/AST).
   • Edaravone (Radicava): Free radical scavenger that reduces oxidative stress; slows functional motor decline in early-stage disease.
2. Multidisciplinary Supportive Interventions:
   • Non-Invasive Positive Pressure Ventilation (NIV / BiPAP): Indicated when Forced Vital Capacity (FVC) falls <50% of predicted or symptoms of nocturnal hypoventilation develop. Significantly prolongs survival and improves quality of life.
   • Percutaneous Endoscopic Gastrostomy (PEG) Tube: Indicated for severe dysphagia, choking, and progressive weight loss; should be placed before FVC drops <50% to avoid acute procedural respiratory failure.
   • Pseudobulbar Affect: Treated with Dextromethorphan-Quinidine (Nuedexta).

2. Peripheral Neuropathies: Guillain-Barré Syndrome & Polyneuropathies

1. Guillain-Barré Syndrome (GBS / AIDP)

• Pathophysiology: Acute post-infectious autoimmune polyradiculoneuropathy driven by molecular mimicry between microbial antigens (lipooligosaccharides) and host gangliosides on peripheral nerve axolemma and Schwann cells. Triggered by Campylobacter jejuni (>30% of cases; associated with severe axonal AMAN variant), Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Mycoplasma pneumoniae, Zika virus, or SARS-CoV-2.
• Clinical Presentation:
  • Rapidly progressive, symmetrical, ascending flaccid weakness beginning in the lower extremities and ascending over days to involve the arms, trunk, and cranial nerves (facial diplegia in 50%).
  • Hyporeflexia or complete Areflexia in affected limbs is mandatory for diagnosis.
  • Autonomic Instability (Dysautonomia in 65%): Blood pressure lability (severe hypertension or orthostatic hypotension), cardiac arrhythmias (sinus tachycardia, severe bradycardia, asystole), ileus, and urinary retention. Mandates continuous cardiac telemetry in an ICU/step-down setting.
• Diagnostic Evaluation:
  • Lumbar Puncture (CSF Analysis): Classic Albuminocytologic Dissociation — markedly elevated CSF protein (>45 to 200+ mg/dL) with a normal CSF white blood cell count (<5 to 10 cells/mcL). (Note: CSF protein may be normal during the first 3-5 days; repeat LP if suspicion is high).
  • Pulmonary Mechanics Monitoring: Serial bedside FVC (<15-20 mL/kg) and NIF (worse than -20 to -30 cm H2O) monitoring every 2-4 hours to guide elective intubation before hypoxemic collapse.
• Disease-Modifying Treatment:
  • Intravenous Immunoglobulin (IVIG: 0.4 g/kg/day for 5 days [total 2.0 g/kg]) OR Plasma Exchange (PEX: 4-5 sessions over 7-14 days).
  • Both modalities are equally effective. Combination of IVIG + PEX offers no synergistic benefit.
  • CRITICAL BOARD CONTRAINDICATION: Corticosteroids (systemic steroids) are INEFFECTIVE and may worsen long-term recovery; they must NEVER be administered in Guillain-Barré Syndrome.

2. Diabetic Distal Symmetric Polyneuropathy (DSPN) vs Mononeuritis Multiplex