4.4 ALS, GBS, CIDP & Neuromuscular Disease Rehab

ALS, GBS, CIDP & Neuromuscular Disease Rehab

Neuromuscular disorders encompass pathologies affecting the anterior horn cell, peripheral nerve, neuromuscular junction, and muscle. Physiatrists manage function, mobility, non-invasive ventilation, and adaptive equipment in progressive and acute neuromuscular conditions including Amyotrophic Lateral Sclerosis (ALS), Guillain-Barré Syndrome (GBS), Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), and Myasthenia Gravis (MG).

Amyotrophic Lateral Sclerosis (ALS)

Amyotrophic Lateral Sclerosis (ALS / Lou Gehrig Disease) is a fatal, rapidly progressive neurodegenerative disease characterized by simultaneous degeneration of Upper Motor Neurons (UMN) in the motor cortex and Lower Motor Neurons (LMN) in the brainstem and anterior horn of the spinal cord.

Clinical Presentation and Diagnostic Features

• Combined UMN and LMN Signs: The hallmark of ALS is finding concurrent UMN and LMN deficits in the same anatomical body region:
  • UMN Signs: Spasticity, hyperreflexia, clonus, extensor plantar responses (Babinski sign), and pseudobulbar affect (uncontrollable laughing/crying).
  • LMN Signs: Muscle weakness, muscular atrophy, fasciculations, muscle cramps, and hypotonia.
• Anatomical Regions: Assessed across four body segments: Bulbar (dysarthria, dysphagia, tongue atrophy/fasciculations), Cervical (hand weakness, intrinsic atrophy), Thoracic (trunk weakness, dyspnea), and Lumbosacral (foot drop, leg weakness).
• Sparing: Extraocular movements, bowel/bladder sphincters, and sensory pathways are characteristically preserved.

Disease-Modifying Pharmacotherapy

• Riluzole: Inhibits presynaptic glutamate release and blocks NMDA receptors, mitigating excitotoxic neuronal injury. It extends median survival by 2 to 3 months. Requires baseline and periodic LFT monitoring.
• Edaravone: Intravenous or oral free radical scavenger that reduces oxidative stress, slowing functional decline on the ALS Functional Rating Scale-Revised (ALSFRS-R).
• Tofersen: Antisense oligonucleotide that reduces SOD1 protein synthesis in patients with SOD1 gene mutations.

Pulmonary and Nutritional Rehabilitation

• Non-Invasive Ventilation (NIV / BiPAP): Respiratory failure from diaphragmatic weakness is the primary cause of death in ALS. NIV is indicated when:
  • Forced Vital Capacity (FVC) < 50% of predicted
  • Maximal Inspiratory Pressure (MIP) < 60 cmH2O
  • Nocturnal desaturation or symptomatic hypercapnia.
  • Outcome: NIV prolongs survival, slows FVC decline, and improves quality of life far more than any medication.
• Percutaneous Endoscopic Gastrostomy (PEG) Timing: Dysphagia leads to severe malnourishment and dehydration. PEG tube placement should be performed early while the patient's FVC remains > 50%. When FVC drops below 50%, perioperative respiratory failure and procedure-related mortality rise sharply.
• Exercise Guidelines: Moderate submaximal aerobic exercise and light resistive training are beneficial in early stages. Clinicians must strictly avoid eccentric contractions and high-intensity exhaustive exercise, which cause overwork weakness and irreversible myofiber breakdown in denervated motor units.

Guillain-Barré Syndrome (GBS / AIDP)

Guillain-Barré Syndrome (GBS), most commonly manifesting as Acute Inflammatory Demyelinating Polyneuropathy (AIDP), is an acute, post-infectious autoimmune polyradiculoneuropathy.

Clinical Presentation and Diagnostics

• Etiology: Triggered 1 to 3 weeks prior by respiratory or gastrointestinal infection. The most common inciting pathogen is Campylobacter jejuni (associated with severe axonal variants), followed by Cytomegalovirus (CMV), Epstein-Barr Virus (EBV), and Mycoplasma pneumoniae.
• Clinical Features: Rapidly progressive, symmetric ascending flaccid paralysis, beginning in the lower extremities and ascending to the trunk, upper extremities, and cranial nerves (facial diplegia in 50%). Areflexia (loss of DTRs) is obligatory. Autonomic instability (labile blood pressure, cardiac arrhythmias, paralytic ileus) is common and life-threatening.
• Diagnostic Findings:
  • CSF Analysis: Demonstrates albuminocytologic dissociation—a classic hallmark characterized by markedly elevated CSF protein levels (>45 mg/dL) with a normal CSF white blood cell count (<10 cells/μL). Protein elevation may take 7 to 14 days post-onset to develop.
  • NCS/EMG: Features of primary demyelination: prolonged distal motor latencies, marked conduction velocity slowing (<75% of lower limit of normal), conduction block, temporal dispersion, and prolonged or absent F-waves (reflecting demyelination at the proximal spinal roots).

Disease-Modifying Medical Management

• First-Line Immunotherapies:
  • Intravenous Immunoglobulin (IVIG): 0.4 g/kg/day IV for 5 consecutive days.
  • Plasma Exchange (PLEX): 4 to 5 plasma exchanges over 7 to 14 days.
  • Comparison: IVIG and PLEX are equally effective in shortening time to recovery and ventilator dependence. Combining IVIG and PLEX provides no added clinical benefit.
• Corticosteroids: Systemic corticosteroids ARE NOT EFFECTIVE in GBS and are explicitly contraindicated, as randomized trials show they do not speed recovery and may worsen long-term outcomes.

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP)

Chronic Inflammatory Demyelinating Polyneuropathy (CIDP) is an autoimmune demyelinating polyneuropathy considered the chronic counterpart of GBS.

• Clinical Distinction from GBS: CIDP follows a progressive or relapsing-remitting course lasting greater than 8 weeks (whereas GBS reaches peak disability within 4 weeks). It produces symmetric proximal and distal weakness with generalized areflexia.
• Therapeutic Difference: Unlike GBS, CIDP responds robustly to systemic corticosteroids (prednisone). First-line treatments include corticosteroids, IVIG, and PLEX, often requiring long-term maintenance immunosuppression (e.g., azathioprine, rituximab).

Myasthenia Gravis (MG)

Myasthenia Gravis (MG) is an autoimmune disorder of the neuromuscular junction caused by autoantibodies targeting postsynaptic structures.

Pathophysiology and Clinical Presentation

• Autoantibodies: 85% of cases exhibit autoantibodies against postsynaptic acetylcholine receptors (AChR); remaining cases may have antibodies against muscle-specific kinase (MuSK). Up to 15% of patients have an underlying thymoma, and 70% have thymic hyperplasia.
• Clinical Hallmarks: Fatigable muscle weakness that worsens with repetitive activity and toward the end of the day, improving with rest. Initial symptoms affect extraocular muscles (ptosis, diplopia), progressing to bulbar weakness (dysphagia, dysarthria) and limb/respiratory muscle weakness.

Diagnostic Electrodiagnostics

• Repetitive Nerve Stimulation (RNS): Low-frequency (2–3 Hz) stimulation demonstrates a classic decremental response (>10% drop in CMAP amplitude) between the 1st and 4th stimuli due to depletion of presynaptic ACh vesicles across compromised postsynaptic receptors.
• Single-Fiber EMG (SFEMG): The most sensitive diagnostic test (>95%), revealing increased jitter (variability in inter-potential intervals) and neuromuscular blocking.

Medical and Surgical Management

• Acetylcholinesterase Inhibitors: Pyridostigmine provides symptomatic benefit by prolonging ACh availability in the synaptic cleft.
• Immunosuppression & Crisis: Corticosteroids, azathioprine, or mycophenolate for chronic control; IVIG or PLEX for acute myasthenic crisis.
• Thymectomy: Indicated for all patients with thymoma, and recommended in non-thymomatous generalized AChR-positive MG to induce long-term remission.