9.3 Neuromuscular & Peripheral Nerve Disorders
Key Takeaways
- Guillain-Barré syndrome (GBS) characteristically exhibits albuminocytological dissociation on lumbar puncture, defined as an elevated CSF protein concentration (>1.0 g/L) with a normal white cell count (<10 cells/µL), typically appearing after 7-10 days of symptom onset.
- In acute GBS, monitoring Forced Vital Capacity (FVC) and Negative Inspiratory Force (NIF) is vital; an FVC <20 mL/kg or NIF weaker than -30 cmH₂O indicates impending respiratory muscle fatigue requiring elective ICU admission and mechanical ventilation.
- Myasthenia gravis is associated with an underlying thymic abnormality in 75% of patients (60% thymic hyperplasia, 15% thymoma); CT thorax is mandatory in all newly diagnosed patients, and thymectomy is curative or disease-modifying in anti-AChR positive generalized MG.
- Lambert-Eaton myasthenic syndrome (LEMS) is caused by autoantibodies directed against presynaptic voltage-gated calcium channels (VGCC) and is associated with small cell lung cancer (SCLC) in >50-60% of cases.
- Riluzole, a glutamate neurotransmission inhibitor, is the only disease-modifying pharmacotherapy for Amyotrophic Lateral Sclerosis (ALS), extending median survival by 2 to 3 months when initiated early in the disease course.
9.3 Neuromuscular & Peripheral Nerve Disorders
This section reviews the clinical features, diagnostic workup, and treatment paradigms for peripheral neuropathies, Guillain-Barré syndrome, Myasthenia Gravis, Lambert-Eaton Myasthenic Syndrome, Motor Neurone Disease (ALS), and CSF analysis across neuroinfections for MRCPI General Medicine Part I.
Guillain-Barré Syndrome (GBS)
Guillain-Barré syndrome (Acute Inflammatory Demyelinating Polyradiculoneuropathy - AIDP) is an acute, post-infectious, immune-mediated neuropathy characterized by progressive ascending symmetrical weakness and loss of tendon reflexes.
Pathophysiology & Etiology
• Antecedent Infections: In 60-70% of cases, symptoms occur 1 to 3 weeks following a gastrointestinal or respiratory infection. The most common pathogen is Campylobacter jejuni (associated with molecular mimicry between bacterial lipooligosaccharides and human peripheral nerve gangliosides). Other triggers include Cytomegalovirus (CMV), Epstein-Barr virus (EBV), Mycoplasma pneumoniae, and Zika virus. • Pathogenic Antibodies: Anti-GM1 and anti-GD1a antibodies are strongly linked to the Acute Motor Axonal Neuropathy (AMAN) variant. Anti-GQ1b antibodies are present in >90% of cases of Miller Fisher Syndrome (the triad of Ophthalmoplegia, Ataxia, and Areflexia).
Clinical Presentation & Workup
• Symptom Pattern: Ascending, symmetrical muscle weakness starting in the lower limbs, accompanied by paresthesias in the feet and hands. Areflexia or marked hyporeflexia is universal. Autonomic dysfunction occurs in 50% (labile blood pressure, sinus tachycardia, cardiac arrhythmias, paralytic ileus, urinary retention). • Cerebrospinal Fluid (CSF) Findings: Lumbar puncture demonstrates classic Albuminocytological Dissociation—an elevated CSF protein level (>1.0 g/L) with a normal CSF white cell count (<10 cells/µL). Note: CSF protein may be normal during the first 7 days of illness. • Nerve Conduction Studies (NCS): Demonstrates demyelinating features: delayed distal latencies, marked slowing of conduction velocities, temporal dispersion, and conduction block. • Respiratory Function Monitoring: Impending respiratory failure is evaluated by serial bed-side testing of Forced Vital Capacity (FVC) and Negative Inspiratory Force (NIF) every 4-6 hours: • FVC <20 mL/kg • NIF weaker than -30 cmH₂O • Peak Expiratory Flow <40% predicted (Any of these findings mandates immediate transfer to the ICU for elective endotracheal intubation and mechanical ventilation).
Management
• Immunomodulatory Therapy: Intravenous Immunoglobulin (IVIG) at a total dose of 2 g/kg divided over 5 days, OR Plasma Exchange (PLEX) (5 exchanges over 10 days). Both modalities are equally effective. • Contraindication: Systemic corticosteroids are ineffective and contraindicated in GBS, as clinical trials demonstrate no benefit and potential worsening of long-term recovery.
Myasthenia Gravis & Lambert-Eaton Myasthenic Syndrome
Myasthenia Gravis (MG) and Lambert-Eaton Myasthenic Syndrome (LEMS) are autoantibody-mediated disorders of the neuromuscular junction (NMJ) requiring distinct therapeutic approaches.
| Diagnostic & Clinical Feature | Myasthenia Gravis (MG) | Lambert-Eaton Myasthenic Syndrome (LEMS) |
|---|---|---|
| Pathophysiology | Autoantibodies against postsynaptic Acetylcholine Receptors (AChR) (85%) or Muscle-Specific Tyrosine Kinase (MuSK) (10-15%). | Autoantibodies against presynaptic P/Q-type Voltage-Gated Calcium Channels (VGCC) (90%), reducing ACh release. |
| Weakness Pattern | Fatigable weakness that worsens with repetitive activity and improves with rest. Asymmetric ptosis, diplopia, bulbar weakness, proximal limbs. | Proximal lower limb weakness and gait difficulty. Strength improves after brief voluntary muscle contraction (post-exercise facilitation). |
| Reflexes | Deep tendon reflexes are normal and preserved. | Deep tendon reflexes are depressed or absent, but reappear following 10 seconds of maximal muscle exertion. |
| Autonomic Features | Absent. | Prominent autonomic dysfunction: dry mouth, metallic taste, erectile dysfunction, constipation, sluggish pupillary light reflexes. |
| Systemic Association | Thymic pathology in 75% (60% thymic hyperplasia, 15% Thymoma). CT thorax mandatory at diagnosis. | Small Cell Lung Cancer (SCLC) in >50-60% of cases. CT chest/abdomen/pelvis and PET-CT mandatory. |
| Electrodiagnosis | Repetitive Nerve Stimulation (RNS at 3 Hz) shows decremental CMAP response (>10% drop). Single-fiber EMG shows increased jitter. | RNS at high frequency (20-50 Hz) or post-exercise testing shows a dramatic incremental CMAP response (>100-200% increase). |
| First-Line Pharmacotherapy | Pyridostigmine (oral acetylcholinesterase inhibitor 60 mg 4-6 hourly) + immunosuppression (prednisolone, azathioprine). | Amifampridine (3,4-Diaminopyridine) to enhance presynaptic ACh release + treatment of underlying SCLC. |
Myasthenic Crisis Management: Defined as respiratory failure or severe bulbar dysfunction requiring mechanical ventilation. Treat immediately with IVIG (2 g/kg over 5 days) or Plasma Exchange. Avoid exacerbating drugs: Aminoglycosides (gentamicin), Fluoroquinolones (ciprofloxacin), Macrolides, Beta-blockers, Magnesium sulfate, and Neuromuscular blocking drugs.
Amyotrophic Lateral Sclerosis (ALS / Motor Neurone Disease)
Amyotrophic Lateral Sclerosis (ALS) is a progressive, fatal 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 Sign Combination: The hallmark of ALS is the presence of mixed UMN and LMN signs in the same anatomical segment/limb: • UMN Signs: Hyperreflexia, spasticity, extensor plantar response (Babinski sign), brisk jaw jerk. • LMN Signs: Muscle wasting, weakness, fasciculations (especially of the tongue and limb girdle muscles), hyporeflexia. • Negative Features (Absence of Non-Motor Signs): ALS is a purely motor disorder. There is no sensory loss, no sphincter dysfunction, and no impairment of extraocular eye movements. • Diagnostic Confirmation: Electromyography (EMG) demonstrates active denervation (fibrillation potentials, positive sharp waves) and chronic reinnervation in at least 3 spinal regions (cervical, thoracic, lumbosacral) or bulbar territory. MRI brain and spine must be performed to exclude compressive radiculomyelopathy or structural brainstem lesions. • Evidence-Based Management:
- Riluzole: A glutamate neurotransmission inhibitor (50 mg twice daily). It is the only approved disease-modifying drug, prolonging median survival by 2 to 3 months.
- Non-Invasive Ventilation (NIV / BiPAP): Indicated when FVC falls below 50% predicted or orthopnea develops. NIV significantly prolongs survival and improves quality of life more than any pharmacological agent.
- Enteral Nutrition (PEG): Percutaneous endoscopic gastrostomy inserted before FVC falls below 50% to maintain hydration and nutrition in severe bulbar palsy.
Cerebrospinal Fluid (CSF) Diagnostic Framework
Interpretation of lumbar puncture parameters is a core component of MRCPI Part I examinations across neuroinfections and autoimmune neurological disorders.
| Neurological Condition | Opening Pressure (cmH₂O) | CSF Protein (g/L) (Normal: 0.15-0.45) | CSF Glucose Ratio (Normal: >0.6 of serum) | CSF Cell Count (/µL) & Predominance | Pathognomonic / Diagnostic Tests |
|---|---|---|---|---|---|
| Acute Bacterial Meningitis | Elevated (>30) | Markedly elevated (>1.5 - 5.0) | Markedly decreased (<0.4; <1.5 mmol/L) | Very high (>1,000 - 10,000); Neutrophils (>80%) | Positive Gram stain, bacterial multiplex PCR, positive CSF culture. |
| Viral Meningitis / Encephalitis | Normal / Mildly high (15-25) | Normal to mildly elevated (0.5 - 1.0) | Normal (>0.6) | Elevated (50 - 500); Lymphocytes (>90%) | Positive viral PCR (e.g., HSV-1/2, Enterovirus, VZV). |
| Tuberculous Meningitis | Elevated (>25) | Markedly elevated (>1.0 - 5.0) | Markedly decreased (<0.3; <1.5 mmol/L) | Moderate (100 - 500); Lymphocytes | Acid-fast bacilli stain (Ziehl-Neelsen), GeneXpert MTB/RIF PCR. |
| Guillain-Barré Syndrome | Normal (10-20) | Elevated (>1.0 - 3.0) after 7 days | Normal (>0.6) | Normal (<10); No pleocytosis | Albuminocytological dissociation; absent oligoclonal bands. |
| Multiple Sclerosis (MS) | Normal (10-20) | Normal to mildly high (<0.8) | Normal (>0.6) | Normal or mild pleocytosis (<50); Lymphocytes | Intrathecal Oligoclonal Bands (OCBs) present in CSF, absent in serum. |
A 32-year-old woman is admitted to the neurology ward with a 6-day history of progressive weakness in both legs that has now spread to involve her arms, making it difficult for her to comb her hair. Three weeks ago, she experienced a self-limiting episode of watery diarrhea. On examination, there is symmetrical grade 3/5 weakness in the upper and lower limbs, with total absence of knee and ankle reflexes bilaterally. Sensation is intact. Bedside spirometry demonstrates a Forced Vital Capacity (FVC) of 18 mL/kg. Lumbar puncture reveals a CSF protein of 1.85 g/L (0.15-0.45 g/L) and a CSF white cell count of 4 cells/µL (<5 cells/µL). What is the most appropriate immediate management intervention?
A 48-year-old woman presents with a 4-month history of fluctuating double vision and drooping of her left eyelid, which worsens significantly towards the end of the day. She also notes fatigue when chewing meat. On examination, asking her to sustain upward gaze for 60 seconds reproduces left ptosis. Deep tendon reflexes are brisk and normal bilaterally. Anti-acetylcholine receptor (AChR) antibodies are strongly positive. Which diagnostic investigation is mandatory in the initial staging of this patient's condition?
A 64-year-old heavy smoker presents with a 5-month history of progressive weakness and stiffness in his thighs, making it difficult to rise from a seated position. He complains of marked dry mouth and erectile dysfunction. On examination, proximal muscle power in the lower limbs is initially grade 3/5, but after 10 seconds of maximum isometric thigh contraction, muscle power improves to grade 4+/5. Knee and ankle reflexes are absent at baseline but return immediately following voluntary contraction. Anti-VGCC antibodies are detected. Which underlying disease entity is most strongly associated with this clinical syndrome?