NCS Neuromuscular Disorders 3 — Questions and Answers
Question 1: A patient with myasthenia gravis develops acute respiratory failure requiring intubation (myasthenic crisis). After airway stabilization, which intervention provides the most rapid immunomodulation?
- Starting oral prednisone at 60 mg daily as sole therapy
- Initiating azathioprine for long-term immunosuppression
- Plasmapheresis or intravenous immunoglobulin (IVIG) (Correct answer)
- Maximizing oral pyridostigmine to 120 mg every 3 hours
Correct answer: Plasmapheresis or intravenous immunoglobulin (IVIG)
Plasmapheresis (removes AChR antibodies) and IVIG both act within days to weeks — the fastest immunomodulatory options for myasthenic crisis; azathioprine takes months, and pyridostigmine alone cannot manage crisis.
Question 2: Physical therapy for a child with Duchenne muscular dystrophy (DMD) should prioritize:
- High-intensity eccentric strengthening to stimulate muscle hypertrophy
- Stretching to prevent contractures, functional mobility training, and respiratory support education (Correct answer)
- Daily electrical stimulation of affected proximal muscle groups
- Progressive resistance training targeting hip extensors and knee extensors
Correct answer: Stretching to prevent contractures, functional mobility training, and respiratory support education
DMD management focuses on preventing contractures through stretching, maintaining ambulatory function, adaptive equipment, and preparing for respiratory support — aggressive or eccentric strengthening can accelerate muscle fiber damage.
Question 3: Non-invasive positive pressure ventilation (NIPPV) is typically initiated in ALS when FVC falls to:
- Below 90% predicted, regardless of symptoms
- Below 75% predicted with daytime hypercapnia
- Below 25% predicted as a last resort before intubation
- Below 50% predicted or when symptoms of nocturnal hypoventilation are present (Correct answer)
Correct answer: Below 50% predicted or when symptoms of nocturnal hypoventilation are present
ALS practice guidelines recommend initiating NIPPV when FVC drops below 50% predicted or when patients report symptoms of nocturnal hypoventilation; early initiation prolongs survival and improves quality of life.
Question 4: A patient with biopsy-confirmed inclusion body myositis (IBM) presents for rehabilitation. Which management approach is most appropriate?
- Low-intensity aerobic exercise and occupational therapy for adaptive equipment (Correct answer)
- Aggressive corticosteroid therapy combined with high-dose IVIG
- Mycophenolate mofetil with concurrent resistance strengthening
- Plasmapheresis followed by rituximab for B-cell depletion
Correct answer: Low-intensity aerobic exercise and occupational therapy for adaptive equipment
IBM is uniquely resistant to all immunosuppressive therapies; management focuses on low-intensity aerobic exercise to maintain function and adaptive equipment/occupational therapy for finger flexor and quadriceps weakness.
Question 5: Nusinersen (Spinraza) treats spinal muscular atrophy through which mechanism?
- Replaces the defective SMN1 gene using an adeno-associated virus vector
- Blocks acetylcholinesterase to increase ACh at the neuromuscular junction
- Reduces neuroinflammation by inhibiting microglial activation
- Modifies SMN2 pre-mRNA splicing to include exon 7, producing full-length functional SMN protein (Correct answer)
Correct answer: Modifies SMN2 pre-mRNA splicing to include exon 7, producing full-length functional SMN protein
Nusinersen is an antisense oligonucleotide that redirects splicing of SMN2 to include exon 7, generating more full-length SMN protein and compensating for the absent SMN1 gene.
Question 6: Botulinum toxin reduces spasticity by which mechanism?
- Cleaving SNARE proteins to block acetylcholine vesicle release at presynaptic motor terminals (Correct answer)
- Blocking nicotinic acetylcholine receptors on the postsynaptic motor end plate
- Enhancing glycine and GABA inhibitory interneuron activity in the spinal cord
- Inhibiting myosin-actin cross-bridge formation within the muscle fiber
Correct answer: Cleaving SNARE proteins to block acetylcholine vesicle release at presynaptic motor terminals
Botulinum toxin cleaves SNAP-25, synaptobrevin, or syntaxin (SNARE proteins depending on serotype), preventing ACh-containing vesicle fusion and release at the presynaptic terminal of the neuromuscular junction.
Question 7: According to the MGTX randomized trial, thymectomy in generalized AChR antibody-positive myasthenia gravis patients provides:
- Benefit only in patients under age 30 with recent disease onset
- Improved clinical status and significant reduction in prednisone requirements over 3 years (Correct answer)
- Immediate complete remission in the majority of patients within 6 weeks
- No benefit unless a thymoma is present on CT imaging
Correct answer: Improved clinical status and significant reduction in prednisone requirements over 3 years
The MGTX trial showed thymectomy significantly improved the Quantitative MG score and reduced prednisone doses at 3 years compared to prednisone alone in AChR-positive generalized MG, with sustained benefit.
NCS Neuromuscular Disorders 3
A patient with myasthenia gravis develops acute respiratory failure requiring intubation (myasthenic crisis).
After airway stabilization, which intervention provides the most rapid immunomodulation?