Neuromuscular Disorders

1. Neuromuscular Disorders • Dwayne McClerklin, MD • Assistant Professor • Department of Anesthesiology and Perioperative Medicine • MUSC

2. Myasthenia Gravis • Path: Autoimmune destruction of the postsynaptic Ach receptor • S/Sx: muscle weakness, easy fatiguability ; symptoms worsen with exercise and improve with rest. With bulbar involvement, laryngeal and pharyngeal muscle weakness results in dysarthria, difficulty chewing/ swallowing, problems clearing secretions, or pulmonary aspiration.

3. Myasthenia Gravis

4. Myasthenia Gravis • Rx: Acetylcholinesterase Inhibitors (AchEI) increase the amount of acetylcholine at the neuromuscular junction through inhibition of end-plate acetylcholinesterase • Cholinergic crisis results from excessive AchEI dosing and is characterized by increased weakness and excessive muscarinic effects • Edrophonium test- differentiates cholinergic from muscarinic crisis. Sx of muscarinic crisis worsen with edrophonium administration

5. Myasthenia Gravis • Anesthetic Considerations • Preoperative continuation of AchEI controversial (pros- potential decreased postop weaknes; cons- altered action of NMBAs, bowel hyperactivity) • Pts may be at increased risk of aspiration, respiratory depression (go easy with premedications)

6. Myasthenia Gravis • Deep anesthesia with a volatile agent may produce favorable conditions for tracheal intubation • Pts demonstrate resistance to depolarizing NMBAs, proneness to Phase II blockade • Pts sensitive to nondepolarizing NMBAs

7. Myasthenia Gravis • Patients who have myasthenia gravis are at great risk for postoperative respiratory failure • Disease duration of more than 6 years, concomitant pulmonary disease, a peakinspiratory pressure of < –25 cm H2O (ie, –20 cm H2O), a vital capacity < 4 mL/kg, and a pyridostigmine dose > 750 mg/d are predictive of the need for postoperative ventilation

8. Eaton Lambert Syndrome • Path: Caused by failure of presynaptic Ca2+ entry (which normally stimulates release of Ach); associated with small cell cancer of the lung • S/Sx: muscle weakness that improves with exercise; minimal improvement with AchEI • Rx: Aminopyridines (presynaptic K+ channel blockers which prolong the AP, increasing Ca2+ influx and Ach release)

9. Eaton Lambert Syndrome • Anesthetic Considerations • Pts with ELS are sensitive to both depolarizing and nondepolarizing NMBAs • Deep anesthesia with volatile agents is usually sufficient for intubation

10. Muscular Dystrophies • Duchenne’s Muscular Dystrophy • An X-linked recessive disorder, Duchenne's muscular dystrophy affects males almost exclusively • Affected individuals produce abnormal dystrophin, a protein found on the sarcolemma of muscle fibers.

11. Muscular Dystrophies • Duchenne’s Muscular Dystrophy • S/Sx: Progressive proximal muscle weakness (gait disturbance) and fatty infiltration of calf muscles; respiratory muscle weakness (atelectasis, restrictive lung disease, impaired cough); cardiomyopathy, papillary muscle dysfunction leading to MR

12. Muscular Dystrophies • Duchenne’s Muscular Dystrophy • Dx: Elevated serum creatine kinase (10-100x normal), elevated serum myoglobin levels; Muscle biopsy is definitive • Rx: Supportive care; corticosteroids; spinal rodding and fusion to improve mobility and comfort

13. Muscular Dystrophies • Duchenne’s Muscular Dystrophy • Anesthetic considerations: assess degree of weakness, multisystem involvement; pts may be an aspiration risk; avoid Sux (risk of hyperkalemic arrest, MH); sensitivity to nondepolarizing NMBAs may be increased

14. Muscular Dystrophies • Myotonic Dystrophy • Myotonia-slowing of relaxation after muscle contraction in response to electrical or percussive stimuli. • Myotonic Dystrophy (MD) is the most common cause of myotonia

15. Muscular Dystrophies • Myotonic Dystrophy • S/Sx:Myotonia is the principal manifestation early in the disease, but as the disease progresses, muscle weakness and atrophy become more prominent. • Other manifestations include cardiomyopathy, gastric hypomotility, and alveolar hypoventilation

16. Muscular Dystrophies • Myotonic Dystrophy • Anesthetic Considerations- Pts are aspiration risks; avoid premedication due to proneness to hypoventilation; avoid Sux; Cis is a good choice; Neostigmine can exacerbate myotonia; avoid postoperative shivering

17. Myotonias • Myotonia Congenita • Path:caused by mutations of a gene on chromosome 7q35 encoding a chloride channel of the skeletal muscle fiber surface membrane. • S/Sx:. The disease is confined to skeletal muscle and produces no, minimal, or nonprogressive weakness. There is no cardiac involvement

18. Myotonias • Paramyotonia Congenita • S/Sx:Symptoms of paramyotonia congenita include transient stiffness (myotonia) and, occasionally, weakness after exposure to cold temperatures;The stiffness worsens with activity, in contrast to true myotonia, thus the term "paramyotonia."

19. Myotonias • Anesthetic Considerations • Pts may demonstrate anabnormal response to Sux and troublesome intraoperative myotonic contractions (not associated with MH) • Avoid hypothermia. • NMBAs may paradoxically cause generalized muscle spasms, including trismus, leading to difficulty with intubation and ventilation

20. Periodic Paralysis • Hypokalemic Periodic Paralysis • Path: abnormalities in membrane transport of Na+ and K+, making muscle excitation difficult • S/Sx: autosomal dominant disorder manifesting as acute bouts of weakness/ paralysis of the extremities and trunk muscles (spares diaphragm) lasting about 3 hours

21. Periodic Paralysis • Hypokalemic Periodic Paralysis • Episodes are most common in the early morning and can be precipitated by strenuous exertion, cold weather, high carbohydrate meals, or glc and insulin administration. Mild exertion can actually prevent or delay paralysis.

22. Periodic Paralysis • Hyperkalemic Periodic Paralysis • Path:paralysis is triggered by abnormal inactivation of Na+ channels by a mild increase in K+. Na+ and water flow into the cells with prolonged depolarization; more frequent attacks than hypokalemic variant • S/Sx: weakness triggered by fasting, cold weather, rest following exercise K+ intake; bradycardia

23. Periodic Paralysis • Anesthetic Considerations • Anesthetic management is directed toward preventing attacks • Check K+ often • Glucose-containing intravenous fluids should not be used in patients with hypokalemic paralysis, whereas such solutions may benefit patients with hyperkalemic and normokalemic paralysis

24. Periodic Paralysis • Anesthetic Considerations • In patients with periodic paralysis, the response to NMBAs is unpredictable • Pts with hypokalemic variant are sensitive to nondepolarizing NMBAs • Sux is contraindicated in the hyperkalemic variant • Maintain normothermia