congenital neuromuscular disorders

Question 1

Charcot-Marie-Tooth

• inheritance
• pathophys
• weakness?
• presentation/effects
• anesthetic management
• triggers
• treatment

Answer 1

autosomal dominant mutation in myelin and axonal genes
denervation of the peripheral neuromuscular system.
Muscle weakness and neuropathy occur, with progressive foot deformities, spinal deformities, and respiratory compromise.
slow and progressive distal muscle weakness and wasting.
Avoid depolarizing neuromuscular blocking drugs (DNMBD), and the effects of non-depolarizing neuromuscular blocking drugs (NNMBD) may be prolonged. May have autonomic neuropathy. Monitor twitches at facial n rather than ulnar. Avoid N2O.

Question 2

Friedreich Ataxia

• inheritance
• pathophys
• weakness?
• presentation/effects
• anesthetic management

Answer 2

autosomal recessive
ataxia that manifests as progressive limb ataxia and skeletal muscle weakness. Death occurs from heart failure from myocardial degeneration. The diaphragm can be impaired, making patients prone to respiratory failure.
Avoid DNMBD’s due to denervation. Negative inotropes should be avoided due to myocardial effects.

Question 3

Duchenne Muscular Dystrophy

• inheritance
• pathophys
• weakness?
• presentation/effects
• anesthetic management

Answer 3

X-linked recessive - most common childhood muscular dystrophy.
disorder of dystrophin, a protein that ensures myocyte stability by anchoring muscle cells to the extracellular matrix. In the absence of this protein, muscle fibers are disorganized and replaced with fibrous tissue, giving a pseudohypertrophic appearance. Intracellular calcium is often elevated due to an increasingly permeable sarcolemma.
Progressive weakness and atrophy of proximal muscles are seen. Late stages include respiratory failure and cardiac failure. Scoliosis, restricted lung function, and cardiomyopathies are seen.
Avoid DNMBDs and inhaled anesthetics due to the potential for triggering creatinine kinase release and rhabdomyolysis due to the development of extrajunctional acetylcholine receptors. This response is similar to malignant hyperthermia but occurs through a different mechanism. Nevertheless, due to the catastrophic nature of these reactions, an anesthetic technique without DNMBDs and volatile anesthetics should be used. If NNMBDs are needed, the dose should be reduced and judicious reversal should be employed due to the risk of postoperative respiratory failure from preexisting weakness as well as an exaggerated effect. Additionally, these patients are at increased risk for blood loss due to smooth muscle and platelet dysfunction. Hypovolemia should be avoided due to relatively fixed cardiac output from noncompliant ventricles.

Question 4

Becker Muscular Dystrophy

Answer 4

this disorder is a milder version of Duchenne muscular dystrophy. Respiratory and cardiac failure is not seen until the fourth or fifth decade, and cardiac manifestations are typically dilated cardiomyopathy and cardiac arrhythmia. Anesthetic considerations are similar to Duchenne muscular dystrophy.

Question 5

Myotonic Dystrophy

Answer 5

muscle wasting and weakness are seen, unlike non-dystrophic myotonias, which consist of prolonged muscle contraction after stimulation. This is an autosomal dominant disorder that manifests in early adulthood. Muscle wasting, as well as incomplete muscle relaxation after a stimulus (myotonia), is often seen. Additionally, cardiac abnormalities such as conduction defects and cardiomyopathy may be seen. Restrictive lung disease and obstructive sleep apnea, endocrine dysfunction, and intellectual impairment may be seen. Triggers of myotonia, including hypothermia, shivering, mechanical and electrical stimulation, should be avoided. Increased sensitivity to anesthetic agents may be seen, in particular with respiratory involvement. DNMBDs should be avoided since they can induce global muscle contractions. NNMBDs should be reversed judiciously as anticholinesterase medications may precipitate contractures due to the increased sensitivity to acetylcholine. Pacemaker equipment should be available in the event of cardiac conduction problems. Glucose metabolism may be affected and should be monitored perioperatively. Bulbar weakness may be noted, placing this patient at increased risk for aspiration. Neuromuscular blocking agents do not effectively treat myotonic reactions in patients with myotonic dystrophy.

Question 6

Myotonia Congenita

• inheritance
• pathophys
• weakness?
• presentation/effects
• anesthetic management
• triggers
• treatment

Answer 6

autosomal dominant
dysfunctional chloride channel that is hyperexcitable, resulting in global muscle hypertrophy and severe contractions.
unlike myotonic dystrophy, results in the absence of weakness. Palatopharyngeal dysfunction can occur, with resulting aspiration. Cardiomyopathy may also be present.
DNMBDs should be avoided since severe, intractable myotonias may occur.
Triggers of myotonia such as hypothermia, shivering, and physical manipulation should be avoided. NNMBDs and regional techniques are unable to relax contractions. Topical local anesthetics to cut nerve bundles and sodium channel blockers may be useful in breaking contractures.

Question 7

Familial Periodic Paralysis (PP)
Hyperkalemic PP:
-inheritance
-pathophys
-triggers
-presentation
-treatment
-anesthetic considerations

Answer 7

this is an autosomal dominant disorder of a sodium channel, resulting in hyperexcitability followed by inactive weakness after triggers such as increased serum potassium, cold, hunger, and stress. Along with the characteristic flaccid paralysis, dysrhythmias may be seen. Preoperative potassium depletion with loop diuretics may be employed. Drugs that cause potassium release including DNMBDs and potassium-containing fluids should be avoided. Acidosis should be avoided. Electrocardiogram monitoring and treatments for hyperkalemia such as calcium should be available. Fasting time should be minimized and glucose-containing solutions should be used. These patients may remain paralyzed for hours after surgery.

Question 8

Hypokalemic PP

• inheritance
• pathophys
• triggers
• presentation
• treatment
• anesthetic considerations

Answer 8

this is an autosomal dominant disorder of the calcium channel that presents as asymmetrical muscle paralysis in the setting of low serum potassium. The mutation is located on the dihydropyridine receptor, which has been linked to malignant hyperthermia (MH), and cases of MH in patients with this disorder have been noted. Hence, in these patients, DNMBDs should be avoided and NNMBDs of short duration should be used. Drugs that cause potassium shifts and hypokalemia including glucose, salt solutions, and alkalosis should be avoided. Serum potassium and temperature should be kept within the normal range. Anxiety may precipitate these episodes. Similarly to hyperkalemic PP, cardiac arrhythmias may occur.

Question 9

Metabolic Disorders

Answer 9

Metabolic and Mitochondrial Disorders
Metabolic: various disorders of metabolism such as acid maltase deficiency exist that affect the regulation of muscle contraction, and hence, respiratory and cardiac function. These patients should have their metabolic status monitored closely, and adequate hydration and diuresis should be ensured. Glucose and amino acid infusions may be needed. Hypothermia should be avoided to avoid shivering and increased muscle activity.

Question 10

Mitochondrial disorders

Answer 10

Mitochondrial: mitochondrial disorders lead to adenosine triphosphate (ATP) production abnormalities, leading to downstream muscle weakness. In later stages, movement disorders and heart failure may be seen. Many anesthetics have depressant effects on mitochondria, and complete AV block may occur. Pacemaker options should be available. Excessive fasting should be avoided, and lactate-containing solutions should be used to provide the muscle substrate. Respiratory failure may be seen. Low dose volatile anesthetics and ketamine are thought to be safe. Local anesthetics and propofol should be avoided.