Muscle Disorders and General Anaesthetics Ben Creagh-Brown, UHL

Muscle disease (Myopathy ) can be divided into Myositis – inflammatory disease Muscular dystrophy – inherited disorder with progressive weakness Myotonia - sustained contraction and slow relaxation Channelopathies – disorders of ion channels within skeletal muscle cells

3 main groups to be considered Myasthenia Gravis and LEMS Duchenne’s and Becker’s Muscular Dystrophy Myotonic dystrophy

Myasthenia Gravis and LEMS A 25 year old female presents for thymectomy for myasthenia gravis What is myasthenia gravis? Tell me as much as you know about it How is it diagnosed? (include EMG) What is edrophonium? How does it work? What dose should be used? What are the symptoms? How would you anaesthetise her?

Description Myasthenia Gravis (MG) is an autoimmune condition in which IgG autoantibodies interact with the postsynaptic acetylcholine receptors (AChR) at the nicotinic neuromuscular junction (NMJ). The AChR antibodies reduce the number of functional receptors by: blocking attachment of ACh molecules increasing the rate of degeneration of the receptors complement-induced damage to the NMJ. On average MG patients have 30% of the normal number of functional AChR.

Aetiology and associations Incidence Age Sex Aetiology and associations Pathology 1 in 10,000 of the population Two peaks: 20-30 years in women and 60-70 years in men. Twice as common in women Acquired autoimmune disease of unknown cause. Can be a result of D-penicillamine treatment for rheumatoid arthritis. Associated with other organ-specific autoimmune diseases Thymic hyperplasia is found in 70% of patients below 40 years. 10% have a thymoma, increasing inc. with age. Young patients without a thymoma have increased association with HLA B8 and DR3.

Clinical features Complications Prognosis Progressive weakness and fatiguability of voluntary muscle, particularly ocular, proximal limb, bulbar and facial muscles. Myocardium never involved. Fatiguability is weakness accentuated by exercise and relieved with rest. Respiratory failure. Aspiration from bulbar palsy. Normal or nearly normal lives. Some case of myasthenia gravis may go into remission temporarily. In a few cases, the severe weakness of myasthenia gravis may cause respiratory failure.

Investigations Antibodies Electromyogram Tensilon test Serum AchR antibodies can be found in 90% of generalised MG, not likely to be found in pure ocular disease. Pathognomic Electromyography (EMG). Compound muscle action potentials (CMAP) shows that repetitive stimulation results in progressive decrease in CMAP = fade. These findings are not specific. Edrophonium (tensilon) test. 10mg of this anticholinesterase is given IV as a bolus (after a 1-2mg test dose). Improvements in weakness happen within 30 s and lasts for up to 5 mins. Test dose is because it can cause bronchoconstriction and syncope.

Treatments Anticholinesterase treatment Immunosuppression Plasma exchange and immunoglobulin Thymectomy To enhance NMJ transmission by delaying degradation of Ach. Pyridostigmine is the most commonly used drug. Acts within 30 mins and lasts for 4 hours. Initially works well but effective diminishes over months. Immunosuppression with prednisolone or azathioprine. Start high and taper down Inducing remission of myasthenic crises or pre-op before thymectomy. Both work within days IV Ig has a longer effect. Thymectomy if thymoma either by sternotomy or mediastinoscopy. Can do thymectomy for thymic hyperplasia aiming to induce remission – these may take a long time.

Pyridostigmine Analogue of neostigmine More effectively absorbed from the gut With equipotent doses, pyridostigmine has a slower onset and longer duration of action, and produces fewer gastrointestinal side effects than neostigmine Patients may get the side effects of diarrhoea and abdominal cramps so they take atropine 0.5mg with each dose

Anaesthetic management Avoid drugs that exacerbate MG polymyxin antibiotics (such as colistin) block AChR but are rarely used anyway Aminoglycosides decrease Ach release and AChR sensitivity and should be avoided Procainamide exacerbate weakness Quinine exacerbate weakness Beta blockers exacerbate weakness

Pre operative assessment Assessment of respiratory function (serial FVC on the ward) and bulbar weakness (SALT) Chest physiotherapy Optimise immunosuppression and anticholinesterase therapy Consider IV Ig or plasma exchange Consider ITU bed, prolonged ventilation post op more likely if: Stage III or IV disease Chronic respiratory disease FVC <2.9l Long history of disease (>6 years) Exclude associated thyroid disease or DM Airway ?RA ?Thymic mass compressing

On day of operation Give anticholinesterases or not? Why? Omit anticholinesterase therapy as this may prolong action of sux, require increased doses of non depolarising meuromuscular blocking drugs Increased steroids, IV hydrocortisone

Induction and maintenance Consider IABP as well as routine monitoring if sternotomy Continuously monitor NM blockade Intubate – need to protect the airway. Consider nasotracheal intubation if planned postop ventilation. Some anaesthetists avoid IV induction and paralysis but intubate after deepening with inhalational agents only, MG patients are more susceptible to the muscle relaxant effect of volatile. You may require more sux that usual and consequently get a Phase II block Conversely they are exquisitely sensitive to non depolarising neuromuscular blocking drugs (NDNMB) Use 30-40% of the usual dose of vecuronium or atracurium. Avoid reversing the NDNMB drugs to avoid the risk of cholinergic crisis

Post operative Majority can be safely extubated and go back to the ward HDU may be appropriate ITU if ventilation required Good analgesia including opiates.

LEMS Lambert-Eaton Myasthenic Syndrome - a rare syndrome occurring in association with small cell carcinoma of the bronchus. LEMS results from an autoimmune attack directed against the Voltage Gated Calcium Channels (VGCC) on the presynaptic motor nerve terminal (in 98% of those with cancer) Antibodies have been found in the majority of patients with LEMS. 3% of patients with SSLC. Clinical features similar to MG but facial and bulbar muscles relatively spared Distinguishing between the two diseases on EMG: Facilitation (strength improvement after exercise) is common in LEMS. Facilitation differentiates the 2 diseases only if it is noted after repeated testing of many separate muscle groups They improve with the edrophonium test but not as markedly Very sensitive to both depolarising and non depolarising drugs There are other rare myasthenic syndromes including congenital

Duchenne’s Muscular Dystrophy X linked recessive disorder, A third of cases are from a spontaneous mutation 1 in 3000 live male births Gene located at Xp21 region of X chromosome Gene product is the protein Dystrophni, which is a cytoskeletal muscle protein Clinical features of proximal limb weakness occur by the age of 4 and the diseases usually causes death by 20 years. Becker’s MD is similar but milder and presents later.

Clinical features Difficulty running Gower’s sign of proximal leg weakness Pseudohypertrophy of the calves Myocardium is affected and a cardiomyopathy occurs Usually disabled by the disease by 10 years of age

Investigations Clinical diagnosis. Very high levels of CK. Muscle biopsy shows characteristic changes and immunochemistry confirm absence of dystrophin. EMG shows a myopathic pattern

Management No treatment Carrier detection: females with affected brothers have a 50% chance of carrying the abnormal gene. She are asymptomatic but have high CK levels, abnormal EMGs and muscle biopsies.

Anaesthetic implications Weak respiratory muscles and kyphoscoliosis impair ventilation pre and post op Cardiomyopathy and arrhythmias are common Delayed gastric emptying and poor bulbar function predispose to aspiration Rhabdomyolysis and an MH-like syndrome can follow use of Suxamethonium. Very sensitive to depolarising and non depolarising muscle relaxants.

Myotonic dystrophy Autosomal dominant disease. A triplet repeat disorder. 1 in 20,000 Characterised by myotonia = incomplete muscle relaxation after exercise. Defect in sodium-chloride channels in muscle membrane Onset around 20 to 50 years

Clinical features: Muscle Non muscle Progressive distal muscle weakness Ptosis and bulbar failure Weak and wasted facial muscles and SCM Myotonia Cardiomyopathy and conduction defects Central and Obstructive Sleep Apnoea Non muscle Cataracts, frontal baldness, mild learning difficulties, glucose intolerance, thyroid adenoma

Anaesthetic implications Tolerate surgery very poorly Myotonia can be precipitated by cold, shivering, mechanical or electrical simulation, suxamethonium and anticholinesterases (neostigmine) Increased respiratory complications. Keep normothermic Monitor NM function Increased sensitivity to thiopentone and propofol, suxamethonium and non depolarising muscle relaxants