Please support Burma cyclone relief & Sichuan earthquake relief
Click here to donate

Myasthenia gravis

Epidemiology

- 1/20 000 adults
- females >> males
- peak incidence in 3rd decade in women, in 6th in men
- associated with other auto-immune diseases, particularly other organ-specific auto-immune diseases

Pathophysiology

- auto-immune
- antibodies to post-synaptic ACh receptor in 90%. Usually IgG. Those without antibodies tend to have mild/localised disease
- 2 populations of receptors: stable (t1/2 12/7) and rapid turnover (t1/2 1/7). ? latter precursors of the former. Rapid response to plasmaphoresis due to rapid regeneration of latter
- clinical features manifest when skeletal muscle unable to synthesize receptors at a sufficiently high rate to maintain normal neuromuscular function
- believed that myeloid cells within thymus have ACh receptors on their surface which serve as a source of autoantigen to trigger an immune response
- 70% of patients have thymic hyperplasia (tend to be younger patients) and 10-15% have thymomas (tend to be elderly)
- as disease progresses pre-synapatic receptor may become involved (fade of TOF twitch response seen before NDMR given)

Investigations

- ACh receptor antibodies. NB false positives may occur in: first degree relatives, organ-specific autoimmune disease, thymoma without MG, following penicillamine treatment. Latter will also exacerbate pre-existing MG. Titre of antibody important
- positive edrophonium test. Resuscitation facilities must be available. Atropine 0.6 mg given first or at least drawn up. Give 1 mg edrophonium first followed by a further 4-10 mg 1-2 min later if there is no response. IM neostigmine 1-2 mg may produce a positive response in 5-10% of patients who did not respond to edrophonium
- EMG shows characteristic changes in 90% of patients with generalised MG and many of those with ocular MG only

Treatment

Anticholinesterase

- pyridostigmine PO 60 mg 4-6 hrly. Can be increased to a maximum of 480 mg/day. Onset of action 30-60 min after oral dose
- pyridostigmine IVI in myasthenic crisis (0.5-4 mg/hr titrated against repeated edrophonium tests) Has advantage of avoiding excessive troughs and cholinergic side effects in association with peaks
- neostigmine IV 15 mg 3-4 hrly up to 150 mg/day is an alternative
- complications: bronchorrhoea, bradycardia, diarrhoea, cholinergic crisis

Immunotherapy

- steroids effective in 70%. Start with high dose (eg prednisolone 100mg daily) and then reduce gradually. Transient exacerbation on starting steroids very common. Older patients are more likely to respond but an average of 4 months treatment is required to achieve clinical stability. Majority require indefinite treatment
- azathioprine, cyclophosphamide. Effective adjuncts to steroids, especially in patients with thymoma. Overall 80% are helped but improvement may take months. A few patients achieve complete remission
- plasma exchange produces short-term improvement. Mainly used for myasthenic crisis and to improve severely affected patients before thymectomy. Typically 5 exchanges of 3-4 l performed over 2 weeks. Improvement usually occurs within days but last only weeks
- IV gamma globulin. Similar effects to plasma exchange. 400 mg/kg/day for 5 successive days. Occasionally patients derive long term benefit. No consistent effect on ACh receptor antibodies. Mode of action unknown

Thymectomy

- produces best results
- early thymectomy advocated in virtually all patients, regardless of severity of disease or presence of a thymoma
- results in earlier onset of remission, lower mortality and greater delay in appearance of extrathymic recurrences compared with medical treatment
- pre-operative optimization of neuromuscular function is necessary: use anticholinesterases ± plasmaphoresis
- in immediate post-operative period anticholinesterase requirements usually reduced to about ¾ of pre-op dose
- sustained improvement may not be seen for several months

Response to anaesthetic drugs

- response to both depolarizing and non-depolarizing relaxants unpredictable, depending to some degree on severity and duration of disease
- when in remission response to relaxants is normal
- small doses of both atracurium and vecuronium have been used safely
- continuation of anti-cholinesterases in pre-operative period controversial

if treatment stopped before surgery patient often very weak on presentation in anaesthetic room and may be distressed by this. Need for relaxants much reduced but by end of surgery patient is even more weak and large doses of anticholinesterase may then be indicated with increased risk of a cholinergic crisis
if drugs continued larger doses of NDMRs will be required

- ? post-op IPPV will probably be necessary for patients who have had disease > 6 yrs or who have co-existing respiratory disease with a VC < 2.9 l or who take more than 750 mg pyridostigmine daily. Some advocate stopping anticholinesterases temporarily in those who require mechanical ventilation to reduce respiratory secretions
- epidural anaesthesia is said to exacerbate condition but has been used succesfully for LSCS although dose reduction necessary to prevent excessive motor block

Myasthenic crisis

Predominant problem is neuromuscular respiratory failure
Incidence increases markedly with age

Precipitating factors

intercurrent infection
pregnancy
drugs:
- antibiotics, eg aminoglycosides, polymyxins, tetracycline
- anti-arrhythmics, eg quinidine, quinine, procainamide
- local anaesthetics, eg procaine, lignocaine
- muscle relaxants
- analgesics, eg morphine, pethidine

Complications

aspiration due to bulbar involvement
- check cough and swallowing
nosocomial pneumonia
atelectasis
acute respiratory failure
cardiac arrest

Investigations and monitoring

edrophonium test after stabilization to distinguish between myasthenic and cholinergic crisis. Latter associated with:
- abdominal cramps
- excessive secretions
- sweating
- bradycardia
check VC and max insp force regularly. Best method of monitoring
deterioration of ABG may occur late
avoid hypokalaemia, hypocalcaemia, hypermagnesaemia as all exacerbate weakness
if adjustment of anticholinesterase and aggressive treatment of intercurrent illness does not result in rapid improvement high dose steroids and plasma exchange should be started simultaneously

Management

Intubate when VC falls below 15 ml/kg
Aims of ventilation
- Rest patient
- Prevent collapse and atelectasis
Consider witholding anticholinergics while patient is intubated
Plasmaphoresis and/or IV Ig
Steroids

Prognosis & course

~5% mortality.Usually due to comorbid conditions
usually last weeks, occasionally months

Myasthenic syndrome

- = Eaton-Lambert syndrome
- paraneoplastic
- pre-synaptic disorder
- ? antibody to presynaptic membrane resulting in decreased acetylcholine release
- associated with increased sensitivity to both depolarizing and non-depolarizing muscle relaxants. May even experience significant weakness after single dose of aminoglycoside
- anticholinseterases not helpful
- patients may experience transient increase in muscle strength on exercise, usually followed by a prolonged period of fatigue
- EMG: marked post-tetanic facilitation and steady growth of potential on tetanic stimulation
- removal of tumour may result in a striking, although temporary, improvement in clinical condition