AJNS

EDUCATION / ENSEIGNEMENT
 
MYASTHENIA GRAVIS AND ANESTHESIA - A REVIEW OF THE LITERATURE



  1. Dept of Medicine, Ogun State University Teaching Hospital; Sagamu Ogun State. Nigeria
  2. Dept of Anaesthesia, Ogun State University Teaching Hospital; Sagamu Ogun State. Nigeria

E-Mail Contact - OGUN Shamsideen Abayomi : yomiogun (at) skannet (dot) com


ABSTRACT

Myasthenia gravis (MG) is an immunological disorder characterized by damaged acetylcholine receptors (AchR) due to antibody, which not only blocks the receptor site but also causes degenerations of the receptors.. It is closely associated with disorders of similar pathogenesis, such as pernicious anaemia, thyrotoxicosis, SLE, hypothyroidism, rheumatoid like arthritis, red cell aplasia and polymyositis. The disease is characterized by skeletal muscle weakness and fatigability upon sustained effort and commonly affects the ocular, bulbar and limb muscles.

Anticholinesterases, immunosuppressive drugs, plasmaphresis, and thymectomy are the four strategies in the treatment of myasthenia. The thymus plays a critical role in immuno surveillance and has been incriminated in its pathogenesis. There is therefore a general consensus that adults with myasthenia gravis should have thymectomy.

The anaesthetic management of the myaesthenic patient must be individualized to the severity of the disease and the type of surgery. Such patients may have an abnormal response to muscle relaxants, a restricted respiratory capacity with inability to cough and clear the increased secretions resulting from anticholinesterase therapy or have a co-existing cardiomyopathy.

It may be safe and advantageous to discontinue anticholinesterase therapy just before surgery in order to minimize their vagotonic side effects. It is also safe to decrease the dose of depolarizing and non-depolarising blockers required to maintain muscle relaxation during surgery. Furthermore, MG patients are at increased risk of developing post-operative respiratory failure and it is likely that they would require ventilatory support after surgery. Post-operative care should be done in the intensive care unit with tracheal suction and monitoring of respiratory function as well as chest physiotherapy.

Despite the anaesthetic, intra- and post-operative problems envisaged in patients with myasthenia gravis, cases with mild generalized MG could have uneventful operations if necessary precautions are taken. The course of MG is extremely variable, although, spontaneous remission is common, relapse is the rule.


RESUME

La myasthénie gravis (MG) est liée à un dysfonctionnement du système immunitaire. (Il) Elle se caractérise par une anomalie des récepteurs de l’acétylcholine (AchR) causée par des anticorps avec pour conséquence non seulement un blocage du site des récepteurs mais également leur dégénerescence. Elle peut être associée à des affections de pathogénie identique telles que l’anémie pernicieuse, la thyréotoxicose, l’hypothyroïde ou encore la polyarthrite rhumatoïde, l’aplasie médullaire et la polymyosite.

La maladie se caractérise par une faiblesse des muscles squelettiques et une fatigabilité après un effort soutenu. Elle atteint généralement les muscles oculaires extrinsèques, les muscles pharyngo-laryngés et de la face ainsi que les muscles des membres.

Il existe quatre types de traitement contre la myasthénie : les anticholinesthérasiques, les immunodépresseurs, les échanges plasmatiques et la thymectomie. Le thymus qui joue un rôle décisif dans l’immuno-régulation et est impliquée dans la pathogénie . Ainsi, l’on s’accorde à penser que les adultes atteints de myasthénie gravis devraient avoir recours à une thymectomie.

La prise en charge anesthésique du malade myasthénique doit être individualisée selon la gravité de la maladie et le procédé chirurgical. En effet, ces patients peuvent avoir une réaction négative aux relaxants musculaires, souffrir d’une insuffisance respiratoire ou être dans l’impossibilité de tousser et d’expectorer les sécrétions importantes apparues après un traitement anticholinestérasique ou en rapport avec une myocardiopathie coexistante. Il est prudent d’interrompre le traitement anticholinesthérasique juste avant l’intervention afin de réduire les effets vagotoniques secondaires. Il est également conseillé de réduire la dose de curarisants polarisants et non - polarisants nécessaires au maintien du relâchement musculaire au cours de l’intervention. En outre, les malades myasthéniques sont exposés à des risques respiratoires importants et peuvent développer des défaillances en post-opératoire nécessitant ainsi assistance respiratoire. Des soins post-opératoires devront être apportés dans le service de soins intensifs : aspiration trachéale, monitoring des fonctions respiratoires et kinésithérapie respiratoire.

En dépit des problèmes anesthésiques per-opératoires et post-opératoires pouvant survenir chez les patients atteints de myasthénie gravis, la forme légère généralisée peut être opérée sans complication à condition de prendre les précautions nécessaires. L’évolution de la maladie est extrêmement variée marquée par des poussées et bien qu’une rémission soit courante, il faut néanmoins s’attendre à des rechutes.

INTRODUCTION

Following the description of “the habitual and spurious palsies” by Thomas Willis in 1672, Erb, Goldflam, and Samuel Wilks in 1877 firmly established the clinical features of myasthenia gravis (MG) [1,2]. It is an uncommon disease with an incidence varying from 1 in 10,000 to 50,000 adults [3]. The peak incidence occurs in the third to fifth decade with a second peak in the seventh decade. It affects females more than males at a younger age (20 to 40 years) in the ratio of 2:1, while there is reversal in sex predilection after 40 years with a male to female ratio of 4:1 [3,4]. It is doubtful that myasthenia gravis is increasing in frequency.

Myasthenia gravis is an immunological disorder characterized by damaged acetylcholine receptors (AchR) due to antibody, which not only blocks the receptor site but also causes degenerations of the receptors [5,6,7]. The disease is characterized by skeletal muscle weakness and fatigability upon sustained effort and commonly affects the ocular, bulbar and limb muscles [8,9]. It is closely associated with disorders of similar pathogenesis, such as pernicious anaemia, thyrotoxicosis, SLE, hypothyroidism, rheumatoid like arthritis, red cell aplasia and polymyositis [10,11].

Pathophysiology of myasthenia gravis and neuromuscular blockade A humoral auto-immune mechanism has been implicated [12]. There is increased turnover of AchRs due to cross-linking by antibodies, complement mediated damage to the postsynaptic membrane and direct action of antibodies on acetylcholine binding [13,14]. These result in post synaptic dysfunction at the motor end plate of the neuro-muscular junction. Acedtylcholine is released normally from the pre-synaptic terminal into the synaptic cleft, but three pathologic mechanisms reduce the ability of acetylcholine (Ach) to bind to acetylcholine receptors (AchR) on the muscle end plate. The mechanism believed to be the most important is acetylcholine receptor blockade. This blockade results in fewer available receptors to bind acetylcholine. Antibodies directed at the AchR are responsible for this blockade, and they are classified as binding, blocking and modulating antibodies. The most common type is the binding antibody . The second mechanism is complement mediated end plate destruction. This mechanism is responsible for simplification of the post synaptic membrane resulting in increased distance between the presynaptic terminal and the muscle end plate. The third mechanism is an increased rate of acetycholine receptor endocytosis and degradation on the muscle membrane [15]. Because of these changes, some motor fibres will not be able to generate an action potential during repetitive or sustained muscle contraction.

The serum concentrations of these antibodies as measured by binding assays correlate poorly with the clinical severity of weakness in patients with MG: 100% with moderately severe (IIB); 80% in mild generalized (IIA); 50% in ocular muscle; and 25% in remission [10]. This suggests that factors other than the antibody titer may be important in determining the clinical severity of the weakness [16]. One possible explanation is that the functional activity of the antibodies such as the ability to reduce the number of available AchR may be clinically relevant in its pathogenesis [14]. The thymus plays a critical role in immuno surveillance and has been incriminated in the pathogenesis of MG [8,9]. It is abnormal in approximately 75% of myaesthenics. Sixty-five percent of the patients have thymic hyperplasia with active germinal centers, while 10% have thymic tumors (thymoma) [6].

Decreased release of acetylcholine by the presynaptic nerve terminals may also have a role in the fatigue of MG. Some studies [12,17] found decreased quantal content while many other studies found increased quantal quantity and increased acetylcholine release from nerve terminals in MG [6,14,18]. Thus, it is unclear whether quantal content is decreased or increased or unaffected in this condition. Furthermore, synaptic cleft is widened and post synaptic regions may be present where there is no overlying nerve terminals [13]. The number of postsynaptic cholinergic receptors by far exceeds the number required to trigger a muscle action potential under normal conditions [15]. Thus 70 - 80% of the receptors have to be occupied by an antagonist such as a non-depolarising blocking agent before the response to nerve stimulation is blocked [15]. Non depolarizing neuromuscular blockers (competitive antagonism) competes with the agonist acetylcholine for the binding sites on the postsynaptic receptors and the proportion of receptors occupied by acetylcholine and neuromuscular blocking drug is determined by their respective concentrations and affinities for the receptors. The competition between drug and acetylcholine is biased in favour of the drug [19]. The blocking drug only has to bind to one  - subunit of the receptor to block it, while both  - subunits must be occupied by acetylcholine to open up the ion channel [19]. This may explain why it is very difficult or even impossible by injection of an anticholinesterase drug to reverse an intense neuromuscular block caused by a large dose of a non-depolarising agent.

Phase 1 block: The depolarizing neuromuscular blocking agent suxamethonium (succinylcholine) acts as the name implies by depolarizing the neuromuscular end plate. Unlike acetylcholine, suxamethonium is not hydrolysed by acetylcholinestrase in the synaptic cleft. In the stead, it is hydrolysed by cholinesterase in plasma (pseudocholinesterase, acylcholine-acylhydrolase). As a result, the clearance of suxamethonium from the synaptic cleft, depends on diffusion from the cleft into the plasma and is much slower than the clearance of acetylcholine. Therefore, suxamethonium is able to react repeatedly with the receptor, causing a longer lasting depolarization of the end plate. In contrast, acetylcholine normally only reacts once with the receptor before it is hydrolysed. This continuous depolarization of the end plate inactivates the voltage dependent sodium channels of the muscle membrane adjacent to the end plate, thereby preventing depolarization of the muscle membrane and initiation of an action potential. This inactivation of the voltage dependent sodium channels (sometimes called accommodation block) last until suxamethonium has diffused away from the synaptic cleft and the end plate is repolarized. If suxamethonium remains at the neuromuscular junction for an extended period of time, either because of a prolonged infusion in a patient with normal plasma cholinesterase activity or because a relative overdose has been given to a patient with genotypically abnormal plasma cholinesterase, a phase II block ensues [15]. The membrane potential gradually recovers to normal though the neuromuscular transmission is still blocked. The original depolarizing block changes to a non-depolarising-like block. This change in block characteristics has been described as a change from a phase I to a phase II block. Other less fortunate designations used are dual block, mixed block or desensitization block.

Some antibiotics such as aminoglycosides, polypeptides, tetracyclines, clindamycin and lincomycin may increase the sensitivity of myasthenia to muscle relaxants. Tricyclic antidepressant drugs, and quinidine may cause channel block while -blockers, calcium channel blockers and magnesium sulphate could aggravate or unmask myasthenia gravis [19,20]. Phenytoin, carbamazepine, azathioprine, corticosteroids, and methylxanthines also cause resistance to the effect of non-depolarising muscle relaxant [20].

In MG, there is a decrease in the number of functional AchRs available, with a subsequent decrease of the “safety margin” which is why they may demonstrate resistance to depolarizing blockers but extreme sensitivity to non-depolarising blockers. Intermediate acting relaxant such as atracurium vecurorium are rapidly eliminated and could be used [21,22].

CLINICAL FEATURES

Myasthenia Symptoms could be ocular, bulbar or generalized. Ocular symptoms are diplopia, ptosis and external opthalmoplegia while bulbar symptoms include nasal speech and regurgitation, atrophy of tongue and respiratory embarrassment. Skeletal muscle weakness is usually proximal but could be generalized and asymmetric in up to 85% of patients [12].

Extra ocular muscle involvement may be so severe occasionally to produce complete external opthalmoplegia usually unaccompanied with internal opthalmoplegia. Facial muscle involvement, at least to a minimal degree in the orbicularis oculi muscle region accompanies the extraocular muscle pareses in almost every instance [14]. This is responsible for the characteristic facies in which there is a tendency towards obliteration of the normal folds, as well as a lack of compensatory furrowing of the forehead in the presence of ptosis producing a “snarling” expression.

More widespread bulbar muscle involvement affecting the muscles of mastication, palate, pharynx and larynx may be present initially, or more often constitute a further development during the course of illness [12]. When the bulbar manifestations are conspicuous, it is reasonable to look upon such patients as having a “clinically malignant” form of myasthenia gravis [23]. In some cases, weakness of the muscles of the extremities may represent an early and prominent feature, but only rarely is this unassociated with myaesthenic symptoms in the extraocular or bulbar musculature [14]. In a study by Oosterhuis, the initial signs were ocular in over half of the cases; bulbar weakness was the next most common presentation, followed by weakness of the limbs [24]. In one third of the patients with ocular symptoms, these remained the only feature, while the remainder developed generalized disease, usually within 2 years. Spontaneous remissions in the first year of the disease occurred in 22% of patients: half of these relapsed after 3 to 12 months and the other half after between one and six years [24]. Pregnancy has variable effect on MG [25].

In congenital MG, prominent extra ocular involvement is usually noted in infancy, with relatively mild generalized weakness, which may not develop until later in life. There are pre-synaptic as well as post-synaptic defects. Anti-AchR antibodies are not found and the limited data suggest that it results from genetic defects rather than auto-immune dysfunction.

There is also no consistent response to plasma exchange or thymectomy [16]. The association with consanguineous marriage and the involvement of siblings and other relatives also suggests a genetic basis. Neonatal myasthenia on the other hand, is seen in 10% of babies of myaesthenic mothers. Recovery is usually complete in 3 months without recurrence or sequelae. There is also no correlation between infants’ symptoms and severity or duration of mother’s illness. It is thought to be due to an immune reaction to an agent crossing the placenta and responds to neostigmine [16].

Criteria for diagnosis of MG: These could be clinical, pharmacological or electrophysiological.

  1. Clinical
  2. Pharmacological: increased sensitivity to d tubocurare and resistance to depolarizing agent.
  3. Electrophysiological: decrement of muscle action potential amplitude on supramaximal stimulation at slow rates of 3 per second and post tetanic facilitation in which amplitude increases after tetanic stimulation. SFEMG (Single Fiber Electro Myo Graphy) is the most sensitive technique available to detect Myasthenia gravis.

Osserman and Genkins clinical classification of MG [26].: Stages
1. ocular signs and symptoms only.
2A. generalised mild muscle weakness.
2B: generalised moderate muscle weakness and/or bulbar dysfunction.
3. acute fulminating presentation, and or respiratory dysfunction.
4. late severe generalized MG.

Anticholinesterase preparations were introduced in 1934, and a therapeutic response to these agents is accepted as part of the definition of myaesthenia [14].

The Neostigmine test:
This was first suggested by Viets and Schwab in 1939 [27]. An intramuscular or intravenous administration of neostigmine methylsulphate is used in doses of 1mg/lbs of body weight. Atropine 0.5 mg is administered prior to it, to prevent the muscarinic side effects such as gastro-intestinal symptoms, hypotension, bradycardia, heartblock and cardiac arrest. Improvement of the strength of muscles involved occurs in 5 - 10 minutes and becomes maximal in 30 minutes and last 1 to 3 hours.

When the intravenous technique is to be employed, the patient should have an intravenous infusion of 5% dextrose started and should be in the supine recumbent position. Atropine 0.4 to 0.6 mg is first administered i.v. followed by 0.25 to 0.5 mg neostigmine given i.v. and there should be an improvement in muscle strength in 3 - 5 minutes. If there is insufficient improvement, further dose of neostigmine such as 0.25mg or less may be administered. Improvement of the degree of ptosis, range of ocular movement and force of hand grip are clinical measures of objective assessment.

The Edrophonium test:
This is similar to the neostigmine test, and was originally suggested by Kaplah in 1952 [27]. It is best performed by giving graded doses of edrophonium (tensilon) at 5 minute intervals starting with a 1 mg dose and increasing up to 10mg. Intravenous edrophonium is given in a test dose of 1 mg followed by about 5 mg. Facilities for resuscitation must be available and ideally 2 doctors should be present, one to give the intravenous injections and the other to record objective indices of improvement. It is sometimes worthwhile including a saline placebo in the protocol. About 5% to 10% of patients with generalized myasthenia do not give positive responses to intravenous edrophonium; and in some of these, a positive response is obtained with 1-2 mg intramuscular neostigmine given, again with atropine. False negative responses may be obtained in association with severe weakness, especially if there is muscle wasting [16].

The curare test:
If the above results give equivocal results as in patients with mild generalized myasthenia, curare may be useful. This needs extreme care because of the sensitivity of the myasthenic to curare. D-tubocurarine was first used by Bennett and Cash in 1943, but ganamine - tri-ethiodide may also be used as shown by Dundef in 1951 [27]. Severe paralysis of the respiratory muscles may be precipitated by this test. It is important that all drugs and equipments needed for respiratory resuscitation as well as personnel trained in these methods should be discretely at hand.

The patient is placed in the recumbent position and with an intravenous infusion running. Subjective and objective assessments of muscle strength are made. 0.5 to 1 ml. of d-tubocurarine solution containing 1 mg/ml is injected over a 30 second period and muscle performance is retested 5 minutes later. If there is no marked change another 0.5 to 1 mg is given and muscle performance is tested 3 minutes later. Additional 0.5 to 1 mg. doses can be given at 3 minutes intervals up to a total of 4 mg. If a marked reduction of grip strength or vital capacity does not occur following the administration of 4 mg, it is unlikely that the patient has myasthenia gravis. If less than 4 mg of d -tubocurarine produces a significant decrease of the grip strength or vital capacity the diagnosis of myasthenia gravis is confirmed. The residual effect of d-tubocurarine should be reversed by intravenous neostigmine administered in 0.5 mg increments, the first dose being given with 0.4 to 0.6 mg atropine.

Decamethonium test:
This is well described by Wylie and Churchill Davidson in 1966 [27]. Decamethonium is a short acting muscle relaxant, which acts like acetylcholine on the muscle end plate. The muscles of mild cases of myasthenia gravis show resistance to decamethonium whilst in long standing cases, the muscle fibres are refractory to decamethonium. In between these two extremes, decamethonium may produce dual block in the myaesthenic patient. The decamethonium test is difficult to interpret and may give equivocal results.

Of all the diagnostic tests described above, the edrophonium or neostigmine tests are the easiest, quickest and safest.

Myaesthenic crisis: increasing myaesthenic symptoms resulting in paralysis of the respiratory, laryngeal, or pharyngeal muscles. It may be precipitated by physical exertion, surgery, pregnancy, psychosocial disturbance, anxiety, respiratory infections, emotional upset, infection, drugs (Streptomycin, Neomycin, curare, quinidine, steroids, sedatives, morphine ether, chloroform) and enema by depleting potassium stores. The tensilon test is useful. Treat the precipitating factor if identified and increase anticholinestrase medication and tracheostomy may be needed.

Cholinergic crisis: This is caused by the nicotinic action of excessive anticholinesterase medication on neuromuscular transmission. Features: muscarinic effect - pallor, vomiting, sweating, increase salivation, miosis (best index of toxicity), hypotension, bradycardia, confusion, coma.

Nicotinic effect - fasciculation, progressive muscle weakness from depolarisation block.

Tensilon test is harzardous: Tracheostomy and positive pressure respiration may be indicated. Atropine should be given at a dose of 2 mg hourly until signs of toxicity appear (dry mouth, pupil dilatation etc), or propantheline which is also vagolytic. Stop anticholinesterase therapy [13].

Differential diagnosis: Neurasthenia, psychogenic fatigue, physiologic fatigue drug induced myaesthenia, hyperthyroidism, botulism and Eaton - Lambert syndrome. Other differentials include amytrophic lateral sclerosis (ALS), gullain barre syndrome, poliomyelitis, nerve injury, transverse myelitis, and intracranial mass lesions.

Involvement of muscles innervated by multiple cranial nerves with absence of pupillary involvement suggests MG. Unlike psychogenic fatigue, MG is relieved by rest while unlike physiologic fatigue, there is no accompanying pain. Muscle wasting is very uncommon in MG as distinct from ALS and occurs in 10 to 20% of cases [16], although, some authors reported wasting in 41% of cases [16,28]. This was possibly due to chronic subclinical malnutrition in the study patients and disuse atrophy as a result of reduced muscle activity and mobility. In the Eaton-Lambert myaesthenic syndrome (ELS), fatigability may resemble that in myaesthenia, but other features differ (see table 1). The proximal limb weakness affects especially the pelvic and thigh muscles. Ocular and bulbar involvement is inconspicuous, and there are other symptoms such as aching, paraesthesia, dry mouth and impotence. The absent tendon reflexes, which are facilitated by vigorous muscle contractions, are a distinctive finding in ELS [6]. The diagnosis is confirmed electro physiologically by demonstration of small compound muscle action potentials with a striking incremental response at higher rates of nerve stimulation. Furthermore, there is good response to amantadine or guanidine (20 to 50 mg in divided doses). These agents enhance release of acetylcholine as well as sensitize the chemoreceptors to acetylcholine [29].

TREATMENT

Anticholinesterases, immunosuppressive drugs, plasmaphresis, and thymectomy are the four strategies in the treatment of myasthenia [12,13,14].

General measures: educate the patient of his condition and avoidance of precipitating factors should be emphasised.

Specific measures:

Medical

1. Anticholinesterase drugs - Neostigmine (prostigmine) 15 mg 2-6 hourly Pyridostigmine (Mestinon) 60mg 2 - 6 hourly Galathamine/ Ambenonium chloride (Mytelase)
2. Immunosuppressive agents Steroids : ACTH (long or short courses) / Prednisolone - are indicated if there is failure of anticholinesterase, failure of remission after surgery, when there is disabling diplopia and to improve patient’s strength for thymectomy [20, 30]. Steroids interfere with the production of antibodies responsible for degradation of the cholinergic receptors, protects the Ach receptors from the antibodies and may facilitate neuromuscular transmission [12]. They are started in a dose of 10mg of prednisolone daily and increased gradually by 10mg weekly. This avoids deterioration with high dose steroids of up to 120mg daily. Potassium supplement could be added to prevent hypokalaemia. With adequate control, steroids could be given on alternate days and then gradually decreased. The average time for significant improvement is five months and when improvement reaches plateau, then the dose could be lowered to a maintenance dose (50 -100mg). Corticosteroids may be expected to cause remission in 80% of patients, and the remission can be maintained by relatively small doses given on alternate days [29]. Augmented steroid cover during surgery is indicated in patients who have been on steroid therapy for more than two weeks. Hydrocortisone is given at a dose of 100mg six hourly for 72 hours starting with pre-medication and oral administration is resumed on commencement of oral intake. Hirsutism, flaring up of latent infection such as tuberculosis, hypertension, diabetes mellitus, renal impairment and glaucoma could complicate chronic steroid therapy in these patients.

Extraocular muscle involvement could be relatively refractory to neostigmine or mestinon in terms of only partial subsidence with considerable residual involvement. This results in a variable degree of persistent disability both from cosmetic and occupational standpoints. A noteworthy observation has been that corticotropin (ACTH) therapy administered in a total dosage of 600mg, divided into single doses of 20mg every 6 hours is highly effective in reducing or eliminating the extraocular muscle pareses [29]. The duration of the partial or complete remission has varied from three to as long as long as 12 months. Relapse is to be expected but in the ocular myaesthenic group, it often may be delayed and may be relatively mild. Corticotropin therapy may be repeated when necessary but the interval should not be less than 6 months. Although, corticotropin therapy understandably has been largely rejected for the treatment of generalized MG, it would seem reasonable to continue its use in the treatment of selected patients with ocular myasthenia in whom disability affecting the eyes cannot otherwise be adequately controlled.

Azathioprine (imuran) has been used in the treatment of MG for over 30 years and takes about seven months to achieve remission [31]. Cyclosporin A was shown to produce a significant improvement in muscle strength but was associated with sufficient toxicity to preclude its use as a first line immunosuppressive agent [30].

Cyclophosphamide has also been found promising. Plasmaphresis- with daily exchange of 2 liters of plasma has shown short-term clinical improvement [30]. Intravenous Immunoglobulin usually given at a standard dose of 5 mls every 3 weeks or at a high dose of 0.4 g /Kg/day for 5 days have also been found useful [14,18,32]. Adjuvants include use of potassium salts, ephedrine at a dose of 15 - 30 mg tds. Ephedrine aids neuromuscular transmission by acting on the - and -noradrenergic receptors adjacent to the neuromuscular junction [30].

Emmergency measures are indicated if there is sudden dysphagia and/or respiratory crisis. Patients are advised to always carry 2 ampoules of 0.5 mg of prostigmine. This could be given subcutaneously or intramuscularly at a dose of 1 mg, two to three times in an hour till adequate respiration is achieved. Oxygen, suction apparatus, respirator, endotracheal intubation and/or tracheostomy may be required.

Surgery

Thymectomy :
Indications for thymectomy: sudden deterioration of the clinical state of the patient including severe respiratory embarrassment, poor response to regular medication or as an elective surgery alternative to the regular medication [18,33]. It is becoming more common to perform thymectomy at an earlier stage in the disease process and this is now the commonest cause of presentation for anaesthesia. Of such patients, 96% will experience some benefit from the operation and in 46% this will be of a permanent nature [13, 33]. In acute, fulminating cases, (stage 3), plasmaphresis may cause a transient improvement prior to such surgery and accelerate post-operative recovery. Lymph drainage also has a rapid effect [34]. Transternal or transcervical thymectomy aims to remove as much thymic tissue as possible (anterior mediastinal exenteration). Even small remnants of thymic tissue seem to affect outcome adversely as 2/3rd of patients with thymoma die within 5 years [18]. Tarsorrhaphy is indicated if there is disabling ptosis and for cosmetic reasons.

Radiotherapy before surgery has not been promising [13].

Conduct of anaesthesia in patients with myasthenia gravis: a) premedication: all potent analgesic agents should be avoided unless the patient has pain. Morphia should be avoided because it is potentiated by neostigmine. In very anxious patients or when the operation is to be performed under regional analgesic technique, the judicious combination of a short-acting barbiturate such as 50 - 100 mg pentobarbital (Nembutal) or secobarbitone (seconal) and promethazine (phenergan) 25 to 50 mg could be tried [35]. Anaesthetic management:

Regional analgesia: whenever possible, local or regional technique should be employed. Because local anaesthetic agents may block neuromuscular transmission, it is better to use techniques, which involve the use of small quantities of these agents. Hence sub-arachnoid block (spinal) is preferable to the use of epidural or caudal analgesia [28].

General anaesthesia: When general anaesthesia is indicated, induction could be with light thiopentone, nitrous oxide and oxygen mixture [28,35]. It is however preferable to induce anaesthesia with inhalational agents such as halothane/oxygen, cyclopropane/oxygen or ether/oxygen; and maintain anaesthesia with the same agents. Endotracheal intubation should be performed after adequate topical analgesia of the pharynx and larynx. Cyclopropane may cause bronchospasm from its parasymptomimetic effect and may induce arrythmias because of the degenerative changes described in myasthenics. Ether should not be used for these patients because of its curare -like effect at the neuromuscular junction and also because of its irritant effect on the tracheobronchial tree; but it has been used safely in low analgesic concentration [28].

It is wise to avoid the use of neuromuscular blocking agents as much as possible. However, when their use is indicated as when intubation is difficult or respiration cannot be controlled with the inhalational agents alone, it is better to use small doses (1/10th of the usual dose) of non-depolarising rather than the depolarizing relaxant drugs [36]. There has been a difference of opinion on the latter point. The depolarizing muscle relaxant such as decamethonium or suxamethonium act irregularly; clinically involved muscles of myaesthenic show increased sensitivity, while the non - involved muscles are resistant to the drugs. However, using the increased sensitivity of both the involved and non-involved myaesthenic muscles to non-depolarising muscle relaxants, good muscular relaxation can be produced by small doses of tubocurarine (0.5 - 2 mg) or gallamine tri-ethiodide (2.5 - 10mg). These small doses give constant and reliable action and are to be preferred to the variable effects of depolarizing agents [28,36]. Post-operative care: All myaesthenic patients should be admitted to the recovery ward in the immediate post operative period until their general condition is satisfactory. Those with respiratory complications need to be treated in an intensive care unit. Great attention should be paid to the maintenance of adequate oxygenation, removal of carbon dioxide, and the prevention of chest complications such as atelectasis, pneumonia and pulmonary collapse requiring bronchoscopy and tracheo-bronchial aspirations. Assisted or controlled respiration should be performed with 40% oxygen/60% air saturated with water vapour if tidal volume is less than 300mls or vital capacity is less than 1800 ml in an adult [13]. Post-operative use of anticholinesterase aims to maintain adequate respiratory exchange. Prognosis: The age at onset appeared to have prognostic significance [3]. Patients older than 50 at onset are at greater risk of generalization complicated by respiratory crisis or death, and younger age of onset is associated with a more benign outcome [37]. In nearly all myaesthenic patients, the extraocular muscles are involved at some time in the course of the disease, and in approximately 14 % the weakness remains clinically localized to those muscle groups. After 2 or 3 years, it is likely that myasthenia gravis limited to the eyes will remain ocular and therefore constitute relatively little threat to the life of the individual [14]. There is rapid decline in the risk of generalization with increasing duration of solely ocular symptoms. However, the probability of remission seemed to decrease more slowly with duration of illness than did the probability of generalization [13].

CONCLUSION

In conclusion, the course of MG is extremely variable. Ocular symptoms may recur at intervals or remain static. Spontaneous remission is common but relapse is the rule. After 5 to 10 years, the disease enters a static phase with only moderate response to treatment and varying degree of residual disability. Spontaneous remission could lasts weeks to years and occurs during the first 3 years. At the final stage, patient becomes bed ridden and severely paralysed. Death from bronchopneumonia and respiratory failure are common [37].

TABLE 1. Characteristics of myaesthenia gravis and myaesthenic syndrome

Myaesthenia gravis Myaesthenic syndrome
Sex more common in women almost entirely men
Age commonly 20-40 years commonly 50-70 years
Presenting signs weakness of external ocular, bulbar, and facial muscles weakness and fatigability of proximal limb muscles
fatigue on activity transient increase in strength on activity precedes fatigue
muscle pains uncommon muscle pains common
tendon reflexes normal tendon reflexes reduced/absent
Pathological state thymus gland abnormality, 10 -20% have thymoma small cell bronchogenic ca(+). assoc. with ca. bronchus, breast, stomach, rectum, prostate, intrathoracic growth, may antedate or appear after successful removal of original carcinoma.
Electromygraphic initial muscle action potential relatively normal. initial A.P. abnormally small
anticholinesterases good response to anti-cholinesterases poor response to anti-cholinesterases
Response to non depolarizing relaxants increased sensitivity to non-depolarising blockers increased sensitivity to non-depolarising blockers
Response to suxamethonium variable normal or increased response

REFERENCES

  1. WILLIS, T. Two Discourses Concerning the Soul of Butes, Translated by S. Poordage, Lond 1683, quoted by Viets, H. R.:Historical review of M. Gravis from 1672 to 1900. J.A.M.A. 1953; 153: 1273.
  2. GOLDFRAM, S. Ueber einen scheinbar heilbaren bulbarparalystischen symptomencomplex mit Betheiligun der Extremiaten. Deusche Ztshri Nervenh. 1893 ; 4:312-352.
  3. SCHWAB, R.S., LELAND, C.C. Sex and age in MG as critical factors in incidents and remission J. Amer. Med Ass. 1953;153: 127-0.
  4. BEEKMAN, R., KUKS, J.B.M., OOSTERRHUS, H.J.G.H. Myasthenia gravis: diagnosis and follow-up of 100 consecutive patients J. Neurol 1997, 244: 112-118.
  5. SHINOMUJA, N., SEGAWA, M., YATA, I. In Vitro study of T-Cells regulating anti-AchR antibody formation in MG. Ann NY Acad Sc. 1981; 377: 882-3
  6. Myopathies and disorders of neuromuscular transmission. In Walsh and Hoyt’s Clinical Neuro-opthalmology, edn 5. Edited by Miller, N.J., Newman, N., Baltimore: Williams and Wilkins; 1998: 1351 - 1460.
  7. GRONSETH, G.S., BAROHN, R.J. Thymectomy for autoimmune myasthenia gravis (an evidence - based review)Neurology 2000; 55: 7-15.
  8. LINDSTROM, J.M., SEYBOLD, M.E., LENNON, V.A., WHITTINGHAM, S. D.Prevalence, clinical correlations and diagnostic value. Neurology, 1976;26:1054-1059.
  9. KUPPERSMITH, M.J., MOSTER, M., BHUIYAN, S,.Beneficial effects of ocular myasthenia gravis. Arch Neurol. 1996, 53: 802 -804.
  10. BEHAN, P.O.Immune disease and HLA Associations with myasthenia gravis. J. Neurol Neruosurg phychiatry, 1980; 32: 611-21. [11] TAHA, A.M., HADDAD, R., ALLAM, C., BARAKA, A. The thymus and myasthenia gravis. Middle East J Anaesthesiol 1981; 6:99-112.
  11. DRACHMAN, D.B., ADAMS, R.N., SOSIFEK, L.F., Self, S.G.Functional activities of Autoantibodies to AchR and the clinical severity.of Myasthenia Gravis
  12. DRACHMAN, D.B. Myasthenia gravis New Engl J Med 1994;330: 1797 - 1810
  13. PELAK,, V.S., GALETA, S.L. Ocular myasthenia gravis. Current treatment Options in Neurology. 2001 ; 3 (4): 367 - 376.
  14. PEPER, K., BRADLEY, R.J., DREYER, F. The AchR at the neuromuscular junction. Physiological Reviews 1982; 62: 1271-340.
  15. FENICHEL, G. Clinical syndromes of myasthenia in infancy and childhood. Archives of Neurology. 1978; 35 (2): 97-103.
  16. JARETZKI III, A, BAROHN, R.J., Emstoff, R.M. Myasthenia gravis: recommendeations for clinical research standards. Neurology 2000; 55 : 16-23.
  17. GRONSETH, G.S., BAROHN, R.J. Thymectomy for myasthenia gravis. Current treatment Options in Neurology. 2002 ; 4 (3): 203 -209.
  18. ALMON, K.R., ANDREW, C.G., Appel, S.H. Serum globulin in MG: Inhibition of a-bungarotoxin binding to ach.R Science, 1974;186, 55-57.
  19. WOLFE, G.I., BAROHN, R.J., GALETTA, S.L., Drugs for the diagnosis and treatment of myasthenia gravis.In textbook of ocular pharmacology: Edited by Zimmermeran, T.J., Philadelphia : lippincott - Raven Publishers; 1997: 837 - 848.
  20. BARAKA, A., DAJANI, A. Atracurium in myasthenics undergoing theymectomy. Anesth Analg 1984; 63: 1127-29.
  21. BARAKA, A., TAHA, S., YAZBECK, J., RIZKALLAH, P Vecuronium block in the myasthenic Patient. Anaesthsia 1993; 48:588-90.
  22. GREENWOOD, B.M., FRANCIS, T.I. MG in AfricansW.A.J.M. 1967; 47 -98
  23. Oosterthuis, H.J.G.H., Toyka, K. HJG Long term effects of treatment in 374 patients with MG. In de Beats, M. Oosterhuis, eds Monographs in allergy. Vol 25. Basie: Karger, 1988:75-85.
  24. OSSERMAN, K.E., KOSOVSKY, N., Spurt, H.IN discussion of pregnancy in Myasthenia GravisAm J. Med 1955;19:720
  25. OSSERMAN, K.E., GENKINS, G. (1971) Studies in Myasthenia gravis: Review of a twenty-years experience in over 1,200 patients. Mt Sinai J. Med.,1971 ; 38:497.
  26. DAROFF, R.B.The office tensilon test for ocular myasthenia gravis.Arch Neurol 1986;43:843-844
  27. BADEMOSI, O., OSUNTOKUN, B.O., BADEMOSI, A., ADEBONOJO, S.A.Myaesthenia gravis in Nigerians N.M.J. 1982; 12 (4): 329 - 356.
  28. O’NEIL, J.H., MURRAY, NMF. NEWSOM DAVIS. J. The Lambert Eaton myasthenia syndrome - a review of 50 cases. Brain 1988; 111: 577-96.
  29. Havard, C.W.H., Fonseca, V.New treatment approaches to myasthenia gravis. Drugs 1990; 39:66-73.
  30. Fonseca, V., Havard, C.W.H. Long term treatment of myasthenia gravis with azathiophrine. Postgrad Med J 1990; 66:102-5.
  31. COSI, V., LOMBARDI, M., PICOLO,G., ERBELTA, A. Treatment of MG with high dose intravenous immunoglobnin. Acta Neurologica, Scandinavica 1991; 84: 81-4.
  32. OLANOW, C.W., WECHSTER, A.S., STROTKIN-ROSES, M., STAJICH, J., ROSES, A.D Thymectomy as primary therapy in myasthenia gravis. Ann NY Acad Sci. 1987; 505: 595-606.
  33. SEGGIA, J.C., ABREU, P., TAKATANI, M. Plasmaphresis as preparatory method for thymectomy in myasthenia gravis Arq Neuropsiquiatr 1995; 53: 411 - 415.
  34. ODUNTAN, S.A.The Role of the Anaesthetist in the Management of MG in UCH, Ibadan.W. A. M. J. 1968; 17-20.
  35. OSTERGAARD, D., ENGBAEK, J., VIBY-MOGENSEN, J. Adverse reactions and interactions of the neuromuscular blocking drugs Medical toxicology and adverse drug experience 1989; E: 351-68.
  36. CHRISTENSEN, P.B., JENSEN, T.S., TSIROROPOULOS, I. Mortality and survival in Myasthenia gravis: a Danish population based study J. Neurol Neurosurg Psych 1998; 64:78 - 83.


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