Thymectomy in myasthenia gravis.
Blalock and his associates,, reported a series of patients of myasthenia, gravis who were successfully treated by thymectomy. Since then, the operation has gained increasing acceptance in the management of this disease., Despite the clear understanding about the etiology of myasthenia gravis, it has generally been accepted that the thymus has either a causal or a contributory relationship to myasthenia gravis.
Although the rationale, timing and results of thymectomy in myasthenia gravis are clearly documented, very few authors have discussed the pert-operative management in a comprehensive manner. After critically analysing the problems posed by these patients before, during and after operation, we have streamlined the management and have obtained good results. In the present communication, our short experience during the first 25 consecutive patients undergoing thymectomy for myasthenia gravis is being presented. This is a second report of thymectomy for myasthenia gravis in India.
Forty two patients of myasthenia gravis were seen at the Department of Neurosurgery, K.E.M. Hospital from 1976 to 1983. Six patients had pure ocular myasthenia, and 11 patients refused thymectomy due to various reasons. Of the remaining twenty five patients who underwent thymectomy, 7 were females and 18 males. Their ages ranged from 14 to 70 years, the average being 42 years. The duration of symptoms prior to thymectomy varied from 1 month to 10 years.
All the 25 cases were diagnosed clinically by the neurologists. The diagnosis was further substantiated by prostigmine test and electromyography. Following investigations were routinely carried out before the operation.
1. Chest X-ray: postero-anterior and lateral views.
2. Lateral chest tomograms-to detect thymic mass.
3. 12 lead scalar electrocardiography (ECG).
4. Glucose tolerance test (GTT).
5. Pulmonary function tests-to assess objectively the respiratory muscle dysfunction.
6. Arterial blood gases.
7. Thyroid function tests.
8. RA factor, LE cell and ANA of serum.
Medical treatment was started by the neurologist. Prostigmine or pyridostigmine was tailored according to the patient's requirement. The maximum dose of prostigmine given was 210 mg in 24 hours, and that of the pyridostigmine was 600 mg per day. In some patients, both these drugs were needed for satisfactory control of the disease. Close watch for cholinergic, myasthenic and mixed crises was maintained at all times. Nasogastric feeding was initiated at even the slightest evidence of dysphagia to avoid aspiration pneumonia. Vital capacity was roughly judged twice daily by asking the patient to count numbers in a single breath. If symptoms could not be controlled with anticholinesterase drugs and all three types of crises could be ruled out, infection, stress or trauma was suspected and treated accordingly. In patients who did not respond to above therapy, prednisolone 15 mg per day was started and stepped up by 5 mg every 5th day to a total dose of 1 mg/kg/day, keeping in mind the possibility of myasthenic crisis induced by steroids Plasmapheresis was resorted to in an emergency situation in 4 patients. It was done by using plasmapheresis equipment Haemonetics-30, separating 1 to 1½ liters of plasma during 2 to 3 hours' period. The separated cells were reconstituted with 5% human albumin. Usually, 2 to 3 sittings per week for 2 to 3 weeks sufficed. Response to plasmapheresis was found to be earlier within 2 to 4 days and sometimes late around 3 weeks and lasted for about 4 to 6 weeks. All these patients were submitted for thymectomy when respiratory function was found to be at its best.
Intensive physiotherapy of the chest was initiated at least 15, days prior to surgery. Thymectomy was done at a time when patient's pulmonary function status as evident from his clinical evaluation, blood gases and pulmonary function tests were at their best. Poor respiratory reserve was seen in 3 patients and was considered by us as a relative contraindication to surgery.
During the preanaesthetic visit, the anaesthesiologist reviewed patient's history, investigations, medical treatment and the clinical status in detail. On the day of operation, the patient remained fasting from 6 A.M. onwards. Before that he took his regular dose of prostigmine or pyridostigmine. Next 1 or 2 doses, if possible, were omitted. However, whenever needed, 1.5 mg prostigmine was given intramuscularly. Minimal dose of anticholinesterase drug was preferred throughout anaesthesia. Due to this, endotracheal intubation was easy and no muscle relaxants were used. Induction and maintenance of anaesthesia were done with halothane and oxygen.
All operations were carried out through median sternotomy. The highest point of incision was 2.5 cm below the upper border of manubrium sterni. Dissection of thymus was done in a conventional fashion. Extreme care was taken for removal of all thymic tissues in the neck and chest.
Thymic tails, aberrants and remnants, fat and soft tissues were removed so as to have a good clearing of the anterior mediastinum right upto the diaphragm. Thorough clearance and meticulous haemostasis were the surgeon's goals.
Post-operative management was done by the neurologist, the anaesthetist and the surgeon together. Two hourly critical reassessment was the rule. Post-operatively, the dose of anticholinesterase drug given was one third of the preoperative requirement and was subsequently tailored according to patient's need. It was given by mouth or Ryle's tube. However, when needed in first 6 hours, intramuscular route was also used. 15 mg oral prostigmine was considered roughly equivalent to 1.5 mg of intramuscular prostigmine. Underdosage schedule was preferred to overdosage schedule. As far as possible, respirator and tracheostomy were avoided. Respiratory depressants like morphine, pethidine and diazepam were avoided at all times. Whenever needed, analgin, pentazocine or paracetamol were used for post-operative pain. Early, frequent and regular chest physiotherapy was given to all patients. Steroids, if started pre-operatively, were continued in the same dosage post-operatively. During early post-operative phase, twice daily blood gases and estimation of serum potassium were done in order to judge the pulmonary function and muscle weakness due to hypokalemia. Aminoglycoside group of antibiotics were never used during the post-operative period. Usually patient's condition is satisfactory for the first 48 hours post-operatively. A problem of myasthenic or cholinergic crisis arises from 3rd day onwards to 6th day because of sudden reduction in the requirement of anticholinesterases. This becomes the most critical period and the patient needs to be seen frequently for early diagnosis and treatment of the crisis.
Out of 25 patients, 22 could be preoperatively stabilised only on anticholinesterases, three needed additional prednisolone and four plasmapheresis (2 from each group). Uneventful course was seen in 19 (76%) patients. During dissection of the thymus gland, innominate artery was injured in one patient. Tracheostomy was needed in 3 patients. One of the tracheostomised patients developed severe mediastinitis and sternal dehiscence. Respirator was needed in two patients, for one patient for 12 hours, during the immediate postoperative phase and in another patient for 3 days, during the late post-operative phase. One patient died in cholinergic crisis. The mortality rate in our series was 4%. Excised thymus glands showed evidence of hyperplasia in 23 specimens, thymoma was seen in one and thymolipoma in one patient.
Follow up period varied from 8 months to 7 years. Out of 24 operative survivors, 12 (48%) needed no drugs after 3 months to 5 years after surgery, 9 (36%) had either prolonged remission and/or better control of the disease with less dosage and frequency of drugs and only 2 (8%) patients did not benefit from the operation. Both of them were females of 14 and 25 years respectively at the time of thymectomy. In these two patients, the duration of myasthenia before thymectomy was less than 2 years. They died 2 and 4 years respectively after thymectomy due to myasthenic crisis. One patient committed suicide 4 months after thymectomy, who was in complete remission. One of our patients who had complete remission delivered two children after thymectomy without any symptoms during pregnancy or neonatal myasthenia in siblings.
The clinical course of myasthenia gravis is unpredictable in a given individual inspite of advances in the management. Simpson, on the basis of clinical findings and Nastuk et al based on laboratory data, suggested autoimmune mechanism involved in the pathogenesis of the disease. Thymectomy has been widely accepted as a mode of therapy for myasthenia gravis.,,,,, The report from the Mayo Clinic consisting of a study of 80 surgically treated patients with 80 medically treated, computer matched, non-thymomatous, myasthenia gravis patients, convincingly revealed that the response to thymectomy was excellent. In the surgically treated group of patients, the remission was 4 to 5 times higher, the number of patients improved was double, and the number of patients dying was less than half when compared to those in the medically treated group.
Recent advances in anaesthesia and the post-operative care have reduced the mortality and morbidity considerably following thymectomy. There is 60 to 80% improvement following thymectomy in non thymoma group of patients and complete recovery is observed in 40 to 45% of patients after 5 to 10 years. In this series, 12 patients (48%) had full recovery, 9 patients (36%) showed good improvement and 2 patients did not show any benefit and died subsequently. Indications for thymectomy are increasing even in respect to the duration of the illness. It is not done in pure ocular and congenital myasthenia gravis and is contraindicated when some medical illness makes the patient unfit for general anaesthesia.
Poor respiratory reserve has been considered as a relative contraindication by us. This is because this group of patients not only need a respirator in the postoperative period but also often they become respirator dependant and carry a greater risk. The problem posed by long term ventilatory therapy is too well known. It is for this reason, that in contrast to others we avoid respiratory assistance and tracheostomy as far as possible. We do elective thymectomy only when the patient's respiratory functions are at their best level.
In the post-operative management, the patient needs to be seen by a neurologist quite frequently. Usually, the first 48 hours after surgery are uneventful. The doses of anticholinesterase drugs step down dramatically from 3 to 6 days postoperatively and at this stage one faces the problem of cholinergic crisis. Our experience has taught us to reduce the dose of anticholinesterases to one third of the preoperative requirements and thereafter to tailor them according to the patient's need. We prefer underdosage than overdosage of the anticholinesterase drugs. Post-operatively, the patient needs to be closely watched for early diagnosis and management of myasthenic and/or cholinergic crisis. In exceptional cases, one may encounter borderline or mixed crisis. Sometimes the clinical picture is confusing and one is in doubt about the nature of the crisis. In these situations, when respiratory muscles are affected, it is wise to keep the patient on artificial respirator after omitting the anti-cholinesterases.
Median sternotomy is the exclusive approach to thymectomy. We believe that it is only by this incision that a complete thymectomy can be achieved. It is very important to carry out a thorough anterior mediastinal clearance in order to remove even microscopic foci of thymic tissue. The incision for median sternotomy should be as low as possible so that if the patient needs tracheostomy later, the chances of mediastinitis are reduced.
Close co-operation between the neurologist, anaesthetist, cardiothoracic surgeon and the physiotherapist is needed at all stages in the management to prevent mortality and morbidity. Thymectomy for myasthenia gravis is a team work and no member of the team is more important than the rest.
We are thankful to the Dean, Seth G.S. Medical College and K.E.M. Hospital, Bombay for allowing us to publish the hospital data.