Indian Pediatrics 1998;35:901-903 

Recovery From Myasthenic Crisis After Use of IVIG Therapy

Kamna Jain
Gouri Rao Passi
Manju Rajguru
S. AthIe
D.M. Gandhi

From the Departments of Pediatrics, Neurology and Cardiothoracic Surgery, Choithram Hospital and Research Center, Indore 452 001, India.

Reprint requests: Dr. Kamna Jain, Consultant, Department of Pediatrics, Choithram Hospital and Research Center, Indore 452 001, India.
Manuscript Received: December 17, 1997; Initial review completed: December 19, 1997; Revision Accepted: March 12, 1998

Myasthenia gravis (MG) is an un- common disorder of immune pathogenesis affecting neuromuscular transmission. The prevalence is 0.5-5.0 per 100,000 population. The fluctuating nature of myasthenic weakness and it's myriad presentations make it a unique clinical disorder. Occasionally it presents as an acute exacerbation involving respiratory muscles which may be potentially fatal, unless managed energetically.

Case Report

A six-year-old girl presented to us with the complaints of fever for six days and increasing respiratory distress for one day. There was no history of cough, stridor or wheeze. On direct questioning a history of choking while eating a papaya a few days I before was elicited. On examination the child had severe air hunger with a respiratory rate of 40/ minute and fatigue of the accessory muscles of respiration. The pulse rate was 120/minute, the blood pressure was 120/70 mm Hg and her temperature was 100.6°F. On auscultation of the chest air entry was symmetrically reduced and there were no adventitious sounds. The rest of the systemic examination was normal. Investigations revealed a hemoglobin of 11.9 g/dl, total leukocyte countt (TCL) 6200/cu mm, serum sodium 135 meq/L and serum potassium 4.2 meq/L. The chest X-ray was normal. Arterial blood gas (ABG) analysis was as follows: pH 7.3, p02 168 mm Hg, pC02 44.6 mmHg, standard HC0₃ 20 mmol/L. An urgent bronchoscopy, to rule out any foreign body aspiration was normal. It was done under general anesthesia which included premedication with atropine, followed by succinylcholine 1 mg/kg, halothane and nitrous oxide. However, the child could not be extubated after anesthesia. She was ventilated on a pressure cycled ventilator and intravenous tobramycin in the dose of 7 mg/Kg was added prophylactically against nosocomial pneumonia. The next day the child developed ptosis and careful neurological examination showed bilateral symmetrical hypotonia, reduced power (grade 2 proximally and grade 3 distally) with preserved reflexes.

A possibility of myasthenia gravis was considered in view of the ptosis, proximal muscle weakness and inability to wean off the ventilator following general anesthesia where succinyl choline was used. A neostigmine test was performed, in which 0.04 mg/kg of neostigmine was given intramuscular with injection atropine 0.01 ml/kg. After 20 minutes, power in all four limbs increased dramatically to grade 5 and ptosis disappeared, which confirmed the diagnosis of myasthenia gravis.

She was given high dose intravenous immunoglobulin (IVIG) 2g/kg over 5 days and also started on dexamethasone in the dose 0.4 mg/kg. IV Tobramycin was stopped. On day 4 her power had improved to grade 4, cough reflex had appeared and ptosis had disappeared. She was started on intramuscular (1M) neostigmine 4 hourly and extubated after nine days of ventilation, on the fifth day of IVIG therapy. She was shifted to oral pyridostigmine. Electromyography (EMG) showed a decremental response to repetitive stimulus. A CT chest showed a normal thymus. Serum T3 was 6.0 nmol/l, T4 4.2 µg/dl and TSH 0.5 mU/1 suggestive of a sick euthyroid syndrome. There was no facility to measure antiacetylcholine receptor antibody levels. She was discharged on oral prednisolone (1mg/kg) and pyridostigmine (60 mg/day). At discharge she was walking independently, speaking and able to take a normal diet orally. At 3 months follow up she was admitted for a thymectomy. Lung function tests were performed prior to surgery which showed reduced ventilatory reserve. Hence we subjected her to two cycles of plasmapheresis preoperatively. Thymectomy was done by medial sternotomy incision. The enlarged hypertrophic thymus was removed enmass. Post operative period was uneventful. The thymus gland showed follicular hyperplasia on histopathological examination. She was discharged on oral steroids and pyridostigmine. She is currently under regular follow up in our hospital. Prednisolone has been tapered slowly. Pyridostigmine is being continued in a dose of 45 mg/day.

Discussion

This case was interesting because there was an unusual neurological cause of acute respiratory distress. Further such experience with use of IVIG in acute myasthenic crisis in children is limited. Myasthenia gravis is a disease caused by immunologic neuromuscular blockage. Only 10% of cases of myasthenia gravis occur below 10 years of age(1). Most patients with myasthenia gravis have symptomatic disease for several months before developing respiratory compromise. A practical clinical classification of myasthenia gravis was developed by Osserman in 1958(2). Ocular muscles are usually involved initially in 40% and finally in nearly all patients. Virtually all patients have oropharyngeal muscle involvement at some time or other. Acute respiratory failure occurs in 15- 20%(3). Rarely; they present as acute respiratory failure of unknown cause. Neuro-muscular blocking drugs can precipitate disease in an obstetric delivery or general surgery(4). Failure to wean from ventilator following surgery must raise the suspicion, of myasthenia gravis. Diagnosis is confirmed by clinical response to cholinergic drugs (edrophonium test), or electro-myography which shows decremental response. Elective intubation and mechanical ventilation is needed if the vital capacity falls below 15 ml/Kg. Cholinergic drugs are stopped during ventilation because of excessive secretions. Although corticosteroids are widely used and accepted as potent treatment for myasthenia gravis, their efficacy has never been studied in randomized placebo-controlled clinical trials(5). It is generally started in a dose of 1 mg/Kg/ day and tapered over 6 months. During a crisis response to steroids rarely occurs till 10-14 days.

Most centers use plasmapheresis to treat patients with myasthenia gravis in crisis to reduce ventilation time and morbidity. We also considered plasmapheresis before deciding in favor of high dose IVIG. Recently there has been increasing use of high dose intravenous immunoglobulin in exacerbation's of myasthenia gravis. In a recent randomized controlled trial, efficacy was found to be similar to plasmapheresis though side effects were significantly lower(6). Efficacy was found to be maintained upto 60 days(7). Hyperthyroidism occasionally is associated with myasthenia gravis and must be looked for in any worsening. Thymectomy is currently recommended for most patients of mysthenia gravis, preferably in the first year after diagnosis to improve long term remission rates. Preoperative plasmapheresis is recommended if lung function tests are abnormal. In a study of 28 children with myasthenia gravis between 1-9 years, improvement was seen in 19 (67.8%) and full remission in 12 (42.8%) following thymectomy(8). The mortality rate of crisis has declined from 42% in 1960-65 to almost nil in recent studies(9). Long term outlook for myasthenic children is good. In a follow up of 149 children (85 thymectomised), 30% of non-thymectomised and 40% of thymectomised patients underwent remission(10).

Myasthenic crisis may be considered in any unexplained acute respiratory failure. High dose intravenous immunoglobulin therapy is a safe alternative to plasmapheresis in exacerbation's of myasthenia gravis especially in centers where plasmapheresis is not available or availability of large volumes of screened blood is difficult to get. Thymectomy is recommended for improving long term remission rates.

 

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