Dystrophic and Congenita Myotonias

Munsat, Neurology (1967),262 reported a double-blind crossover study of seven patients with dystrophic myotonia and two with myotonia congenita. The authors found both PHT and procainamide effective in treatment of the myotonic symptoms. PHT was better tolerated and did not increase the preexisting cardiac conductive defects, which were made worse by procainamide.

262. Munsat, T. L., Therapy of myotonia: a double-blind evaluation of diphenylhydantoin, procainamide, and placebo, Neurology, 17: 359-367, 1967.

Bhatt, Vijayan and Dreyfus, California Medicine (1971),825 in a review of clinical and laboratory aspects of myotonia, state that of treatments which have been used successfully for myotonia, including PHT, procainamide, quinine, and adrenocorticotropic hormone, PHT appears to be the most effective, the safest and the best tolerated.

825. Bhatt, G., Vijayan, N. and Dreyfus, P. M., Myotonia, Calif. Med., II 4: 16-22, 1971.

Thompson, New England Journal of Medicine (1972),1614 in a letter to the editor wrote: “In three members of a family in my practice with myotonia congenital PHT, 100 mg three times a day, was started. The patients were sixteen, twenty and twenty-three years of age. Their disabilities included inability to dance, difficulty getting up from a sitting position, difficulty relaxing grips, and some failing because of inability to relax the muscles. On PHT therapy they are all much improved. The sixteen-year-old girl is particularly delighted because she can now dance. No side effects have occurred and the improvement is dramatic.”

1614. Thompson, C. E., Diphenylhydantoin for myotonia congenital, New Eng. J. Med., 286: 893, 1972.

Griggs, Davis, Anderson and Dove, American Journal of Medicine (1975),2558 studied the effect of PHT on cardiac conduction in patients who suffered from myotonic dystrophy. They found that PHT was beneficial, not only for the myotonia, but also for cardiac conduction defects common in this disease. In seven of ten patients treated with oral PHT the P-R interval was shortened by 5 to 50 msec. This was in contrast to quinine and procainamide. Quinine produced P-R interval prolongation in six of thirteen patients, and procainamide produced P-R interval prolongation in eleven of twelve patients. The authors state that since they and others have found that PHT is an effective antimyotonic agent and since their own findings have shown that it does not have negative effects on cardiac conduction abnormalities as do quinine and procainamide, PHT is the treatment of choice in myotonic dystrophy. (See also Ref. 764.)

2558. Griggs, R. C., Davis, B. J., Anderson, D. C., Dove, J. T., Cardiac conduction in myotonic dystrophy, Am. J. Med., 59: 37-42, 1975.
764. Anderson, D. C., Davis, R. J., Dove, J. T., and Griggs, R. C., Cardiac conduction during treatment of myotonia, Neurology, 23: 390, 1973.

Biryukov, Zh Nevropatol Psikhiatr (1976),1752 compared the effects of PHT and novocainamid in two groups of myotonic patients. With PHT, 400-500 mg/day for a period of three to four weeks, there was a significant improvement in nine of the fourteen patients treated. The myotonic contractures disappeared almost completely in six with myotonia congenital and the myotonic component was significantly reduced within two weeks in three with myotonic dystrophy. Sixteen patients were treated with novocainamid, 0.75-1.5 g/day. In two, treatment had to be stopped because significant brachycardia developed. There was some improvement in six of fourteen patients, four with myotonia congenita and two with myotonic dystrophy. The author notes that PHT was not only more effective, but also better tolerated than novocainamid. Its lack of adverse effects on cardiac function distinguished it from novocainamid.

1752. Biryukov, V. B., The treatment of patients with different forms of myotonia with diphenine and novocainamide, Zh. Neurepatol, Psikhiatr., 76: 1333-5, 1976.

Durelli, Mutani, Sechi, Traccis, Monaco and Glorioso, Electroencephalograpby and Clinical Neurophysiology (1982),2469 compared PHT, carbamazepine and placebo in a double-blind study of eight patients with dystrophic myotonia (Steinert’s disease). Criteria included subjective and objective clinical findings as well as EMG evaluation. Both drugs were found to be effective.

2469. Durelli, L., Mutani, R., Sechi, G. P., Traccis, S., Monaco, F., Glorioso, N., Treatment of human myotonia. Double-blind trial carbamazepine and diphenylhydantoin, Electroencephalogr. Clin. Neurophysiol., 54: 5p, 1982.

Striano, Meo, Bilo and Vitolo, Encephalography and Clinical Neurophysiology (1983),2986 report a patient with typical Thomsen’s disease (myotonia congenital, who also had evidence of sleep-induced apnea and excessive daytime somnolence. All-night polysomnography demonstrated obstructive and central apneas with accompanying cardiac arrhythmias. PHT improved not only the myotonia, but also the breathing patterns, sleep soundness and excessive daytime somnolence. See also Refs. 1073, 1939, 2446, 2867.

2986. Striano, S., Meo, R., Bilo, L., Vitolo, S., Sleep apnea syndrome in Thomsen’s disease. A case report, Electroencephalogr. Clin. Neurophysiol., 56: 323-5, 1983.
1073. Gimenez-Roldan, S. and Esteban, A., Orbicularis oculi  “myotonia” in hypothyroid myopathy, Europ. Neurol., 9: 44-55, 1973.
1939. Kurihara, T., Tawara, S., Araki, S., Okamoto, S. and Shirabe, T., The therapeutic effects of diphenylhydantoin for myotonia and electron microscopic studies of Thomsen’s disease, Clin. Neurol. (Tokyo), 16: 661-8, 1976.
2446. Delandsheer, E., Guieu, J. D., Bouchez, B., Reant, O., Effect of intravenous diphenylhydantoin on myotonia in myotonic dystrophy, Lyon Med., 252: 279-84, 1984.
2867. Pettengell, K. E., Spitaels, J. M., Sirnjee, A. E., Dysphagia and dystrophia myotonica: a case report, S. Afr. Med. J., 68: 113-14, 1985.

Lehkuniec, Micheli, De Arbelaiz, Torres and Paradiso, Movement Disorders (1990), 3203 describe a 29-year-old patient with 3-6 daily episodes of paroxysmal dystonia. Attacks lasting 40 to 50 seconds would begin suddenly with dystonic spasms in the right leg, spreading rapidly to the left leg, arms, trunk and face. Tachycardia and 20-second apnea episodes occurred. The patient was conscious, but could not walk or talk during these attacks. Treatment with phenobarbital, trihexyphenidyl and haloperidol was unsuccessful. Carbamazepine had to be withdrawn immediately due to an allergic rash. Phenytoin, 300 mg/day decreased the number of episodes to one every two weeks. At 8 months follow-up, improvement was sustained.

3203. Lehkuniec, E., Micheli, F., De Arbelaiz, R., Torres, M., and Parasiso, G., Concurrent hypnogenic and reflex paroxysmal dystonia, Mov. Disord., 3(4): 290-94,1990.

Gutmann and Phillips, Seminars in Neurology (1991), 3204 present a review of the two types of myotonia congenita: autosomal dominant and autosomal recessive. The clinical findings and the differential diagnosis are described. In discussing treatment, the authors state that, "Treatment of myotonia is not always necessary, but when it is, the most effective medications are those that stabilize the muscle membrane. Phenytoin is frequently the first choice because it has a more benign side effect profile than other drugs and a reasonable response rate."

3204. Gutmann, L., Phillips, L.H., Myotonia congenital, Semin. Neurol., 11(3): 244-48, 1991.

Pusponegoro, Zacharia and Passat, Paediatrica Indonesiana, (1991), 3205 present a report of five siblings (ages 8-20) with myotonia congenita (Thomsen's disease). The diagnosis was based on family history and clinical findings and confirmed by electromyography. These patients were treated with phenytoin (up to 100 mg t.i.d) with good results (i.e., decreased abnormal muscle tone). Quinine sulfate (300-600 mg) was used as an alternative drug, also with good results.

3205. Pusponegoro, H.D., Zacharia, J., and Passat, J., Myotonia congenital (Thomsen's disease): report of five cases in a family, Paediatr. Indones., 31: 170-8, 1991.

Russman, Diamond, De Vivo, Kula, Tsairis, Spiro and DMD Clinical Trials Study Group, Annals of Neurology (1991), 3206 report the treatment of 42 patients with Duchenne muscular dystrophy in a randomized open-label 3-month clinical trial. Prednisone (0.75 mg/kg/day) was taken by 17 patients; phenytoin (5 mg/kg/day) taken by 12 patients; and dantrolene (4 mg/kg/day) was taken by 13 patients. There was a statistical comparison of the annualized rate of change in disease progression. The authors' findings confirmed the previously reported benefit of prednisone and suggest a mitigating effect of phenytoin on the natural course of Duchenne muscular dystrophy.

3206. Russman, B., Diamond, B., De Vivo, D.C., Kula, R., Tsairis, P., Spiro, A., and DMD Clinical Trials Study Group, Duchenne Muscular Dystrophy: an open label trial of prednisone, phenytoin and dantrolene, Ann. Neurol., 30(3): 486, 1991.

Kwiecinski, Ryniewicz and Ostrzycki, Acta Neurologica Scandinavica (1992), 3207 compared the effects of disopyramide (600 mg/day), phenytoin (600 mg/day), mexiletine (600 mg/day), tocainide (1200 mg/day) and placebo in 30 patients with myotonic disorders. The severity of myotonia was objectively assessed by clinical and electromyographic criteria before treatment (control) and at the end of each four-week medication period. Four objectives test were used: the time needed to open the eyes; the time needed to open the hand after grip; the time needed to climb 10 stairs; and the EMG relaxation time. The mean value of three measurements for each test was used to compare the results of the therapy. When compared with placebo, the group mean time of each test was significantly decreased after treatment with MXT or TCD. PHT showed similar antimyotonic potency, with the exception of the eye-opening test where results failed to reach significance. Antimyotonic action of DPM is less potent or even negligible. The patients were also required to provide subjective responses (no change, worse or improved) to each therapy and placebo condition. Good or moderate improvement of myotonic symptoms was reported by most patients receiving phenytoin (18 of 30), mexiletine (18 of 24) or tocainide (12 of 18).

3207. Kwiecinski, H., Ryniewicz, B., and Ostrzycki, A., Treatment of myotonia with antiarrhythmic drugs, Acta Neurol. Scand., 86(4):371-375, 1992.

See also Ref.

3208. Editor, Treatment of myotonia, Lancet, 1(8544): 1242-4, 1987.

3209. Kingston W.J. and Moxley, R.T., Treatment of muscular dystrophies and inflammatory myopathies, Clin. Neuropharmacol., 9(4):361-72, 1986.

3210. Phanthumchinda, K., Yodnoplaklao, P., Familial paroxysmal dyskinesia, J. Med. Assoc. Thai., 80(6):402-405, 1997.