Other Muscular Disorders

Restless Legs

Hogg, Practitioner (1972),1155 describes the successful treatment of seven cases of “restless legs,” or Ekbom’s syndrome, with PHT. For this syndrome, of unknown etiology, vasodilators, intravenous iron and Dextran have been tried with only partial success. The syndrome, he states, derives its name “restless legs” from the fact that the majority of these patients are unable to rest in bed at night and take to moving their legs sometimes vigorously because of the gnawing aches and “crawling pains.” In each of the seven patients, 100 mg of PHT daily resulted in cessation of symptoms. Since the symptoms occurred at night, and interrupted sleep, PHT was given before going to bed.

1155. Hogg, P. S., Three cases of  ‘restless legs’ or ‘Ekbom’s syndrome’ as seen in general practice, Practitioner, 209: 82-83, 1972.

Qi, Liu, Mong, Liu and Huang, National Workshop of Clinical Use of Phenytoin, Chengdu, China (1995), 3214 describe the results of phenytoin (200 mg per night for 15 days) treatment for 8 patients with restless legs or Ekbom's syndrome. There were 5 patients cured (symptom ceased, no relapse within 2 months); 1 patient improved (symptom ceased or partially improved or relapsed within 2 months); and 2 patients did not improve. No adverse effects were reported.

3214. Qi, L., Liu, D., Mong, W., Liu, Y., and Huang, M., The effect of phenytoin on 8 cases of restless legs, Presented at the National Workshop of Clinical Use of Phenytoin, Chengdu, China, 1995.

Steroid Myopathy

Stern, Gruener and Amundsen, Journal of the American Medical Association (1973),1594 report on a forty-seven-year-old man suffering with steroid myopathy, who was successfully treated with PHT. The patient required steroids (prednisolone) for his rheumatoid arthritis. Without changing the regimen of prednisolone, two six-week trial periods of PHT and placebo capsules were instituted with crossover every three weeks. The results of the two trials revealed that while on PHT there was a significant improvement in hip flexor strength, as contrasted to placebo. Muscle strength was measured with a dynamometer. The authors state that although this was only one case, the results suggest that PHT might be used along with steroids to decrease the risk of steroid myopathy. (See also Ref. 1103.)

1594. Stern, L. Z., Gruener, R., and Amundsen, P., Diphenylhydantoin for steroid-induced muscle weakness, JAMA, 223: 1287-1288, 1973. 1103. Gruener, R. P. and Stern, L. Z., Diphenylhydantoin reverses membrane effects in steroid myopathy, Nature New Bio., 235: 54-55, 1972.

Dropcho and Soong, Neurology (1991), 3215 report that clinically significant steroid myopathy (SM) occurred in twenty-three (10.6%) of 216 adult patients with primary brain tumors who received two or more continuous weeks of daily dexamethasone therapy. SM occurred over a wide range of peak and cumulative doses of dexamethasone, as well as periods of continuous treatment. However, two-thirds of the patients developed their weakness during the ninth through the twelfth week of continuous dexamethasone treatment. Patients who were taking phenytoin at standard clinical dosages, either singly or in combination with other anticonvulsants, had a significantly lower risk for developing SM than patients who received no anticonvulsants. The authors believe that "the dominant mechanism for the protective effect of phenytoin is induction of the hepatic metabolism of dexamethasone; phenytoin thus reduces the effective exposure of muscle cells to the glucocorticoid."

3215. Dropcho, E.J., Soong, S.J., steroid-induced weakness in patients with primary brain tumors, Neurology, 41: 1235-39, 1991.

Intractable Hiccups

Petroski and Patel, Lancet (1974),1411 in a letter to the editor, report on a patient with refractory hiccups and an old right hemiparesis. He was mentally alert, but repetitive attacks of hiccups seriously interfered with his feeding and sleep and left him exhausted. The hiccups did not respond to pharyngeal stimulation by catheter or parenteral prochlorperazine. On the sixth day, the frequency of hiccups increased to more than thirty per minute. PHT (200 mg), given intravenously over five minutes, completely eliminated hiccuping within an hour. Then 100 mg q.i.d. orally was continued until the eleventh day without any recurrence of hiccups.

1411. Petroski, D. and Patel, A. N., Diphenylhydantoin for intractable hiccups, Lancet, 1: 739, 1974.

See also Ref.

3216. Lewis, J.H., Hiccups. Causes and cures, Curr. Ther., 28: 169-173, 1987.

3217. Chen, T., et al., The effect of phenytoin on five cases with intractable hiccups, West China Med. J., 7(1): 61-62, 1992.

3218. Lipsky, M.S., Chronic hiccups, Am. Fam. Physician, 34: 173-7, 1986.

Respitory Myoclonus

Phillips and Eldridge, New England Journal of Medicine (1973),1414 describe a case of abnormal repetitive diaphragmatic contractions, which they refer to as respiratory myocionus. In the case reported, treatment with quinidine had been ineffective. Because of PHT’s membrane stabilizing and synaptic effects, it was tried. A dose of 400 mg of PHT daily was sufficient to inhibit the abnormal muscle activity as demonstrated by diaphragmatic, scalene and intercostal muscle electromyography. PHT was discontinued on three occasions with a return of symptoms. At the time of the writing the patient had taken PHT daily for a year with no recurrence. The authors state that in the past the only effective form of therapy for this disorder has been phrenicectomy. They suggest a trial of PHT first.

1414. Phillips, J. R. and Eldridge. F. L., Respiratory myoclonus (Leeuwenhoek’s disease), New Eng. J. Med., 289: 13901395. 1973.

Kobayashi, Suzuki, Kondo, Yamauchi, Ohta and Yamabayashi, Nippon Kyobu Shikka Zasshi (1990), 3219 describe an 18-year-old female with shortness of breath and involuntary movement in the epigastrium/diaphragm. On physical examination, fine rhythmic movements in the epigastrium (at a rate of 5-10 per breath) were observed on each inspiration. Analysis of her respiratory flow patterns revealed that her spontaneous breathing consisted of short inspirations (with associated flutter waves of 150-170 beats per minute). With an intravenous injection of 200 mg of phenytoin, the flutter waves disappeared within ten minutes. During a one-year follow up period, there were no further attacks.

3219. Kobayashi, I., Suzuki, H., Kondo, T., Yamauchi, T., Ohta, Y., Yamabayashi, H., A case report of diaphragmatic flutter, Nippon Kyobu Shikkan Gakkai Zasshi, 28(5): 777-80, 1990.

Palatal Myoclonus

Ferro and Castro-Caldas, Annals of Neurology (1981),2181 report on a case of palatal myoclonus observed in a hypertensive sixty-five-year-old male. Neurological examination, electroencephalogram and CT scan were performed. The lower half of the right side of the face, both eyelids, the tongue, lower jaw, soft palate, and posterior pharyngeal wall showed a rhythmic myoclonus that disturbed speech and swallowing, and persisted during sleep. Clonazepam improved the myoclonus but caused intolerable drowsiness and confusion. Sodium valproate had no effect, and carbamazepine worsened the condition. PHT (600 mg/day) improved the myoclonus, reducing its amplitude and the area of the body it affected.

2181. Ferro, J.M. and Castro-Caidas, A., Palatal myoclonus and carbamazepine, Ann. Neural., 10(4): 402, 1981.

Fitzgerald, Laryngoscope (1984),2500 presented a case of palatal myoclonus related to acoustical stimulation and tinnitus. Diazepam was tried with little effect. The patient was switched to carbamazepine without change. He was then placed on a combination of PHT and phenobarbital with remarkable improvement in tinnitus and myoclonus.

2500. Fitzgerald, D. C., Palatal myoclonous. Case report, Laryngoscope, 94(2): 217-19, 1984.

Spasms in Multiple Sclerosis

Matthews, Brain (1958),1342 reported the effectiveness of PHT in the treatment of frequent painful spasms in a patient with multiple sclerosis. When PHT, 100 mg t.i.d. was prescribed, the attacks stopped within two days. The author did not claim that PHT had a primary beneficial action on multiple sclerosis itself, but that it was useful in the treatment of the painful spasms.

1342. Matthews, W. B., Tonic seizures in disseminated sclerosis, Brain, 81: 193-206, 1958.

Joynt and Green, Archives of Neurology (1962),1192 found that PHT had definite suppressing effects on muscle spasms in three patients with multiple sclerosis.

1192. Joynt, R. J. and Green, D., Tonic seizures as a rnanifestation of multiple sclerosis, Arch. Neurol., 6: 293-299, 1962.

Kuroiwa and Shibasaki, Folia Psychiatrica et Neurologica Japonica (1968),1243 found that PHT and/or carbamazepine were useful in suppressing the painful tonic spasms in four patients with multiple sclerosis. The authors noted that, before PHT, a wide variety of drugs had been tried in all four cases, without success. (See also Ref. 1541.)

1243. Kuroiwa, Y. and Shibasakil H., Painful tonic seizures in multiple sclerosis-treatment with diphenylhydantoin and carbamazepine, Folia. Psychiat. Neurol. Jap., 22: 107-119, 1968.

1541. Shibasaki, H. and Kuroiwa, Y., Painful tonic seizure in multiple sclerosis, Arch. Neurol., 30: 47-51, 1974.

Weintraub, Megahed and Smith, New York State Journal of Medicine (1970)710 describe three patients with multiple sclerosis presenting with spasticity affecting the flexor muscles of the forearm. In two patients, the use of PHT resulted in increased strength and ability to move the extremities. In the third case quinine resulted in slight improvement in strength.

710. Weintraub, M. I., Megahed, M. S., and Smith, B. H., Myotonic-like syndrome in multiple sclerosis, New York J. Med., 70: 677-679, 1970.

Berger, Sheremata and Melamed, Archives of Neurology (1984),2322 report the use of PHT in the treatment of four patients in whom paroxysmal dystonia was the initial manifestation of multiple sclerosis. Three of the patients had a good response to PHT.

2322. Berger, J. R., Sheremata, W. A., Melamed, E., Paroxysmal dystonia as the initial manifestation of multiple sclerosis., Arch. Neurol., 4 1; 747-50, 1984.

Spasms, Other

Minaker, Flier, Landsberg, Young, Moxley, Kingston, Meneilly and Rowe, Archives of Neurology (1989), 3220 describe the clinical and metabolic effects of a therapeutic trial of phenytoin in three patients with the syndrome of insulin resistance, acanthosis nigricans, and acral hypertrophy. These patients and four healthy controls underwent tests of oral glucose tolerance and insulin receptor binding before and after therapy with phenytoin (300 mg/day). In addition, the euglycemic insulin infusion technique was used to examine the influence of phenytoin on whole-body glucose utilization, potassium homeostasis, and insulin clearance in the patients and controls.

For all three PHT-treated patients, muscle cramps dramatically improved. Both the frequency and severity of cramps diminished within 2 days of therapy in each case. In patients 1 and 3, cramps were virtually eliminated during a follow-up period of more than 1 year. In patient 2, the cramps improved, but were not eliminated entirely. Glucose tolerance and several metabolic markers of carbohydrate economy improved in two of the three patients. There were no changes in any of these characteristics in the normal control subjects. No adverse effects of phenytoin were observed in the patients or control subjects. The authors suggest that phenytoin is useful in the treatment of muscle cramps associated with this syndrome and may be useful in the therapy of the associated defects in carbohydrate metabolism.

3220. Minaker, K.L., Flier, J.S., Landsberg, L., Young, J.B., Moxley, R.T., Kingston, W.J., Meneilly, G.S., Rowe, J.W., Phenytoin-induced improvement in muscle cramping and insulin action in three patients with the syndrome of insulin resistance, acanthosis nigricans, and icral hypertrophy, Arch. Neurol., 46: 981-5, 1989.

Jansen, Joosten and Vingerhoets, Acta Neurologica Belgica (1992), 3221 report on five patients with neuromuscular disorders, who were experiencing frequent, severe muscle cramps. Two patients were treated with phenytoin. One patient had a six-year history of increasing severity and frequency of calf and foot cramps. In addition, he was experiencing almost continuous involuntary vibratory sensations in his muscles. Neurological examination, including electromyography and concentric needle investigation, confirmed the presence of continuous generalized fasciculations in his leg musculature, especially the calves. Prior treatment with multivitamins and physical therapy had brought no relief. A three-month trial with oral phenytoin reduced his complaints, including the severe cramping, substantially. The restless moving sensations in his legs disappeared, as did his calf hypertonicity. A second patient with incapacitating muscle cramps also benefited greatly from a trial of oral phenytoin.

3221. Jansen, P.H., Joosten, E.M., Vingerhoets, H.M., Muscle cramp as a feature neuromuscular disease - five neuromuscular disorders, accompanied by frequent muscle cramps, Acta. Neurol. Belg., y2(3): 138-147, 1992. v

Tetanus

Rodriguez, Perez, Quintero, Hernandez, Macias, Chiapa and Andrade, European Journal of Clinical Investigation (1984),2913 reported that intravenous PHT was rapidly effective as antispasm therapy in eighteen patients with severe tetanus. Substantial amounts of PHT were used in combination with the usual antibacterial and antitoxin measures. After the spasms were under control, the patients were watched, carefully, twenty-four hours a day, and additional intravenous PHT was given promptly to keep the spasms under control. The authors noted that PHT did not sedate the patients or depress respiratory function, as did other drugs they used to control spasms, and the need for respiratory support was decreased. No cardiovascular, sympathetic or autonomic disturbances, frequently seen in these patients, occurred. Compared with the authors’ experience, tetanus-related mortality decreased markedly, as did hospitalization time. Additional unpublished data from Mexico, Brazil and India give further indication of the usefulness of PHT against this disease. It is reported that large amounts of intravenous PHT may be needed in the acute stage (1500 mg a day or more in an adult is not unusual). Dosage depends on patient condition. When contractions recur, more PHT is indicated promptly. Later, when the bacteria and toxin are under control, less PHT should be needed. It is reported that PHT can be used in combination with other medications commonly used in the treatment of tetanus.

See also Basic Mechanisms of Action: Muscle section.

2913. Rodriguez-Noriega, E., Perez-Ruvalcaba, J. A., Quintero-Perez, N. P., Hernandez-Bugarin, O., Macias-Hernandez, O., Chapa-Alvarez, J. R., Andrade-Perez, J. S., The effect of phenytoin on muscle spasms and the hyperactive sympathetic syndrome of tetanus, Eur. J. Clin. Invest., 14; 36, 1984.

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