Methsuximide Therapy of Juvenile Myoclonic Epilepsy

Seizure 1996; 5:47-50

Methsuximide therapy of juvenile myoclonic epilepsy

DANIEL L. HURST

Department of Neurology, Texas Tech University Health Sciences Center, Lubbock, Texas, USA

Currently valproic acid is considered to be the drug of first choice for juvenile myoclonic epilepsy (JME) resulting in a 70-90% control rate for all seizure types associated with JME. In those situations where valproic acid fails to control seizure activity, results in unacceptable side-effects, or is declined due to potential side-effects, an alternative effective monotherapy would be desirable. Five adolescent female patients were placed on methsuximide for JME. All five patients have been seizure free with the use of methsuximide and four out of five are now on methsuximide monotherapy with good success. C.L. has now had complete seizure control on methsuximide monotherapy, a total of 1200 mg a day, for 7 years with the exception of one seizure event occurring on an attempted discontinuation of methsuximide after being 5 years seizure free. Methsuximide monotherapy as demonstrated in these five patients is an effective treatment for JME.

Key words: methsuximide; juvenile myoclonic epilepsy; valproic acid; myoclonic seizures.

INTRODUCTION METHOD

Juvenile myoclonic epilepsy (JME) is an epileptic All medical records in the Texas Tech University syndrome which in most cases has the onset Health Sciences Center Neurology Clinic were during adolescence of the following three seizure reviewed for a diagnosis of JME and treatment types: (1) myoclonic jerks, frequently bilateral with methsuximide. This was a retrospective involving both arms, predominantly seen upon review covering a period of nine years. Inclusion awakening in the morning; (2) tonic clonic events criteria for the diagnosis of JME were typical case frequently in association with myoclonic jerks; histories, an established clinical diagnosis of JME, and (3) infrequent absence episodes ~-5. Prior to and supportive EEG data. Supportive EEG data the introduction of valproic acid for the treatment included (1) normal background activity, and (2) of JME, a variety of other medications were used generalized polyspike-wave complexes, (3) 4- with only partial Success 6"7. With the introduction 6 Hz generalized spike wave activity, (4) 3 Hz of valproic acid a high percentage, approximately generalized spike wave activity, or (5) irregular 70-90%, of patients with JME have seizure spike wave complexes. control 3"8. Some patients fail to have their seizures controlled related to side effects from valproic acid 9. Particularly in adolescent females, RESULTS weight gain may be a problem with valproic acid resulting in its discontinuation ~°. When valproic Five females with JME on methsuximide were acid monotherapy fails to achieve complete identified. Four out of the five are currently on seizure control, other anticonvulsants may be methusximide monotheraphy. One individual is added in a two drug combination. Methsuximide on treatment with valproic acid in addition to presents a unique anticonvulsant profile which methsuximide, but in the past had been treated potentially would allow for the treatment of JME successfully with methsuximide monotherapy. in monotheraphy. Methsuximide is known to The therapeutic approach was changed in this treat all three seizure types seen in JME ~~-~3. Five individual due to a complaint of sedation. The patients are presented who have had meth- patient felt the combination of valproic acid, suximide used in monotherapy for the treatment which failed in monotherapy, with methsuximide of JME. gave satisfactory seizure control with fewer

1059-1311/96/010047 + 04 $12.00/0 © 1996 British Epilepsy Association 48 D.L. Hurst side-effects. These five patients are being con- time of the seizure but reported the increased tinued on methsuximide long-term (see Table 1). stress of final exams. The methsuximide was At this time all five patients are under good restarted at 1200mg a day and the patient has seizure control. been completely seizure free since that time (for 2 years). Current plans are to continue the methsuximide as prescribed for an indefinite time CASE HISTORY period.

C.L. is now a 22-year-old female. She was first seen at the age of 13 years for a history of having DISCUSSION had two tonic-clonic seizure events lasting approximately 5 minutes each. Her initial seizure manifestation occurred 3 months earlier, at which Methsuximide is primarily considered a second time she was noted to have bilateral jerks of her line anticonvulsant for absence epilepsy because arms in the morning which caused her to drop ethosuximide is more effective than meth- whatever she was holding. She was described as suximide in the treatment of absence seizures t4. alert and able to talk during these episodes. Her Methsuximide, however, has a wider spectrum of second tonic-clonic seizure, occurring 2 days anti-seizure activity than ethosuximide'~"2 prior to her initial evaluation, was preceded by Methsuximide is an effective adjunctive therapy bilateral arm jerks during which she stated, 'Oh, for other generalized epilepsies, particularly in Mom, I can't stop them from shaking' and then combination with valproic acid ~5. Methsuximide proceeded directly into a tonic-clonic seizure. has also been documented to be successful in The patient's past medical history was unremark- controlling myoclonic epilepsy or myoclonic able. Family history was significant for a 20-year- atonic seizures in some patients ~3't~'~7. old female sibling with epilepsy. Review of Valproic acid is the only currently marketed systems was otherwise unremarkable. Her neuro- anticonvulsant which is considered both safe and logic examination was normal. An EEG was effective in controlling all the individual seizure obtained and showed a generalized spike wave types, namely, generalized tonic-clonic, myo- discharge at 5 Hz. A CT scan with and without clonic, and absence seizures seen in JME ~s-2°. contrast was normal. She was given a diagnosis of Therefore, it is not surprising that valproic acid JME and methsuximide, 750mg per day, was has been found to be an effective treatment for started. This resulted in a normethsuximide level JME as an epilepsy syndrome 2'. Those anticon- of 16/zg/ml; therapeutic range 10-40/zg/ml. vulsants which treat partial and tonic-clonic When a few further myoclonic jerks were noted, seizures alone fail to address the myoclonic and the dosage was increased to 1200mg a day, absence components of JME. Likewise those resulting in a normethsuximide level of 30/,tg/ml. medications, such as clonazepam and tri- After five years of complete seizure control on methadione, which treat absence and myoclonic methsuximide, a follow up EEG was obtained seizures but do not control primary generalized which was normal and the patient began a slow tonic clonic seizures, are not effective as taper off methsuximide. After being completely monotherapy 2''22. An additional effective medi- off methsuximide for two weeks, the patient had a cation for treatment of JME, either in mono- tonic clonic seizure lasting approximately 30 therapy or as an adjunctive to valproic acid would seconds. The patient denied any illness at the be very desirable. Currently no series has been

Table 1: Patient treatment group Patients l 2 3 4 5

Age 17 years 23 years 22 years 25 years 16 years Sex female female female female female JME onset 12 years 15 years 13 years 15 years 12 years Seizure type M, A, T M, A, T M, T M, A, T M, A, T EEG pS&W. pS&W pS&W 3HzS&W 5HzS&W Rx MS MS, VA MS MS MS Dose 1 200 1 050 I 200 900 900 Seizure free 2 years 3 years 6 years 6 months 6 months M, Myoclonic seizures; A, absence seizures; T, tonic-clonic seizures; MS, methsuximide: VA, valproic acid; pS & W, polyspike and wave: S & W, Spike and wave. Methsuximide therapy of juvenile myoclinic epilepsy 49

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