Withdrawal Of Valproate Research Articles

The use of lamotrigine in juvenile myoclonic epilepsy

Lamotrigine (LTG) was used in 12 patients with juvenile myoclonic epilepsy (JME) who either had sodium valproate (VPA) side effects or did not wish to take VPA. Five patients are now fully controlled on LTG monotherapy. Side-effects were corrected by VPA withdrawal or reduction except for severe weight gain. In three patients it was not possible to withdraw VPA due to the re-emergence of myoclonus, suggesting LTG-VPA synergism. Two patients had successful pregnancies whilst taking LTG. Lamotrigine is a useful alternative in the management of JME.

Reversible dementia and apparent brain atrophy during valproate therapy.

Two children developed severe cognitive and behavioral deterioration suggestive of a degenerative disease while being treated with sodium valproate for idiopathic, localization-related epilepsy with centrotemporal spikes. Magnetic resonance imaging revealed marked central and generalized cortical and cerebellar atrophy. In both patients, clinical symptoms and signs cleared in a few weeks following valproate withdrawal. The magnetic resonance imaging appearance improved within 3 months in 1 of the patients and normalized in both after 6 and 12 months. No metabolic changes were associated with the clinical or imaging abnormalities. Although the mechanism of this rare idiosyncratic complication of valproate therapy is unknown, we advocate discontinuing valproate therapy in all epileptic patients with neuromental deterioration or brain atrophy of unknown etiology.

Negative myoclonus during valproate-related stupor. Neurophysiological evidence of a cortical non-epileptic origin

We retrospectively reviewed clinical and neurophysiological data of 6 epileptic patients who developed negative myoclonus and stupor a few days after introduction of valproate (VPA). Prompt remission of clinical signs and symptoms followed valproate withdrawal. We attempted to elucidate the pathophysiological mechanism of VPA-induced stupor and provide further polygraphic and backaveraging EEG documentation of negative myoclonus. During VPA-induced stupor electroencephalograms revealed posterior background slowing in all patients. Interictal epileptiform discharges were present in 3 patients. In all 6 patients close examination using simultaneous video-polygraphic recording showed negative myoclonus which was not time-related to lateralized spike discharges. In 2 of 3 patients with no spikes on conventional EEG who underwent backaveraged EEG recordings we detected a large (5 μV) cortical positive-negative wave time-locked (30–40 msec) with the postural modification of the contralateral wrist. This cortical potential was similar to that observed in patients with asterixis secondary to metabolic or toxic encephalopathies. In one patient i.v. administration of 10 mg diazepam did not modify this cortical potential and did not reverse the clinical manifestations. In all patients the only abnormal laboratory finding was an increased level of venous ammonemia. Our findings are against an epileptic origin of VPA encephalopathy and provide further argument in favour of a cortical non-epileptic mechanism mediating negative myoclonus. Benzodiazepines should be avoided in the management of this condition.

Effects of discontinuation of individual antiepileptic drugs on mood

AbstractForty‐four patients undergoing withdrawal of phenytoin, carbamazepine or sodium valproate and 21 patients on stable medication were assessed using standardised, objective ratings of mood, notably the Mood Adjective Checklist and the Middlesex Hospital Questionnaire. The study followed a prospective, double‐blind, placebo‐controlled design. Patients' mood was assessed before and after drug withdrawal with an additional assessment being made four weeks after the completion of withdrawal. The number of seizures, serum anticonvulsant levels and EEGs were assessed at the same time as the mood assessments. In addition, the potential influence of life events on mood was monitored.Anxiety, as measured by the Middlesex Hospital Questionnaire, increased on withdrawal of carbamazepine. This change was not related to seizure rate. Withdrawal of phenytoin or sodium valproate did not appear to have an impact on mood. Concomitant changes in serial EEGs are discussed in relation to the changes in mood.

Nonketotic hyperglycinemia: Treatment with NMDA antagonist and consideration of neuropathogenesis

Patients with neonatal-onset nonketotic hyperglycinemia have high-glycine content in cerebrospinal fluid (CSF) which is believed to be a cause of intractable neurologic manifestations. The glycine receptor was believed to be inhibitory in the central nervous system; however, a newly discovered glycine receptor is of the excitatory N-methyl- d-aspartate (NMDA) receptor type, which cannot be antagonized by strychnine. The NMDA receptor antagonist, ketamine, was administered to a patient with nonketotic hyperglycinemia; he demonstrated some improvement in hyperirritability, voluntary movement, and electroencephalographic findings. Strychnine therapy had been administered before this trial of NMDA antagonist, but without improvement. The respiratory condition improved with the reduction of the CSF glycine level after withdrawal of sodium valproate. Our findings indicate that high-glycine content in CSF may affect the brain in different ways via NMDA and classic glycine receptors.

Variant acute intermittent porphyria in a child

A child who was grossly malnourished and who showed increased excretion of porphyrin and porphyrin precursor had normal activity of erythrocyte porphobilinogen deaminase (EC 4.3.1.8) and leukocyte protoporphyrinogen oxidase (EC 1.3.3.4). Clinical symptoms, coincident with the excretion of rose-colored urine, were consistent with the diagnosis of an acute porphyria. The disease resolved spontaneously after the withdrawal of carbamazepine and sodium valproate and the commencement of parenteral nutrition with subsequent carbohydrate loading. In addition to normal concentrations of enzyme activities, the patient is unusual in presenting before puberty and in having no family history of porphyria.

Side effects of carbamazepine, valproate and clonazepam during long-term treatment of epilepsy.

Side effects of carbamazepine (CBZ), valproate (VPA) and clonazepam (CZP) are rare during long-term use but rather common and usually transient during the early phases of treatment. The usual side effects of CBZ are drowsiness, dizziness, and diplopia, which are dose dependent in long-term use, but CBZ does not seem to cause cognitive disturbances, as do phenobarbital and phenytoin. Other reactions to CBZ may include leukopenia, hyponatremia, disturbances of vitamin D metabolism and fortunately rarely, agranulocytosis and hepatitis. Use of VPA can lead to gastrointestinal discomfort, weight gain, hair loss, tremor and sedation, but these side effects are rather uncommon, mild, and transient during VPA monotherapy. Potentially hazardous reactions such as hepatitis and pancreatitis have occurred in a few patients on VPA, generally with multidrug therapy. Some of the side effects are dose related. They infrequently lead to withdrawal of VPA. Side effects limited to initiation of CZP therapy include drowsiness, ataxia, and behavioral changes; they are usually transient but can lead to dose reduction or even withdrawal of the drug. Except for development of tolerance, CZP seems to be practically free of long-term side effects.

Stuporous Episodes During Treatment with Sodium Valproate: Report of Seven Cases

Of 13 patients with complex partial seizures who experienced stuporous states during treatment with sodium valproate (VPA), 4 received VPA only, 4 VPA and phenobarbital (PB) and 5 VPA, PB, and a third anticonvulsant. Seven cases were described in detail. Side effects-stupor or confusion-appeared a few days after efficacious drug plasma levels were attained, persisted until therapy was readjusted, and disappeared 24 to 72 h after VPA withdrawal. Therapeutic trials established the role of VPA in the onset of stuporous states. The adverse effects of VPA were potentiated by the concomitant administration of other anticonvulsants. Stupor was not due to VPA overdoses, and plasma concentration of the drugs were not correlated with the electroclinical signs. The EEG showed spike and wave discharges or continuous sharp theta and delta waves persisting during VPA treatment. The fact that all 13 stuporous, VPA-treated patients were subjected to partial seizures with complex symptomatology, and none were cases of generalized epilepsy, together with the observations that the disturbances of consciousness started with focal symptoms and EEG signs resembling those of spontaneously occurring partial seizures, suggest that VPA given alone or in association with other antiepileptics has a paradoxical epileptogenic effect in certain forms of epilepsy.