J. Kiffin Penry

Prevention of intractable partial seizures by intermittent vagal stimulation in humans : preliminary results

Summary: Intermittent stimulation of the vagus nerve in four patients resulted in complete seizure control in two, a 40% reduction of seizure frequency in one, and no change in seizure frequency in the other. Side effects (hoarseness, stimulation sensation in the neck, and hiccups) were transient and occurred concomitantly with stimulation. All patients tolerated increasing stimulation parameters well. The results, however, are inconclusive because of the brief duration (6–12 months) of follow‐up. Vagal stimulation represents a novel approach for seizure control in patients who have intractable epilepsy, but additional studies are needed to clarify the efficacy and safety of the procedure and to define selection criteria for patients.

Some clinical and EEG aspects of benign juvenile myoclonic epilepsy.

Summary: Twelve patients with benign juvenile myoclonic epilepsy (BJME) representing 4% of our population of epileptics (n = 275) are presented. Only two patients (17%) had myoclonic jerks as the only seizure type. Seven (58%) had generalized tonic‐clonic seizures (GTCS) and myoclonus. Three patients (25%) had absence seizures (AS), GTCS, and myoclonic jerks. Electroencephalographic evidence of photosensitivity was found in four (33%). Auditory precipitation of seizures was found in one patient. As is the case with other primary generalized epilepsies, the onset of BJME seems to be age specific. In our series the mean age of onset in years was 4.3 for AS, 14.75 for myoclonic jerks, and 16.4 for GTCS. It took an average of 8.5 years from the onset of BJME (range, 2–20 years) and 6.5 years from the onset of GTCS (range, 2 months‐6 years) until the condition was properly recognized. Five patients experienced at least one episode of myoclonic status epilepticus. Generalized, paroxysmal, symmetric poly spike and slow wave discharges are the typical EEG finding. These complexes, however, showed considerable interpatient variability. Sleep deprivation proved to be the most valuable activating procedure. Valproic acid monotherapy effectively controlled myoclonic jerks as well as associated GTCS in most patients.

Juvenile Myoclonic Epilepsy: Long‐Term Response to Therapy

Summary: Data from 50 patients with juvenile myoclonic epilepsy (JME) were analyzed retrospectively to assess the response to drug therapy–long‐term seizure control, relapse rates, and confounding factors in seizure recurrence. Valproate is the only available antiepileptic drug that has been shown to be effective in controlling the generalized seizure components of JME–myoclonic, tonoclonic, and absence seizures–without significant side effects. Data were collected using the EpiMonitor software and represented case follow‐up from 2 months to 9 years. Forty‐three patients (86%) were seizure free for at least 1 year; 25 patients (50%) relapsed at some point during follow‐up. Relapses were precipitated most frequently by fatigue, noncompliance, stress, sleep deprivation, and alcohol consumption. With accurate diagnosis and appropriate therapy, seizures in JME can be adequately controlled, although JME is a chronic disorder that may require lifelong therapy. To minimize relapse, patient management must also focus on patient lifestyle to eliminate or control lifestyle‐associated precipitants of seizure relapse.

Clinical and EEG Asymmetries in Juvenile Myoclonic Epilepsy

Summary: We reviewed records of 85 patients with juvenile myoclonic epilepsy (JME) for significant asymmetries in clinical seizures or the EEG. We noted asymmetries in 26 of 85 patients (30.6%). Only 2 patients had both clinical and EEG asymmetries; 12 had clinical asymmetries and 12 had EEG asymmetries exclusively. Analysis of patients with and without asymmetries showed no statistically significant differences in comparisons of sex, age at seizure onset, family history of epilepsy, seizure type, or response to treatment. The delay in diagnosis was greater in JME patients with asymmetries (9.5 years) than in JME patients with no asymmetries (7.5 years), but this difference was not statistically significant. Fourteen of the 26 patients with asymmetries (53.8%) were initially misdiagnosed as having partial seizures. Asymmetries in JME patients are not only common, but are also a frequent cause of misdiagnosis.

Valproate-Associated Pancreatitis

Summary: To assess the clinical characteristics of valproate (VPA)‐associated pancreatitis, information from three sources was gathered: (a) a survey among 507 physicians with a special interest in treatment of epilepsy, (b) a review of the authors’ patient population, and (c) a review of the literature. Of 366 physicians answering the survey, 53 (14.5%) reported a case of pancreatitis. Thirty‐nine cases were available for review (24 from the medical literature, 12 from the survey, and 3 from the authors). Pancreatitis appeared to be more frequent in young persons (mean age 16.4 years) but may occur at any age. The highest risk appears to exist during the first months of treatment: 43.8% of the cases developed during the first 3 months, and 68.8% developed during the first year. Seventy‐six percent of patients were receiving polytherapy, and 41% had some form of associated chronic encephalopathy. In most patients, the reaction was rapidly reversible when VPA was discontinued. It was severe in 6 patients, with 3 deaths reported. Rechallenge with VPA was attempted in 9 patients, with a high incidence of relapses. Asymptomatic elevation of serum amylase in patients receiving VPA was reported by 40 (10.9%) of the physicians surveyed. Awareness of the problem and early discontinuation of VPA may be effective in preventing serious reactions.

Psychogenic seizures in adults: a longitudinal analysis

The clinical characteristics, psychosocial background, neuropsychological testing, clinical and social outcome were analysed in 93 adults with psychogenic seizures (PS). Thirteen (14%) were males and 80 (86%) were females. Mean age was 31.7 years (range 16 to 55 years). Lack of responsiveness associated with motor activity was the most common finding. Neuropsychological testing done in 46 cases revealed hysteroid traits and coping mechanisms and depression to be the most prevalent underlying problems. History of sexual abuse was evident in 10 (10.7%) cases. Social impact analysis revealed that of 62 patients who were working at the onset of PS, 34 were not working at the time of the diagnosis of PS. In 25 cases, PS were the reason for not working. After a mean follow-up of 60.7 months done in 63 patients, 16 (25.4%) patients were seizure-free. There were no obvious significant predictors of poor prognosis.

Reduction of Steady-State Valproate Levels by Other Antiepileptic Drugs

Summary: Steady‐state plasma valproate (VPA) levels were analyzed in 37 children after 6 weeks of VPA therapy. Twenty‐six patients were receiving other antiepileptic drugs in addition to VPA (experimental group). Eleven patients who received VPA alone served as controls. The mean VPA dose was not statistically different for the two groups (experimental group, 35.4 mg/kg/ day, 11.6 SD; control group, 31.1 mg/kg/day, SD 6.6) The mean plasma VPA level was significantly lower for the experimental group (63.0 μg/m1, SD 21.8) than for the control (99.3 μg/m1), SD 23.3) (p < 0.01). VPA levelrdose ratio (LDR) was also reduced in the experimental group (1.92, SD 0.75) as compared to controls (3.26, SD 0.65) (p < 0.01). Within the experimental group the VPA levels and VPA LDR were significantly reduced in patients receiving either phenytoin or phenobarbital. The data suggest that other antiepileptic drugs significantly alter the steady‐state level to dose relationship for VPA.

Clinical management of recurrent postictal psychosis

Abstract Although there are numerous reports of interictal psychosis in epileptic patients, there are few studies describing the longitudinal course and treatment of postictal psychosis. The goal of this study was to define the clinical features, natural history, and possible interventional methods in a group of patients with complex partial seizures and postictal psychosis. We studied seven patients who manifested psychotic behavior following an increase in their seizure frequency. Mean follow-up was 83 months. Patients underwent neuropsychiatric testing, cranial magnetic resonance imaging, and extensive EEG evaluation. All but one patient had severe epilepsy. An increased number of seizures was followed by a brief period of lucidity and then psychosis, which lasted between 2 and 14 days and tended to recur (mean, one episode every 4 months). EEGs done during the psychotic episodes generally demonstrated a mild diffuse background slowing without evidence of ictal epileptiform discharges. Evaluation between episodes revealed no persistent psychiatric features. The patients rarely required hospitalization or neuroleptic medications. Patients usually responded to mild sedation, close observation, and a supportive environment.

Quality of Life in Epilepsy: The Clinician's View

Summary: Quality of life in patients with epilepsy may be impaired by seizures, side effects of medication, and psychosocial problems. Doctors tend to focus their attention on managing the seizures and the side effects, but may not be meeting all of the patients needs because of differences between their perception of these concerns and the patients. Further, psychosocial problems often are addressed only superficially or not at all during office visits. The challenge is to integrate quality‐of‐life issues into clinical practice and to better assess the patients perception of the disorder, the seizures, and the medications, as they impact on cognitive function, emotional well‐being, and social and economic functioning.

Valproate Monotherapy in 30 Patients with Partial Seizures

Summary: This retrospective pilot study describes 30 patients diagnosed and treated for complex partial seizures (CPS) and simple partial seizures (SPS) with and without generalization who received valproate (VPA) monotherapy after lack of response or allergic reaction for car‐bamazepine (CBZ), phenytoin (PHT), or phenobarbital (PB). Seizures were tabulated daily on seizure calendars by the patients. Three time periods were examined for seizure frequency, 90 days before VPA treatment and 90 and 180 days after VPA treatment. Twenty‐two were “controlled” or “improved” (reduction of seizure activity by &51%) 6 months following the initiation of VPA. VPA was particularly effective in 17 patients who had secondarily generalized tonic‐clonic seizures (GTCS) as a subtype of partial seizures. Failure of response to VPA in eight patients appears to be related to their type of partial seizure (SPS or CPS alone, without GTCS) and duration of uncontrolled recurrent seizures. Etiology and compliance were not related to treatment failure. This study supports the need for a double‐blind controlled trial with VPA in patients with partial seizures.