Use of Acetazolamide as an Adjunct to Carbamazepine in Refractory Partial Seizures

Acetazolamide (Diamox) (AZM) was evaluated as an adjunct to carbamazepine (CBZ) monotherapy in 48 refractory partial seizure patients at a tertiary care referral center. Patient ages ranged from 6 to 64 years (average 28 years). Seizure frequencies for the pre-AZM baseline period (CBZ monotherapy) were compared with the seizure frequencies at different daily doses of AZM. Patients with a 50% decrease in seizure frequency were considered responders. Twenty-one patients were responders (44%) and three became completely seizure-free. Effective doses ranged from 3.8 to 22.0 mg/kg/day. Effective plasma concentrations ranged from 1 to 22 micrograms/ml in selected patients. Durations of response time to AZM ranged from 3 to 30 months (average 12.9 months). Three patients lost response, one temporarily. Side effects were seen in 10 patients, requiring discontinuation in three.     

Topiramate Monotherapy for Partial Onset Seizures

Summary: Purpose: Evaluation of topiramate (TPM) as monotherapy in patients with uncontrolled partial onset seizures.
Methods: A total of 48 patients were evaluated in a doubleblind, parallel-group trial. During a 56-day baseline period, patients had at least eight partial onset seizures while being treated with one or two standard antiepileptic drugs (AEDs). After 1–2 weeks of open-label treatment with TPM 100 mg/day, patients were randomly assigned, in equal proportions, to receive double-blind therapy with TPM 100 or 1,000 mg/day in a 5-week conversion and an 11-week monotherapy period. The study endpoint was completion of 112 study days (success) or fulfillment of one or more exit criteria: doubling of average 28- day or highest 2-day baseline seizure rate, a generalized tonic-clonic seizure (GTCS) if none had occurred at baseline, or significant prolongation of generalized seizure duration.
Results: Time until exit was longer (p = 0.002) and success frequency was higher (p = 0.005) with TPM 1,000 as compared with 100 mg/day. Seizure-rate reductions of 50, 75, or 100% were achieved by 46, 25, and 13% of the 1,000-mg/day group, respectively, as compared with 13, 8, and 0% of the 100-mg/day group, respectively. Most adverse events (AE) were mild or moderate in severity.
Conclusions: Monotherapy with TPM 1,000 mg/day for partial onset seizures with or without secondarily generalized seizures was effective, with a favorable safety profile.     

Partial Motor Epilepsy with "Negative Myoclonus"

Three children had both nocturnal unilateral motor seizures and daytime ipsilateral "negative myoclonus" which occurred so frequently that it resembled asterixis. Neurophysiologic studies demonstrated lateralized spike discharges that were time-locked to postural lapse in the contralateral outstretched arm. The clinical course was characterized by good seizure control with benzodiazepines.     

Carbamazepine Versus Phenobarbital for Partial Onset Seizures in Children

Thirty-nine children were treated with either phenobarbital (PB) or carbamazepine (CBZ) for newly diagnosed partial onset seizures. Drug selection was randomized in 33 subjects. Parents and the psychologist evaluating the child were blind to drug identity. Psychometric and behavioral evaluations were done at intake and at 6- and 12-month follow-ups. There were no significant differences between drugs in effect on behavior or cognitive function. CBZ caused more systemic problems. There was a trend toward better seizure control with CBZ, but this was not statistically significant. Although individual children in each group had changes in behavior or cognitive status, neither group changed significantly, in either acute or chronic follow-up.     

Dissociation in Epilepsy and Conversion Nonepileptic Seizures

Summary: Purpose: We examined the dimensionality of the item content of the Dissociative Experiences Scale (DES) in relation to the clinical diagnosis of conversion nonepileptic seizures (C-NES) versus complex partial epilepsy (CPE).
Methods : The DES was administered to a sex- and agematched sample of 132 patients with C-NES and 169 with CPE and was factor analyzed with principal components analysis (PCA) with varimax rotation.
Results : The mean total DES score was 15.1 in the C-NES group and 12.7 in the CPE group (p = 0.079). The factors obtained by PCA differentiated the CPE and C-NES groups more strongly than did the total DES score. The factor accounting for the most variance, interpreted as "depersonalizationderealization," was significantly greater in C-NES than CPE (p = 0.005). An "absorption-imaginative involvement" factor, which included some of the clinical features of posttraumatic stress disorder was elevated only in subjects reporting histories of childhood abuse (p = 0.001) regardless of the diagnosis of CPE or C-NES. An "amnestic" factor appearing to represent memory problems related to neurologic impairment showed a trend toward elevation in CPE (p = 0.056) and may have confounded the CPE versus C-NES distinction using total DES scores.
Conclusions : The DES has separate underlying dimensions that appear to relate distinctively to depersonalization and derealization, childhood trauma, and neurologic impairment. The heterogeneous item content of the DES is a potential confound that should be appreciated when this instrument is used to study dissociation in neuropsychiatric populations.     

De Novo Psychogenic Nonepileptic Seizures After Epilepsy Surgery

Summary: Purpose: The occurrence of de novo nonepileptic seizures (NES) after epilepsy surgery have been reported only twice in the literature (one article and one abstract).
Methods: We report three patients whose de novo NES were documented by video-EEG telemetry after epilepsy surgery. These patients were drawn from a sample of 166 consecutive patients who underwent epilepsy surgery at our center between 1989 and 1996.
Results: Two patients became seizure free after surgery, and one had significant improvement of her seizures. The interval between the date of surgery and the development of the symptoms was variable (8, 10, and 47 months, respectively). The clinical phenomena of NES differed from those of the epileptic seizures preceding surgery. Their diagnosis had not been suspected in two patients before the diagnostic video-EEG monitoring study. After the diagnosis of NES, spells stopped in two patients and recurred rarely in one.
Conclusions: We conclude that de novo NES appears to occur rarely after epilepsy surgery. Given that the possibility of NES was suspected in only one patient, its incidence after surgery may be higher than so far reported. Physicians should therefore consider NES in the differential diagnosis of recurrent seizures after a seizure-free period after epilepsy surgery.     

De Novo Nonepileptic Seizures after Cranial Surgery for Epilepsy: Incidence and Risk Factors

We evaluated the incidence of de novo nonepileptic seizures (NES), confirmed by EEG monitoring, after cranial surgery for intractable epilepsy in 228 surgery patients. Eight patients (3.5%) developed de novo NES at 6 weeks to 6 years (mean, 23 months) after surgery. Six had undergone a resection and two complete callosotomy. They did not differ from a larger surgical group with respect to sex, side of surgery, age at onset, or duration of epilepsy, Full Scale Intelligence Quotient, seizure outcome, or preoperative interictal dysphoric disorder (IDD), but there was a significant excess of postoperative IDD and operative complications (bone flap infections); the callosotomy patients had marked hemisphere disconnection syndromes. Repeat EEG videotelemetry monitoring is important to detect postoperative NES so that inappropriate therapeutic measures may be avoided. Risk factors may be exacerbation or persistence of IDD and surgical complications. The etiology of NES is discussed.     

Early-Childhood Progressive Myoclonus Epilepsy Presenting as Partial Seizures in Dentatorubral-Pallidoluysian Atrophy

Summary: Purpose: We explored the characteristics of epileptic seizures of progressive myoclonus epilepsy (PME) in 2 brothers with dentatorubral-pallidoluysian atrophy (DRPLA).
Methods: We obtained the case history of the siblings and ictal and interictal EEGs. Postmortem examination or demonstration of elongated CAG repeat in the gene for DRPLA was used to confirm the diagnosis.
Results: Two Japanese siblings developed PME characterized by versive or himiclonic seizures with or without secondarily generalized tonic-clonic convulsions. The elder brother regressed mentally and exhibited increasing spasticity after age 1 year. Myoclonus and seizures developed at age 4 years. The younger brother had shown psychomotor retardation before age 4 years, when he began to deteriorate further neurologically as the elder brother had. He also developed myoclonus and seizures at that age. Seizures in both patients remained partial until their deaths at ages 19 and 15 years, respectively. Ictal EEG verified partial onset of seizure evolving to generalized tonic-clonic seizure (GTCS). Interictal EEGs showed multifocal paroxysmal discharges with little or no diffuse paroxysms. Postmortem examination or genetic study confirmed the diagnosis of DRPLA.
Conclusions: Seizures of patients with DRPLA may present as partial seizures in children with early-onset PME.     

Anticonvulsant Action of Oxcarbazepine, Hydroxycarbamazepine, and Carbamazepine Against Metrazol-Induced Motor Seizures in Developing Rats

Summary: Antimetrazol effects of carbamazepine (CBZ, 5, 12.5, 25, or 50 mg/kg), oxcarbazepine (OCBZ, 5, 10, 30, or 60 mg/kg), and hydroxycarbamazepine (HCBZ, the main human metabolite of OCBZ, 10, 30, or 60 mg/kg) were studied in 7–, 12–, 18–, 25–, and/or 90-day-old laboratory rats. No drug tested affected the incidence of minimal (clonic) metrazol seizures (mMs) in animals aged ≥18 days; in rats aged 7 or 12 days in which mMs are rare under control conditions, the incidence of mMs was increased by lower doses of CBZ and HCBZ. All drugs tested specifically abolished the tonic phase of major generalized tonic-clonic seizures (MMs) in a dose-dependent manner. In addition, CBZ and OCBZ were able to suppress all phases of MMs in the two youngest groups (7-and 12-day-old). There were no marked differences among the three drugs tested (CBZ, OCBZ, and HCBZ) on their action against metrazol-induced seizures during ontogenesis of rats; i.e., all these drugs appeared to possess an identical profile of anticonvulsant action.     

Absence Seizures and Carbamazepine in Adults

Summary: Carbamazepine (CBZ) therapy was associated with development of absence seizures in 4 adults with generalized epilepsy. Two patients had new appearance of absence seizures and 2 patients had recrudesence of remote absence seizures. The seizures abated after discontinuation of CBZ therapy or addition of ethosuximide (ESM) in 1 patient intolerant of valproate (VPA).     

Classification of Partial Epilepsies According to the Symptomatology of Seizures: Practical Value and Prognostic Implications

Among 1,000 outpatient epileptics who visited the Epilepsy Center of Bologna consecutively from 1974 to 1978, 596 cases of partial epilepsy (PE) were chosen, representing 62.9% of all cases classified according to the International Classification of epilepsies. Fifty-four of these cases (5.7%) of those classifiable) that were affected by benign infantile epilepsy with rolandic spikes were not analyzed further. The remaining cases were divided up into three groups based on the symptomatology of the seizures: (1) partial elementary epilepsy (PEE), 102 cases (10.8%); (2) partial complex epilepsy (PCE), 332 cases (35%); and (3) partial secondarily generalized epilepsy (PSGE), 108 cases (11.4%). The three groups were compared according to the parameters that distinguish recognized epileptic syndromes, in order to see whether they constitute autonomous nosographic entities. Among the three groups, significant differences did not arise with regard to the incidence of single lesional etiological factors, the age of onset of the epilepsy, the neurological context, and the general features of interictal EEG. PSGE instead differs significantly from the other two forms for the minor severity of the epilepsy at first examination and for its more favorable course: after at least 2 years of follow-up under treatment, the epilepsy appeared to be controlled in 60.6% of the cases with PSGE, in 31.6% of those with PEE, and in 37.5% of those with PCE (p less than 0.05). For those with PE, globally considered, only three parameters have a favorable prognostic value: the brief duration of the epilepsy at the first observation, the rarity of the seizures, and the presence of only one type of seizure.     

The Influence of Electroencephalographic Focus Laterality on Efficacy of Carbamazepine in Complex Partial and Secondarily Generalized Tonic-Clonic Seizures

Forty-five outpatients with chronic epilepsy with complex partial seizures (CPS) alone or associated with secondarily generalized tonic-clonic seizures (SGTCS) were treated with carbamazepine (CBZ) monotherapy. All patients had only a unilateral scalp electroencephalographic (EEG) focus. Left- (n = 29) and right- (n = 16) sided foci patients were comparable for age, sex, duration, and etiology of epilepsy as well as total and free CBZ serum levels. CBZ significantly improved CPS irrespective of the side of the EEG focus, whereas SGTCS were controlled for greater than 1 year in 15 of 19 patients with left focus and in three of 11 patients with right focus. When patients with poorly controlled seizures discontinued CBZ and changed to other therapies, they achieved a significant reduction in number of SGTCS, whereas the number of CPS was unchanged. The side of EEG focus seemed to be relevant to the control of SGTCS by CBZ. Interhemispheric neurotransmitter asymmetries may be involved in the EEG focus side-dependent CBZ response.     

Evidence That Emotional Maladjustment Is Worse in Men Than in Women with Psychogenic Nonepileptic Seizures

The purpose of this study is to examine the effects of gender on adjustment and cognition in patients with psychogenic nonepileptic seizures (NES) and on patients with epilepsy. We compared 57 women and 27 men, all at least 16 years old, with only NES as documented by long-term EEG-video monitor studies, to equal numbers of randomly selected women and men with only epileptic seizures. Variables examined included age, age of onset, education, scales from the MMPI, the WAIS-R, and the number of tests outside normal limits from the Neuropsychological Battery for Epilepsy. We found no significant differences in mean age, intelligence, or percentage of neuropsychological tests outside normal limits across the four groups. Women and men with NES had significantly later age of onset of attacks compared with subjects of either gender with epilepsy (26 years vs 13 years, P < 0.001) and men with NES had greater educational achievement than women with NES or patients with epilepsy (P < 0.02). However, the most important findings were seen on the MMPI. Men with NES exhibited significantly greater elevations on multiple scales (especially Hysteria, Depression, Hypochondriasis, Psychoasthenia, Schizophrenia) compared with men with epilepsy or women with either epilepsy or NES. We conclude that men with NES have significantly worse patterns of emotional adjustment, as measured by the MMPI, than women with NES or subjects of either gender with epilepsy.     

Facilitation of Infantile Spasms by Partial Seizures

Summary: We report 16 patients with infantile spasms in whom onset of the clusters of spasms appeared to be triggered by close temporal association with partial seizures. Common features included the presence of focal cerebral lesions in 12 infants (3 were classifiable as cryptogenic); all had partial seizures with EEG localization, clusters of bilateral spasms always preceded by partial seizures, and response to adrenocorticotropic hormone (ACTH) and traditional antiepileptic drugs (AEDs) generally was poor. Three had complete agenesis of the corpus callosum, which argues against interhemispheric callosal spread of focal discharges resulting in the generalized spasms. Surgical cortical resections were performed in 6 of the infants, with good outcomes. This group of patients supports a model in which the spasms, although probably generated at a subcortical level, are facilitated or possibly induced by focal discharges from cortical pathology.     

Double-Blind Withdrawal of Phenytoin and Carbamazepine in Patients Treated with Progabide for Partial Seizures

Of 30 patients who completed a study of progabide (PGB) as an add-on to both phenytoin (PHT) and carbamazepine (CBZ), 11 volunteered for a double-blind withdrawal protocol in which the PHT and CBZ were to be withdrawn. All patients were receiving 24-32 mg/kg/day PGB in combination with PHT and CBZ. Each patient was randomly assigned to withdrawal of either CBZ or PHT in the first block, and then withdrawal from the other in the second block in an attempt to achieve PGB monotherapy. Seizure occurrence was monitored by sequential analysis, and if a significant increase over baseline seizure frequency occurred, the dose of PGB was increased to a maximum of 45 mg/kg/day. If seizure frequency remained above baseline, the drug being withdrawn was added back and an attempt made to withdraw the other. The study was terminated if these adjustments were not successful in decreasing seizure frequency to baseline. At the conclusion of the study, three patients were being treated with PGB and PHT, two with CBZ and PGB, and six with all three. This study demonstrated the applicability of sequential analysis to antiepileptic drug trials.     

Awareness and Responsiveness During Partial Seizures

Summary: We examined the impairment of consciousness during partial seizures (PS) arising from various brain sites according to the operational definition of the international classification, i.e., altered awareness and/or responsiveness. The subjects were 142 patients who underwent intracranial EEG evaluation and subsequent resective surgery. First, the patients were examined to determine whether they usually had been partially or completely aware of their seizures. Second, spontaneous habitual seizures that had been videotaped with simultaneous intracranial EEG recording were reviewed to determine responsiveness and recall during ictal behavioral alterations. In all, 114 patients were partially or completely aware of their seizures. Patients who tended not to be aware of their seizures were those with frontal lobe epilepsy (FLE) with extensive epileptogenic regions on the language nondominant side and those with temporal lobe epilepsy (TLE) with seizure origin in the lateral cortex of the language dominant side. Of the 21 patients with FLE, 88 with TLE, and 4 with occipital lobe epilepsy, 7, 22, and 2 patients responded to stimuli during the seizure, respectively, but only 11 of the patients with FLE and none of the other patients could recall the stimuli applied during the behavioral alterations. Bilateralization of seizure discharges correlated with impaired responsiveness. According to the International Classification, about half of patients with FLE had only simple partial seizures (SPS) and the other patients had complex partial seizures (CPS). Altered awareness and/or responsiveness occurred in most habitual partial seizures in our subjects. The term "complex" appears to be useful in clinical practice, although the contents of ictal behavior and the site or side of seizure origin are not implied.     

Prognosis of Partial Epileptic Seizures in the Adolescent

Actuarial analysis was applied to the notes of 235 patients having a partial seizure for the first time between the ages of 12 and 18 years to establish the best predictive indicators of outcome. Among the factors considered to affect significantly the outcome were the seizure type (elementary or complex symptomatology), the initial EEG, the seizure frequency, the etiological factors, and an association with generalized seizures. Sex, age of onset, and topography of EEG paroxysmal abnormalities had no significance. An algorithm allows the prediction of the prognosis of these seizures at two different times immediately after a first seizure in some cases and after a 1-year survey in others.