Daniel Luciano

Nonepileptic seizures and childhood sexual and physical abuse

Nonepileptic seizures (NES) must be distinguished from epilepsy to avoid the adverse effects of unnecessary antiepileptic drugs and to initiate appropriate psychiatric treatment. A higher frequency of prior sexual abuse has been suspected in NES, although no prospective controlled study has compared patients with NES and epilepsy, A series of patients with conversion disorder presenting as epilepsy and 140 patients with complex partial epilepsy (CPE) without evidence of conversion were selected from a series of consecutive admissions to a comprehensive epilepsy center. The groups did not differ with respect to age, years of education, race, or marital status, but the percentage of women was greater in the conversion NES group (73.2%) than in the CPE control group (50.7%; p < 0.002). The frequency of a history of sexual or physical abuse was greater in the NES group (32.4%) than in the CPE controls (8.6%; p < 0.000). Severity of sexual but not physical abuse was significantly greater in the NES group relative to controls (p < 0.05). There was a trend for a closer relationship of the perpetrator of sexual abuse to the victim among the NES patients compared with CPE controls (p < 0.1). These results support the impression that childhood abuse is more common among patients with conversion NES than with epilepsy, and suggests that in some cases childhood abuse may be a contributory pathogenetic factor.

Epilepsy and sleep apnea syndrome

We identified seven patients with refractory partial epilepsy and sleep apnea. Treatment of the sleep apnea with nasal continuous positive airway pressure (CPAP), protriptyline, trazodone, acetazolamide, or tracheostomy reduced seizure frequency and severity in six patients. Success with CPAP depended largely on compliance. Four of five patients had a clear reduction in seizure frequency with the use of CPAP. Sleep apnea may exacerbate epilepsy by causing sleep disruption and deprivation, hypoxemia, and decreased cerebral blood flow. In epilepsy patients with risk factors (eg, obesity) or markers (eg, habitual snoring, daytime somnolence) for sleep apnea, a careful sleep history should be elicited and a polysomnogram obtained when indicated. Treatment of the sleep disorder can improve seizure control.

Genome Scan of Idiopathic Generalized Epilepsy: Evidence for Major Susceptibility Gene and Modifying Genes Influencing the Seizure Type

Idiopathic generalized epilepsy (IGE) is a common, complex disease with an almost exclusively genetic etiology but with variable phenotypes. Clinically, IGE can be divided into different syndromes. Varying lines of evidence point to the involvement of several interacting genes in the etiology of IGE. We performed a genome scan in 91 families ascertained through a proband with adolescent‐onset IGE. The IGEs included juvenile myoclonic epilepsy (JME), juvenile absence epilepsy (JAE), and epilepsy with generalized tonic clonic seizures (EGTCS). Our linkage results support an oligogenic model for IGE, with strong evidence for a locus common to most IGEs on chromosome 18 (lod score 4.4/5.2 multipoint/two‐point) and other loci that may influence specific seizure phenotypes for different IGEs: a previously identified locus on chromosome 6 for JME (lod score 2.5/4.2), a locus on chromosome 8 influencing non‐JME forms of IGE (lod score 3.8/2.5), and, more tentatively, two newly discovered loci for absence seizures on chromosome 5 (lod scores 3.8/2.8 and 3.4/1.9). Our data also suggest that the genetic classification of different forms of IGE is likely to cut across the clinical classification of these subforms of IGE. We hypothesize that interactions of different combinations of these loci produce the related heterogeneous phenotypes seen in IGE families. Ann Neurol 2001;49:328–335

Treatment of Acute Opioid Withdrawal with Ibogaine

Ibogaine is an alkaloid with putative effect in acute opioid withdrawal. Thirty-three cases of treatments for the indication of opioid detoxification performed in non-medical settings under open label conditions are summarized involving an average daily use of heroin of .64 +/- .50 grams, primarily by the intravenous route. Resolution of the signs of opioid withdrawal without further drug seeking behavior was observed within 24 hours in 25 patients and was sustained throughout the 72-hour period of posttreatment observation. Other outcomes included drug seeking behavior without withdrawal signs (4 patients), drug abstinence with attenuated withdrawal signs (2 patients), drug seeking behavior with continued withdrawal signs (1 patient), and one fatality possibly involving surreptitious heroin use. The reported effectiveness of ibogaine in this series suggests the need for systematic investigation in a conventional clinical research setting.

Postictal psychosis: A case control series of 20 patients and 150 controls

We compared clinical data, EEG, and video-EEG studies in a consecutive series of 20 patients with postictal psychosis (PP) to 150 consecutive epilepsy patients with complex partial (CPS) or generalized tonic-clonic (GTCS) seizures but without PP. There was a lucid interval between last seizure and onset of psychosis ranging from 2.3 to 72 h (mean, 25 h). Duration of PP ranged from 16 to 432 h (mean, 83 h). Age, sex, epilepsy type (partial vs. generalized), and history of febrile seizures were similar in the PP and control groups. Patients with PP had more frequent GTCS during monitoring than controls (2.8 vs. 1.3; P < 0.001). Patients with PP were more likely to have a history of encephalitis (P < 0.0001) and psychiatric hospitalization (P < 0.002). More patients with PP had bilateral interictal epileptiform discharges during monitoring than controls (P < 0.0002). Postictal psychosis most often develops in patients with bilateral dysfunction following a cluster of GTCS.

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).

Clinical profile of patients with epileptic and nonepileptic seizures

Epileptic seizures (ES) and nonepileptic seizures (NES) often coexist in patients with treatment-refractory seizures. There are few data on ictal features of these different seizure types in the same patient. We identified 20 patients with ES from a group of 99 NES patients (ES/NES) and compared this group with patients with only ES or NES. All 20 ES/NES patients developed NES after ES. Clinical features of NES clearly differed from ES in 18 of 20 cases. In patients with ES/NES their ES were similar to seizures in patients with only ES, and their NES were similar to spells in patients with only NES. ES/NES patients were similar to ES patients in electrodiagnostic and neuroimaging studies, and similar to NES patients in psychiatric interviews and inventories. The clinical manifestations of ES and NES in the same patient are usually different. Both types of events may be stereotypic and can be distinguished and characterized during video-EEG recording. Determining what events are more prevalent or disturbing is critical. Psychiatric and antiepileptic drug treatment may be provided accordingly. NEUROLOGY 1996;46: 1530-1533

The prolonged QT syndrome presenting as epilepsy A report of two cases and literature review

The prolonged QT syndrome is associated with ventricular tachyarrhythmias and sudden death. We report two patients and review eight previously reported cases of this syndrome, presenting as epilepsy. The average age at the time of the first convulsion was 4.7 years. Episodes were often infrequent, and the time to correct diagnosis ranged from 1 to 28 years. Only one-half the patients had histories suggestive of a familial syndrome. Presyncopal complaints and “lifelessness” prior to seizure activity were common findings in retrospect. Beta-blockade was effective in preventing recurrences in all patients who received treatment.

Provocation of nonepileptic seizures by suggestion in a general seizure population

Summary: Nonepileptic seizures (NES) are common and are often diagnosed at epilepsy centers by video‐EEG recording of both spontaneous and suggestion‐induced episodes, but no study has evaluated provocative testing in a general seizure population. We studied consecutive patients with a tentative diagnosis of epilepsy using saline provocation during video–EEG recording, suggesting that this could produce a typical seizure. Of 52 patients, 40% had no response, 23% had responses unlike their seizures, and 37% had typical episodes (positive test). Patients whose usual episodes resembled complex partial seizures (CPS) were more likely to have NES than were patients with a history of generalized tonic‐clonic seizures (GTC). Of patients with positive provocations, the primary physician predicted NES in 68% of cases. This preliminary study suggests that NES are frequent in a general neurology setting, and that saline provocation is a sensitive method of identifying NES.

Evidence for Linkage of Adolescent-Onset Idiopathic Generalized Epilepsies to Chromosome 8—and Genetic Heterogeneity

Several loci and candidate genes for epilepsies or epileptic syndromes map or have been suggested to map to chromosome 8. We investigated families with adolescent-onset idiopathic generalized epilepsy (IGE), for linkage to markers spanning chromosome 8. The IGEs that we studied included juvenile myoclonic epilepsy (JME), epilepsy with only generalized tonic-clonic seizures occurring either randomly during the day (random grand mal) or on awakening (awakening grand mal), and juvenile absence epilepsy (JAE). We looked for a gene common to all these IGEs, but we also investigated linkage to specific subforms of IGE. We found evidence for linkage to chromosome 8 in adolescent-onset IGE families in which JME was not present. The maximum multipoint LOD score was 3.24 when family members with IGE or generalized spike-and-waves (SW) were considered affected. The LOD score remained very similar (3.18) when clinically normal family members with SW were not considered to be affected. Families with either pure grand mal epilepsy or absence epilepsy contributed equally to the positive LOD score. The area where the LOD score reaches the maximum encompasses the location of the gene for the beta3-subunit of the nicotinic acetylcholine receptor (CHRNB3), thus making this gene a possible candidate for these specific forms of adolescent-onset IGE. The data excluded linkage of JME to this region. These results indicate genetic heterogeneity within IGE and provide no evidence, on chromosome 8, for a gene common to all IGEs.