Stress and other psychosocial characteristics of patients with psychogenic nonepileptic seizures

Research on psychogenic nonepileptic seizures (PNES) has focused on childhood abuse, but less is known about other stressors and psychosocial risk factors. The authors compared 25 patients with PNES with 33 control subjects with epilepsy on stressful life events and other risk factors for somatoform disorders. Compared with control subjects, patients with PNES reported significantly more prevalent and stressful negative life events (including adulthood abuse) and more current rumination, stress-related diseases, somatic symptoms, bodily awareness, and marginally more anxiety and depression. However, the relationship of many of these variables to PNES was accounted for by life stress. Groups did not differ on illness worry, alexithymia, or psychotic symptoms. The results suggest that PNES are part of a larger pattern of somatic symptoms responses to a wide range of negative events, including stress in adulthood.     

Neuropsychologic impairment in patients with nonepileptic seizures.

Patients with nonepileptic seizures (NES), those with epileptic seizures (ES), and normal controls were compared on a battery of neuropsychologic tests. Diagnoses were made after intensive electroencephalogram (EEG) monitoring. Excluded from the study were patients with both ES and NES, as well as patients with ES who had evidence of structural brain damage. On all neuropsychologic measures, the two seizure groups were significantly impaired relative to the controls, but there were no significant differences between the ES and NES group performances. Additional neuropsychologic measures were obtained on the two seizure groups but not controls, and again there were no significant differences between the two seizure groups. Further analyses suggested that the NES group's impairment was related to emotional factors. The Minnesota Multiphasic Personality Inventory (MMPI)/MMPI-2 and the Portland Digit Recognition Test were helpful in classifying patients by seizure group. Our results, which are consistent with those of previous studies, suggest that neuropsychologic abnormalities are not pathognomonic of brain dysfunction in this population. However, the Portland Digit Recognition Test (PDRT) and measures of personality are useful for classification purposes in the differential diagnosis of epileptic and nonepileptic seizures.     

Confrontation naming in individuals with temporal lobe epilepsy: a quantitative analysis of paraphasic error subtypes

Although confrontation naming deficits have been observed in dominant temporal lobe epilepsy (DTLE), the relative contribution of impoverished phonologic word retrieval and/or semantic knowledge remains unclear. Analysis of verbal-semantic, phonemic-literal, and combination paraphasias produced during confrontation naming by participants with seizure disorders (52 DTLE; 47 nondominant temporal lobe epilepsy [NDTLE]; 54 psychogenic nonepileptic seizures [PNES]) indicated that the frequency of: (a) verbal-semantic paraphasias was similar across groups, (b) phonemic-literal paraphasias was highest in DTLE, and (c) combination paraphasias was lowest in PNES. Confrontation naming ability was most strongly related to phonemic-literal paraphasia frequency in DTLE and to verbal IQ in both NDTLE and PNES. Greater confrontation naming deficits in DTLE may be attributed to impairments in phonological processing.     

Clinical and genetic spectrum of a large cohort of children with epilepsy in China

PurposeGenetic diagnosis for children suffering from epilepsy has important implications for treatment, prognosis, and development of precision medicine strategies.MethodsWe performed exome sequencing (ES) or targeted sequencing on 733 children with epilepsy onset within the first year of life. We subgrouped our patients based on the onset age of seizure into neonatal and before 1 year (1–12 months), to compare the clinical and genetic features.ResultsThe subgroups with different onset age of seizure showed different pathogenic variant spectrum, and the 1-year age group was more likely to have developmental delays than the neonate group (p = 0.000614). The diagnostic rate was 26.7% for targeted sequencing using a 2742-gene panel, and 42% for ES. We identified 12 genes, which covered 48.7% of diagnostic cases. Our data revealed that 41.9% of patients in the neonate group and 49.7% patients in the 1-year group had treatment options based on molecular diagnosis.ConclusionThe 12 most commonly implicated genes in this cohort and the genes with treatment options should be considered as part of the essential panel for early diagnosis of epilepsy onset, if large medical exome analyses or ES are not feasible as first-tier analysis. Genetic results are beginning to improve therapy by antiepileptic medication selections and precision medicine approaches.     

Clinical impact of genomic testing in patients with suspected monogenic kidney disease

PurposeTo determine the diagnostic yield and clinical impact of exome sequencing (ES) in patients with suspected monogenic kidney disease.MethodsWe performed clinically accredited singleton ES in a prospectively ascertained cohort of 204 patients assessed in multidisciplinary renal genetics clinics at four tertiary hospitals in Melbourne, Australia.ResultsES identified a molecular diagnosis in 80 (39%) patients, encompassing 35 distinct genetic disorders. Younger age at presentation was independently associated with an ES diagnosis (p < 0.001). Of those diagnosed, 31/80 (39%) had a change in their clinical diagnosis. ES diagnosis was considered to have contributed to management in 47/80 (59%), including negating the need for diagnostic renal biopsy in 10/80 (13%), changing surveillance in 35/80 (44%), and changing the treatment plan in 16/80 (20%). In cases with no change to management in the proband, the ES result had implications for the management of family members in 26/33 (79%). Cascade testing was subsequently offered to 40/80 families (50%).ConclusionIn this pragmatic pediatric and adult cohort with suspected monogenic kidney disease, ES had high diagnostic and clinical utility. Our findings, including predictors of positive diagnosis, can be used to guide clinical practice and health service design.     

Clinical predictors of drug-resistant epilepsy in children

Background/aimIn up to 20% of epilepsy patients, seizures may not be controlled despite the use of antiepileptic drugs, either alone or in combination. These individuals are considered to have drug-resistant epilepsy. Drug-resistant epilepsy is usually associated with intellectual disability, psychiatric comorbidity, physical injury, sudden unexpected death, and low quality of life. Early detection and prediction of drug-resistant epilepsy are essential in determining the patient’s most appropriate treatment option. This retrospective study aimed to determine the clinical, electroencephalographic, and radiological factors associated with medically intractable childhood seizures.Materials and methods Data regarding 177 patients diagnosed with drug-resistant epilepsy were compared with 281 patients with drug-responsive epilepsy. Results Univariate analysis showed that age at seizure onset, having mixed seizure types, history of status epilepticus, history of neonatal seizures, history of both having febrile and afebrile seizures, daily seizures at the onset, abnormality on the first electroencephalogram, generalized epileptic abnormality on electroencephalogram, abnormal neurodevelopmental status, abnormal neuroimaging, and having symptomatic etiology were significant risk factors for the development of drug-resistant epilepsy (p < 0.05). In multivariable analysis, having mixed seizure types, history of status epilepticus, having multiple seizures in a day, intellectual disability, symptomatic etiology, and neuroimaging abnormality remained significant predictors for developing drug-resistant epilepsy.ConclusionsIn the course of childhood epilepsy, some clinical features may predict the outcome. Early identification of patients with high risk for drug-resistant epilepsy will help plan the appropriate treatment option. Further prospective studies should confirm these findings.     

Retrograde amnesia and brain seizures in mice

These experiments examined in Swiss-Webster mice the effects of variation in intensity of transcorneal electroshock stimulation on: (1) convulsion threshold; (2) brain seizure thresholds; and, (3) retrograde amnesia (RA) in an inhibitory avoidance task. In unanesthetized mice the current intensities required for eliciting brain seizures and RA were lower than that required for elicitation of convulsions. Further, the brain seizure and RA thresholds were comparable. Light ether anesthesia administered prior to the electroshock (ES) stimulation prevented the convulsions and significantly increased both the brain seizure and RA thresholds. The results indicate that the degree of amnesia produced by ES does not depend upon the ES current level per se, but rather upon the alteration in CNS activity produced by the ES. At ES current levels sufficient to produce RA in ether anesthetized mice the primary afterdischarge of the seizure was not followed by postictal depression. Thus, postictal depression appears not to contribute to RA.     

Eye movement desensitization and reprocessing in the psychological treatment of trauma‐based psychogenic non‐epileptic seizures

Little is known about the types of mental health treatment that are most effective for psychogenic non‐epileptic seizure (PNES) patients who have high rates of comorbid post‐traumatic stress disorder (PTSD) and dissociation. Eye movement desensitization and reprocessing (EMDR) has proved to be effective in the treatment of PTSD, anxiety states, dissociative symptoms and somatoform disorders. This study, which utilized a non‐controlled qualitative multiple revelatory case design, integrates EMDR into the psychological treatment of PNES patients with confirmed trauma experiences. With EMDR targeting trauma and dissociative symptoms in three patients, PNES were extinguished in two. Those patients have remained seizure‐free for 12–18 months. Copyright © 2007 John Wiley & Sons, Ltd.     

Phenotype based prediction of exome sequencing outcome using machine learning for neurodevelopmental disorders

PurposeAlthough the introduction of exome sequencing (ES) has led to the diagnosis of a significant portion of patients with neurodevelopmental disorders (NDDs), the diagnostic yield in actual clinical practice has remained stable at approximately 30%. We hypothesized that improving the selection of patients to test on the basis of their phenotypic presentation will increase diagnostic yield and therefore reduce unnecessary genetic testing.MethodsWe tested 4 machine learning methods and developed PredWES from these: a statistical model predicting the probability of a positive ES result solely on the basis of the phenotype of the patient.ResultsWe first trained the tool on 1663 patients with NDDs and subsequently showed that diagnostic ES on the top 10% of patients with the highest probability of a positive ES result would provide a diagnostic yield of 56%, leading to a notable 114% increase. Inspection of our model revealed that for patients with NDDs, comorbid abnormal (lower) muscle tone and microcephaly positively correlated with a conclusive ES diagnosis, whereas autism was negatively associated with a molecular diagnosis.ConclusionIn conclusion, PredWES allows prioritizing patients with NDDs eligible for diagnostic ES on the basis of their phenotypic presentation to increase the diagnostic yield, making a more efficient use of health care resources.     

Lorazepam for the prevention of recurrent seizures related to alcohol

BACKGROUND AND METHODS: Alcohol abuse is one of the most common causes of seizures in adults. In a randomized, double-blind study, we compared lorazepam with placebo for the prevention of recurrent seizures related to alcohol. Over a 21-month period, we studied consecutive patients with chronic alcohol abuse who were at least 21 years of age and who presented to the emergency departments of two hospitals in Boston after a witnessed, generalized seizure. The patients were randomly assigned to receive either 2 mg of lorazepam in 2 ml of normal saline or 4 ml of normal saline intravenously and then observed for six hours. The primary end point was the occurrence of a second seizure during the observation period. RESULTS: Of the 229 patients who were initially evaluated, 186 met the entry criteria. In the lorazepam group, 3 of 100 patients (3 percent) had a second seizure, as compared with 21 of 86 patients (24 percent) in the placebo group (odds ratio for seizure with the use of placebo, 10.4; 95 percent confidence interval, 3.6 to 30.2; P<0.001). Forty-two percent of the placebo group were admitted to the hospital, as compared with 29 percent of the lorazepam group (odds ratio for admission, 2.1; 95 percent confidence interval, 1.1 to 4.0; P=0.02). Seven patients in the placebo group and one in the lorazepam group were transported to an emergency department in Boston with a second seizure within 48 hours after hospital discharge. CONCLUSIONS: Treatment with intravenous lorazepam is associated with a significant reduction in the risk of recurrent seizures related to alcohol.     

Neonatal hypocalcemia,neonatal seizures,and intellectual disability in 22q11.2 deletion syndrome

PurposeHypocalcemia is a common endocrinological condition in 22q11.2 deletion syndrome. Neonatal hypocalcemia may affect neurodevelopment. We hypothesized that neonatal hypocalcemia would be associated with rare, more severe forms of intellectual disability in 22q11.2 deletion syndrome.MethodsWe used a logistic regression model to investigate potential predictors of intellectual disability severity, including neonatal hypocalcemia, neonatal seizures, and complex congenital heart disease, e.g., interrupted aortic arch, in 149 adults with 22q11.2 deletion syndrome. Ten subjects had moderate-to-severe intellectual disability.ResultsThe model was highly significant (P < 0.0001), showing neonatal seizures (P = 0.0018) and neonatal hypocalcemia (P = 0.047) to be significant predictors of a more severe level of intellectual disability. Neonatal seizures were significantly associated with neonatal hypocalcemia in the entire sample (P < 0.0001), regardless of intellectual level. There was no evidence for the association of moderate-to-severe intellectual disability with other factors such as major structural brain malformations in this sample.ConclusionThe results suggest that neonatal seizures may increase the risk for more severe intellectual deficits in 22q11.2 deletion syndrome, likely mediated by neonatal hypocalcemia. Neonatal hypocalcemia often remains unrecognized until the postseizure period, when damage to neurons may already have occurred. These findings support the importance of early recognition and treatment of neonatal hypocalcemia and potentially neonatal screening for 22q11.2 deletions.Genet Med16 1, 40–44.     

Long-term economic impacts of exome sequencing for suspected monogenic disorders: diagnosis,management, and reproductive outcomes

PurposeTo undertake the first end-to-end cost-effectiveness analysis of exome sequencing (ES) in rare disease diagnosis.MethodsA cohort of 80 infants who underwent ES and usual diagnostic care in parallel were used to model incremental cost and health outcomes (quality adjusted life-years, QALYs) attributable to ES diagnosis over a 20-year horizon. Three models were developed: (1) outcomes in patients only, (2) outcomes in patients and first-degree relatives as a result of cascade testing, and (3) outcomes in patients and first-degree relatives including parental reproductive outcomes.ResultsWhen the directly observed cost and health outcomes of the cohort participants were projected, the use of ES resulted in a gain of 7.39 QALYs and an incremental cost-effectiveness ratio (ICER) of AU$31,144.35 (i.e., cost per additional QALY gained). When cascade testing in first-degree relatives was added, cost-effectiveness increased, to a gain of 11.62 QALYs and an ICER of AU$20,839.57. When parental reproductive outcomes were added, cost-effectiveness increased again, with 36.00 QALYs gained and an ICER of AU$14,235.28.ConclusionUse of ES in suspected monogenic disorders becomes increasingly cost-effective as the benefits of ES data reanalysis, cascade testing in first-degree relatives, and parental reproductive outcomes are incorporated into modeling.     

Corpus callosum size,hypnotic susceptibility and empathy in women with alleged mediumship: a controlled study

AimEvidence indicates that highly hypnotizable subjects may have larger area of the rostrum of the corpus callosum (CC). Mediumship can be defined as the alleged ability to communicate regularly with deceased personalities, and self-hypnosis is postulated as an underlying mechanism for this ability. Therefore, we aimed to investigate the CC area, hypnotic susceptibility, self-reported dissociation, and empathy in alleged mediums in comparison with healthy, non-medium controls.MethodsThe study sample consisted of 16 Spiritist mediums (medium group (MG)) and 16 non-medium controls. Magnetic resonance imaging scans were performed to measure the CC areas (total and subdivisions). The Harvard Group Scale of Hypnotic Susceptibility was used to assess hypnotizability, and self-reported measures were used to investigate anomalous experiences, mental health using the Self-Reporting Questionnaire-SRQ, dissociative experiences using the Dissociative Experiences Scale, and empathy using the Interpersonal Reactivity Index.ResultsNo between-group differences were found in the total or subdivided CC areas or in hypnotizability, with both groups showing intermediate levels. The rostrum of the CC area and hypnotizability were not correlated. The MG presented with significantly more anomalous experiences, but the two groups had similar scores for dissociation, empathy, and mental health.ConclusionThe normal CC areas found in the MG are in contrast with the abnormal results typically observed in subjects with psychotic and dissociative disorders. Although hypnotizability was not different between groups, further studies are needed to replicate these findings in other samples.     

Childhood Psychological and Physical Abuse: Psychopathology,Dissociation, and Axis I Diagnosis

ABSTRACT

The present study compared (1) college students who reported childhood physical and psychological abuse (combined; N = 35) with (2) students who reported psychological abuse alone (psychological; N = 30), and with (3) students who reported no history of childhood abuse (no abuse; N = 35). Combined abuse and psychological abuse participants were more likely to receive an Axis I diagnosis on a structured interview and to report more dissociative experiences than were no abuse participants. In addition, a structured interview for dissociative disorders was the single measure that differentiated psychologically abused participants from participants reporting combined abuse and no abuse. However, the most psychological impairment was evident in the combined abuse group. Relative to participants who reported no abuse history, combined abuse participants reported more dissociative symptoms on a structured interview and more symptoms of general psycho-pathology, depression, and state and trait anger on self-report measures.     

Seizures in trisomy 18: Prevalence,description, and treatment

Changes in medical intervention over the last decade have improved outcomes for individuals with trisomy 18, the second most common human aneuploidy syndrome at birth. As children with trisomy 18 live longer, a shared concern of medical experts and parents is the occurrence and treatment of seizures. Previously published surveillance guidelines for this condition have not addressed seizure management. Using parent-reported data collected as part of the Tracking Rare Incidence Syndromes project, we report on the prevalence, course, and management of seizures in individuals with trisomy 18. Twenty-eight percent (52/186) of individuals diagnosed with trisomy 18 in our retrospective cohort experienced generalized, focal, or mixed seizures at some point in their lifetime. For many individuals, seizures were effectively managed by broad-spectrum anti-seizure medications. Correlation analysis showed that focal and generalized seizures were more likely to occur in individuals who had previously experienced infantile spasms or central apnea. Electroencephalogram testing should be considered as part of a standard screening approach in individuals with trisomy 18 to enable early diagnosis and treatment of seizures. An international registry that incorporates parent-reported and clinical data for patients with trisomy 18 may facilitate ongoing research and recruitment into clinical trials for seizure management.     

Phenotypic and molecular spectrum of pyridoxamine‐5′‐phosphate oxidase deficiency: A scoping review of 87 cases of pyridoxamine‐5′‐phosphate oxidase deficiency

Pyridoxamine‐5′‐phosphate oxidase (PNPO) deficiency is an autosomal recessive pyridoxal 5′‐phosphate (PLP)‐vitamin‐responsive epileptic encephalopathy. The emerging feature of PNPO deficiency is the occurrence of refractory seizures in the first year of life. Pre‐maturity and fetal distress, combined with neonatal seizures, are other associated key characteristics. The phenotype results from a dependency of PLP which regulates several enzymes in the body. We present the phenotypic and genotypic spectrum of (PNPO) deficiency based on a literature review (2002‐2020) of reports (n = 33) of patients with confirmed PNPO deficiency (n = 87). All patients who received PLP (n = 36) showed a clinical response, with a complete dramatic PLP response with seizure cessation observed in 61% of patients. In spite of effective seizure control with PLP, approximately 56% of patients affected with PLP‐dependent epilepsy suffer developmental delay/intellectual disability. There is no diagnostic biomarker, and molecular testing required for diagnosis. However, we noted that cerebrospinal fluid (CSF) PLP was low in 81%, CSF glycine was high in 80% and urinary vanillactic acid was high in 91% of the cases. We observed only a weak correlation between the severity of PNPO protein disruption and disease outcomes, indicating the importance of other factors, including seizure onset and time of therapy initiation. We found that pre‐maturity, the delay in initiation of PLP therapy and early onset of seizures correlate with a poor neurocognitive outcome. Given the amenability of PNPO to PLP therapy for seizure control, early diagnosis is essential.     

Predictors and mechanisms of epilepsy occurrence in cerebral gliomas: What to look for in clinicopathology

Gliomas, especially low-grade gliomas, are highly epileptogenic brain tumors. Histopathological information is valuable in evaluating the diagnosis and/or biologic behavior of various gliomas. Here we explored the clinical data and histopathological predictors of the occurrence of epilepsy in patients with gliomas. A retrospective study examined 310 consecutive patients who had undergone surgical treatment for gliomas in our institution from January 2013 to January 2015. Clinical data and pathological examination results were analyzed. Literatures regarding the predictors and etiology of glioma associated epileptic seizures in the period of 1995–2015 were also reviewed. A total of 234 (75.5%) astrocytic tumors and 76 (24.5%) oligodendrial tumors were included. At diagnosis, 33.6% of patients had epileptic seizures. Multivariate analysis revealed cortex involvement (OR = 7.991, 95%CI = 1.599–39.926), lower World Health Organization grade (OR = 3.584, 95%CI = 1.032–12.346) and topoisomerase II (TopoII) positivity (OR = 0.943, 95%CI = 0.903–0.982) were strong predictors for preoperative epileptic seizures. Gender, disease course, tumor classification, location or volume did not significantly affect epileptic seizure occurrence. Forty-three publications involved glioma-associated epilepsy were found in PubMed online database and key data were extracted and summarized. The present studies on glioma-related epilepsy are relatively limited and inconsistent. Low-grade gliomas, cortex involvement and TopoII positivity were independent predictors of a history of epileptic seizures at diagnosis. Further studies to examine the underlying mechanism of topoisomerase II as well as other molecules in epilepsy occurrence in brain gliomas are needed in the future.     

癫癎发作早期Video-EEG监测的临床价值

目的 :探讨Video -EEG监测癫发作早期脑电变化的临床应用价值。方法 :对 96例临床确诊的癫患者进行发作早期Video -EEG监测并分析其结果。结果 :共监测到 3 2例癫发作(3 3 % ) ,其中全身性癫 4例 ;颞叶癫 16例 ,颞外癫 12例。发作早期脑电异常主要分快活动、慢活动及快慢混合活动三大类。根据发作早期脑电变化 ,2 3例 (72 % )作出定位诊断。结论 :癫发作早期脑电图脑电变化对致灶的定位 (定侧 )诊断有重要价值     

Cost-effectiveness frameworks for comparing genome and exome sequencing versus conventional diagnostic pathways: A scoping review and recommended methods

PurposeMethodological challenges have limited economic evaluations of genome sequencing (GS) and exome sequencing (ES). Our objective was to develop conceptual frameworks for model-based cost-effectiveness analyses (CEAs) of diagnostic GS/ES.MethodsWe conducted a scoping review of economic analyses to develop and iterate with experts a set of conceptual CEA frameworks for GS/ES for prenatal testing, early diagnosis in pediatrics, diagnosis of delayed-onset disorders in pediatrics, genetic testing in cancer, screening of newborns, and general population screening.ResultsReflecting on 57 studies meeting inclusion criteria, we recommend the following considerations for each clinical scenario. For prenatal testing, performing comparative analyses of costs of ES strategies and postpartum care, as well as genetic diagnoses and pregnancy outcomes. For early diagnosis in pediatrics, modeling quality-adjusted life years (QALYs) and costs over ≥20 years for rapid turnaround GS/ES. For hereditary cancer syndrome testing, modeling cumulative costs and QALYs for the individual tested and first/second/third-degree relatives. For tumor profiling, not restricting to treatment uptake or response and including QALYs and costs of downstream outcomes. For screening, modeling lifetime costs and QALYs and considering consequences of low penetrance and GS/ES reanalysis.ConclusionOur frameworks can guide the design of model-based CEAs and ultimately foster robust evidence for the economic value of GS/ES.     

Comparative fos immunoreactivity in the brain after forebrain, brainstem, or combined seizures induced by electroshock, pentylenetetrazol, focally induced and audiogenic seizures in rats

To help discern sites of focal activation during seizures of different phenotype, the numbers of Fos immunoreactive (FI) neurons in specific brain regions were analyzed following "brainstem-evoked," "forebrain-evoked" and forebrain/brainstem combination seizures induced by a variety of methods. First, pentylenetetrazol (PTZ, 50 mg/kg) induced forebrain-type seizures in some rats, or forebrain seizures that progressed to tonic/clonic brainstem-type seizures in other rats. Second, minimal electroshock induced forebrain seizures whereas maximal electroshock (MES) induced tonic brainstem-type seizures in rats. Third, forebrain seizures were induced in genetically epilepsy-prone rats (GEPRs) by microinfusion of bicuculline into the area tempestas (AT), while brainstem seizures in GEPRs were induced by audiogenic stimulation. A final set was included in which AT bicuculline-induced forebrain seizures in GEPRs were transiently interrupted by audiogenic seizures (AGS) in the same animals. These animals exhibited a sequence combination of forebrain clonic seizure, brainstem tonic seizure and back to forebrain clonic seizures. Irrespective of the methods of induction, clonic forebrain- and tonic/clonic brainstem-type seizures were associated with considerable Fos immunoreactivity in several forebrain structures. Tonic/clonic brainstem seizures, irrespective of the methods of induction, were also associated with FI in consistent brainstem regions. Thus, based on Fos numerical densities (FND, numbers of Fos-stained profiles), forebrain structures appear to be highly activated during both forebrain and brainstem seizures; however, facial and forelimb clonus characteristic of forebrain seizures are not observable during a brainstem seizure. This observation suggests that forebrain-seizure behaviors may be behaviorally masked during the more severe tonic brainstem seizures induced either by MES, PTZ or AGS in GEPRs. This suggestion was corroborated using the sequential seizure paradigm. Similar to findings using MES and PTZ, forebrain regions activated by AT bicuculline were similar to those activated by AGS in the GEPR. However, in the combination seizure group, those areas that showed increased FND in the forebrain showed even greater FND in the combination trial. Likewise, those areas of the brainstem showing FI in the AGS model, showed an even greater effect in the combination paradigm. Finally, the medial amygdala, ventral hypothalamus and cortices of the inferior colliculi showed markedly increased FND that appeared dependent upon activation of both forebrain and brainstem seizure activity in the same animal. These findings suggest these latter areas may be transitional areas between forebrain and brainstem seizure interactions. Collectively, these data illustrate a generally consistent pattern of forebrain Fos staining associated with forebrain-type seizures and a consistent pattern of brainstem Fos staining associated with brainstem-type seizures. Additionally, these data are consistent with a notion that separate seizure circuitries in the forebrain and brainstem mutually interact to facilitate one another, possibly through involvement of specific "transition mediating" nuclei.