Prospective multicenter cohort study of possible psychogenic nonepileptic seizure cases-Results at 1-year follow-up examinations.

OBJECTIVE: The primary purpose of this prospective multicenter study was to examine clinical and demographic feature differences according to the diagnostic level of psychogenic nonepileptic seizures (PNES) and then clarify whether prognosis may also differ accordingly. METHODS: Two hundred forty-two consecutive patients strongly suspected of having PNES attacks were invited to participate, of whom 52 did not consent or contact was lost. At the 1-year follow-up examination, PNES diagnosis was reconsidered in nine patients. In 96 patients, the diagnostic level remained the same (P-group), with that in 43 considered to be clinically established (CE-group) and in 42 documented (D-group). The Qolie-10 and NDDI-E questionnaires were examined at both the study entry and the follow-up examination. RESULTS: Multiple regression analysis of quality of life (QoL) score (n = 173; R2  = 0.374; F = 7.349; P < 0.001) revealed NDDI-E score (t = -6.402; P < 0.001), age of PNES onset (t = -3.026; P = 0.003), and ethnic minority status (t = 3.068; P = 0.003) as significant contributors. At entry, the P-group showed the lowest PNES attack frequency (P < 0.000), the lowest rate of antiseizure, antidepressant, and antipsychotic medication (P < 0.000; P = 0.031; P = 0.013, respectively), and the lowest proportion of psychosis (P = 0.046). At follow-up, PNES attack frequency (P < 0.000), number of admittances to emergency room (P < 0.000), and scores for QoL (P < 0.000) as well as depression (P = 0.004) were found to be significantly improved together with other collateral indicators, such as rate of antiseizure medication prescription (P = 0.001) and psychiatric symptoms (P = 0.03). Multiple regression analysis of a sample limited to patients with intellectual disability (ID) (n = 44; R2  = 0.366; F = 4.493; P = 0.002) revealed continued psychotherapy at follow-up (t = 2.610, P = 0.013) and successful reduction in antiseizure medication (t = 2.868; P = 0.007) as positively related with improved QoL. SIGNIFICANCE: Clinical and the socio-psychological constellation of possible, clinically established, and documented PNES were found to differ greatly. Unexpectedly, significant effects of the continuous psychotherapeutic intervention were confirmed in PNES patients with ID.

Behavioral disorder in people with an intellectual disability and epilepsy: A report of the Intellectual Disability Task Force of the Neuropsychiatric Commission of ILAE.

The management and needs of people with intellectual disability (ID) and epilepsy are well evidenced; less so, the comorbidity of behavioral disorder in this population. "Behavioral disorder" is defined as behaviors that are difficult or disruptive, including stereotypes, difficult or disruptive behavior, aggressive behavior toward other people, behaviors that lead to injury to self or others, and destruction of property. These have an important link to emotional disturbance. This report, produced by the Intellectual Disability Task Force of the Neuropsychiatric Commission of the ILAE, aims to provide a brief review of some key areas of concern regarding behavioral disorder among this population and proposes a range of research and clinical practice recommendations generated by task force members. The areas covered in this report were identified by experts in the field as being of specific relevance to the broad epilepsy community when considering behavioral disorder in persons with epilepsy and ID; they are not intended to be exhaustive. The practice recommendations are based on the authors' review of the limited research in this field combined with their experience supporting this population. These points are not graded but can be seen as expert opinion guiding future research and clinical practice.

RASA1 functions in EPHB4 signaling pathway to suppress endothelial mTORC1 activity.

Vascular malformations are linked to mutations in RAS p21 protein activator 1 (RASA1, also known as p120RasGAP); however, due to the global expression of this gene, it is unclear how these mutations specifically affect the vasculature. Here, we tested the hypothesis that RASA1 performs a critical effector function downstream of the endothelial receptor EPHB4. In zebrafish models, we found that either RASA1 or EPHB4 deficiency induced strikingly similar abnormalities in blood vessel formation and function. Expression of WT EPHB4 receptor or engineered receptors with altered RASA1 binding revealed that the ability of EPHB4 to recruit RASA1 is required to restore blood flow in EPHB4-deficient animals. Analysis of EPHB4-deficient zebrafish tissue lysates revealed that mTORC1 is robustly overactivated, and pharmacological inhibition of mTORC1 in these animals rescued both vessel structure and function. Furthermore, overexpression of mTORC1 in endothelial cells exacerbated vascular phenotypes in animals with reduced EPHB4 or RASA1, suggesting a functional EPHB4/RASA1/mTORC1 signaling axis in endothelial cells. Tissue samples from patients with arteriovenous malformations displayed strong endothelial phospho-S6 staining, indicating increased mTORC1 activity. These results indicate that deregulation of EPHB4/RASA1/mTORC1 signaling in endothelial cells promotes vascular malformation and suggest that mTORC1 inhibitors, many of which are approved for the treatment of certain cancers, should be further explored as a potential strategy to treat patients with vascular malformations.

Long-term outcome of severe stroke patients: is the ADL status at discharge from a stroke center indicative of the long-term outcome?

The objective of this study was to examine the possibility of predicting the long-term outcome of severe stroke patients from the ADL status at discharge. The design is a retrospective observational study in the stroke center at Tokushima University Hospital. Severe stroke patients at discharge with Barthel Index (BI) scores ≤ 40 (N=51) were divided into two subgroups retrospectively, improved and unimproved. The Functional Independence Measure (FIM) and BI were analyzed at discharge, 3 and 6 months after onset. Correlation analysis between BI and FIM showed good correlation, especially between BI and motor FIM (mFIM). In conclusion, the ADL status at discharge from a stroke center is not definitely indicative of the long-term outcome, although good recovery of severe stroke cases was observed in males and younger patients, and in patients with motor FIM score>25. This result shows that the first 3 months after the attack should be regarded as an important time window for intensive rehabilitation.

Duration of postictal psychotic episodes.

PURPOSE: To clarify duration of postictal psychosis (PIP) episodes and identify factors that influence its duration. METHODS: Fifty-eight patients with epilepsy exhibited 151 PIP episodes during a mean follow-up period of 12.8 years. Distribution of the duration of these episodes was determined, and factors potentially affecting were analyzed. Factors analyzed included PIP-related variables (i.e., antecedent seizures and the lucid interval) and patient characteristics (i.e., type of epilepsy, lateralization of EEG abnormalities, and intellectual functioning). RESULTS: The mean duration of the 58 first PIP episodes was 10.5 days, and that of all 151 PIP episodes (including multiple episodes) was 9.2 days. Approximately 95% of the PIP episodes resolved within 1 month. Most PIP-related variables, except for antipsychotic drugs administered, were not associated with duration of the episodes. Several patient characteristics, i.e., history of interictal psychosis, family history of psychosis, and intellectual functioning, were associated with duration of the PIP episodes. CONCLUSIONS: This study showed that most PIP episodes last less than 1 month. PIP episodes appear to be prolonged when individuals have an underlying vulnerability to psychosis. Clinical phenomena that can trigger PIP may not determine the course of the PIP episode.

Intellectual prognosis of status epilepticus in adult epilepsy patients: analysis with Wechsler Adult Intelligence Scale-revised.

PURPOSE: Status epilepticus (SE) appears to cause cognitive dysfunction as well as other serious neurologic sequelae. To confirm whether SE produces a subsequent intellectual decline, we evaluated intellectual function prospectively in adult epilepsy patients with and without SE. METHODS: Of 1,685 patients with epilepsy who underwent comprehensive neuropsychological testing in two national hospitals in Japan, 15 patients experienced an episode of SE afterward and underwent the second neuropsychological examination after the SE episode. Forty clinically matched patients with epilepsy, but without an episode of SE since their initial neuropsychological examination, were also reevaluated. We compared IQs and subscores from the Wechsler Adult Intelligence Scale-Revised between the two groups by repeated measures analysis of variance. In the patients who experienced an SE episode, SE-related variables (i.e., age at the SE episode and type and duration of SE) and epilepsy-related variables such as epilepsy type, lateralization of EEG abnormalities, the presence of mesial temporal sclerosis, and previous history of SE, were evaluated in relation to intellectual outcome. RESULTS: Patients with SE, in comparison to those without SE, failed to show any significant post-SE intellectual decline. Furthermore, neither the SE-related variables nor the clinical characteristics were correlated with intellectual outcome. CONCLUSIONS: Our findings suggest that SE does not lead to a significant intellectual decline in adult patients receiving treatment for epilepsy.

Prolonged postictal psychosis with forced normalization (Landolt) in temporal lobe epilepsy.

We report two patients with temporal lobe epilepsy who developed prolonged episodes of postictal psychosis (12 weeks) following a bout of seizures and a lucid interval. No drug toxicity was noted, and no recurrent or continuous seizures were observed during their prolonged psychotic episodes. Repeated EEGs during the period of psychosis showed that their habitual focal epileptiform abnormalities had disappeared. Responses to neuroleptic treatments were not remarkable. Their psychotic symptoms gradually dispelled after their epileptiform abnormalities reappeared. These observations may suggest possible overlapping mechanisms between a prolongation of psychosis and suppression of epileptiform discharges on a scalp EEG.

Electron microscopic evaluations of clot morphology during thrombelastography.

In this study, we characterized clot morphology with a scanning electron microscope (SEM) at time points corresponding to the commonly used thrombelastography (TEG) variables, illustrating the correlation of the physical clot formation with TEG(R) tracings. The first channel of the TEG analyzer was used to obtain the tracings of clot formation, while the sub-samples for the SEM were obtained from the second TEG channel. Different types of samples were examined, including whole blood, abciximab-treated whole blood, platelet-rich plasma (PRP), and abciximab-treated PRP. The SEM images were obtained at reaction time, different amplitudes (5-30 mm), maximum amplitude (MA), and at amplitude 60 min after MA. In the whole blood, coarse fibrin and activated platelets were observed at reaction time and fibrin strands progressively became more solid and intertwined at amplitude 10 mm and thereafter. Red blood cells were surrounded with fibrin strands at amplitude 30 mm and were tightly packed by fibrin strands at MA. In abciximab-treated whole blood, red blood cell shape was maintained at MA. The process of fibrin formation and platelet activation was also examined in PRP. Abciximab did not block platelet shape change, although the blockage of fibrin binding to platelets was shown on the TEG analyzer. In summary, we have shown structural changes of the forming clot in relation to TEG variables.

[Blood lactate levels during fast-track cardiac anesthesia].

BACKGROUND: Lactate is a very sensitive marker of outcomes in critically ill patients. The aim of this study was to investigate the significance of blood lactate measurement during fast-track cardiac anesthesia. METHODS: We examined arterial blood lactate levels of 12 patients following coronary artery bypass graft surgery under intermittent aortic cross clamping with fast-track cardiac anesthesia. Anesthesia was induced with propofol and fentanyl, and maintained with propofol, fentanyl (total 400-1000 micrograms) and isoflurane. Blood samples were collected from a radical artery catheter. RESULTS: At the termination of the extracorporeal circulation, the blood lactate was 10.3 +/- 2.0 (7.4-12.5) mmol.l-1. This value decreased slowly to 1.5 +/- 0.4 mmol.l-1 on the second postoperative day. All patients were extubated within 4 hours after surgery. Vital signs were stable, and no cardiac events occurred perioperatively. CONCLUSIONS: A continuous decline in blood lactate levels was related to a favorable postoperative course. Further research might be required to prevent transient hyperlactecemia at the end of cardiopulmonary bypass.

Re-examination of the value of localising aura sensations and lateralising interictal epileptiform discharges in view of structural lesions demonstrated by MRI.

We examined the relationship between MRI lesions and electro-clinical findings with special attention to the localising value of aura sensations and the sides of interictal epileptiform discharges in 327 patients with symptomatic localisation-related epilepsy. As a result, while autonomic as well as psychic auras were correlated with temporal lesions, simple motor seizures were associated with extra-temporal ones. Within the group of patients with temporal lobe epilepsy, autonomic but not psychic auras concurred significantly more often with medial temporal structural lesions. Furthermore, there was a significant difference between concordance rates between sides of MRI lesions and EEG foci as a function of laterality: while the right-sided MRI lesions constantly showed ipsilateral EEG foci, EEG foci concurring with the left-sided MRI lesions proved to be often falsely lateralising. From these results, we assumed that lateral as well as medial temporal involvement is needed in the genesis of the psychic aura in contrast to the autonomic aura, which could be induced without lateral temporal involvement, and lesions in the left hemisphere are more apt to induce secondarily epileptogenic than those in the right hemisphere.

Use of clobazam for the treatment of refractory complex partial seizures.

Clobazam (CLB) add-on therapy was attempted in 183 patients with intractable complex partial seizures in whom conventional benzodiazepines had been successfully discontinued before initiation of CLB. Although complete remission was initially achieved in 61, tolerance developed in almost half (49.2%) within the first 3 months, whereas 23 out of 31 patients (74.2%) who remained seizure free for the first 3 months continued to be so over the next 3 months. CLB add-on therapy proved to be significantly more effective when concurrent GTC occurred more often than yearly. In the current series, no frank psychotic episodes were elicited among the 61 patients who achieved complete suppression of long-standing complex partial seizures, which was in agreement with previous studies. From these results, we believe that CLB is an effective, safe, and inexpensive medication for add-on therapy in difficult to treat focal epilepsies, especially without concurrent use of conventional benzodiazepine compounds.

Increased frequency of interleukin-1beta-511T allele in patients with temporal lobe epilepsy, hippocampal sclerosis, and prolonged febrile convulsion.

PURPOSE: To confirm the high frequency of interleukin (IL)-1beta-511T allele occurrence in patients with temporal lobe epilepsy (TLE) and hippocampal sclerosis (HS), with special attention given to the impact of prolonged febrile convulsions (PFCs) on IL-1beta genotype distribution. METHODS: Patients with evidence of unilateral HS on magnetic resonance (MR) images were chosen as study subjects (TLE+HS; n = 66). Other patients with essentially normal MRI findings or only foreign tissue (TLE without HS; TLE-HS; n = 64), and those with symptomatic localization-related epilepsy but without TLE (SLE; n = 89) were selected as disease controls. A single base pair polymorphism at position 2511 in the promoter region of the IL-1beta gene was analyzed. RESULTS: The distribution of IL-1beta-511 genotypes as well as allele frequency was significantly different between TLE+HS patients and controls. In contrast, no difference was found between TLE-HS patients and controls or between SLE patients and controls. Further, in the group of patients with TLE+HS, the frequency of the IL-1beta-511T allele tended to increase as a function of febrile convulsions [0.531 without either PFC or simple febrile convulsion (SFC); 0.633 with SFC; 0.686 with PFC]. Although no statistically significant difference was noted between patients without PFC and the controls, a chi2 analysis of allele distribution revealed a significant difference between those with PFC and the controls. CONCLUSIONS: PFC proved to be a potent determinant of IL-1beta-511T allele frequency; thus a discrepancy of PFC incidence should be considered an explanation of recent conflicting results regarding the association between the gene polymorphisms of IL-1beta-511 and TLE+HS.

Association of partial epilepsy with brain-derived neurotrophic factor (BDNF) gene polymorphisms.

In search of a gene polymorphism that may contribute to the development of partial epilepsy, we focused on brain-derived neurotrophic factor (BDNF), since the functional effects of insult-induced neurotrophin changes are reported to be protection against neuronal damage and stimulation of synaptic reorganization. Two hundred nineteen patients with partial epilepsy were selected for study and 311 individuals were used as healthy controls. A single base pair (bp) polymorphism at position 240 in the non-coding region of the BDNF gene and at position 480 within the proBDNF sequence were analyzed, and the frequency of the 240T allele was found to be significantly increased in partial epilepsy patients as compared with the controls (chi(2)=8.59, P=0.0034). In contrast, no significant differences were found between the two groups in any combination of the G480A BDNF gene polymorphism. Our results suggest that the 240T allele in the BDNF gene may be a genetic marker that indicates an enhanced susceptibility to seizures, setting up a cascade leading eventually to chronic partial epilepsy in patients with such a genetic predisposition.

Death in epilepsy with special attention to suicide cases.

To examine clinical features of cases of death among epilepsy patients as a case-control study, with special attention to suicide, we analyzed the records of 43 deceased patients with well-classified epilepsy. The subjects were compared with 1,722 control patients who showed definite subtypes of epilepsy. As a result, among the major causes of death, 13 of the subjects suffered accidents (mostly drowning), ten experienced sudden unexpected death, seven had status epilepticus, and six committed suicide. There were no significant differences with regard to clinical variables except for psychotic episodes, which were more frequently encountered in subjects than in controls (chi(2)=6.771, P=0.009, Yates' modification). Statistically significant differences were found by epilepsy type as well (chi(2)=14.72, P=0.002), with temporal lobe epilepsy (TLE) proving to be most closely associated with death among the epilepsy patients. Further, suicide was only encountered in patients with TLE and the association was statistically significant (chi(2)=5.119, P=0.024). Half of those who committed suicide (n=3), did so by jumping in front of an oncoming train while in the midst of an episode of postictal psychosis. In conclusion, most cases of suicide in patients with epilepsy were found to be the result of an immediate causal relationship with ictal or interictal epileptic manifestations, rather than a result of augmentation of psychosocial stressors generated by a long-standing handicap derived from the severe illness.