Seizures and antiepileptic drugs in patients with spontaneous intracerebral hemorrhages

AbstractPurposePatients with intracerebral hemorrhage (ICH) are often initiated on antiepileptic drugs without a clear indication. We compared the percentage of patients with spontaneous ICH who had seizures at onset or during hospitalization, and examined empiric use of antiepileptic drugs (AEDs) in these patients in 2 cohorts 10 years apart.MethodsUsing a clinical data registry at a tertiary care adult hospital, we retrospectively selected admissions for spontaneous ICH between 1/1/99–12/31/00 (Cohort A, n=30) and 1/1/09–12/31/10 (Cohort B, n=108). Clinical, neurophysiological and radiological data were collected in both cohorts.ResultsIn Cohorts A and B respectively, AEDs were started in 53.3% and 50.0%, and continued on discharge in 50.0% and 20.4% of patients; 86.6% and 59.1% of patients discharged on AEDs did not have a clinical/electrographic seizure or epileptiform EEG findings. Seizures occurred in 6.6% and 13.0% in Cohorts A and B respectively. The presence of a seizure at presentation (p=0.01) and during hospitalization (p=0.02) were predictors for continuing AED on discharge.ConclusionIn both cohorts, a significant number of patients were discharged on AEDs without a clear indication, though there is a change in practice between the two cohorts

Driving a motor vehicle and psychogenic nonepileptic seizures: ILAE Report by the Task Force on Psychogenic Nonepileptic Seizures

Objectives This International League Against Epilepsy (ILAE) Report: (a) summarizes the literature about “driving and psychogenic nonepileptic seizures (PNES)”; (b) presents the views of international experts; and (c) proposes an approach to assessing the ability of persons with PNES (PwPNES) to drive. Methods Phase 1: Systematic literature review. Phase 2: Collection of international expert opinion using SurveyMonkey®. Experts included the members of the ILAE PNES Task Force and individuals with relevant publications since 2000. Phase 3: Joint analysis of the findings and refinement of conclusions by all participants using email. As an ILAE Report, the resulting text was reviewed by the Psychiatry Commission, the ILAE Task Force on Driving Guidelines, and Executive Committee. Results Eight studies identified by the systematic review process failed to provide a firm evidence base for PNES‐related driving regulations, but suggest that most health professionals think restrictions are appropriate. Twenty‐six experts responded to the survey. Most held the view that decisions about driving privileges should consider individual patient and PNES characteristics and take account of whether permits are sought for private or commercial driving. Most felt that those with active PNES should not be allowed to drive unless certain criteria were met and that PNES should be thought of as “active” if the last psychogenic seizure had occurred within 6 months. Significance Recommendations on whether PwPNES can drive should be made at the individual patient level. Until future research has determined the risk of accidents in PwPNES a proposed algorithm may guide decisions about driving advice

The role of evidence-based guidelines in the diagnosis and treatment of functional neurological disorder

Evidence-based clinical practice guidelines, based on systematic reviews of existing evidence, play an important role in improving and standardizing the quality of patient care in many medical and psychiatric disorders, and could play an important role in the diagnosis and treatment of functional seizures and other functional neurological disorder (FND) subtypes. There are several reasons to think that evidence-based guidelines might be especially beneficial for the management of FND. In particular, the interdisciplinary and multidisciplinary teamwork necessary for the care of people with FND, the current lack of formal clinical training in FND, and the rapidly expanding body of evidence relating to FND all make guidelines based on systematic literature reviews especially valuable. In this perspective piece, we review clinical practice guidelines, their advantages and limitations, the reasons why evidence-based guidelines might be especially beneficial in the diagnosis and treatment of FND, and the steps that must be taken to create such guidelines for FND. We propose that professional organizations such as the American Academy of Neurology and the American Psychiatric Association undertake guideline development, ideally to create a co-authored or jointly endorsed set of guidelines that can set standards for interdisciplinary care for neurologists and mental health clinicians alike

Characterization of sequences in human TWIST required for nuclear localization

<p>Abstract</p> <p>Background</p> <p>Twist is a transcription factor that plays an important role in proliferation and tumorigenesis. Twist is a nuclear protein that regulates a variety of cellular functions controlled by protein-protein interactions and gene transcription events. The focus of this study was to characterize putative nuclear localization signals (NLSs) ³⁷RKRR⁴⁰and ⁷³KRGKK⁷⁷in the human TWIST (H-TWIST) protein.</p> <p>Results</p> <p>Using site-specific mutagenesis and immunofluorescences, we observed that altered TWIST^NLS1K38R, TWIST^NLS2K73R and K77R constructs inhibit nuclear accumulation of H-TWIST in mammalian cells, while TWIST^NLS2K76R expression was un-affected and retained to the nucleus. Subsequently, co-transfection of TWIST mutants K38R, K73R and K77R with E12 formed heterodimers and restored nuclear localization despite the NLSs mutations. Using a yeast-two-hybrid assay, we identified a novel TWIST-interacting candidate TCF-4, a basic helix-loop-helix transcription factor. The interaction of TWIST with TCF-4 confirmed using NLS rescue assays, where nuclear expression of mutant TWIST^NLS1with co-transfixed TCF-4 was observed. The interaction of TWIST with TCF-4 was also seen using standard immunoprecipitation assays.</p> <p>Conclusion</p> <p>Our study demonstrates the presence of two putative NLS motifs in H-TWIST and suggests that these NLS sequences are functional. Furthermore, we identified and confirmed the interaction of TWIST with a novel protein candidate TCF-4.</p

Ictal asystole with convulsive syncope mimicking secondary generalisation: a depth electrode study

Two invasive and five surface monitored seizures recorded over two years in a 51 year old woman with post-traumatic epilepsy characterised by seizure-triggered asystole were analysed. All seven seizures showed left temporal onset. Both intracranially recorded events started in the left anterior hippocampus/amygdala, spreading to the contralateral hippocampus in 35 and 25 seconds. Within 10 seconds an electrocardiogram showed asystole lasting 21 and 28 seconds, associated with suppression of recorded cerebral electrical activity, except a polyspike suppression pattern remaining in the hippocampi. Clinically, the patient, concomitantly with the cerebral suppression, developed myoclonic twitches of the limbs. A dual chamber cardiac pacemaker was implanted; at 11 months follow up, the patient has experienced only infrequent partial seizures, with none involving falls or shaking. Left temporal lobe seizures produced convulsive syncope initiated by ictal asystole. These observations suggest that intertemporal spread is necessary, though not sufficient, to produce bradycardia and asystole. Furthermore, pacemakers may decrease seizure severity, as well as potentially protect against malignant bradyarrhythmias

Progressive changes in the protein composition of the nuclear matrix during rat osteoblast differentiation.

Primary cultures of fetal rat calvarial osteoblasts undergo a developmental sequence with respect to the temporal expression of genes encoding osteoblast phenotypic markers. Based on previous suggestions that gene-nuclear matrix associations are involved in regulating cell- and tissue-specific gene expression, we investigated the protein composition of the nuclear matrix during this developmental sequence by using high-resolution two-dimensional gel electrophoresis. The nuclear matrix was isolated at times during a 4-week culture period that represent the three principal osteoblast phenotypic stages: proliferation, extracellular matrix (ECM) maturation, and mineralization. The most dramatic changes in the nuclear matrix protein patterns occurred during transitions from the proliferation to the ECM maturation stage and from ECM maturation to the mineralization period, with only minor variations in the profiles within each period. These stage-specific changes, corresponding to the major transition points in gene expression, indicate that the nuclear matrix proteins reflect the progressive differentiation of the bone cell phenotype. Subcultivation of primary cells delays mineralization, and a corresponding delay was observed for the nuclear matrix protein patterns. Thus, the sequential changes in protein composition of the nuclear matrix that occur during osteoblast differentiation represent distinct stage-specific markers for maturation of the osteoblast to an osteocytic cell in a bone-like mineralized ECM. These changes are consistent with a functional involvement of the nuclear matrix in mediating modifications of developmental gene expression

Sequence-specific DNA-binding proteins are components of a nuclear matrix-attachment site.

We have identified a nuclear matrix-attachment region within an upstream element of a human H4 histone gene promoter. Nuclear matrix proteins, isolated and solubilized from HeLa S3 cells, were found to interact with sequence specificity at this matrix-attachment region. Several types of assays for protein-DNA interaction showed that the minimal sequence for the nuclear matrix protein-DNA interaction was 5'-TGACGTCCATG-3'; the underlined region corresponds to the core consensus sequence for ATF transcription factor binding. Two proteins with molecular masses of 43 and 54 kDa were identified by UV-crosslinking analysis as integral components of this protein-DNA complex. The molecular masses of these proteins and the ATF-binding site consensus sequence suggest that these proteins are members of the ATF family. Our results provide direct evidence for nuclear matrix localization of sequence-specific DNA-binding factors for an actively transcribed gene. The proximity of a strong positive transcriptional regulatory element to the matrix-attachment region of this gene suggests that the nuclear matrix may serve to localize and concentrate trans-acting factors that facilitate regulation of gene expression