Predicting outcome of status epilepticus.

BACKGROUND: Status epilepticus (SE) is a frequent neurological emergency complicated by high mortality and often poor functional outcome in survivors. The aim of this study was to review available clinical scores to predict outcome. METHODS: Literature review. PubMed Search terms were "score", "outcome", and "status epilepticus" (April 9th 2015). Publications with abstracts available in English, no other language restrictions, or any restrictions concerning investigated patients were included. RESULTS: Two scores were identified: "Status Epilepticus Severity Score--STESS" and "Epidemiology based Mortality score in SE--EMSE". A comprehensive comparison of test parameters concerning performance, options, and limitations was performed. Epidemiology based Mortality score in SE allows detailed individualization of risk factors and is significantly superior to STESS in a retrospective explorative study. In particular, EMSE is very good at detection of good and bad outcome, whereas STESS detecting bad outcome is limited by a ceiling effect and uncertainty of correct cutoff value. Epidemiology based Mortality score in SE can be adapted to different regions in the world and to advances in medicine, as new data emerge. In addition, we designed a reporting standard for status epilepticus to enhance acquisition and communication of outcome relevant data. A data acquisition sheet used from patient admission in emergency room, from the EEG lab to intensive care unit, is provided for optimized data collection. CONCLUSION: Status Epilepticus Severity Score is easy to perform and predicts bad outcome, but has a low predictive value for good outcomes. Epidemiology based Mortality score in SE is superior to STESS in predicting good or bad outcome but needs marginally more time to perform. Epidemiology based Mortality score in SE may prove very useful for risk stratification in interventional studies and is recommended for individual outcome prediction. Prospective validation in different cohorts is needed for EMSE, whereas STESS needs further validation in cohorts with a wider range of etiologies. This article is part of a Special Issue entitled "Status Epilepticus".

Perampanel in patients with refractory and super-refractory status epilepticus in a neurological intensive care unit.

INTRODUCTION: In refractory status epilepticus (SE), because of subcellular maladaptive changes, GABAergic drugs are no longer effective, and the excitatory neurotransmitter glutamate (Glu) plays a major role in seizure perpetuation. Perampanel (PER, licensed since 09/2012) is the first orally active noncompetitive AMPA receptor antagonist for adjunctive treatment of refractory focal epilepsy. METHODS: We analyzed treatment response, seizure outcome, and adverse effects of add-on treatment with perampanel in patients with refractory status epilepticus in the Neurological Intensive Care Unit (NICU), Salzburg, Austria between 09/2012 and 11/2014 by retrospective chart review. RESULTS: Twelve patients (75% women) with refractory status epilepticus were treated with PER administered per nasogastric tube between 09/2012 and 11/2014. Median age was 75 years [range: 60-91]. The most frequent SE type was nonconvulsive SE (NCSE) with (5/12, 42%) and without coma (6/12, 50%). In seven patients (58%), SE arose de novo, with an acute symptomatic cause in five patients (42%). Cerebrovascular diseases (4/12, 33%) and cerebral tumors (4/12, 33%) were the most common etiologies. Perampanel was given after a median number of four antiepileptic drugs [range: 2-7] and a median time of 1.5 days [range: 0.8-18.3]. In one patient (8%), clinical improvement was observed within 24h and EEG improvement within 60 h after administration of PER, while in another patient (8%), clinical and EEG improvement was observed more than 48 h after administration. Median initial dose was 4 mg [range: 2-12; SD: 4.11], titrated up to a median of 12 mg [range: 4-12] in steps of 2 to 4 mg per day. No adverse effects were reported regarding cardiorespiratory changes or laboratory parameters. Outcomes after SE were moderate disability in five patients (42%), death in three patients (25%), and persistent vegetative state in two patients (17%). CONCLUSION: Though glutamate plays a major role in seizure perpetuation, the noncompetitive AMPA receptor antagonist PER could only ameliorate seizure activity in a few patients with refractory SE. The long duration of SE before the administration of PER via nasogastric tube, as well as relatively low doses of PER, might be responsible for the modest result. Perampanel was well tolerated, and no adverse events were reported. This article is part of a Special Issue entitled Status Epilepticus.

Accelerated clearance alone explains ultra-large multimers in von Willebrand disease Vicenza.

BACKGROUND: von Willebrand disease (VWD) Vicenza is characterized by low plasma von Willebrand factor (VWF) levels, the presence of ultra-large (UL) VWF multimers and less prominent satellite bands on multimer gels, and the heterozygous amino acid substitution R1205H in the VWF gene. The pathogenesis of VWD Vicenza has been elusive. Accelerated clearance is implicated as a cause of low VWF level. OBJECTIVES: We addressed the question, whether the presence of ultra-large multimers is a cause, or a result of accelerated VWF clearance, or whether it is an unrelated phenomenon. PATIENTS/METHODS: We studied the detailed phenotype of three Hungarian patients with VWD Vicenza, expressed the mutant VWF-R1205H in 293T cells and developed a mathematical model to simulate VWF synthesis and catabolism. RESULTS: We found that the half-life of VWF after DDAVP was approximately one-tenth of that after the administration of Haemate P, a source of exogenous wild-type (WT) VWF (0.81 + or - 0.2 vs. 7.25 + or - 2.38 h). An analysis of recombinant mutant VWF-R1205H showed that the biosynthesis and multimer structure of WT and mutant VWF were indistinguishable. A mathematical model of the complex interplay of VWF synthesis, clearance and cleavage showed that decreasing VWF half-life to one-tenth of normal reproduced all features of VWD Vicenza including low VWF level, ultra-large multimers and a decrease of satellite band intensity. CONCLUSION: We conclude that accelerated clearance alone may explain all features of VWD Vicenza.

Mutations affecting the indirect flight muscles of Drosophila melanogaster.

The development of the indirect flight muscles of Drosophila melanogaster was studied by analysing mutations that cause flightlessness. Twenty-five mutations on the X-chromosome and two on the third chromosome were examined. The X-chromosomal mutations form ten complementation units. The ten loci were assigned preliminary map positions by meiotic recombination and deficiencies and duplications. The two autosomal mutations represent two genes. Gynandromorph analyses suggest that many of these mutations have their primary effect in the presumptive thoracic muscle region of the embryo. The mutations cause a variety of characteristic defects, such as absence of the bulk of the thoracic muscle mass, or absence of only one of the two fibrillar muscle groups. Electronmicroscopic studies of sixteen mutants representing all twelve loci reveal abnormal myofibrillar organization in some of these mutants, e.g. aberrant or missing Z-bands, or absence of the thin filaments. Mutant protein patterns, obtained by SDS-polyacrylamide gel electrophoresis, show the following differences from wild type: ten mutants are characterized by absence of reduction of the 54 K protein, and most mutants exhibit a reduction and modification of the 80 and 90 K proteins. The absence of reduction of the 54 K protein was strongly correlated with aberrant Z-bands.

Mutations of Drosophila melanogaster that affect muscles.

Eight X-chromosome mutations (falling into five complementation groups) that affect the development and morphology of the indirect flight muscles of Drosophila melanogaster were investigated using histological, behavioural and genetic techniques. All of these mutations result in flightlessness, in a marked reduction in the ability of the flies to jump, and in the wings being held in abnormal positions. Mutations in each of the complementation groups have different effects on the morphology of the muscles. Two (flapwing, vertical wing) result in absence of most of the indirect flight muscle fibres, a third (upheld) is required for the gross organization of muscle structure, another (heldup) is involved in the maintenance of muscle structure once formed, and the fifth seems to be necessary for the detailed architecture of the muscle fibre (indented thorax). The analysis of flies genetically mosaic with respect to each mutation by the technique of fate-mapping suggests that three (heldup, upheld and indented thorax) of the genes concerned have their primary site of action in the musculature itself, while the other two (flapwing and vertical wing) may function primarily in the fat-body and tracheae respectively.

A histochemical study of the muscles of Drosophila melanogaster.

The thoracic muscles of Drosophila melanogaster can be classified into two classes, the fibrillar and the tubular muscles, on morphological grounds. Histochemical techniques were used to characterize these two classes of muscle according to their content of various enzymes (alpha-glycerophosphate, NAD-dependent isocitrate, malate and succinate dehydrogenases, fumarase, acid phosphatase, adenosine triphosphatase and acetylcholinesterase) and of glycogen. These investigations showed that the two muslces types are histochemically very different and, further, that the morphologically similar tubular muscles are heterogeneous with respect to their enzyme content. In particular, the tergal depressor of the trochanter of the second leg, the largest of the tubular muslces, has considerably less of all the enzymes studied, with the exception of acetylcholinesterase, than all the other tubular muscles examined. The histochemical techniqes were also used to follow the changes in enzyme levels that occur during development of the indirect flight muscle fibres. All the enzymes that are present in adult flight muslces showed an increase in staining intensity throughout muscle development. Some minor differences were observed in the time of appearance and rate of increase of intensity of the different enzymes.

Detection of clones in the nervous system ofDrosophila melanogaster.

Mitotic recombination was induced, by X-irradiation at the blastoderm stage, in flies heterozygous for one of the temperature-sensitive paralytic mutationsshibire andtp-2. The results show that these mutations can be used to detect the presence of clones in the central nervous system through the temperature-sensitive paralysis of individual legs. Mitotic recombination can also be used to examine the effects of these mutations in the peripheral nervous system; shibire is thus shown to affect the function of sensory neurons.

Effects of discrete nuclear u.v-microbeam irradiation on herpes virus and SV40 infection.

The requirement for a nucleolus in the expression of structural genes of nuclear viruses was examined by means of experiments in which the nucleolus or other parts of the nucleus was inactivated by a microbean of unltraviolet light. These experiments showed that the expression of such genes is not dependent on cucleolar function. This conclusion is discussed in the light of previous experiments in which similar inactiviation of nucleolus was shown to prevent the expression of cellular structural genes.