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.

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.

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.