Visual Naming Performance after ATL Resection: Impact of Atypical Language Dominance.

Purpose- To characterize the interaction between language dominance and lateralization of the epileptic focus for pre- and postoperative Boston Naming Test (BNT) performance in patients undergoing anterior temporal lobectomy (ATL). Methods- Analysis of pre- and postoperative BNT scores depending on lateralization of language as measured by the intracarotid amobarbital procedure (IAP) versus lateralization of the temporal lobe epileptic focus. Results- Changes between pre- and postoperative BNT performance depended on epilepsy lateralization (effect size = 0.189) with significant decrease in patients undergoing left ATL. Subgroup analysis in these showed that postoperative decline in BNT scores was significant in patients with atypical (n = 14; p \u3c 0.05), but did not reach statistical significance in patients with left language dominance (n = 36; p = 0.09). Chi-square test revealed a trend of higher proportions of patients experiencing significant postsurgical deterioration in naming performance in atypical (57.1%) as compared to left language dominance (30.6%; p = 0.082). Surgical failure was also associated with greater decline of BNT scores and was more common in atypical than in left language dominant patients (χ2 (1, n = 98) = 4.62, p = 0.032). Age of onset, duration of epilepsy, and seizure frequency had no impact on changes in BNT performance. Conclusion- Atypical language dominance is a predictor of change in visual naming performance after left ATL and may also impact postsurgical seizure control. This should be considered when counseling surgical candidates

Frequency of seizures and epilepsy in neurological HIV-infected patients

SummaryBackgroundInfection with the human immunodeficiency virus (HIV) is associated both with infections of the central nervous system and with neurological deficits due to direct effects of the neurotropic virus. Seizures and epilepsy are not rare among HIV-infected patients. We investigated the frequency of acute seizures and epilepsy of patients in different stages of HIV infection. In addition, we compared the characteristics of patients who experienced provoked seizures only with those of patients who developed epilepsy.MethodsThe database of the Department of Neurology, University of Münster, was searched for patients with HIV infection admitted between 1992 and 2004. Their charts were reviewed regarding all available sociodemographic, clinical, neurophysiological, imaging and laboratory data, therapy and outcome. Stage of infection according to the CDC classification and the epileptogenic zone were determined.ResultsOf 831 HIV-infected patients treated in our department, 51 (6.1%) had seizures or epilepsy. Three of the 51 patients (6%) were diagnosed with epilepsy before the onset of the HIV infection. Fourteen patients (27%) only had single or few provoked seizures in the setting of acute cerebral disorders (eight patients), drug withdrawal or sleep withdrawal (two patients), or of unknown cause (four patients). Thirty-four patients (67%) developed epilepsy in the course of their HIV infection. Toxoplasmosis (seven patients), progressive multifocal leukencephalopathy (seven patients) and other acute or subacute cerebral infections (five patients) were the most frequent causes of seizures. EEG data of 38 patients were available. EEG showed generalized and diffuse slowing only in 9 patients, regional slowing in 14 patients and regional slowing and epileptiform discharges in 1 patient. Only 14 of the patients had normal EEG. At the last contact, the majority of the patients (46 patients=90%) were on highly active antiretroviral therapy (HAART). Twenty-seven patients (53%) were on anticonvulsant therapy (gabapentin: 14 patients, carbamazepine: 9 patients, valproate: 2 patients, phenytoin: 1 patient, lamotrigine: 1 patient). Patients with only provoked seizures had no epilepsy risk factors except HIV infection, and were less likely to be infected via intravenous drug abuse.ConclusionsSeizures are a relevant neurological symptom during the course of HIV infection. Although in some patients seizures only occur provoked by acute disease processes, the majority of patients with new onset seizures eventually develops epilepsy and require anticonvulsant therapy. Intravenous drug abuse and the presence of non-HIV-associated risk factors for epilepsy seem to be associated with the development of chronic seizures in this patient group

Functional characterisation of the mammalian NDR1 and NDR2 protein kinases and their regulation by the mammalian Ste20-like kinase MST3

Protein modification is a common regulatory mechanism in order to transduce a signal from one molecule to another. One of the best-studied protein modifications is phosphorylation. The enzymes that are capable of transferring phosphate groups onto other proteins are called protein kinases. Depending on the acceptor group, kinases can be distinguished into tyrosine, serine/threonine and dual-specificity kinases. This work describes the characterisation of human and mouse NDR1 and NDR2 kinases, members of the AGC group of serine/threonine kinases. The NDR protein kinase family is highly conserved between yeast and human, and several members have been shown to be involved in the regulation of cell morphology and the control of cell cycle progression. For example, the yeast NDR kinases Sid2p (Schizosaccharomyces pombe) and Dbf2p (Saccharomyces cerevisiae) are central components of the septation-initiation network and the mitosis exit network, respectively. The closest yeast relatives Cbk1p and Orb6p, members of the regulation of Ace2p transcription and morphogenesis network and Orb6 signalling pathways, are implicated in the coordination of cell cycle progression and cell morphology. This study, as well as studies using worms and flies, provide evidence that not only NDR is conserved, but also the NDR signalling pathway and regulation. Similar to yeast, NDR kinase activation is regulated by phosphorylation at the activation segment phosphorylation site and the hydrophobic motif phosphorylation site. This phosphorylation is regulated by a conserved signaling module consisting of MOB proteins and a STE20–like kinase. Here we show that the STE20-like kinase MST3 activates NDR by phosphorylation specifically at the hydrophobic motif in vitro and in vivo. Furthermore, MOB1A binding is important for the release of autoinhibition and full kinase activation. The data also indicate that NDR is part of a feedback mechanism, which induces cleavage and nuclear translocation of MST3. The data presented here also show that NDR1 and NDR2 are differentially expressed, but regulated in a similar manner. Mouse Ndr1 mRNA is mainly expressed in spleen, thymus and lung, whereas Ndr2 mRNA is more ubiquitously expressed, with the highest levels in the gastrointestinal tract. Both, NDR1 and NDR2, are activated by S100B protein and okadaic acid stimulated phosphorylation; NDR1 and NDR2 are also indistinguishable in the biochemical assays used: membrane targetting, phosphorylation by MST3, and activation by MOB. Further, this work describes the generation and initial characterisation of a mouse model for NDR1 deficiency. Protein analysis using NDR1 knockout mouse embryonic fibroblasts suggest a compensation of the loss of NDR1 by upregulation of NDR2 expression

Efficacy, Retention, and Tolerability of Brivaracetam in Patients With Epileptic Encephalopathies: A Multicenter Cohort Study From Germany

Objective: To evaluate the efficacy and tolerability of brivaracetam (BRV) in a severely drug refractory cohort of patients with epileptic encephalopathies (EE).Method: A multicenter, retrospective cohort study recruiting all patients treated with EE who began treatment with BRV in an enrolling epilepsy center between 2016 and 2017.Results: Forty-four patients (27 male [61%], mean age 29 years, range 6 to 62) were treated with BRV. The retention rate was 65% at 3 months, 52% at 6 months and 41% at 12 months. A mean retention time of 5 months resulted in a cumulative exposure to BRV of 310 months. Three patients were seizure free during the baseline. At 3 months, 20 (45%, 20/44 as per intention-to-treat analysis considering all patients that started BRV including three who were seizure free during baseline) were either seizure free (n = 4; 9%, three of them already seizure-free at baseline) or reported at least 25% (n = 4; 9%) or 50% (n = 12; 27%) reduction in seizures. An increase in seizure frequency was reported in two (5%) patients, while there was no change in the seizure frequency of the other patients. A 50% long-term responder rate was apparent in 19 patients (43%), with two (5%) free from seizures for more than six months and in nine patients (20%, with one [2 %] free from seizures) for more than 12 months. Treatment-emergent adverse events were predominantly of psychobehavioural nature and were observed in 16%.Significance: In this retrospective analysis the rate of patients with a 50% seizure reduction under BRV proofed to be similar to those seen in regulatory trials for focal epilepsies. BRV appears to be safe and relatively well tolerated in EE and might be considered in patients with psychobehavioral adverse events while on levetiracetam

Adsorption of finite polymers in different thermodynamic ensembles

We investigate the cooperative effects of a single finite chain of monomers near an attractive substrate by first constructing a conformational pseudo-phase diagram based on the thermal fluctuations of energetic and structural quantities. Then, the adsorption transition is analyzed in more detail. This is conveniently done by a microcanonical analysis of densities of states obtained by extensive multicanonical Monte Carlo simulations. For short chains and strong surface attraction, the microcanonical entropy turns out to be a convex function of energy in the transition regime. This is a characteristic physical effect and deserves a careful consideration in analyses of cooperative macrostate transitions in finite systems. (C) 2010 Elsevier B.V. All rights reserved

Akute tubulointerstitielle Nephritis bei HIV-Erkrankung

We report about a patient with human immunodeficiency virus infection who developed acute renal failure after therapy with atazanavir. Renal biopsy showed acute interstitial nephritis. After discontinuing medication with atazanavir serum creatinine level decreased spontaneously without steroids. The different etiologies of acute renal failure in patients with human immunodeficiency infection are discussed. Die Fallbeschreibung illustriert den Verlauf eines akuten Nierenversagens bei einer Atazanavir-assoziierten akuten tubulointerstitiellen Nephritis bei HIV-Erkrankung im CDC-Stadium B2. Nach Absetzen des Virostatikums Atazanavir war das akute Nierenversagen unter konservativer Therapie ohne Einsatz von Steroiden reversibel. Die Differenzialdiagnose des akuten Nierenversagens bei HIV-Erkrankung wird dargestellt

The Inflammatory Chemokine CXCL10 Modulates Synaptic Plasticity and Neuronal Activity in the Hippocampus

Chemokines, a family member of cytokines, have been shown to play a major role in central nervous system inflammation. Among other chemokines, CXCR3 and its ligand CXCL10 are involved in the pathophysiology of several neuroinflammatory conditions. Most of these conditions are also associated with an increased incidence of seizure or epilepsy. Using age-matched wild-type (WT), as well as CXCR3-receptor-deficient (CXCR3-KO) mice, the present study aimed to investigate the effect of the chemokine CXCL10 and its receptor CXCR3 on synaptic plasticity as well as neuronal activities in hippocampal brain slices. Using field potential and intracellular recordings, the effect of exogenous CXCL10 on tetanus-induced long-term potentiation (LTP) as well as the neuronal spike activity was evaluated in hippocampal CA1 area. Exogenous application of CXCL10 enhanced LTP in WT mice, whereas it exerted no significant effect on CXCR3-KO mice. During intracellular recordings of spontaneous spike activity, exogenous application of CXCL10 significantly enhanced the amplitude, duration, and after-hyperpolarization of action potentials in slices obtained from WT mice compared to CXCR3-KO mice. In addition, CXCR3-KO mice exhibited a lower GABA A -mediated excitation in hippocampal CA1 neurons compared to WT mice. These data show that the inflammatory chemokine CXCL10, probably via its receptor CXCR3, modulates neuronal activity and synaptic plasticity in the hippocampus. CXCL10 may be involved in seizures observed during neuroinflammatory diseases such as meningitis and encephalitis