Memory impairment is not necessarily related to seizure frequency in mesial temporal lobe epilepsy with hippocampal sclerosis.

OBJECTIVE: To investigate the effect of seizure frequency on memory, we performed a cross sectional study comparing mesial temporal lobe epilepsy (MTLE) patients with frequent and infrequent seizures. METHODS: We performed magnetic resonance imaging (MRI) hippocampal volume (HV) measurements and neuropsychological assessment in 22 patients with frequent seizures (at least one dyscognitive seizure [DS] per month) that were refractory to antiepileptic drugs and 20 patients with infrequent seizures (three or less DS per year and no event evolving to a bilateral convulsive seizure), all with MRI signs of hippocampal sclerosis (HS) on visual analysis. We also included 29 controls for comparison of volumetric data. RESULTS: There was no difference in memory performance between patients with frequent seizures and infrequent seizures. We observed a significant bilateral reduction of HV in patients with MTLE when compared to controls (p < 0.001). The degree of hippocampal atrophy (HA) between patients with frequent and infrequent seizures was not different. There was a negative correlation between seizure frequency and HV, with r = -0.3 for the HV ipsilateral to the HS and r = -0.55 for the contralateral side, thus, explaining only 9% and 30% of the HV loss. There was a positive correlation between age of onset and degree of HA (r = 0.37). SIGNIFICANCE: Our data suggest that seizure frequency does not explain most of the HV loss or memory impairment in MTLE. Memory impairment appears to be more influenced by hippocampal damage than by seizure frequency. Further studies are necessary to identify the factors that influence memory decline in patients with MTLE.

A multimodal evaluation of microstructural white matter damage in spinocerebellar ataxia type 3.

Although white matter damage may play a major role in the pathogenesis of spinocerebellar ataxia 3 (SCA3), available data rely exclusively upon macrostructural analyses. In this setting we designed a study to investigate white matter integrity. We evaluated 38 genetically-confirmed SCA3 patients (mean age, 52.76 ± 12.70 years; 21 males) with clinical scales and brain magnetic resonance imaging (MRI) and 38 healthy subjects as a control group (mean age, 48.86 ± 12.07 years, 20 male). All individuals underwent the same protocol for high-resolution T1 and T2 images and diffusion tensor imaging acquisition (32 directions) in a 3-T scanner. We used Tract-Based Spatial Statistics (FSL 4.1.4) to analyze diffusion data and SPM8/DARTEL for voxel-based morphometry of infratentorial structures. T2-relaxometry of cerebellum was performed with in-house-developed software Aftervoxel and Interactive Volume Segmentation (IVS). Patients' mean age at onset was 40.02 ± 11.48 years and mean duration of disease was 9.3 ± 2.7 years. Mean International Cooperative Ataxia Rating Scale (ICARS) and Scale for Assessment and Rating of Ataxia (SARA) scores were 32.08 ± 4.01 and 14.65 ± 7.33, respectively. Voxel-based morphometry demonstrated a volumetric reduction of gray and white matter in cerebellum and brainstem (P <.001). We found reduced fractional anisotropy (P <.05) in the cerebellum and brainstem. There were also areas of increased radial diffusivity (P <.05) in the cerebellum, brainstem, thalamus, frontal lobes, and temporal lobes. In addition, we found decreased T2-relaxation values in the white matter of the right cerebellar hemisphere. Microstructural white matter dysfunction, not previously reported, occurs in the cerebellum and brainstem of SCA3 patients.

Characterization of dual effects induced by antimicrobial peptides: regulated cell death or membrane disruption.

BACKGROUND: Some reports describe lysis mechanisms by antimicrobial peptides (AMPs), while others describe the activation of regulated cell death. In this study, we compare the cell death-inducing activities of four ß-hairpin AMPs (gomesin, protegrin, tachyplesin and polyphemusin II) along with their linear analogs in the human erythroleukemia K562 cell line to investigate the relationship between their structure and activity. METHODS: K562 cells were exposed to AMPs. Morphological and biochemistry alterations were evaluated using light microscopy, confocal microscopy and flow cytometry. RESULTS: Gomesin and protegrin displayed cytotoxic properties that their linear counterparts did not. Tachyplesin and polyphemusin II and also their linear analogs induced cell death. We were able to distinguish two ways in which these AMPs induced cell death. Lower concentrations of AMPs induced controlled cell death mechanisms. Gomesin, tachyplesin and linear-tachyplesin promoted apoptosis that was characterized by annexin labeling, sensitivity to Z-VAD, and caspase-3 activation, but was also inhibited by necrostatin-1. Gomesin and protegrin induced cell death was dependent on intracellular Ca2+ mechanisms and the participation of free radicals was observed in protegrin induced cell death. Polyphemusin II and its linear analog mainly induced necrosis. Conversely, treatment with higher concentrations of AMPs primarily resulted in cell membrane disruption, but with clearly different patterns of action for each AMP tested. CONCLUSION: Different actions by ß-hairpin AMPs were observed at low concentrations and at higher concentrations despite the structure similarity. GENERAL SIGNIFICANCE: Controlled intracellular mechanism and direct membrane disruption were clearly distinguished helping to understand the real action of AMPs in mammalian cells.