bluuebunny/crossref_metadata_2025_split huggingface dataset:
Activity, tolerability and efficacy of levetiracetam on cerebellar symptoms in multiple sclerosis patients: a pilot kinematic study
Authors: Solaro C. , Brichetto G. , Capello E. , Abuarqub S. , Sanguineti V. 
Published: May 2008

Background and purpose:  The aim of this study was to evaluate the activity measured by kinematic analysis, tolerability and efficacy of levetiracetam (LEV) in multiple sclerosis (MS) patients affected by cerebellar symptoms, in a randomized single‐blind, placebo‐controlled cross‐over study.Methods:  Eight MS subjects with cerebellar signs (five female and three male; mean EDSS: 4.77; mean disease duration 9.2) performed a reaching task on a digitizing tablet and their trajectories went through a kinematic analysis. The subjects were assessed at baseline, after 21 days of treatment, after wash‐out period (day 35) and after 21 days of treatment (day 56). LEV was used at the maximum dosage of 1500 mg daily. The primary outcome was the modification on smoothness (JERK) whilst aiming error (AAI) and centripetal acceleration (CA) were considered as secondary outcomes.Results:  Two subjects were excluded from the final analysis. Primary outcome (i.e. JERK) was significantly affected by the administration of LEV overtime (nine arms in active treatment versus three arms in placebo decreased the mean values of their JERK). Regarding secondary outcomes CA was significantly affected by the administration of LEV. No statistical significant results were found comparing clinical scales during the four assessments.Discussion:  The results indicate that LEV was able to modify kinematic parameter so the medication was active but no improvement in clinical scales was observed. LEV needs to be tested in a larger group of subjects designed to verify treatment efficacy using higher dosage of the medication.
Gelsolin concentration in cerebrospinal fluid from patients with multiple sclerosis and other neurological disorders
Authors: Kulakowska A. , Drozdowski W. , Sadzynski A. , Bucki R. , Janmey P. A. 
Published: May 2008

Background:  Gelsolin is a highly conserved intracellular actin‐binding protein with an extracellular isoform, plasma gelsolin, for which there is not yet a clearly defined function. Materials and methods:  In this study, we determined gelsolin concentrations in blood and cerebrospinal fluid (CSF) obtained from 25 subjects using immunoblotting and a functional assay that quantifies gelsolin’s ability to accelerate actin polymerization. Results:  The gelsolin concentration in CSF, determined by quantitative immunoblotting was 1.2–15.9 μg/ml (average 5.9 ± 3.8 μg/ml). In samples obtained from patients diagnosed with conditions that do not alter standard CSF clinical tests [(idiopathic cephalgia, ischialgia due to discopathy, and idiopathic (Bell’s) facial nerve palsy or entrapment radial neuropathy)], the average gelsolin concentration was 7.2 ± 4.3 μg/ml. In contrast, the gelsolin concentration in samples obtained from patients diagnosed with multiple sclerosis was 2.1 ± 0.7 μg/ml, and a similar low concentration was found in a patient recovering from a subarachnoid hemorrhage. The range of CSF gelsolin concentrations determined by the actin polymerization assay was 0.61–9.97 μg/ml (average 3.6 ± 2.2 μg/ml). These lower values compared with those obtained from immunoblotting analysis suggest that CSF gelsolin may bind other CSF molecules leading to a reduction of its actin‐binding activity. Conclusions:  The results presented here show that CSF gelsolin concentration is significantly altered in certain neurological conditions, including multiple sclerosis, indicating the possible utility of CSF gelsolin levels for diagnostic purposes.
Microtubules in basalt glass from Hawaii Scientific Driling Project #2 phase 1 core and Hilina slope, Hawaii: evidence of the occurrence and behavior of endolithic microorganisms
Authors: WALTON A. W 
Published: May 2008

ABSTRACTElongate, fine tubes, ~1 µm wide and up to 200 µm long, extend from fractured surfaces, vesicle walls, and internal fractures into fragments of basalt glass in samples from the Hawaii Scientific Drilling Project #2 phase 1 (HSDP #21) core and the Hilina slope, Hawaii. Several features indicate that these tubes are microbial endolithic microborings: the tubes resemble many described microborings from oceanic basalt glass, their formation is postdepositional but restricted to certain but different ranges of time in the two sets of samples, and they are not uniformly distributed throughout glass fragments. Microtubules record several characteristic behaviors including boring into glass, mining, seeking olivine, and avoiding plagioclase. They also are highly associated with a particular form of glass‐replacing smectite. Evidence of behavior should join morphological and geochemical criteria in indicating microbial alteration of basalt glass.In some samples, steeply conical tubes, ~10–20 µm in diameter tapering to 1 µm and commonly filled with smectite, appear to be modifications or elaborations of the microtubules. These also curve toward olivine and are associated with replacement smectite. In HSDP #21samples, microtubules initiated at margins of shards before palagonite replaced those margins and are preserved during palagonitization. In fact, microtubules appear to have provided routes that enhanced the efficiency of water's reaching of unaltered glass. In Hilina Slope samples, the microtubules appear to postdate palagonitization because they initiate at the boundary between palagonite and unaltered sideromelane.Preservation of microtubules during palagonitization in samples together with recognition of other associated characteristics representing behavior suggests that such features may be recognizable in more heavily altered ancient rocks.
Clinical correlates of pathological gambling symptoms in patients with epilepsy
Authors: Cavanna Andrea E. , Mula Marco , Strigaro Gionata , Servo Serena , Tota Grazia , Barbagli Davide , Collimedaglia Laura , Viana Michele , Cantello Roberto , Monaco Francesco 
Published: May 2008

Summary Pathological gambling symptoms (PGS), that is, the subjective urge to gamble and the actual gambling behaviors, are currently acknowledged as relatively common symptoms among Western countries, with an estimated point prevalence of 0.6–1.1% in the general population. Converging evidence suggests that PGS are overrepresented in patients with neurological conditions affecting dopaminergic reward pathways, and can be expressed in both impulse control disorders and obsessive‐compulsive spectrum disorders. This study explored the clinical correlates of PGS in patients with epilepsy. Eighty‐eight consecutive adult outpatients recruited at three epilepsy clinics in northern Italy were assessed using the Gambling‐Symptom Assessment Scale (G‐SAS), along with a battery of psychometric instruments to index depression (Beck Depression Inventory [BDI]), anxiety (Spielberger State‐Trait Anxiety Inventory [STAI]), and obsessionality (Yale‐Brown Obsessive Compulsive Scale [YBOCS]) symptoms. On the G‐SAS, patients with a diagnosis of temporal lobe epilepsy (TLE) reported a mean [sd] G‐SAS score of 2.0 [5.7], significantly higher than patients with frontal lobe epilepsy (FLE) (0.6 [1.7]) and idiopathic generalized epilepsy (IGE) (0.4 [1.4]). Moreover, multiple regression analysis showed that G‐SAS scores were selectively predicted by YBOCS scores, thus suggesting an association between the expression of obsessional spectrum symptoms and PGS in patients with TLE. Alterations in the mesolimbic reward system could represent the putative neuropathological substrate for this multifaceted clinical picture.
Occurrence of seizures in association with work‐related stress in young male army recruits
Authors: Moshe Shlomo , Shilo Michal , Chodick Gabriel , Yagev Yaron , Blatt Ilan , Korczyn Amos D. , Neufeld Miri Y. 
Published: May 2008

Summary
Purpose: To examine the risk of undergoing an epileptic seizure as a function of differing levels of occupational stress (physical and mental) in new military recruits with no previous history of epilepsy or with epilepsy in remission for over 2 years.
Methods: The medical records of over 300,000 18‐year‐old men recruited to the Israeli army between mid‐eighties and mid‐nineties were used to assemble a cohort, which was followed for a period of 30 months. The severity of epilepsy at recruitment was determined according to four categories, 0 (no history of seizures) and 1–3 (history of seizures with different relapse‐free periods, with or without treatment). The soldiers were subdivided according to their occupational categories to: combat units (CU), maintenance units (MU), and administrative units (AU).
Results: The annual incidence rates per 100,000 in category 0 were 317, 298, and 401 in AU, MU, and CU, respectively. The incidence of seizures in category 0 was higher (relative risk [RR]= 1.29, CI = 1.03–1.62) in CU compared to AU and MU. No differences were found for seizure recurrence among various occupational groups.
Conclusion: The increased risk of seizures in CU compared to AU and MU may indicate contribution of service conditions in CU, like physical and mental stress. The equivalent rates of seizure relapse, regardless of the type of occupation, suggests the need for minimal occupational restrictions for epilepsy patients who have been free of seizures for long periods.
Microchromosomal deletions involving SCN1A and adjacent genes in severe myoclonic epilepsy in infancy
Authors: Wang Ji‐wen , Kurahashi Hirokazu , Ishii Atsushi , Kojima Toshio , Ohfu Masaharu , Inoue Takahito , Ogawa Atsushi , Yasumoto Sawa , Oguni Hirokazu , Kure Shigeo , Fujii Tatsuya , Ito Masatoshi , Okuno Takehiko , Shirasaka Yukiyoshi , Natsume Jun , Hasegawa Aki , Konagaya Akihiko , Kaneko Sunao , Hirose Shinichi 
Published: May 2008

Summary
Purpose: Genetic abnormalities of the gene encoding α1 subunit of the sodium channel (SCN1A), which can be detected by direct sequencing, are present in more than 60% of patients with severe myoclonic epilepsy in infancy (SMEI) or its borderline phenotype (SMEB). Microchromosomal deletions have been recently reported as additional causes of SMEI. This study examines whether such microdeletions are associated with SMEI as well as with SMEB.
Methods: We recruited patients with SMEI (n = 35) and SMEB (n = 34), who were confirmed previously to have no mutations of SCN1A by direct sequencing. Microdeletions were sought by multiplex ligation‐dependent probe amplification (MLPA), and then confirmed and characterized by fluorescence in situ hybridization (FISH) and array‐based comparative genomic hybridization (aCGH), respectively.
Results: Heterozygous multiple exonic deletions were identified in 7/35 SMEI patients (20%) and 0/34 SMEB patients (0%), with a net frequency of 10.1% (7/69 patients). Deletions were confirmed by FISH and aCGH analysis. The concomitant deletions of adjacent genes were revealed by aCGH. None of the parents who agreed to undergo the analysis had such deletions suggesting that the deletions were de novo. The phenotypes of patients with the deletions were indistinguishable from those of SMEI resulting from point mutations.
Discussion: Our findings indicate that microchromosomal deletion, often involving not only SCN1A but also several adjacent genes, is associated with core SMEI. As microchromosomal deletion cannot be anticipated by the phenotypes or detected by conventional methods, genetic abnormalities in SMEI should be carefully sought by techniques that can detect microdeletions.
Psychoses of epilepsy in Babylon: The oldest account of the disorder
Authors: Reynolds Edward H. , Kinnier Wilson James V. 
Published: May 2008

Summary We have previously published translations of Babylonian texts on epilepsy and stroke, which we believe to be the oldest detailed accounts of these neurological disorders from the second millennium BC. We now present a short Babylonian text, which clearly describes what are today known as interictal or schizophrenia‐like psychoses of epilepsy. The text includes many of the classical symptoms of the syndrome, for example, paranoid delusions, hallucinations and mood disorders, as well as religiosity and hyposexuality, which have only been crystallized in the twentieth century. The Babylonians were remarkably good observers of human disease and behavior but had little or no understanding of pathology or brain function. Although they recognized many natural causes of disease, epilepsy and behavior disorders were attributed to supernatural, usually evil forces, the forerunner of the Greek concept of the Sacred Disease.
A cellular mechanism for dendritic spine loss in the pilocarpine model of status epilepticus
Authors: Kurz Jonathan E. , Moore Bryan J. , Henderson Scott C. , Campbell John N. , Churn Severn B. 
Published: May 2008

SummaryPurpose:  Previous studies have documented a synaptic translocation of calcineurin (CaN) and increased CaN activity following status epilepticus (SE); however, the cellular effect of these changes in CaN in the pathology of SE remains to be elucidated. This study examined a CaN‐dependent modification of the dendritic cytoskeleton. CaN has been shown to induce dephosphorylation of cofilin, an actin depolymerization factor. The ensuing actin depolymerization can lead to a number of physiological changes that are of interest in SE.Methods:  SE was induced by pilocarpine injection, and seizure activity was monitored by video‐EEG. Subcellular fractions were isolated by differential centrifugation. CaN activity was assayed using a paranitrophenol phosphate (pNPP) assay protocol. Cofilin phosphorylation was assessed using phosphocofilin‐specific antibodies. Cofilin–actin binding was determined by coimmunoprecipitation, and actin polymerization was measured using a triton‐solubilization protocol. Spines were visualized using a single‐section rapid Golgi impregnation procedure.Results:  The immunoreactivity of phosphocofilin decreased significantly in hippocampal and cortical synaptosomal samples after SE. SE‐induced cofilin dephosphorylation could be partially blocked by the preinjection of CaN inhibitors. Cofilin activation could be further demonstrated by increased actin–cofilin binding and a significant depolymerization of neuronal actin, both of which were also blocked by CaN inhibitors. Finally, we demonstrated a CaN‐dependent loss of dendritic spines histologically.Discussion:  The data demonstrate a CaN‐dependent, cellular mechanism through which prolonged seizure activity results in loss of dendritic spines via cofilin activation. Further research into this area may provide useful insights into the pathology of SE and epileptogenic mechanisms.
Impaired NaV1.2 function and reduced cell surface expression in benign familial neonatal‐infantile seizures
Authors: Misra Sunita N. , Kahlig Kristopher M. , George Alfred L. 
Published: May 2008

Summary
Purpose: Mutations in SCN2A, the gene encoding the brain voltage‐gated sodium channel α‐subunit Na
V
1.2, are associated with inherited epilepsies including benign familial neonatal‐infantile seizures (BFNIS). Functional characterization of three BFNIS mutations was performed to identify defects in channel function that underlie this disease.
Methods: We examined three BFNIS mutations (R1319Q, L1330F, and L1563V) using whole‐cell patch‐clamp recording of heterologously expressed human Na
V
1.2. Membrane biotinylation was employed to examine the cell surface protein expression of the four Na
V
1.2 alleles.
Results: R1319Q displayed mixed effects on activation and fast inactivation gating, consistent with a net loss of channel function. L1563V exhibited impaired fast inactivation predicting a net gain of channel function. The L1330F mutation significantly decreased overall channel availability during repetitive stimulation. Patch‐clamp analysis also revealed that cells expressing BFNIS mutants exhibited lower levels of sodium current compared to wild type (WT) Na

V

1.2. Biochemical experiments demonstrated that all three BFNIS mutations exhibited a significant reduction in cell surface expression compared to WT.
Discussion: Our findings indicate that BFNIS is associated with a range of biophysical defects accompanied by reduced levels of channel protein at the plasma membrane.
Refractory status epilepticus during pregnancy secondary to cavernous angioma
Authors: Aladdin Yasser , Gross Donald W. 
Published: May 2008

Summary First‐time seizure and status epilepticus during pregnancy have been previously reported as the initial manifestation of intracranial cavernous hemangioma. We report a woman with no history of seizures who presented with refractory status epilepticus at 10 weeks gestation. Cranial MRI revealed a right frontal cavernous hemangioma. The seizures remained refractory to conventional anticonvulsant medications and 48 h of general anesthetic. Termination of the pregnancy resulted in almost immediate resolution of the seizures. The dramatic response of the seizures to termination of the pregnancy suggests that hormonal factors were primarily responsible for the precipitous presentation in this patient.
Exposure to antiepileptic drugs and the risk of hip fracture: A case‐control study
Authors: Tsiropoulos Ioannis , Andersen Morten , Nymark Tine , Lauritsen Jens , Gaist David , Hallas Jesper 
Published: May 2008

SummaryPurpose:  To investigate whether the use of antiepileptic drugs (AEDs) increases the risk of hip fracture.Methods:  We performed a case‐control study using data from the Funen County (population 2004: 475,000) hip fracture register. Cases (n = 7,557) were all patients admitted to county hospitals with a hip fracture during the period 1996–2004. Controls (n = 27,575) were frequency matched by age and gender. Information on use of AEDs, other drugs, and hospital contacts was available from local registers. Odds ratios (ORs) with 95% confidence intervals (CI) for hip fracture were estimated by unconditional logistic regression.Results:  Fracture risk was increased with ever use of any AED (OR: 1.31; 95% CI: 1.16–1.48). The risk was also increased with use of only enzyme inducing (OR: 1.31; 95% CI: 1.14–1.51), but not with use of only noninducing AEDs (OR: 1.03; 95% CI: 0.77–1.37). Current (OR: 1.92; 95% CI: 1.58–2.33) and recent use, as well as high daily (OR: 1.50; 95% CI: 1.24–1.82) and cumulative dose increased fracture risk, but long treatment duration or previous use did not. The risk was modified by the presence of an epilepsy diagnosis.Conclusion:  Use of AEDs modestly increases the risk of hip fracture. The risk increase is probably associated to a higher degree with a dose dependent effect on CNS with current and recent use, than with an effect on bone tissue.
Interictal spikes on intracranial recording: Behavior, physiology, and implications
Authors: Spencer Susan S. , Goncharova Irina I. , Duckrow Robert B. , Novotny Edward J. , Zaveri Hitten P. 
Published: May 2008

SummaryPurpose:  The physiological, pathological, and clinical meaning of interictal spikes (IISs) remains controversial. We systematically analyzed the frequency, occurrence, and distribution of IISs recorded from multiple intracranial electrodes in 34 refractory epileptic patients with respect to seizures and antiepileptic drug (AED) changes.Methods:  Continuous spike counts from all recorded contacts of all implanted electrodes, and also separately for the subset of contacts involved at seizure onset, were tabulated for every hour of every day of recording, and expressed as spikes per hour in six preselected, 24‐h intervals (defined to exclude seizures): (1) on medications; (2) prepreseizure; (3) preseizure; (4) postseizure; (5) off meds; and (6) resumed meds. Mean spike rates were analyzed for differences between designated 24‐h intervals.Results:  Spike rate in all recorded contacts consistently and significantly decreased after AED withdrawal, despite variability in initial spike rate, diurnal occurrence, seizure character/number/localization of onset, and type(s) of AED continued or withdrawn (p < 0.0001). A significant increase in spike rate was noted in the 24 h after seizures of medial temporal origin, in the medial temporal lobe contacts; neocortical onset seizures did not show any increase.Conclusions:  These observations confirm and extend previous reports, suggesting a general effect of AED withdrawal, and a more specific effect of medial temporal lobe seizures, on IIS rate. AED mechanisms and efficacy might be demonstrated by quantifying IIS with changes in AEDs. Furthermore, variability in IIS rate after seizures distinguishes localization of seizure onset in medial temporal versus neocortical locations.
Glutamine synthetase becomes nitrated and its activity is reduced during repetitive seizure activity in the pentylentetrazole model of epilepsy
Authors: Bidmon Hans‐J. , Görg Boris , Palomero‐Gallagher Nicola , Schleicher Axel , Häussinger Dieter , Speckmann Erwin J. , Zilles Karl 
Published: May 2008

SummaryPurpose:  The astrocyte‐specific glutamine synthetase (GS) plays a key role in glutamate recycling and Gamma‐aminobutyric acid (GABA) metabolism. Changes in the expression or activity of GS have been proposed to contribute to epileptogenesis. The mechanisms or how and where GS may contribute to epilepsy is still a matter of discussion. Here we asked the question whether brain regions, which show an astrocytic stress response respond with alterations of GS.Methods:  Biochemical and histological alterations of GS, HSP‐27, and GFAP were studied after pentylenetetrazole‐induced repetitive epileptic seizures (PIRS) in rats using a topographical quantification of the GS‐immunoreactivity (GSIR) in relation to the focal heat shock response (HSR). Saline‐treated rats served as controls and rats treated by the GS‐inhibitor, L‐methionine‐sulfoximine (MSO) served as a positive control.Results:  No changes in the amount of GSIR and GS‐protein occurred during PIRS. A significant reduction of GSIR was observed by histochemistry (in situ) and in native (nonheated) protein extracts of MSO‐treated rats. In rats affected by PIRS, GS‐activity showed a significant, region‐specific reduction in association with a nitration of the enzyme.Discussion:  These results show that neither PIRS nor GS‐inhibition reduced the amount of GS protein, but that MSO interferes with antibody binding to native GS. PIRS resulted in a focal increase of astrocytic stress response, whereas MSO caused a widespread, homogeneous astrocytic HSR independent from quantitative changes of GS content. In rats with PIRS the regions showing a strong glial HSR, respond with reduced GS‐activity and GS‐nitration, which all together are clear indicators of a nitrosative stress response.