bluuebunny/crossref_metadata_2025_split huggingface dataset:
Adverse drug interactions as a high‐risk factor for lethal post‐transplant complications in Chinese population
Authors: Yang Ting , Wu Xue Mei , Qiu Hong Qiang , Fu Dan Hui , Hu Jian Da , Li Jian , Zheng Xiao Yun , Luo Xiao Feng , Yuan Xiao Hong , Chen Ru Ling , Chen Zhi Zhe 
Published: January 2013

AbstractMetabolism of triazole antifungal agents is highly competitive to conventional post‐transplant immunosuppressants like cyclosporine A (CsA) via the cytochrome P450‐dependent pathway. We present the first report on lethal complications that may arise due to this type of drug interaction. A retrospective survey identified 10 of 104 cases (9.62%) that suffered life‐threatening complications associated with the interaction between CsA and itraconazole or voriconazole following allogeneic hematopoietic stem cell transplantation (allo‐HSCT) at our center. According to the close drug monitoring, all 10 patients experienced supratherapeutic levels of CsA even with a preemptive CsA dosage reduction and prompt dose adjustment. Six patients developed grade I to III acute graft‐versus‐host disease (aGVHD) and eventually died from either idiopathic pneumonia syndrome or diffuse alveolar hemorrhage; another four patients died from CSA‐associated neurological complications. Impaired hepatic and renal function was noted in only one of these 10 cases. The high frequency as well as the unpredictability of severe complications lead us to suggest that triazole should always be replaced by another antifungal medication (e.g., amphotericin B or Echincandins) while patients receive CsA after HSCT, especially in the Chinese population.
Pathological mandibular fractures: a review of the literature of the last two decades
Authors: Boffano Paolo , Roccia Fabio , Gallesio Cesare , Berrone Sid 
Published: January 2013

AbstractPathological mandibular fractures are rare, accounting for fewer than 2% of all fractures of the mandible. They could be defined as fractures that occur in regions where bone has been weakened by an underlying pathological process. Pathological fractures usually may follow surgical interventions such as third molar removal or implant placement, result from regions of osteomyelitis, osteoradionecrosis, and bisphosphonate‐related osteonecrosis of the jaw, occur because of idiopathic reasons or be facilitated by cystic lesions, benign, malignant, or metastatic tumors. Pathological mandibular fractures may be challenging to treat because of their different etiology and peculiar local and general conditions, often requiring a more rigid fixation. In patients with poor medical conditions, simpler and more limited options may be preferred.
Replication and meta‐analysis of common variants identifies a genome‐wide significant locus in migraine
Authors: Esserlind A.‐L. , Christensen A. F. , Le H. , Kirchmann M. , Hauge A. W. , Toyserkani N. M. , Hansen T. , Grarup N. , Werge T. , Steinberg S. , Bettella F. , Stefansson H. , Olesen J. 
Published: January 2013

Background and purposeGenetic factors contribute to the aetiology of the prevalent form of migraine without aura (MO) and migraine with typical aura (MTA). Due to the complex inheritance of MO and MTA, the genetic background is still not fully established. In a population‐based genome‐wide association study by Chasman et al. (Nat Genet 2011: 43: 695–698), three common variants were found to confer risk of migraine at a genome‐wide significant level (P < 5 × 10−8). We aimed to evaluate the top association single nucleotide polymorphisms (SNPs) from the discovery set by Chasman et al. in a primarily clinic‐based Danish and Icelandic cohort.MethodsThe top association SNPs were assessed in 2523 cases and 38 170 controls, and a meta‐analysis was performed, combining the discovery set with all the follow‐up studies. Finally the confirmed SNPs were assessed in a genotype–phenotype analysis.ResultsTwo out of three SNPs that showed genome‐wide significant associations in the previous study: rs10166942 (near TRPM8) and rs11172113 (in LRP1) were significantly associated with migraine in the present study. The meta‐analysis confirmed the previous three genome‐wide significant associated SNPs (rs2651899, rs10166942 and rs11172113) to confer risk of migraine. In addition, the C‐allele of rs2078371 (near TSPAN‐2) also reached genome‐wide significance for association with migraine [OR = 1.14; CI = (1.09–1.20); P = 2.55 × 10−8].ConclusionTSPAN‐2 encodes an integral membrane protein involved in oligodendrogenesis. This new finding supports the plausible implication of neuroglia in the pathophysiology of MO and MTA.
Do systolic BP and pulse pressure relate to ventricular enlargement?
Authors: Graff‐Radford N. R. , Knopman D. S. , Penman A. D. , Coker L. H. , Mosley T. H. 
Published: January 2013

Background and purposeTo evaluate the association between systolic, diastolic and pulse pressure, and increase in ventricular size (VS). Observations in laboratory animals suggest intraventricular pulse pressure (systolic–diastolic) may play a role in ventricular enlargement.MethodsInitial magnetic resonance (MR) scans and vascular risk factors evaluation were performed in 1812 Atherosclerosis Risk in Communities participants in 1994–1995. In 2004–2006, 1130 participants underwent repeat MR. VS was rated using a validated nine‐point scale. Multiple logistic regression analysis assessed association between blood pressure measures and pulse pressure, and the change between the MR scans of VS controlling for age, sex and race.ResultsAt baseline 1112 participants (385 black women, 200 black men, 304 white women and 223 white men) had a mean age of 61.7 ± 4.3 years. In adjusted models pulse pressure at baseline was associated with an increase in VS [odds ratio (OR) 1.19, 95% confidence interval (CI) 1.01–1.40], as was systolic pressure (OR 1.28, 95% CI 1.03–1.58).ConclusionsSystolic pressure and pulse pressure are associated with future development of increased VS. The findings are consistent with the animal literature that increased pulse pressure predisposes to risk of future increased VS. High pulse pressure might play a role in the pathogenesis of normal pressure hydrocephalus.
Antibody response against gastrointestinal antigens in demyelinating diseases of the central nervous system
Authors: Banati M. , Csecsei P. , Koszegi E. , Nielsen H. H. , Suto G. , Bors L. , Trauninger A. , Csepany T. , Rozsa C. , Jakab G. , Molnar T. , Berthele A. , Kalluri S. R. , Berki T. , Illes Z. 
Published: January 2013

BackgroundAntibodies against gastrointestinal antigens may indicate altered microbiota and immune responses in the gut. Recent experimental data suggest a connection between gastrointestinal immune responses and CNS autoimmunity.MethodsAntibodies against gliadin, tissue transglutaminase (tTG), intrinsic factor (IF), parietal cells (PC) and Saccharomyces cerevisiae (ASCA) were screened in the sera of 45 patients with AQP4‐seropositive neuromyelitis optica (NMO) and NMO spectrum diseases (NMO/NMO‐SD), 17 patients with AQP4‐seronegative NMO, 85 patients with clinically definite multiple sclerosis (MS), and 48 healthy controls (HC).ResultsThirty‐seven percentages of patients with AQP4‐seropositive NMO/NMO‐SD and 28% of patients with MS had at least one particular antibody in contrast to 8% of HC (P < 0.01, respectively). Antibodies were most common (46%) in AQP4‐seropositive myelitis (P = 0.01 versus HS, P = 0.05 versus MS). Anti‐gliadin and ASCA were more frequent in the AQP4‐seropositive NMO‐spectrum compared to controls (P = 0.01 and P < 0.05, respectively).ConclusionAntibody responses against gastrointestinal antigens are common in MS and AQP4‐seropositive NMO/NMO‐SD, especially in longitudinally extensive myelitis.
The epileptic aura in literature: Aesthetic and philosophical dimensions. An essay
Authors: Wolf Peter 
Published: January 2013

SummaryIn literary accounts of epilepsy the aura has a prominent place as the subjective aspect of the seizure experience. Descriptions by authors with their own aura experiences stand out by their precision and authenticity. Many different aura types are mentioned, but the ecstatic aura described by Dostoyevsky has received particular attention and is echoed in many later works. Some authors are interested primarily in the possibilities provided by auras to react, for example, by hiding, seeking help, counteracting the oncoming seizure, or taking measures to prevent damage. Others by their unique aura experiences are inspired to create specific literary flavors like oxymora, spectacular metaphors, or the depiction of complex perceptions and states of mind. Some authors, adding a philosophical dimension, proceed to analyze the consequences of patients’ subjective seizure experiences for their identity and their self‐perception as creative or religious persons. To sum up, the works discussed herein strongly support that literary texts provide valuable insights beyond those of medical texts.
Reduced default mode network connectivity in treatment‐resistant idiopathic generalized epilepsy
Authors: Kay Benjamin P. , DiFrancesco Mark W. , Privitera Michael D. , Gotman Jean , Holland Scott K. , Szaflarski Jerzy P. 
Published: January 2013

SummaryPurposeIdiopathic generalized epilepsy (IGE) resistant to treatment is common, but its neuronal correlates are not entirely understood. Therefore, the aim of this study was to examine resting‐state default mode network (DMN) functional connectivity in patients with treatment‐resistant IGE.MethodsTreatment resistance was defined as continuing seizures despite an adequate dose of valproic acid (valproate, VPA). Data from 60 epilepsy patients and 38 healthy controls who underwent simultaneous electroencephalography (EEG) and resting‐state functional magnetic resonance imaging (fMRI) were included (EEG/fMRI). Independent component analysis (ICA) and dual regression were used to quantify DMN connectivity. Confirmatory analysis using seed‐based voxel correlation was performed.Key FindingsThere was a significant reduction of DMN connectivity in patients with treatment‐resistant epilepsy when compared to patients who were treatment responsive and healthy controls. Connectivity was negatively correlated with duration of epilepsy.SignificanceOur findings in this large sample of patients with IGE indicate the presence of reduced DMN connectivity in IGE and show that connectivity is further reduced in treatment‐resistant epilepsy. DMN connectivity may be useful as a biomarker for treatment resistance.
Increased excitability and molecular changes in adult rats after a febrile seizure
Authors: Reid Aylin Y. , Riazi Kiarash , Campbell Teskey G. , Pittman Quentin J. 
Published: January 2013

SummaryBoth early life inflammation and prolonged febrile seizures have been associated with increased excitation in the adult brain. We hypothesized this may be due in part to changes in the cation‐chloride cotransporter system. Rat pups received saline or lipopolysaccharide/kainic acid (LPS/KA) resulting in inflammation, followed by a behavioral febrile seizure (FS) in approximately 50% of rats. Adult animals from the saline, inflammation, or inflammation + FS groups underwent the following: (1) in vitro electrophysiologic studies; (2) Western blotting or polymerase chain reaction; or (3) application of the Na‐K‐Cl cotransporter 1 (NKCC1) blocker bumetanide to determine its effect on reversing increased excitability in vitro. The inflammation and inflammation + FS groups demonstrated increased excitability in vitro and increased hippocampal protein expression of NR2B and GABAA α5 receptor subunits and mRNA expression of NKCC1. The inflammation + FS group also had decreased protein expression of GluR2 and GABAA α1 receptor subunits and mRNA and protein expression of KCC2. Bumetanide decreased in vitro 4‐aminopyridine‐induced inter‐ictal activity in the inflammation and inflammation + FS groups. The results demonstrate early‐life inflammation with or without a behavioral FS can lead to long‐lasting molecular changes and increased excitability in the adult rat hippocampus, although some changes are more extensive when inflammation is accompanied by behavioral seizure activity. Bumetanide is effective in reversing increased excitability in vitro, providing evidence for a causal role for cation‐chloride cotransporters and suggesting this drug may prove useful for treating epilepsy that develops after a FS.
Down‐regulation of gephyrin and GABAA receptor subunits during epileptogenesis in the CA1 region of hippocampus
Authors: González Marco I. , Cruz Del Angel Yasmin , Brooks‐Kayal Amy 
Published: January 2013

SummaryPurposeEpileptogenesis is the process by which a brain becomes hyperexcitable and capable of generating recurrent spontaneous seizures. In humans, it has been hypothesized that following a brain insult there are a number of molecular and cellular changes that underlie the development of spontaneous seizures. Studies in animal models have shown that an injured brain may develop epileptiform activity before appearance of epileptic seizures and that the pathophysiology accompanying spontaneous seizures is associated with a dysfunction of γ‐aminobutyric acid (GABA)ergic neurotransmission. Here, we analyzed the effects of status epilepticus on the expression of GABAA receptors (GABAARs) and scaffolding proteins involved in the regulation of GABAAR trafficking and anchoring.MethodsWestern blot analysis was used to determine the levels of proteins involved in GABAAR trafficking and anchoring in adult rats subjected to pilocarpine‐induced status epilepticus (SE) and controls. Cell surface biotinylation using a cell membrane–impermeable reagent was used to assay for changes in the expression of receptors at the plasma membrane. Finally, immunoprecipitation experiments were used to evaluate the composition of GABAARs. We examined for a correlation between total GABAAR subunit expression, plasma membrane expression, and receptor composition.Key FindingsAnalysis of tissue samples from the CA1 region of hippocampus show that SE promotes a loss of GABAAR subunits and of the scaffolding proteins associated with them. We also found a decrease in the levels of receptors located at the plasma membrane and alterations in GABAAR composition.SignificanceThe changes in protein expression of GABAARs and scaffolding proteins detected in these studies provide a potential mechanism to explain the deficits in GABAergic neurotransmission observed during the epileptogenic period. Our current observations represent an additional step toward the elucidation of the molecular mechanisms underlying GABAAR dysfunction during epileptogenesis.
Cognitive impairment and cortical reorganization in children with benign epilepsy with centrotemporal spikes
Authors: Datta Alexandre N. , Oser Nadine , Bauder Florian , Maier Oliver , Martin Florence , Ramelli Gian Paolo , Steinlin Maja , Weber Peter , Penner Iris‐Katharina 
Published: January 2013

SummaryPurposeBenign epilepsy with centrotemporal spikes (BECTS) is associated with mild cognitive deficits, especially language impairment. This study aimed to clarify whether children withBECTSwith left‐ or right‐hemispheric, or bilateral focus have specific neuropsychological language deficits when compared to healthy controls, whether these deficits correlate functionally with language network organization (typical vs. atypical), and whether cofactors such as duration, handedness, and medication have a relevant impact on language reorganization processes.MethodsTwenty‐seven patients and 19 healthy controls were examined with several neuropsychological tests (German version of theWechsler Intelligence Scale for Children [WISC‐IV], Regensburger verbal fluency test [RWT], Corsiblock forward and backward andHand‐Dominanz‐Test [HDT]) and with two language paradigms on functional magnetic resonance imaging (fMRI):silent reading of word‐pairsandsilent generation of simple sentences.Key FindingsAlthough neuropsychological test results only differed by trend betweenBECTSpatients and controls, language laterality indices (LIs) in fMRIwere significantly lower in patients than in controls. In particular, the anterior language network withBroca's area and the supplementary motor area (SMA) revealed the lowestLIs and showed the most bilateral or right hemispheric activations in the sentence generation task. Medication and duration of epilepsy did not have any significant effect on language reorganization and patients' performances.SignificanceLanguage reorganization inBECTSpatients takes place in bilateral or right hemispheric language networks, with a strong focus in anterior language regions. These functional changes can be interpreted as important compensatory strategies of the central nervous system (CNS) to stabilize cognitive, especially language performance.
Use of the modified Atkins diet for treatment of refractory childhood epilepsy: A randomized controlled trial
Authors: Sharma Suvasini , Sankhyan Naveen , Gulati Sheffali , Agarwala Anuja 
Published: January 2013

SummaryPurposeThe aim of this study was to evaluate the efficacy of the modified Atkins diet in a randomized controlled trial in children with refractory epilepsy.MethodsChildren aged 2–14 years who had daily seizures despite the appropriate use of at least three anticonvulsant drugs were enrolled. Children were randomized to receive either the modified Atkins diet or no dietary intervention for a period of 3 months. The ongoing anticonvulsant medications were continued unchanged in both the groups. Seizure control at 3 months was the primary end point. Analysis was intention to treat. Adverse effects of the diet were assessed by parental reports (ClinicalTrials.gov Identifier: NCT00836836).Key FindingsAmong a total of 102 children, 50 were in the diet group and 52 in the control group. Four children discontinued the diet before the study end point, and three children in the control group were lost to follow‐up. The mean seizure frequency at 3 months, expressed as a percentage of the baseline, was significantly less in the diet group: 59 ± 54 (95% confidence interval [CI] 44–74.5) versus 95.5 ± 48 (95% CI 82–109), p = 0.003. The proportion of children with >90% seizure reduction (30% vs. 7.7%, p = 0.005) and >50% seizure reduction was significantly higher in the diet group (52% vs. 11.5%, p < 0.001). Constipation was the most common adverse effect among children on the diet (23, 46%).SignificanceThe modified Atkins diet was found to be effective and well tolerated in children with drug‐refractory epilepsy.
High‐frequency oscillations, extent of surgical resection, and surgical outcome in drug‐resistant focal epilepsy
Authors: Haegelen Claire , Perucca Piero , Châtillon Claude‐Edouard , Andrade‐Valença Luciana , Zelmann Rina , Jacobs Julia , Collins D. Louis , Dubeau François , Olivier André , Gotman Jean 
Published: January 2013

SummaryPurposeRemoval of areas generating high‐frequency oscillations (HFOs) recorded from the intracerebral electroencephalography (iEEG) of patients with medically intractable epilepsy has been found to be correlated with improved surgical outcome. However, whether differences exist according to the type of epilepsy is largely unknown. We performed a comparative assessment of the impact of removing HFO‐generating tissue on surgical outcome between temporal lobe epilepsy (TLE) and extratemporal lobe epilepsy (ETLE). We also assessed the relationship between the extent of surgical resection and surgical outcome.MethodsWe studied 30 patients with drug‐resistant focal epilepsy, 21 with TLE and 9 with ETLE. Two thirds of the patients were included in a previous report and for these, clinical and imaging data were updated and follow‐up was extended. All patients underwent iEEG investigations (500 Hz high‐pass filter and 2,000 Hz sampling rate), surgical resection, and postoperative magnetic resonance imaging (MRI). HFOs (ripples, 80–250 Hz; fast ripples, >250 Hz) were identified visually on a 5–10 min interictal iEEG sample. HFO rates inside versus outside the seizure‐onset zone (SOZ), in resected versus nonresected tissue, and their association with surgical outcome (ILAE classification) were assessed in the entire cohort, and in the TLE and ETLE subgroups. We also tested the correlation of resected brain hippocampal and amygdala volumes (as measured on postoperative MRIs) with surgical outcome.Key FindingsHFO rates were significantly higher inside the SOZ than outside in the entire cohort and TLE subgroup, but not in the ETLE subgroup. In all groups, HFO rates did not differ significantly between resected and nonresected tissue. Surgical outcome was better when higher HFO rates were included in the surgical resection in the entire cohort and TLE subgroup, but not in the ETLE subgroup. Resected brain hippocampal and amygdala volumes were not correlated with surgical outcome.SignificanceIn TLE, removal of HFO‐generating areas may lead to improved surgical outcome. Less consistent findings emerge from ETLE, but these may be related to sample size limitations of this study. Size of resection, a factor that was ignored and that could have affected results of earlier studies did not influence results.
Siblings with refractory occipital epilepsy showing localized network activity on EEG‐fMRI
Authors: Carney Patrick W. , Harvey A. Simon , Berkovic Samuel F. , Jackson Graeme D. , Scheffer Ingrid E. 
Published: January 2013

SummaryThe benign occipital epilepsies of childhood include Panayiotopoulos and Gastaut syndromes; a third syndrome, idiopathic photosensitive occipital epilepsy may also begin in childhood or adolescence. We describe siblings with occipital epilepsy characterized by refractory, frequent, brief visual seizures and normal magnetic resonance imaging (MRI). Electroencephalography (EEG) with functional MRI (fMRI) supports localization of interictal epileptiform activity to the occipital lobes. Our hypothesis is that the siblings share a genetic focal epilepsy arising from a localized occipital network. Although they share many features of Gastaut syndrome, their refractory ongoing seizures in adolescence is unusual and likely due to underlying genetic determinants.
Progressive fiber tract affections after temporal lobe surgery
Authors: Faber Jennifer , Schoene‐Bake Jan‐Christoph , Trautner Peter , von Lehe Marec , Elger Christian E. , Weber Bernd 
Published: January 2013

SummarySeveral studies reported changes in white matter architecture following temporal lobe surgery in patients with temporal lobe epilepsy (TLE) at short intervals after surgery. We investigated 20 patients with left‐sided TLE using diffusion‐imaging at two time points, that is, at 3–6 months and 12 months after surgery, to investigate postsurgical plasticity. We observed a loss of fiber tract integrity mainly in fiber tracts of the ipsilateral temporal lobe. Our data show that the remodeling of brain connectivity after surgical interventions continues for longer time periods. The functional implications of these plastic changes will have to be explored.