GENES, CHROMOSOMES AND CANCER, Issue 4 2010
Anu Usvasalo
Copy number losses in chromosome arm 9p are well-known aberrations in malignancies, including leukemias. The CDKN2A gene is suggested to play a key role in these aberrations. In this study overviewing 9p losses in hematologic neoplasias, we introduce the term focal 9p instability to indicate multiple areas of copy number loss or homozygous loss within a larger heterozygous one in 9p. We have used microarray comparative genomic hybridization to study patients with acute lymphoblastic leukemia (ALL, n = 140), acute myeloid leukemia (n = 50), chronic lymphocytic leukemia (n = 20), and myelodysplastic syndromes (n = 37). Our results show that 9p instability is restricted to ALL. In total, 58/140 (41%) patients with ALL had a loss in 9p. The 9p instability was detected in 19% of the patients with ALL and always included homozygous loss of CDKN2A along with loss of CDKN2B. Other possibly important genes included MTAP, IFN, MLLT3, JAK2, PTPLAD2, and PAX5. 13/27 (48%) patients with the instability had the BCR/ABL1 fusion gene or other oncogene-activating translocation or structural aberrations. Two patients had homozygous loss of hsa-mir ,31, a microRNA known to regulate IKZF1. IKZF1 deletion at 7p12.1 was seen in 10 (37%) patients with the 9p instability. These findings suggest that, in ALL leukemogenesis, loss of CDKN2A and other target genes in the instability region is frequently associated with BCR/ABL1 and IKZF1 dysfunction. The multiple mechanisms leading to 9p instability including physical or epigenetic loss of the target genes, loss of the microRNA cluster, and the role of FRA9G fragile site are discussed. © 2009 Wiley-Liss, Inc. [source]

On the Atrial Response to Focal Discharges in Man

JOURNAL OF CARDIOVASCULAR ELECTROPHYSIOLOGY, Issue 6 2004
HEMANTH RAMANNA M.D.
Introduction: Triggers and vulnerability are key factors for the occurrence of atrial fibrillation (AF). The aim of this study was to assess spatial dispersion of atrial refractoriness and vulnerability in response to both focal discharges as well as programmed electrical stimulation in patients undergoing ablation of atrial arrhythmogenic foci. Methods and Results: Twenty-nine patients were studied, and 12 right atrial unipolar electrograms were recorded. Inducibility of AF was assessed by a pacing protocol that started with one extrastimulus, followed by more aggressive pacing until AF was obtained. Mean fibrillatory intervals were used to assess the local refractoriness of each recording site. Spatial dispersion of refractoriness was calculated as the coefficient of dispersion (CD value: standard deviation of the mean of all local mean fibrillatory intervals as a percentage of the overall mean fibrillatory interval). Based on our previous study, a CD value , 3.0 was defined as normal, whereas a CD value >3.0 was considered enhanced spatial dispersion of refractoriness. Fifteen of 29 patients had normal dispersion of refractoriness (mean CD value 1.65 ± 0.43), and AF was inducible with burst pacing only. These patients had focal discharges causing rapid atrial tachycardia with a focal activation pattern. Activation mapping of focal activity was possible in 14 of 15 patients. Focal triggering of AF occurred in only 1 of 15 patients. Fourteen of 29 patients had enhanced dispersion (mean CD value 4.2 ± 0.72). AF was inducible with a single extrastimulus in 11 of 14 patients (P < 0.001). Focal triggering of AF occurred in all 14 patients. Conclusion: Spatial dispersion of atrial refractoriness determines whether focal atrial discharges trigger AF with disorganized activity or, alternatively, only rapid atrial tachycardia. (J Cardiovasc Electrophysiol, Vol. 15, pp. 1-8, June 2004) [source]

Glomerulosclerosis: A paraneoplastic phenomenon?

NEPHROLOGY, Issue 6 2004
Case Report
SUMMARY: Glomerulosclerosis is not classically considered a paraneoplastic glomerular lesion. Focal and segmental glomerulosclerosis (FSGS) has rarely been reported in association with solid tumours. We report three cases of FSGS and an additional case of collapsing glomerulosclerosis in patients presenting with nephrotic syndrome and malignancy. [source]

Intensive and Prolonged Treatment of Focal and Segmental Glomerulosclerosis Recurrence in Adult Kidney Transplant Recipients: A Pilot Study

AMERICAN JOURNAL OF TRANSPLANTATION, Issue 5 2009
G. Canaud
No treatment has consistently induced long-term remission of proteinuria in adult patients with focal segmental glomerulosclerosis (FSGS) recurrence after kidney transplantation. We undertook an open-label, nonrandomized pilot trial of intensive and prolonged treatment of FSGS recurrence. Over an 18-month period, 10 adult kidney transplant recipients with FSGS recurrence received concomitantly high-dose steroids, intravenous cyclosporine for 14 days followed by oral cyclosporine therapy, and an intensive and prolonged course of plasma exchanges (PE). We compared this treatment with those of a control group of 19 patients with a FSGS recurrence transplanted between 1997 and 2005. Complete, rapid (mean 23 ± 7 days) and sustained remission was obtained in 9/10 patients (90%) as opposed to 27% in the control group. At month 3 and month 12, proteinuria was 0.16 g/day (range 0.05,0.3 g/day) and 0.19 g/day (range 0.05,1 g/day) respectively. Only one patient remained in partial remission at month 12 but he had already lost two previous grafts due to FSGS recurrence. PEs were stopped at month 9 in all patients except for the patient with a partial remission who remains PE-dependent. This small pilot study provides very encouraging results demonstrating that this treatment rapidly achieves complete and sustained remission in a high proportion of patients. [source]

Delivery of photocoagulation treatment for diabetic retinopathy at a large Australian ophthalmic hospital: comparisons with national clinical practice guidelines

CLINICAL & EXPERIMENTAL OPHTHALMOLOGY, Issue 2 2002
Parapun Bamroongsuk MD
Abstract Objective: To determine if the delivery of photocoagulation for diabetic retinopathy at a large Australian ophthalmic hospital conforms with Australian National Health and Medical Research Council clinical practice guidelines. Methods: A retrospective medical record review was conducted of all patients who had initial laser treatment for diabetic retinopathy at the Royal Victorian Eye and Ear Hospital from January 1997 to December 1998. Results: The study included 322 eyes from 203 patients. The mean age was 65.8 years (range 18,89 years) and the mean duration of diabetes was 14.7 years (range 1,40 years). Panretinal photocoagulation (PRP) alone was performed in 37 eyes over a mean number of 2.6 sessions. The median waiting time for these procedures was 14 days (range 0,146 days) and the median follow-up time was 7.1 weeks (range 1,25 weeks). Focal treatment was performed (without PRP) in 238 eyes and 55.5% of these cases required repeat focal treatment for persistent clinically significant macular oedema. Median waiting time for focal treatment was 20 days (range 0,302 days) and the median follow-up time after treatment was 12.1 weeks (range 1.7,42.0 weeks). Focal and PRP treatment was used in 47 eyes that had maculopathy concurrently with proliferative retinopathy. Focal treatment was applied before (or at the same session as) the PRP wherever possible. Conclusions: The study indicates that the application of photocoagulation and follow up for diabetic retinopathy at this tertiary referral institution conforms closely with Australian clinical practice guidelines. [source]

The use of p63 as an effective immunomarker in the diagnosis of pulmonary squamous cell carcinomas on de-stained bronchial lavage cytological smears

CYTOPATHOLOGY, Issue 1 2010
M. Uke
M. Uke, B. Rekhi, D. Ajit and N. A. Jambhekar The use of p63 as an effective immunomarker in the diagnosis of pulmonary squamous cell carcinomas on de-stained bronchial lavage cytological smears Objectives:, A diagnosis in pulmonary onco-cytopathology primarily necessitates distinguishing small cell carcinoma (SCLC) from non-small cell carcinoma (NSCLC), which includes squamous cell carcinoma and adenocarcinoma. Lately, p63 antibody has been used for distinguishing squamous cell carcinoma from SCLC and adenocarcinoma. We present an analysis of p63 expression in cytological smears from 100 bronchial lavage specimens comprising 51 cases of SCLC and 49 cases of NSCLC. Methods:, A single Papanicolaou-stained conventional smear was de-stained and re-fixed with cold acetone and methanol for immunocytochemical staining with p63 antibody. Staining results were graded as 0 (nil), 1+ (focal), 2+ (moderate, diffuse) and 3+ (strong, diffuse). Results:, Out of 100 cases, 21 were cytologically diagnosed as squamous cell carcinoma. Twenty of these showed 2+ or 3+ p63 positivity, whereas one, which was adenocarcinoma on histology, showed 1+ staining. Of seven cases cytologically diagnosed as adenocarcinoma, six showed no p63 staining, whereas one, which was squamous cell carcinoma on histology, showed 1+ staining. All 48 cases cytologically diagnosed as SCLC were confirmed as such on histology and showed no p63 staining. Four cases were cytologically designated as poorly differentiated carcinomas, of which three showed no p63 staining and one showed 3+ staining. The former three were found to be SCLC on histology while the latter was squamous cell carcinoma. The remaining 20 cases were cytologically designated as NSCLC. Of these, eight showed no p63 staining, whereas 10 showed 1+ and two showed 2+ staining. The former eight were adenocarcinoma on histology and the latter two were squamous cell carcinoma. The 10 cases that showed 1+ p63 staining were adenocarcinomas (n = 5), squamous cell carcinoma (n = 4) and NSCLC, not otherwise specified (n = 1). Positive staining was seen in normal basal cells, which acted as an internal control. Overall sensitivity of p63 for squamous cell carcinoma was 100% and specificity was 90.4%. Conclusions:, p63 immunostaining on processed cytology smears can be used to help identify squamous cell carcinoma. Its diffuse expression was specific for squamous cell carcinoma while focal staining was also seen in adenocarcinoma. [source]

State of Research in High-consequence Hospital Surge Capacity

ACADEMIC EMERGENCY MEDICINE, Issue 11 2006
Carl H. Schultz MD
High-consequence surge research involves a systems approach that includes elements such as healthcare facilities, out-of-hospital systems, mortuary services, public health, and sheltering. This article focuses on one aspect of this research, hospital surge capacity, and discusses a definition for such capacity, its components, and future considerations. While conceptual definitions of surge capacity exist, evidence-based practical guidelines for hospitals require enhancement. The Health Resources and Services Administration's (HRSA) definition and benchmarks are extrapolated from those of other countries and rely mainly on trauma data. The most significant part of the HRSA target, the need to care for 500 victims stricken with an infectious disease per one million population in 24 hours, was not developed using a biological model. If HRSA's recommendation is applied to a sample metropolitan area such as Orange County, California, this translates to a goal of expanding hospital capacity by 20%,25% in the first 24 hours. Literature supporting this target is largely consensus based or anecdotal. There are no current objective measures defining hospital surge capacity. The literature identifying the components of surge capacity is fairly consistent and lists them as personnel, supplies and equipment, facilities, and a management system. Studies identifying strategies for hospitals to enhance these components and estimates of how long it will take are lacking. One system for augmenting hospital staff, the Emergency System for Advance Registration of Volunteer Health Professionals, is a consensus-derived plan that has never been tested. Future challenges include developing strategies to handle the two different types of high-consequence surge events: 1) a focal, time-limited event (such as an earthquake) where outside resources exist and can be mobilized to assist those in need and 2) a widespread, prolonged event (such as pandemic influenza) where all resources will be in use and rationing or triage is needed. [source]

The use of neuroimaging in the diagnosis of mitochondrial disease

DEVELOPMENTAL DISABILITIES RESEARCH REVIEW, Issue 2 2010
Seth D. Friedman
Abstract Mutations in nuclear and mitochondrial DNA impacting mitochondrial function result in disease manifestations ranging from early death to abnormalities in all major organ systems and to symptoms that can be largely confined to muscle fatigue. The definitive diagnosis of a mitochondrial disorder can be difficult to establish. When the constellation of symptoms is suggestive of mitochondrial disease, neuroimaging features may be diagnostic and suggestive, can help direct further workup, and can help to further characterize the underlying brain abnormalities. Magnetic resonance imaging changes may be nonspecific, such as atrophy (both general and involving specific structures, such as cerebellum), more suggestive of particular disorders such as focal and often bilateral lesions confined to deep brain nuclei, or clearly characteristic of a given disorder such as stroke-like lesions that do not respect vascular boundaries in mitochondrial myopathy, encephalopathy, lactic acidosis, and stroke-like episode (MELAS). White matter hyperintensities with or without associated gray matter involvement may also be observed. Across patients and discrete disease subtypes (e.g., MELAS, Leigh syndrome, etc.), patterns of these features are helpful for diagnosis. However, it is also true that marked variability in expression occurs in all mitochondrial disease subtypes, illustrative of the complexity of the disease process. The present review summarizes the role of neuroimaging in the diagnosis and characterization of patients with suspected mitochondrial disease. © 2010 Wiley-Liss, Inc. Dev Disabil Res Rev 2010;16:129,135. [source]

Baseline cognition, behavior, and motor skills in children with new-onset, idiopathic epilepsy

DEVELOPMENTAL MEDICINE & CHILD NEUROLOGY, Issue 1 2010
VIKRAM V BHISE
Aim, Epilepsy is associated with difficulties in cognition and behavior in children. These problems have been attributed to genetics, ongoing seizures, psychosocial issues, underlying abnormality of the brain, and/or antiepileptic drugs. In a previous study, we found baseline cognitive differences between children with partial versus generalized and convulsive versus non-convulsive seizures. Measures in that study focused primarily on IQ scores. In the present study, we assessed baseline function with respect to new learning, attention, and memory, thus providing a more comprehensive profile than our previous study. Method, We examined 57 children (42 females, 15 males), aged 6 to 17 years (mean 10y 1mo, SD 2y 9mo), with new-onset, idiopathic epilepsy, using tests of cognitive function reflective of new learning, memory, and attention. Seizures were classified as generalized convulsive (n=5), generalized non-convulsive (n=18), or focal (n=34). Focal seizures were divided into unilateral versus bilateral independent foci, and presence versus absence of secondary generalization. Results, Attention was a particular area of weakness across all groups. The Vocabulary score of an intelligence screen was higher for the focal seizure groups (p=0.012), primarily because of a difference between the unilateral focal and the primary generalized groups (p<0.047). Children with generalized, non-convulsive seizures performed significantly worse than the focal group on a measure of short-term auditory memory (p=0.019). All groups performed poorly on a test of visual,motor speed. Interpretation, These findings suggest intrinsic abnormalities in children with new-onset, idiopathic epilepsy at baseline. [source]

A shift from diffuse to focal cortical activity with development

DEVELOPMENTAL SCIENCE, Issue 1 2006
Sarah Durston
Recent imaging studies have suggested that developmental changes may parallel aspects of adult learning in cortical activation becoming less diffuse and more focal over time. However, while adult learning studies examine changes within subjects, developmental findings have been based on cross-sectional samples and even comparisons across studies. Here, we used functional MRI in children to test directly for shifts in cortical activity during performance of a cognitive control task, in a combined longitudinal and cross-sectional study. Our longitudinal findings, relative to our cross-sectional ones, show attenuated activation in dorsolateral prefrontal cortical areas, paralleled by increased focal activation in ventral prefrontal regions related to task performance. [source]

,-Methylacyl-CoA racemase (AMACR) in fine-needle aspiration specimens of prostate lesions

DIAGNOSTIC CYTOPATHOLOGY, Issue 11 2009
Gordana Kai, M.D.
Abstract The elevated expression of P504S gene and its product ,-methylacyl-CoA racemase (AMACR) can serve as a molecular marker for prostate cancer. The goal of this study is to investigate P504S/AMACR expression in fine-needle aspiration smears and correlate it with cytological diagnosis. Immunocytochemistry was performed in 35 patients with morphological diagnosis of prostate carcinoma (n = 16), atypia (n = 15), and benign hyperplasia (n = 4). Among 16 malignant cases there were two low-grade, eight intermediate, and six high-grade prostate carcinomas. Cytoplasmic positivity is analyzed qualitatively as predominantly diffuse or focal and quantitatively as <5%, 5,50%, and >50% of cells. Benign cases showed no P504S/AMACR expression. Positive staining was recorded in 75% of malignant cases, but in the majority of them it was weak and focal or diffuse and in a small amount of cells. The most intensive staining was seen in low-grade carcinomas and some atypical cases. This observation indicates a correlation between P504S/AMACR expression and differentiation of cells. P504S/AMACR staining might be of great value in cytodiagnosis of prostate lesions as well as an example of the characterization of cells at the molecular level using fresh tissue obtained by fine-needle aspiration. Diagn. Cytopathol. 2009. © 2009 Wiley-Liss, Inc. [source]

Immunocytochemical study of the expression of mesothelin in fine-needle aspiration biopsy specimens of pancreatic adenocarcinoma

DIAGNOSTIC CYTOPATHOLOGY, Issue 3 2007
Amy C. Baruch M.D.
Abstract Mesothelin is a potential marker of pancreatic adenocarcinoma that was recently identified by serial analysis of gene expression. We evaluated the sensitivity and specificity of mesothelin as a marker of pancreatic adenocarcinoma on destained Papanicolaou (Pap) smears and unstained cellblocks from 28 patients using a monoclonal antibody to mesothelin. Intensity and proportion of staining was semiquantitatively graded on a scale of 1,3, and as 0%, 1 to <10%, 10,50%, or >50%. Positive staining for mesothelin was seen in 64% of the direct smears and in 36% of cell block sections. Focal positivity for mesothelin was noted in benign pancreatic tissue in one of 10 cases. Staining was most often focal (<50% of cells) in both direct smears and cell block sections. The overall sensitivity and specificity of mesothelin as a marker for pancreatic adenocarcinoma were 68% and 90%, respectively. Sensitivity was higher in Pap smears than in cell block sections (64% versus 36%). The presence of occasional mesothelin expression in benign tissue, its very focal expression in malignant tissue may limit the utility of mesothelin as a marker of pancreatic adenocarcinomas in fine-needle aspiration (FNA) specimens. Diagn. Cytopathol. 2007;35:143,147. © 2007 Wiley-Liss, Inc. [source]

Exporting the German Model: The Establishment of a New Automobile Industry Cluster in Shanghai

ECONOMIC GEOGRAPHY, Issue 1 2005
Heiner Depner
Abstract: Recent work has provided evidence that the establishment of new industry clusters cannot be jump-started through policy initiatives alone. This evidence does not imply, however, that the genesis of a new cluster cannot be planned at all. Especially in the context of a developing economy, it seems useful to reinvestigate the relation among economic development, the strategies of multinational firms, and state intervention in this respect. Drawing from the case of the automobile industry and its supplier system in Shanghai in which German firms play an important role, we provide empirical evidence of the evolution of a new cluster that is supported by the state in various forms and characterized by a focal, hierarchically structured production system. We use a multidimensional approach to clusters, which leads to a more nuanced understanding of the evolution and growth of a cluster than that provided by earlier accounts. This approach allows us to distinguish the development of the Shanghai automobile industry cluster along its vertical, horizontal, external, institutional, and power dimensions. We provide evidence that another dimension,"culture",plays an important role, especially in its relation to issues of power and institutions. The role of this dimension is demonstrated in the case of German firms, which tap into the Chinese innovation system. This system is characterized by particular business relations, institutions, norms, and various social practices that are new to German firms. We demonstrate how this difference creates problems in establishing local production and supplier relations and how these problems can be overcome. [source]

Revised terminology and concepts for organization of seizures and epilepsies: Report of the ILAE Commission on Classification and Terminology, 2005,2009

EPILEPSIA, Issue 4 2010
Anne T. Berg
Summary The International League Against Epilepsy (ILAE) Commission on Classification and Terminology has revised concepts, terminology, and approaches for classifying seizures and forms of epilepsy. Generalized and focal are redefined for seizures as occurring in and rapidly engaging bilaterally distributed networks (generalized) and within networks limited to one hemisphere and either discretely localized or more widely distributed (focal). Classification of generalized seizures is simplified. No natural classification for focal seizures exists; focal seizures should be described according to their manifestations (e.g., dyscognitive, focal motor). The concepts of generalized and focal do not apply to electroclinical syndromes. Genetic, structural,metabolic, and unknown represent modified concepts to replace idiopathic, symptomatic, and cryptogenic. Not all epilepsies are recognized as electroclinical syndromes. Organization of forms of epilepsy is first by specificity: electroclinical syndromes, nonsyndromic epilepsies with structural,metabolic causes, and epilepsies of unknown cause. Further organization within these divisions can be accomplished in a flexible manner depending on purpose. Natural classes (e.g., specific underlying cause, age at onset, associated seizure type), or pragmatic groupings (e.g., epileptic encephalopathies, self-limited electroclinical syndromes) may serve as the basis for organizing knowledge about recognized forms of epilepsy and facilitate identification of new forms. [source]

Coexistence of symptomatic focal and absence seizures: Video-EEG and EEG-fMRI evidence of overlapping but independent epileptogenic networks

EPILEPSIA, Issue 7 2009
Serge Chassagnon
Summary The distinction between typical absences and hypomotor seizures in patients having frontal lesions is difficult. In focal epilepsy, generalized-like interictal discharges can reflect either a coexistent generalized epileptic trait or a secondary bilateral synchrony. Using combined measures of the EEG and blood oxygenation level dependent (BOLD) activity, we studied a 50-year-old patient with both absence-like and symptomatic focal motor seizures. Focal activity induced activation in the lesional area and deactivation in the contralateral central cortex. Generalized spike-and-wave discharges (GSWDs) resulted also in perilesional activation, and multifocal symmetrical cortical and thalamic activations, and deactivation in associative cortical areas. Although the central cortex was involved during both types of epileptic activity, electroencephalography (EEG),functional magnetic resonance imaging (fMRI) revealed distinct neuronal networks at the time of the focal or generalized discharges, allowing a clear-cut differentiation of the generators. Whether the patient had distinct epileptic syndromes or distinct electrographic patterns from the lesional trigger remains debatable. [source]

Generalized-onset seizures with secondary focal evolution

EPILEPSIA, Issue 7 2009
Randy Williamson
Summary The international seizure classification recognizes that partial-onset seizures can become secondarily generalized, but generalized-onset seizures are expected to remain generalized. We report six patients who had recorded seizures with generalized onset, but subsequent evolution into a focal discharge. The clinical seizure onset was generalized absence or myoclonic, and the most common subsequent clinical pattern was prolonged behavioral arrest with mild automatisms, and then postictal confusion. The ictal discharge started with generalized spike-and-wave activity and then acquired a focal predominance. Interictal epileptiform activity was generalized. There were no focal magnetic resonance imaging abnormalities. Four patients were misdiagnosed with complex partial seizures. All patients were initially refractory, but three became seizure-free and three improved after treatment with antiepileptic medications appropriate for absence or myoclonic seizures. Generalized-onset seizures that acquire focal features are easily misdiagnosed as complex partial. These seizures have a more favorable response to medications effective against generalized absence and myoclonic seizures. [source]

Panayiotopoulos Syndrome: An Important Electroclinical Example of Benign Childhood System Epilepsy

EPILEPSIA, Issue 6 2007
Michael Koutroumanidis
Summary:, As a result of the converging evidence from multiple large independent studies, Panayiotopoulos syndrome (PS) is now formally recognized as a distinct clinical entity within the spectrum of benign focal epilepsies of childhood. Clinically, PS is manifested by predominantly autonomic seizures and electrographically with multifocal interictal spikes, while the few published ictal recordings have documented onsets of variable lobar topography. These typical electroclinical features do not allow straightforward assignment to a distinctive cortical area, rendering the term "focal",as we currently understand it,problematic. This is a critical review of the clinical and EEG features of PS, focusing on those characteristics that may shed some light on its so far elusive pathophysiology. We also explore its electroclinical similarities to other idiopathic "focal" epilepsies and its differences to symptomatic focal epilepsies that may also manifest with autonomic ictal symptoms and signs. This methodology allows the formation of a rational hypothesis on the pathophysiology of PS that seems to be emerging as a good model for the so-called "system" (nonsymptomatic) epilepsies, with potentially important taxonomic implications. [source]

Epilepsy in Colombia: Epidemiologic Profile and Classification of Epileptic Seizures and Syndromes

EPILEPSIA, Issue 1 2006
Alberto Velez
Summary:,Purpose: A national study was performed in Colombia to determine the general and regional prevalence of epilepsy, clinical profiles, seizure types, and clinical syndromes. Methods: Based on the National Epidemiological Study of Neurological Diseases (EPINEURO), we evaluated and followed up for 1 year all the subjects with epilepsy from the National Sample. Clinical profiles were further assessed. Seizure types and epilepsy syndromes were established according to the international classifications. Results: General prevalence was found to be 11.3 per 1,000, with little variation among regions, except the eastern region, where prevalence was 23 per 1,000; prevalence for active epilepsy was 10.1 per 1,000. Women have a slightly greater (not statistically significant) risk. Most seizures are focal (partial), frequently with secondary generalization. The most frequent epilepsy syndrome encountered was partial symptomatic/cryptogenic (80%). Epilepsy onset in Colombia occurs most frequently in childhood. Conclusions: Prevalence rates of epilepsy in Colombia are similar to those reported in nations with comparable developmental status and have diminished over time. The study presents the distribution of seizures and syndromes. The most frequent types are focal syndromes. [source]

Computerized Tremor Analysis of Valproate-induced Tremor: A Comparative Study of Controlled-release versus Conventional Valproate

EPILEPSIA, Issue 2 2005
Martina Rinnerthaler
Summary:,Purpose: Valproate (VPA) induces postural tremor in 6,45% of patients. The characteristics of VPA-induced tremor have not yet been quantitatively assessed, and it is not known whether tremor prevalence or severity is affected by VPA formulation (controlled-release CR-VPA vs. conventional VPA). The aim of this study was quantitatively to assess tremor in epilepsy patients receiving VPA and to compare the effects of two VPA formulations (CR-VPA vs. VPA) on tremor severity. Methods: In a prospective study, 18 consecutive patients with newly diagnosed focal or generalized epilepsy were assigned to receive alternately either VPA (n = 10) or CR-VPA (n = 8) monotherapy. Computerized tremor analysis was performed at baseline 1 day before initiating VPA treatment and repeated after a seizure-free period of ,8 weeks, during which VPA doses had remained stable. Rest and postural tremor were recorded by accelerometry, and surface electromyograms (EMGs) were recorded from the wrist flexors and extensors. Results: At baseline, the two groups had similar postural tremor amplitudes. At follow-up, the CR-VPA group had remained at the same level, whereas VPA subjects exhibited a significant increase in tremor amplitudes (p < 0.05) despite comparable VPA doses and comparable plasma VPA concentrations at the time of tremor testing. Conclusions: This is the first study to assess quantitatively VPA-induced tremor by standardized tremor analysis. These results suggest that CR-VPA may cause less tremorigenic activity as compared with standard VPA. The mechanisms underlying this difference are unclear but may include greater peak,trough variation with VPA than with CR-VPA. [source]

Seizure Semiology in the Elderly: A Video Analysis

EPILEPSIA, Issue 3 2004
Christoph Kellinghaus
Summary: Purpose: To describe the seizure semiology of patients older than 60 years and to compare it with that of a control group of younger adults matched according to the epilepsy diagnosis. Methods: Available videotapes of all patients aged 60 years and older who underwent long-term video-EEG evaluation at the Cleveland Clinic Foundation (CCF) between January 1994 and March 2002 were analyzed by two observers blinded to the clinical data. A younger adult control group was matched according to the epilepsy diagnosis, and their seizures also were analyzed. Results: Fifty-four (3.3%) of the 1,633 patients were 60 years or older at the time of admission. For 21 of them, at least one epileptic seizure was recorded. Nineteen patients had focal epilepsy (nine temporal lobe, two frontal lobe, two parietal lobe, eight nonlocalized), and two patients had generalized epilepsy. Seventy-three seizures of the elderly patients and 85 seizures of the 21 control patients were analyzed. In nine elderly patients and 14 control patients, at least one of their seizures started with an aura. Eleven elderly patients and 19 control patients lost responsiveness during their seizures. Approximately two thirds of the patients in both groups had automatisms during the seizures. Both focal and generalized motor seizures (e.g., clonic or tonic seizures) were seen less frequently in the elderly. Conclusions: Only a small percentage of the patients admitted to a tertiary epilepsy referral center for long-term video-EEG monitoring are older than 60 years. All seizure types observed in the elderly also were seen in the younger control group, and vice versa. Simple motor seizures were seen less frequently in the elderly. [source]

Specific Epileptic Syndromes Are Rare Even in Tertiary Epilepsy Centers: A Patient-oriented Approach to Epilepsy Classification

EPILEPSIA, Issue 3 2004
Christoph Kellinghaus
Summary: Purpose: To assess the practicability and reliability of a five-dimensional patient-oriented epilepsy classification and to compare it with the International League Against Epilepsy (ILAE) classification of epilepsy and epileptic syndromes. The dimensions consist of the epileptogenic zone, semiologic seizure type(s), etiology, related medical conditions, and seizure frequency. Methods: The 185 epilepsy patients (94 adults, 91 children, aged 18 years or younger) were randomly selected from the database of a tertiary epilepsy center and the general neurological department of a metropolitan hospital (28 adults). The charts were reviewed independently by two investigators and classified according to both the ILAE and the patient-oriented classification. Interrater reliability was assessed, and a final consensus among all investigators was established. Results: Only four (4%) adults and 19 (21%) children were diagnosed with a specific epilepsy syndrome of the ILAE classification. All other patients were in unspecific categories. The patient-oriented classification revealed that 64 adults and 56 children had focal epilepsy. In an additional 34 adults and 45 children, the epileptogenic zone could be localized to a certain brain region, and in 14 adults and five children, the epileptogenic zone could be lateralized. Fourteen adults and 21 children had generalized epilepsy. In 16 adults and 14 children, it remained unclear whether the epilepsy was focal or generalized. Generalized simple motor seizures were found in 66 adults and 52 children, representing the most frequent seizure type. Etiology could be determined in 40 adults and 45 children. Hippocampal sclerosis was the most frequent etiology in adults (10%), and cortical dysplasia (9%), in children. Seven adults and 31 children had at least daily seizures. Seventeen adults and 26 children had rare or no seizures at their last documented contact. The most frequent related medical conditions were psychiatric disorders and mental retardation. Interrater agreement was high (kappa values of 0.8 to 0.9) for both the patient-oriented and the ILAE classification. Conclusions: Specific epilepsy syndromes included in the current ILAE classification are rare even in a tertiary epilepsy center. Most patients are included in unspecific categories that provide only incomplete information. In contrast, all of the patients could be classified by the five-dimensional patient-oriented classification, providing all essential information for the management of the patients with a high degree of interrater reliability. [source]

MRI Volumetric Analysis in Rasmussen Encephalitis: A Longitudinal Study

EPILEPSIA, Issue 2 2003
Masanori Takeoka
Summary: ,Purpose: Rasmussen encephalitis is a progressive inflammatory process with difficult-to-control focal or lateralized seizure activity, leading to hemispheric dysfunction and atrophy in advanced stages. Anatomic changes of atrophy may be subtle in earlier phases of the disease, and progressive changes on serial scans may be difficult to detect. We report a case of early-stage Rasmussen encephalitis with a relatively stable clinical course in whom we performed magnetic resonance imaging (MRI)-based volumetric analysis over an interval of 1 year, to assess for volumetric changes. Methods: Volumetric analysis was performed on two successive MRI scans obtained at age 5 and 6 years, by using the CARDVIEWS program (J Cogn Neurosci, 1996). The images were segmented into gray- and white-matter structures according to signal intensity of their borders semiautomatically, with manual corrections. The cerebral cortex was further subdivided into smaller parcellation units according to anatomic landmarks identifiable on MRI. Results: Stable left cerebral hemispheric atrophy and progressive atrophy in the left precentral gyrus, left inferior frontal gyrus, and left cerebellar atrophy were detected over the 1-year interval. Conclusions: Volumetric analysis enables early detection and quantification of anatomic changes, identification of focal involvement, and assists in determining the severity of disease and timing for surgical interventions such as hemispherectomy. [source]

Focal Ictal , Discharge on Scalp EEG Predicts Excellent Outcome of Frontal Lobe Epilepsy Surgery

EPILEPSIA, Issue 3 2002
Gregory A. Worrell
Summary: ,Purpose: To determine whether a focal ,-frequency discharge at seizure onset on scalp EEG predicts outcome of frontal lobe epilepsy (FLE) surgery. Methods: We identified 54 consecutive patients with intractable FLE who underwent epilepsy surgery between December 1987 and December 1996. A blind review of EEGs and magnetic resonance images (MRIs) was performed. Lesional epilepsy is defined as presence of an underlying structural abnormality on MRI. Results: Overall, 28 (52%) patients were seizure free, with a mean follow-up of 46.5 months. Presence of a focal ,-frequency discharge at seizure onset on scalp EEG predicted seizure-free outcome in lesional (p = 0.02) and nonlesional (p = 0.01) epilepsy patients. At least 90% of patients who had either lesional or nonlesional epilepsy were seizure free if scalp EEG revealed a focal , discharge at ictal onset. Moreover, logistic regression analysis showed that focal ictal , pattern and completeness of lesion resection were independently predictive of seizure-free outcome. Ictal onset with lateralized EEG activity of any kind and postresection electrocorticographic spikes did not predict surgical outcome (p > 0.05). Conclusions: Only about 25% of FLE surgical patients have a focal ,-frequency discharge at seizure onset on scalp EEG. However, its presence is highly predictive of excellent postsurgical seizure control in either lesional or nonlesional FLE surgical patients. [source]

Four New Families with Autosomal Dominant Partial Epilepsy with Auditory Features: Clinical Description and Linkage to Chromosome 10q24

EPILEPSIA, Issue 1 2002
Melodie R. Winawer
Summary: ,Purpose: Autosomal dominant partial epilepsy with auditory features (ADPEAF) is a rare form of nonprogressive lateral temporal lobe epilepsy characterized by partial seizures with auditory disturbances. The gene predisposing to this syndrome was localized to a 10-cM region on chromosome 10q24. We assessed clinical features and linkage evidence in four newly ascertained families with ADPEAF, to refine the clinical phenotype and confirm the genetic localization. Methods: We genotyped 41 individuals at seven microsatellite markers spanning the previously defined 10-cM minimal genetic region. We conducted two-point linkage analysis with the ANALYZE computer package, and multipoint parametric and nonparametric linkage analyses as implemented in GENEHUNTER2. Results: In the four families, the number of individuals with idiopathic epilepsy ranged from three to nine. Epilepsy was focal in all of those with idiopathic epilepsy who could be classified. The proportion with auditory symptoms ranged from 67 to 100%. Other ictal symptoms also were reported; of these, sensory symptoms were most common. Linkage analysis showed a maximum 2-point LOD score of 1.86 at (, = 0.0 for marker D10S603, and a maximum multipoint LOD score of 2.93. Conclusions: These findings provide strong confirmation of linkage of a gene causing ADPEAF to chromosome 10q24. The results suggest that the susceptibility gene has a differential effect on the lateral temporal lobe, thereby producing the characteristic clinical features described here. Molecular studies aimed at the identification of the causative gene are underway. [source]

Febrile Seizures: Treatment and Prognosis

EPILEPSIA, Issue 1 2000
Finn Ursin Knudsen
Summary: Recent epidemiologic data indicate that the vast majority of children with febrile seizures have a normal long-term outcome. A precise knowledge of the short- and long-term outcome with or without treatment, and short- and long-term side effects is an important prerequisite for assessing the various treatment strategies. We focus on the impact of short-term or prophylactic treatment on the short- and long-term outcome of various types of febrile seizures. There is universal agreement that daily prophylaxis with antiepileptic agents should never be used routinely in simple febrile seizures, but only in highly selected cases, if at all. Intermittent diazepam (DZP) prophylaxis at times of fever may or may not reduce the recurrence rate, but it does not appear to improve the long-term outcome as compared with short-term seizure control. The treatment may be used to reduce the recurrence rate for a small arbitrarily defined group with multiple simple febrile seizures, complex febrile seizures, especially focal, prolonged or both, febrile status, and when parental anxiety is severe. However, there is no evidence that treatment of simple febrile seizures can prevent the rare cases of later epilepsy, and many children with complex febrile seizures have a benign long-term outcome, even without treatment. Many prefer a "wait and see" policy. An attractive alternative is to treat new febrile seizures with rectal DZP in solution at seizure onset, given by the parents at home to prevent febrile status. Newer, less well documented short-term strategies include nasal, oral, or rectal administration of other benzodiazepines. Short-term seizure control of febrile status and careful parental counseling are the two most important targets of treatment. [source]

Differences between the effects of three plasticity inducing protocols on the organization of the human motor cortex

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 3 2006
Karin Rosenkranz
Abstract Several experimental protocols induce lasting changes in the excitability of motor cortex. Some involve direct cortical stimulation, others activate the somatosensory system and some combine motor and sensory stimulation. The effects usually are measured as changes in amplitude of the motor-evoked-potential (MEP) or short-interval intracortical inhibition (SICI) elicited by a single or paired pulses of transcranial magnetic stimulation (TMS). Recent work has also tested sensorimotor organization within the motor cortex by recording MEPs and SICI during short periods of vibration applied to single intrinsic hand muscles. Here sensorimotor organization is focal: MEPs increase and SICI decreases in the vibrated muscle, whilst the opposite occurs in neighbouring muscles. In six volunteers we compared the after effects of three protocols that lead to lasting changes in cortical excitability: (i) paired associative stimulation (PAS) between a TMS pulse and an electrical stimulus to the median nerve; (ii) motor practice of rapid thumb abduction; and (iii) sensory input produced by semicontinuous muscle vibration, on MEPs and SICI at rest and on the sensorimotor organization. PAS increased MEP amplitudes, whereas vibration changed sensorimotor organization. Motor practice had a dual effect and increased MEPs as well as affecting sensorimotor organization. The implication is that different protocols target different sets of cortical circuits. We speculate that protocols that involve repeated activation of motor cortical output lead to lasting changes in efficacy of synaptic connections in output circuits, whereas protocols that emphasize sensory inputs affect the strength of sensory inputs to motor circuits. [source]

Right-hemisphere motor facilitation by self-descriptive personality-trait words

EUROPEAN JOURNAL OF NEUROSCIENCE, Issue 7 2005
Istvan Molnar-Szakacs
Abstract The emergent picture from the literature on the processing of self-related information suggests that in addition to the neural mechanisms involved in recognizing one's own face, there may also be neural representations of the self that are modality independent and favour the right hemisphere. We used focal, single-pulse transcranial magnetic stimulation in human subjects to assess cortical excitability during covert reading of self-descriptive personality-trait words. We hypothesized that the right hemisphere would show a greater overall facilitation to personality-trait words than the left hemisphere. Overall, personality-trait words led to significantly greater motor facilitation in the right hemisphere than in the left hemisphere. In addition, words rated as ,never' self-characteristic yielded significant right hemisphere facilitation, and words rated as ,always' self-characteristic showed a similar trend. The results are discussed in terms of the notion that the right hemisphere plays a dominant role in both self-relevant processing and the processing of affective stimuli. [source]

INDIRECT GENETIC EFFECTS INFLUENCE ANTIPREDATOR BEHAVIOR IN GUPPIES: ESTIMATES OF THE COEFFICIENT OF INTERACTION PSI AND THE INHERITANCE OF RECIPROCITY

EVOLUTION, Issue 7 2009
Bronwyn H. Bleakley
How and why cooperation evolves, particularly among nonrelatives, remains a major paradox for evolutionary biologists and behavioral ecologists. Although much attention has focused on fitness consequences associated with cooperating, relatively little is known about the second component of evolutionary change, the inheritance of cooperation or reciprocity. The genetics of behaviors that can only be expressed in the context of interactions are particularly difficult to describe because the relevant genes reside in multiple social partners. Indirect genetic effects (IGEs) describe the influence of genes carried in social partners on the phenotype of a focal individual and thus provide a novel approach to quantifying the genetics underlying interactions such as reciprocal cooperation. We used inbred lines of guppies and a novel application of IGE theory to describe the dual genetic control of predator inspection and social behavior, both classic models of reciprocity. We identified effects of focal strain, social group strain, and interactions between focal and group strains on variation in focal behavior. We measured ,, the coefficient of the interaction, which describes the degree to which an individual's phenotype is influenced by the phenotype of its social partners. The genetic identity of social partners substantially influences inspection behavior, measures of threat assessment, and schooling and does so in positively reinforcing manner. We therefore demonstrate strong IGEs for antipredator behavior that represent the genetic variation necessary for the evolution of reciprocity. [source]

The association between endothelin-1 gene polymorphisms and susceptibility to vitiligo in a Korean population

EXPERIMENTAL DERMATOLOGY, Issue 7 2007
Hyun-Jin Kim
Abstract:, Background:, Vitiligo is a skin disorder affected by genetic, environmental, local and endocrine factors. Endothelin-1, which is expressed by keratinocytes, has paracrine effects on melanocytes, influencing their homeostasis, proliferation and pigmentation. It is thought to play a role in the skin response to 311-nm, narrow-band ultraviolet irradiation. Objective:, To investigate the association of endothelin-1 gene (EDN1) polymorphisms with vitiligo in a Korean population. Methods:, To evaluate the expression of endothelin-1 in cultured human keratinocytes after irradiation with narrow-band ultraviolet B (NBUVB), we performed RT-PCR and ELISA. In addition, we genotyped 312 vitiligo patients and 313 matched-healthy controls, and compared the genotype, allele and haplotype frequencies of EDN1 polymorphisms (intron 4 G/A, rs2071942 and exon 5 G/T, rs5370) between the two groups, using PCR-restriction fragment length polymorphism. The effects of sex, onset age, the presence of autoimmune diseases, family history and clinical type were analysed statistically. Results:, NBUVB induced the expression of endothelin-1 in cultured human keratinocytes. The genotype distributions and allele frequencies of EDN1 polymorphisms did not differ significantly between vitiligo patients and healthy controls. Moreover, the results were not related to sex, onset age, the presence of autoimmune diseases or family history. Interestingly, the haplotype frequencies of EDN1 polymorphisms differed significantly between vitiligo patients and healthy controls. When analysed according to clinical type, the haplotype frequencies in the focal and segmental clinical types differed significantly from healthy controls. Conclusion:, This study suggests that EDN1 is related to the development of vitiligo in the Korean population. [source]