Functionalization of AFM Tips and Supports for Molecular Recognition Force Spectroscopy and Recognition Imaging.

Linking of sensor molecules (e.g., antibodies) to an AFM tip converts it into a biosensor by which single target molecules (e.g., antigens) can be detected and localized on the sample surface. Moreover, the mechanism of interaction can be studied by force spectroscopy if purified target molecules are linked to an ultra-flat surface, such as mica or silicon (nitride). Rapid imaging of the binding sites and force spectroscopy studies are greatly facilitated if 6-10 nm long polyethylene glycol (PEG) chains are used as flexible tethers between the sensor molecule and the tip. Here, we describe a set of methods by which a variety of proteins, oligonucleotides, or small molecules can be tethered to silicon (nitride) tips or to mica. Methods are included which afford site-specific and oriented coupling of the sensor molecules.

A reference high-pressure CO2 adsorption isotherm for ammonium ZSM-5 zeolite: results of an interlaboratory study.

This paper reports the results of an international interlaboratory study led by the National Institute of Standards and Technology (NIST) on the measurement of high-pressure surface excess carbon dioxide adsorption isotherms on NIST Reference Material RM 8852 (ammonium ZSM-5 zeolite), at 293.15 K (20 °C) from 1 kPa up to 4.5 MPa. Eleven laboratories participated in this exercise and, for the first time, high-pressure adsorption reference data are reported using a reference material. An empirical reference equation n e x = d ( 1 + exp [ - ln ( P ) + a / b ] ) c , [n ex -surface excess uptake (mmol/g), P-equilibrium pressure (MPa), a = -6.22, b = 1.97, c = 4.73, and d = 3.87] along with the 95% uncertainty interval (U k = 2 = 0.075 mmol/g) were determined for the reference isotherm using a Bayesian, Markov Chain Monte Carlo method. Together, this zeolitic reference material and the associated adsorption data provide a means for laboratories to test and validate high-pressure adsorption equipment and measurements. Recommendations are provided for measuring reliable high-pressure adsorption isotherms using this material, including activation procedures, data processing methods to determine surface excess uptake, and the appropriate equation of state to be used.

Agranulocitosis secundaria a clozapina: un estudio descriptivo en pacientes chilenos / Agranulocytosis secondary to clozapine: a descriptive study in Chilean patients

Introduction: Agranulocytosis is one of the most serious adverse effects of clozapine. The Latin American literature is currently scarce on the subject. Objective: To describe the occurrence of agranulocytosis or leukopenia secondary to clozapine and its associated factors in a sample of Chilean patients between the years 2011-2016. Materials and Methods: An observational, retrospective type of study was designed base on virtual information from the National Pharmacovigilance Registry and definition of alarm levels according to the Technical Standard of clozapine, later performing statistical analysis. Results: total n 60 patients, 8 patients with some alarm event; Alarm 1:5; Alarm II: 1; Alarm III: 2. Alarms were distributed between week 1 and week 242. The incidence was higher between weeks 0 and 12 (1.26%). Until week 18,53% of alarms I and 100% of alarms III occurred, alarm II occurred in month 10. Discussion: When comparing patients with and without alarm, significant differences were found in the basal count of leukocytes and neutrophils, with no differences in age and sex. Patients who presented alarms and/or lower baseline leukocyte or neutrophil counts could eventually benefit from a longer weekly follow-up. Conclusion: This study constitutes the first step towards exploring the adverse effects profile of clozapine in Chilean patients.

Introducción: La agranulocitosis es uno de los efectos adversos más graves de la clozapina. Existe escasa literatura latinoamericana al respecto. Objetivo: Describir la ocurrencia de agranulocitosis o leucopenia secundaria a clozapina y sus factores asociados en una muestra de pacientes chilenos entre los años 2011-2016. Materiales y Métodos: Se diseñó un estudio de tipo observacional, retrospectivo con información virtual del Registro Nacional de Farmacovigilancia y definición de niveles de alarma según Norma Técnica de clozapina, realizando posteriormente análisis estadístico. Resultados: En total 60 pacientes, 8 pacientes con algún evento de alarma; Alarma 1:5; Alarma II: 1; Alarma III: 2. Las alarmas se distribuyeron entre la semana 1 y la 242. La incidencia fue mayor entre las semanas 0 y 12 (1,26%). Hasta la semana 18 habían ocurrido el 53% de alarmas I y 100% de alarmas III, la alarma II ocurrió en el mes 10. Discusión: Al comparar a los pacientes con y sin alarma, se encontraron diferencias significativas en el conteo basal de leucocitos y neutrófilos, sin diferencias en edad y sexo. Aquellos pacientes que han presentado alarmas y/o menores conteos basales de leucocitos o neutrófilos, eventualmente, podrían beneficiarse de un seguimiento semanal más prolongado. Conclusión: Este estudio corresponde a un primer paso hacia explorar el perfil de efectos adversos de clozapina en pacientes chilenos.

Depresión en atención primaria: caracterización clínica-epidemiológica en centro de salud familiar Garín, Chile, 2006-2015 / Depression in primary care: clinical-epidemiological characterization in family health center Garín, Chile, 2006-2015

Introducción: La depresión es una patología prevalente en la población chilena, por lo tanto, fue necesario idear un programa de atención primaria para poder abarcar esta enfermedad. El objetivo del presente estudio fue analizar la situación respecto del diagnóstico de depresión en la población del Centro de Salud Familiar (CESFAM) Garín ubicado en la comuna de Quinta Normal en la Región Metropolitana, analizando los datos entre los años 2006-2015. Material y Métodos: Estudio descriptivo, la información fue obtenida de cartolas de salud mental de los equipos de salud de la población inscrita del CESFAM Garín evaluándose diferentes parámetros: edad, sexo, severidad, derivación, atención por psicología y tratamiento farmacológico. Resultados: Universo total de 356 pacientes con un promedio de edad de 52,3 años con una desviación estándar de +/- 18,5. El 85,6% corresponden a mujeres, siendo la mayor parte de los episodios de depresión catalogados como moderados. Se evidencia que una de cada cuatro personas mayores de 65 años con diagnóstico de depresión consumen benzodiazepinas (BZD). Discusión: La razón de mujeres/hombres con diagnóstico de depresión en la población estudiada fue considerablemente más alta que en otros estudios. A pesar de que el uso de BZD no es tratamiento de primera línea en depresión, son frecuentemente utilizados en todas las edades incluso en población geriátrica, por lo que recomendamos reconsiderar su uso dado sus potenciales complicaciones. El hipotiroidismo es un diagnóstico diferencial de importancia en los pacientes con depresión dado su coexistencia e influencia en el tratamiento.

Introduction: Depression is a prevalent pathology in the Chilean population. Therefore, it was necessary to think up a primary health care program in order to cover this disease. The objective of this study was to analyze the situation with regard to the diagnosis of depression in the population of CESFAM Garin located in Quinta Normal, Región Metropolitana, analyzing data from the years 2006-2015. Material and method: Descriptive study. The information was gathered from the health teams reports of the registered population of CESFAM Garin and assessing different parameters: age, sex, severity, derivation, attention by psychology and drug treatment. Results: From a total of 356 patients with an average age of 52.3 years with a standard deviation of +/- 18.5. 85.6% are women, in which most of the episodes are categorized as moderate in severity. It's evident that 1 in 4 people over 65 years diagnosed with depression consume benzodiazepines (BZD). Discussion: the ratio of women/men diagnosed with depression in the studied population was considerably higher than in other studies. Even though BZD use is not a first line treatment for depression, it is frequently used in all ages even in geriatric population. Consequently, we recommend re considering its use, despite their potential complications. Hypothyroidism is a key differential diagnosis in patients with depression given its coexistence and influence on treatment.

Caracterización epidemiológica de atenciones en un servicio de atención primaria de urgencias de la región metropolitana, Chile 2015 / Epidemiological characterization of attention in a primary attention and emergency service of the metropolitan region, Chile 2015

Introducción: Los Servicios de Atención Primaria de Urgencia (SAPU) juegan un rol clave en la atención en salud. Existe escasa caracterización de la población consultante de estos centros. Objetivo: Caracterización clínica y epidemiológica de las atenciones de urgencia del SAPU adosado al centro de salud familiar Garín durante el año 2015. Materiales y método: Estudio descriptivo de corte transversal. Información obtenida de tablas digitales de Datos de Atención de Usuarios durante el período enero ­ diciembre 2015. Se analizaron las variables: edad, sexo, previsión, causa de derivación y lugar de destino así como también grupos diagnósticos generales clasificando cada consulta. Resultados: El número total de pacientes fue 51.630. La edad promedio fue 34,3 años y el 61,8% pertenecía al grupo de 15 ­ 65 años. El 58% fueron mujeres. El 4,1% de la población estudiada fue derivada. Se derivan al mes en promedio 5,9 casos por Accidente Cerebro Vascular (ACV) y 7,8 por Síndrome Coronario Agudo (SCA). Las consultas más frecuentes fueron por causa respiratoria (31,3%) y gastrointestinales (17,7%). Discusión: Las características predominantes de la población son concordantes con estudios nacionales e internacionales en donde las consultas de urgencia, la mayoría corresponden a mujeres alrededor de 35 años. Un pequeño porcentaje de la población consultante es derivada a atención secundaria. Sugerimos continuar el énfasis en las enfermedades cardiovasculares (ACV y SCA) porque a pesar de no concentrar un gran número de derivación, sí cobran relevancia dado su alta morbi-mortalidad. El conocimiento de las características de la población es vital para optimizar las estrategias en la atención de salud.

Introduction: Primary Attention Emergency Services (PAES) play a crucial role in the Chilean health system. The characteristics of the population which uses these services are relatively unknown. Objetive: Clinical and epidemiological characterization of emergency care of PAES attached to the family health center Garín during the year 2015. Materials and methods: Descriptive, cross-section, retrospective study. Information obtained from digital user data for the period January-December 2015. The variables analyzed were age, sex, health insurance, cause and location of patient referral, as well as the general diagnostic groupings which classify each consultation. Results: The total number of patients was 51,631 and 58% were women. The average age was 34.3 years, and 61.8% belonged to the 15-65 years age group. A total of 4.1% of patients were referred to other centers. A monthly average of 5.9 cases is referred because of stroke and 7.8 cases for acute coronary syndrome (ACS). The most frequent consultations were due to respiratory (31.3%) and gastrointestinal (17.7%) causes. Discussion: The predominant characteristics of the reviewed patient population are consistent with national and international studies which show that most emergency consultations are made by women about 35 years old. A small percentage of patients is referred to secondary medical care. We suggest continuing the focus on cardiovascular diseases (stroke and ACS) becauses, although they do not represent a large number of referrals, they are significant because of their high rate of morbidity and mortality. Knowledge about the characteristics of the patient population is vital for optimizing health-care strategies.

A single-molecule approach to explore binding, uptake and transport of cancer cell targeting nanotubes.

In the past decade carbon nanotubes (CNTs) have been widely studied as a potential drug-delivery system, especially with functionality for cellular targeting. Yet, little is known about the actual process of docking to cell receptors and transport dynamics after internalization. Here we performed single-particle studies of folic acid (FA) mediated CNT binding to human carcinoma cells and their transport inside the cytosol. In particular, we employed molecular recognition force spectroscopy, an atomic force microscopy based method, to visualize and quantify docking of FA functionalized CNTs to FA binding receptors in terms of binding probability and binding force. We then traced individual fluorescently labeled, FA functionalized CNTs after specific uptake, and created a dynamic 'roadmap' that clearly showed trajectories of directed diffusion and areas of nanotube confinement in the cytosol. Our results demonstrate the potential of a single-molecule approach for investigation of drug-delivery vehicles and their targeting capacity.

Temporal lobe surgery in Germany from 1988 to 2008: diverse trends in etiological subgroups.

BACKGROUND AND PURPOSE: In the epilepsy community, there is talk that the number of classical patients with early onset temporal lobe epilepsy (TLE) and Ammon's horn sclerosis (AHS) is decreasing. This is counterintuitive, considering the success story of epilepsy surgery, improved diagnostic methods and the current recommendation of early admission to surgery. In order to recognize trends, the development of temporal lobe surgery over 20 years in three major German epilepsy centers was reviewed. METHODS: Age at surgery and duration of epilepsy, which was differentiated according to histopathology (AHS, developmental, tumor, vascular), year of surgery and center, were evaluated in a cohort of 2812 patients from three German epilepsy centers who underwent temporal lobe surgery between 1988 and 2008. The analysis was carried out for the pooled cohort as well as for each center separately. RESULTS: Of all patients, 52% showed AHS. Compared with other pathologies, the AHS group had the earliest epilepsy onset and the longest duration of epilepsy. Across five time epochs, the diagnosis of AHS increased in the first epoch, remaining constant thereafter. Contrary to the trends in other pathologies, in the AHS group the mean age of patients at surgery increased by 7 years and the duration of epilepsy until surgery increased by 5 years. This trend could be replicated in all three centers. As initially hypothesized for all groups, age and duration of epilepsy in other pathology groups remained constant or indicated earlier submission to surgery. CONCLUSIONS: During the first few years studied, most probably due to progress in brain imaging, the proportion of patients with AHS increased. However, despite stable numbers over time, and contrary to the trends in other pathology groups, age and duration of epilepsy in mesial TLE with AHS (mTLE + AHS) increased over time. This supports the hypothesis of a decreasing incidence of AHS. This trend is discussed with respect to disease-modifying factors which have changed the incidence of classical mTLE + AHS or, alternatively, to recent developments in antiepileptic drug treatment, the appraisal of surgery and economic incentives for treatment options other than surgery.

Mapping the intracellular distribution of carbon nanotubes after targeted delivery to carcinoma cells using confocal Raman imaging as a label-free technique.

The uptake of carbon nanotubes (CNTs) by mammalian cells and their distribution within cells is being widely studied in recent years due to their increasing use for biomedical purposes. The two main imaging techniques used are confocal fluorescence microscopy and transmission electron microscopy (TEM). The former, however, requires labeling of the CNTs with fluorescent dyes, while the latter is a work-intensive technique that is unsuitable for in situ bio-imaging. Raman spectroscopy, on the other hand, presents a direct, straightforward and label-free alternative. Confocal Raman microscopy can be used to image the CNTs inside cells, exploiting the strong Raman signal connected to different vibrational modes of the nanotubes. In addition, cellular components, such as the endoplasmic reticulum and the nucleus, can be mapped. We first validate our method by showing that only when using the CNTs' G band for intracellular mapping accurate results can be obtained, as mapping of the radial breathing mode (RBM) only shows a small fraction of CNTs. We then take a closer look at the exact localization of the nanotubes inside cells after folate receptor-mediated endocytosis and show that, after 8-10 h incubation, the majority of CNTs are localized around the nucleus. In summary, Raman imaging has enormous potential for imaging CNTs inside cells, which is yet to be fully realized.

Limbic encephalitis in children and adolescents.

OBJECTIVE: Limbic encephalitis is rare in people <18 years of age and rarely given a formal diagnosis. DESIGN: Retrospective study on presentation and outcome of children and adolescents with the clinico-radiological syndrome of limbic encephalitis tested for specific neuronal autoantibodies (Abs) over 3.5 years. SETTING: Assessment, diagnosis, treatment and follow-up at 12 neuropaediatric and neurological departments in Europe, with Abs determined in Bonn, Germany and Oxford, UK. PATIENTS: Ten patients <18 years of age who presented with a disorder mainly affecting the limbic areas of <5 years' duration with MRI evidence of mediotemporal encephalitis (hyperintense T2/FLAIR signal, resolving over time). RESULTS: Median age at disease onset was 14 years (range 3-17). Eight patients had defined Abs: one each with Hu or Ma1/2 Abs, four with high titre glutamic acid decarboxylase (GAD) Abs, two of whom had low voltage-gated potassium channel (VGKC) Abs and two with only low titre VGKC Abs. A tumour was only found in the patient with Hu Abs (a neuroblastoma). After a median follow-up of 15 months with corticosteroid or intravenous immunoglobulin treatment, starting after a median of 4 months, two patients recovered, eight remained impaired and one died. CONCLUSIONS: Limbic encephalitis is a disease that can occur in childhood or adolescence with many of the hallmarks of the adult disorder, suggesting that both result from similar pathogenic processes. Since most of the cases were non-paraneoplastic, as now also recognised in adults, more systematic and aggressive immunotherapies should be evaluated in order to improve outcomes.

Improved localization of cellular membrane receptors using combined fluorescence microscopy and simultaneous topography and recognition imaging.

The combination of fluorescence microscopy and atomic force microscopy has a great potential in single-molecule-detection applications, overcoming many of the limitations coming from each individual technique. Here we present a new platform of combined fluorescence and simultaneous topography and recognition imaging (TREC) for improved localization of cellular receptors. Green fluorescent protein (GFP) labeled human sodium-glucose cotransporter (hSGLT1) expressed Chinese Hamster Ovary (CHO) cells and endothelial cells (MyEnd) from mouse myocardium stained with phalloidin-rhodamine were used as cell systems to study AFM topography and fluorescence microscopy on the same surface area. Topographical AFM images revealed membrane features such as lamellipodia, cytoskeleton fibers, F-actin filaments and small globular structures with heights ranging from 20 to 30 nm. Combined fluorescence and TREC imaging was applied to detect density, distribution and localization of YFP-labeled CD1d molecules on alpha-galactosylceramide (alphaGalCer)-loaded THP1 cells. While the expression level, distribution and localization of CD1d molecules on THP1 cells were detected with fluorescence microscopy, the nanoscale distribution of binding sites was investigated with molecular recognition imaging by using a chemically modified AFM tip. Using TREC on the inverted light microscope, the recognition sites of cell receptors were detected in recognition images with domain sizes ranging from approximately 25 to approximately 160 nm, with the smaller domains corresponding to a single CD1d molecule.

Periictal heart rate variability analysis suggests long-term postictal autonomic disturbance in epilepsy.

BACKGROUND: One of the possible pathomechanisms of sudden death in epilepsy (SUDEP) is a postictal dysregulation of autonomic nervous system. We performed a heart rate variability (HRV) analysis of the periictal state to analyze whether a cardiac autonomic disturbance exists after an epileptic seizure. METHODS: We included 31 periictal video-EEG-ECG recordings of 31 patients with epilepsy who had consecutively undergone pre-surgical evaluation. Nine generalized tonic-clonic (GTCS), 15 complex partial, and seven simple motor seizures were included. HRV was evaluated by analyzing 5-min-long ECG epochs, sampling from baseline, direct preictal, early-postictal (<15 min after the seizure), and late-postictal (5-6 h after the seizure) periods. RESULTS: The heart rate was elevated immediately after the seizures, but 5-6 h postictally returned to the baseline level. Time-domain components of HRV decreased after the seizure and this decrease lasted for 5-6 h. Low-frequency power decreased in the early-postictal phase and high-frequency power of HRV dropped in the late-postictal phase. GTCS had an impact on short-term but not on long-term postictal HRV decrease. CONCLUSIONS: We found decreased HRV immediately after the seizures, which lasted at least 5-6 h postictally, indicating a long-term postictal disturbance of the autonomous nervous system. GTCS were accompanied by a more decreased HRV than other seizures. Our results may have relevance in explaining pathomechanism of SUDEP.

AFM imaging of functionalized carbon nanotubes on biological membranes.

Multifunctional carbon nanotubes are promising for biomedical applications as their nano-size, together with their physical stability, gives access into the cell and various cellular compartments including the nucleus. However, the direct and label-free detection of carbon nanotube uptake into cells is a challenging task. The atomic force microscope (AFM) is capable of resolving details of cellular surfaces at the nanometer scale and thus allows following of the docking of carbon nanotubes to biological membranes. Here we present topographical AFM images of non-covalently functionalized single walled (SWNT) and double walled carbon nanotubes (DWNT) immobilized on different biological membranes, such as plasma membranes and nuclear envelopes, as well as on a monolayer of avidin molecules. We were able to visualize DWNT on the nuclear membrane while at the same time resolving individual nuclear pore complexes. Furthermore, we succeeded in localizing individual SWNT at the border of incubated cells and in identifying bundles of DWNT on cell surfaces by AFM imaging.

AFM imaging of functionalized double-walled carbon nanotubes.

We present a comparative study of several non-covalent approaches to disperse, debundle and non-covalently functionalize double-walled carbon nanotubes (DWNTs). We investigated the ability of bovine serum albumin (BSA), phospholipids grafted onto amine-terminated polyethylene glycol (PL-PEG(2000)-NH(2)), as well as a combination thereof, to coat purified DWNTs. Topographical imaging with the atomic force microscope (AFM) was used to assess the coating of individual DWNTs and the degree of debundling and dispersion. Topographical images showed that functionalized DWNTs are better separated and less aggregated than pristine DWNTs and that the different coating methods differ in their abilities to successfully debundle and disperse DWNTs. Height profiles indicated an increase in the diameter of DWNTs depending on the functionalization method and revealed adsorption of single molecules onto the nanotubes. Biofunctionalization of the DWNT surface was achieved by coating DWNTs with biotinylated BSA, providing for biospecific binding of streptavidin in a simple incubation step. Finally, biotin-BSA-functionalized DWNTs were immobilized on an avidin layer via the specific avidin-biotin interaction.

Long-term outcome of lesional posterior cortical epilepsy surgery in adults.

OBJECTIVE: The aim of this study was to evaluate the short- and long-term seizure outcome and to find predictors of outcome after epilepsy surgery in lesional posterior cortical epilepsies (PCEs). METHODS: The operative outcome in 80 consecutive adult patients with lesional PCEs who underwent resective surgery for intractable partial epilepsy between 1991 and 2006 was retrospectively studied. RESULTS: The probability of remaining in Engel Class I was 66.3% (95% CI 60 to 72) at 6 months, 52.5% (95% CI 47 to 57) at 2 years, 52.9% (CI 45 to 59) at 5 years and 47.1% (CI 42 to 52) at 10 years. Factors predicting poor outcome were the presence of a somatosensory aura, extraregional spikes, incomplete resection, interictal epileptiform discharge (IED) in EEG 6 months and 2 years postsurgery, history of generalised tonic-clonic seizure (GT-CS) and the presence of focal cortical dysplasia in the resected specimen. Factors predicting good outcome were childhood onset of epilepsy, short epilepsy duration, ipsilateral spikes, visual aura, presence of well-circumscribed lesion in preoperative MRI and a pathologically defined tumour. In the multivariate analysis, predictors were different in the long and short term as follows: incomplete resection as proven by postoperative MRI (hazard ratio (HR) 2.059 (CI 1.19 to 3.67)) predicts seizure relapse in short-term follow-up. The presence of IED in the EEG performed 6 months after surgery (HR 2.3 (CI 1.128 to 4.734)) predicts seizure relapse in the long-term fellow-up. However, the absence of a history of GT-CS independently predicts seizure remission in short- and long-term follow-up. CONCLUSIONS: Surgery in PCEs proved to be effective in short- and long-term follow-up. Lesional posterior cortical epilepsy may be a progressive process in a substantial number of cases.

Imaging and detection of single molecule recognition events on organic semiconductor surfaces.

The combination of organic thin film transistors and biological molecules could open new approaches for the detection and measurement of properties of biological entities. To generate specific addressable binding sites on such substrates, it is necessary to determine how single biological molecules, capable of serving as such binding sites behave upon attachment to semiconductor surfaces. Here, we use a combination of high-resolution atomic force microscopy topographical imaging and single molecule force spectroscopy (TREC), to study the functionality of antibiotin antibodies upon adsorption on pentacene islands, using biotin-functionalized, magnetically coated AFM tips. The antibodies could be stably adsorbed on the pentacene, preserving their functionality of recognizing biotin over the whole observation time of more than one hour. We have resolved individual antigen binding sites on single antibodies for the first time. This highlights the resolution capacity of the technique.

Outcome and predictors of interstitial radiosurgery in the treatment of gelastic epilepsy.

BACKGROUND: Gelastic epilepsy due to hypothalamic hamartomas is usually a severe condition encompassing both epileptic seizures and an epileptic encephalopathy associated with behavioral and cognitive impairments. Here we report the effects of interstitial radiosurgery in the treatment of this generally pharmacoresistant epilepsy syndrome. METHODS: Twenty-four consecutive patients (3-46 years of age, 7 women, mean age 21.9 years, mean duration of epilepsy 17.6 years) with gelastic epilepsy due to MR-ascertained hypothalamic hamartoma and a minimum follow-up period of 1 year were included in this evaluation. Treatment was performed by interstitial radiosurgery using stereotactically implanted (125)I seeds. Effects of treatment on seizure frequency and possible side effects were assessed prospectively. Factors influencing outcome and side effects were analyzed statistically. RESULTS: After a mean 24-month follow-up period following the last radiosurgical treatment, 11/24 patients were seizure free or had seizure reduction of at least 90% (Engel class I and II), in some cases only after repeated treatment. The duration of epilepsy prior to radiosurgery negatively influenced outcome. Treatment was well tolerated in most patients. Headache, fatigue, and lethargy were transient side effects associated with the development of brain edema extending from the implantation site in five patients. Four patients had a weight gain of more than 5 kg which was severe in two patients. The majority of those patients whose cognitive functions initially deteriorated showed subsequent recovery of cognitive functions, but episodic memory in two patients showed persistent decline at 1 year follow-up. Longer disease duration increased the risk for cognitive side effects, and larger hamartoma size and eccentric seed positioning increased the risk for radiogenic brain edema. Neither perioperative mortality nor neurologic impairments, visual field defects, or endocrinologic disturbances were encountered following treatment. CONCLUSION: Interstitial radiosurgery was efficacious in significantly improving gelastic epilepsy in about half of the patients treated in this series. Weight gain may occur as a side effect, whereas other severe side effects reported following microsurgical removal of the hamartoma were absent. The study results strongly suggest early causal treatment, as chances for seizure control are higher and the risk for cognitive side effects is lower in patients with shorter disease duration.

Peri-ictal vegetative symptoms in temporal lobe epilepsy.

We investigated peri-ictal vegetative symptoms (PIVS) in 141 patients with adult temporal lobe epilepsy (TLE) and assessed frequency, gender effect, and lateralizing value of peri-ictal autonomic signs. We recorded abdominal auras in 62%, goosebumps in 3%, hypersalivation in 12%, spitting in 1%, cold shivering in 3%, urinary urge in 3%, water drinking in 7%, postictal nose wiping (PNW) in 44%, and postictal coughing in 16%. At least one vegetative sign appeared in 86% of the patients. The presence of PIVS did not have a significant lateralizing value. PNW occurred in 52% of women and in 33% of men, whereas any PIVS was present in 93% of women and 77% of men. In summary, contradictory to previous studies, the presence of PIVS has no lateralizing value, which may be linked to a low frequency of occurrence of PIVS. PIVS, especially PNW, occurred more frequently in women, supporting the gender differences in epilepsy.

Presurgical seizure frequency and tumoral etiology predict the outcome after extratemporal epilepsy surgery.

OBJECTIVE: To examine the predictive value of demographic data for the seizure outcome after extratemporal epilepsy surgery. METHODS: Eightyone patients who underwent resective extratemporal epilepsy surgery were retrospectively studied concerning (a) age at surgery, (b) onset of epilepsy, (c) duration of epilepsy, (d) number of seizures at the time of presurgical evaluation, (d) number of presurgically tested antiepileptic substances and (f) number of seizure types. The data were correlated to the postoperative seizure outcome after two years. RESULTS: 33 patients (40.7%) were seizure free two years after surgery. Univariate and multivariate analysis revealed that both tumor etiology and low presurgical seizure frequency were independently associated with seizure freedom after epilepsy surgery. The recurrence rate in patients with one or more seizures per day was more than two-fold if compared with patients with fewer seizures. The remaining demographic factors did not show a significant association with seizure outcome in our 81 patients. CONCLUSIONS: Fewer than daily seizures prior to surgery and a tumoral etiology independently increase the likelihood of remaining seizure free two years after extratemporal epilepsy surgery.

Assessment of cognitive functions before and after stereotactic interstitial radiosurgery of hypothalamic hamartomas in patients with gelastic seizures.

We assessed cognitive functions before and 3 months after interstitial radiotherapy in 14 patients with gelastic seizures caused by hypothalamic hamartoma. Cognitive functioning was assessed before temporary implantation of (125)I-seed and 3 months after seed explantation. Performance was compared with that of a selected control group of conservatively treated patients with symptomatic focal epilepsy tested before add-on treatment with a new antiepileptic drug and after reaching steady state. No short-term negative side effects of the interstitial radiosurgery could be observed for the domains of attention and executive functions and verbal and figural memory performance. Cognitive development of the patients treated with seeds was comparable to that of the control group at both assessments. Thus, the stereotactic implantation of (125)I-seeds in this patient group with gelastic seizures caused by hypothalamic hamartoma provides a well-tolerated minimally invasive method in the treatment of this severe epileptic syndrome without negative cognitive side effects.

Patients' ability to react before complex partial seizures.

OBJECTIVE: The purpose of the study described here was to investigate the pathophysiology of patients' ability to react during the conscious (aura) phase of complex partial seizures (CPS) originating from the temporal lobe. METHODS: We reviewed video recordings of CPS experienced by 130 adult patients who had undergone epilepsy surgery for intractable medial temporal lobe epilepsy. All patients were instructed to push the alarm button when they felt an aura. We defined the preictal reactivity as the ability to push the alarm button before the complex partial (unconscious) phase of seizures. RESULTS: Seventy-seven patients (59%) pushed the alarm button before seizures. Patients with preictal reactivity were significantly younger, more often had lateralized EEG seizure patterns, and had a better postoperative outcome. Patients who did not push the alarm button had secondarily generalized seizures more often. CONCLUSIONS: Ability to react before CPS is associated with a circumscribed region involved at seizure onset and spread, and with a seizure-free postoperative outcome.