Clinical significance of glutamic acid decarboxylase antibodies in patients with epilepsy

Purpose: Glutamic acid decarboxylase antibodies (GADAs) have been detected in patients with epilepsy, but the clinical determinants of epilepsy associated with GADA have not been defined. Methods: We analyzed GADA with a radioimmunoassay in sera of 253 well‐characterized patients with epilepsy and 200 control subjects. The positive samples were confirmed by immunohistochemistry and western blotting (WB). Sera were screened for other autoantibodies. Results: GADA were detected in 15 patients (5.9%) and in three control subjects (1.5%) (p = 0.026). Seven patients (2.8%) had high GADA titers [≥1,000 relative units (RUs)/ml], six of whom had temporal lobe epilepsy (TLE). All three GADA‐positive control subjects had low titers. Two of the five patients with high GADA titers and available cerebrospinal fluid (CSF) samples had intrathecal synthesis (IS) of GADA; one patient had CSF oligoclonal bands. The prevalence of increased levels of GADA tended to be higher in patients with TLE than in patients with extra‐TLE [odds ratio (OR) 1.32, 95% confidence interval (CI) 0.39–4.42; p = 0.657]. The patients with high GADA titers had significantly higher number of other autoantibodies compared to the patients with low GADA titers (p = 0.001) and the patients with normal GADA (p < 0.001). Discussion: High GADA titers were present in a subgroup of patients; close to 90% had TLE. The immunologic profile of these patients suggests that the most probable origin of their epilepsy is autoimmune. A positive IS of GADA may be a marker of an ongoing immune response that could identify those patients in whom a trial with immunosuppressive therapy might be warranted.     

The effect of model order selection in group PICA

Independent component analysis (ICA) of functional MRI data is sensitive to model order selection. There is a lack of knowledge about the effect of increasing model order on independent components' (ICs) characteristics of resting state networks (RSNs). Probabilistic group ICA (group PICA) of 55 healthy control subjects resting state data was repeated 100 times using ICASSO repeatability software and after clustering of components, centrotype components were used for further analysis. Visual signal sources (VSS), default mode network (DMN), primary somatosensory (S₁), secondary somatosensory (S₂), primary motor cortex (M₁), striatum, and precuneus (preC) components were chosen as components of interest to be evaluated by varying group probabilistic independent component analysis (PICA) model order between 10 and 200. At model order 10, DMN and VSS components fuse several functionally separate sources that at higher model orders branch into multiple components. Both volume and mean z‐score of components of interest showed significant (P < 0.05) changes as a function of model order. In conclusion, model order has a significant effect on ICs characteristics. Our findings suggest that using model orders ≤20 provides a general picture of large scale brain networks. However, detection of some components (i.e., S₁, S₂, and striatum) requires higher model order estimation. Model orders 30–40 showed spatial overlapping of some IC sources. Model orders 70 ± 10 offer a more detailed evaluation of RSNs in a group PICA setting. Model orders > 100 showed a decrease in ICA repeatability, but added no significance to either volume or mean z‐score results. Hum Brain Mapp, 2010. © 2010 Wiley‐Liss, Inc.     

A Randomized,Sham-Controlled Trial of Repetitive Transcranial Magnetic Stimulation Targeting M1 and S2 in Central Poststroke Pain: A Pilot Trial

ObjectivesCentral poststroke pain (CPSP), a neuropathic pain condition, is difficult to treat. Repetitive transcranial magnetic stimulation (rTMS) targeted to the primary motor cortex (M1) can alleviate the condition, but not all patients respond. We aimed to assess a promising alternative rTMS target, the secondary somatosensory cortex (S2), for CPSP treatment.Materials and MethodsThis prospective, randomized, double-blind, sham-controlled three-arm crossover trial assessed navigated rTMS (nrTMS) targeted to M1 and S2 (10 sessions, 5050 pulses per session at 10 Hz). Participants were evaluated for pain, depression, anxiety, health-related quality of life, upper limb function, and three plasticity-related gene polymorphisms including Dopamine D2 Receptor (DRD2). We monitored pain intensity and interference before and during stimulations and at one month. A conditioned pain modulation test was performed using the cold pressor test. This assessed the efficacy of the descending inhibitory system, which may transmit TMS effects in pain control.ResultsWe prescreened 73 patients, screened 29, and included 21, of whom 17 completed the trial. NrTMS targeted to S2 resulted in long-term (from baseline to one-month follow-up) pain intensity reduction of ≥30% in 18% (3/17) of participants. All stimulations showed a short-term effect on pain (17–20% pain relief), with no difference between M1, S2, or sham stimulations, indicating a strong placebo effect. Only nrTMS targeted to S2 resulted in a significant long-term pain intensity reduction (15% pain relief). The cold pressor test reduced CPSP pain intensity significantly (p = 0.001), indicating functioning descending inhibitory controls. The homozygous DRD2 T/T genotype is associated with the M1 stimulation response.ConclusionsS2 is a promising nrTMS target in the treatment of CPSP. The DRD2 T/T genotype might be a biomarker for M1 nrTMS response, but this needs confirmation from a larger study.     

Higher Preimplantation Opioid Doses Associated With Long‐Term Spinal Cord Stimulation Failure in 211 Patients With Failed Back Surgery Syndrome

ObjectiveSpinal cord stimulation (SCS) is an effective treatment in failed back surgery syndrome (FBSS). We studied the effect of preimplantation opioid use on SCS outcome and the effect of SCS on opioid use during a two-year follow-up period.Materials and methodsThe study cohort included 211 consecutive FBSS patients who underwent an SCS trial from January 1997 to March 2014. Participants were divided into groups, which were as follows: 1) SCS trial only (n = 47), 2) successful SCS (implanted and in use throughout the two-year follow-up period, n = 131), and 3) unsuccessful SCS (implanted but later explanted or revised due to inadequate pain relief, n = 29). Patients who underwent explantation for other reasons (n = 4) were excluded. Opioid purchase data from January 1995 to March 2016 were retrieved from national registries.ResultsHigher preimplantation opioid doses associated with unsuccessful SCS (ROC: AUC = 0.66, p = 0.009), with 35 morphine milligram equivalents (MME)/day as the optimal cutoff value. All opioids were discontinued in 23% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.004). Strong opioids were discontinued in 39% of patients with successful SCS, but in none of the patients with unsuccessful SCS (p = 0.04). Mean opioid dose escalated from 18 ± 4 MME/day to 36 ± 6 MME/day with successful SCS and from 22 ± 8 MME/day to 82 ± 21 MME/day with unsuccessful SCS (p < 0.001).ConclusionsHigher preimplantation opioid doses were associated with SCS failure, suggesting the need for opioid tapering before implantation. With continuous SCS therapy and no explantation or revision due to inadequate pain relief, 39% of FBSS patients discontinued strong opioids, and 23% discontinued all opioids. This indicates that SCS should be considered before detrimental dose escalation.     

Bacterial infection (BI)-INDEX: an improved and simplified rapid flow cytometric bacterial infection marker

The aim of this study was to develop a rapid and simple flow cytometric bacterial infection marker. In this prospective comparative study, quantitative flow cytometric analysis of CD10, CD35, CD66b, CD282, and MHC Class I molecules on human neutrophils, monocytes, and B-lymphocytes from 141 hospitalized febrile patients with suspected infection and from 50 healthy controls was performed. We developed a flow cytometric marker of local and systemic bacterial infections, designated “bacterial infection (BI)-INDEX”, incorporating the quantitative analysis of CD10, CD35, MHCI, CD66b, and CD282 on neutrophils, monocytes, and B-lymphocytes, which displayed 90% sensitivity and 96% specificity in distinguishing between microbiologically confirmed bacterial (n = 31) and viral infections (n = 27) within a 1-h time-frame. We propose that our novel rapid BI-INDEX test will be useful in assisting physicians to ascertain whether antibiotic treatment is required, thus limiting unnecessary antimicrobial usage.     

Prognostic factors in laryngeal carcinoma: the role of apoptosis,p53, proliferation (Ki-67) and angiogenesis

Even though the roles of different known or suggested prognostic factors in laryngeal cancer have been studied in detail, clinical stage at time of diagnosis and anatomic subsite of the tumour remain the only practical predictors of clinical outcome and offer the only guidelines in the planning of treatment. In this study, the relative roles of known demographic and clinical prognostic factors, in addition to four histopathological factors, were evaluated in a sample of 100 laryngeal carcinoma patients with multivariate analysis using the Cox regression model. In addition to advanced stage (stage III-IV) (relative hazard of death (HR) 8.9, p=0.01) and supraglottic disease (HR 5.6, p=0.02), high apoptotic index (HR 11.1, p=0.05) was significantly associated with poor survival. Cell proliferation, p53 and angiogenesis did not significantly affect the prognosis. In the future, high degree of apoptosis could be used to identify patients with poor prognosis in laryngeal cancer.     

Three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology: Formulation development and in vitro anticancer activity

Despite recent advances in cancer therapy, many malignant tumors still lack effective treatment and the prognosis is very poor. Paclitaxel is a potential anticancer drug, but its use is limited by the facts that paclitaxel is a P-gp substrate and its aqueous solubility is poor. In this study, three-step tumor targeting of paclitaxel using biotinylated PLA-PEG nanoparticles and avidin-biotin technology was evaluated in vitro as a way of enhancing delivery of paclitaxel. Paclitaxel was incorporated both in biotinylated (BP) and non-biotinylated (LP) PEG-PLA nanoparticles by the interfacial deposition method. Small (mean size approximately 110nm), spherical and slightly negatively charged (-10mV) BP and LP nanoparticles achieving over 90% paclitaxel incorporation were obtained. The successful biotinylation of nanoparticles was confirmed in a novel streptavidin assay. BP nanoparticles were targeted in vitro to brain tumor (glioma) cells (BT4C) by three-step avidin-biotin technology using transferrin as the targeting ligand. The three-step targeting procedure increased the anti-tumoral activity of paclitaxel when compared to the commercial paclitaxel formulation Taxol((R)) and non-targeted BP and LP nanoparticles. These results indicate that the efficacy of paclitaxel against tumor cells can be increased by this three-step targeting method.     

Risk factors for poor tuberculosis treatment outcome in Finland: a cohort study

Background  

We investigated the patient- and treatment-system dependent factors affecting treatment outcome in a two-year cohort of all treated culture-verified pulmonary tuberculosis (TB) cases to establish a basis for improving outcomes.     

Sampling rate causes bias in APACHE II and SAPS II scores

OBJECTIVE: To study the effect of sampling rate of laboratory and haemodynamic data on severity scorings and predicted risk of hospital death. DESIGN: Prospective study. SETTING: Medical-surgical intensive care unit (ICU) with 23 beds in a university hospital. PATIENTS: Sixty-nine consecutive emergency admission patients. INTERVENTIONS: Blood samples were drawn from indwelling arterial lines for the laboratory tests of all variables contained in the APACHE II and SAPS II scores at 2-hourly intervals from the time of admission up to 24 h or earlier discharge or death of the patient. Haemodynamic data and temperature were collected either manually by the attending nurse once an hour or as 2-min median values automatically using a Clinical Information Management System (CIMS, Clinisoft, Datex-Ohmeda, Helsinki, Finland). Three sets of severity scores were obtained. (1) "Traditional" scores (haemodynamic data from manual records and laboratory values from tests taken at admission and subsequently on clinical basis only). (2) "CIMS" scores (haemodynamic data from 2-min median values and laboratory values prescribed on clinical indication) and (3) "High rate" scores (haemodynamic data from 2-min median values and laboratory values at 2-hourly intervals). Probability of hospital death was calculated using the SAPS II and APACHE II scores, respectively. RESULTS: Increasing the sampling rate of haemodynamic monitoring interval to 2-min from once per hour resulted in 7.8 % and 11.5 % increases (p < 0.001) in the APACHE II and SAPS II scores, respectively. The combined effect of increased sampling rate of haemodynamic and laboratory tests on the APACHE II and SAPS II scores was 14.4 % and 14.5 % compared to traditional scores (p < 0.001), respectively. The probability of hospital death increased from 0.23 and 0.21 ("traditional" SAPS II and APACHE II) to 0.31 and 0.25 ("high rate" SAPS II and APACHE II), respectively, and, because eight patients died, standardised mortality ratio (SMR) decreased from 0.53 to 0.41 (SAPS II) and from 0.60 to 0.50 (APACHE II). CONCLUSIONS: Increased sampling rate results in higher scores and lower SMR. Comparisons between hospitals using severity scores are biased due to differences in the sampling rates.