Anti-LM1 antibodies in the sera of patients with Guillain-Barré syndrome, Miller Fisher syndrome, and motor neuron disease

This study is designed to establish whether sialosylneolactotetraosylceramide (LM1), a major component of human peripheral nerve ganglioside, is a potential target antigen for the development of peripheral autoimmune neuropathies such as Guillain-Barré syndrome (GBS) and Miller Fisher syndrome (MFS). Serum antibodies against LM1 in 116 patients with GBS, 56 patients with MFS, 88 patients with motor neuron disease (MND) and 60 normal control subjects were quantified using enzyme-linked immunosorbent assay (ELISA). The presence of anti-LM1 antibodies were confirmed using an immunostaining method on high-performance thin-layer chromatographic plates (HPTLC). Anti-LM1 IgG antibodies were detected in 22% (25/116) of patients with GBS. The ratio of the demyelination type to the axonal type of GBS was approximately 3:1. Among the 25 anti-LM1-positive GBS patients, additional anti-GM1 IgG antibodies were detected in 7 patients, 4 of whom possessed the axonal form of GBS. Anti-LM1 antibodies were also detected in a significant portion of patients with MFS (20%, 11/56). In contrast, anti-LM1 antibodies were detected in only 2% (2/88) of patients with MND, and 7% (4/60) of normal control subjects. The results of this study suggest that serum antibodies against LM1 may have a pathogenic role in the development of GBS and MFS.     

Measles antibodies, κ-λ light chain distribution and immunoglobulins in serum,cerebrospinal fluid and brain of a patient affected with multiple sclerosis

Summary The serum, cerebrospinal (CSF) and brain of a patient (NAG) affected with multiple sclerosis (MS) were examined for measles antibodies with CF and HI techniques, and the - light chain ratios of all samples available were evaluated. - populations of the matched serum, CSF and brain specimens were all -predominant and in agreement with each other; the light chain distribution of the brain specimens confirmed previous findings [3].Only the serum immunoglobulins showed significant measles antibody titers, but slightly increased measles antibody titers were also observed in ventricular plaques.The amount of immunoglobulin G (IgG) synthesized per day by the central nervous system (CNS) was estimated.The IgG synthesis in CNS NAG (11.6mg/day) was above the upper limit of the normal range (3.3 mg/day), but apparently there was no positive correlation between the intracerebral IgG synthesis and specific anti-measles IgG.

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Zusammenfassung Das Serum und der Liquor sowie das Gehirn eines Patienten (NAG), der an Multipler Sklerose (MS) litt, wurden auf das Vorhandensein von Masernantikörper mit der CF- und HI-Technik untersucht und die --Relation der leichten Ketten aller vorhandenen Proben wurde ausgewertet. In allen Proben lag eine -Dominanz vor, sowohl im Serum, im Liquor als auch im Gehirn. Die Verteilung der leichten Ketten in den Gehirnproben bestätigt frühere Ergebnisse [3].Nur in den Serumimmunoglobulinen konnten signifikante Masernantikörpertiter nachgewiesen werden, jedoch waren leicht erhöhte Masernantikörpertiter auch in den ventrikelnahen Plaques vorhanden.Es wurde die Menge des täglich durch das zentrale Nervensystem synthetisierte Immunoglobulin G (IgG) geschätzt.Die IgG-Synthese im Zentralnervensystem der Patientin NAG (11.6 mg/Tag) lag über der üblichen Normgrenze (3.3 mg/Tag) aber es schien keine positive Korrelation zwischen der intrazerebralen IgG-Synthese einerseits und den spezifischen Antimasern-IgG andererseits vorzuliegen.

     

Predictors and dynamic online nomogram for postoperative delayed hyponatremia after endoscopic transsphenoidal surgery for pituitary adenomas: a single-center,retrospective, observational cohort study with external validation

Background Postoperative delayed hyponatremia (PDH) is a major cause of readmission after endoscopic transsphenoidal surgery (eTSS) for pituitary adenomas (PAs). However, the risk factors associated with PDH have not been well established, and the development of a dynamic online nomogram for predicting PDH is yet to be realized. We aimed to investigate the predictive factors for PDH and construct a dynamic online nomogram to aid in its prediction.Methods We analyzed the data of 226 consecutive p...     

Differences between the production of [s] and [ʃ] in the speech of adults,typically developing children,and children with speech sound disorders: An ultrasound study

This study describes the criteria that are used in ultrasound to measure the differences between the tongue contours that produce [s] and [?] sounds in the speech of adults, typically developing children (TDC), and children with speech sound disorder (SSD) with the phonological process of palatal fronting. Overlapping images of the tongue contours that resulted from 35 subjects producing the [s] and [?] sounds were analysed to select 11 spokes on the radial grid that were spread over the tongue contour. The difference was calculated between the mean contour of the [s] and [?] sounds for each spoke. A cluster analysis produced groups with some consistency in the pattern of articulation across subjects and differentiated adults and TDC to some extent and children with SSD with a high level of success. Children with SSD were less likely to show differentiation of the tongue contours between the articulation of [s] and [?].     

The “Seroquel” Outcomes Study (SOS): Efficacy and tolerability of quetiapine in a long-term,naturalistic study of patients with schizophrenia

Objective. The “Seroquel” Outcomes Study (SOS) aimed to assess the efficacy and tolerability of quetiapine in patients with schizophrenia in the clinical practice setting. Methods. A 6-month, non-comparative, open-label study in adults with schizophrenia in a standard care setting in Spain. Outpatients received flexibly dosed quetiapine. Efficacy was evaluated using the Brief Psychiatry Rating Scale (BPRS) and the Clinical Global Impression (CGI) scale. BPRS response was defined as≥30% decrease from baseline. Tolerability was assessed using the Simpson–Angus Scale (SAS) and a modified Udvalg for Kliniske Undersogelser (UKU) side-effects scale. Results. A total of 2029 patients enrolled. Significant changes from baseline to Month 6 were recorded for BPRS total and subscale scores (P<0.001). Compared with doses of≥600 mg/day, doses of<400 mg/day were a strong predictor of a lower response rate (OR 0.62; 95% CI: 0.48, 0.82) and higher withdrawal rate (OR 3.3; 95% CI: 2.5, 4.4). Mean change in weight was minimal (+0.4 kg). Somnolence (26.7%), asthenia (12.5%), and constipation (9.8%) were the most common adverse events. Conclusion. Quetiapine was found to improve symptoms of schizophrenia, as indicated by a significant decrease in BPRS scores, and was well tolerated by patients in clinical practice.     

Prevalence and risk markers of behavior problems among adults with intellectual disabilities: A total population study in Örebro County,Sweden

The aim of the present study was to investigate the prevalence of behavior problems among people with administratively defined intellectual disability (ID) and identify possible risk markers for behavior problems using the Behavior Problems Inventory (BPI). Sixty-two percent of the ID population (n = 915) had a behavior problem (self-injurious, stereotyped, or aggressive/destructive behavior) and 18.7% had a behavior problem identified as challenging behavior, resulting in a prevalence of 80.3 per 100,000 in the base population. The most pronounced risk markers for behavior problems were severity of ID, autism, night sleep disturbances, sensory hypersensitivity, communication dysfunction, social deficits, psychiatry involvement, and psychotropic medication. About 50% of people with behavior problems were on psychotropic drugs. Protective markers were Down's syndrome and, to some extent, cerebral palsy. The results were largely consistent with those reported in previous studies. Findings not previously reported were that prevalence of aggressive/destructive behavior peaked among those ≥70 years. Highlighting groups within a population at particular risk has implications for management and treatment of individuals with behavior problems.     

Levodopa-carbidopa intestinal gel (LCIG) treatment in routine care of patients with advanced Parkinson’s disease: An open-label prospective observational study of effectiveness,tolerability and healthcare costs

BackgroundContinuous infusion of levodopa-carbidopa intestinal gel (LCIG) can effectively manage motor and non-motor complications in advanced Parkinson’s disease (PD). Healthcare costs, quality of life (QoL), effectiveness, and tolerability were assessed in routine care treatment with LCIG.MethodsThe seventy-seven patients enrolled in this prospective, open-label, 3-year study in routine medical care were LCIG-naïve (N = 37), or had previous LCIG treatment for <2 (N = 22), or ≥2 (N = 18) years. Healthcare costs were collected monthly. PD symptoms and QoL were assessed with the Unified Parkinson’s Disease Rating Scale (UPDRS), 39-item Parkinson’s Disease Questionnaire (PDQ-39), and EuroQoL 5-Dimension Visual Analog Scale (EQ-5D VAS); LCIG dose, safety, and tolerability were monitored.ResultsMean monthly costs per patient (€8226 ± 5952) were similar across cohorts, remained steady during 3-year follow-up, and increased with PD severity and QoL impairment. In LCIG-naïve patients, significant improvements compared to baseline were observed on the UPDRS total score and PDQ-39 summary index score through 18 months (n = 24; UPDRS, p = 0.033; PDQ-39, p = 0.049). Symptom control was maintained during 3-year follow-up in LCIG-experienced cohorts. Small changes in mean daily LCIG dose were observed. Adverse events were common and generally related to the device, procedure, levodopa, or laboratory evaluations.ConclusionsCosts in LCIG-treated patients were stable over 3 years. LCIG treatment led to significant improvements in motor function and QoL over 18 months in LCIG-naïve patients and no worsening was observed in LCIG-experienced patients over 3 years despite natural PD progression over time. The long-term safety was consistent with the established LCIG profile.     

Sensitivity of kinetic macro parameters to changes in dopamine synthesis, storage, and metabolism: a simulation study for [¹⁸F]FDOPA PET by a model with detailed dopamine pathway

Quantitative interpretation of brain [¹⁸F]FDOPA PET data has been made possible by several kinetic modeling approaches, which are based on different assumptions about complex [¹⁸F]FDOPA metabolic pathways in brain tissue. Simple kinetic macro parameters are often utilized to quantitatively evaluate metabolic and physiological processes of interest, which may include DDC activity, vesicular storage, and catabolism from ¹⁸F‐labeled dopamine to DOPAC and HVA. A macro parameter most sensitive to the changes of these processes would be potentially beneficial to identify impaired processes in a neurodegenerative disorder such as Parkinson's disease. The purpose of this study is a systematic comparison of several [¹⁸F]FDOPA macro parameters in terms of sensitivities to process‐specific changes in simulated time‐activity curve (TAC) data of [¹⁸F]FDOPA PET. We introduced a multiple‐compartment kinetic model to simulate PET TACs with physiological changes in the dopamine pathway. TACs in the alteration of dopamine synthesis, storage, and metabolism were simulated with a plasma input function obtained by a non‐human primate [¹⁸F]FDOPA PET study. Kinetic macro parameters were calculated using three conventional linear approaches (Gjedde‐Patlak, Logan, and Kumakura methods). For simulated changes in dopamine storage and metabolism, the slow clearance rate (k_loss) as calculated by the Kumakura method showed the highest sensitivity to these changes. Although k_loss performed well at typical ROI noise levels, there was large bias at high noise level. In contrast, for simulated changes in DDC activity it was found that K_i and V_T, estimated by Gjedde‐Patlak and Logan method respectively, have better performance than k_loss. Synapse 2011. © 2011 Wiley‐Liss, Inc.     

Repetitive transcranial magnetic stimulation combined with cognitive training is a safe and effective modality for the treatment of Alzheimer’s disease: a randomized, double-blind study

Cortical excitability can be modulated using repetitive transcranial magnetic stimulation (rTMS). Previously, we showed that rTMS combined with cognitive training (rTMS-COG) has positive results in Alzheimer’s disease (AD). The goal of this randomized double-blind, controlled study was to examine the safety and efficacy of rTMS-COG in AD. Fifteen AD patients received 1-h daily rTMS-COG or sham treatment (seven treated, eight placebo), five sessions/week for 6 weeks, followed by biweekly sessions for 3 months. The primary outcome was improvement of the cognitive score. The secondary outcome included improvement in the Clinical Global Impression of Change (CGIC) and Neuropsychiatric Inventory (NPI). There was an improvement in the average ADAS-cog score of 3.76 points after 6 weeks in the treatment group compared to 0.47 in the placebo group and 3.52 points after 4.5 months of treatment, compared to worsening of 0.38 in the placebo (P = 0.04 and P = 0.05, respectively). There was also an improvement in the average CGIC score of 3.57 (after 6 weeks) and 3.67 points (after 4.5 months), compared to 4.25 and 4.29 in the placebo group (mild worsening) (P = 0.05 and P = 0.05, respectively). NPI improved non-significantly. In summary, the NeuroAD system offers a novel, safe and effective therapy for improving cognitive function in AD.