The possible association between neurodegenerative/demyelinating neurological disorders in achalasia patients.

The precise pathogenesis of achalasia is still unclear. Neurodegenerative and/or demyelinating disorders (NDD) appear to share some common pathophysiological pathways described in achalasia such as inflammation, autoimmune, mitochondrial dysfunction, and neurodegeneration. Jerie et al. have published on the October issue a prospective study assessing the prevalence of several NDD in achalasia patients. In this commentary, we shed some light on the possible link between achalasia and NDD as well as comment on the study by Jerie et al.

The role of chronobiology in drug-resistance epilepsy: The potential use of a variability and chronotherapy-based individualized platform for improving the response to anti-seizure drugs.

Despite progress in the development of anti-seizure drugs, drug-resistant epilepsy (DRE) occurs in a third of patients. DRE is associated with poor quality of life and increased risk of sudden, unexplained death. The autonomic nervous system and chronobiology play a role in DRE. In the present paper, we provide a narrative review the mechanisms that underlie DRE and characterize some of the autonomic- and chronotherapy-associated parameters that contribute to the degree of response to therapy. Variability describes the functions of many biological systems, which are dynamic and continuously change over time. These systems are required for responses to continuing internal and external triggers, in order to maintain homeostasis and normal function. Both intra- and inter-subject variability in biological systems have been described. We present a platform, which comprises a personalized-based machine learning closed loop algorithm built on epilepsy-related signatures, autonomic signals, and chronotherapy, as a means for overcoming DRE, improving the response, and reducing the toxicity of current therapies.

T cell vaccination benefits relapsing progressive multiple sclerosis patients: a randomized, double-blind clinical trial.

BACKGROUND: T-cell vaccination (TCV) for multiple sclerosis (MS) refers to treatment with autologous anti-myelin T-cells, attenuated by irradiation. Previously published clinical trials have been all open-labeled. AIM: To evaluate the safety and efficacy of TCV in progressive MS, in a double-blind, controlled clinical trial. METHODOLOGY: Twenty-six patients with relapsing-progressive MS were enrolled in the study (mean age: 39±9.8 years; mean EDSS: 4.4±1.7). T-cell lines reactive to 9 different peptides of the myelin antigens, MBP, MOG and PLP were raised from the patients' peripheral blood. The patients were randomized into two groups: 19 were treated with TCV (four subcutaneous injections of 10-30×10(6) T-cells, attenuated by irradiation, on days 1, 30, 90 and 180) and 7 patients were treated with sham injections. Twenty-four patients (17 in the TCV group and 7 in the placebo) were eligible for per-protocol analysis. RESULTS: At one year following the inclusion, an increase in the EDSS (+0.50) and an increase in 10-meter walking time (+0.18 sec), were observed in the placebo group; in the TCV group there was a decrease in the EDSS (-0.44; p<0.01) and in the 10-meter walking time (0.84 sec; p<0.005). Sixteen of the 17 patients (94.1%) in the TCV group remained relapse-free during the year of the study, as compared to 42.9% in the placebo group (p = 0.01 and p = 0.03 with adjustment). The proportion of patients with any relapse during the year of the study in the TCV-group, was reduced by 89.6%., as compared to the placebo-treated group. MRI parameters did not change significantly. CONCLUSIONS: This is the first controlled, double-blind trial with TCV in progressive MS. The results demonstrate the feasibility and safety of the procedure, and provide significant indications of clinical efficacy. Further studies with larger groups of subjects are warranted. TRIAL REGISTRATION: ClinicalTrials.gov NCT01448252.

Intraarterial multi-modal reperfusion therapy for acute ischemic stroke: a10 year single-center experience.

BACKGROUND: Only 0.5% of stroke patients in Israel are treated with endovascular multi-modal reperfusion therapy (MMRT) each year. OBJECTIVES: To assess our experience with MMRT over the last decade. METHODS: We analyzed data from our stroke registry of patients undergoing MMRT during 2002-2011. All patients underwent multi-parametric imaging studies including subtraction angiography according to a predetermined algorithm. Stroke severity was measured with the National Institutes of Health Stroke Scale (NIHSS). Disability was measured with the modified Ranking Scale (mRS) and classified as favorable (mRS < or = 2) or unfavorable. Target vessel recanalization was determined with the thrombolysis in myocardial infarction (TIMI) scale. RESULTS: During the study period 204 patients were treated; 166 of them had complete data sets including mRS scores at 90 days and were included in the analysis. Favorable outcomes at 90 days post-stroke were observed in 37% of patients and the mortality rate was 25%. Patients with favorable outcomes were younger, had significantly lower NIHSS scores on admission and discharge, and more often had complete target vessel recanalization (TIMI 3). On regression analysis the only factor associated with favorable outcome was TIMI 3, whereas increasing age and NIHSS scores on admission and discharge were predictors of poor outcome. CONCLUSIONS: Our data show that MMRT can be successfully implemented in patients with severe stroke in Israel. More than a third of our patients with severe ischemic strokes who could not receive acute treatment were functionally independent after MMRT, demonstrating that this procedure is an important alternative for patients who are not candidates for intravenous tissue plasminogen activator (tPA) or do not achieve recanalization with tPA.

Misleading one detail: a preventable mode of diagnostic error?

RATIONALE, AIMS AND OBJECTIVES: Despite advances in our understanding of cognitive biases in clinical practice, little is known about correction or prevention of diagnostic errors. The presence of a single misleading detail may lead clinicians down a cognitive and actual path toward an incorrect diagnosis. METHODS: In a large teaching hospital, we surveyed 51 attending doctors in internal medicine, presenting each with 10 clinical vignettes and soliciting their diagnosis of the condition leading to the presentation. Each of the 10 clinical cases included a single misleading detail. RESULTS: This survey elicited a wrong diagnosis in 90% of cases, which was reduced to 30% when omitting the misleading detail from the vignette. Diagnostic accuracy did not improve by warning doctors about potentially misleading information. Asking doctors to identify a leading diagnostic detail and then to formulate an alternative diagnosis after omission of the detail, significantly reduced diagnostic error rate by nearly 50%. CONCLUSION: Systematic re-examination of leading diagnostic clues may help to reduce errors in diagnosis.

Prior use of statins improves outcome in patients with intracerebral hemorrhage: prospective data from the National Acute Stroke Israeli Surveys (NASIS).

BACKGROUND AND PURPOSE: Intracerebral hemorrhage (ICH) is a deadly form of stroke. Pretreatment with statins exerts protective effects in patients with ischemic stroke, but their effects in patients with ICH remains unclear. METHODS: The National Acute Stroke Israeli Surveys (NASIS) included all patients admitted with acute stroke to any of the 28 hospitals nationwide during February through March 2003 and March through April 2007. We compared stroke severity and outcomes of ICH patients who received statins before the index event with those who did not, using multivariable logistic regression models adjusting for the propensity to use statins before the event. RESULTS: Among 3212 stroke patients, 312 had ICH and 89 of them were receiving statins at the time of the ICH. Patients on statins before ICH had lower baseline NIHSS scores, less systemic complications, higher proportions of good outcome (modified Rankin scale 0 to 3), lower death rates, and higher rates of discharge home or to a rehabilitation facility. On logistic regression analyses statin use before the event was associated with odds ratios of 0.46 for having a severe stroke defined as baseline NIHSS >15 (95% CI; 0.23 to 0.93), 2.97 for having good outcome (95% CI; 1.25 to 7.35) at discharge, and 0.25 for death or nursing facility disposition (95% CI; 0.09 to 0.63). CONCLUSIONS: Use of statins before ICH is associated with reduced mortality and neurological disability and with a higher chance for good outcome, suggesting that statins may be protective in the setting of ICH.