Low clinical conversion rate in clinically isolated syndrome patients - diagnostic benefit of McDonald 2010 criteria?

BACKGROUND AND PURPOSE: New diagnostic criteria of multiple sclerosis (MS) increase the number of patients being diagnosed with MS whilst a substantial part might not convert to clinically definite MS (CDMS). The diagnostic accuracy of the McDonald 2005 and 2010 criteria for conversion to CDMS was evaluated in an unselected cohort of patients in whom an MS diagnostic work-up was decided. METHODS: Clinical, magnetic resonance imaging and cerebrospinal fluid data were analysed for all patients who presented with symptoms suspicious for MS at the university based MS outpatient clinic between 2006 and 2010 (n = 165). RESULTS: Follow-up was available for 131 patients. During the mean follow-up period of 2 years, 19% of patients developed CDMS whereas 64% of the patients fulfilling McDonald 2010 criteria did not convert to CDMS. CONCLUSION: The low clinical conversion rate indicates that the new diagnostic criteria may increase the incidence of MS cases with a less active disease course.

[fMRI and DTI in delayed development of number processing]. / fMRT und DTI bei Entwicklungsverzögerung der Zahlenverarbeitung.

The neuronal correlate of the current cultural performance arose from developmental processes that can be observed by functional and anatomical magnetic resonance imaging. The velocity of these maturation processes occurs differently between adolescents, causing implications for both school career and academic performance. Regarding spatial-numerical cognition the myelinization of the superior longitudinal bundle appears to be crucial because this fiber connection intermediates between the linguistic nature of number words and conception of their spatial-numerical magnitude. The neuroscientific observation of anatomical brain maturation and its influence on school-relevant number processing may be helpful for educational purposes as well as for school psychology.

A web-based tool for personalized prediction of long-term disease course in patients with multiple sclerosis.

BACKGROUND AND PURPOSE: The Evidence-Based Decision Support Tool in Multiple Sclerosis (EBDiMS) is the first web-based prognostic calculator in multiple sclerosis (MS) capable of delivering individualized estimates of disease progression. It has recently been extended to provide long-term predictions based on the data from a large natural history cohort. METHODS: We compared the predictive accuracy and consistency of EBDiMS with that of 17 neurologists highly specialized in MS. RESULTS: We show that whilst the predictive accuracy was similar, neurologists showed a significant intra-rater and inter-rater variability. CONCLUSIONS: Because EBDiMS was consistent, it is of superior utility in a specialist setting. Further field testing of EBDiMS in non-specialist settings, and investigation of its usefulness for counselling patients in treatment decisions, is warranted.

HAGIL (Hamburg Vigil Study): a randomized placebo-controlled double-blind study with modafinil for treatment of fatigue in patients with multiple sclerosis.

OBJECTIVE: To reassess the effect of modafinil, a wakefulness-promoting artificial psychostimulant, on fatigue and neuropsychological measures in patients with multiple sclerosis. METHODS: Multiple sclerosis (MS) patients with a baseline score of ≥4 on the Fatigue Severity Scale (FSS) and an Expanded Disability Status Scale score <7 were eligible for the 8-week randomized, double-blind, placebo-controlled study. Modafinil was dosed up to 200 mg/day within 1 week. Assessments were performed at baseline and after 4 and 8 weeks. The primary outcome parameter was the mean change of the FSS mean score. Secondary outcome variables were other questionnaires covering fatigue, daytime sleepiness and sleep quality. Cognitive impairment was assessed by the oral version of the Symbol Digit Modalities Test (SDMT) and the Paced Auditory Serial Addition Test (PASAT). RESULTS: The study included 121 MS patients. Dropout rate was 9%. Both treatment groups showed improvements through time. While mean FSS at 8 weeks showed a trend difference between groups in the intention-to-treat analysis, the primary endpoint was not met. Assessment of cognitive impairment by SDMT and PASAT showed contradictory results. All other secondary endpoints were not met. There was no major safety concern. CONCLUSIONS: In general, the study does not support modafinil as an effective treatment for MS fatigue. However, the study shows the need for new study designs and endpoints in MS fatigue studies.

Differential Contribution of ASPECTS Regions to Clinical Outcome after Thrombectomy for Acute Ischemic Stroke.

BACKGROUND AND PURPOSE: Ischemic stroke is the leading cause of long-term disability in adults, but our ability to prognosticate from baseline imaging data is limited. The ASPECTS measures ischemic change in the middle cerebral artery territory on noncontrast CT based on 10 anatomic regions. Here, we investigated whether infarction in particular regions was associated with worse long-term outcome. MATERIALS AND METHODS: We identified consecutive patients receiving mechanical thrombectomy for ICA/MCA occlusion at 2 comprehensive stroke centers. Pretreatment ASPECTS was assessed by 2 blinded reviewers. Clinical data including demographics, baseline NIHSS score, and 90-day mRS were collected. The relationship between individual ASPECTS regions and the mRS score (0-2 versus 3-6) was assessed using multivariable logistic regression. RESULTS: Three hundred fifty-three patients were included (mean age, 70 years; 46% men), of whom 214 had poor outcome (mRS = 3-6). Caudate (OR = 3.26; 95% CI, 1.33-8.82), M4 region (OR = 2.94; 95% CI, 1.09-9.46), and insula (OR = 1.75; 95% CI, 1.08-2.85) infarcts were associated with significantly greater odds of poor outcome, whereas M1 region infarction reduced the odds of poor outcome (OR = 0.38; 95% CI, 0.14-0.99). This finding remained unchanged when restricted to only patients with good recanalization. No significant associations were found by laterality. Similarly, no region was predictive of neurologic improvement during the first 24 hours or of symptomatic intracerebral hemorrhage. CONCLUSIONS: Our results indicate that ASPECTS regions are not equal in their contribution to functional outcome. This finding suggests that patient selection based on total ASPECTS alone might be insufficient, and infarct topography should be considered when deciding eligibility for thrombectomy.

Location-Specific ASPECTS Paradigm in Acute Ischemic Stroke: A Systematic Review and Meta-Analysis.

BACKGROUND: Weighting neuroimaging findings based on eloquence can improve the predictive value of ASPECTS, possibly aiding in informed treatment decisions for acute ischemic stroke. PURPOSE: Our aim was to study the contribution of region-specific ASPECTS infarction to acute ischemic stroke outcomes. DATA SOURCES: We searched MEDLINE and EMBASE for reports on ASPECTS in patients with acute ischemic stroke from 2000 to March 2019. STUDY SELECTION: Two investigators independently reviewed articles and extracted data. Three-month poor functional outcome defined as mRS >2 was the primary end point. DATA ANALYSIS: A random-effects meta-analysis was performed to compare the association between infarct and mRS >2 among ASPECTS regions. Subanalyses included the following: laterality of stroke (left/right), imaging technique (NCCT or advanced imaging with DWI, CTP, or CTA), and interventional technique (IV-tPA/conservative management or mechanical thrombectomy). DATA SYNTHESIS: M6 infarct was most associated with poor functional outcome (OR = 3.26; 95% CI, 2.21-4.80; P < .001). Pair-wise comparisons of ASPECTS regions regarding the association between infarct and mRS >2 were not significant, with the exception of M6 versus lentiform (P = .009). However, pair-wise comparisons among ASPECTS regions were not significant among subgroup analyses. LIMITATIONS: Limitations were the heterogeneity of time points, neuroimaging modalities, and interventional techniques; limited studies for inclusion; publication bias among some comparisons; and the retrospective nature of included studies. CONCLUSIONS: Our study indicated an unequal impact of some ASPECTS subregions in predicting outcomes of patients with acute ischemic stroke. Stroke laterality, imaging technique, and interventional technique subgroup analyses showed no differences among ASPECTS regions in predicting outcome. Investigation in larger cohorts is required to assess the association of ASPECTS with acute ischemic stroke outcome.

COMT Val 158 Met polymorphism is associated with cognitive flexibility in a signal discrimination task in schizophrenia.

BACKGROUND: Associations between the well-known functional single nucleotide polymorphism Val (158)Met in the gene encoding catechol- O-methyltransferase (COMT) and cognitive do-mains affected in schizophrenia are inconsistent regarding directionality and specific impact and call for a more fundamental cognitive endophenotype. Recent studies suggest that the COMT genotype contributes to cognitive flexibility, a fundamental cognitive ability that potentially influences an individual's performance in a variety of other neurocognitive tasks. METHODS: We investigated the association between COMT Val (158)Met genotype and cognitive flexibility as assessed by signal discrimination in the Continuous Performance Test - Identical Pairs version in a cohort of 111 German schizophrenic patients. RESULTS: COMT genotype was significantly associated with signal discrimination index d' in schizophrenia. The Val/Val genotype was associated with the highest and the Met/Met genotype with the lowest scores; heterozygous individuals displayed an intermediate performance. CONCLUSIONS: Our data suggest that allelic variation at the COMT Val (158)Met locus may influence signal discrimination capacity in schizophrenia and confirm that Val loading, probably due to decreased prefrontal dopamine availability, is associated with greater cognitive flexibility, which in turn may influence other cognitive measures that have been associated with COMT to date.

P300 is enhanced in responders to vagus nerve stimulation for treatment of major depressive disorder.

BACKGROUND: Vagus nerve stimulation (VNS) is a new therapy option for treatment of otherwise therapy-refractory major depressive disorder. However, the mechanism of central nervous action is poorly understood. Electroencephalographic (EEG) studies may be of interest since chronic peripheral current application to the vagus nerve may exert lasting neurophysiologically detectable effects on central electrical activity. In an exploratory study, we investigated the effects of VNS on auditory event-related potentials (ERP). METHODS: Thirteen depressive patients (mean Hamilton depression score (HAMD) at baseline=24.2) receiving VNS were investigated prior to implantation and 10 weeks after standard cycling VNS. Stimulation intensity was 0.94+/-0.46 mA, pulse width 0.250 mus, and frequency 20 Hz. 1 h prior to follow-up investigation, VNS was turned off. Auditory ERP were elicited using a standard auditory oddball paradigm and were recorded with 29-channel EEG. RESULTS: Post VNS, grand averages of the auditory ERP did not show significant differences as compared to baseline recording. However, differential effects were found when separating ERP of responders (N=5, mean HAMD post VNS=8.8) and non-responders (N=8, mean HAMD post VNS=22.4). In VNS responders only, P300 at midline electrodes Fz and Cz was significantly increased and correlated with HAMD scores. CONCLUSION: Auditory ERP seem to provide a useful tool for investigating VNS-induced changes concerning information processing in major depressive disorder. In our sample, enhancement of P300 distinguished VNS responders from non-responders 10 weeks after therapy onset. Our findings may be relevant for the understanding of both neurophysiological mechanism of action of VNS and pathophysiology of depression.

Prognosis of the individual course of disease--steps in developing a decision support tool for Multiple Sclerosis.

BACKGROUND: Multiple sclerosis is a chronic disease of uncertain aetiology. Variations in its disease course make it difficult to impossible to accurately determine the prognosis of individual patients. The Sylvia Lawry Centre for Multiple Sclerosis Research (SLCMSR) developed an "online analytical processing (OLAP)" tool that takes advantage of extant clinical trials data and allows one to model the near term future course of this chronic disease for an individual patient. RESULTS: For a given patient the most similar patients of the SLCMSR database are intelligently selected by a model-based matching algorithm integrated into an OLAP-tool to enable real time, web-based statistical analyses. The underlying database (last update April 2005) contains 1,059 patients derived from 30 placebo arms of controlled clinical trials. Demographic information on the entire database and the portion selected for comparison are displayed. The result of the statistical comparison is provided as a display of the course of Expanded Disability Status Scale (EDSS) for individuals in the database with regions of probable progression over time, along with their mean relapse rate. Kaplan-Meier curves for time to sustained progression in the EDSS and time to requirement of constant assistance to walk (EDSS 6) are also displayed. The software-application OLAP anticipates the input MS patient's course on the basis of baseline values and the known course of disease for similar patients who have been followed in clinical trials. CONCLUSION: This simulation could be useful for physicians, researchers and other professionals who counsel patients on therapeutic options. The application can be modified for studying the natural history of other chronic diseases, if and when similar datasets on which the OLAP operates exist.

Ecological validity of walking capacity tests in multiple sclerosis.

BACKGROUND: Ecological validity implicates in how far clinical assessments refer to real life. Short clinical gait tests up to ten meters and 2- or 6-Minutes Walking Tests (2MWT/6MWT) are used as performance-based outcomes in Multiple Sclerosis (MS) studies and considered as moderately associated with real life mobility. OBJECTIVE: To investigate the ecological validity of 10 Meter Walking Test (10mWT), 2MWT and 6MWT. METHODS: Persons with MS performed 10mWT, 6MWT including 2MWT and 7 recorded days by accelerometry. Ecological validity was assumed if walking tests represented a typical walking sequence in real-life and correlations with accelerometry parameters were strong. RESULTS: In this cohort (n=28, medians: age=45, EDSS=3.2, disease duration=9 years), uninterrupted walking of 2 or 6 minutes occurred not frequent in real life (2.61 and 0.35 sequences/day). 10mWT correlated only with slow walking speed quantiles in real life. 2MWT and 6MWT correlated moderately with most real life walking parameters. CONCLUSION: Clinical gait tests over a few meters have a poor ecological validity while validity is moderate for 2MWT and 6MWT. Mobile accelerometry offers the opportunity to control and improve the ecological validity of MS mobility outcomes.

Pulmonary embolism in respiratory failure.

The occurrence of pulmonary emboli in 617 patients admitted to a respiratory intensive care unit was studied. Pulmonary emboli were found in 18 (27 percent) of 66 autopsies. Half of these pulmonary emboli were not diagnosed before death, despite persistent aggressive attempts to document pulmonary emboli. In this subpopulation of patients with respiratory failure, the usual clinical manifestations of pulmonary emboli (symptoms, signs, chest x-ray film, electrocardiogram, and changes in arterial blood gas levels) frequently are already present, due to the severe underlying pulmonary disease, and any superimposed manifestations of pulmonary emboli are often inapparent. In this group under study, the ventilation/perfusion lung scan correlated poorly with pulmonary angiographic results and with examinations at autopsy; the scan generally was inadequate to rule in or rule out pulmonary emboli. Again, this was due to the distortion of both ventilation and perfusion by the severe underlying pulmonary disease. Currently, pulmonary angiographic studies remain the only reliable technique to confirm or exclude pulmonary emboli in patients with respiratory failure.

Modification of the effect of fiberoptic bronchoscopy on pulmonary mechanics.

Thirty-three patients who were to undergo diagnostic fiberoptic bronchoscopy were studied. Pulmonary function tests were performed before the procedure, after topical lidocaine anesthesia, and immediately and four hours after bronchoscopy. Nine patients received aerosolized isoproterenol (Isuprel) before the topical anesthesia, and nine received aerosolized atropine. Pulmonary function tests were also performed after this intervention. In those patients receiving no premedication, all the indices of expiratory flow were reduced significantly immediately after bronchoscopy, and after the topical anesthesia, the FEV1 and FVC were significantly reduced. In the atropine groups, the FVC and FEV1 increased significantly after atropine, and increased still further following topical lidocaine anesthesia. By four hours after bronchoscopy, however, the midmaximal expiratory flow ws significantly reduced. In the isoproterenol group, only the FEV1 was significantly improved by the drug, and this improvement persisted even after the lidocaine. It decreased transiently immediately after bronchoscopy, but by four hours, was significantly above baseline again. The FVC diminished significantly immediately after bronchoscopy. It is concluded that fiberoptic bronchoscopy deleteriously affects pulmonary function and that inhaled isoproterenol or atropine largely protects against these deleterious effects.

A prospective evaluation of intracorporeal laparoscopic small bowel anastomosis during gastric bypass.

BACKGROUND: We evaluated the safety and feasibility of performing a laparoscopic intracorporeal end-to-side small bowel anastomosis using a stapling technique as part of a Roux-en-Y gastric bypass operation (RYGBP). METHODS: 80 consecutive patients who underwent RYGBP with laparoscopic jejunojejunostomy were evaluated. Operative time and intraoperative and postoperative complications directly related to the jejunojejunostomy anastomosis were recorded. RESULTS: All 80 laparoscopic jejunojejunostomy procedures were successfully performed without conversion to laparotomy. Mean operative time was longer for the first 40 laparoscopic RYGBP than for the last 40 RYGBP (32+/-18 min vs 21+/-14 min, respectively, p<0.05). Intraoperative complications were staple-line bleeding (2 patients) and narrowing of the anastomosis (1 patient). Postoperative complications were four small bowel obstructions: technical narrowing at jejunojejunostomy site (2 patients), angulation of the afferent limb (1 patient), and food impaction at the jejunojejunostomy anastomosis (1 patient). These four patients underwent successful laparoscopic re-exploration and creation of another jejunojejunostomy proximal to the original anastomosis. There were no small bowel anastomotic leaks. The median time to resuming oral diet was 2 days. CONCLUSIONS: Laparoscopic jejunojejunostomy as part of the RYGBP operation is a safe and technically feasible procedure. Postoperative small bowel obstruction is a potential complication, which can be prevented by avoiding technical narrowing of the afferent limb.

The role of duplex ultrasound arterial imaging in patients with penetrating extremity trauma.

OBJECTIVE: To investigate the role of color-flow duplex ultrasound vascular imaging in screening patients for potential arterial injuries following penetrating trauma of the extremities. DESIGN: In this prospective study, patients with penetrating trauma in proximity to major peripheral vessels but without signs of arterial injury underwent color-flow duplex imaging. Patients with abnormal color-flow duplex examination results were then studied with angiography, and the results of the two studies were compared. In patients who presented with signs of arterial injury, immediate operative exploration and/or angiography was performed. SETTING: An urban trauma center. PATIENTS: Patients entering the trauma center with penetrating trauma between April 1991 and December 1992. RESULTS: Seventy-seven patients with 86 extremity injuries were initially screened with color-flow duplex imaging. Four patients had positive study results, and all injuries were confirmed with angiography (100% true positive). No missed arterial injuries were detected in clinical follow-up. CONCLUSIONS: Color-flow duplex imaging reliably detects occult arterial injuries and may also have a role in following up minor injuries treated without surgery.

The effects of fiberoptic bronchoscopy with and without atropine premedication on pulmonary function in humans.

Pulmonary function studies, including arterial blood gas analysis, were performed in 21 patients undergoing fiberoptic bronchoscopy. Eight received premedication with atropine and 13 did not. In the atropine-treated group there was no significant deterioration in pulmonary function immediately after bronchoscopy compared with baseline. Compared with the values obtained after topical lidocaine anesthesia, however, there was a decrease in peak expiratory flow rate (PEFR) (20 +/- 20%), forced expiratory volume in one second (FEV1.0) (11 +/- 12%), forced expiratory flow between 25 and 75% of vital capacity (FEF25-75) (22 +/- 16%), and forced expiratory flow at 75% of exhaled vital capacity (FEF75) (28 +/- 38%) and an increase in residual volume (RV) (16 +/- 19%). In the no-atropine group, postbronchoscopy values showed a decrease in PEFR (13 +/- 19%), forced vital capacity (FVC) (13 +/- )9%), FEV1.0 (14 +/- 16%), and oxygen partial pressure (Pa02) (11 +/- 9%) and an increase in RV (19 +/- 31%) and alveolar-arterial oxygen pressure gradient (deltaAaPO2) (91 +/- 129%) compared with baseline values. In this group also, topical lidocaine anesthesia resulted in a decrease in FVC compared with baseline. We conclude that the deleterious effect of bronchoscopy on pulmonary function is counterbalanced by the beneficial effect of atropine and that atropine is therefore a useful premedication for fiberoptic bronchoscopy.

Age and disability accumulation in multiple sclerosis.

OBJECTIVES: We tested the hypothesis that age is a prognostic factor with respect to long-term accumulation of disability in multiple sclerosis (MS). METHODS: Kaplan-Meier analysis and binary logistic regression models determined the effect of age at disease onset, age at onset of progression, and current age on attainment of severe disability levels (Disability Status Scale [DSS] 6-8-10) from the London, Ontario, database (n = 1,023). RESULTS: Older age at relapsing-remitting (RR) phase onset was associated with higher risk of reaching advanced DSS scores. This was independent of disease duration and early relapse frequency but secondary to increased risk of conversion to secondary progressive (SP) MS. Onset at age 40 (odds ratio [OR] = 4.22) and at age 50 (OR = 6.04) doubled and tripled risks of developing SP, compared to age 20 (OR = 2.05). Younger age at conversion to SPMS was associated with shorter times to high DSS scores from disease onset. The progressive course, unaffected by age at RR onset, was only modestly affected by age at SP onset. Among primary progressive and RR/SP patients, median ages at attainment of DSS scores were strikingly similar: DSS = 6, 49 vs 48 years; DSS = 8, 58 vs 58 years; and DSS = 10, 78 years for both (p = NS for all comparisons). CONCLUSIONS: Development of SP is the dominant determinant of long-term prognosis, independent of disease duration and early relapse frequency. Age independently affects disability development primarily by changing probability and latency of SP onset, with little effect on the progressive course.

Persistent deficits of visual recall in Kleine-Levin syndrome.

Kleine-Levin syndrome (KLS) is commonly described as a self-limiting disorder exhibiting episodes of hypersomnia and psychiatric symptoms but without any enduring disabilities. Recently, some authors have reported persistent or even progressive memory deficits associated with the disorder. Nevertheless, literature about cognitive disturbances in KLS is rare. Our report describes a patient with deficits of visual and verbal recall after remission of an episode, as well as selective deficits of visual recall 6 months later. Neuropsychological testing is necessary in all patients with KLS to further characterize the profile and impact of associated cognitive deficits.