French consensus procedure for neuropsychological assessment in multiple sclerosis.

Cognitive impairment is one of the invisible symptoms of Multiple sclerosis (MS), which could be associated with depression, unemployment, reduced social interaction, inability to drive, and compromised quality of life. Moreover, the presence of cognitive impairment can be considered as a long-term prognostic factor and in the follow-up of disability. So, cognitive assessment is a crucial element in clinical follow-up of patients with MS (pwMS). International recommendations mention the use of the Brief International Cognitive Assessment in MS (BICAMS). The BICAMS, that has been recently validated in French is a brief non-exhaustive assessment, developed as a short screening battery, hence needing other supplemented tests. The present paper aims to propose a consensus, approved by expert French consensus from the Cognition group of the SF-SEP (http://sfsep.org [Société Francophone de la Sclérose en Plaques]), for cognitive assessment of pwMS suggesting the tools that should be used in order to apprehend the other cognitive impairments that could appear in MS.

Design and construction of a simplified, gas-driven, pressure-controlled emergency ventilator.

INTRODUCTION: Due to the COVID-19 crisis or any other mass casualty situation it might be necessary to give artificial ventilation to many affected patients. Contrarily, the worldwide availability of emergency ventilators is still a shortage, especially in developing countries. METHODS: Modes of artificial ventilation were compared and the most safe, easy to use, and lung protecting principle was optimized to fit all requirements of both emergency ventilation and cost-effective mass production. RESULTS: The presented research results describe a simplified device for a pressure-controlled ventilation which works without electricity according to a known principle. Just pressurized gas and a patient connection is required. The device enables the control of basic ventilator parameters such as peak inspiratory pressure, positive end-expiratory pressure and the ventilation frequency. Further, the device is semiadaptive to the patient's lung stiffness and automatically maintains minute volume through frequency adjustment. The machine can be manufactured by turning, milling and drilling and needs purchased components with costs less than 100 USD. A sterilization and thus a reuse is possible. DISCUSSION: The presented development does not describe a ready-to-purchase ventilator, it rather outlines a refined working principle for emergency ventilation and its easiest methods of production with a minimum of requirements. The presented research aims on providing an open-source guideline for production of an emergency ventilator using worldwide available methods and thus should inspire local researchers to do a reverse engineering and eventually to put it into operation following country-specific regulations. For long-term ventilation exceeding emergency purposes, a monitoring of alarms for disconnection and violation of desired ventilator parameters should be established. The ventilator is limited to a fixed ratio between PIP and PEEP. Moreover, the ventilation frequency depends on two parameters, which needs some training. Nevertheless, the ventilator provides basic features to enable an emergency ventilation with minimal prerequisites.

New brain lesions with no impact on physical disability can impact cognition in early multiple sclerosis: A ten-year longitudinal study.

OBJECTIVE: In early multiple sclerosis, although brain T2 lesions accrual are hallmark of the disease, only weak correlations were found between T2 lesions accrual and EDSS progression, the disability scale commonly used in multiple sclerosis studies. This may be related to the very poor sensitivity of EDSS to cognitive dysfunctions that may occur and progress from the first stage of the disease. In the present study, we aimed to demonstrate that cognitive deficits progress during the first ten years of MS and are significantly impacted by new T2 lesions. METHODS: EDSS and extensive neuropsychological battery (22 measures) exploring memory, attention/speed of information processing and executive functions were assessed at baseline, Year 1 and Year 10 in 26 patients enrolled after their first clinical attack. To limit the bias of test-retest effect, only measures obtained at Year 1 and Year 10 were reported in the analysis. Raw scores of patients were transformed into z-scores using published normative data when available or scores of matched controls. Lesion probability mapping was used to assess the potential relationships between T2 lesions accumulation, cognitive decline and EDSS progression (P<0.05, FWE-corrected). RESULTS: At Year 1, 27% of patients showed attention/speed of information processing deficits, 11.5% executive dysfunction and 11.5% memory impairment. During the follow-up, frequency and severity of executive dysfunction increased (from 11.5% of patients at Year 1 to 42% at Year 10, p<0.01) while no significant changes were evidenced for the other cognitive domains. Median EDSS increased from 0.5 [range: 0-3] at Year 1 to 2.5 [range: 0-6.5] at Year 10 (p<0.001). During the ten-year follow-up, lesions accumulation in the left cerebellum and semi-ovale centers was associated with EDSS progression. In contrast, most lesions accumulation in the frontal, parietal and temporal lobes were associated with cognitive decline but had no effect on EDSS progression. CONCLUSION: The present study provides strong evidence that clinically silent T2 lesions impact cognition in early MS. In daily practice, early prevention of T2 lesions accrual may be useful to limit cognitive decline.

[Paced Auditory Serial Addition Test: normative data in a French population]. / Paced Auditory Serial Addition Test : données normatives dans une population française.

INTRODUCTION: The Paced Auditory Serial Addition Test (PASAT) is recognized as a sensitive measure of working memory, attention, and information processing speed in multiple sclerosis. The aim of this work was to provide normative data for PASAT in a healthy French population. OBSERVATIONS: A total of 360 subjects were recruited from volunteers (24 groups, 15 subjects per group, considering four age classes, three educational levels and gender). The PASAT was administered in a standardized way, by the same psychologist. CONCLUSION: Normative values were presented expressed as the means and standard deviations of T-score (Z-score*10+50).

Plasticity in MS: from Functional Imaging to Rehabilitation.

One of the main characteristics of multiple sclerosis (MS) is the existence of a "clinico-radiological paradox". The discrepancies observed between the clinical and radiological findings might be partly attributable to lack of specificity of the imaging measures, but also to functional reorganization mechanisms occurring at both the brain and spinal cord levels. These neuroplastic processes might provide a means of delaying the clinical expression of some functional symptoms. Functional MRI (fMRI) methods provide a useful means of determining whether functional reorganization mechanisms of this kind are at work. It has been established, for example, that these neuroplastic mechanisms occur right from the start of the disease and may contribute to reducing the expression of the symptoms resulting from pathological tissue damage. This functional reorganization may therefore constitute an important adaptive mechanism during the early stages of the disease. One potential practical application of the findings made on these neuroplastic processes is likely to be the development of specific rehabilitation methods, which can be used to enhance these reactive mechanisms in order to maintain MS patients functional abilities, and other specifically targeted approaches will also predictably be developed.

[Cognitive impairment]. / Les troubles cognitifs.

Cognitive impairment is common in multiple sclerosis (MS), occurring at all stages of the disease, even at the earliest, and can be a major source of disability, social impairment, and impoverished quality of life. Cognitive dysfunction is mainly focused on working memory, conceptual reasoning, verbal fluency, speed of information processing, attention and executive function. Measures of information-processing speed appear to be the most robust and sensitive markers of cognitive impairment in MS patients. Cognitive testing in MS patients is complex and cognitive screening tests are time- and cost-saving test instruments. A comprehensive and sensitive cognitive test procedure should be administered to detect cognitive dysfunction, and recent studies demonstrate that single, predominantly speed-related cognitive tests may be superior to extensive and time-consuming test batteries in screening cognitive decline. Additional clinical factors, including disease course, fatigue, and affective disturbance, can impact the degree of MS-related cognitive impairment. Despite weak correlation with disease duration and physical disability status, the degree of cognitive impairment in MS has been related to the extent of topographically specific neuronal tissue damage and loss. Numerous studies have applied conventional and quantitative magnetic resonance imaging (MRI) techniques to correlate the profile and degree of cognitive impairment with various MRI-detectable abnormalities. The burden of MRI-visible lesions does not fully account for the degree of MS-related cognitive impairment. Nonconventional MRI findings suggest the extent of subtle tissue damage in normal-appearing white and grey matter to correlate best with the severity of cognitive impairment in MS patients. Structural MRI approaches have recently been extended by functional MRI studies scrutinizing the brain's ability for adaptive functional reorganization in the presence of widespread tissue damage. Cognitive impairment in MS seems to be not simply the result of tissue destruction, but also a balance between tissue destruction, tissue repair, and adaptive functional reorganization. These findings highlight the need to screen for cognitive deficits in MS patients to conduct potential cognitive rehabilitation intervention.

Motor evoked potentials in clinically isolated syndrome suggestive of multiple sclerosis.

The aim of the present study was to determine the sensitivity and the profile of motor evoked potentials (MEP) in patients with clinically isolated syndrome (CIS) suggestive of multiple sclerosis (MS). We measured the central motor conduction time (CMCT), amplitude ratio (AR), and surface ratio (SR) in tibialis anterior and first dorsal interosseous muscles in 22 patients with CIS. In 12 patients, the triple stimulation technique (TST) was also performed. AR was abnormal in 50% of patients, CMCT in 18% of patients, and TST in 25% of patients. AR had the highest sub-clinical sensitivity and the best positive predictive value. In the absence of clinical pyramidal signs, an early AR decrease seems to result from demyelination inducing excessive temporal dispersion of the MEP, while in territories with clinical pyramidal signs, it seems to result from conduction failure, which suggests that clinical pyramidal signs may be attributable to conduction failure. This study demonstrates that MEP, especially the AR, is sensitive to motor pathway dysfunction right from the early stages of MS.

Efficiency of cognitive control recruitment in the very early stage of multiple sclerosis: a one-year fMRI follow-up study.

Functional magnetic resonance imaging (FMRI) studies have established that patients with multiple sclerosis show stronger activation in the lateral prefrontal cortices (LPFC) than healthy control subjects during effortful cognitive tasks. The aim of the present study was to assess the impact of these activation changes on cognitive performances. In addition to 19 controls, who were tested at a single time-point to define a standard pattern of fMRI activation during the performance of the Paced Auditory Serial Addition Task (PASAT), 13 patients with clinically isolated syndrome underwent a longitudinal fMRI examination while performing the PASAT at the beginning of the study (M0) and one year later (M12). Relative to the M0 scores, PASAT performances improved in eight patients (group A) and either decreased (n = 4) or remained unchanged (n = 1) (group B) in five patients at M12. Random effect analyses (SPM2; Wellcome Institute, London, England) were performed to compare intra-group time-related effects on brain activation (paired t-test between M0 and M12), and inter-group differences were also compared between the two groups of patients (analysis of covariance with PASAT performances as the covariate). Relative to group B, group A showed larger increase in activation between M0 and M12 in the right LPFC. In the whole group of patients, interaction analyses showed that the differences in the PASAT scores between M0 and M12 were correlated with the differences in activation observed in the right LPFC. This longitudinal study shows that in patients with early multiple sclerosis, the increased levels of activation in the right LPFC was associated with improved individual working memory and processing speed performances.

[Twiddler's syndrome in a left pectoral implanted defibrillator]. / Twiddler-Syndrom bei einem links pektoral implantierten Defibrillator.

Twiddler's syndrome describes a rare complication following implantation of a pacemaker/defibrillator and is characterized by spontaneous, repeated rotation of the generator in the subpectoral pocket. We describe the case of a 78-year-old man who presented with an exit block 7 months after defibrillator implantation. As cause, a 15-fold rotation of the defibrillator's generator around its own axis could be verified, which entailed dislocation of the defibrillator's electrode. Safe fixation of the electrode and generator in the subpectoral pocket is of paramount importance, particularly in patients with loose subcutaneous fatty tissue, to prevent this rare complication.

Using generic pheromone lures to expedite identification of aggregation pheromones for the cerambycid beetles Xylotrechus nauticus, Phymatodes lecontei, and Neoclytus modestus modestus.

Males of several species of longhorned beetles in the subfamily Cerambycinae produce sex or aggregation pheromones consisting of 2,3-hexanediols and/or hydroxyhexanones. We tested the hypothesis that this diol/hydroxyketone pheromone motif is highly conserved within the subfamily, and the resulting prediction that multiple cerambycine species will be attracted to compounds of this type. We also tested the concept that live traps baited with generic blends of these compounds could be used as a source of live insects from which pheromones could be collected and identified. Traps placed in a mature oak woodland and baited with generic blends of racemic 2-hydroxyhexan-3-one and 3-hydroxyhexan-2-one captured adults of both sexes of three cerambycine species: Xylotrechus nauticus (Mannerheim), Phymatodes lecontei Linsley, and Phymatodes decussatus decussatus (LeConte). Odors collected from male X. nauticus contained a 9:1 ratio of two male-specific compounds, (R)- and (S)-3-hydroxyhexan-2-one. Field trials with synthetic compounds determined that traps baited with (R)-3-hydroxyhexan-2-one (94% ee), alone or in blends with other isomers, attracted similar numbers of X. nauticus of both sexes, whereas (S)-3-hydroxyhexan-2-one (94% ee) attracted significantly fewer beetles. Phymatodes lecontei and P. d. decussatus also were caught in traps baited with hydroxyhexanones, as well as a few specimens of two other cerambycine species, Neoclytus modestus modestus Fall (both sexes) and Brothylus gemmulatus LeConte (only females). Male N. m. modestus produced (R)-3-hydroxyhexan-2-one, which was not present in extracts from females. Neoclytus m. modestus of both sexes also responded to lures that included (R)-3-hydroxyhexan-2-one as one of the components. The only male-specific compound found in extracts from P. lecontei was (R)-2-methylbutan-1-ol, and adults of both sexes were attracted to racemic 2-methylbutan-1-ol in field bioassays. Surprisingly, P. lecontei of both sexes also were attracted to (R)- and (S)-3-hydroxyhexan-2-ones, although neither compound was detected in extracts from this species. Males of all five beetle species had gland pores on their prothoraces that were similar in structure to those that have been associated with volatile pheromone production in other cerambycine species. The attraction of multiple cerambycine species of two tribes to (R)-3-hydroxyhexan-2-one in this study, and in earlier studies with other cerambycine species, suggests that this compound is a widespread aggregation pheromone component in this large and diverse subfamily. Overall, the attraction of multiple species from different cerambycine tribes to this compound at a single field site supports the hypothesis that the hydroxyketone pheromone structural motif is highly conserved within this subfamily.

Onset and underpinnings of white matter atrophy at the very early stage of multiple sclerosis--a two-year longitudinal MRI/MRSI study of corpus callosum.

BACKGROUND: Atrophy of corpus callosum (CC), a white matter structure linking the two hemispheres, is commonly observed in multiple sclerosis (MS). However, the occurrence and processes leading to this alteration are not yet determined. GOAL AND METHODS: To better characterize the onset and progression of CC atrophy from the early stage of MS, we performed a two-year follow-up magnetic resonance imaging/magnetic resonance spectroscopic imaging (MRI/MRSI) exploration of CC in 24 patients with clinically isolated syndrome. These patients were explored using the same protocol at month (M)6, M12 and M24. MRI/MRSI techniques were applied to measure CC volume, and relative concentrations of N-acetylaspartate (NAA), creatine/phosphocreatine (Cr) and choline-containing compounds (Cho). A group of matched controls was also explored. RESULTS: Atrophy of CC, not present at baseline, was observed at M12 and progressed over the second year (M24). At baseline, a decrease in relative NAA level was observed in the anterior and posterior body of CC, with normalization during the follow-up period. In the anterior body, an increase in relative Cho level was observed, with normalization at M6. Normal relative Cr levels were observed at all time points in all sub-regions. The rate of CC atrophy was correlated with the change in the Expanded Disability Status Scale (EDSS) during the follow-up period. CONCLUSION: These results suggest that CC atrophy appears over a period of one year after the first acute inflammatory episode, and that this atrophy is accompanied, especially in the anterior body of CC, by a normalization of the relative Cho levels, marker of acute inflammation, and NAA levels, marker of neuronal dysfunction and/or loss.

Early cognitive impairment in patients with clinically isolated syndrome suggestive of multiple sclerosis.

Cognitive impairment in patients with multiple sclerosis (MS) is a common occurrence and is generally fairly circumscribed. The prevalence of the cognitive deficits usually encountered could vary with the clinical course of the disease. To investigate whether the presence of cognitive impairment may occur in the very early stage of MS, we assessed the cognitive status of a group of 40 patients presenting with a recently diagnosed clinically isolated syndrome suggestive of MS (CISSMS), in comparison with 30 age-, sex-, and educational level-matched healthy control subjects. An extensive battery of neuropsychological tests was used to explore verbal and non-verbal memory, attention, concentration, speed of information processing, language and abstract reasoning. Patients with CISSMS had a significant, frequent (57%), and circumscribed cognitive impairment, focused on memory, speed of information processing, attention and executive functions.

[Value of laparoscopy in suspected appendicitis]. / Stellenwert der Laparoskopie bei Appendicitisverdacht.

By laparoscopy the rate of negative appendectomies was reduced to 3.4%. Decision-making regarding open or laparoscopic appendectomy and selection of suitable cases has improved the results in operating time and complication rate. In patients with non-typical clinical signs of suspected appendicitis the therapeutic decision was influenced in 30% or 6%, respectively.

Laparoscopic colon resection and intracorporeal hand-sewn anastomosis.

The application of laparoscopic surgical techniques to colonic surgery is restricted to selected cases and to rather few surgical centers. On the one hand, the disadvantages of the open approach involves the sizable laparotomy incision for mobilization of the viscera, especially if the colonic flexures are to be mobilized. On the other hand, in the minimally invasive approach the extent of dissection requires additional skills and a well honed endoscopic surgical team is needed especially if laparoscopic reconstruction of the large colon is to be accomplished. The teamwork is more critical for colon procedures than for laparoscopic gallbladder surgery.