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.

Impact of methodological choices in comparative effectiveness studies: application in natalizumab versus fingolimod comparison among patients with multiple sclerosis.

BACKGROUND: Natalizumab and fingolimod are used as high-efficacy treatments in relapsing-remitting multiple sclerosis. Several observational studies comparing these two drugs have shown variable results, using different methods to control treatment indication bias and manage censoring. The objective of this empirical study was to elucidate the impact of methods of causal inference on the results of comparative effectiveness studies. METHODS: Data from three observational multiple sclerosis registries (MSBase, the Danish MS Registry and French OFSEP registry) were combined. Four clinical outcomes were studied. Propensity scores were used to match or weigh the compared groups, allowing for estimating average treatment effect for treated or average treatment effect for the entire population. Analyses were conducted both in intention-to-treat and per-protocol frameworks. The impact of the positivity assumption was also assessed. RESULTS: Overall, 5,148 relapsing-remitting multiple sclerosis patients were included. In this well-powered sample, the 95% confidence intervals of the estimates overlapped widely. Propensity scores weighting and propensity scores matching procedures led to consistent results. Some differences were observed between average treatment effect for the entire population and average treatment effect for treated estimates. Intention-to-treat analyses were more conservative than per-protocol analyses. The most pronounced irregularities in outcomes and propensity scores were introduced by violation of the positivity assumption. CONCLUSIONS: This applied study elucidates the influence of methodological decisions on the results of comparative effectiveness studies of treatments for multiple sclerosis. According to our results, there are no material differences between conclusions obtained with propensity scores matching or propensity scores weighting given that a study is sufficiently powered, models are correctly specified and positivity assumption is fulfilled.

French validation of the Brief International Cognitive Assessment for Multiple Sclerosis.

BACKGROUND: Cognitive impairment is important to consider in the assessment of multiple sclerosis (MS) patients. A short battery of cognitive assessment, the Brief International Cognitive Assessment for Multiple Sclerosis (BICAMS), has been developed to address the need for rapid assessment by combining 3 tests assessing the main cognitive spheres reached in MS. OBJECTIVES: To establish regression-based norms of the BICAMS in French speaking healthy subjects (HS) and validate its use in persons with multiple sclerosis (PwMS). METHODS: In all, 123 PwMS including 40 with relapsing-remitting MS, 41 patients with secondary progressive MS and 42 with primary progressive MS and 276 HS were evaluated by the BICAMS including 3 tests, the Symbol Digit Modalities Test (SDMT), the French Verbal learning test (FVLT) a French-adapted memory test, (or the California Verbal Learning Test (CVLT) at retesting) and the Brief Visuo-Spatial Memory Test (BVMT-R). The standards for these tests were established in the healthy population using a multiple regression technique. Validity in MS was measured. RESULTS: Regression-based norms of BICAMS tests have been established in the HS population. 50.4% of PwMS have impairment for at least one BICAMS test (-1.5SD on the Z-score). The most common pathological test was the FVLT altered in 36.6% of patients, followed by the SDMT and the BVMT-R. The re-test reliability was good for the various BICAMS tests, 0.891 for SDMT, 0.781 for FVLT/CVLT and 0.669 for BVMT-R. CONCLUSION: This study establishes the validity of the BICAMS as a short and easy to apply battery for a brief assessment of the speed of information processing and episodic memory in MS.

MRI characteristics of MOG-Ab associated disease in adults: An update.

Our knowledge of the radiological spectrum of myelin oligodendrocyte glycoprotein antibody associated disease (MOGAD) is growing rapidly. An update on the radiological features of the disease, and its evolution is thus necessary. Magnetic resonance imaging (MRI) has an increasingly important role in the differential diagnosis of MOGAD particularly from aquaporin-4 antibody-positive neuromyelitis optica spectrum disorder (AQP4-NMOSD), and multiple sclerosis (MS). Differentiating these conditions is of prime importance because the management is different between the three inflammatory diseases, and thus could prevent further attack-related disability. Therefore, identifying the MRI features suggestive of MOGAD has diagnostic and prognostic implications. We herein review optic nerve, spinal cord and the brain MRI findings from MOGAD adult patients, and compare them to AQP4-NMOSD and MS.

[Lower Urinary Tract Dysfunction (LUTD) in institutionalized handicapped adults]. / Troubles vésicosphinctériens chez les personnes adultes en situation de handicap hébergées en établissement médico-social.

OBJECTIVES: To assess the prevalence and the management of the lower urinary tract dysfunction (LUTD) in institutionalized handicapped adults. MATERIALS AND METHODS: Descriptive transversal observational study. Epidemiological study. RESULTS: In this study realized in 150 residents of 6 nursing homes for adult, the prevalence of LUTD in institutionalized handicapped adults was 88.67% (133/150). This prevalence was 91.36% (74/81) for women versus 85.51% (59/69) for men, (P=0.260); 93.33% (14/15) in medical housing units [foyer d'accueil médicalisé (FAM)] versus 88.15% (119/135) in specialized housing units [maison d'accueil spécialisé (MAS)], (P=1); 80% (52/65) for those who walked without technical support, 89.47% (17/19) for those who walked with technical support, 98.08% (51/52) for the wheelchair users who were not able to walk, and 92.86% (13/14) for those who were not able to walk or to use wheelchair, (P=0.004); 69.81% (37/53) for those who were able to signal the need to void versus 98.97% (96/97) for those who were not able, (P=0.0000003); 76.92% (50/60) for those who were able to realize the transfers independently, versus 97.65% (83/85) for those who were not able, (P=0.0002); 67.39% (31/46) for those who could dress and undress by themselves versus 98.08% (102/104) for those who could not, (P=0.0000002); 77.27% (17/22) for water intake>2L, 91.67% (55/60) between 1.5 and 2L, 87.5% (49/56) between 1 and 1.5L, and 100% (12/12) for water intake<1L, (P=0.170). The LUTD were more frequent in people with physical disability (OR=10.70[1.53-75.09], P=0.017), in those with mental disability (OR=5.85[1.39-24.67], P=0.016), and in those with urological comorbidity (OR=9.70[1.25-75.55], P=0.03). For the management of the LUTD, the prevalence of expert medical advice was 9.77%, 24.81% (33/133) for the further examination, 16.54% (22/133) for rehabilitation treatment, 6.77% (9/133) for drug treatment, 2.26% (3/133) for surgical treatment, and 82.71% (110/133) for medical device. CONCLUSION: In this study, the prevalence of LUTD in institutionalized handicapped adults was 88.67%. LEVEL OF EVIDENCE: 4.

Update on pediatric-onset multiple sclerosis.

Pediatric-onset multiple sclerosis (POMS) has distinctive features compared with adult-onset multiple sclerosis (AOMS), and warrants caution despite being a rare form of MS. POMS diagnostic criteria are somewhat different from those used in AOMS, with acute disseminated encephalomyelitis being a key differential diagnosis of MS in children. Other differential diagnoses that have to be ruled out before diagnosing MS include demyelinating syndromes, autoimmune and systemic pathologies, and infectious, genetic, metabolic and neoplastic diseases. Compared with AOMS, POMS has several different clinical, biological and imaging findings. At onset, high-level inflammatory activity is mainly reported, and patients with POMS are also at high risk of developing early physical disabilities and early cognitive impairment. Yet, treating patients with POMS is challenging due to a lack of randomized controlled trials. Some of the disease-modifying drugs currently prescribed are analogous to therapies used in adults, and are associated with good tolerability in pediatric patients. However, a few clinical trials dedicated to POMS are now in progress, and the future outlook is to improve the long-term prognosis of POMS patients with early effective and safe treatments.

Late Functional Changes Post-Severe Traumatic Brain Injury Are Related to Community Reentry Support: Results From the PariS-TBI Cohort.

OBJECTIVES: To explore late functional changes after a traumatic brain injury and their relation to patients' characteristics and reentry support. DESIGN: Prospective follow-up of an inception cohort of adults with severe traumatic brain injury recruited in 2005-2007 in the Parisian area, France. One and 4-year assessments were performed by trained neuropsychologists. One-to-4-year change in the Glasgow Outcome Scale-Extended defined 3 groups: "improvement," "stability," and "worsening." Relationships between these groups and patients' characteristics were analyzed. RESULTS: Among 504 recruited patients and 245 four-year survivors, 93 participated in both evaluations. Overall Glasgow Outcome Scale-Extended improved by 0.4. Forty percent of the sample improved, 44% were stable, and 16% worsened. Being in a more unfavorable group was related to preinjury alcohol abuse and to higher anxiety and depression at 4 years. Attendance to a specialized community reentry unit was related to higher chances of being in the "improvement" group in univariate analyses and after adjustment for age, time to follow command, preinjury alcohol and occupation, and mood disorders (adjusted odds ratio [OR] = 4.6 [1.1-20]). CONCLUSION: Late functional changes were related to psychosocial variables and to reentry support. The effect of reentry support on late recovery needs to be confirmed by further investigations.

Beliefs relating to recurrence of heterotopic ossification following excision in patients with spinal cord injury: a review.

STUDY DESIGN: Review of the literature. OBJECTIVES: It is widely believed that the timing of surgery and the size of the initial Neurological Heterotopic Ossification (NHO) affect the recurrence risk of NHO after SCI. A large number of studies were published in the 80s and the 90s, mostly of poor quality despite the fact that they were carried out by experienced surgical teams. The aim of this study was to suggest recommendations relating to the timing of excision of heterotopic ossification after SCI following the analysis of a recent review of the literature. SETTING: France. METHODS: A systematic literature search was performed in the PubMed Embase from January 2002 until June 2014 using the MESH headings 'spinal cord injury', 'paraplegia', 'heterotopic ossification' and 'surgery'. Results were compared with results from epidemiological studies based on the BANKHO database (patients who underwent surgery for troublesome HO after central neurological system (CNS) lesions in our center (357 patients, 539 surgeries)). RESULTS: Few studies were found in the literature, results were sometimes contradictory and practices heterogeneous. Results from the BANKHO database showed that troublesome recurrence of NHO was not associated with 'early' surgery (before 6 months), and no association was found between recurrence and the size of the NHO around the joint (Brooker status). CONCLUSION: We suggest that surgical excision of the NHO should be carried out when it begins to be troublesome, as soon as comorbid factors are under control and the HO is sufficiently constituted for excision.

A field approach to observing changes in behavioural welfare indicators over 2 years in stabled horses.

In stabled horses, several behaviours are considered to be important indicators of the state of welfare at the individual level: stereotypies, aggressive behaviours towards humans and the "withdrawn", alert, sternal, lateral and observation postures. Until now, these behaviours have been extensively studied in relation to different horse management practices. However, little is known about their changes or consistency over time. This study aimed to investigate differences in the expression of these behaviours assessed on 44 stabled horses during an initial 3-month period and then again on the same individuals 2 years later. Out of the six behaviours studied, two showed significant differences between the 2 years with medium effect sizes: the levels of aggressiveness towards humans increased (Wilcoxon signed-rank test: V = 65, P = 0.005) and those of recumbent rest during the day decreased (V = 416, P < 0.001) over time. The results also suggested limited evidence of major changes over time in the expression of stereotypies, the "withdrawn", alert and observation postures. However, the principal component analyses carried out on all the behaviours showed that alert and observation postures may slightly decrease over time for some individuals. Regarding stereotypies and the "withdrawn" posture, the results mainly suggested a change at the individual level in the expression of these behaviours over time. This study provided new insights into the dynamic nature of several behaviours when the horses' living conditions are not fundamentally altered and raised hypotheses about the state of welfare of stabled individuals over a 2-year period.

Transcriptomic signature related to poor welfare of sport horses.

The improvement of horse welfare through housing conditions has become a real issue in recent years and have highlighted the detrimental effect of individual housing of horses on their health and behaviour. In this new study, we analysed the blood transcriptome of 45 sport horses housed individually that were previously examined for their behaviour and gut microbiota. We performed differential and regression analyses of gene expression, followed by downstream bioinformatic analyses, to unveil the molecular pathways related to the behavioural changes associated with welfare impairment in these sport horses. We found that aggressiveness towards humans was the behavioural indicator the most correlated to blood gene expression and that the pathways involved belonged mainly to systemic inflammation. In contrast, the correlations between genes, alert postures and unresponsiveness towards the environment were weak. When blood gene expression profiling was combined with faecal microbiota of a sub-population of horses, stereotypies came out as the most correlated to blood gene expression. This study shows that aggressiveness towards humans and stereotypies are behavioural indicators that covary with physiological alterations. Further studies are needed regarding the biological correlates of unresponsiveness to the environment and alert postures.

Validation of a Denoising Method Using Deep Learning-Based Reconstruction to Quantify Multiple Sclerosis Lesion Load on Fast FLAIR Imaging.

BACKGROUND AND PURPOSE: Accurate quantification of WM lesion load is essential for the care of patients with multiple sclerosis. We tested whether the combination of accelerated 3D-FLAIR and denoising using deep learning-based reconstruction could provide a relevant strategy while shortening the imaging examination. MATERIALS AND METHODS: Twenty-eight patients with multiple sclerosis were prospectively examined using 4 implementations of 3D-FLAIR with decreasing scan times (4 minutes 54 seconds, 2 minutes 35 seconds, 1 minute 40 seconds, and 1 minute 15 seconds). Each FLAIR sequence was reconstructed without and with denoising using deep learning-based reconstruction, resulting in 8 FLAIR sequences per patient. Image quality was assessed with the Likert scale, apparent SNR, and contrast-to-noise ratio. Manual and automatic lesion segmentations, performed randomly and blindly, were quantitatively evaluated against ground truth using the absolute volume difference, true-positive rate, positive predictive value, Dice similarity coefficient, Hausdorff distance, and F1 score based on the lesion count. The Wilcoxon signed-rank test and 2-way ANOVA were performed. RESULTS: Both image-quality evaluation and the various metrics showed deterioration when the FLAIR scan time was accelerated. However, denoising using deep learning-based reconstruction significantly improved subjective image quality and quantitative performance metrics, particularly for manual segmentation. Overall, denoising using deep learning-based reconstruction helped to recover contours closer to those from the criterion standard and to capture individual lesions otherwise overlooked. The Dice similarity coefficient was equivalent between the 2-minutes-35-seconds-long FLAIR with denoising using deep learning-based reconstruction and the 4-minutes-54-seconds-long reference FLAIR sequence. CONCLUSIONS: Denoising using deep learning-based reconstruction helps to recognize multiple sclerosis lesions buried in the noise of accelerated FLAIR acquisitions, a possibly useful strategy to efficiently shorten the scan time in clinical practice.

High-risk syndrome for neuromyelitis optica: a descriptive and comparative study.

BACKGROUND: Neuromyelitis optica (NMO) frequently begins with a monofocal episode of optic neuritis or myelitis. A concept named high-risk syndrome (HRS) for NMO has been proposed for patients with monofocal episodes and NMO-IgG antibodies. OBJECTIVE: To describe HRS patients and compare them with NMO patients. METHODS: We identified 30 patients with HRS: 18 with extensive myelitis (HRM) and 12 with optic neuritis (HRON), in a database pooling patients from 25 centres in France. Clinical, laboratory/magnetic resonance imaging (MRI) data and outcome were analysed and compared with a national cohort of 125 NMO patients extracted from the same database. RESULTS: Mean follow-up was 4.8 years. Mean age at onset was 42.8 years (range: 12.4-70) with a female:male ratio of 0.9. Asymptomatic lesions were report on visual evoked potentials in 4/8 tested HRM patients and on spinal cord MRI in 2/7 HRON patients. Three patients died, two owing to a cervical lesion. HRS and NMO patients had similar clinical/paraclinical data, except for a predominance of men in the HRS group and a later mean age at onset in the HRM subgroup. CONCLUSION: The description of HRS patients is compatible with a monofocal form of NMO. Asymptomatic lesions could be included in a new set of NMO diagnostic criteria.

SMILE: a predictive model for Scoring the severity of relapses in MultIple scLErosis.

BACKGROUND: In relapsing-remitting multiple sclerosis (RRMS), relapse severity and residual disability are difficult to predict. Nevertheless, this information is crucial both for guiding relapse treatment strategies and for informing patients. OBJECTIVE: We, therefore, developed and validated a clinical-based model for predicting the risk of residual disability at 6 months post-relapse in MS. METHODS: We used the data of 186 patients with RRMS collected during the COPOUSEP multicentre trial. The outcome was an increase of ≥ 1 EDSS point 6 months post-relapse treatment. We used logistic regression with LASSO penalization to construct the model, and bootstrap cross-validation to internally validate it. The model was externally validated with an independent retrospective French single-centre cohort of 175 patients. RESULTS: The predictive factors contained in the model were age > 40 years, shorter disease duration, EDSS increase ≥ 1.5 points at time of relapse, EDSS = 0 before relapse, proprioceptive ataxia, and absence of subjective sensory disorders. Discriminative accuracy was acceptable in both the internal (AUC 0.82, 95% CI [0.73, 0.91]) and external (AUC 0.71, 95% CI [0.62, 0.80]) validations. CONCLUSION: The predictive model we developed should prove useful for adapting therapeutic strategy of relapse and follow-up to individual patients.

Effect of cognitive rehabilitation on neuropsychological and semiecological testing and on daily cognitive functioning in multiple sclerosis: The REACTIV randomized controlled study.

BACKGROUND: Specific cognitive rehabilitation (SCR) has been suggested for multiple sclerosis (MS). A randomized controlled trial (RCT) evaluating the therapeutic effects of SCR is necessary. OBJECTIVE: To demonstrate the superiority of a SCR program (REACTIV) over nonspecific intervention (NSI) for neuropsychological (NP) assessment, virtual reality (VR) cognitive testing and daily cognitive functioning. METHODS: A single-blind RCT compared SCR and NSI in patients with MS with cognitive complaint. Both programs included 50 individual sessions, 3 times a week for 17 weeks in a real-world setting. The primary end-point was NP assessment. Secondary end-points included semiecological VR tasks (Urban Daily Cog®) and daily cognitive functioning assessment. Maintenance of the effects at 8 months was studied. RESULTS: Of the 35 patients, 18 completed the SCR, and 17 completed the NSI. Several NP and semiecological scores improved significantly more after SCR than after NSI. More NP scores improved significantly after SCR than after NSI. SCR improved daily cognitive functioning. Most improvements were maintained at 8 months. CONCLUSION: SCR performed in a real-world setting is superior to NSI for improving performance in specific cognitive domains and information processing speed, and for improving cognitive functioning, as evaluated by ecological tools close to daily life and a daily cognitive functioning questionnaire.

Genetic interaction between transcription elongation factor TFIIS and RNA polymerase II.

Little is known about the regions of RNA polymerase II (RNAPII) that are involved in the process of transcript elongation and interaction with elongation factors. One elongation factor, TFIIS, stimulates transcript elongation by binding to RNAPII and facilitating its passage through intrinsic pausing sites in vitro. In Saccharomyces cerevisiae, TFIIS is encoded by the PPR2 gene. Deletion of PPR2 from the yeast genome is not lethal but renders cells sensitive to the uracil analog 6-azauracil (6AU). Here, we show that mutations conferring 6AU sensitivity can also be isolated in the gene encoding the largest subunit of S. cerevisiae RNAPII (RPO21). A screen for mutations in RPO21 that confer 6AU sensitivity identified seven mutations that had been generated by either linker-insertion or random chemical mutagenesis. All seven mutational alterations are clustered within one region of the largest subunit that is conserved among eukaryotic RNAPII. The finding that six of the seven rpo21 mutants failed to grow at elevated temperature underscores the importance of this region for the functional and/or structural integrity of RNAPII. We found that the 6AU sensitivity of the rpo21 mutants can be suppressed by increasing the dosage of the wild-type PPR2 gene, presumably as a result of overexpression of TFIIS. These results are consistent with the proposal that in the rpo21 mutants, the formation of the RNAPII-TFIIS complex is rate limiting for the passage of the mutant enzyme through pausing sites. In addition to implicating a region of the largest subunit of RNAPII in the process of transcript elongation, our observations provide in vivo evidence that TFIIS is involved in transcription by RNAPII.

History of traumatic brain injury in prison populations: A systematic review.

Traumatic brain injury (TBI) can lead to cognitive, behavioural and social impairments. The relationship between criminality and a history of TBI has been addressed on several occasions. OBJECTIVE: The objective of this review was to present an update on current knowledge concerning the existence of a history of TBI in prison populations. METHODS: PubMed and PsycINFO databases were searched for relevant papers, using the PRISMA guidelines. We selected papers describing TBI prevalence among incarcerated individuals and some that also discussed the validity of such studies. RESULTS: Thirty-three papers were selected. The majority of the papers were on prison populations in Australia (3/33), Europe (5/33) and the USA (22/33). The selected studies found prevalence rates of the history of TBI ranging from 9.7% and 100%, with an average of 46% (calculated on a total population of 9342). However, the level of evidence provided by the literature was poor according to the French national health authority scale. The majority of the prisoners were males with an average age of 37. In most of the papers (25/33), prevalence was evaluated using a questionnaire. The influence of TBI severity on criminality could not be analysed because of a lack of data in the majority of papers. Twelve papers mentioned that several comorbidities (mental health problems, use of alcohol…) were frequently found among prisoners with a history of TBI. Two papers established the validity of the use of questionnaires to screen for a history of TBI. CONCLUSION: These results confirmed the high prevalence of a history of TBI in prison populations. However, they do not allow conclusions to be drawn about a possible link between criminality and TBI. Specific surveys need to be performed to study this issue. The authors suggest ways of improving the screening and healthcare made available to these patients.

A comprehensive picture of 4-year outcome of severe brain injuries. Results from the PariS-TBI study.

OBJECTIVES: Survivors of severe traumatic brain injury have a great variety of impairments and participation restrictions. Detailed descriptions of their long-term outcome are critical. We aimed to assess brain injury outcome for subjects with traumatic brain injury in terms of the International classification of functioning, disability and health. MATERIALS AND METHODS: Four-year follow-up of an inception cohort of adults with severe traumatic brain injury by using face-to-face interviews with patients and proxies. RESULTS: Among 245 survivors at 4 years, 147 were evaluated (80% male, mean age: 32.5±14.2 years at injury); 46 (32%) presented severe disability, 58 (40%) moderate disability, and 40 (28%) good recovery. Most frequent somatic problems were fatigue, headaches, other pain, and balance. One quarter of subjects had motor impairments. Rates of cognitive complaints ranged from 25 to 68%, the most frequent being memory, irritability, slowness and concentration. With the Hospital Anxiety and Depression Scale, 43% had anxiety and 25% depression. Overall, 79% were independent in daily living activities and 40 to 50% needed help for outdoor or organizational activities on the BICRO-39. Most had regular contacts with relatives or close friends but few contacts with colleagues or new acquaintances. Subjects spent little time in productive activities such as working, studying, looking after children or voluntary work. Quality of life on the QOLIBRI scale was associated with disability level (P<0.0001). CONCLUSION: Management of late brain injury needs to focus on cognitive difficulties, particularly social skills, to enhance patient participation in life.

Conditional mutants of RPC160, the gene encoding the largest subunit of RNA polymerase C in Saccharomyces cerevisiae.

A 18.4-kb fragment of the yeast genome containing the gene of the largest subunit of RNA polymerase C (RPC160) was cloned by hybridization to a previously isolated fragment of that gene. RPC160 maps on chromosome XV, tightly linked but not allelic to the essential gene TSM8740. Temperature sensitive (ts) mutant alleles were constructed by in vitro mutagenesis with NaHSO3 and substituted for the wild-type allele on the chromosome. Four of them were unambiguously identified as rpc160 mutants by failure to complement a fully defective mutation rpc160::URA3. The faithful transcription of a yeast tRNA gene by mutant cell-free extracts is strongly reduced as compared to wild-type. In vivo, the rpc160 mutations specifically affect the synthesis of tRNA in a temperature sensitive way, with comparatively little effect on the synthesis of 5S rRNA and no effect on 5.8S rRNA. An unlinked mutation (pcil-3) suppresses the temperature sensitive phenotype of the rpc160-41 mutation.

Botulinum toxin A for treating spasticity in adults: costly for French hospitals?

INTRODUCTION: Intramuscular injection of botulinum toxin (BoNTA) is one of the primary treatments for focal spasticity. This treatment is considered costly and the level of reimbursement by health insurance has been decreasing in many countries for several years. The aim of this study was to determine the real cost of treating spasticity with BoNTA and to compare this with the level of reimbursement by the national health insurance in France in 2008 and with a new fee, specific to the injection of BoNTA in ambulatory services. METHOD: A single-center, retrospective study using the 2008 database from a French secondary-care day-hospital unit (treating spasticity in adults with sequelae of stroke, multiple sclerosis or traumatic brain injuries). The level of reimbursement by the French ministry of health for BoNTA treatment for adults with spasticity constituted the "calculated cost" and corresponded to the hospital's "budget". The "real cost" (incurred by the hospital) included the sum of staffing and material costs as well as the number of toxin vials used. The calculated costs for 2009 and 2013 were based on the levels of reimbursement during those years. The difference between real and calculated cost for 2009 and 2013 was estimated considering that the real cost of 2008 was stable. RESULTS: In 2008, 364 patients received BoNTA, resulting in 870 day-hospital admissions. The calculated cost was 459,056€/year and the real cost was 567,438€/year (equivalent to 4.27€/day/patient). The total budget deficit (hospital income minus hospital costs) was 108,383€. The deficit was estimated at 222,892€ in 2009 and 241,188€ in 2013. CONCLUSION: The daily cost of BoNTA treatment for spasticity is reasonable; however, because of the level of reimbursement by the national health insurance in France, the treatment is costly for French hospitals.

MS lesions are better detected with 3D T1 gradient-echo than with 2D T1 spin-echo gadolinium-enhanced imaging at 3T.

BACKGROUND AND PURPOSE: In multiple sclerosis, gadolinium enhancement is used to classify lesions as active. Regarding the need for a standardized and accurate method for detection of multiple sclerosis activity, we compared 2D-spin-echo with 3D-gradient-echo T1WI for the detection of gadolinium-enhancing MS lesions. MATERIALS AND METHODS: Fifty-eight patients with MS were prospectively imaged at 3T by using both 2D-spin-echo and 3D-gradient recalled-echo T1WI in random order after the injection of gadolinium. Blinded and independent evaluation was performed by a junior and a senior reader to count gadolinium-enhancing lesions and to characterize their location, size, pattern of enhancement, and the relative contrast between enhancing lesions and the adjacent white matter. Finally, the SNR and relative contrast of gadolinium-enhancing lesions were computed for both sequences by using simulations. RESULTS: Significantly more gadolinium-enhancing lesions were reported on 3D-gradient recalled-echo than on 2D-spin-echo (n = 59 versus n = 30 for the junior reader, P = .021; n = 77 versus n = 61 for the senior reader, P = .017). The difference between the 2 readers was significant on 2D-spin-echo (P = .044), for which images were less reproducible (κ = 0.51) than for 3D-gradient recalled-echo (κ = 0.65). Further comparisons showed that there were statistically more small lesions (<5 mm) on 3D-gradient recalled-echo than on 2D-spin-echo (P = .04), while other features were similar. Theoretic results from simulations predicted SNR and lesion contrast for 3D-gradient recalled-echo to be better than for 2D-spin-echo for visualization of small enhancing lesions and were, therefore, consistent with clinical observations. CONCLUSIONS: At 3T, 3D-gradient recalled-echo provides a higher detection rate of gadolinium-enhancing lesions, especially those with smaller size, with a better reproducibility; this finding suggests using 3D-gradient recalled-echo to detect MS activity, with potential impact in initiation, monitoring, and optimization of therapy.