Constance Flamand-Roze

Validation of a New Language Screening Tool for Patients With Acute Stroke The Language Screening Test (LAST)

Background and Purpose— Standard aphasia scales such as the Boston Diagnosis Aphasia Evaluation are inappropriate for use in acute stroke. Likewise, global stroke scales do not reliably detect aphasia, and existing brief aphasia screening scales suitable for patients with stroke have several limitations. The objective of this study was to generate and validate a bedside language screening tool, the Language Screening Test, suitable for use in the emergency setting. Methods— The Language Screening Test comprises 5 subtests and a total of 15 items. To avoid retest bias, we created 2 parallel versions of the scale. We report the equivalence of the 2 versions, their internal and external validity, and their interrater reliability. We validated the scale by administering it to 300 consecutive patients within 24 hours after admission to our stroke unit and to 104 stabilized patients with and without aphasia using the Boston Diagnosis Aphasia Evaluation as a reference. Results— The 2 versions of the Language Screening Test were equivalent with an intraclass correlation coefficient of 0.96. Internal validity was good; none of the items showed a floor or ceiling effect with no redundancy and good internal consistency (Cronbach &agr; 0.88). External validation against the Boston Diagnosis Aphasia Evaluation showed a sensitivity of 0.98 and a specificity of 1. Interrater agreement was near perfect (intraclass correlation coefficient, 0.998). The median time to complete the Language Screening Test was approximately 2 minutes. Importantly, the Language Screening Test does not need to be administered by a speech and language therapist. Conclusions— This comprehensively validated language rating scale is simple and rapid, making it a useful tool for bedside evaluation of patients with acute stroke in routine clinical practice.

RAD51 Haploinsufficiency Causes Congenital Mirror Movements in Humans

Congenital mirror movements (CMM) are characterized by involuntary movements of one side of the body that mirror intentional movements on the opposite side. CMM reflect dysfunctions and structural abnormalities of the motor network and are mainly inherited in an autosomal-dominant fashion. Recently, heterozygous mutations in DCC, the gene encoding the receptor for netrin 1 and involved in the guidance of developing axons toward the midline, have been identified but CMM are genetically heterogeneous. By combining genome-wide linkage analysis and exome sequencing, we identified heterozygous mutations introducing premature termination codons in RAD51 in two families with CMM. RAD51 mRNA was significantly downregulated in individuals with CMM resulting from the degradation of the mutated mRNA by nonsense-mediated decay. RAD51 was specifically present in the developing mouse cortex and, more particularly, in a subpopulation of corticospinal axons at the pyramidal decussation. The identification of mutations in RAD51, known for its key role in the repair of DNA double-strand breaks through homologous recombination, in individuals with CMM reveals a totally unexpected role of RAD51 in neurodevelopment. These findings open a new field of investigation for researchers attempting to unravel the molecular pathways underlying bimanual motor control in humans.

RAD51 deficiency disrupts the corticospinal lateralization of motor control

Mirror movements are involuntary symmetrical movements of one side of the body that mirror voluntary movements of the other side. Congenital mirror movement disorder is a rare condition characterized by mirror movements that persist throughout adulthood in subjects with no other clinical abnormalities. The affected individuals have mirror movements predominating in the muscles that control the fingers and are unable to perform purely unimanual movements. Congenital mirror movement disorder thus provides a unique paradigm for studying the lateralization of motor control. We conducted a multimodal, controlled study of patients with congenital mirror movements associated with RAD51 haploinsufficiency (n = 7, mean age 33.3 ± 16.8 years) by comparison with age- and gender-matched healthy volunteers (n = 14, mean age 33.9 ± 16.1 years). We showed that patients with congenital mirror movements induced by RAD51 deficiency had: (i) an abnormal decussation of the corticospinal tract; (ii) abnormal interhemispheric inhibition and bilateral cortical activation of primary motor areas during intended unimanual movements; and (iii) an abnormal involvement of the supplementary motor area during both unimanual and bimanual movements. The lateralization of motor control thus requires a fine interplay between interhemispheric communication and corticospinal wiring. This fine interplay determines: (i) the delivery of appropriate motor plans from the supplementary motor area to the primary motor cortex; (ii) the lateralized activation of the primary motor cortex; and (iii) the unilateral transmission of the motor command to the limb involved in the intended movement. Our results also unveil an unexpected function of RAD51 in corticospinal development of the motor system.

Poststroke Aphasia Frequency, Recovery, and Outcomes: A Systematic Review and Meta-Analysis

OBJECTIVES To conduct a systematic review to elucidate the frequency, recovery, and associated outcomes for poststroke aphasia over the long-term. DATA SOURCES Using the Cochrane Stroke Strategy, we searched 10 databases, 13 journals, 3 conferences, and the gray literature. STUDY SELECTION Our a priori protocol criteria included unselected samples of adult stroke patients from randomized controlled trials or consecutive cohorts. Two independent reviewers rated abstracts and articles for exclusion or inclusion, resolving discrepancies by consensus. DATA EXTRACTION We documented aphasia frequencies by stroke type and setting, and computed odds ratios (ORs) with their 95% confidence intervals (CIs) for outcomes. DATA SYNTHESIS We retrieved 2168 citations, reviewed 248 articles, and accepted 50. Median frequencies for mixed stroke (ischemic and hemorrhagic) were 30% and 34% for acute and rehabilitation settings, respectively. Frequencies by stroke type were lowest for acute subarachnoid hemorrhage (9%) and highest for acute ischemic stroke (62%) when arrival to the hospital was ≤3 hours from stroke onset. Articles monitoring aphasia for 1 year demonstrated aphasia frequencies 2% to 12% lower than baseline. Negative outcomes associated with aphasia included greater odds of in-hospital death (OR=2.7; 95% CI, 2.4-3.1) and longer mean length of stay in days (mean=1.6; 95% CI, 1.0-2.3) in acute settings. Patients with aphasia had greater disability from 28 days (OR=1.5; 95% CI, 1.3-1.7) to 2 years (OR=1.7; 95% CI, 1.6-2.0) than those without aphasia. By 2 years, they used more rehabilitation services (OR=1.5; 95% CI, 1.3-1.6) and returned home less frequently (OR=1.4; 95% CI, 1.2-1.7). CONCLUSIONS Reported frequencies of poststroke aphasia range widely, depending on stroke type and setting. Because aphasia is associated with mortality, disability, and use of health services, we recommend long-term interdisciplinary vigilance in the management of aphasia.

Borderzone Strokes and Transcortical Aphasia

Borderzone infarcts (BZIs) are anatomically defined as ischemic lesions occurring at the junction between two arterial territories, accounting for 2% to 10% of strokes. Three types of hemispheric BZIs are described according to topography (ie, superficial anterior, posterior, and deep). Although published series on related aphasia are rare in the setting of BZI, aphasia is of transcortical (TCA) type, characterized by the preservation of repetition. TCA can be of motor, sensory, or mixed type depending on whether expression, understanding, or both are impaired. Recent studies have reported specific aphasic patterns. BZI patients initially presented with mixed TCA. Aphasia specifically evolved according to the stroke location, toward motor or sensory TCA in patients with respectively anterior or posterior BZI. TCA was associated with good long-term prognosis. This specific aphasic pattern is interesting in clinical practice because it prompts the suspicion of a BZI before the MRI is done, and it helps in the planning of rehabilitation and in providing adapted information to the patient and family concerning the likelihood of language recovery.

Tools and early management of language and swallowing disorders in acute stroke patients.

The role of the stroke units in improving morbidity, mortality, and recovery from stroke is clearly demonstrated. However, acute management of language disorders in these specialized units remains controversial, and management of swallowing disorders is usually nonstandardized. The recent validation of a scale for rapid screening of language disorders (LAST [Language Screening Test]) in acute stroke patients should allow optimization of their detection and early management. Swallowing disorders should be screened and managed using a standardized protocol. Following early initial evaluation repeated on a daily basis, they justify tailored rehabilitation sessions, adaptation of food textures, team formation, and families’ information. The use of these protocols implies the cooperation and coordination of the medical and paramedical teams and the daily presence of speech therapists. These aspects are crucial for patients in the stroke units to achieve full benefits from the management proposed in this paper, leading to diminution of complications and better long-term functional prognosis.

English adaptation, international harmonisation, and normative validation of the Language Screening Test (LAST)

Background: The Language Screening Test (LAST) is a unique bedside tool, designed to rapidly and reliably evaluate aphasia during the acute and chronic phases of stroke. Two equivalent reliable and validated versions of the LAST exist in French. Aims: Our objective was to conduct a linguistic adaptation for English (LASTen) through a process of translation, international harmonisation, and normalisation in multiple English-speaking countries. Methods & Procedures: There were four progressive stages in the adaptation of the LASTen including a series of sequential evaluations to identify problematic items, with selection of alternatives by consensus and in collaboration with the original LAST developers. First, three Canadian translators independently adapted the 29 items of the original LAST into English, resolving discrepancies by consensus to produce adaptation I. Evaluations of adaptation I involved ratings of translation difficulty and multidisciplinary expert panel review to produce adaptation II. Evaluations of adaptation II included ratings of translation quality by three different translators followed by healthy native speaker testing in Canada to produce adaptation III. Evaluations of adaptation III included expert review in Australia, Canada, England, and the USA for cultural acceptability and naturalness, followed by healthy native speaker testing in all the four countries to produce adaptation IV. Adaptation IV constituted a linguistically valid LASTen for four English dialects. We documented consensus decisions to modify or retain problematic items. We evaluated group differences using the Kruskal–Wallis test for continuous variables and chi-squared analyses for frequency variables with statistical significance of alpha ≤.05. Outcomes & Results: During the translation and the evaluations, we reconsidered 22 of the 29 items, revising 20 to produce adaptation IV of the LASTen. Normative testing in the four English-speaking countries involved 109 participants (mean age 60 years, SD ±16.1). Fifty-five percent were women, and 32% lacked postsecondary education. Fourteen participants made errors across nine items. There were no significant differences in errors for age, sex, or country. However, participants with postsecondary education made fewer errors than those without (p = .04). Conclusions: We achieved a linguistically compatible adaptation of the French LAST for English, confirming naturalness and cultural appropriateness in healthy native speakers of four English dialects. Our systematic multistep approach delineates rigorous methods for the adaptation of aphasia tools. Our normative validation of the LASTen in healthy native speakers of English provides the impetus for its validation in stroke patients within the four English-speaking countries.

Miming neurological syndromes improves medical student's long-term retention and delayed recall of neurology

Basic examination and diagnostic skills in neurology are important for every graduating medical student. However, a majority of medical students consider neurology as complex and difficult to master. We evaluate the impact a learner-friendly, innovative simulation-based training programme has on long-term retention and delayed recall of neurological semiology amongst third-year medical students from the University Pierre et Marie Curie in Paris, France. The 2013 class received standard teaching in neurological semiology. The 2015 class who received the same standard teaching in neurological semiology were also invited to voluntarily participate in The Move, a mime-based role-play training programme of neurological semiology. During the Move, students were trained to simulate a patient with a neurological syndrome or the physician examining the patient. Students were evaluated with an assessment thirty months after their neurological rotation, including 15 questions to evaluate long-term retention of neurological semiology, and 10 to test background knowledge in general semiology. The semiology test was performed by 366/377 students from the 2013 class (standard education group) and by 272/391 students from the 2015 class, among which 186 participated in The Move (The Move group) and 86 did not (standard education group). The mean neurological semiology score was higher in the 2015 class compared to the 2013 class (p = 0.007) and remained so after adjustment for the general semiology performance (p = 0.003). The adjusted mean neurological semiology score was 1.21/15 points higher [95% CI 0.66, 1.75] in The Move group compared to the standard education group, corresponding to a 14% better ranking. The Move programme improves medical students long-term retention and delayed recall of neurological semiology. This learner-friendly interactive teaching may in turn enhance clinical proficiency of future physicians in neurological semiology.

A randomized, controlled, double-blind, crossover trial of triheptanoin in alternating hemiplegia of childhood

BackgroundBased on the hypothesis of a brain energy deficit, we investigated the safety and efficacy of triheptanoin on paroxysmal episodes in patients with alternating hemiplegia of childhood due to ATP1A3 mutations.MethodsWe conducted a randomized, double-blind, placebo-controlled crossover study of triheptanoin, at a target dose corresponding to 30% of daily calorie intake, in ten patients with alternating hemiplegia of childhood due to ATP1A3 mutations. Each treatment period consisted of a 12-week fixed-dose phase, separated by a 4-week washout period. The primary outcome was the total number of paroxysmal events. Secondary outcomes included the number of paroxysmal motor-epileptic events; a composite score taking into account the number, severity and duration of paroxysmal events; interictal neurological manifestations; the clinical global impression-improvement scale (CGI-I); and safety parameters. The paired non-parametric Wilcoxon test was used to analyze treatment effects.ResultsIn an intention-to-treat analysis, triheptanoin failed to reduce the total number of paroxysmal events (p = 0.646), including motor-epileptic events (p = 0.585), or the composite score (p = 0.059). CGI-I score did not differ between triheptanoin and placebo periods. Triheptanoin was well tolerated.ConclusionsTriheptanoin does not prevent paroxysmal events in Alternating hemiplegia of childhood. We show the feasibility of a randomized placebo-controlled trial in this setting.Trial registrationThe study has been registered with clinicaltrials.gov (NCT002408354) the 03/24/2015.