The supplementary motor area modulates interhemispheric interactions during movement preparation.

The execution of coordinated hand movements requires complex interactions between premotor and primary motor areas in the two hemispheres. The supplementary motor area (SMA) is involved in movement preparation and bimanual coordination. How the SMA controls bimanual coordination remains unclear, although there is evidence suggesting that the SMA could modulate interhemispheric interactions. With a delayed-response task, we investigated interhemispheric interactions underlying normal movement preparation and the role of the SMA in these interactions during the delay period of unimanual or bimanual hand movements. We used functional MRI and transcranial magnetic stimulation in 22 healthy volunteers (HVs), and then in two models of SMA dysfunction: (a) in the same group of HVs after transient disruption of the right SMA proper by continuous transcranial magnetic theta-burst stimulation; (b) in a group of 22 patients with congenital mirror movements (CMM), whose inability to produce asymmetric hand movements is associated with SMA dysfunction. In HVs, interhemispheric connectivity during the delay period was modulated according to whether or not hand coordination was required for the forthcoming movement. In HVs following SMA disruption and in CMM patients, interhemispheric connectivity was modified during the delay period and the interhemispheric inhibition was decreased. Using two models of SMA dysfunction, we showed that the SMA modulates interhemispheric interactions during movement preparation. This unveils a new role for the SMA and highlights its importance in coordinated movement preparation.

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.

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.

Brazilian Portuguese Adaptation and Validation of the Language Screening Test for Poststroke Patients.

BACKGROUND: There is a lack of standardized assessment tools for poststroke aphasia in Brazil, particularly bedside screenings for early identification of patients with suspected language disorders. The Language Screening Test (LAST) is a valid and reliable method for screening hospitalized patients following a stroke. This tool was first developed in French and then translated and validated in other languages. PURPOSE: This study aimed to translate, culturally adapt, and validate the LAST into Brazilian Portuguese. METHOD: Following a systematic, multistep approach to translation and cultural adaptation of language instruments, this study developed the two parallel versions of the Brazilian Portuguese LAST (pLAST) Versions A and B. The final versions were applied to 70 healthy and 30 poststroke adults across age and educational levels. Subtests of the Boston Diagnostic Aphasia Examination (BDAE) were used to assess the external validity of the pLAST. RESULTS: Findings showed that the two versions (A and B) of the pLAST were equivalent (intraclass correlation coefficient = .91; p < .001). No floor or ceiling effects were observed, and internal validity was excellent (Cronbach's α = .85). Moreover, its external validity against the BDAE was moderate to strong. Test sensitivity and specificity were 0.88 and 1, respectively, and accuracy was 0.96. CONCLUSION: The Brazilian Portuguese version of the LAST is a valid, simple, easy, and rapid test to screen poststroke aphasia in hospital settings. SUPPLEMENTAL MATERIAL: https://doi.org/10.23641/asha.23548911.

Cortical border-zone infarcts: clinical features, causes and outcome.

OBJECTIVE: To report the clinical features, causes and outcome of cerebral cortical border-zone infarcts BZI (C-BZI). METHODS: The authors prospectively included patients with MRI-confirmed C-BZI among individuals consecutively admitted in Stroke Unit. RESULTS: Forty-five patients presented C-BZI out of 589 with MRI-confirmed cerebral infarcts (7.6%). Particular clinical characteristics existed in C-BZI in comparison with other cerebral infarctions as a whole, including: (1) frequent transient symptoms at onset (27% vs 9%; p<0.001) and low severity score (NIHSS=3.1±3.0 vs 5.2±6.1; p=0.02); (2) early seizures in first 2 weeks (7/45 (15.6%) vs 12/544 (2.2%); p<0.001), even when focusing only on other infarctions involving the cerebral cortex (15.6% vs 4.3%; p<0.01); (3) heterogeneous clinical presentation but specific transcortical aphasia allowing a clinical suspicion of BZI before MRI; and (4) frequently associated internal carotid disease (69%), with subsequent early surgery in 75% of the cases. Following adapted care in stroke unit, C-BZIs' prognosis appeared good (Rankin score ≤2 at D90) for 82% of the patients. CONCLUSION: Some clinical features are overrepresented in such infarctions, including initial transient symptoms preceding the onset of a completed deficit, transcortical aphasia and early seizures. Despite lower initial severity, C-BZIs justify early management in stroke unit, often followed by carotid surgery, leading to an overall good prognosis.

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.

Neurorehabilitation through Hippotherapy on Neurofunctional Sequels of Stroke: Effect on Patients' Functional Independence, Sensorimotor/Cognitive Capacities and Quality of Life, and the Quality of Life of Their Caregivers-A Study Protocol.

BACKGROUND: Stroke is a high burden illness and the second leading cause of worldwide disability with generally poor recovery rates. Robust benefits of hippotherapy, a novel neurorehabilitation approach, in functional recovery following various severe neurological disabling conditions has been shown. In the present study, we will analyze the effect of a hippotherapy program on the outcome of post-stroke patients in the first year post-stroke. METHOD: A randomized controlled clinical trial on the effectiveness of hippotherapy (4 weeks/18 weeks hippotherapy/conventional neurorehabilitation) versus conventional neurorehabilitation alone (22 weeks) will be conducted over 48 weeks. In the treated group, one-hour daily hippotherapy sessions will be exclusively conducted during the hippotherapy's cycles, alternated with periods of conventional neurorehabilitation. A test battery will measure both the functional and psychological outcomes. The primary endpoint will be the patient's functional independence. The secondary endpoints will measure the sensorimotor function, autonomy, and quality of life, as well as the caregivers' quality of life. RESULTS AND CONCLUSION: Individual brain connectome, life history and personality construct influence the brain's functional connectivity and are central to developing optimal tailored neurorehabilitation strategies. According to our current practice, hippotherapy allows the enhancement of substantial neuroplastic changes in the injured brain with significant neurological recovery. The protocol aims to confirm those issues. Trial registration in ClinicalTrials.gov NCT04759326 accessed on 19 February 2021.

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 α 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.

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.

NeuroQ: A neurophobia screening tool assesses how roleplay challenges neurophobia.

BACKGROUND: Neurophobia is a chronic disease of medical students and junior doctors. Early detection is needed to facilitate prevention and management as this fear can negatively impact patient care. METHODS: We conducted a two-part mono-centric study at the faculty of Medicine, Sorbonne University, in Paris. Part one: a cross-sectional study to validate a newly constructed neurophobia scale, NeuroQ. Part two: a prospective longitudinal study to assess the impact of The Move on student neurophobia using NeuroQ. A population-based sample of second-year medical students of the 2019 and 2020 class of the Faculty of Medicine of Sorbonne University were invited to participate. RESULTS: NeuroQ incorporates the main themes of the neurophobia definition and demonstrates uni-dimensionality. Three hundred and ninety-five medical students participated in the study (mean age was 20.0 years, SD: 2.1 years) assessing the effect of The Move teaching on neurophobia. Two hundred and eighty-eight (72.9%) students were female. After the Move teaching the mean NeuroQ score was significantly lower compared to the baseline NeuroQ score (mean [SD] variation, -1.1 [2.6], p < 0.001). There was a 22.3% relative reduction in the number of neurophobic students after The Move teaching. CONCLUSION: Our results highlight the utility of NeuroQ in assessing (i) baseline neurophobia and (ii) the impact of pre-clinical educational interventions on neurophobia. Furthermore, we have shown the importance of pre-clinical educational interventions, such as The Move, in tackling neurophobia.

A Reliable and Rapid Language Tool for the Diagnosis, Classification, and Follow-Up of Primary Progressive Aphasia Variants.

Background: Primary progressive aphasias (PPA) have been investigated by clinical, therapeutic, and fundamental research but examiner-consistent language tests for reliable reproducible diagnosis and follow-up are lacking. Methods: We developed and evaluated a rapid language test for PPA ("PARIS") assessing its inter-examiner consistency, its power to detect and classify PPA, and its capacity to identify language decline after a follow-up of 9 months. To explore the reliability and specificity/sensitivity of the test it was applied to PPA patients (N = 36), typical amnesic Alzheimer's disease (AD) patients (N = 24) and healthy controls (N = 35), while comparing it to two rapid examiner-consistent language tests used in stroke-induced aphasia ("LAST", "ART"). Results: The application duration of the "PARIS" was ~10 min and its inter-rater consistency was of 88%. The three tests distinguished healthy controls from AD and PPA patients but only the "PARIS" reliably separated PPA from AD and allowed for classifying the two most frequent PPA variants: semantic and logopenic PPA. Compared to the "LAST" and "ART," the "PARIS" also had the highest sensitivity for detecting language decline. Conclusions: The "PARIS" is an efficient, rapid, and highly examiner-consistent language test for the diagnosis, classification, and follow-up of frequent PPA variants. It might also be a valuable tool for providing end-points in future therapeutic trials on PPA and other neurodegenerative diseases affecting language processing.

A Chinese version of the Language Screening Test (CLAST) for early-stage stroke patients.

There is a severe lack of aphasia screening tools for bedside use in Chinese. A number of aphasia assessment tools have recently been developed abroad, but some of these scales were not suitable for patients with acute stroke. The Language Screening Test (which includes two parallel versions [a/b]) in French has been proven to be an effective and time-saving aphasia screening scale for early-stage stroke patients. Therefore, we worked out a Chinese version of the LAST taking into consideration Chinese language and culture. Two preliminary parallel versions (a/b) were tested on 154 patients with stroke at acute phase and 107 patients with stroke at non-acute phase, with the Western Aphasia Battery serving as a gold standard. The equivalence between the two parallel versions and the reliability/validity of each version were assessed. The median time to complete one preliminary Chinese version (each had some item redundancy) was 98 seconds. Two final parallel versions were established after adjustment/elimination of the redundant items and were found to be equivalent (intra-class correlation coefficient: 0.991). Internal consistency is(Cronbach α for each version [a/b] was 0.956 and 0.965, respectively) good. Internal validity was fine: (a) no floor or ceiling effect/item redundancy; (b) construct validity revealed a 1-dimension structure, just like the French version. The higher educated subjects scored higher than their lower educated counterparts (p<0.01). The external validity: at the optimum cut-off point where the score of version a/b <14 in higher educated group(<13 in lower): the specificity of each version was 0.878/0.902(1/1 in lower) and sensitivity was 0.972/0.944(0.944/0.944 in lower). Inter-rater equivalence (intra-class correlation coefficient) was 1. The Chinese version of the Language Screening Test was proved to be an efficient and time-saving bedside aphasia screening tool for stroke patients at acute phase and can be used by an average medical physician.

Correction: A Chinese version of the Language Screening Test (CLAST) for early-stage stroke patients.

[This corrects the article DOI: 10.1371/journal.pone.0196646.].

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 student's 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.

BACKGROUND: Based 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. METHODS: We 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. RESULTS: In 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. CONCLUSIONS: Triheptanoin does not prevent paroxysmal events in Alternating hemiplegia of childhood. We show the feasibility of a randomized placebo-controlled trial in this setting. TRIAL REGISTRATION: The study has been registered with clinicaltrials.gov ( NCT002408354 ) the 03/24/2015.