Latent disconnectome prediction of long-term cognitive-behavioural symptoms in stroke.

Stroke significantly impacts the quality of life. However, the long-term cognitive evolution in stroke is poorly predictable at the individual level. There is an urgent need to better predict long-term symptoms based on acute clinical neuroimaging data. Previous works have demonstrated a strong relationship between the location of white matter disconnections and clinical symptoms. However, rendering the entire space of possible disconnection-deficit associations optimally surveyable will allow for a systematic association between brain disconnections and cognitive-behavioural measures at the individual level. Here we present the most comprehensive framework, a composite morphospace of white matter disconnections (disconnectome) to predict neuropsychological scores 1 year after stroke. Linking the latent disconnectome morphospace to neuropsychological outcomes yields biological insights that are available as the first comprehensive atlas of disconnectome-deficit relations across 86 scores-a Neuropsychological White Matter Atlas. Our novel predictive framework, the Disconnectome Symptoms Discoverer, achieved better predictivity performances than six other models, including functional disconnection, lesion topology and volume modelling. Out-of-sample prediction derived from this atlas presented a mean absolute error below 20% and allowed personalize neuropsychological predictions. Prediction on an external cohort achieved an R2 = 0.201 for semantic fluency. In addition, training and testing were replicated on two external cohorts achieving an R2 = 0.18 for visuospatial performance. This framework is available as an interactive web application (http://disconnectomestudio.bcblab.com) to provide the foundations for a new and practical approach to modelling cognition in stroke. We hope our atlas and web application will help to reduce the burden of cognitive deficits on patients, their families and wider society while also helping to tailor future personalized treatment programmes and discover new targets for treatments. We expect our framework's range of assessments and predictive power to increase even further through future crowdsourcing.

International Recommendations to Manage Poststroke Equinovarus Foot Deformity Validated by a Panel of Experts Using Delphi.

OBJECTIVE: To establish international recommendations for the management of spastic equinovarus foot deformity. DESIGN: Delphi method. SETTING: International study. PARTICIPANTS: A total of 24 international experts (N=24) in neuro-orthopedic deformities, from different specialties (Physical and Rehabilitation Medicine physicians, neurologists, geriatricians, orthopedic surgeons, neurosurgeons, plastic surgeons). INTERVENTIONS: Experts answered 3 rounds of questions related to important aspects of diagnosis, assessment, and treatment of spastic equinovarus foot deformity. MAIN OUTCOME MEASURES: A consensus was established when at least 80% of experts agreed on a statement RESULTS: A total of 52 items reached consensus. Experts recommend assessing effect of the deformity on functional activities before treatment. Before treatment, it is crucial to differentiate spastic muscle overactivity from soft tissue contractures, identify which muscles are involved in the deformity, and evaluate the activity of antagonist muscles. Motor nerve blocks, 2-dimensional video analysis, and radiologic examinations are often required to complement a clinical examination. The treatment of equinovarus foot depends on the correctability of the deformity and the patient's ability to stand or walk. The preoperative assessment should include an interdisciplinary consultation that must finalize a formal agreement between physicians and the patient, which will define personalized attainable goals before surgery. CONCLUSION: The establishment of guidelines on managing equinovarus foot will help physicians and surgeons, specialists, and nonspecialists to diagnoses and assess the deformity and direct patients to a network of experts to optimize patient functional recovery and improve their autonomy.

Évolution des séquelles cognitivo-comportementales d'un traumatisme cranio-cérébral modéré à sévère plusieurs années après sa survenue. Synthèse et perspectives.

Résumé Chaque année, 150 000 nouveaux cas de traumatismes cranio-cérébraux (TCC) sont recensés en France. Les TCC représentent une cause majeure de handicap chez les sujets jeunes. De nombreuses études se sont intéressées aux conséquences d'un TCC durant les premiers mois, en mettant en évidence des difficultés somatiques et cognitivo-comportementales qui impactent la vie sociale, affective et professionnelle des personnes victimes. Selon la sévérité du TCC, ces difficultés peuvent, totalement ou en partie seulement, régresser durant les premiers mois et jusqu'à deux ans après le TCC. L'évolution puis la consolidation des séquelles cognitivo-comportementales peuvent se poursuivre jusqu'à cinq ans après le TCC. Peu d'études ont porté sur l'évolution des séquelles cognitivo-comportementales avec l'avancée en âge des personnes victimes d'un TCC. Celle-ci semble être influencée par des facteurs spécifiques comme l'âge de survenue du TCC, le sexe, être porteur du gène ApoE4 mais également des facteurs environnementaux comme, la qualité des interactions cognitives et sociales. Abstract Traumatic Brain Injuries (TBI) result in cognitive and behavioral impairment inducing a disability in daily life for the TBI victims, but also for the families in social, professional and emotional domains. Evolution of these consequences has been widely described during the first few months after TBI (up two years after the TBI), but few studies are carried on the becoming of these impairments when TBI subjects are growing old. Evolution seems to be affected by endogenous factors such as gender, age, and ApoE4, and exogenous factors such as social interactions. Some studies suggest that TBI is a risk factor to develop a neurodegenerative disease.

Adjunct therapies after botulinum toxin injections in spastic adults: Systematic review and SOFMER recommendations.

BACKGROUND: Adjunct therapies (ATs) may further improve outcomes after botulinum toxin injections in spastic patients, but evidence was unclear in previous systematic reviews. OBJECTIVE: To assess the efficacy of non-pharmacological ATs in spastic adults according to the International Classification of Functioning, Disability and Health and build an expert consensus-based on a Delphi process. METHODS: Four electronic databases were searched up to May 2020 for reports of comparative trials of non-pharmacologic ATs after botulinum toxin injections in spastic adults. Then, 25 French experts participated in a two-round Delphi process to build recommendations on the use of ATs. RESULTS: We included 32 studies (1202 participants, median 32/study) evaluating the effects of physical agents (n=9), joint posture procedures (JPPs, n=11), and active ATs (n=14), mainly after stroke. The average quality of articles was good for randomised controlled trials (median [interquartile range] PEDro score=7 [6-8]) but moderate (n=2) or poor (n=2) for non-randomised controlled trials (Downs & Black checklist). Meta-analysis was precluded owing to the heterogeneity of ATs, control groups and outcome measures. There is evidence for the use of JPPs except low-dose manual stretching and soft posture techniques. Continuous postures (by taping or casting) are recommended; discontinuous postures (by orthosis) may be preferred in patients with active function. Device-free or device-assisted active ATs may be beneficial in the mid-term (>3months after botulinum toxin injections), particularly when performed at a high-intensity (>3h/week) as in constraint-induced movement therapy. Self-rehabilitation remains understudied after a focal treatment, but its interest is highlighted by the experts. The use of physical agents is not recommended. CONCLUSIONS: JPPs and active ATs (device-assisted or device-free) may further improve impairments and activities after botulinum toxin injections. Further studies are needed to better define the best strategies for ATs as a function of the individual treatment goals, participation and quality of life. REVIEW REGISTRATION: PROSPERO (CRD42018105856).

Carbapenemase-producing Enterobacteriaceae in an inpatient post-acute care facility: Impact on time to functional recovery.

BACKGROUND: The carriage of carbapenemase-producing Enterobacteriaceae (CPE) might lengthen the time to functional recovery (TTFR) for inpatients in post-acute care (PAC) units. OBJECTIVE: We aimed to assess the impact of CPE carriage on TTFR in a PAC facility. METHODS: This 2-year retrospective cohort study included 20 CPE-positive patients and 54 CPE-negative patients admitted to 3 PAC units (general, orthopaedic and neurological rehabilitation units) in a teaching hospital from January 2017 to December 2019. Potential risk factors and demographic data were collected from patients' medical records, the French national hospital discharge database, and the hospital's CPE surveillance database. Functional recovery was defined as the median difference in functional independence measure (FIM) between admission and discharge from each unit. Survival analysis and multiple Cox regression models were used to predict the TTFR and identify factors associated with functional recovery. RESULTS: The overall median [interquartile range] TTFR was 50 days [36-66]. Longer median TTFR was associated with CPE carriage (63 vs 47 days in the CPE-negative group; adjusted hazard ratio (aHR) 0.35, 95% CI 0.13-0.97) and presence of a peripheral venous catheter (aHR 3.51, 1.45-8.46); shorter TTFR was associated with admission to an orthopaedic versus general rehabilitation unit (aHR 3.11, 1.24-7.82). CONCLUSIONS: CPE carriage in inpatient PAC facilities was associated with long TTFR. Further studies are needed to explore the mechanisms involved in these adverse events and to identify possible preventive measures.

Neuro-Orthopedic Surgery for Equinovarus Foot Deformity in Adults: A Narrative Review.

Neuro-orthopedic surgery is an alternative to the conservative treatment of spastic equinovarus foot (SEF) in adults. The objective of the present narrative review was to summarize current practice with regard to patient assessment, the choice of treatment, the various neuro-orthopedic procedures, and the latter's outcomes. We searched literature databases (MEDLINE, EMBASE, Cochrane) for original articles or opinion papers on surgical treatment of spastic equinovarus foot in adults. Neuro-orthopedic approaches require a careful analysis of the patient's and/or his/her caregiver needs and thus relevant treatment goals. Surgical planning requires detailed knowledge of impairments involved in the spastic equinovarus foot deformity based on a careful clinical examination and additional information from diagnostic nerve blocks and/or a quantitative gait analysis. Procedures mainly target nerves (neurotomy) and tendons (lengthening, transfer, tenotomy). These procedures reduce impairments (spasticity, range of motion, and foot position), improve gait and walking function, but their impact on participation and personalized treatment goals remains to be demonstrated. Neuro-orthopedic surgery is an effective treatment option for spastic equinovarus foot in adults. However, practice is still very heterogeneous and there is no consensus on the medical strategies to be applied before, during and after surgery (particularly the type of anesthesia, the need for immobilization, rehabilitation procedures).

Late cortical disinhibition in focal hand dystonia.

In writer's cramp (WC), a form of focal hand dystonia, cortical GABAergic inhibitory mechanisms are altered and may cause involuntary tonic contractions while writing. The objective of this study was to explore the time course of long-interval intracortical inhibition (LICI) that involves gamma-amino butyric acid (GABA)-B transmission and late cortical disinhibition (LCD) (that combines GABA-A and GABA-B mechanisms) in patients with WC and in control subjects. A double pulse transcranial magnetic stimulation protocol was used to evoke LICI and LCD while the subjects either gripped a cylinder between their thumb and index fingers or relaxed all their upper limb muscles. We measured the ratio between primed and unprimed motor evoked potential in the first dorsal interosseous at interstimulus intervals ranging between 60 and 300 ms. Though the cortical silent period was not different between the groups, LICI lasted longer in patients with WC, that is, LCD was delayed for more than 30 ms and reached a higher level. In addition to the alteration of inhibitory mechanism mediated by GABA-B transmission, LCD which probably involves presynaptic inhibition is also modified in patients with WC with possible consequences on the activity of primary motor cortex inhibitory and excitatory circuits which control the hand muscles.caus.

Can dual-task paradigms predict Falls better than single task? - A systematic literature review.

With about one third of adults aged 65 years and older being reported worldwide to fall each year, and an even higher prevalence with advancing age, aged-related falls and the associated disabilities and mortality are a major public health concern. In this context, identification of fall risk in healthy older adults is a key component of fall prevention. Since dual-task outcomes rely on the interaction between cognition and motor control, some studies have demonstrated the role of dual-task walking performance or costs in predicting future fallers. However, based on previous reviews on the topic, (1) discriminative and (2) predictive powers of dual tasks involving gait and a concurrent task are still a matter of debate, as is (3) their superiority over single tasks in terms of fall-risk prediction. Moreover, less attention has been paid to dual tasks involving postural control and transfers (such as gait initiation and turns) as motor tasks. In the present paper, we therefore systematically reviewed recent literature over the last 7 years in order to answer the three above mentioned questions regarding the future of lab-based dual tasks (involving posture, gait initiation, gait and turning) as easily applicable tests for identifying healthy older adult fallers. Despite great heterogeneity among included studies, we emphasized, among other things, the promising added value of dual tasks including turns and other transfers, such as in the Timed Up and Go test, for prediction of falls. Further investigation of these is thus warranted.

Predictors of outcome in 1-month survivors of large middle cerebral artery infarcts treated by decompressive hemicraniectomy.

BACKGROUND: Decompressive hemicraniectomy (DH) increases survival without severe dependency in patients with large middle cerebral artery (LMCA) infarcts. The objective was to identify predictors of 1-year outcome after DH for LMCA infarct. METHODS: We conducted this study in consecutive patients who underwent DH for LMCA infarcts, in a tertiary stroke centre. Using multivariable logistic regression analyses, we evaluated predictors of (1) 30-day mortality and (2) poor outcome after 1 year (defined as a modified Rankin Scale score of 4-6) in 30-day survivors. RESULTS: Of 212 patients (133 men, 63%; median age 51 years), 35 (16.5%) died within 30 days. Independent predictors of mortality were infarct volume before DH (OR 1.10 per 10 mL increase, 95% CI 1.04 to 1.16), delay between symptom onset and DH (OR 0.41, 95% CI 0.23 to 0.73 per 12 hours increase) and midline shift after DH (OR 2.59, 95% CI 1.09 to 6.14). The optimal infarct volume cut-off to predict death was 210 mL or more. Among the 177 survivors, 77 (43.5%) had a poor outcome at 1 year. Independent predictors of poor outcome were age (OR 1.08 per 1 year increase, 95% CI 1.03 to 1.12) and weekly alcohol consumption of 300 g or more (OR 5.30, 95% CI 2.20 to 12.76), but not infarct volume. CONCLUSION: In patients with LMCA infarcts treated by DH, stroke characteristics (infarct volume before DH, midline shift after DH and early DH) predict 30-day mortality, while patients' characteristics (age and excessive alcohol intake) predict 1-year outcome survivors.

Influence of Motor Deficiency and Spatial Neglect on the Contralesional Posterior Parietal Cortex Functional and Structural Connectivity in Stroke Patients.

The posterior parietal cortex (PPC) is a key structure for visual attention and upper limb function, two features that could be impaired after stroke, and could be implied in their recovery. If it is well established that stroke is responsible for intra- and interhemispheric connectivity troubles, little is known about those existing for the contralesional PPC. In this study, we aimed at mapping the functional (using resting state fMRI) and structural (using diffusion tensor imagery) networks from 3 subparts of the PPC of the contralesional hemisphere (the anterior intraparietal sulcus), the posterior intraparietal sulcus and the superior parieto-occipital cortex to bilateral frontal areas and ipsilesional homologous PPC parts in 11 chronic stroke patients compared to 13 healthy controls. We also aimed at assessing the relationship between connectivity and the severity of visuospatial and motor deficiencies. We showed that interhemispheric functional and structural connectivity between PPCs was altered in stroke patients compared to controls, without any specificity among seeds. Alterations of parieto-frontal intra- and interhemispheric connectivity were less observed. Neglect severity was associated with several alterations in intra- and interhemispheric connectivity, whereas we did not find any behavioral/connectivity correlations for motor deficiency. The results of this exploratory study shed a new light on the influence of the contralesional PPC in post-stroke patients, they have to be confirmed and refined in further larger studies.

Audiovisual speech segmentation in post-stroke aphasia: a pilot study.

Background: Stroke may cause sentence comprehension disorders. Speech segmentation, i.e. the ability to detect word boundaries while listening to continuous speech, is an initial step allowing the successful identification of words and the accurate understanding of meaning within sentences. It has received little attention in people with post-stroke aphasia (PWA).Objectives: Our goal was to study speech segmentation in PWA and examine the potential benefit of seeing the speakers' articulatory gestures while segmenting sentences.Methods: Fourteen PWA and twelve healthy controls participated in this pilot study. Performance was measured with a word-monitoring task. In the auditory-only modality, participants were presented with auditory-only stimuli while in the audiovisual modality, visual speech cues (i.e. speaker's articulatory gestures) accompanied the auditory input. The proportion of correct responses was calculated for each participant and each modality. Visual enhancement was then calculated in order to estimate the potential benefit of seeing the speaker's articulatory gestures.Results: Both in auditory-only and audiovisual modalities, PWA performed significantly less well than controls, who had 100% correct performance in both modalities. The performance of PWA was correlated with their phonological ability. Six PWA used the visual cues. Group level analysis performed on PWA did not show any reliable difference between the auditory-only and audiovisual modalities (median of visual enhancement = 7% [Q1 - Q3: -5 - 39]).Conclusion: Our findings show that speech segmentation disorder may exist in PWA. This points to the importance of assessing and training speech segmentation after stroke. Further studies should investigate the characteristics of PWA who use visual speech cues during sentence processing.

French clinical guidelines for peripheral motor nerve blocks in a PRM setting.

INTRODUCTION: Motor nerve blocks with anesthetic drug for local anesthesia are commonly used in physical and rehabilitation medicine (PRM), especially in the field of spasticity. Guidelines in this context are currently lacking. METHOD: Eighteen experts selected on the basis of their recognized experience by the scientific committees of the French PRM (SOFMER) and Anesthesia and Intensive care (SFAR) societies were invited to work and propose guidelines for the use of loco-regional anesthetic drug for motor nerve blocks in PRM setting. Eight issues were addressed: which neural blocks for which indications; drugs and contraindications; medical survey and attitude in case of adverse event; injection and guidance material; patient preparation and pain relief; efficacy assessment; patient information; education of PRM physiatrists. The Medline, Cochrane and Embase databases for the period 1999 to 2018 were consulted and 355 papers analyzed. The drafts were commented then approved by the whole group using electronic vote, before final approval by scientific committee of each society. RESULTS: No scientific evidence emerged from the literature. Thus, these guidelines are mainly based on the opinion of the expert panel. Guidelines for each issue are reported with the main points of arguments. The main question deals with the recommendation about doses for each drug: for lidocaine - up to 2mg/kg - "check contraindications, emergency truck available, no need of previous anesthetic consultation nor presence of anesthetic physician"; for ropivacaine - up to 1.5mg/kg, with a maximum of 100mg - the same but after intravenous line. Beyond these doses, SFAR guidelines have to be applied with the need of anesthetic physician. CONCLUSION: These are the first organizational guidelines devoted to increase the security of motor nerve block use in PRM settings.

Contribution of transcranial magnetic stimulation in assessing parietofrontal connectivity during gesture production in healthy individuals and brain-injured patients.

Parietofrontal (PF) networks link the posterior parietal cortex to premotor and prefrontal areas, and are involved in the control of many motor and cognitive behaviors in healthy humans. In recent years, electrophysiological experiments have provided a better understanding of the functional specificity and temporal involvement of the PF networks' different components during the planning of visually guided upper limb movements. In particular, transcranial magnetic stimulation has been used to temporarily inactivate a cortical area (virtual lesions) or to assess connectivity using paired-pulse protocols)). This approach has shed new light on the neural mechanisms that underlie the planning stages of the reaching and grasping phases of transitive movements. Reaching and grasping were often presented as two distinct processes; in fact, the respective involvement of dorsolateral and dorsomedial networks may depend on the movement's complexity and the need for precise coordination between the two phases. The dorsolateral parietofrontal network (linking the anterior part of the intraparietal sulcus to the ventral premotor cortex) is involved in the grasping phase (i.e. hand shape and grip force scaling), whereas the dorsomedial part (from the posterior part of the intraparietal sulcus and the superior parieto-occipital cortex to the dorsal premotor cortex) appears to be involved not only in the reaching phase but also in more complex visually guided grasping movements. Changes in parietofrontal connectivity following brain injury might explain the impairments in visually guided upper limb movements observed in patients (such as optic ataxia and the motor component of spatial neglect). Lastly, parietofrontal changes may reflect neuronal plasticity in motor function recovery.

Spastic paraplegia due to recessive or dominant mutations in ERLIN2 can convert to ALS.

OBJECTIVE: The aim of this study was to evaluate whether mutations in ERLIN2, known to cause SPG18, a recessive hereditary spastic paraplegia (SP) responsible for the degeneration of the upper motor neurons leading to weakness and spasticity restricted to the lower limbs, could contribute to amyotrophic lateral sclerosis (ALS), a distinct and more severe motor neuron disease (MND), in which the lower motor neurons also profusely degenerates, leading to tetraplegia, bulbar palsy, respiratory insufficiency, and ultimately the death of the patients. METHODS: Whole-exome sequencing was performed in a large cohort of 200 familial ALS and 60 sporadic ALS after a systematic screening for C9orf72 hexanucleotide repeat expansion. ERLIN2 variants identified by exome analysis were validated using Sanger analysis. Segregation of the identified variant with the disease was checked for all family members with available DNA. RESULTS: Here, we report the identification of ERLIN2 mutations in patients with a primarily SP evolving to rapid progressive ALS, leading to the death of the patients. These mutations segregated with the disease in a dominant (V168M) or recessive (D300V) manner in these families or were found in apparently sporadic cases (N125S). CONCLUSIONS: Inheritance of ERLIN2 mutations appears to be, within the MND spectrum, more complex that previously reported. These results expand the clinical phenotype of ERLIN2 mutations to a severe outcome of MND and should be considered before delivering a genetic counseling to ERLIN2-linked families.

Tibialis posterior transfer for foot drop due to central causes: Long-term hindfoot alignment.

BACKGROUND: Tibialis posterior transfer (TPT) is the treatment most widely used to palliate foot drop due to dorsiflexor palsy. TPT has been extensively studied in patients with peripheral neurological causes of foot drop. In contrast, data are scarce on central foot drop, in which TPT is often blamed for causing flattening of the arches. The primary objective of this study was to assess the impact on foot alignment of TPT in patients with central foot drop. The secondary objective was to determine whether TPT combined with other surgical procedures improved gait. HYPOTHESIS: TTP can induce flattening of the medial arch of the foot. PATIENTS AND METHODS: We retrospectively identified 13 patients managed with TPT (1 foot per patient). Mean follow-up was 65 months (range, 12-108 months). The causes were stroke (n=5), head injury (n=3), spinal cord injury (n=2), cervical spondylotic myelopathy (n=1), cerebral palsy (n=1), and a brain tumour (n=1). The clinical assessment focused chiefly on forefoot alignment and footprint parameters. The following variables were collected from weight-bearing radiographs: Djian-Annonier angle, Méary-Toméno angle, lateral arch angle, and calcaneal pitch angle in the sagittal plane; talo-metatarsal angle in the transverse plane; and rearfoot valgus angle in the coronal plane. RESULTS: Of the 13 feet, 6 had normal footprint parameters and 7 pes cavus. There were no cases of flatfoot. Pronation deformities and supination deformities were each found in 2 patients. Comparing the radiographic parameters between the two feet in each patient identified differences only for the lateral arch angle and calcaneal pitch angle, which indicated pes cavus on the operated side (operated side: 142.7° [range, 136°-156°], p=0.041; and 24° [range, 14°-33°], p=0.028, respectively). DISCUSSION: In contrast to the working hypothesis, we found no evidence of progression to valgus flatfoot after TPT transfer performed to treat central foot drop. LEVEL OF EVIDENCE: IV, retrospective study with no control group.