SPIDOL study protocol for the assessment of intrathecal ziconotide antalgic efficacy for severe refractory neuropathic pain due to spinal cord lesions.

RATIONALE: Central neuropathic pain resulting from spinal cord injury is notoriously debilitating and difficult to treat with few currently available treatments. A novel molecule with intrathecal administration: Ziconotide has been approved for treatment of refractory neuropathic pain in general. It acts as a presynaptic calcium channel blocker. A pilot study has shown its potential in SCI neuropathic pain patients. OBJECTIVE: The aim of this study is to determine the long-term (6 months) efficacy of chronic intrathecal ziconotide for the treatment of neuropathic SCI pain. STUDY DESIGN: Multicenter, Randomized, Comparative, Placebo controlled, Double blind clinical trial, with a crossover of random alternated periods of 6 months (placebo or ITZ) for a total of 15 months including a total of 44 patients. STUDY POPULATION: • Patients with SCI of various etiologies exhibiting neuropathic pain refractory to non-invasive treatments. • > 18 years. INTERVENTION: Intrathecal administration of ziconotide via an implanted pump. STUDY OUTCOMES: Primary study outcome Difference in pain intensity for all patients between effective treatment and placebo periods. Secondary study outcomes 1. Continuous evaluation of pain intensity. 2. Percentage of patients with at least 30% of pain reduction. 3. Satisfaction level of the patient pain relief. 4. Declarations of serious adverse events. 5. Duration and intensity of spontaneous and provoked pain. 6. Quality of life. 7. Patient global impression of change. 8. Quantification of daily dosages of analgesic drug intake. 9. Long term memory and neurocognitive effects. 10. Assessment of the patient's physical and emotional distress. NATURE AND EXTENT OF THE BURDEN AND RISKS ASSOCIATED WITH PARTICIPATION, BENEFIT, AND GROUP RELATEDNESS: Participation in this study is in accordance with current treatment protocols for SCI neuropathic pain in France therefore it proposes a treatment that would currently be considered regular practice even though no RCT evidence is yet available. The study gives patients the advantage of directly testing versus placebo a treatment that otherwise entails significant constraints. A Data Safety Monitoring board (DSMB) will be created for continuous safety analysis. Furthermore, patients will be followed in specialized pain centers offering the possibility of continuing their treatment after the study period.

Evaluation of the long-term effect of selective tibial neurotomy for the treatment of spastic foot using a personal goal-centered approach.

OBJECTIVE: The objective of this study was to evaluate the long-term effectiveness of selective tibial neurotomy (STN) for the treatment of the spastic foot using a goal-centered approach. METHODS: Between 2011 and 2018, adult patients with a spastic foot (regardless of etiology) who received STN followed by a rehabilitation program were included. The primary outcome was the achievement of individual goals defined preoperatively (T0) and compared at 1-year (T1) and 5-year (T5) follow-up by using the Goal Attainment Scaling methodology (T-score). The secondary outcomes were the presence of spastic deformities (equinus, varus, and claw toes), modified Ashworth scale (MAS) score for the targeted muscles, and modified Rankin Scale (mRS) score at T0, T1, and T5. RESULTS: Eighty-eight patients were included. At T5, 88.7% of patients had achieved their goals at least "as expected." The mean T-score was significantly higher at T1 (62.5 ± 9.5) and T5 (60.6 ± 11.3) than at T0 (37.9 ± 2.8) (p < 0.0001), and the difference between T1 and T5 was not significant (p = 0.2). Compared to T0, deformities (equinus, varus, and claw toes; all p < 0.0001), MAS score (p < 0.0001), and mRS score (p < 0.0001) were significantly improved at T1 and T5. Compared to T1, MAS score increased slightly only at T5 (p = 0.05) but remained largely below the preoperative value. There was no difference between T1 and T5 regarding other clinical parameters (e.g., deformities, walking abilities, mRS score). CONCLUSIONS: This study found that STN associated with a postoperative rehabilitation program can enable patients to successfully achieve personal goals that are sustained within a 5-year follow-up period.

Electrophysiological abnormalities of the neuromuscular transmission in two patients with botulism-like syndrome following Botulinum-A muscle injections.

Botulinum neurotoxin serotype A (BoNT-A) has several therapeutic indications such as spasticity and dystonia. Although its use is generally considered safe, a systemic diffusion can lead to systemic complications, and a botulism-like syndrome can occur after intramuscular injections. Herein, two adult cases who developed general muscle weakness after a BoNT-A intramuscular injection are reported. Both presented with a progressive decrement on low-frequency (LF) repetitive nerve stimulation (RNS). It is suggested that a progressive decrement on LF-RNS in muscles distant from the injection site strongly supports the diagnosis of iatrogenic botulism.

Locked-in syndrome after central pontine myelinolysis, an outstanding outcome of two patients.

OBJECTIVE: Central pontine myelinolysis (CPM) is a rare demyelinating disease that affects the pons and which can cause extreme disabilities such as locked-in syndrome (LIS) in the initial phase. The aim of the study was to describe the evolution over a 12-month period of two patients with CPM causing an initial LIS. METHOD: We retrospectively report the unexpected clinical outcome of these two patients in relation with the anatomical damages documented by brain MRI, associated with diffusion tensor imaging and reconstruction of corticospinal tracts in tractography. The following clinical parameters systematically assessed at 3, 6, 9, and 12 months: muscle testing on 12 key muscles (Medical Research Council), prehension metrics (box and block test and purdue pegboard), and independence for acts of daily living (functional independence measure). RESULTS: Both patients showed a progressive recovery beginning between 2 and 3 months after the onset of symptoms, leading to almost complete autonomy at 12 months (FIM > 110), with motor strength greater than 4/5 in all joint segments (MRC > 50/60). On brain MRI with tractography, CST appeared partially preserved at pons level. INTERPRETATION: The possibility of a near-complete functional recovery at 12 months is important to consider given the ethical issues at stake and the discussions about limiting care that may take place initially. It seems to be the consequence of reversible myelin damage combined with partially preserved neurons. Development of collateral pathways or resolution of conduction block may explain this recovery. MRI comprising DTI and tractography could play a key role in the prognosis of motor recovery.

The challenge of controlling an auditory BCI in the case of severe motor disability.

BACKGROUND: The locked-in syndrome (LIS), due to a lesion in the pons, impedes communication. This situation can also be met after some severe brain injury or in advanced Amyotrophic Lateral Sclerosis (ALS). In the most severe condition, the persons cannot communicate at all because of a complete oculomotor paralysis (Complete LIS or CLIS). This even prevents the detection of consciousness. Some studies suggest that auditory brain-computer interface (BCI) could restore a communication through a « yes-no¼ code. METHODS: We developed an auditory EEG-based interface which makes use of voluntary modulations of attention, to restore a yes-no communication code in non-responding persons. This binary BCI uses repeated speech sounds (alternating "yes" on the right ear and "no" on the left ear) corresponding to either frequent (short) or rare (long) stimuli. Users are instructed to pay attention to the relevant stimuli only. We tested this BCI with 18 healthy subjects, and 7 people with severe motor disability (3 "classical" persons with locked-in syndrome and 4 persons with ALS). RESULTS: We report online BCI performance and offline event-related potential analysis. On average in healthy subjects, online BCI accuracy reached 86% based on 50 questions. Only one out of 18 subjects could not perform above chance level. Ten subjects had an accuracy above 90%. However, most patients could not produce online performance above chance level, except for two people with ALS who obtained 100% accuracy. We report individual event-related potentials and their modulation by attention. In addition to the classical P3b, we observed a signature of sustained attention on responses to frequent sounds, but in healthy subjects and patients with good BCI control only. CONCLUSIONS: Auditory BCI can be very well controlled by healthy subjects, but it is not a guarantee that it can be readily used by the target population of persons in LIS or CLIS. A conclusion that is supported by a few previous findings in BCI and should now trigger research to assess the reasons of such a gap in order to propose new and efficient solutions. CLINICAL TRIAL REGISTRATIONS: No. NCT02567201 (2015) and NCT03233282 (2013).

Twenty-four-hour rhythmicities in disorders of consciousness are associated with a favourable outcome.

Fluctuations of consciousness and their rhythmicities have been rarely studied in patients with a disorder of consciousness after acute brain injuries. 24-h assessment of brain (EEG), behaviour (eye-opening), and circadian (clock-controlled hormones secretion from urine) functions was performed in acute brain-injured patients. The distribution, long-term predictability, and rhythmicity (circadian/ultradian) of various EEG features were compared with the initial clinical status, the functional outcome, and the circadian rhythmicities of behaviour and clock-controlled hormones. Here we show that more physiological and favourable patterns of fluctuations are associated with a higher 24 h predictability and sharp up-and-down shape of EEG switches, reminiscent of the Flip-Flop model of sleep. Multimodal rhythmic analysis shows that patients with simultaneous circadian rhythmicity for brain, behaviour, and hormones had a favourable outcome. Finally, both re-emerging EEG fluctuations and homogeneous 24-h cycles for EEG, eye-opening, and hormones appeared as surrogates for preserved functionality in brainstem and basal forebrain, which are key prognostic factors for later improvement. While the recovery of consciousness has previously been related to a high short-term complexity, we suggest in this exploratory study the importance of the high predictability of the 24 h long-term generation of brain rhythms and highlight the importance of circadian body-brain rhythms in awakening.

Common Data Elements for Disorders of Consciousness: Recommendations from the Working Group on Behavioral Phenotyping.

BACKGROUND: The recent publication of practice guidelines for management of patients with disorders of consciousness (DoC) in the United States and Europe was a major step forward in improving the accuracy and consistency of terminology, diagnostic criteria, and prognostication in this population. There remains a pressing need for a more precise brain injury classification system that combines clinical semiology with neuroimaging, electrophysiologic, and other biomarker data. To address this need, the National Institute of Neurological Disorders and Stroke launched the Common Data Elements (CDEs) initiative to facilitate systematic collection of high-quality research data in studies involving patients with neurological disease. The Neurocritical Care Society's Curing Coma Campaign expanded this effort in 2018 to develop CDEs for DoC. Herein, we present CDE recommendations for behavioral phenotyping of patients with DoC. METHODS: The Behavioral Phenotyping Workgroup used a preestablished, five-step process to identify and select candidate CDEs that included review of existing National Institute of Neurological Disorders and Stroke CDEs, nomination and systematic vetting of new CDEs, CDE classification, iterative review, and approval of panel recommendations and development of corresponding case review forms. RESULTS: We identified a slate of existing and newly proposed basic, supplemental, and exploratory CDEs that can be used for behavioral phenotyping of adult and pediatric patients with DoC. CONCLUSIONS: The proposed behavioral phenotyping CDEs will assist with international harmonization of DoC studies and allow for more precise characterization of study cohorts, favorably impacting observational studies and clinical trials aimed at improving outcome in this population.

Self-processing in coma, unresponsive wakefulness syndrome and minimally conscious state.

Introduction: Behavioral and cerebral dissociation has been now clearly established in some patients with acquired disorders of consciousness (DoC). Altogether, these studies mainly focused on the preservation of high-level cognitive markers in prolonged DoC, but did not specifically investigate lower but key-cognitive functions to consciousness emergence, such as the ability to take a first-person perspective, notably at the acute stage of coma. We made the hypothesis that the preservation of self-recognition (i) is independent of the behavioral impairment of consciousness, and (ii) can reflect the ability to recover consciousness. Methods: Hence, using bedside Electroencephalography (EEG) recordings, we acquired, in a large cohort of 129 severely brain damaged patients, the brain response to the passive listening of the subject's own name (SON) and unfamiliar other first names (OFN). One hundred and twelve of them (mean age ± SD = 46 ± 18.3 years, sex ratio M/F: 71/41) could be analyzed for the detection of an individual and significant discriminative P3 event-related brain response to the SON as compared to OFN ('SON effect', primary endpoint assessed by temporal clustering permutation tests). Results: Patients were either coma (n = 38), unresponsive wakefulness syndrome (UWS, n = 30) or minimally conscious state (MCS, n = 44), according to the revised version of the Coma Recovery Scale (CRS-R). Overall, 33 DoC patients (29%) evoked a 'SON effect'. This electrophysiological index was similar between coma (29%), MCS (23%) and UWS (34%) patients (p = 0.61). MCS patients at the time of enrolment were more likely to emerged from MCS (EMCS) at 6 months than coma and UWS patients (p = 0.013 for comparison between groups). Among the 72 survivors' patients with event-related responses recorded within 3 months after brain injury, 75% of the 16 patients with a SON effect were EMCS at 6 months, while 59% of the 56 patients without a SON effect evolved to this favorable behavioral outcome. Discussion: About 30% of severely brain-damaged patients suffering from DoC are capable to process salient self-referential auditory stimuli, even in case of absence of behavioral detection of self-conscious processing. We suggest that self-recognition covert brain ability could be an index of consciousness recovery, and thus could help to predict good outcome.

Optimising recovery of consciousness after coma. From bench to bedside and vice versa.

BACKGROUND: Several methods have been proposed to foster recovery of consciousness in patients with disorders of consciousness (DoC). OBJECTIVE: Critically assess pharmacological and non-pharmacological treatments for patients with chronic DoC. METHODS: A narrative mini-review, and critical analysis of the scientific literature on the various proposed therapeutic approaches, with particular attention to level of evidence, risk-benefit ratio, and feasibility. RESULTS AND DISCUSSION: Personalised sensory stimulation, median nerve stimulation, transcranial direct current stimulation (tDCS), amantadine and zolpidem all have favourable risk-benefit ratios and are easy to implement in clinical practice. These treatments should be proposed to every patient with chronic DoC. Comprehensive patient management should also include regular lifting, pain assessment and treatment, attempts to restore sleep and circadian rhythms, implementation of rest periods, comfort and nursing care, and a rehabilitation program with a multi-disciplinary team with expertise in this field. More invasive treatments may cause adverse effects and require further investigation to confirm preliminary, encouraging results and to better define responders' intervention parameters. Scientific studies are essential and given the severity of the disability and handicap that results from DoC, research in this area should aim to develop new therapeutic approaches.

Evaluation of Selective Tibial Neurotomy for the Spastic Foot Treatment Using a Personal Goal-Centered Approach: A 1-Year Cohort Study.

BACKGROUND: Selective tibial neurotomy (STN) has already demonstrated its effectiveness to reduce foot deformities and spasticity, but assessment according to a goal-centered approach is missing. OBJECTIVE: To evaluate the effectiveness of STN associated with a postoperative rehabilitation program for the treatment of the spastic foot, according to a goal-centered approach. METHODS: Interventional study (before-after STN and rehabilitation program) with observational design including consecutive adult patients with spastic foot, who received STN followed by a rehabilitation program, was performed. The primary outcome measure was the achievement of individual goals at the 1-year follow-up using the Goal Attainment Scaling methodology (with T-score). The secondary outcomes measures were the Modified Ashworth Scale and the modified Rankin Score. RESULTS: A total of 104 patients were included. At the 1-year follow-up, 228/252 (90.5%) goals were achieved: 62/252 (24.6%) were achieved as initially expected, 86/252 (34.1%) were achieved better than initially expected, and 80 (31.7%) were achieved much better than initially expected. The mean T-score was significantly increased at the 1-year follow-up (61.5 ± 10.5) compared with the preoperative period (38.1 ± 2.9, P < .00001), and 95/104 (91.3%) patients had a T-score ≥50, meaning that these patients have achieved their goals. At follow-up, spastic deformities were all significantly decreased ( P < .0001), the Modified Ashworth Scale was significantly lower for each muscle targeted ( P < .0001), and the modified Rankin Score was significantly decreased ( P < .0001) allowing the patient population to improve from a moderate to a slight disability status. CONCLUSION: This study showed that STN, associated with a postoperative rehabilitation program, successfully achieve personal goals in patients with spastic foot.

Infraclinical detection of voluntary attention in coma and post-coma patients using electrophysiology.

OBJECTIVE: Early functional evaluation and prognosis of patients with disorders of consciousness is a major challenge that clinical assessments alone cannot solve. Objective measures of brain activity could help resolve this uncertainty. We used electroencephalogram at bedside to detect voluntary attention with a paradigm previously validated in healthy subjects. METHODS: Using auditory-oddball sequences, our approach rests on detecting known attentional modulations of Event Related Potentials that reflect compliance with verbal instructions. Sixty-eight unresponsive patients were tested in their first year after coma onset (37 coma and 31 first year post-coma patients). Their evolution 6 months after the test was considered. RESULTS: Fourteen of the 68 patients, showed a positive response. Nine were in a coma and 5 in a minimally conscious state (MCS). Except for one who died early, all responders evolved to exit-MCS within 6 months (93%), while 35 (65%) among non-responders only. CONCLUSIONS: Among those patients for whom the outcome is highly uncertain, 21% responded positively to this simple but cognitively demanding test. Strikingly, some coma patients were among responders. SIGNIFICANCE: The proposed paradigm revealed cognitive-motor dissociation in some coma patients. This ability to sustain attention on demand predicted awakening within 6 months and represents an immediately useful information for relatives and caregivers.

Case Report: True Motor Recovery of Upper Limb Beyond 5 Years Post-stroke.

Most of motor recovery usually occurs within the first 3 months after stroke. Herein is reported a remarkable late recovery of the right upper-limb motor function after a left middle cerebral artery stroke. This recovery happened progressively, from two to 12 years post-stroke onset, and along a proximo-distal gradient, including dissociated finger movements after 5 years. Standardized clinical assessment and quantified analysis of the reach-to-grasp movement were repeated over time to characterize the recovery. Twelve years after stroke onset, diffusion tensor imaging (DTI), functional magnetic resonance imaging (fMRI), and transcranial magnetic stimulation (TMS) analyses of the corticospinal tracts were carried out to investigate the plasticity mechanisms and efferent pathways underlying motor control of the paretic hand. Clinical evaluations and quantified movement analysis argue for a true neurological recovery rather than a compensation mechanism. DTI showed a significant decrease of fractional anisotropy, associated with a severe atrophy, only in the upper part of the left corticospinal tract (CST), suggesting an alteration of the CST at the level of the infarction that is not propagated downstream. The finger opposition movement of the right paretic hand was associated with fMRI activations of a broad network including predominantly the contralateral sensorimotor areas. Motor evoked potentials were normal and the selective stimulation of the right hemisphere did not elicit any response of the ipsilateral upper limb. These findings support the idea that the motor control of the paretic hand is mediated mainly by the contralateral sensorimotor cortex and the corresponding CST, but also by a plasticity of motor-related areas in both hemispheres. To our knowledge, this is the first report of a high quality upper-limb recovery occurring more than 2 years after stroke with a genuine insight of brain plasticity mechanisms.

Multiprofessional intervention to improve adherence to medication in stroke patients: a study protocol for a randomised controlled trial (ADMED AVC study).

INTRODUCTION: Adherence to secondary preventive medications is often suboptimal in patients with stroke, exposing them to an increased risk of recurrent cerebral and/or cardiovascular events. Effective actions in the long term to improve adherence to medication are needed. The study will evaluate the efficacy of a collaborative multiprofessional patient-centred intervention conducted by a pharmacist on adherence to secondary preventive medication in stroke survivors. METHODS AND ANALYSIS: This is a multicentre cluster-randomised controlled trial. Two groups of 91 patients (intervention vs standard care) will be recruited. The clinical pharmacist intervention targeting secondary preventive medication will consist of three parts over 1 year: (1) an individual semi-structured interview at hospital discharge; (2) follow-up telephone interviews at 3, 6 and 9 months after discharge; and (3) a final individual semi-structured interview 1 year after discharge. Information on patient follow-up will be shared with the general practitioner and the community pharmacist by sending a report of each interview. The primary outcome is adherence to medication during the 12 months after hospital discharge, assessed using a composite endpoint: the medication possession ratio associated with a self-administered questionnaire. ETHICS AND DISSEMINATION: The local ethics committee, the national committee for use of personal data in medical research and the national data protection agency approved the study. The sponsor has no role in study design; collection, analysis and interpretation of data; or report writing. DISCUSSION: This pharmacist-led educational programme has the potential to significantly improve adherence to medication in stroke survivors which could lead to a decrease in recurrent cerebral and/or cardiovascular events. TRIAL REGISTRATION NUMBER: NCT02611440.

Effects of prismatic adaptation on balance and postural disorders in patients with chronic right stroke: protocol for a multicentre double-blind randomised sham-controlled trial.

INTRODUCTION: Patients with right stroke lesion have postural and balance disorders, including weight-bearing asymmetry, more pronounced than patients with left stroke lesion. Spatial cognition disorders post-stroke, such as misperceptions of subjective straight-ahead and subjective longitudinal body axis, are suspected to be involved in these postural and balance disorders. Prismatic adaptation has showed beneficial effects to reduce visuomotor disorders but also an expansion of effects on cognitive functions, including spatial cognition. Preliminary studies with a low level of evidence have suggested positive effects of prismatic adaptation on weight-bearing asymmetry and balance after stroke. The objective is to investigate the effects of this intervention on balance but also on postural disorders, subjective straight-ahead, longitudinal body axis and autonomy in patients with chronic right stroke lesion. METHODS AND ANALYSIS: In this multicentre randomised double-blind sham-controlled trial, we will include 28 patients aged from 18 to 80 years, with a first right supratentorial stroke lesion at chronic stage (≥12 months) and having a bearing ≥60% of body weight on the right lower limb. Participants will be randomly assigned to the experimental group (performing pointing tasks while wearing glasses shifting optical axis of 10 degrees towards the right side) or to the control group (performing the same procedure while wearing neutral glasses without optical deviation). All participants will receive a 20 min daily session for 2 weeks in addition to conventional rehabilitation. The primary outcome will be the balance measured using the Berg Balance Scale. Secondary outcomes will include weight-bearing asymmetry and parameters of body sway during static posturographic assessments, as well as lateropulsion (measured using the Scale for Contraversive Pushing), subjective straight-ahead, longitudinal body axis and autonomy (measured using the Barthel Index). ETHICS AND DISSEMINATION: The study has been approved by the ethical review board in France. Findings will be submitted to peer-reviewed journals relative to rehabilitation or stroke. TRIAL REGISTRATION NUMBER: NCT03154138.

Virtually spatialized sounds enhance auditory processing in healthy participants and patients with a disorder of consciousness.

Neuroscientific and clinical studies on auditory perception often use headphones to limit sound interference. In these conditions, sounds are perceived as internalized because they lack the sound-attributes that normally occur with a sound produced from a point in space around the listener. Without the spatial attention mechanisms that occur with localized sounds, auditory functional assessments could thus be underestimated. We hypothesize that adding virtually externalization and localization cues to sounds through headphones enhance sound discrimination in both healthy participants and patients with a disorder of consciousness (DOC). Hd-EEG was analyzed in 14 healthy participants and 18 patients while they listened to self-relevant and irrelevant stimuli in two forms: diotic (classic sound presentation with an "internalized" feeling) and convolved with a binaural room impulse response (to create an "externalized" feeling). Convolution enhanced the brains' discriminative response as well as the processing of irrelevant sounds itself, in both healthy participants and DOC patients. For the healthy participants, these effects could be associated with enhanced activation of both the dorsal (where/how) and ventral (what) auditory streams, suggesting that spatial attributes support speech discrimination. Thus, virtually spatialized sounds might "call attention to the outside world" and improve the sensitivity of assessment of brain function in DOC patients.

Stroke patients' support: evaluation of knowledge, practices and training needs of French community pharmacists.

Background Stroke represents a major Public Health issue in industrialized countries because of its frequency and severity. In secondary stroke prevention, treatment efficacy is correlated to medication adherence. However, it remains suboptimal in stroke patients. Community pharmacists, in light of their positioning in the care pathway and proximity to patients, can play an essential role in patient support and improving treatment adherence. However, it is currently unknown whether pharmacists are ready to perform this task. Objective Evaluate knowledge, practices and training needs for community pharmacists in therapeutic stroke management to improve long term care for stroke patients. Setting Community pharmacies in the Rhone Alpes region (France). Method We conducted a cross sectional study via a standardized self-assessment questionnaire consisting of 40 questions divided into three parts. The latter was designed by a multidisciplinary team and distributed electronically to community pharmacists of the Rhône-Alpes region (France). Main outcome measure (a) global knowledge score on the pathology, risk factors and clinical care management, (b) description of the support practices for stroke patients, (c) training needs for pharmacists. Results The 104 participants presented a moderate level of knowledge (global score: 12/20 ± 3). Topics best mastered were: pathophysiology, target blood pressure and place of antiplatelets in the therapeutic strategy. Knowledge items that needed improvement were: warning signs correctly identified by 44% of participants, time delay for thrombolysis for which 14% answered correctly, target glycated hemoglobin levels were correct for 41%, and the 3 recommended antihypertensive drug classes were only identified by 5% of participants. Patient education received from pharmacists concerned dosage (89%), treatment adherence (88%), benefits (66%) and administration modalities of medicines (64%), management of risk factors (75% for diet, 73% for physical activity, 70% for smoking and 53% for alcohol). All pharmacists wanted additional training on risk factors and clinical management guidelines. Conclusion Based on this small study, the fragmented knowledge and varied practices promote the need for further training for pharmacists to optimize support of stroke patients. This study promotes the elaboration of training systems adapted to pharmacists' needs. This will help support the development of a targeted pharmaceutical care approach for stroke patients.

Changes in Prefrontal Cortical Activity During Walking and Cognitive Functions Among Patients With Parkinson's Disease.

Background: Walking becomes more and more degraded as Parkinson's Disease (PD) progresses. Previous research examined factors contributing to this deterioration. Among them, changes in brain cortical activity during walking have been less studied in this clinical population. Objectives: This study aimed to: (1) investigate changes in dorsolateral prefrontal cortex (DLPFC) activation during usual walking and dual-task walking conditions in patients with PD; (2) examine the association between cortical activity and behavioral/cognitive outcomes; and (3) explore which factors best predict increased activation of the DLPFC during usual walking. Methods: Eighteen patients with early stage PD and 18 controls performed 4 conditions: (1) standing while subtracting, (2) usual walking, (3) walking while counting forward, and (4) walking while subtracting. Cortical activity in DLPFC, assessed by changes in oxy-hemoglobin (ΔHbO2) and deoxy-hemoglobin (ΔHbR), was measured using functional near infrared spectroscopy (fNIRS). Gait performance was recorded using wearables sensors. Cognition was also assessed using neuropsychological tests, including the Trail Making Test (TMT). Results: DLPFC activity was higher in patients compared to controls during both usual walking and walking while subtracting conditions. Patients had impaired walking performance compared to controls only during walking while subtracting task. Moderate-to-strong correlations between ΔHbO2 and coefficients of variation of all gait parameters were found for usual walking and during walking while counting forward conditions. Part-B of TMT predicted 21% of the variance of ΔHbO2 during usual walking after adjustment for group status. Conclusions: The increased DLPFC activity in patients during usual walking suggests a potential compensation for executive deficits. Understanding changes in DLPFC activity during walking may have implications for rehabilitation of gait in patients with PD.