Parkinson’s disease is a neurological disease with a rising incidence and prevalence. Patients with Parkinson’s disease may receive antipsychotics, for example, due to Parkinson’s disease psychosis. Parkinson’s disease psychosis is characterised by visual hallucinations and other psychotic symptoms. To date, no systematic review has evaluated the effects of antipsychotics in patients with Parkinson’s disease. Therefore, this review aims to assess the beneficial and harmful effects of antipsychotics for Parkinson’s disease.

This is a protocol for a systematic review. A search specialist will perform a search in major medical databases (eg, MEDLINE (Medical Literature Analysis and Retrieval System Online), EMBASE (Excerpta Medica database), CENTRAL (Cochrane Central Register of Controlled Trials)) and clinical trial registries. Published and unpublished randomised clinical trials comparing antipsychotics to any control (placebo, standard care or other antipsychotics) in patients with Parkinson’s disease will be included. Two review authors will independently extract data and conduct risk of bias assessments with the Cochrane Risk of Bias tool—V.2. Primary outcomes will be all-cause mortality, serious adverse events and significant falls. Secondary outcomes will be hospitalisations, non-serious adverse events, Unified Parkinson’s Disease Rating Scale total score and psychotic symptoms using any valid symptom scale. Data will be synthesised by aggregate meta-analysis, trial sequential analysis and network meta-analysis. Several subgroup analyses are planned. An eight-step procedure will be used to assess if the thresholds for clinical significance are crossed, and the certainty of the evidence will be assessed by GRADE (Grading of Recommendations Assessment, Development and Evaluations) and CiNeMA (Confidence in Network Meta-Analysis) approach.

This protocol does not include results, and ethics approval is not required for the project. The findings from the systematic review will be published in international peer-reviewed scientific journals.

PROSPERO ID: CRD42025633985. Available from https://www.crd.york.ac.uk/PROSPERO/view/CRD42025633985.

Amyotrophic lateral sclerosis (ALS) is a rapidly progressive, fatal motor neuron disease. Diagnostic delay severely impairs patient access to ALS multidisciplinary clinics, available disease-modifying medications and therapies that may prolong survival.

To investigate how patient and physician perspectives might be leveraged to promote timely ALS diagnosis, and how system-level barriers might be addressed to promote appropriate referral to ALS multidisciplinary care.

A qualitative study in Alberta, Canada, used human-centred design and interviews to map the diagnostic journeys of ALS patients and identify individual-level and system-level diagnostic barriers and opportunities.

30 semistructured interviews (10 patients; 20 physicians) were conducted. Data were inductively analysed with the aid of Miro board software. Patient and physician data were triangulated to identify key phases of the journey from symptom onset to confirmed ALS diagnosis and themes related to the diagnostic barriers and opportunities. Journey maps were created to visualise the diagnostic journey.

Patient journeys were comprised of five phases and commonly involved iterative cycles of referral and testing before an ALS diagnosis was confirmed. Four primary themes related to diagnostic barriers: difficulty recognising and responding effectively to early-stage ALS symptoms, absence of a single definitive diagnostic test, long wait times between referrals and clinical visits, and physician reluctance to pronounce an ALS diagnosis. Analysis indicated three approaches for improving diagnostic processes: increase ALS awareness; improve communication between referring physicians and physicians receiving referrals (consultants); and develop physician, diagnostic testing and multidisciplinary clinic referral forms that will guide symptom assessment and accurate referral.

Timely ALS diagnosis is challenging for patients navigating the frequently prolonged, circuitous diagnostic journey and physicians who struggle with referral pathways and the efficient diagnosis of this rare disease. Findings demonstrate the importance of increased ALS awareness and effective communication and response within referral pathways. Recommendations include strengthening the clinical approach of community-based physicians and supporting access and referral pathways. Current initiatives arising from this investigation seek to achieve meaningful change in timely referrals for progressive neurological diseases like ALS.

Multiple sclerosis (MS) is a chronic neurological condition that affects approximately 150 000 people in the UK and presents a significant healthcare burden, including the high costs of disease-modifying treatments (DMTs). DMTs have substantially reduced the risk of relapse and moderately reduced disability progression. Patients exhibit a wide range of responses to available DMTs. The Predicting Optimal INdividualised Treatment response in MS (POINT-MS) cohort was established to predict the individual treatment response by integrating comprehensive clinical phenotyping with imaging, serum and genetic biomarkers of disease activity and progression. Here, we present the baseline characteristics of the cohort and provide an overview of the study design, laying the groundwork for future analyses.

POINT-MS is a prospective, observational research cohort and biobank of 781 adult participants with a diagnosis of MS who consented to study enrolment on initiation of a DMT at the Queen Square MS Centre (National Hospital of Neurology and Neurosurgery, University College London Hospital NHS Trust, London) between 01/07/2019 and 31/07/2024. All patients were invited for clinical assessments, including the expanded disability status scale (EDSS) score, brief international cognitive assessment for MS and various patient-reported outcome measures (PROMs). They additionally underwent MRI at 3T, optical coherence tomography and blood tests (for genotyping and serum biomarkers quantification), at baseline (i.e., within 3 months from commencing a DMT), and between 6–12 (re-baseline), 18–24, 30–36, 42–48 and 54–60 months after DMT initiation.

748 participants provided baseline data. They were mostly female (68%) and White (75%) participants, with relapsing–remitting MS (94.3%), and with an average age of 40.8 (±10.9) years and a mean disease duration of 7.9 (±7.4) years since symptom onset. Despite low disability (median EDSS 2.0), cognitive impairment was observed in 40% of participants. Most patients (98.4%) had at least one comorbidity. At study entry, 59.2% were treatment naïve, and 83.2% initiated a high-efficacy DMT. Most patients (76.4%) were in either full- or part-time employment. PROMs indicated heterogeneous impairments in physical and mental health, with a greater psychological than physical impact and with low levels of fatigue. When baseline MRI scans were compared with previous scans (available in 668 (89%) patients; mean time since last scan 9±8 months), 26% and 8.5% of patients had at least one new brain or spinal cord lesion at study entry, respectively. Patients showed a median volume of brain lesions of 6.14 cm³, with significant variability among patients (CI 1.1 to 34.1). When brain tissue volumes z-scores were obtained using healthy subjects (N=113, (mean age 42.3 (± 11.8) years, 61.9% female)) from a local MRI database, patients showed a slight reduction in the volumes of the whole grey matter (–0.16 (–0.22 to –0.09)), driven by the deep grey matter (–0.47 (–0.55 to –0.40)), and of the whole white matter (–0.18 (–0.28 to –0.09)), but normal cortical grey matter volumes (0.10 (0.05 to 0.15)). The mean upper cervical spinal cord cross-sectional area (CSA), as measured from volumetric brain scans, was 62.3 (SD 7.5) mm². When CSA z-scores were obtained from the same healthy subjects used for brain measures, patients showed a slight reduction in CSA (–0.15 (–0.24 to –0.10)).

Modelling with both standard statistics and machine learning approaches is currently planned to predict individualised treatment response by integrating all the demographic, socioeconomic, clinical data with imaging, genetic and serum biomarkers. The long-term output of this research is a stratification tool that will guide the selection of DMTs in clinical practice on the basis of the individual prognostic profile. We will complete long-term follow-up data in 4 years (January 2029). The biobank and MRI repository will be used for collaborative research on the mechanisms of disability in MS.

Stroke is a leading cause of death and disability worldwide, with spasticity affecting 4%–42.6% of stroke survivors. Prolonged spasticity can lead to pain, restricted joint mobility and muscle weakness. Current non-pharmacological treatments include physical therapy, orthoses and surgery. Muscle energy techniques (METs) and blood flow restriction training (BFRT) have shown promise in improving muscle function and reducing spasticity. This study aims to investigate the combined effect of MET and BFRT on upper limb motor function in patients with poststroke spasticity.

This study is a single-blind randomised controlled trial involving patients with poststroke spasticity. Participants will be randomly assigned to either the MET+BFRT group or the passive stretching group. Both groups will receive conventional rehabilitation therapy, with additional MET+BFRT or passive stretching interventions. The intervention will last for 6 weeks, with four sessions per week. Primary outcomes include the simplified Fugl-Meyer assessment (FMA) and surface electromyography, while secondary outcomes include the Modified Barthel Index and the Modified Ashworth Scale.

Based on literature data, patients who had a stroke have an average baseline upper limb FMA score of 40 points. Conventional rehabilitation typically improves FMA to 46 points (SD=8). This trial expects an additional 6-point improvement from the intervention. With α=0.05 (two-sided), 90% power (1–β=0.90) and 10% dropout rate, PASS V.11.0 calculation indicates a minimum requirement of 42 participants per group.

Statistical analysis will be conducted using IBM SPSS Statistics V.25. Intention-to-treat analysis will be used to analyse the result, which means the last observation will be used for interpolation when data are missing. Continuous variables will be summarised as mean±SD for normally distributed data or as median and IQRs for non-normally distributed data. Categorical variables will be presented as frequencies and percentages. For continuous variables that meet the criteria of normal distribution and homogeneity of variance, two-way analysis of variance with repeated measures will be applied; for those that do not meet these criteria, the Mann-Whitney U test will be used. Categorical variables will be analysed with the ² test or Fisher’s exact test.

The study protocol has been approved by the ethics committee of Jiaxing Hospital of Traditional Chinese Medicine (2024-016). Participants will provide written informed consent before inclusion. The results will be disseminated through peer-reviewed journals and conference presentations.

ChiCTR2400085996.

Hand-arm Bimanual Intensive Therapy Including Lower Extremities (HABIT-ILE) is an intensive rehabilitation programme for children with cerebral palsy (CP) delivered in a day camp setting recognised to promote the acquisition of specific functional abilities and independence. Currently, during HABIT-ILE camps, families are minimally involved in their child’s motor learning processes. This explains the challenges reported by both families and therapists, including difficulties in reinforcing skills at home, limited transfer to other functional goals and a lack of confidence in parents’ adaptive competence (self-determination and empowerment). Increasing family involvement in intensive motor rehabilitation programmes and the child’s developmental process by reinforcing skills at home could help reduce the parental impact of the child’s disability, enhance family satisfaction and strengthen their resources to support their child’s daily learning during and after the camp.

To address this, we developed the PARTNER programme, which combines HABIT-ILE with a structured home component focused on parent coaching.

We designed a non-inferiority, mixed-methods, multicentre randomised controlled trial to compare the efficacy at 3 months of the PARTNER programme (35 hours HABIT-ILE+15 hours home programme) with the standard HABIT-ILE programme (50 hours) on the bimanual performance (Assisting Hand Assessment) of children with unilateral CP aged 3–5 years. The secondary aims are to compare the 3-month efficacy of the programmes on occupational performance, functional skills and upper limb activity levels, as well as families’ resources, the parent–child relationship, the quantity and quality of resources available in the home to stimulate the child’s motor development, and parental perceptions of their child’s disability and their child’s abilities (qualitative study). The tertiary aim is to conduct a cost-effectiveness analysis of care consumption in each group up to 6 months after the end of the programmes.

Target recruitment is 66 children (33 in each group) from 3 centres in France. Outcomes will be evaluated before the interventions, immediately after, at 3 months and up to 6 months for the cost-effectiveness analysis. Families in the PARTNER group will receive specific coaching and extensive support to perform the home programme. The coaching will focus on enhancing their resources.

The study protocol has been reviewed, and ethics approval obtained from the Protection of Persons Committee (PPC) (PPC number: 2024-A01051-46). The results from this study will be actively disseminated through manuscript publications and conference presentations.

NCT06963151.

Although as many as 92% of survivors of physical intimate partner violence (IPV) report impacts to the head and/or non-fatal strangulation (NFS) that raise clinical suspicion of brain injury (BI), there are no evidence-based methods to document and characterise BI in this vulnerable population, limited clinical practice guidelines and insufficient understanding about long-term risks for conditions including Alzheimer’s Disease and Related Dementias (ADRD). This leaves most survivors of IPV-caused BI (IPV-BI), overwhelmingly women, without adequate access to medical care and support, safe housing, back-to-school/work accommodations or follow-up care for long-term neurocognitive health. Although traumatic brain injury (TBI) is an established ADRD risk factor, little is known about the attributable risk of ADRD due to IPV-BI, particularly in women.

Our overarching objectives are to (1) use plasma biomarkers as novel tools to assist clinicians to improve diagnosis of IPV-BI at the acute, subacute and chronic stages in a manner sensitive to the needs of this vulnerable population and (2) raise awareness of the importance of considering IPV-BI as a potential ADRD risk factor. A prospective observational study funded by the US Department of Defense (HT9425-24-1-0462), Brain Canada (6200) and the Canadian Institutes of Health Research (523320-NWT-CAAA-37499) leverages collaborative research at multiple clinical sites in British Columbia to maximise equity, diversity and inclusion among participants, with a target enrolment of n=600 participants.

The Advocates, Academics, Survivors and Clinicians to END Intimate Partner Violence Biomarkers study, which is predicated on pre-specified research questions, represents one of the most significant community-based studies on plasma biomarkers affected by an IPV-BI incident. Of particular significance is the fact our study uses robust biomarker approaches being applied in the TBI and ADRD fields to determine how the biomarker profile after IPV-BI compares to typical TBI and the early stage of neurodegenerative disorders.

This study was approved by the University of British Columbia Clinical Research Ethics Board (H24-01990, H22-02241 and H16-02792) and the Island Health Research Ethics Board (H22-03510). Upon publication of primary papers, de-identified data and biospecimens will be made widely available, including the US Federal Interagency Traumatic Brain Injury Research (FITBIR) federated database. Our data and integrated knowledge translation activities with persons with lived experience of IPV-BI and those working in the healthcare sector will be synthesised into co-designed and implemented knowledge tools to improve outcomes for survivors of IPV-BI.

Traumatic brain injury (TBI) is a leading cause of mortality and disability worldwide. In the USA, individuals who racially identify as African American or Black experience disproportionately higher rates of TBI and sustain worse prognosis compared with White patients; however, this population continues to be under-represented in contemporary translational research agendas. This protocol aims to comprehensively evaluate and synthesise what is currently known about the molecular epidemiology of TBI outcome among individuals of Black racial identity or African ancestry.

This review will use the established scoping review framework from the Joanna Briggs Institute. The search strategy will be implemented in PubMed (MEDLINE) and expanded to Embase and Cochrane CENTRAL Library (Wiley) databases in the final review. The date range will span from database inception to 20 July 2025 (date of final search). A two-stage screening process will be performed first at the title and abstract level before full-text assessment. Screening will be performed by two independent reviewers and discrepancies will be reconciled by a third reviewer. Articles that meet the following inclusion criteria will be considered: we will include human studies that investigate molecular and biochemical markers associated with TBI outcome. Studies must include individuals who are (A) of Black or African American racial identity, (B) of African ancestry and/or (C) performed in Sub-Saharan African countries. There is no eligibility criteria related to participant age, sex or gender. Eligible studies will be limited to English, Spanish or French. Data extracted from will be analysed and presented as written narrative, summary statistics of study characteristics and graphical or tabular displays.

Ethical approval is not required for this scoping review. The results of this review will be disseminated through peer-reviewed publications and academic conferences.

Sleep disturbances are highly prevalent among individuals with psychiatric conditions and significantly impair cognitive, emotional and behavioural functioning. Pharmacotherapy for sleep disturbances carries a risk of dependence and adverse effects, while behavioural therapies are often insufficient. Therefore, there is an urgent need for novel interventions. Non-invasive brain stimulation (NIBS) techniques, including repetitive transcranial magnetic stimulation, transcranial electrical stimulation and electroconvulsive therapy, have shown potential in modulating neural circuits involved in sleep regulation, yet their clinical utility remains uncertain. This protocol outlines a systematic review aiming to evaluate the efficacy, safety and optimal parameters of NIBS for treating sleep disturbances in psychiatric conditions.

The review will adhere to Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines and is registered with PROSPERO. Two reviewers will independently perform a literature search, extract data and assess research quality. A comprehensive literature search will be conducted in four databases: PubMed/MEDLINE, Cochrane Library, Embase and Web of Science. Eligible studies will comprise randomised and non-randomised controlled trials, open-label studies, observational designs, case reports and case series. Analysed outcomes will include subjective and objective sleep measures, daytime functioning, changes in psychiatric symptoms and adverse events. Risk of bias will be assessed using the Cochrane Risk of Bias Tool, ROBINS-I and the Newcastle-Ottawa Scale. Where possible, data will be synthesised through meta-analysis; otherwise, tabular summary and narrative synthesis will be provided. The certainty of evidence will be assessed using the grading of recommendations assessment, development and evaluation framework.

No ethical approval is required as this study will involve analysis of already published data. Findings will be disseminated via peer-reviewed publication and conference presentations.

CRD420251053488.

Carers of people with non-memory-led dementias such as posterior cortical atrophy (PCA), primary progressive aphasia (PPA) and behavioural variant frontotemporal dementia (bvFTD) face unique challenges. Yet, little evidence-based support and guidance are available for this population. To address this gap in services, we have developed a novel, web-based educational programme: the Better Living with Non-memory-led Dementia programme (BELIDE). BELIDE was co-designed with people with lived experience of non-memory-led dementia and a previous pilot study confirmed its feasibility as an online intervention. This protocol outlines the randomised controlled trial (RCT) to evaluate the clinical and cost-effectiveness of BELIDE.

This is a parallel-group, single-blind, RCT of 238 unpaid caregivers of people diagnosed with PCA, PPA or bvFTD recruited internationally among members of the UK-based organisation Rare Dementia Support. The intervention (BELIDE programme) consists of six structured online educational modules tailored to each phenotype, a virtual onboarding session, real-life practice tasks and up to two follow-up facilitation sessions. The group receiving the intervention will be given access to the programme, while the control group will receive treatment as usual and be placed on a wait-list to receive access to the programme once they complete their participation in the trial. The allocation ratio will be 1:1 stratified by dementia diagnosis and gender. The primary outcome is reduction in caregiver depressive symptoms. Secondary outcomes include stress, anxiety, self-efficacy, quality of life and caregiver-patient relationship quality. Data will be collected online via Qualtrics surveys at baseline, 8 weeks and 6 months post-randomisation. A mixed-method process evaluation with a subgroup of intervention participants will explore barriers and facilitators for engagement. A health economics evaluation will also be conducted to assess cost-effectiveness. If effective, this programme could improve access to caregiver support for non-memory-led dementias by providing scalable, tailored education.

Ethical approval has been granted by University College London Research Ethics Committee (8545/007). The results will be disseminated via peer-reviewed publications, conferences, stakeholder events and open-access resources.

This trial has been registered prospectively on the Clinical Trials registry, first posted on 5 February 2024 under registration number NCT06241287.

Difficulty with walking can lead to reduced quality of life for people with Parkinson’s disease (pwPD); improving walking is considered a treatment priority. Drug therapies can control PD symptoms; however, pwPD often still experience mobility problems.

Functional electrical stimulation (FES) induces movement in weak muscles via external electrical stimulation. FES is used in stroke and multiple sclerosis patients to correct dropped foot by stimulating the common peroneal nerve and is associated with improved quality of life and mobility. The randomised feasibility study preceding this definitive study showed that daily FES can produce a clinically meaningful improvement in walking speed in pwPD; this was sustained 4 weeks after FES was withdrawn. STEPS II is the first definitive randomised controlled trial, with blinded outcome assessment, aiming to determine the efficacy of FES in pwPD.

STEPS II is a two-group, parallel, assessor-blinded, superiority randomised controlled trial with an internal pilot, designed to compare FES plus usual care versus usual care alone. 234 participants will be randomised across eight UK sites. Telephone pre-screening and face-to-face screening will determine eligibility. The intervention group will attend four unblinded FES visits to receive the device and assess walking with and without FES. All participants have blinded assessments at baseline and weeks 2, 6, 18 and 22. The primary objective is to compare whole body bradykinesia at 18 weeks post-baseline via changes in 10m walking speed. Secondary objectives will assess the wider effects of FES on Parkinsonian gait and quality of life. An embedded qualitative component will explore wider experiences of FES.

This study received ethical approval from the Yorkshire and The Humber-Sheffield Research Ethics Committee (reference 23/YH/0193). A Data Monitoring Committee and Trial Steering Committee will provide independent oversight. Dissemination will be via publications, conferences and social media. FES intervention and training materials will be made open access.

ISRCTN13120555.

Traumatic brain injury (TBI) often causes permanent neurological dysfunction. Although no medication has been validated yet to prevent secondary injury of brain tissue, recent animal studies have reported that perampanel, a glutamine receptor antagonist, could improve the neurological functions of animals with TBI by mitigating the abnormal calcium influx and cell death around the site of primary injury. The present study aims to elucidate the efficacy of perampanel administration in improving the neurological function of patients with TBI.

The perampanel for alleviation of secondary injury in TBI trial is a multicentre, phase-II, open-label randomised controlled trial targeting patients with mild-to-moderate TBI. This trial will include adult TBI patients with a Glasgow Coma Scale score of 9–14 from five tertiary centres. Patients with epilepsy as a comorbidity, delayed presentation of symptoms (>24 hours after injury) or Injury Severity Score of ≥25 will be excluded. The study participants will be randomly assigned to either the perampanel group (2 mg/day) or the control group (fosphenytoin administered at a dose of 15–18 mg/kg/day, followed by 5–7.5 mg/kg/day of fosphenytoin). In both groups, the medication will be initiated within 12 hours of the TBI diagnosis and continued for 7 days. The antiepileptic drugs can be increased, changed or added as necessary if early post-traumatic seizures are observed. The primary outcome is favourable neurological outcome, defined as a Glasgow Outcome Scale Extended score of ≥5 at 90 days after the TBI diagnosis, which will then be compared between the groups through an intention-to-treat analysis.

The present study has been approved by the Certified Review Board of Keio at the principal institution (approval number: N20240004). Written informed consent will be obtained from all participants or their legal representatives. The results will be disseminated via publications and presentations.

Japan Registry of Clinical Trials (jRCTs031250067).

Migraine is a primary headache showing a multifactorial component that includes altered pain processing, psychological/emotional problems, neurocognitive and executive function deficits, all with a possible genetic association. The aim of the current study will be to evaluate the association between sensitisation, psychological/emotional, neurocognitive and genetic profile on conditioned pain modulation (CPM) in women with migraine from a multidisciplinary perspective.

A cross-sectional observational case–control study including 90 women with chronic migraine, 90 women with episodic migraine and 90 women without migraine (as controls) will be conducted. Clinical variables (disability, pain), processing (sensitisation-associated, neuropathic-like symptoms), psychological/emotional (anxiety, depression, sleep quality, catastrophising), neurocognitive (attention), executive functions (memory, mental inhibition, speed processing) and genetics (Val158Met polymorphism rs4680 gene) will be assessed in all subjects by healthcare professionals. Subsequently, CPM will be evaluated with the cold-pressor test paradigm by assessing changes obtained in mechanical and thermal stimuli. The association of each group of variables on CPM will be analysed with multivariate analyses (OMNIBUS analysis of variance). A network model will also be created to identify those variables showing the greatest key measure of centrality with the rest of the severity indicators (strength, intermediation and closeness) to establish the potentially therapeutic targets in patients with migraine from a multidisciplinary point of view.

The protocol of the current study has been approved by the Ethics Committee of all involved institutions (Hospital Universitario Fundación Alcorcón 24–117, Universidad Rey Juan Carlos 010220240912024). All procedures will be conducted following the Declaration of Helsinki. Participants will be informed of the aims and procedures of the study and will receive the informed written consent which should be signed before their inclusion. Study results will be disseminated through peer-reviewed publications and presentations at scientific meetings.

This study aimed to assess the general population’s knowledge (K) of Parkinson’s disease symptoms and management, their attitudes (A) towards early detection and treatment, and their health-related practices (P) relevant to prevention and care.

A cross-sectional study.

This study was conducted between February and September 2023 at the Third Affiliated Hospital of Sun Yat-sen University, Yuedong Hospital.

This study was conducted among the general population.

Demographic information and KAP scores were collected through a self-administered questionnaire.

A total of 835 valid questionnaires were enrolled, including 445 (53.29%) men. The mean knowledge, attitudes and practices scores were 7.72±2.15 (possible range: 0–13), 30.75±2.74 (possible range: 9–45) and 45.22±5.31 (possible range: 13–65), respectively. Multivariate logistic regression analysis showed that knowledge score (OR=1.12, 95% CI 1.03 to 1.21, p=0.005), attitudes score (OR=1.10, 95% CI 1.03 to 1.18, p=0.002), being female (OR=3.34, 95% CI 2.39 to 4.66, p

The general population had inadequate knowledge, suboptimal attitudes and moderate practices towards Parkinson’s disease. It is recommended to implement targeted educational interventions to improve Parkinson’s disease knowledge, especially among those with lower educational attainment and income.

A large number of basic and clinical studies have demonstrated that remote ischaemic conditioning (RIC) has neuroprotective effects. Recently, RIC has made gratifying progress in the field of ischaemia stroke treatment. A considerable number of basic and clinical studies have also revealed the possible therapeutic effects of RIC on subarachnoid haemorrhage. However, the neuroprotective effect of RIC on subarachnoid haemorrhage is still lacking convincing evidence and deserves further study.

To explore the efficacy and safety of RIC for aneurysmal subarachnoid haemorrhage.

An investigator-initiated, multicentre, randomised, double-blind, sham-controlled, parallel-group trial to evaluate the effect of RIC intervention compared to sham RIC intervention for the neurological function improvement of patients with aneurysmal subarachnoid haemorrhage.

The protocol was approved by the IRB of Beijing Tiantan Hospital, Capital Medical University (KY2024-080-03). Progress and safety of the trial are monitored by an independent Data and Safety Monitoring Board. Study results will be published in peer-reviewed medical journals. Written informed consent will be obtained from all participants.

NCT06711302.

Frontotemporal lobar degeneration (FTLD) is the second most common early-onset dementia. Several studies demonstrated that neuroinflammation and iron accumulation occur in FTLD. However, the timing and relevance of these processes and whether these two are merely cause or consequence remains unclear. Elucidating the role is crucial to assess the rationale for using anti-inflammatory therapies in FTLD. Additionally, the process of glymphatic brain clearance has gained attention as a potential contributor in the disease pathophysiology.

In this multimodal biomarker study, we use a combination of ultra-high field (7T) MR, blood and cerebrospinal fluid (CSF) biomarkers to investigate the role of neuroinflammation, iron accumulation and brain clearance in FTLD, and to identify biomarkers to differentiate FTLD-TDP from FTLD-tau. We aim to include 25 patients with probable FTLD-tau, 25 with probable FTLD-TDP and 50 healthy individuals with 50% risk to develop FTLD. We will use several MRI techniques, including magnetic resonance spectroscopy, diffusion weighted spectroscopy and quantitative susceptibility mapping. In addition, we will assess the prevalence of perivascular spaces (PVS) and the mobility of CSF to address glymphatic brain clearance. We will compare quantitative MR markers between patients with FTLD-tau and FTLD-TDP, presymptomatic mutation carriers and healthy controls, and correlate these measures with clinical data and biomarkers in blood and CSF.

We obtained ethical approval from the Medical Ethics Committee Leiden Den Haag Delft (NL78272.058.21). The results will be disseminated through presentations at national and international conferences, open-access peer-reviewed publications, ClinicalTrials.gov and to the public through social media posts and annual newsletters.

NCT06870838; Pre-results.

Parkinson’s disease (PD) is a progressive neurodegenerative disorder characterised by heterogeneous motor and non-motor symptoms. The classification of PD into distinct subtypes remains a major challenge, limiting the development of precision medicine approaches. Existing subtyping methods have relied on clinical features, genetic markers or isolated biomarkers, but an integrated classification system incorporating neuroimaging and fluid biomarkers is lacking. The Prospective Assessments with Neuroimaging and fluid Data Analysis in PD (PANDA) study is a single-centre, longitudinal cohort study designed to explore PD heterogeneity by integrating multimodal neuroimaging, fluid biomarkers and comprehensive clinical assessments.

The PANDA study aims to recruit 500 PD patients and 100 healthy controls (HC) at Guangdong Provincial People’s Hospital from March 2021 to July 2026. Participants undergo three study visits: baseline, 2-year and 4-year follow-ups. Data collection includes brain MRI scans, blood and cerebrospinal fluid sampling, clinical scales, gait assessment, ambulatory blood pressure monitoring and eye-tracking evaluations. A standardised electronic data capture system ensures data accuracy and completeness. The primary objective is to identify biologically and neuroimaging-defined PD subtypes, track disease progression and explore potential biomarkers for stratification. Statistical analyses will include data-driven clustering techniques and longitudinal modelling to assess subtype stability over time.

The PANDA study has been approved by the Institutional Review Board of Guangdong Provincial People’s Hospital (No KY2024-719-01) and is conducted in accordance with the Declaration of Helsinki. Written informed consent is obtained from all participants or their legal guardians prior to study enrolment. The findings from this study will be disseminated through peer-reviewed journals and conference presentations, ensuring accessibility to researchers, clinicians and stakeholders involved in PD research and treatment.

ChiCTR2400091709.

Dysarthria is one of the most prevalent communication disorders following a stroke, and it can lead to social isolation and depression, significantly hindering rehabilitation progress. Recent studies suggest that acoustic startle priming (ASP) tasks may enhance speech performance and motor initiation through the corticoreticulospinal tract. This has opened up new possibilities for the application of ASP in the rehabilitation of poststroke dysarthria. The aim of this study is to investigate whether ASP can improve rehabilitation outcomes in individuals with poststroke dysarthria.

This prospective, randomised, controlled clinical trial plans to enrol 48 participants diagnosed with poststroke dysarthria. Participants will be randomly assigned to either the ASP group (n=24) or the control group (n=24). Both groups will undergo 30 min of standard dysarthria rehabilitation training daily, 5 days per week for 2 weeks. The ASP group will receive an additional 30 min articulation training with ASP, while the control group will receive an equivalent 30 min articulation training with normal acoustic stimuli. Speech and voice characteristics will be assessed using Frenchay Dysarthria Assessment, PRAAT software at baseline, 1 week and 2 weeks postintervention. Furthermore, Functional Near Infrared Spectroscopy will be employed during ASP tasks to investigate cortical activation and changes in brain network connectivity.

The study has been approved by the Tongji Hospital Medical Ethics Committee (TJ-IRB202312100). Raw data from this trial will be publicly available on the Public Management Platform for Clinical Research. The findings will be disseminated through international conferences and peer-reviewed journals.

ChiCTR2400081279.

Progressive supranuclear palsy (PSP) is a devastating neurodegenerative disease characterised by cognitive, behavioural and motor problems. Motor symptoms are highly disabling, while cognitive and behavioural changes have a major impact on carer burden, quality of life and prognosis. Apathy and impulsivity are very common, often coexistent in PSP, and negatively predict survival. In preclinical models and other diseases, apathy and impulsivity are associated with noradrenergic deficits, which can be severe in PSP.

Noradrenaline for Progressive Supranuclear Palsy Syndromes trial is a randomised, double-blind, placebo-controlled, crossover design, Phase IIb clinical trial to evaluate the efficacy and safety of oral atomoxetine for the treatment of cognitive and behavioural changes in PSP. Participants receive atomoxetine 40 mg (10 mg/mL oral solution) once daily or a matched placebo solution, in random order, each for 8 weeks. An ‘informant’, who knows the patient with PSP well, is co-recruited to complete some of the trial outcome measures. Participants remain in the trial for 22 weeks after randomisation. The primary objectives are to assess (1) safety and tolerability and (2) efficacy versus placebo on challenging behaviours as reported in a subscale of the Cambridge Behavioural Inventory. Secondary and exploratory measures relate to cognition, the PSP Rating Scale, mood and potential baseline predictors of individual response to atomoxetine computed from imaging, genetic and cognitive measures at baseline.

The trial was approved by the South Central-Oxford B Research Ethics Committee (REC) and the Medicines and Healthcare products Regulatory Agency (REC reference: 20/SC/0416). Dissemination will include publication in peer-reviewed journals, presentations at academic and public conferences and engagement with patients, the public, policymakers and practitioners.

ISRCTN99462035; DOI: https://doi.org/10.1186/ISRCTN99462035; EudraCT (European Union Drug Regulating Authorities Clinical Trials Database)/CTIS (Clinical Trial Information System) number: 2019-004472-19; IRAS (Integrated Research Application System) number: 272063; Secondary identifying numbers: CPMS (Central Portfolio Management System) 44441.

Acute intracerebral haemorrhage (ICH) is devastating with a 1 month mortality rate of ~40%. Cerebral oedema can complicate acute ICH and is associated with poor outcome. In patients with large ICH, the accompanying swelling increases mass effect and causes brain herniation. Mannitol, an osmotic diuretic, is used to treat cerebral oedema after traumatic brain injury, but its safety and efficacy in ICH is unclear. We aim to assess the feasibility of a phase II randomised, controlled trial of mannitol in patients with ICH with, or at risk of, cerebral oedema to inform a definitive trial.

The mannitol for cerebral oedema after acute intracerebral haemorrhage trial (MACE-ICH) aims to include 45 ICH participants from 10 UK sites with estimated largest diameter of haematoma volume >2 cm, presenting within 72 hours of onset with, or at risk of, cerebral oedema (limited Glasgow Coma Scale (GCS)8) with or without mass effect. Participants will be randomised (1:1:1) to 1 g/kg 10% single-dose intravenous mannitol, 1 g/kg 10% mannitol followed by a second dose at 24 hours, or standard care alone. Outcome assessors will be masked to treatment allocation. Feasibility outcomes include proportion of patients approached being randomised, participants receiving allocated treatment, recruitment rate, treatment adherence and follow-up. Secondary outcomes include serum electrolytes and osmolality at days 1–2; change in ICH and oedema volume at day 5; number of participants who developed urinary tract infection, GCS and National Institutes of Health Stroke Scale at day 5±2; length of hospital stay, discharge destination and death up to day 28; death and death or dependency by day 180 and disability (Barthel Index), quality of life (EuroQol, 5-D) and cognition (telephone mini-mental state examination) at day 180.

MACE-ICH received ethics approval from the East Midlands-Leicester Central research ethics committee (22/EM/0242). The trial is funded by a National Institute for Health and Care Research RfPB grant (203080). The results will be published in an academic journal and disseminated through academic conferences and patient support groups. Reporting will be in line with Consolidated Standards of Reporting Trials recommendations.

ISRCTN15383301; EUDRACT 2022-000283-22.

Hyperosmolar therapy is crucial for the management of cerebral oedema and high intracranial pressure. Mannitol and hypertonic saline (HTS) at different concentrations are commonly used in clinical practice, but evidence of their use is mostly derived from studies about traumatic brain injury. The aim of this study was to evaluate the efficacy and safety of hyperosmolar therapy for severe aneurysmal subarachnoid haemorrhage (SAH).

This is a prospective multicentre observational study in which adult patients with severe aneurysmal SAH (Hunt–Hess score ≥3) will be enrolled. At least 124 patients will be enrolled over 2 years. Each enrolled patient will be treated in accordance with relevant management guidelines. The hypertonic agent used will be 20% mannitol (3 mL/kg) or 10% sodium chloride (HTS) (1 mL/kg). The choice and daily dose of the hypertonic agent will be determined by the attending doctor. The primary outcome will be the modified Rankin scale (mRS) score at 30 days after ictus. The secondary outcomes will be the mRS score at 6 months and the incidence of complications during hospitalisation, including phlebitis, acute kidney injury (AKI), hypokalaemia, hyperkalaemia, hyponatraemia, hypernatraemia, vessel spasm, delayed cerebral ischaemia (DCI), subdural effusion and hydrocephalus. An mRS score 0–2 will indicate a favourable outcome, whereas an mRS score 3–6 will indicate an unfavourable outcome. Logistic analysis will be performed to evaluate the association between the hyperosmolar agent and outcome (favourable or unfavourable).

The aim of this multicentre observational study is to provide evidence on the efficacy and safety of hyperosmolar therapy for severe aneurysmal SAH.

This study was approved by the Ethics Committee of Xuanwu Hospital (approval date: 10 July 2023) under protocol V.2.0 (version date: 26 April 2023) (reference number: [2023]086). The results will be published in a peer-reviewed journal and reported at relevant professional conferences.

NCT05858060.