Determining the role and responsibilities of the community epilepsy nurse in the management of epilepsy.

AIMS AND OBJECTIVES: The aim of this study is to enhance the understanding of the core elements and influencing factors on the community-based epilepsy nurse's role and responsibilities. BACKGROUND: Internationally, epilepsy nurse specialists play a key role in providing person-centred care and management of epilepsy but there is a gap in understanding of their role in the community. DESIGN: A national three-stage, mixed-method study was conducted. METHODS: One-on-one, in-depth semi-structured qualitative interviews were conducted online with 12 community-based epilepsy nurses (Stage 1); retrospective analysis of data collected from the National Epilepsy Line, a nurse-led community helpline (Stage 2); and focus group conducted with four epilepsy nurses, to delve further into emerging findings (Stage 3). A thematic analysis was conducted in Stages 1 and 3, and a descriptive statistical analysis of Stage 2 data. Consolidated Criteria for Reporting Qualitative studies checklist was followed for reporting. RESULTS: Three key themes emerged: (1) The epilepsy nurse career trajectory highlighted a lack of standardised qualifications, competencies, and career opportunities. (2) The key components of the epilepsy nurse role explored role diversity, responsibilities, and models of practice in the management of living with epilepsy, and experiences navigating complex fragmented systems and practices. (3) Shifting work practices detailed the adapting work practices, impacted by changing service demands, including COVID-19 pandemic experiences, role boundaries, funding, and resource availability. CONCLUSION: Community epilepsy nurses play a pivotal role in providing holistic, person-centred epilepsy management They contribute to identifying and addressing service gaps through innovating and implementing change in service design and delivery. RELEVANCE TO CLINICAL PRACTICE: Epilepsy nurses' person-centred approach to epilepsy management is influenced by the limited investment in epilepsy-specific integrated care initiatives, and their perceived value is impacted by the lack of national standardisation of their role and scope of practice. NO PATIENT OR PUBLIC CONTRIBUTION: Only epilepsy nurses' perspectives were sought.

Neurodegenerative and Neurodevelopmental Diseases and the Gut-Brain Axis: The Potential of Therapeutic Targeting of the Microbiome.

The human gut microbiome contains the largest number of bacteria in the body and has the potential to greatly influence metabolism, not only locally but also systemically. There is an established link between a healthy, balanced, and diverse microbiome and overall health. When the gut microbiome becomes unbalanced (dysbiosis) through dietary changes, medication use, lifestyle choices, environmental factors, and ageing, this has a profound effect on our health and is linked to many diseases, including lifestyle diseases, metabolic diseases, inflammatory diseases, and neurological diseases. While this link in humans is largely an association of dysbiosis with disease, in animal models, a causative link can be demonstrated. The link between the gut and the brain is particularly important in maintaining brain health, with a strong association between dysbiosis in the gut and neurodegenerative and neurodevelopmental diseases. This link suggests not only that the gut microbiota composition can be used to make an early diagnosis of neurodegenerative and neurodevelopmental diseases but also that modifying the gut microbiome to influence the microbiome-gut-brain axis might present a therapeutic target for diseases that have proved intractable, with the aim of altering the trajectory of neurodegenerative and neurodevelopmental diseases such as Alzheimer's disease, Parkinson's disease, multiple sclerosis, autism spectrum disorder, and attention-deficit hyperactivity disorder, among others. There is also a microbiome-gut-brain link to other potentially reversible neurological diseases, such as migraine, post-operative cognitive dysfunction, and long COVID, which might be considered models of therapy for neurodegenerative disease. The role of traditional methods in altering the microbiome, as well as newer, more novel treatments such as faecal microbiome transplants and photobiomodulation, are discussed.

Hospital service use for young people with chronic health conditions: A population-based matched retrospective cohort study.

AIM: This study aims to identify the hospitalised morbidity associated with three common chronic health conditions among young people using a population-based matched cohort. METHODS: A population-level matched case-comparison retrospective cohort study of young people aged ≤18 years hospitalised with asthma, type 1 diabetes (T1D) or epilepsy during 2005-2018 in New South Wales, Australia using linked birth, health and mortality records. The comparison cohort was matched on age, sex and residential postcode. Adjusted rate ratios (ARR) were calculated by sex and age group. RESULTS: There were 65 055 young people hospitalised with asthma, 6648 with epilepsy, and 2209 with T1D. Young people with epilepsy (ARR 10.95; 95% confidence interval (CI) 9.98-12.02), T1D (ARR 8.64; 95% CI 7.72-9.67) or asthma (ARR 4.39; 95% CI 4.26-4.53) all had a higher risk of hospitalisation than matched peers. Admission risk was highest for males (ARR 11.00; 95% CI 9.64-12.56) and females with epilepsy (ARR 10.83; 95% CI 9.54-12.29) compared to peers. The highest admission risk by age group was for young people aged 10-14 years (ARR 5.50; 95% CI 4.77-6.34) living with asthma, children aged ≤4 years (ARR 12.68; 95% CI 11.35-14.17) for those living with epilepsy, and children aged 5-9 years (ARR 9.12; 95% CI 7.69-10.81) for those living with T1D compared to peers. CONCLUSIONS: The results will guide health service planning and highlight opportunities for better management of chronic health conditions, such as further care integration between acute, primary and community health services for young people.

Hospital service utilization trajectories of individuals living with epilepsy in New South Wales, Australia, 2012-2016: A population-based study.

OBJECTIVES: This study aimed to examine five-year trajectories of hospital service utilization among individuals living with epilepsy in New South Wales (NSW), Australia, and to identify factors predictive of trajectory group membership. METHODS: This study used group-based trajectory modeling of hospital admissions over a five-year period for individuals living with epilepsy who had an epilepsy-related hospitalization during 1 January 2012 and 31 December 2012 in NSW, Australia (n = 5762). RESULTS: The analysis revealed the following five distinct hospital service utilization trajectory groups: "one-off users" (Group 1; 22.9%), "low-chronic users" (Group 2; 47.1%), "moderate-declining users" (Group 3; 10.3%), "moderate-chronic users" (Group 4; 18.3%), and "high-chronic users" (Group 5; 1.5%). There were key features that defined trajectory group membership, in particular the relative proportions of group members with chronic health conditions, other comorbid conditions, refractory epilepsy, and status epilepticus. For instance, "high-chronic users" (Group 5) had higher proportions of individuals with chronic health conditions (34.8%) and refractory epilepsy (19.1%); "moderate-declining users" (Group 3) had higher proportions of individuals with chronic health conditions (35.1%) and status epilepticus (9.8%); and "low-chronic users" (Group 2) had the lowest proportion of individuals with chronic health conditions. CONCLUSION: It is important to gain a better understanding of hospital service utilization among individuals living with epilepsy. This research has identified trajectory groups of hospital service utilization profiles of individuals living with epilepsy. Identification of predictors of trajectory group membership allows targeting of strategies to reduce hospital admissions, inform healthcare service delivery, and improve the health and wellbeing of individuals living with epilepsy.

Enhancing quality of life among epilepsy surgery patients: Interlinking multiple social and relational determinants.

BACKGROUND: Achieving seizure control through resective brain surgery is a major predictor of improved quality of life (QOL) among people with refractory (drug-resistant) epilepsy. Nevertheless, QOL is a comprehensive and dynamic construct, consisting of broad dimensions such as physical health, psychosocial well-being, level of independence, social relationships, and beyond. This study highlights the interlinkage and complementarity of these diverse dimensions, and how in practice, patients, clinicians, and others in a social support system can actively promote QOL among surgery patients. METHOD: Twenty-one qualitative in-depth interviews with patients with refractory epilepsy who are either undergoing presurgical assessment or postsurgery follow-up were conducted, to consider their perspective on QOL in relation to their experience of illness and surgical treatment. Data were thematically analyzed, resulting in three key thematic findings. RESULTS: (1) A myriad of QOL dimensions are highly interrelated and interdependent with mutual 'spin-off' effects: Uncontrolled seizures impacted beyond physical and cognitive health, disrupting important social identities such as being successful parents, spouses, and career professionals. The desire for good clinical outcomes from surgery was justified against the need to mitigate these social and personal concerns. (2) In postsurgery care, there were complementary effects of clinical interventions and social factors on patients' QOL. Psychosocial well-being was supported by a combination of improved physical health, self-confidence, psychological interventions, and social support from employers and educators who were sensitive to patients' specialized needs. (3) Engaging in education, employment, and government services influenced not only socioeconomic well-being, but also a sense of social inclusion. Advocacy made on behalf of patients by clinicians and family members has helped to better manage patients' eligibility for social services provision. CONCLUSION: Quality of life is achieved through a comprehensive and interactive social process, and not simply an outcome measure of clinical treatment. The responses and interactions of many others within the patients' life and treatment process, including family members, clinicians, and social service workers, can culminate to influence QOL, highlighting the importance of a relational and social determinants perspective in patient care.

Identification and referral of patients with refractory epilepsy from the primary to the tertiary care interface in New South Wales, Australia.

OBJECTIVES: This mixed-method feasibility study conducted in New South Wales (NSW), Australia, aimed to explore clinical practices around the identification of patients with refractory epilepsy and referral from primary care to Tertiary Epilepsy Centers. The perceptions of general practitioners, neurologists, and adults living with refractory epilepsy were considered. METHODS: Fifty-two data collection events were achieved through 22 semi-structured interviews with six neurologists and 12 adults who currently have, or have had refractory epilepsy, and four family members, 10 clinical observations of patient consultations and 20 surveys with general practitioners. A thematic analysis was conducted on the qualitative data alongside assessment of observational fieldnotes and survey data. FINDINGS: Two main themes emerged: 1) Patient healthcare pathways and care experiences highlighted the complex and deeply contextualized experiences of both patients and healthcare professionals, from first identification of people's seizures, in primary and community care settings, to referral to Tertiary Epilepsy Centers, shedding light on a fragmented, nonstandardized referral process, influenced by both individual and shared-care practices. 2) Factors impacting referrals and patient pathways indicated that onward referral to a Tertiary Epilepsy Center is affected by the knowledge, or the lack thereof, of healthcare professionals regarding treatment options. Barriers include limited person-centered care, shared decision-making, and refractory epilepsy education for healthcare professionals, which can delay patients' disease identification and can hinder speedy referral pathways and processes, in Australia for up to 17 years. In addition, person-centered communication around care pathways is affected by relationships between clinicians, patients, and family members. CONCLUSION: This study has identified a noticeable lack of standardized care across epilepsy-related healthcare sectors, which recognizes a need for developing and implementing clearer epilepsy-related guidelines and Continuing Professional Development in the primary and community care settings. This, however, requires greater collaboration and commitment in the primary, community, and tertiary care sectors to address the ongoing misconceptions around professional roles and responsibilities to optimize shared-care practices. Ultimately, prioritizing person-centered care on both patients' and professionals' agendas, in order to improve satisfaction with care experiences of people living with complex epilepsy.

Guillain-Barré syndrome: clinical features, treatment choices and outcomes in an Australian cohort.

BACKGROUND: Guillain-Barré syndrome (GBS) causes acute neuromuscular weakness. Severe cases are life-threatening and many are left disabled. Intravenous immunoglobulin (IVIg) and plasma exchange (PE), along with supportive care, are the mainstays of treatment. Treatment choice is influenced by multiple factors. The clinico-epidemiological features of GBS in Australia have not been reviewed in 30 years and few studies have assessed contemporary treatment choices. AIMS: To investigate the clinico-epidemiological features, choice of treatment, clinical course and outcomes of GBS patients in an Australian tertiary metropolitan hospital. METHODS: A retrospective observational study was performed of GBS presentations to a tertiary hospital in Sydney, Australia, over 5 years. Clinico-epidemiological features, treatment choices, clinical course and outcomes were assessed. RESULTS: We reviewed 46 GBS patients (54% male), average age 55 years. Antecedent infection was identified in 61%. Twenty-eight per cent had preceding immunogenic events or conditions. Acute inflammatory demyelinating polyradiculoneuropathy was the most common subtype (78%). Cerebrospinal fluid albumino-cytologic dissociation was present in 43%. Electrodiagnostic testing most frequently demonstrated demyelination (64%). Ninety-eight per cent received immunotherapy, mostly IVIg (93%). Twenty-two per cent received further treatment due to treatment-related fluctuations or lack of improvement. Thirteen per cent required ICU admission and 46% needed rehabilitation. There were no deaths or need for mechanical ventilation. Seventy-one per cent of the follow-up cohort had residual disability at 6 months, but this was generally mild. CONCLUSIONS: The clinico-epidemiological features are consistent with previous cohorts. Our experience in a large Australian tertiary centre demonstrates a clear preference for IVIg over PE.

Promoting faster pathways to surgery: a clinical audit of patients with refractory epilepsy.

BACKGROUND: Individuals with epilepsy who cannot be adequately controlled with anti-epileptic drugs, refractory epilepsy, may be suitable for surgical treatment following detailed assessment. This is a complex process and there are concerns over delays in referring refractory epilepsy patients for surgery and subsequent treatment. The aim of this study was to explore the different patient pathways, referral and surgical timeframes, and surgical and medical treatment options for refractory epilepsy patients referred to two Tertiary Epilepsy Clinics in New South Wales, Australia. METHODS: Clinical records were reviewed for 50 patients attending the two clinics, in two large teaching hospitals (25 in Clinic 1; 25 in Clinic 2. A purpose-designed audit tool collected detailed aspects of outpatient consultations and treatment. Patients with refractory epilepsy with their first appointment in 2014 were reviewed for up to six visits until the end of 2016. Data collection included: patient demographics, type of epilepsy, drug management, and assessment for surgery. Outcomes included: decisions regarding surgical and/or medical management, and seizure status following surgery. Patient-reported outcome measures to assess anxiety and depression were collected in Clinic 1 only. RESULTS: Patient mean age was 38.3 years (SD 13.4), the mean years since diagnosis was 17.3 years (SD 9.8), and 88.0% of patients had a main diagnosis of focal epilepsy. Patients were taking an average of 2.3 (SD 0.9) anti-epileptic drugs at the first clinic visit. A total of 17 (34.0%) patients were referred to the surgical team and 11 (22.0%) underwent a neuro-surgical procedure. The average waiting time between visit 1 to surgical referral was 38.8 weeks (SD 25.1), and between visit 1 and the first post-operative visit was 55.8 weeks (SD 25.0). CONCLUSION: The findings confirm international data showing significant waiting times between diagnosis of epilepsy and referral to specialist clinics for surgical assessment and highlight different approaches in each clinic in terms of visit numbers and recorded activities. A standardised pathway and data collection, including patient-reported outcome measures, would provide better evidence for whether promoting earlier referral and assessment for surgery improves the lives of this disease group.

Determinants of health and wellbeing in refractory epilepsy and surgery: The Patient Reported, ImpleMentation sciEnce (PRIME) model.

This paper offers a new way of understanding the course of a chronic, neurological condition through a comprehensive model of patient-reported determinants of health and wellbeing: The Patient Reported ImpleMentation sciEnce (PRIME) model is the first model of its kind to be based on patient-driven insights for the design and implementation of initiatives that could improve tertiary, primary, and community healthcare services for patients with refractory epilepsy, and has broad implications for other disorders; PRIME focuses on: patient-reported determinants of health and wellbeing, pathways through care, gaps in treatment and other system delays, patient need and expectation, and barriers and facilitators to high-quality care provision; PRIME highlights that in the context of refractory epilepsy, patients value appropriate, clear, and speedy referrals from primary care practitioners and community neurologists to specialist healthcare professionals based in tertiary epilepsy centers. Many patients also want to share in decisions around treatment and care, and gain a greater understanding of their debilitating disease, so as to find ways to self-manage their illness more effectively and plan for the future. Here, PRIME is presented using refractory epilepsy as the exemplar case, while the model remains flexible, suitable for adaptation to other settings, patient populations, and conditions; PRIME comprises six critical levels: 1) The Individual Patient Model; 2) The Patient Relationships Model; 3) The Patient Care Pathways Model; 4) The Patient Transitions Model; 5) The Pre- and Postintervention Model; and 6) The Comprehensive Patient Model. Each level is dealt with in detail, while Levels 5 and 6 are presented in terms of where the gaps lie in our current knowledge, in particular in relation to patients' journeys through healthcare, system intersections, and individuals adaptive behavior following resective surgery, as well as others' views of the disease, such as family members.

Evidence for cannabis and cannabinoids for epilepsy: a systematic review of controlled and observational evidence.

Review evidence for cannabinoids as adjunctive treatments for treatment-resistant epilepsy. Systematic search of Medline, Embase and PsycINFO was conducted in October 2017. Outcomes were: 50%+ seizure reduction, complete seizure freedom; improved quality of life (QoL). Tolerability/safety were assessed by study withdrawals, adverse events (AEs) and serious adverse events (SAEs). Analyses were conducted in Stata V.15.0. 36 studies were identified: 6 randomised controlled trials (RCTs), 30 observational studies. Mean age of participants was 16.1 years (range 0.5-55 years). Cannabidiol (CBD) 20 mg/kg/day was more effective than placebo at reducing seizure frequency by 50%+(relative risk (RR) 1.74, 95% CI 1.24 to 2.43, 2 RCTs, 291 patients, low Grades of Recommendation, Assessment, Development and Evaluation (GRADE) rating). The number needed to treat for one person using CBD to experience 50%+ seizure reduction was 8 (95% CI 6 to 17). CBD was more effective than placebo at achieving complete seizure freedom (RR 6.17, 95% CI 1.50 to 25.32, 3 RCTs, 306 patients, low GRADE rating), and improving QoL (RR 1.73, 95% CI 1.33 to 2.26), however increased risk of AEs (RR 1.24, 95% CI 1.13 to 1.36) and SAEs (RR 2.55, 95% CI 1.48 to 4.38). Pooled across 17 observational studies, 48.5% (95% CI 39.0% to 58.1%) of patients reported 50%+ reductions in seizures; in 14 observational studies 8.5% (95% CI 3.8% to 14.5%) were seizure-free. Twelve observational studies reported improved QoL (55.8%, 95% CI 40.5 to 70.6); 50.6% (95% CI 31.7 to 69.4) AEs and 2.2% (95% CI 0 to 7.9) SAEs. Pharmaceutical-grade CBD as adjuvant treatment in paediatric-onset drug-resistant epilepsy may reduce seizure frequency. Existing RCT evidence is mostly in paediatric samples with rare and severe epilepsy syndromes; RCTs examining other syndromes and cannabinoids are needed. PROSPERO REGISTRATION NUMBER: CRD42017055412.

Examining health service utilization, hospital treatment cost, and mortality of individuals with epilepsy and status epilepticus in New South Wales, Australia 2012-2016.

This study examined the health service utilization and hospital treatment cost of individuals with epilepsy by age group, mortality within 30days, and surgical outcomes for individuals with refractory epilepsy in New South Wales (NSW), Australia. A retrospective examination of linked hospitalization and mortality data for individuals hospitalized with a diagnosis of epilepsy during 2012-2016. Hospitalized incidence rates per 1000 population were calculated, and negative binomial regression was used to examine temporal trends. Mortality within 30days of hospitalization was identified, along with cause of death. There were 44,722 hospitalizations during the five-year period, with a hospitalization rate of 85.6 per 1000 population (95% confidence interval (CI): 84.7-86.4). Total hospital treatment costs were AUD$402.9 million. Children aged ≤17years accounted for 32.0% of hospitalizations. Just over half to two-thirds of hospitalizations for each age group were for a principal diagnosis of epilepsy, with 2976 hospitalizations of individuals for status epilepticus. The overall mean hospital length of stay (LOS) for epilepsy hospitalizations was 5.1days (standard deviation (SD)=9.0). Thirty-day mortality was highest for individuals aged ≥65years (6.7%), and epilepsy was identified as the underlying cause of death for 18.2% of deaths. This research has provided insight into the healthcare utilization profiles of individuals with epilepsy at different ages. Epilepsy hospitalizations constitute a substantial cost to the healthcare system, and better overall management of seizures and comorbid conditions is likely to lead to a reduction in the need for hospitalization.

Leading up to saying "yes": A qualitative study on the experience of patients with refractory epilepsy regarding presurgical investigation for resective surgery.

OBJECTIVES: Adult patients with refractory epilepsy who are potential candidates for resective surgery undergo a period of presurgical investigation in tertiary epilepsy centers (TECs), where they engage extensively with healthcare professionals and receive a range of treatment-related information. This qualitative study aimed to examine the experiences of adult patients with refractory epilepsy leading up to and during presurgical investigation and how their perceptions of resective surgery are shaped. METHODS: In-depth interviews with 12 patients and six epilepsy specialist clinicians and 12 observations of routine patient-clinician consultations took place at two TECs in Sydney, Australia. Data were thematically analyzed via group work. RESULTS: Patients reflected on prior experiences of poor seizure control and inadequate antiepileptic drug management and a lack of clarity about their condition before referral to tertiary care. Poor continuity of care and disrupted care transitions affected patients from regional locations. Tertiary referral increased engagement with personalized information about refractory epilepsy, which intensified during presurgical assessments with additional hospital visits and consultations. Experiential information, such as testimonials of other patients, influenced perceptions of surgery and fostered more trust and confidence towards healthcare professionals. CONCLUSION: Qualitative inquiry detailed multifaceted effects of information on patients' overall treatment trajectory and experience of healthcare. Earlier patient identification for surgical assessments should be accompanied by access to good quality information at primary and community care levels and strengthened referral processes.

Reversible cerebral vasoconstriction syndrome.

Reversible cerebral vasoconstriction syndrome (RCVS) is a relatively rare, non-progressive angiopathy frequently heralded by severe thunderclap headache. It is characterised by vasoconstriction of cerebral arteries which usually resolves within three months of onset. Transient focal neurological signs may occur, and persistent deficits associated with haemorrhagic comorbidities have been reported in a small percentage of individuals. In this paper we report the case of RH, a 36-year-old woman who presented at a university teaching hospital in Sydney with a clinical history and radiological evidence consistent with RCVS. There were no haemorrhagic events during the course of her illness, and vasoconstriction resolved within a few days, following treatment with verapamil. Neuropsychological evaluation 16 months later revealed significant deficits in autobiographical memory, verbal and non-verbal new learning and active delayed recall, cognitive flexibility, abstraction and (to a lesser extent) immediate attention span and information processing speed. RH's case was unusual because the "trigger" for RCVS (Ear, Nose and Throat surgery) has not been previously reported, and because despite there being no haemorrhagic complications during the course of RCVS and no subsequent radiological abnormalities, she had significant cognitive impairment. To date, persistent neuropsychological deficits have not been recognised as a feature of RCVS.

Risk-adjusted hospital mortality rates for stroke: evidence from the Australian Stroke Clinical Registry (AuSCR).

OBJECTIVES: Hospital data used to assess regional variability in disease management and outcomes, including mortality, lack information on disease severity. We describe variance between hospitals in 30-day risk-adjusted mortality rates (RAMRs) for stroke, comparing models that include or exclude stroke severity as a covariate. DESIGN: Cohort design linking Australian Stroke Clinical Registry data with national death registrations. Multivariable models using recommended statistical methods for calculating 30-day RAMRs for hospitals, adjusted for demographic factors, ability to walk on admission, stroke type, and stroke recurrence. SETTING: Australian hospitals providing at least 200 episodes of acute stroke care, 2009-2014. MAIN OUTCOME MEASURES: Hospital RAMRs estimated by different models. Changes in hospital rank order and funnel plots were used to explore variation in hospital-specific 30-day RAMRs; that is, RAMRs more than three standard deviations from the mean. RESULTS: In the 28 hospitals reporting at least 200 episodes of care, there were 16 218 episodes (15 951 patients; median age, 77 years; women, 46%; ischaemic strokes, 79%). RAMRs from models not including stroke severity as a variable ranged between 8% and 20%; RAMRs from models with the best fit, which included ability to walk and stroke recurrence as variables, ranged between 9% and 21%. The rank order of hospitals changed according to the covariates included in the models, particularly for those hospitals with the highest RAMRs. Funnel plots identified significant deviation from the mean overall RAMR for two hospitals, including one with borderline excess mortality. CONCLUSIONS: Hospital stroke mortality rates and hospital performance ranking may vary widely according to the covariates included in the statistical analysis.

Parkinson's Disease and Photobiomodulation: Potential for Treatment.

Parkinson's disease is the second most common neurodegenerative disease and is increasing in incidence. The combination of motor and non-motor symptoms makes this a devastating disease for people with Parkinson's disease and their care givers. Parkinson's disease is characterised by mitochondrial dysfunction and neuronal death in the substantia nigra, a reduction in dopamine, accumulation of α-synuclein aggregates and neuroinflammation. The microbiome-gut-brain axis is also important in Parkinson's disease, involved in the spread of inflammation and aggregated α-synuclein. The mainstay of Parkinson's disease treatment is dopamine replacement therapy, which can reduce some of the motor signs. There is a need for additional treatment options to supplement available medications. Photobiomodulation (PBM) is a form of light therapy that has been shown to have multiple clinical benefits due to its enhancement of the mitochondrial electron transport chain and the subsequent increase in mitochondrial membrane potential and ATP production. PBM also modulates cellular signalling and has been shown to reduce inflammation. Clinically, PBM has been used for decades to improve wound healing, treat pain, reduce swelling and heal deep tissues. Pre-clinical experiments have indicated that PBM has the potential to improve the clinical signs of Parkinson's disease and to provide neuroprotection. This effect is seen whether the PBM is directed to the head of the animal or to other parts of the body (remotely). A small number of clinical trials has given weight to the possibility that using PBM can improve both motor and non-motor clinical signs and symptoms of Parkinson's disease and may potentially slow its progression.

A novel transcranial photobiomodulation device to address motor signs of Parkinson's disease: a parallel randomised feasibility study.

Background: Parkinson's disease is a progressive neurological disease with limited treatment options. Animal models and a proof-of-concept case series have suggested that photobiomodulation may be an effective adjunct treatment for the symptoms of Parkinson's disease. The aim was to determine the safety and feasibility of transcranial photobiomodulation (tPBM) to reduce the motor signs of Parkinson's disease. Methods: In this double-blind, randomised, sham-controlled feasibility trial, patients (aged 59-85 years) with idiopathic Parkinson's disease were treated with a tPBM helmet for 12 weeks (72 treatments with either active or sham therapy; stage 1). Treatment was delivered in the participants' homes, monitored by internet video conferencing (Zoom). Stage 1 was followed by 12 weeks of no treatment for those on active therapy (active-to-no-treatment group), and 12 weeks of active treatment for those on sham (sham-to-active group), for participants who chose to continue (stage 2). The active helmet device delivered red and infrared light to the head for 24 min, 6 days per week. The primary endpoints were safety and motor signs, as assessed by a modified Movement Disorders Society revision of the Unified Parkinson's Disease Rating Scale Part III (MDS-UPDRS-III)-motor scale. This trial is registered with ANZCTR, ACTRN 12621001722886. Findings: Between Dec 6, 2021, and Aug 12, 2022, 20 participants were randomly allocated to each of the two groups (10 females plus 10 males per group). All participants in the active group and 18 in the sham group completed 12 weeks of treatment. 14 participants in the sham group chose to continue to active treatment and 12 completed the full 12 weeks of active treatment. Treatment was well tolerated and feasible to deliver, with only minor, temporary adverse events. Of the nine suspected adverse events that were identified, two minor reactions may have been attributable to the device in the sham-to-active group during the active treatment weeks of the trial. One participant experienced temporary leg weakness. A second participant reported decreased fine motor function in the right hand. Both participants continued the trial. The mean modified MDS-UPDRS-III scores for the sham-to-active group at baseline, after 12 weeks of sham treatment, and after 12 weeks of active treatment were 26.8 (sd 14.6), 20.4 (sd 12.8), and 12.2 (sd 8.9), respectively, and for the active-to-no-treatment group these values were 21.3 (sd 9.4), 16.5 (sd 9.4), and 15.3 (sd 10.8), respectively. There was no significant difference between groups at any assessment point. The mean difference between groups at baseline was 5.5 (95% confidence interval (CI) -2.4 to 13.4), after stage 1 was 3.9 (95% CI -3.5 to 11.3 and after stage 2 was -3.1 (95% CI 2.7 to -10.6). Interpretation: Our findings add to the evidence base to suggest that tPBM is a safe, tolerable, and feasible non-pharmaceutical adjunct therapy for Parkinson's disease. While future work is needed our results lay the foundations for an adequately powered randomised placebo-controlled clinical trial. Funding: SYMBYX Pty Ltd.

A Randomized Placebo-Controlled Study of a Transcranial Photobiomodulation Helmet in Parkinson's Disease: Post-Hoc Analysis of Motor Outcomes.

Emerging evidence is increasingly supporting the use of transcranial photobiomodulation (tPBM) to improve symptoms of neurodegenerative diseases, including Parkinson's disease (PD). The objective of this study was to analyse the safety and efficacy of tPBM for PD motor symptoms. The study was a triple blind, randomized placebo-controlled trial with 40 idiopathic PD patients receiving either active tPBM (635 nm plus 810 nm LEDs) or sham tPBM for 24 min per day (56.88J), six days per week, for 12 weeks. The primary outcome measures were treatment safety and a 37-item MDS-UPDRS-III (motor domain) assessed at baseline and 12 weeks. Individual MDS-UPDRS-III items were clustered into sub-score domains (facial, upper-limb, lower-limb, gait, and tremor). The treatment produced no safety concerns or adverse events, apart from occasional temporary and minor dizziness. There was no significant difference in total MDS-UPDRS-III scores between groups, presumably due to the placebo effect. Additional analyses demonstrated that facial and lower-limb sub-scores significantly improved with active treatment, while gait and lower-limb sub-scores significantly improved with sham treatment. Approximately 70% of participants responded to active treatment (≥5 decrease in MDS-UPDRS-III score) and improved in all sub-scores, while sham responders improved in lower-limb sub-scores only. tPBM appears to be a safe treatment and improved several PD motor symptoms in patients that responded to treatment. tPBM is proving to be increasingly attractive as a possible non-pharmaceutical adjunct therapy.

Risk of impaired school performance in children hospitalized with concussion: a population-based matched cohort study.

Aim: To examine the impact of concussion on objective measures of school performance. Materials & methods: Population-based matched cohort study using linked health and education records of young people aged ≤18 years hospitalized with concussion in New South Wales, Australia, during 2005-2018, and matched comparisons not hospitalized with any injury. Results: Young people with concussion had higher risk of not achieving the national minimum standards for literacy and numeracy assessments, ranging from 30% for numeracy to 43% for spelling, and not completing high school, ranging from 29% for year 10 to 77% for year 12, compared with matched peers. Conclusion: Young people hospitalized with concussion have impaired school performance compared with uninjured matched peers.

The impact of childhood epilepsy on academic performance: A population-based matched cohort study.

OBJECTIVES: To compare academic performance and high school completion of young people admitted to hospital with epilepsy and matched peers from the general population not admitted to hospital with epilepsy during the study period. METHODS: A population-based matched case-comparison cohort study of young people aged ≤18 years hospitalised with epilepsy during 2005-2018 in New South Wales, Australia, using linked birth, health, education, and mortality records. The comparison cohort was matched on age, sex, and residential postcode. Generalised linear mixed modelling examined risk of school performance below the national minimum standard (NMS), and generalised linear regression examined risk of not completing high school for young people hospitalised with epilepsy compared to matched peers not hospitalised with epilepsy during the study period. Adjusted relative risks (ARRs) with 95% confidence intervals (CIs) were derived from the final models. RESULTS: Young people hospitalised with epilepsy had more than 3 times higher risk of not achieving the NMS for numeracy (ARR: 3.40; 95%CI 2.76‒4.18) and reading (ARR: 3.15; 95%CI 2.60‒3.82), compared to matched peers. Young people hospitalised with epilepsy had a 78% higher risk of not completing year 10 (ARR: 1.78; 95%CI 1.14‒2.79), 18% higher risk of not completing year 11 (ARR: 1.18; 95%CI 0.97‒1.45), and 38% higher risk of not completing year 12 (ARR: 1.38; 95%CI 1.14‒1.67), compared to matched counterparts. CONCLUSION: Young people hospitalised with epilepsy have higher risk of not achieving minimum standards for numeracy and reading and not completing high school compared to matched peers. There is a need for effective strategies and interventions (e.g., early seizure control and improved multidisciplinary management and care coordination) to minimise the potential adverse effect of epilepsy on education and its sequelae such as early school leaving, unemployment and poverty in adulthood.

Protocol for randomized controlled trial to evaluate the safety and feasibility of a novel helmet to deliver transcranial light emitting diodes photobiomodulation therapy to patients with Parkinson's disease.

Introduction: Parkinson's disease (PD) is the second most common, progressive, and debilitating neurodegenerative disease associated with aging and the most common movement disorder. Photobiomodulation (PBM), the use of non-thermal light for therapeutic purposes using laser or light emitting diodes (LED) is an emerging non-invasive treatment for a diverse range of neurological conditions. The main objectives of this clinical trial are to investigate the feasibility, safety, tolerability, and efficacy of a novel transcranial LED helmet device (the "PDNeuro") in the alleviation of symptoms of PD. Methods and analysis: This is a 24-week, two-arm, triple-blinded randomized placebo-controlled clinical trial of a novel transcranial "PDNeuro" LED Helmet, comparing an active helmet to a sham helmet device. In a survey, 40 PD participants with Hoehn and Yahr Stage I-III during ON periods will be enrolled and randomly assigned into two groups. Both groups will be monitored weekly for the safety and tolerability of the "PDNeuro" LED Helmet. Clinical signs and symptoms assessed will include mobility, fine motor skills and cognition, with data collected at baseline, 12 weeks, and 24 weeks. Assessment tools include the TUG, UPDRS, and MoCA all validated for use in PD patients. Patient's adherence to the device usage and participant drop out will be monitored weekly. At 12 weeks both placebo and treatment groups will crossover and placebo participants offered the treatment. The main indicator for clinical efficacy of the "PDneuro" Helmet is evidence of sustained improvements in motor and non-motor symptoms obtained from participant self-reported changes, carer reporting of changes and objective reassessment by the investigators. The outcomes will assist in a future larger randomized trial design. Clinical Trial Registration: [https://www.anzctr.org.au], identifier [12621001722886].