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.

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.

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.

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.

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.

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].

Neurological adverse effects associated with anti-PD1 antibodies alone or in combination with ipilimumab: a multicenter case series.

Anti-programmed cell death protein 1 (PD1) antibodies, pembrolizumab and nivolumab, alone or in combination with ipilimumab, have become standard treatment for melanoma and multiple other malignancies. Neurological adverse effects are rare and have not been well characterized to date. Patients who developed neurological adverse effects while being treated with PD1, alone or in combination with ipilimumab, were retrospectively identified from 10 cancer centers. Fifty-eight patients were included, and the median time from treatment initiation to development of neurological adverse effects was 7 weeks (range, 1-86.5 weeks). Thirty-seven (64%) toxicities affected the peripheral nervous system. Fifty (86%) patients were treated with corticosteroids, with 22 (37%) patients requiring further immunomodulation including intravenous immunoglobulin (16), plasmapheresis (7), mycophenolate mofetil (4), cyclophosphamide (1), and rituximab (1). Twenty-seven (46%) had a complete resolution of their neurological symptoms, and two (4%) patients died secondary to complications from their neurological adverse effects. The response rate of the cancer to immunotherapy was 78%, and the median progression free survival was not reached. Neurological adverse effects can occur with PD1 treatment, do not appear to impact treatment response, but may be irreversible or worsen in some patients. Management may require immunomodulation beyond corticosteroids.

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.

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.

Determining the role and responsibilities of the Australian epilepsy nurse in the management of epilepsy: a study protocol.

INTRODUCTION: Epilepsy is a common neurological condition affecting between 3% and 3.5% of the Australian population at some point in their lifetime. The effective management of chronic and complex conditions such as epilepsy requires person-centred and coordinated care across sectors, from primary to tertiary healthcare. Internationally, epilepsy nurse specialists are frequently identified as playing a vital role in improving the integration of epilepsy care and enhancing patient self-management. This workforce has not been the focus of research in Australia to date. METHODS AND ANALYSIS: This multistage mixed-method study examines the role and responsibilities of epilepsy nurses, particularly in primary and community care settings, across Australia, including through the provision of a nurse helpline service. A nationwide sample of 30 epilepsy nurses will be purposively recruited via advertisements distributed by epilepsy organisations and through word-of-mouth snowball sampling. Two stages (1 and 3) consist of a demographic questionnaire and semistructured interviews (individual or group) with epilepsy nurse participants, with the thematic data analysis from this work informing the areas for focus in stage 3. Stage 2 comprises of a retrospective descriptive analysis of phone call data from Epilepsy Action Australia's National Epilepsy Line service to identify types of users, their needs and reasons for using the service, and to characterise the range of activities undertaken by the nurse call takers. ETHICS AND DISSEMINATION: Ethics approval for this study was granted by Macquarie University (HREC: 52020668117612). Findings of the study will be published through peer-reviewed journal articles and summary reports to key stakeholders, and disseminated through public forums and academic conference presentations. Study findings will also be communicated to people living with epilepsy and families.

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.

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.

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.

Impact of chronic health conditions and injury on school performance and health outcomes in New South Wales, Australia: a retrospective record linkage study protocol.

INTRODUCTION: Children who have sustained a serious injury or who have a chronic health condition, such as diabetes or epilepsy, may have their school performance adversely impacted by the condition, treatment of the condition and/or time away from school. Examining the potential adverse impact requires the identification of children most likely to be affected and the use of objective measures of education performance. This may highlight educational disparities that could be addressed with learning support. This study aims to examine education performance, school completion and health outcomes of children in New South Wales (NSW), Australia, who were hospitalised with an injury or a chronic health condition compared with children who have not been hospitalised for these conditions. METHOD AND ANALYSIS: This research will be a retrospective population-level case-comparison study of hospitalised injured or chronically ill children (ie, diabetes, epilepsy, asthma or mental health conditions) aged ≤18 years in NSW, Australia, using linked health and education administrative data collections. It will examine the education performance, school completion and health outcomes of children who have been hospitalised in NSW with an injury or a chronic health condition compared with children randomly drawn from the NSW population (matched on gender, age and residential postcode) who have not been hospitalised for these conditions. ETHICS AND DISSEMINATION: The study received ethics approval from the NSW Population Health Services Research Ethics Committee (2018HRE0904). Findings from the research will be published in peer-reviewed journals and presented at scientific conferences.

Republished: Successful thrombolysis for acute ischaemic stroke after reversal of dabigatran etexilate with idarucizumab.

In conjunction with BMJ Case Reports, DTB will feature occasional drug-related cases that are likely to be of interest to readers. These will include cases that involve recently marketed drugs for which there is limited knowledge of adverse effects and cases that highlight unusual reactions to drugs that have been marketed for several years.

Successful thrombolysis for acute ischaemic stroke after reversal of dabigatran etexilate with idarucizumab.

We report the experience of reversing dabigatran prior to administering systemic thrombolysis for acute ischaemic cerebellar stroke, which was well tolerated with no haemorrhagic complications after thrombolysis. Given the increasingly common use of dabigatran for atrial fibrillation, the use of idarucizumab to reverse of dabigatran is a novel treatment that should be considered as an important adjunct to facilitate thrombolysis for ischaemic strokes and minimise haemorrhagic complications.

Heidenhain variant sporadic Creutzfeldt-Jakob disease diagnosed as an autoimmune encephalitis due to a false-positive GAD autoantibody.

A 64-year-old man presented with a subacute history progressive visual field defects, illusions and misperceptions. An initial MRI brain revealed a right occipital signal abnormality on diffusion-weighted imaging (DWI) with serum glutamic acid decarboxylase (GAD) autoantibodies markedly elevated. A diagnosis of autoimmune encephalitis was made, with the patient being treated with intravenous immunoglobulin. One month after discharge, the patient represented with worsening frank and well-formed visual hallucinations, ataxia and progressive cognitive impairment. Progress MRI displayed characteristic T2 ribboning on diffusion weighted imaging (DWI) and fluid-attenuated inversion recovery (FLAIR) sequences, along with periodic sharp wave complexes on electroencephalogram (EEG) and a raised CSF protein 14-3-3. Repeat serum, as well as cerebrospinal fluid (CSF), GAD antibodies were again markedly elevated as measured by ELISA (RSR, Cardiff, UK), although archival CSF from the original presentation as well as CSF from the second presentation had undetectable GAD autoantibodies as measured via radioimmunoassay (DIAsource, Ottignies-Louvain-la-Neuve, Belgium). Creutzfeldt-Jakob disease was confirmed at autopsy.

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.