Search

Patients diagnosed with functional (psychogenic nonepileptic) seizures have similar or greater levels of disability, morbidity and mortality than people with epilepsy, but there are far fewer treatment services. In contrast to epilepsy, the current understanding of pathophysiological mechanisms and the development of evidence-based treatments for functional seizures is rudimentary. This leads to high direct healthcare costs and high indirect costs to the patient, family and wider society. There are many patient, clinician and system-level barriers to improving outcomes for functional seizures. At a patient level, these include the heterogeneity of symptoms, diagnostic uncertainty, family factors and difficulty in perceiving psychological aspects of illness and potential benefits of treatment. Clinician-level barriers include sub-specialism, poor knowledge, skills and attitudes and stigma. System-level barriers include the siloed nature of healthcare, the high prevalence of functional seizures and funding models relying on individual medical practitioners. Through the examination of international examples and expert recommendations, several themes emerge that may address some of these barriers. These include (1) stepped care with low-level, brief generalised interventions, proceeding to higher level, extended and individualised treatments; (2) active triage of complexity, acuity and treatment readiness; (3) integrated interdisciplinary teams that individualise formulation, triage, and treatment planning and (4) shared care with primary, emergency and community providers and secondary consultation. Consideration of the application of these principles to the Australian and New Zealand context is proposed as a significant opportunity to meet an urgent need. [ABSTRACT FROM AUTHOR]

Objective: Schizophrenia, a complex psychiatric disorder, is often associated with cognitive, neurological and neuroimaging abnormalities. The processes underlying these abnormalities, and whether a subset of people with schizophrenia have a neuroprogressive or neurodegenerative component to schizophrenia, remain largely unknown. Examining fluid biomarkers of diverse types of neuronal damage could increase our understanding of these processes, as well as potentially provide clinically useful biomarkers, for example with assisting with differentiation from progressive neurodegenerative disorders such as Alzheimer and frontotemporal dementias. Methods: This study measured plasma neurofilament light chain protein (NfL) using ultrasensitive Simoa technology, to investigate the degree of neuronal injury in a well-characterised cohort of people with treatment-resistant schizophrenia on clozapine (n = 82), compared to first-degree relatives (an at-risk group, n = 37), people with schizophrenia not treated with clozapine (n = 13), and age- and sex-matched controls (n = 59). Results: We found no differences in NfL levels between treatment-resistant schizophrenia (mean NfL, M = 6.3 pg/mL, 95% confidence interval: [5.5, 7.2]), first-degree relatives (siblings, M = 6.7 pg/mL, 95% confidence interval: [5.2, 8.2]; parents, M after adjusting for age = 6.7 pg/mL, 95% confidence interval: [4.7, 8.8]), controls (M = 5.8 pg/mL, 95% confidence interval: [5.3, 6.3]) and not treated with clozapine (M = 4.9 pg/mL, 95% confidence interval: [4.0, 5.8]). Exploratory, hypothesis-generating analyses found weak correlations in treatment-resistant schizophrenia, between NfL and clozapine levels (Spearman's r = 0.258, 95% confidence interval: [0.034, 0.457]), dyslipidaemia (r = 0.280, 95% confidence interval: [0.064, 0.470]) and a negative correlation with weight (r = −0.305, 95% confidence interval: [−0.504, −0.076]). Conclusion: Treatment-resistant schizophrenia does not appear to be associated with neuronal, particularly axonal degeneration. Further studies are warranted to investigate the utility of NfL to differentiate treatment-resistant schizophrenia from neurodegenerative disorders such as behavioural variant frontotemporal dementia, and to explore NfL in other stages of schizophrenia such as the prodome and first episode. [ABSTRACT FROM AUTHOR]

Objectives: Survival information in dementia is important for future planning and service provision. There have been limited Australian data investigating survival duration and risk factors associated with mortality in younger-onset dementia. Methods: This was a cross-sectional retrospective study investigating survival in inpatients with a diagnosis of dementia admitted to a tertiary neuropsychiatry service from 1991 to 2014. The Australian Institute of Health and Welfare National Death Index was used to obtain mortality information. Results: A total of 468 inpatients were identified, of which 75% had symptom onset at ⩽65 years of age (defined as younger-onset dementia). Dementia was categorised into four subtypes, Alzheimer's dementia, frontotemporal dementia, vascular dementia and other dementias; 72% of the patients had died. Overall median survival duration was 10.6 years with no significant differences in duration within the dementia subtypes (p = 0.174). Survival in older-onset dementia (symptom onset at >65 years of age) was about half of that in younger-onset dementia (median survival 6.3 years compared to 12.7 years, respectively). Independent predictors of mortality were having older-onset dementia (hazard ratio: 3.2) and having initial presenting symptoms being cognitive in nature (hazard ratio: 1.5). Females with an older-onset dementia had longer survival compared to males with an older-onset dementia, and this was reversed for younger-onset dementia. Older-onset dementia and younger-onset dementia conferred 3 and 6 times, respectively, increased risk of death compared to the general population. Conclusion: This is the largest Australian study to date investigating survival and risk factors to mortality in dementia. We report important clinical information to patients with dementia and their families about prognosis which will assist with future planning. Our findings suggest that for both older-onset dementia and younger-onset dementia, 'new onset' psychiatric symptoms precede the cognitive symptoms of a neurodegenerative process. This, and sex differences in survival depending on the age of onset of the dementia warrant further investigation. [ABSTRACT FROM AUTHOR]

Deep brain stimulation has shown promise for the treatment of severe, treatment-refractory obsessive-compulsive disorder. With the recent publication of the first Australian, randomised, sham-controlled trial of deep brain stimulation for obsessive-compulsive disorder, there are now four placebo-controlled trials demonstrating the efficacy of this therapy. Together with recent data identifying a biological substrate of effective stimulation that can predict response and that has been successfully reproduced, studies comparing and finding equivalent efficacy among different targets, as well as recent, large, open trials supporting the long-term effectiveness of deep brain stimulation, we argue that this should now be considered an accepted therapy for a select group of patients in the Australasian setting. We call on the Royal Australian and New Zealand College of Psychiatrists to revise their memorandum describing deep brain stimulation for obsessive-compulsive disorder as an ' experimental ' treatment and recognise that it has proven efficacy. We stress that this should remain a therapy offered only to those with high treatment-refractory illnesses and only at specialised centres where there is an experienced multidisciplinary team involved in work-up, implantation and follow-up and also where frameworks are in place to provide careful clinical governance and ensure appropriate fully informed consent. [ABSTRACT FROM AUTHOR]

The authors comment on the need for action to improve identification, diagnosis, treatment and care of patients with young onset dementia (YOD) in Australia. Topics discussed include the aetiology of YOD, the two Australian Royal Commissions affecting people with YOD, the need to improve professional understanding of YOD to reduce the time of diagnosis, and the need to improve diagnostic accuracy.

Although COVID-19 is predominantly a respiratory disease, it is known to affect multiple organ systems. In this article, we highlight the impact of SARS-CoV-2 (the coronavirus causing COVID-19) on the central nervous system as there is an urgent need to understand the longitudinal impacts of COVID-19 on brain function, behaviour and cognition. Furthermore, we address the possibility of intergenerational impacts of COVID-19 on the brain, potentially via both maternal and paternal routes. Evidence from preclinical models of earlier coronaviruses has shown direct viral infiltration across the blood–brain barrier and indirect secondary effects due to other organ pathology and inflammation. In the most severely ill patients with pneumonia requiring intensive care, there appears to be additional severe inflammatory response and associated thrombophilia with widespread organ damage, including the brain. Maternal viral (and other) infections during pregnancy can affect the offspring, with greater incidence of neurodevelopmental disorders, such as autism, schizophrenia and epilepsy. Available reports suggest possible vertical transmission of SARS-CoV-2, although longitudinal cohort studies of such offspring are needed. The impact of paternal infection on the offspring and intergenerational effects should also be considered. Research targeted at mechanistic insights into all aspects of pathogenesis, including neurological, neuropsychiatric and haematological systems alongside pulmonary pathology, will be critical in informing future therapeutic approaches. With these future challenges in mind, we highlight the importance of national and international collaborative efforts to gather the required clinical and preclinical data to effectively address the possible long-term sequelae of this global pandemic, particularly with respect to the brain and mental health. [ABSTRACT FROM AUTHOR]

Objective: Neurofilament light has shown promise as a biomarker for diagnosis, staging and prognosis in a wide range of neurological and neurodegenerative disorders. This study explored the utility of cerebrospinal fluid neurofilament light in distinguishing primary psychiatric disorders from neurodegenerative and neurological disorders, a common diagnostic dilemma for psychiatrists and neurologists. Methods: This cross-sectional retrospective pilot study assessed cerebrospinal fluid neurofilament light on patients referred to a tertiary neuropsychiatry service from 2009 to 2017 for diagnostic assessment of neuropsychiatric and neurocognitive symptoms, where a neurodegenerative disorder was a differential diagnosis, who received lumbar punctures as part of a comprehensive workup. The most recent gold-standard clinical consensus diagnosis was categorised into psychiatric disorder or neurodegenerative or neurological disorder. Data from healthy controls were available for comparison. Data extraction and diagnostic categorisation was blinded to neurofilament light results. Results: A total of 129 participants were included: 77 neurodegenerative or neurological disorder (mean age 57 years, including Alzheimer's dementia, frontotemporal dementia), 31 psychiatric disorder (mean age 51 years, including schizophrenia, major depressive disorder) and 21 healthy controls (mean age 66 years). Neurofilament light was significantly higher in neurodegenerative or neurological disorder (M = 3560 pg/mL, 95% confidence intervals = [2918, 4601]) compared to psychiatric disorder (M = 949 pg/mL, 95% confidence intervals = [830, 1108]) and controls (M = 1036 pg/mL, 95% confidence intervals = [908, 1165]). Neurofilament light distinguished neurodegenerative or neurological disorder from psychiatric disorder with an area under the curve of 0.94 (95% confidence intervals = [0.89, 0.98]); a cut-off of 1332 pg/mL was associated with 87% sensitivity and 90% specificity. Conclusion: Cerebrospinal fluid neurofilament light shows promise as a diagnostic test to assist with the often challenging diagnostic dilemma of distinguishing psychiatric disorders from neurodegenerative and neurological disorders. Further studies are warranted to replicate and expand on these findings, including on plasma neurofilament light. [ABSTRACT FROM AUTHOR]

Objective: Deep brain stimulation can be of benefit in carefully selected patients with severe intractable obsessive-compulsive disorder. The aim of this paper is to describe the outcomes of the first seven deep brain stimulation procedures for obsessive-compulsive disorder undertaken at the Neuropsychiatry Unit, Royal Melbourne Hospital. The primary objective was to assess the response to deep brain stimulation treatment utilising the Yale-Brown Obsessive Compulsive Scale as a measure of symptom severity. Secondary objectives include assessment of depression and anxiety, as well as socio-occupational functioning. Methods: Patients with severe obsessive-compulsive disorder were referred by their treating psychiatrist for assessment of their suitability for deep brain stimulation. Following successful application to the Psychosurgery Review Board, patients proceeded to have deep brain stimulation electrodes implanted in either bilateral nucleus accumbens or bed nucleus of stria terminalis. Clinical assessment and symptom rating scales were undertaken pre- and post-operatively at 6- to 8-week intervals. Rating scales used included the Yale-Brown Obsessive Compulsive Scale, Obsessive Compulsive Inventory, Depression Anxiety Stress Scale and Social and Occupational Functioning Assessment Scale. Results: Seven patients referred from four states across Australia underwent deep brain stimulation surgery and were followed for a mean of 31 months (range, 8–54 months). The sample included four females and three males, with a mean age of 46 years (range, 37–59 years) and mean duration of obsessive-compulsive disorder of 25 years (range, 15–38 years) at the time of surgery. The time from first assessment to surgery was on average 18 months. All patients showed improvement on symptom severity rating scales. Three patients showed a full response, defined as greater than 35% improvement in Yale-Brown Obsessive Compulsive Scale score, with the remaining showing responses between 7% and 20%. Conclusion: Deep brain stimulation was an effective treatment for obsessive-compulsive disorder in these highly selected patients. The extent of the response to deep brain stimulation varied between patients, as well as during the course of treatment for each patient. The results of this series are comparable with the literature, as well as having similar efficacy to ablative psychosurgery techniques such as capsulotomy and cingulotomy. Deep brain stimulation provides advantages over lesional psychosurgery but is more expensive and requires significant multidisciplinary input at all stages, pre- and post-operatively, ideally within a specialised tertiary clinical and/or academic centre. Ongoing research is required to better understand the neurobiological basis for obsessive-compulsive disorder and how this can be manipulated with deep brain stimulation to further improve the efficacy of this emerging treatment. [ABSTRACT FROM AUTHOR]