Autoinflammatory syndromes in neurology: when our first line of defence misbehaves.

Autoinflammatory syndromes result from a defective innate immune system. They are characterised by unexplained fever and systemic inflammation involving the skin, muscle, joints, serosa and eyes, along with elevated acute phase reactants. Autoinflammatory syndromes are increasingly recognised as a cause of neurological disease with a diverse range of manifestations. Corticosteroids, colchicine and targeted therapies are effective if started early, and hence the importance of recognising these syndromes. Here, we review the neurological features of specific autoinflammatory syndromes and our approach (as adult neurologists) to their diagnosis.

Incidence of Transient Ischemic Attack in Auckland, New Zealand, in 2011 to 2012.

BACKGROUND AND PURPOSE: There have been few recent population-based studies reporting the incidence (first ever) and attack rates (incident and recurrent) of transient ischemic attack (TIA). METHODS: The fourth Auckland Regional Community Stroke study (ARCOS IV) used multiple overlapping case ascertainment methods to identify all hospitalized and nonhospitalized cases of TIA that occurred in people ≥16 years of age usually resident in Auckland (population ≥16 years of age is 1.12 million), during the 12 months from March 1, 2011. All first-ever and recurrent new TIAs (any new TIA 28 days after the index event) during the study period were recorded. RESULTS: There were 785 people with TIA (402 [51.2%] women, mean [SD] age 71.5 [13.8] years); 614 (78%) of European origin, 84 (11%) Maori/Pacific, and 75 (10%) Asian/Other. The annual incidence of TIA was 40 (95% confidence interval, 36-43), and attack rate was 63 (95% confidence interval, 59-68), per 100 000 people, age standardized to the World Health Organization world population. Approximately two thirds of people were known to be hypertensive or were being treated with blood pressure-lowering agents, half were taking antiplatelet agents and just under half were taking lipid-lowering therapy before the index TIA. Two hundred ten (27%) people were known to have atrial fibrillation at the time of the TIA, of whom only 61 (29%) were taking anticoagulant therapy, suggesting a failure to identify or treat atrial fibrillation. CONCLUSIONS: This study describes the burden of TIA in an era of aggressive primary and secondary vascular risk factor management. Education programs for medical practitioners and patients around the identification and management of atrial fibrillation are required.

Autonomic dysfunction is a major feature of cerebellar ataxia, neuropathy, vestibular areflexia 'CANVAS' syndrome.

Cerebellar ataxia, neuropathy and vestibular areflexia syndrome (CANVAS) is a recently recognized neurodegenerative ganglionopathy. Prompted by the presence of symptomatic postural hypotension in two patients with CANVAS, we hypothesized that autonomic dysfunction may be an associated feature of the syndrome. We assessed symptoms of autonomic dysfunction and performed autonomic nervous system testing among 26 patients from New Zealand. After excluding three patients with diabetes mellitus, 83% had evidence of autonomic dysfunction; all patients had at least one autonomic symptom and 91% had more than two symptoms. We also found a higher rate of downbeat nystagmus (65%) than previously described in CANVAS. We confirmed that sensory findings on nerve conduction tests were consistent with a sensory ganglionopathy and describe two patients with loss of trigeminal sensation consistent with previous pathological descriptions of trigeminal sensory ganglionopathy. Our results suggest that autonomic dysfunction is a major feature of CANVAS. This has implications for the management of patients with CANVAS as the autonomic symptoms may be amenable to treatment. The findings also provide an important differential diagnosis from multiple system atrophy for patients who present with ataxia and autonomic failure.

'A divine right to photograph': E. Graeme Robertson's (1903-1975) historical motion pictures of National Hospital staff in 1933.

In the course of researching and writing the first-ever book length biography of Edward Graeme Robertson's (1903-1975) eventful life and career in Australasian neurology, a rare 1933 cinema film recording of National Hospital staff at Queen Square has recently been rediscovered. Graeme completed his residency in neurology at Queen Square in the early 1930s and maintained close connections with his colleagues in London, thoughtfully recording them at different times using early movie cameras. Two versions of Graeme's 1933 film have been preserved, and there are also other color clips of his colleagues from later in life in the UCL Neurology archives and Robertson family collection. These remarkable films contain images of several historically significant neurologists, including Gordon Morgan Holmes (1876-1965), Samuel Alexander Kinnier Wilson (1878-1937), Derek Denny-Brown (1901-1981), Macdonald Critchley (1900-1997), and several others. We provide a contextual summary of the many clips recorded alongside an in-depth inventory of all the personalities represented in the 1933 film. Selected photographs are used to indicate the contents of these remarkable films.

Neuronal intranuclear inclusion disease in New Zealand: A novel discovery.

Neuronal intranuclear inclusion disease, caused by a GGC repeat expansion in the 5'-untranslated region of NOTCH2NLC, is a rare neurodegenerative condition with highly variable clinical manifestations. In recent years, the number of reported cases have increased dramatically in East Asia. We report the first four genetically confirmed cases of neuronal intranuclear inclusion disease in New Zealand, all having Polynesian ancestry (three New Zealand Maori and one Cook Island Maori). Phenotypically, they resemble cases reported from recent large East Asian cohorts.

Cannabis, ischemic stroke, and transient ischemic attack: a case-control study.

BACKGROUND AND PURPOSE: There is a temporal relationship between cannabis use and stroke in case series and population-based studies. METHODS: Consecutive stroke patients, aged 18 to 55 years, who had urine screens for cannabis were compared with a cohort of control patients admitted to hospital without cardiovascular or neurological diagnoses. RESULTS: One hundred sixty of 218 (73%) ischemic stroke/transient ischemic attack patients had urine drug screens (100 men; mean [SD] age, 44.8 [8.7] years). Twenty-five (15.6%) patients had positive cannabis drug screens. These patients were more likely to be men (84% versus 59%; χ2: P=0.016) and tobacco smokers (88% versus 28%; χ2: P<0.001). Control urine samples were obtained from 160 patients matched for age, sex, and ethnicity. Thirteen (8.1%) control participants tested positive for cannabis. In a logistic regression analysis adjusted for age, sex, and ethnicity, cannabis use was associated with increased risk of ischemic stroke/transient ischemic attack (odds ratio, 2.30; 95% confidence interval, 1.08-5.08). However after adjusting for tobacco use, an association independent of tobacco could not be confirmed (odds ratio, 1.59; 95% confidence interval, 0.71-3.70). CONCLUSIONS: This study provides evidence of an association between a cannabis lifestyle that includes tobacco and ischemic stroke. Further research is required to clarify whether there is an association between cannabis and stroke independent of tobacco. CLINICAL TRIAL REGISTRATION URL: http://www.anzctr.org.au. Unique identifier: ACTRN12610000198022.

Neurological manifestations of phaeochromocytomas and secretory paragangliomas: a reappraisal.

OBJECTIVE: To determine the frequency and range of neurological manifestations of phaeochromocytomas and secretory paragangliomas. METHODS: A retrospective review of case notes of patients admitted to Auckland Hospital from 1985 to 2011 with a discharge diagnosis of phaeochromocytoma or secretory paraganglioma. RESULTS: Ninety-three patients were admitted with a phaeochromocytoma or secretory paraganglioma. Sixty-eight patients (73%) had neurological symptoms, but only 15 patients (16%) received a neurological consultation. Neurological manifestations occurred in three main clinical contexts. First, paroxysmal symptoms occurred in 66 of 93 patients (71%). Neurological symptoms were common features of these attacks and included headache (47 patients), anxiety (24 patients), tremulousness (15 patients) and dizziness (12 patients). The headaches typically had an explosive onset. Delay in diagnosis was common. Second, 28 patients (30%) had an acute crisis, which was associated with neurological symptoms in 11 (39%) of the episodes: headache (10 patients); seizures (five patients); strokes (three patients); delirium (three patients) and subarachnoid haemorrhage (one patient). Third, five of six patients with a head and neck secretory paraganglioma had neurological symptoms related to infiltration of the middle ear or compression of cranial nerves. Reversible cerebral vasoconstriction syndrome (RCVS) was documented in three patients. CONCLUSIONS: Neurological manifestations of phaeochromocytomas and secretory paragangliomas were common, and these tumours can present with various neurological manifestations. The paroxysmal symptoms can be incorrectly attributed to other headache syndromes, panic attacks or cerebral vasculitis. RCVS may play a role in the pathogenesis of the neurological symptoms associated with acute crises and paroxysmal attacks.

Rates and predictors of risk of stroke and its subtypes in diabetes: a prospective observational study.

BACKGROUND: Small vessel disease is reported to be a more common cause of ischaemic stroke in people with diabetes than in others. However, population based studies have shown no difference between those with and those without diabetes in the subtypes of stroke. We determined the rates and predictors of risk of stroke and its subtypes in the Fenofibrate Intervention and Event Lowering in Diabetes (FIELD) trial. METHODS: 9795 patients aged 50-75 years with type 2 diabetes were followed up for a median of 5 years. Annual rates were derived by the Kaplan-Meier method and independent predictors of risk by Cox proportional hazards regression analyses. RESULTS: The annual rate of stroke was 6.7 per 1000 person years; 82% were ischaemic and caused by small artery disease (36%), large artery disease (17%) and embolism from the heart (13%); 10% were haemorrhagic. Among the strongest baseline predictors of ischaemic or unknown stroke were age (60-65 years, HR 1.98; >65 years, HR 2.35) and a history of stroke or transient ischaemic attack (TIA) (HR 2.06). Other independent baseline predictors were male sex, smoking, history of hypertension, ischaemic heart disease, nephropathy, systolic blood pressure and blood low density lipoprotein (LDL) cholesterol, HbA(1c) and fibrinogen. A history of peripheral vascular disease, low high density lipoprotein, age and history of hypertension were associated with large artery ischaemic stroke. A history of diabetic retinopathy, LDL cholesterol, male sex, systolic blood pressure, smoking, diabetes duration and a history of stroke or TIA were associated with small artery ischaemic stroke. CONCLUSIONS: Older people with a history of stroke were at highest risk of stroke, but the prognosis and prognostic factors of subtypes were heterogeneous. The results will help clinicians quantify the absolute risk of stroke and its subtypes for typical diabetes patients.

Alexander disease: The story behind an eponym.

In 1949, William Stewart Alexander (1919-2013), a young pathologist from New Zealand working in London, reported the neuropathological findings in a 15-month-old boy who had developed normally until the age of seven months, but thereafter had progressive enlargement of his head and severe developmental delay. The most striking neuropathological abnormality was the presence of numerous Rosenthal fibers in the brain. The distribution of these fibers suggested to Alexander that the primary pathological change involved astrocytes. In the next 15 years, five similar patients were reported, and in 1964 Friede recognized these cases reflected a single disease process and coined the eponym "Alexander's disease" to describe the disorder. In the 1960s, electron microscopy confirmed that Rosenthal fibers were localized to astrocytes. In 2001, it was shown that Alexander disease is caused by mutations in the gene encoding glial fibrillary acidic protein, the major intermediate filament protein in astrocytes. Although the clinical, imaging, and pathological manifestations of Alexander disease are now well known, few people are familiar with Alexander's career. Although he did not make a further contribution to the literature on Alexander disease, his observations and accurate interpretation of the neuropathology have justified the continued use of the eponym "Alexander disease."

The Socioeconomic Impact of Diseases of Working Equids in Low and Middle-Income Countries: A Critical Review.

Working equids provide a crucial contribution to the livelihoods and food security of communities in low- and middle-income countries (LMICs). Nevertheless, they are a neglected category within animal health policies and interventions of governmental and non-governmental institutions. This critical review aims to assess the socioeconomic impact of diseases of working equids in LMICs. By highlighting the implications of diseases on working equid welfare, human wellbeing and livelihoods, this review seeks to sensitise policymakers within governments and international organisations to develop policies and interventions aimed at protecting the health of working equids and, consequently, the health and livelihoods of their dependent communities. Twenty relevant publications were identified through the search of five databases (CAB Abstracts, Web of Science Core Collection, BIOSIS, EMBASE and Scopus), backward citation searching and screening of indexes of proceedings and Special Issues retrieved from the database search. The review findings show that diseases of working equids have detrimental socioeconomic effects. However, this subject is under-researched and restricted to few diseases and geographical settings. Considering the complexity of the issue, this review demonstrates that the 'One Health' approach represents an opportunity to clarify the link between equid health, human wellbeing and livelihoods, facilitating the translation of research into policy.

Seroprevalence of canine distemper virus (CDV) in the free-roaming dog (Canis familiaris) population surrounding Chitwan National Park, Nepal.

Canine distemper virus (CDV) is a global multi-host pathogen that is capable of causing considerable mortality in a range of species and is important in the field of conservation medicine. Nepal's Chitwan National Park is a protected area providing habitat for 32% of the country's mammal species including endangered carnivores such as the Bengal tiger (Panthera tigris tigris) that are susceptible to CDV. The presence of free-roaming dogs around protected areas could represent a source of infectious disease for transmission to local wildlife. A cross-sectional demographic and canine distemper virus seroprevalence study of 100 free-roaming dogs from the Chitwan National Park buffer zone and surrounding area was conducted in November 2019. The overall seroprevalence indicating past exposure to canine distemper virus was 80.0% (95% CI: 70.8-87.3). Of the host variables assessed, sex and age were positively associated with seroprevalence at the univariable level, with male dogs demonstrating lower seroprevalence than females (OR = 0.32, 95% CI: 0.11-0.91) and adult dogs demonstrating higher seroprevalence than juveniles (OR = 13.94, 95% CI: 1.37-142.29). The effect of sex was no longer significant at the multivariable level, but the direction of the effect remained the same. The effect of age remained significant after multivariable analysis (OR = 9.00, 95% CI: 1.03-192.75). No spatial associations were demonstrated in relation to the buffer zone area or boundary of Chitwan National Park. Free-roaming dog neutering and vaccination programmes can provide a useful baseline for future CDV studies in the region, and a proxy to monitor disease threats to susceptible wildlife.

Data analysis of zoonoses notifications in Aboriginal and Torres Strait Islander populations in Australia 1996-2021: implications for One Health.

Introduction: Zoonoses are a health concern for Aboriginal and Torres Strait Islander peoples in Australia that face elevated risk of disease related to the environment and animals. Internationally, One Health is encouraged to effectively manage zoonoses by taking integrated approaches involving animal, human, and environmental health sectors to improve health outcomes. However, Australia's health systems manage zoonotic diseases in animals and people separately which does not support a One Health approach. For the effective management of zoonoses, a strong evidence base and database regarding the epidemiology of zoonotic pathogens is needed. However, we currently lack this evidence limiting our understanding of the impact of zoonoses on Aboriginal and Torres Strait Islander populations. Methods: As a first step towards building the evidence base, we undertook a descriptive analysis of Aboriginal and Torres Strait Islander zoonotic notifications in Australia from 1996 to 2021. We presented notifications as annual notification rates per 100,000 population, and percentages of notifications by state, remoteness, sex, and age group. Results: Salmonellosis and campylobacteriosis were the most notified zoonoses with the highest annual notification rates of 99.75 and 87.46 per 100,000 population, respectively. The north of Australia (Queensland, Northern Territory and Western Australia), remote and outer regional areas, and young children (0-4 years of age) had the highest percentages of notifications. Discussion: To our knowledge, these findings are the first national presentation of the epidemiology of zoonoses within Aboriginal and Torres Strait Islander populations. A greater understanding of transmission, prevalence and impact of zoonoses on Aboriginal and Torres Strait Islander peoples (including animal and environmental health factors) is required to inform their effective management through a One Health approach.

One Health and Australian Aboriginal and Torres Strait Islander Communities: A One Health Pilot Study.

Many Aboriginal and Torres Strait Islander communities face barriers in accessing animal healthcare and are exposed to disproportionate environmental health exposures leading to increased risk of disease. A One Health approach has been promoted to address public health risks and improve human, animal, and environmental health outcomes in communities. We undertook a pilot One Health study in Aboriginal and Torres Strait Islander communities in Queensland collecting animal, human, and environmental health data from 82 households. We performed a descriptive analysis and assessed the association between human and environmental health exposures and animal health outcomes. Most households were not crowded (82.9%) but did report a high level of environmental health concerns (86.6%). The majority of households owned cats and dogs (81.7%), with most animals assessed as healthy. There was no association between human and environmental health exposures and animal health outcomes. As most households experienced concerns regarding housing conditions, environmental health programs should prioritise improving household factors. There was also strong support for animal healthcare (including access to medicines and veterinarians, education programs and population management), indicating that a One Health approach is desired by communities.

Encephalitis in adults in the Auckland and Northland regions of New Zealand, 2009 to 2018.

We conducted a retrospective study to determine the incidence and frequency of different subtypes of encephalitis in patients aged 15 and older in the Auckland and Northland regions of New Zealand between 2009 and 2018. Residents in Auckland and Northland presenting with encephalitis between 2009 and 2018 were identified from three overlapping databases: positive cerebrospinal fluid (CSF) viral polymerase chain reaction (PCR) tests, CSF neuronal antibody requests, and CSF neuronal antibody tests sent overseas. A diagnosis of autoimmune encephalitis required fulfilment of diagnostic criteria published by Graus and colleagues (2016). One hundred and thirty-six (69, 50.7% female) patients met study inclusion criteria. The median age was 59 (range 15-92). The annual incidence was 1.10 cases per 100,000 person-years. Of these 136 patients, 56 (41.2%) had an infectious aetiology, with varicella zoster (26, 46.4%) and herpes simplex (23, 41.1%) being the most common agents. Autoimmune encephalitis was diagnosed in 32 patients (23.5%). LGI-1 antibody was the most commonly identified neuronal autoantibody (10 patients, 13.2%). Forty-eight patients (35.3%) had encephalitis of unknown cause. In-hospital mortality for infectious encephalitis was 12.5%, autoimmune encephalitis 6.3%, and encephalitis of unknown cause 10.4%. Compared to a previous analysis of encephalitis in adults in Auckland, the incidence of encephalitis and autoimmune encephalitis had increased. The proportion of patients with an unknown cause for encephalitis had decreased.