Cerebrovascular Disease Profiles of Culturally and Linguistically Diverse Communities in South Western Sydney and New South Wales.

INTRODUCTION: Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in CALD communities may improve health outcomes through culturally specific interventions. We compared rates of transient ischaemic attack (TIA)/stroke (ischaemic stroke, intracerebral haemorrhage) and stroke risk factor prevalence in overseas and Australian-born people in South Western Sydney (SWS) and New South Wales (NSW). METHODS: This was a 10-year retrospective analysis (2011-2020) of SWS and NSW age-standardized rates per 100,000 person-years of TIA/stroke. Data were extracted from Health Information Exchange and Secure Analytics for Population Health Research and Intelligence systems. Rates of hypertension, type 2 diabetes mellitus (T2DM), atrial fibrillation (AF), smoking, and obesity were also calculated. RESULTS: The SWS and NSW age-standardized rate of TIA/stroke for people born in Australia was 100 per 100,000 person-years (100/100,000/year). In SWS, 56.6% of people were overseas-born compared to 29.8% for NSW. The age-standardized rate of TIA/stroke for Polynesian-born people was more than double that of Australian-born people (p < 0.001). Hypertension (33 [SWS] vs. 27/100,000/year [NSW]) and T2DM (36 [SWS] vs. 26/100,000/year [NSW]) were the most common risk factors with rates >50/100,000/year (hypertension) and >80/100,000/year (T2DM) for people born in Polynesia, Melanesia, and Central America. Rates of T2DM, AF, and obesity for Polynesian-born people were over threefold greater than people born in Australia. DISCUSSION/CONCLUSION: Greater rates of TIA/stroke were observed in specific CALD communities, with increased rates of cerebrovascular risk factors. Culturally specific, targeted interventions may bridge health inequalities in cerebrovascular disease.

Pilot Study: The Queen Square Screening Test for Visual Deficits in Dementia.

The Queen Square Screening Test for Visual Deficits (QS test) screens for changes in visual processing. Our pilot study aimed to review the applicability of the QS test in individuals with dementia compared with those with normal cognition. Participants with major and minor neurocognitive disorder scored 50/71 (n=12) and 61/71 (n=10) respectively on the QS test, compared to 65/71 for age-matched healthy controls (n=11). The QS test score correlated with cognitive impairment as measured using the Rowland Universal Dementia Assessment Scale (r = 0.74). The QS test is an affordable and easy bedside screening test for visual processing changes.

Kufs disease due to mutation of CLN6: clinical, pathological and molecular genetic features.

Kufs disease is the major adult form of neuronal ceroid lipofuscinosis, but is rare and difficult to diagnose. Diagnosis was traditionally dependent on the demonstration of characteristic storage material, but distinction from normal age-related accumulation of lipofuscin can be challenging. Mutation of CLN6 has emerged as the most important cause of recessive Kufs disease but, remarkably, is also responsible for variant late infantile ceroid lipofuscinosis. Here we provide a detailed description of Kufs disease due to CLN6 pathogenic variants. We studied 20 cases of Kufs disease with CLN6 pathogenic variants from 13 unrelated families. Mean age of onset was 28 years (range 12-51) with bimodal peaks in teenage and early adult life. The typical presentation was of progressive myoclonus epilepsy with debilitating myoclonic seizures and relatively infrequent tonic-clonic seizures. Patients became wheelchair-bound with a mean 12 years post-onset. Ataxia was the most prominent motor feature. Dementia appeared to be an invariable accompaniment, although it could take a number of years to manifest and occasionally cognitive impairment preceded myoclonic seizures. Patients were usually highly photosensitive on EEG. MRI showed progressive cerebral and cerebellar atrophy. The median survival time was 26 years from disease onset. Ultrastructural examination of the pathology revealed fingerprint profiles as the characteristic inclusions, but they were not reliably seen in tissues other than brain. Curvilinear profiles, which are seen in the late infantile form, were not a feature. Of the 13 unrelated families we observed homozygous CLN6 pathogenic variants in four and compound heterozygous variants in nine. Compared to the variant late infantile form, there was a lower proportion of variants that predicted protein truncation. Certain heterozygous missense variants in the same amino acid position were found in both variant late infantile and Kufs disease. There was a predominance of cases from Italy and surrounding regions; this was partially explained by the discovery of three founder pathogenic variants. Clinical distinction of type A (progressive myoclonus epilepsy) and type B (dementia with motor disturbance) Kufs disease was supported by molecular diagnoses. Type A is usually caused by recessive pathogenic variants in CLN6 or dominant variants in DNAJC5. Type B Kufs is usually associated with recessive CTSF pathogenic variants. The diagnosis of Kufs remains challenging but, with the availability of genetic diagnosis, this will largely supersede the use of diagnostic biopsies, particularly as biopsies of peripheral tissues has unsatisfactory sensitivity and specificity.

Clot Histopathology in Ischemic Stroke with Infective Endocarditis.

BACKGROUND: Endovascular thrombectomy (EVT) has shown efficacy in acute ischemic stroke (AIS) patients with infective endocarditis (IE). The possibility to undertake advanced histopathological clot analysis following EVT offers a new avenue to establish the etiological basis of the stroke - which is often labelled "cryptogenic." In this paper, we present our findings from four consecutive patients with IE who underwent EVT following an AIS at our tertiary referral comprehensive stroke centre. METHODS: Comprehensive histopathological analysis of clot retrieved after EVT, including morphology, was undertaken. RESULTS: The consistent observation was the presence of dense paucicellular fibrinoid material mixed/interspersed with clusters of bacterial cocci. This clot morphology may be specific to septic embolus due to IE unlike incidental bacteraemia and could possibly explain the refractoriness of such clots to systemic thrombolysis. CONCLUSION: Detailed morphological and histopathological analysis of EVT-retrieved clots including Gram staining can assist in etiological classification of the clot. Understanding the composition of the clot may be of clinical value in early diagnostics and mapping treatment planning in IE.

Trends in acute stroke presentations to an emergency department: implications for specific communities in accessing acute stroke care services.

BACKGROUND AND PURPOSE: South Western Sydney comprises of a culturally and linguistically diverse (CALD) and lower socioeconomic status population group within the state of New South Wales. Geographic location and sociodemographic factors play important roles in access to healthcare and may be crucial in the success of time-critical acute stroke intervention. The aim of this study was to examine the trends in the delayed presentation to emergency department (ED) and identify factors associated with prehospital delay for an acute stroke/transient ischaemic attack (TIA) at a comprehensive stroke centre. METHODS: Patient health-related data were extracted for stroke/TIA discharges for the period 2009-2017. Electronic medical record data were used to determine sociodemographic characteristics and prehospital factors, and their associations with delayed presentation≥4.5 hours from stroke onset were studied. RESULTS: During the 9-year period, population-adjusted stroke/TIA discharge rates increased from 540 to 676 per 100 000. A significant reduction in the proportion of patients presenting to ED<4.5 hours (56% in 2009 versus 46% in 2017, p<0.001) was observed. Younger patients aged 55-64 and 65-74 years, those belonging to Polynesia, South Asia and Mainland Southeast Asia, and those not using state ambulance as the mode of arrival to the hospital were at increased risk of prehospital delay. CONCLUSIONS: Comprehensive reappraisal of educational programmes for early stroke recognition is required in our region due to delayed ED presentations of younger and specific CALD communities of stroke/TIA patients.

Factors Associated with Stroke Misdiagnosis in the Emergency Department: A Retrospective Case-Control Study.

BACKGROUND: Failure to recognise acute stroke may result in worse outcomes due to missed opportunity for acute stroke therapies. Our study examines factors associated with stroke misdiagnosis in patients admitted to a large comprehensive stroke centre. METHODS: Retrospective review comparing 156 consecutive stroke patients misdiagnosed in emergency department (ED) with 156 randomly selected stroke controls matched for age, gender, language spoken and stroke subtype for the period 2014-2016. RESULTS: There were 141 ischemic and 15 hemorrhagic misdiagnosed strokes (median age: 77 years, male:female = 1.3: 1). Symptom resolution, altered mental status, nausea/vomiting, dizziness and vertigo favored misdiagnosis (p < 0.05). Hemiparesis and dysarthria favored an accurate diagnosis (p < 0.05). Misdiagnosed patients were more commonly triaged into a lower ED category (62 vs. 42%, p = 0.001), clinically assessed as Face, Arm, Speech and Time (FAST) - negative (78 vs. 22%, p < 0.001) and underwent delayed CT imaging (median 4.1 vs. 1.5 h, p < 0.001). Misdiagnosed patients were more likely to have posterior circulation stroke (PCS; 39 vs. 22%, p = 0.01) and be admitted under non-neurological services (35 vs. 11%, p < 0.001) with worse discharge outcomes including increased mortality. CONCLUSIONS: Patients with stroke misdiagnosis were commonly FAST-negative with nonspecific symptoms including altered mental status, dizziness and nausea/vomiting often associated with PCS. Improved diagnostic accuracy may increase access to acute therapies.

Reflection on stroke deaths and end-of-life stroke care.

BACKGROUND: The benefit of palliative care referral for severe stroke patients on end-of-life care pathway (EOLCP) is increasingly recognised. Palliative care provides assistance with symptom management and transition to end-of-life care. Advance care planning (ACP) may help accommodate patient/family expectations and guide management. METHODS: This is a retrospective study of all stroke deaths (2014-2015) at Liverpool Hospital, Sydney, Australia. Data examined included age, comorbidities, living arrangements, pre-existing ACP, palliative care referral rates and 'survival time'. RESULTS: In total, 123 patient (mean age ± SD = 76 ± 13 years) deaths were identified from 1067 stroke admissions (11.5% mortality); 64 (52%) patients had ischaemic stroke and 59 (48%) intracerebral haemorrhage (ICH), and 40% suffered a prior stroke, and 43% required a carer at home or were in an aged care facility. Survival time from admission was significantly longer in patients with ischaemic stroke compared to intracerebral haemorrhage (median, interquartile range [IQR]: 9.5 [18] vs 2 [4] days, P < 0.001). Only two patients had pre-existing ACP; 44% of patients were referred to palliative care and 41% were commenced on dedicated EOLCP. Palliative care referral was less likely in patients who died under neurosurgery. EOLCP were significantly less likely to be commenced in patients who underwent acute intervention or were not referred to palliative care. CONCLUSION: In this cohort, palliative care referral and EOLCP were commenced in less than 50% of patients, highlighting significant variations in clinical care. These data support the need to promote awareness of ACP, particularly in patients with prior stroke or significant comorbidities. This may help reduce potentially futile invasive investigations and treatment.

Kufs disease, the major adult form of neuronal ceroid lipofuscinosis, caused by mutations in CLN6.

The molecular basis of Kufs disease is unknown, whereas a series of genes accounting for most of the childhood-onset forms of neuronal ceroid lipofuscinosis (NCL) have been identified. Diagnosis of Kufs disease is difficult because the characteristic lipopigment is largely confined to neurons and can require a brain biopsy or autopsy for final diagnosis. We mapped four families with Kufs disease for whom there was good evidence of autosomal-recessive inheritance and found two peaks on chromosome 15. Three of the families were affected by Kufs type A disease and presented with progressive myoclonus epilepsy, and one was affected by type B (presenting with dementia and motor system dysfunction). Sequencing of a candidate gene in one peak shared by all four families identified no mutations, but sequencing of CLN6, found in the second peak and shared by only the three families affected by Kufs type A disease, revealed pathogenic mutations in all three families. We subsequently sequenced CLN6 in eight other families, three of which were affected by recessive Kufs type A disease. Mutations in both CLN6 alleles were found in the three type A cases and in one family affected by unclassified Kufs disease. Mutations in CLN6 are the major cause of recessive Kufs type A disease. The phenotypic differences between variant late-infantile NCL, previously found to be caused by CLN6, and Kufs type A disease are striking; there is a much later age at onset and lack of visual involvement in the latter. Sequencing of CLN6 will provide a simple diagnostic strategy in this disorder, in which definitive identification usually requires invasive biopsy.

Comparative Prevalence of Cerebrovascular Disease in Vietnamese Communities in South-Western Sydney.

Culturally and linguistically diverse (CALD) communities are growing globally. Understanding patterns of cerebrovascular disease in these communities may improve health outcomes. We aimed to compare the rates of transient ischaemic attack (TIA), ischaemic stroke (IS), intracerebral haemorrhage (ICH), intracranial atherosclerosis (ICAD), and stroke risk factors in Vietnamese-born residents of South-Western Sydney (SWS) with those of an Australian-born cohort. A 10-year retrospective analysis (2011-2020) was performed using data extracted from the Health Information Exchange database characterising stroke presentations and risk factor profiles. The rates of hypertension (83.7% vs. 70.3%, p < 0.001) and dyslipidaemia (81.0% vs. 68.2%, p < 0.001) were significantly higher in Vietnamese patients, while the rates of ischaemic heart disease (10.4% vs. 20.3%, p < 0.001), smoking (24.4% vs. 40.8%, p < 0.001), and alcohol abuse (>1 drink/day) (9.6% vs. 15.9%, p < 0.001) were lower. The rates of ICAD and ICH were higher in Vietnamese patients (30.9% vs. 6.9%, p < 0.001 and 24.7% vs. 14.4%, p = 0.002). Regression analysis revealed that diabetes (OR: 1.86; 95% CI: 1.14-3.04, p = 0.014) and glycosylated haemoglobin (OR: 1.51; 95% CI: 1.15-1.98, p = 0.003) were predictors of ICAD in Vietnamese patients. Vietnamese patients had higher rates of symptomatic ICAD and ICH, with unique risk factor profiles. Culturally specific interventions arising from these findings may more effectively reduce the community burden of disease.

Musical hallucinations: a rare and atypical presentation of anti-IgLON5 disease responsive to immunosuppressive therapy.

IgLON5 antibodies are typically associated with the insidious onset of sleep disorder, parasomnia, gait disturbance and abnormal movements, with variable response to immunosuppressive therapy. We describe a case of a 50-year-old man who presented with acute speech difficulties, headache and focal seizures followed by well-formed visual hallucinations, and later, musical hallucinations of mainstream popular music. MRI of the brain demonstrated right temporal lobe changes with corresponding epileptiform activity seen on electroencephalogram. Subsequently, IgLON5 antibodies were detected in the serum. The patient was treated with anticonvulsants, as well as azathioprine with a tapering oral prednisone course with a complete resolution of the symptoms. Our case demonstrates an unusual presentation of the rare but increasingly described anti-IgLON5 disease, with musical hallucinations. The case highlights the variable and evolving clinical phenotypes that can be seen in autoimmune central nervous system disorders.

Validation of emergency and final diagnosis coding in transient ischemic attack: South Western Sydney transient ischemic attack study.

BACKGROUND: It is important to establish the validity of diagnostic coding in administrative datasets used in stroke and transient ischemic attack (TIA) research. This study examines the accuracy of emergency department (ED) TIA diagnosis and final diagnostic coding after hospital admission. METHODS: Using administrative datasets, we identified all patients with an ED TIA diagnosis (435.9; ICD-9) admitted to Liverpool Hospital from January 2003 to December 2007. ED and hospital admission records were matched and final diagnosis codes (ICD-10-AM) recorded. All records were expertly reviewed to determine coding validity. RESULTS: 570 patients were admitted with an ED TIA diagnosis. According to ICD-10-AM coding, 46% had TIA, 29% stroke and 25% TIA mimic diagnoses. Expert review determined final diagnoses of TIA in 51.4%, stroke in 26.1% and TIA mimic in 22.5% of the patients. The positive predictive value of a final TIA diagnosis (ICD-10-AM) was 88.2% when subjected to expert review. TIA mimic disorders diagnosed after admission included serious conditions. CONCLUSIONS: Half of the emergency diagnoses retained a TIA diagnosis after hospital admission. In the setting of neurological admission there were small percentage differences between coded final diagnosis for TIA, stroke and mimic and diagnoses at expert review. Admission of ED TIA cases permitted identification of TIA mimics with serious conditions requiring non-TIA management.

Impact of interhospital transfer on patients undergoing endovascular thrombectomy for acute ischaemic stroke in an Australian setting.

OBJECTIVE: To assess the impact of interhospital transfer on the interplay between functional outcome, mortality, reperfusion rates and workflow time metrics in patients undergoing endovascular thrombectomy (EVT) for acute ischaemic stroke due to large vessel occlusion (LVO) in the anterior cerebral circulation. DESIGN SETTING AND PARTICIPANTS: This is an analysis of a prospective database of consecutive patients undergoing EVT for LVO presenting between January 2017 and December 2018 at a single Australian comprehensive stroke centre (CSC). Patients presented directly or were transferred to the CSC from 21 sites across New South Wales and the Australian Capital Territory. MAIN OUTCOME MEASURES: The main outcome measures were rate of good 90-day functional outcome (modified Rankin Scale 0-2), successful reperfusion (Thrombolysis in Cerebral Infarction scale grade 2b or 3), symptomatic intracerebral haemorrhage (sICH) and 90-day mortality. Key workflow time metric milestones were examined. RESULTS: 154 of 213 (72%) patients were interhospital transfers. There was no significant difference in baseline characteristics including age, National Institutes of Health Stroke Scale score, intravenous thrombolysis administration or procedure time between transferred and direct presenters (all p>0.05). Transferred patients had worse 90-day functional outcome (39.6% vs 61.0%, OR 0.42, 95% CI 0.23 to 0.78), higher mortality (25.3% vs 6.8%, OR 4.66, CI 1.59 to 13.70) and longer stroke onset to treatment (groin puncture) time (298 min vs 205 min, p<0.01). Successful reperfusion rates and sICH were similar between the cohorts (96.8% vs 98.3%, and 7.8% vs 3.4%). CONCLUSION: Interhospital transfer is associated with longer stroke onset to treatment, worse 90-day functional outcome and higher mortality compared with patients presenting directly to the CSC.

Decreasing presentations of seizures to emergency departments in a large Australian population.

This study was designed (1) to compare the prevalence of emergency department (ED) presentations in Western Zone Sydney South West Area Health Service (WZS) between 1998-2002 and 2003-2007 for epilepsy (including status epilepticus (SE) and convulsions), hospital admission rates, and proportion of first seizure presentations; and (2) to compare these data with those for New South Wales (NSW) and Australia-wide figures. Using health department data sets, we found 19,834 presentations to WZS EDs between 1998 and 2007 (24.85/10,000 population/year). When the periods 2003-2007 and 1998-2002 in WZS are compared, ED presentations fell by 3% (P=0.03) and hospital admissions fell by 6% (P=0.001). The prevalence of ED presentations for seizures in NSW did not change (P=0.92), but hospital admissions fell by 3% (P<0.0001). When 1999/2000-2002/2003 was compared with 2003/2004-2006/2007, the prevalence of hospital admissions in Australia fell by 1% (P=0.0002). Rates of presentation for epilepsy in WZS have fallen over the last decade. Most presentations were first seizures rather than recurrences. The reason for this is speculative, but may reflect improved levels of education and health care delivery.

Endovascular Thrombectomy >24-hr From Stroke Symptom Onset.

Background: Trials have demonstrated efficacy for endovascular thrombectomy (EVT) for anterior circulation acute ischaemic stroke (AIS) up to 24-h from symptom onset. The magnitude of effect suggests benefit may exist beyond 24-h. Objectives: To perform a retrospective review of all patients undergoing EVT for anterior circulation LVO stroke beyond 24-h from symptom onset and assess safety and efficacy. Methods:A prospectively maintained database of EVT patients treated at two comprehensive stroke centers between January 2016 and December 2017 was retrospectively screened. Patients undergoing EVT for anterior circulation AIS >24-h from symptom onset were selected. Results: A total of 429 AIS patient underwent EVT in the study period. Five patients treated >24-h from symptom onset were identified. The median age was 72 (range 42-84); median ASPECTS 8 (range 6-8); median baseline-NIHSS 9 (range 4-17); and median time from symptom onset to groin puncture 44 h and 55 min (range 25:07-90:10). One patient underwent CT perfusion imaging. The remaining four patients were selected based on non-contrast CT brain and CT-angiography. Two patients had tandem cervical carotid lesions and underwent acute stenting. Modified thrombolysis in cerebral ischaemia (mTICI) 3 reperfusion was achieved in four patients. No hemorrhagic transformation occurred. All patients were alive at 90-day follow-up. Four patients achieved functional independence at 90-days (mRS 0-2). Conclusion: Endovascular thrombectomy for AIS patients beyond 24-h from symptom onset appears to be safe and effective in this limited study. There is a need for further evidence-based trials of benefit vs. risk in very prolonged time windows.

Prevalence of positive syphilis serology and meningovascular neurosyphilis in patients admitted with stroke and TIA from a culturally diverse population (2005-09).

The study aims were to determine the prevalence of positive syphilis serology and meningovascular neurosyphilis (NS) in patients admitted with transient ischaemic attack (TIA) and stroke to a tertiary hospital serving a culturally diverse community. A retrospective cohort analysis was conducted using routinely collected administrative data and medical records to identify patients admitted with TIA, stroke and other conditions, with positive syphilis serology, between 2005 and 2009. Direct medical record review confirmed diagnoses of meningovascular NS. Syphilis serology was requested in 27% (893/3270) of all patients with TIA and stroke (2005-09) of whom 4% (38/893) were positive. Thirty-seven patients with positive serology had clinical characteristics consistent with meningovascular NS. Their mean age was 72±13 years; 65% were male and 68% had a recorded place of birth in South-East Asia or the Pacific Islands. One of 12 patients with suspected meningovascular NS with cerebrospinal fluid (CSF) analysis had a positive CSF Venereal Disease Research Laboratory (VDRL) test. Three patients (8%) met diagnostic criteria for "definite or probable" meningovascular NS. All three patients with a "definite or probable" meningovascular NS and 15 (44%) of the remainder who had positive serology without confirmation of NS were treated with intravenous or intramuscular penicillin. Lumbar puncture (LP) and penicillin were underutilised in patients with TIA and stroke with positive serology. In conclusion, syphilis testing should be considered part of the diagnostic work-up of TIA and stroke, particularly in ethnically diverse populations. In patients with TIA and stroke with positive syphilis serology, it would seem appropriate to further pursue diagnosis and treatment and in patients unable to undergo LP, empiric treatment for NS should be considered.

Endovascular treatment of an acute left middle cerebral artery >6 h post stroke in a patient presenting with dysphasia and dense right hemiplegia.

This paper describes the case of a 32-year-old man presenting with dense right hemiplegia and global aphasia caused by an acute left middle cerebral artery infarct that underwent successful endovascular therapy after being determined ineligible for intravenous tissue plasminogen activator. Clot transversion and balloon disruption followed by intra-arterial Alteplase resulted in successful re-canalization of his middle cerebral artery at 7 h 30 min. At 3 months post stroke, the patient had moderately severe expressive dysphasia but was mobilizing independently with normal right upper and lower limb strength. In conclusion, the 3 month outcome suggests that the therapeutic time window for endovascular therapy might exceed 6 h post stroke.

Outcomes of patients with transient ischaemic attack after hospital admission or discharge from the emergency department.

OBJECTIVE: To compare outcomes at 28 days and 1 year between patients admitted to hospital and those discharged after presenting to the emergency department (ED) with transient ischaemic attack (TIA). DESIGN AND SETTING: All TIA presentations to EDs in a large metropolitan and rural region of Sydney and its surroundings, New South Wales, between 2001 and 2005 were extracted from state health department databases and followed up over 1 year. Admission and discharge data and subsequent TIA or stroke presentations were identified. MAIN OUTCOME MEASURES: TIA recurrence or stroke. RESULTS: Of 2535 presentations to an ED with TIA during the 5-year period, 1816 patients were admitted to hospital (71.6%) and 719 were discharged from the ED (28.4%). At 28 days, the discharged group had significantly higher rates of recurrence than the admitted group for all events (TIA or stroke) (5.3% v 2.3%, P < 0.001), stroke (2.1% v 0.7%, P = 0.002), and recurrent TIA (3.2% v 1.6%, P = 0.01). During the 29-365-day follow-up period, there was no significant difference between the discharged and admitted groups for all events (4.2% v 5.1%; P = 0.37), stroke (1.3% v 2.5%; P = 0.06) or recurrent TIA (2.9% v 2.6%; P = 0.65). CONCLUSION: Patients with an ED diagnosis of TIA may benefit from admission to hospital through a reduced risk of early stroke.