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Purpose: Delays in outpatient specialist neurologist care for people with epilepsy are common despite recommendations for prompt access. There is evidence to suggest that there are interventions that can minimise waitlists and waiting time. However, little is known about whether such interventions can result in sustained improvements in waiting. The aim of this study was to determine the extent to which an intervention to reduce waiting in an epilepsy specialist outpatient clinic demonstrated sustained outcomes two years after the intervention was implemented. Methods: This observational study analysed routinely collected epilepsy clinic data over three study periods: pre-intervention, post-intervention and at two-year follow-up. The intervention, Specific Timely Assessment and Triage (STAT), combined a short-term backlog reduction strategy and creation of protected appointments for new referrals based on analysis of demand. After the initial intervention, there was no further active intervention in the following two years. The primary outcome was waiting measured by 1.) waiting time for access to a clinic appointment, defined as the number of days between referral and first appointment for all patients referred to the epilepsy clinic during the three study periods; and 2.) a snapshot of the number of patients on the waitlist at two time points for each of the three study periods. Results: Two years after implementing the STAT model in an epilepsy clinic, median waiting time from post-intervention to two-year follow-up was stable (52-51 days) and the interquartile range of days waited reduced from 37 to 77 days post-intervention to 45-57 days at two-year follow-up, with a reduction in the most lengthy wait times observed. After a dramatic reduction of the total number of patients on the waitlist immediately following the intervention, a small rise was seen at two years (n = 69) which remained well below the pre-intervention level (n = 582). Conclusion: The STAT model is a promising intervention for reducing waiting in an epilepsy clinic. While there was a small increase in the waitlist after two years, the median waiting time was sustained.
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OBJECTIVE: Blood biomarkers of neuronal injury such as neurofilament light (NfL) show promise to improve diagnosis of neurodegenerative disorders and distinguish neurodegenerative from primary psychiatric disorders (PPD). This study investigated the diagnostic utility of plasma NfL to differentiate behavioural variant frontotemporal dementia (bvFTD, a neurodegenerative disorder commonly misdiagnosed initially as PPD), from PPD, and performance of large normative/reference data sets and models. METHODS: Plasma NfL was analysed in major depressive disorder (MDD, n = 42), bipolar affective disorder (BPAD, n = 121), treatment-resistant schizophrenia (TRS, n = 82), bvFTD (n = 22), and compared to the reference cohort (Control Group 2, n = 1926, using GAMLSS modelling), and age-matched controls (Control Group 1, n = 96, using general linear models). RESULTS: Large differences were seen between bvFTD (mean NfL 34.9 pg/mL) and all PPDs and controls (all < 11 pg/mL). NfL distinguished bvFTD from PPD with high accuracy, sensitivity (86%), and specificity (88%). GAMLSS models using reference Control Group 2 facilitated precision interpretation of individual levels, while performing equally to or outperforming models using local controls. Slightly higher NfL levels were found in BPAD, compared to controls and TRS. CONCLUSIONS: This study adds further evidence on the diagnostic utility of NfL to distinguish bvFTD from PPD of high clinical relevance to a bvFTD differential diagnosis, and includes the largest cohort of BPAD to date. Using large reference cohorts, GAMLSS modelling and the interactive Internet-based application we developed, may have important implications for future research and clinical translation. Studies are underway investigating utility of plasma NfL in diverse neurodegenerative and primary psychiatric conditions in real-world clinical settings.
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Doença de Alzheimer , Transtorno Bipolar , Transtorno Depressivo Maior , Demência Frontotemporal , Transtornos Psicóticos , Humanos , Doença de Alzheimer/diagnóstico , Biomarcadores , Transtorno Bipolar/diagnóstico , Transtorno Depressivo Maior/diagnóstico , Demência Frontotemporal/diagnóstico , Filamentos IntermediáriosRESUMO
BACKGROUND AND OBJECTIVES: Understanding the multi-faceted treatment outcomes of newly diagnosed epilepsy is critical for developing rational therapeutic strategies. A meta-analysis was conducted to derive pooled estimates of a range of seizure outcomes in children and adults with newly diagnosed epilepsy commenced on antiseizure medication treatment, and to identify factors associated with different outcomes. METHODS: PubMed/EMBASE were screened for eligible articles between 1 January, 1995 and 1 May, 2021 to include unselected cohort studies with a ≥ 12-month follow-up of seizure outcomes. Proportions of patients seizure free at different follow-up timepoints and their characteristics at the study population level were extracted. The patients were group-wise aggregated using a random-effects model. Primary outcomes were proportions of patients with cumulative 1-year seizure freedom (C1YSF), and 1-year and 5-year terminal seizure freedom (T1YSF and T5YSF). Secondary outcomes included the proportions of patients with early sustained seizure freedom, drug-resistant epilepsy and seizure-free off antiseizure medication at the last follow-up (off antiseizure medications). A separate random-effects meta-analysis was performed for nine predictors of importance. RESULTS: In total, 39 cohorts (total n = 21,139) met eligibility criteria. They included 15 predominantly adult cohorts (n = 12,024), 19 children (n = 6569), and 5 of mixed-age groups (n = 2546). The pooled C1YSF was 79% (95% confidence interval [CI] 74-83). T1YSF was 68% (95% CI 63-72) and T5YSF was 69% (95% CI 62-75). Children had higher C1YSF (85% vs 68%, p < 0.001) and T1YSF than adult cohorts (74% vs 61%, p = 0.007). For secondary outcomes, 33% (95% CI 27-39) of patients achieved early sustained seizure freedom, 17% (95% CI 13-21) developed drug resistance, and 39% (95% CI 30-50) were off antiseizure medications at the last follow-up. Studies with a longer follow-up duration correlated with higher C1YSF (p < 0.001) and being off antiseizure medications (p = 0.045). Outcomes were not associated with study design (prospective vs retrospective), cohort size, publication year, or the earliest date of recruitment. Predictors of importance in newly diagnosed epilepsy include etiology, epilepsy type, abnormal diagnostics (neuroimaging, examination, and electroencephalogram findings), number of seizure types, and pre-treatment seizure burden. CONCLUSIONS: Seizure freedom is achieved with currently available antiseizure medications in most patients with newly diagnosed epilepsy, yet this is often not immediate, may not be sustainable, and has not improved over recent decades. Symptomatic etiology, abnormal neuro-diagnostics, and increased pre-treatment seizure burden and seizure types are important predictors for unfavorable outcomes in newly diagnosed epilepsy. The study findings may be used as a quantitative benchmark on the efficacy of future antiseizure medication therapy for this patient population.
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Anticonvulsivantes , Epilepsia , Adulto , Criança , Humanos , Anticonvulsivantes/uso terapêutico , Estudos Retrospectivos , Estudos Prospectivos , Epilepsia/tratamento farmacológico , Convulsões/tratamento farmacológico , Resultado do TratamentoRESUMO
INTRODUCTION: The head impulse test (HIT) and HIT combined with direction-changing Nystagmus-Test of Skew deviation (HINTS) have been proposed as bedside tests to differentiate between peripheral and central causes of vertigo in the emergency department (ED). We conducted a meta-analysis of the HIT and HINTS tests to diagnose peripheral vertigo (PV) and central vertigo. METHODS: Pubmed, Google Scholar, EmBase, and articles references published in English up to July 2021 were searched for keywords "vertigo" or "acute vestibular syndrome" or "dizziness" and "head impulse" and "stroke." The bivariate method for meta-analysis was used to calculate positive (PLR) and negative likelihood ratios (NLR) and summary receiver operating characteristics area under the curve (AUC). RESULTS: A total of 11 studies were included analysing both HIT (8 studies, N = 417) and HINTS (6 studies, N = 405). HIT and HINTS were performed within 24 h in 4 of 11 studies. PLR and NLR for HIT in PV was 4.85 (95% CI: 2.83-8.08) and 0.19 (95% CI: 0.12-0.29, I2 63.25%), respectively. The AUC for HIT the diagnosis of PV and stroke was 0.90 and 0.92, respectively. PLR and NLR for a negative HIT in stroke was 5.85 (95% CI: 3.07-10.6) and 0.17 (95% CI: 0.08-0.30), respectively. PLR and NLR for peripheral HINTS pattern for PV was 17.3 (95% CI: 8.38-32.1) and 0.15 (95% CI: 0.07-0.26), respectively. PLR and NLR for central HINTS pattern for stroke: 5.61 (95% CI: 4.19-7.7) and 0.06 (95% CI: 0.03-0.12). In all included studies, HIT and HINTS exams were administered by neurology residents or neurology specialists with additional neuro-otology or neuro-ophthalmology subspeciality experience, and two studies included ED physicians. Raters reported high degree of bias and high concern regarding applicability in most domains of the quality assessment of diagnostic accuracy studies (QUADAS-2) tool. Meta-regression did not demonstrate a statistically significant effect of publication year, time to test, and type of assessor on sensitivity or false positive rate. CONCLUSION: The HIT and HINTS exams appear to be moderately good discriminators of central and PV. However, in most papers, the tests were administered by neurologists and were evaluated beyond 24 h, which may limit utility in the ED setting.
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Nistagmo Patológico , Acidente Vascular Cerebral , Humanos , Teste do Impulso da Cabeça/métodos , Vertigem/diagnóstico , Nistagmo Patológico/diagnóstico , Acidente Vascular Cerebral/diagnóstico , Serviço Hospitalar de EmergênciaRESUMO
BACKGROUND: Frontotemporal dementia (FTD) syndromes, mimics, phenocopy (phFTD), and slowly progressive behavioral variant FTD (bvFTD) can be difficult to distinguish clinically. Biomarkers such as neurofilament light chain (NfL) may be helpful. OBJECTIVE: To study plasma NfL levels in people with FTD syndromes and determine if plasma NfL can distinguish between FTD syndromes and phFTD. METHODS: Plasma NfL levels were estimated using both Simoa® Quanterix HD-X™ and SR-X™ machines grouped via final diagnosis after investigation and review. RESULTS: Fifty participants were studied: bvFTDâ=â20, semantic variant FTD (svFTD)â=â11, non-fluent variant FTD (nfvFTD)â=â9, FTD with motor neuron disease (MND)â=â4, phFTDâ=â2, slow progressorsâ=â3, FTD mimicâ=â1, mean age 67.2 (SD 8.4) years. NfL levels were significantly higher in the FTD group compared to phenocopy group (pâ=â0.003). Median NfL (IQR) pg/mL was comparable in the FTD syndromes: bvFTD 41.10 (50.72), svFTD 44.38 (16.61), and nfvFTD 42.61 (22.93), highest in FTD with MND 79.67 (45.32) and lowest in both phFTD 13.99 (0.79) and slow progressors 17.97 (3.62). CONCLUSION: Plasma NfL appears to differentiate FTD syndromes and mimics. However, a lower NfL may predict a slower, but not necessarily absence of neurodegeneration, and therefore appears limited in distinguishing slow progressors from FTD phenocopies. Larger numbers of patients from all clinical groups are required to strengthen diagnostic utility.
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Demência Frontotemporal , Idoso , Biomarcadores , Demência Frontotemporal/diagnóstico , Humanos , Filamentos Intermediários , Proteínas de NeurofilamentosRESUMO
The diagnosis of fat embolism syndrome typically involves neurological, respiratory and dermatological manifestations of microvascular occlusion 24-72 h after a precipitating event. However, fat embolism causing cerebral large vessel occlusion strokes and their sequelae have rarely been reported in the literature. This case series reports three patients with fat emboli post operatively causing cerebral large vessel occlusions, as well as a review of the literature to identify differences in clinical presentations and outcomes in stroke secondary to fat emboli causing large vessel occlusions compared to those with fat embolism syndrome.
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RATIONALE: To determine the prevalence of epileptic seizures in multiple sclerosis (MS) at an Australian tertiary hospital and to define their clinical features. METHODS: We retrospectively analysed adult patients at the Royal Melbourne Hospital electronically identified to have ICD codes for MS and seizures and/or epilepsy between 1996 to 2019, utilising paper and electronic-based records. RESULTS: Of the 2,125 MS patients identified, 16 (0.75%) experienced epileptic seizures during a mean follow-up period of 12.9 years. Median age of MS diagnosis (SD) was 38 (9.3) years. Four patients had relapsing remitting MS (25%), 10 secondary progressive MS (63.5%), and 2 primary progressive MS (12.5%). More than two-thirds of patients had seizure onset following the diagnosis of MS, and the majority of these had advanced disease (approximate EDSS >6) at the time of seizure onset. Focal onset-seizures occurred in 87.5% of patients with seizures. CONCLUSION: The estimated prevalence of seizures in our cohort was lower than in previous studies (0.75 vs 2-4%). In most cases, seizures occurred after the diagnosis of MS in the context of advanced disease. Further studies are required to determine if MS disease modifying treatments reduce the risk of seizures in this cohort.
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Intracranial epithelioid haemangioendothelioma (EHE) is a rare intermediate grade vascular tumour with heterogeneous clinical and histopathological behaviour. We present the surgical considerations of an exceptionally large skull-based EHE in an 11-year old female who presented to our institution with headaches and a protuberance over the left parietal area. Magnetic resonance imaging (MRI) demonstrated a left sided 10.5 × 6.6 × 11.1 cm extra-axial tumour arising from the parieto-temporaloccipital region which was continuous with the calvarium. An initial biopsy confirmed EHE. Staged treatment involved preoperative angiography and embolization. The patient underwent an extensive tumour excision and acrylic cranioplasty. Residual tumour persists in the petrous temporal bone. No neurological deficit was sustained. Postoperatively, we proceeded to tumour surveillance rather than adjuvant therapies, and follow-up imaging up to 36 months postoperatively has shown no tumour progression. We illustrate our surgical management of this large EHE and review the literature of this rare pathological entity with variable tumour behaviour and potential role for adjuvant therapy.