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INTRODUCTION: COVID-19 has challenged global health care systems and resulted in prehospital delays for time-sensitive emergencies, like stroke and transient ischemic attacks (TIA). However, there are conflicting international reports on the level of effect of the pandemic on ambulance response intervals and emergency call volumes for these conditions. OBJECTIVES: The purpose of this study was to synthesize the international evidence on the effect of COVID-19 on ambulance response intervals and emergency call volume for suspected stroke and TIA. METHODS: Following a published protocol, we conducted a systematic search of six databases through May 31, 2022. We re-ran this search on April 14, 2023, to check for any new papers. We considered for inclusion peer-reviewed quantitative studies comparing prehospital emergency care for adults with suspected stroke/TIA before and during the COVID-19 pandemic. Two authors screened title/abstract and full text articles. One author carried out data extraction, with a random selection of articles being checked by another author. We calculated overall pooled estimates of ambulance intervals (activation, response, patient care, and total prehospital intervals) and stroke/TIA emergency call volume. Subgroup and sensitivity analyses included location and stroke/TIA diagnosis. Two authors assessed study quality using the appropriate Joanna Briggs Institute tool. We worked with patient and public involvement contributors and clinical and policy stakeholders throughout the review. RESULTS: Of 4,083 studies identified, 52 unique articles met the inclusion criteria. Mean response interval (-1.29 min [-2.19 to -0.38]) and mean total prehospital interval (-6.42 min [-10.60 to -2.25]) were shorter in the pre-COVID-19 period, compared to the COVID-19 period. Furthermore, there was a higher incidence rate of emergency call volume for suspected stroke/TIA per day pre-COVID-19 compared with the COVID-19 period (log IRR = 0.17 [0.02 to 0.33]). Ambulance response interval definitions and terminology varied between regions and countries. CONCLUSIONS: Our review indicates that prehospital delays for suspected stroke/TIA increased during the COVID-19 pandemic. Furthermore, emergency call volume for suspected stroke/TIA decreased during this period. In order to minimize delays in future pandemics or other health care emergencies future research may involve understanding the potential reasons for these delays.
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INTRODUCTION: The 5-year recurrence risk after ischaemic stroke and transient ischaemic attack (TIA) is 25-30%. Although inflammation may be a target for prevention trials, the contribution of plaque inflammation to acute cerebrovascular events remains unclear. We investigated the association of acute inflammatory cytokines and high-sensitivity C-reactive protein (CRP) with recently symptomatic carotid atherosclerosis in a prospective cohort study. METHODS: Blood and Imaging markers of TIA BIO-TIA) is a multicentre prospective study of imaging and inflammatory markers in patients with TIA. Exclusion criteria were infection and other co-morbid illnesses associated with inflammation. CRP and serum cytokines (interleukin [IL]-6, IL-1ß, IL-8, IL-10, IL-12, interferon-γ [IFN-γ] and tumour necrosis factor-α [TNF-α]) were measured. All patients had carotid imaging. RESULTS: Two hundred and thirty-eight TIA cases and 64 controls (TIA mimics) were included. Forty-nine (20.6%) cases had symptomatic internal carotid artery stenosis. Pro-inflammatory cytokine levels increased in a dose-dependent manner across controls, TIA without carotid stenosis (CS), and TIA with CS (IL-1ß, ptrend = 0.03; IL-6, ptrend < 0.0001; IL-8, ptrend = 0.01; interferon (IFN)-γ, ptrend = 0.005; TNF-α, ptrend = 0.003). Results were unchanged when DWI-positive cases were excluded. On multivariable linear regression, only age (p = 0.01) and CS (p = 0.04) independently predicted log-IL-6. On multivariable Cox regression, CRP was the only independent predictor of 90-day stroke recurrence (adjusted hazard ratio per 1-unit increase 1.03 [95% CI: 1.01-1.05], p = 0.003). CONCLUSION: Symptomatic carotid atherosclerosis was associated with elevated cytokines in TIA patients after controlling for other sources of inflammation. High-sensitivity CRP was associated with recurrent ischaemic stroke at 90 days. These findings implicate acute plaque inflammation in the pathogenesis of cerebral thromboembolism and support a rationale for randomized trials of anti-inflammatory therapy for stroke patients, who were excluded from coronary trials.
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Isquemia Encefálica , Doenças das Artérias Carótidas , Estenose das Carótidas , Ataque Isquêmico Transitório , AVC Isquêmico , Placa Aterosclerótica , Acidente Vascular Cerebral , Isquemia Encefálica/complicações , Doenças das Artérias Carótidas/complicações , Doenças das Artérias Carótidas/diagnóstico por imagem , Estenose das Carótidas/complicações , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/terapia , Ensaios Clínicos como Assunto , Citocinas , Humanos , Inflamação/complicações , Interleucina-6 , Interleucina-8 , Ataque Isquêmico Transitório/complicações , Ataque Isquêmico Transitório/etiologia , Placa Aterosclerótica/complicações , Estudos Prospectivos , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/etiologia , Fator de Necrose Tumoral alfaRESUMO
Cerebral white matter pathology is a common CNS manifestation of Fabry disease, visualized as white matter hyperintensities on MRI in 42-81% of patients. Diffusion tensor imaging (DTI) MRI is a sensitive technique to quantify microstructural damage within the white matter with potential value as a disease biomarker. We evaluated the pattern of DTI abnormalities in Fabry disease, and their correlations with cognitive impairment, mood, anxiety, disease severity and plasma lyso-Gb3 levels in 31 patients with genetically proven Fabry disease and 19 age-matched healthy control subjects. We obtained average values of fractional anisotropy and mean diffusivity within the white matter and performed voxelwise analysis with tract-based spatial statistics. Using a standardized neuropsychological test battery, we assessed processing speed, executive function, anxiety, depression and disease severity. The mean age (% male) was 44.1 (45%) for patients with Fabry disease and 37.4 (53%) for the healthy control group. In patients with Fabry disease, compared to healthy controls the mean average white matter fractional anisotropy was lower in [0.423 (standard deviation, SD 0.023) versus 0.446 (SD 0.016), P = 0.002] while mean average white matter mean diffusivity was higher (749 × 10-6 mm2/s (SD 32 × 10-6) versus 720 × 10-6 mm2/s (SD 21 × 10-6), P = 0.004]. Voxelwise statistics showed that the diffusion abnormalities for both fractional anisotropy and mean diffusivity were anatomically widespread. A lesion probability map showed that white matter hyperintensities also had a wide anatomical distribution with a predilection for the posterior centrum semiovale. However, diffusion abnormalities in Fabry disease were not restricted to lesional tissue; compared to healthy controls, the normal appearing white matter in patients with Fabry disease had reduced fractional anisotropy [0.422 (SD 0.022) versus 0.443 (SD 0.017) P = 0.003] and increased mean diffusivity [747 × 10-6 mm2/s (SD 26 × 10-6) versus 723 × 10-6 mm2/s (SD 22 × 10-6), P = 0.008]. Within patients, average white matter fractional anisotropy and white matter lesion volume showed statistically significant correlations with Digit Symbol Coding Test score (r = 0.558, P = 0.001; and r = -0.633, P ≤ 0.001, respectively). Average white matter fractional anisotropy correlated with the overall Mainz Severity Score Index (r = -0.661, P ≤ 0.001), while average white matter mean diffusivity showed a strong correlation with plasma lyso-Gb3 levels (r = 0.559, P = 0.001). Our findings using DTI confirm widespread areas of microstructural white matter disruption in Fabry disease, extending beyond white matter hyperintensities seen on conventional MRI. Moreover, diffusion measures show strong correlations with cognition (processing speed), clinical disease severity and a putative plasma biomarker of disease activity, making them promising quantitative biomarkers for monitoring Fabry disease severity and progression.
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Doença de Fabry/diagnóstico por imagem , Doença de Fabry/psicologia , Substância Branca/diagnóstico por imagem , Adulto , Idoso , Idoso de 80 Anos ou mais , Ansiedade/etiologia , Ansiedade/psicologia , Encéfalo/diagnóstico por imagem , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/psicologia , Depressão/etiologia , Depressão/psicologia , Imagem de Tensor de Difusão , Função Executiva , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Transtornos do Humor/etiologia , Transtornos do Humor/psicologia , Testes Neuropsicológicos , Triexosilceramidas/sangue , Adulto JovemRESUMO
In this article, we report four new patients, from three kindreds, with pathogenic variants in RBCK1 and a multisystem disorder characterised by widespread polyglucosan storage. We describe the clinical presentation of progressive skeletal and cardiac myopathy, combined immunodeficiencies and auto-inflammation, illustrate in detail the histopathological findings in multiple tissue types, and report muscle MRI findings.
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Glucanos/metabolismo , Doença de Depósito de Glicogênio/genética , Doença de Depósito de Glicogênio/metabolismo , Fatores de Transcrição/genética , Ubiquitina-Proteína Ligases/genética , Criança , Pré-Escolar , Feminino , Humanos , Inflamação/patologia , Masculino , Músculo Esquelético/patologia , Doenças Musculares/patologia , Reinfecção/patologiaRESUMO
Adult-onset leukodystrophies and genetic leukoencephalopathies comprise a diverse group of neurodegenerative disorders of white matter with a wide age of onset and phenotypic spectrum. Patients with white matter abnormalities detected on MRI often present a diagnostic challenge to both general and specialist neurologists. Patients typically present with a progressive syndrome including various combinations of cognitive impairment, movement disorders, ataxia and upper motor neuron signs. There are a number of important and treatable acquired causes for this imaging and clinical presentation. There are also a very large number of genetic causes which due to their relative rarity and sometimes variable and overlapping presentations can be difficult to diagnose. In this review, we provide a structured approach to the diagnosis of inherited disorders of white matter in adults. We describe clinical and radiological clues to aid diagnosis, and we present an overview of both common and rare genetic white matter disorders. We provide advice on testing for acquired causes, on excluding small vessel disease mimics, and detailed advice on metabolic and genetic testing available to the practising neurologist. Common genetic leukoencephalopathies discussed in detail include CSF1R, AARS2, cerebral arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), and mitochondrial and metabolic disorders.
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Leucoencefalopatias/diagnóstico , Leucoencefalopatias/genética , Adulto , Idade de Início , HumanosRESUMO
INTRODUCTION: Metabolic encephalopathy is a rare but potentially devastating complication of diabetic ketoacidosis (DKA). This case highlights the dramatic cognitive decline of a young man due to metabolic encephalopathy complicating DKA. The aims of this case report are to highlight metabolic encephalopathy as a complication of DKA and to explore the current research in diabetic related brain injury. The importance of investigation and treatment of reversible causes of encephalopathy is also demonstrated. CASE PRESENTATION: A 35-year-old man with a background of type 1 diabetes mellitus (T1DM) and relapsing remitting multiple sclerosis (RRMS) presented to the emergency department (ED) in a confused and agitated state. Prior to admission he worked as a caretaker in a school, smoked ten cigarettes per day, took excess alcohol and smoked cannabis twice per week. Following initial investigations, he was found to be in DKA. Despite timely and appropriate management his neurological symptoms and behavioural disturbance persisted. Neuroimaging revealed temporal lobe abnormalities consistent with an encephalopathic process. The patient underwent extensive investigation looking for evidence of autoimmune, infective, metabolic, toxic and paraneoplastic encephalopathy, with no obvious cause demonstrated. Due to persistent radiological abnormalities a temporal lobe biopsy was performed which showed marked astrocytic gliosis without evidence of vasculitis, inflammation, infarction or neoplasia. A diagnosis of metabolic encephalopathy secondary to DKA was reached. The patient's cognitive function remained impaired up to 18 months post presentation and he ultimately required residential care. CONCLUSIONS: Metabolic encephalopathy has been associated with acute insults such as DKA, but importantly, the risk of cerebral injury is also related to chronic hyperglycaemia. Mechanisms of cerebral injury in diabetes mellitus continue to be investigated. DKA poses a serious and significant neurological risk to patients with diabetes mellitus. To our knowledge this is the second case report describing this acute complication.
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Encefalopatias Metabólicas/diagnóstico , Disfunção Cognitiva/etiologia , Diabetes Mellitus Tipo 1/complicações , Cetoacidose Diabética/complicações , Adulto , Encefalopatias Metabólicas/etiologia , Diagnóstico Diferencial , Humanos , Masculino , Lobo Temporal/diagnóstico por imagemRESUMO
Leukodystrophies and genetic leukoencephalopathies are a rare group of disorders leading to progressive degeneration of cerebral white matter. They are associated with a spectrum of clinical phenotypes dominated by dementia, psychiatric changes, movement disorders and upper motor neuron signs. Mutations in at least 60 genes can lead to leukoencephalopathy with often overlapping clinical and radiological presentations. For these reasons, patients with genetic leukoencephalopathies often endure a long diagnostic odyssey before receiving a definitive diagnosis or may receive no diagnosis at all. In this study, we used focused and whole exome sequencing to evaluate a cohort of undiagnosed adult patients referred to a specialist leukoencephalopathy service. In total, 100 patients were evaluated using focused exome sequencing of 6100 genes. We detected pathogenic or likely pathogenic variants in 26 cases. The most frequently mutated genes were NOTCH3, EIF2B5, AARS2 and CSF1R. We then carried out whole exome sequencing on the remaining negative cases including four family trios, but could not identify any further potentially disease-causing mutations, confirming the equivalence of focused and whole exome sequencing in the diagnosis of genetic leukoencephalopathies. Here we provide an overview of the clinical and genetic features of these disorders in adults.
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Exoma/genética , Predisposição Genética para Doença/genética , Leucoencefalopatias/diagnóstico , Leucoencefalopatias/genética , Adolescente , Adulto , Feminino , Humanos , Masculino , Mutação , Análise de Sequência de DNA , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Few recent studies have investigated the rates and predictors of early and late stroke recurrence using prospective population-based methodology. We investigated recurrent stroke at 2 years in the North Dublin Population Stroke Study (NDPSS). METHODS: Patients were ascertained from December 2005 to 2006 from overlapping community and hospital sources using hot and cold pursuit. Stroke recurrence, survival, and functional outcome were ascertained at 72 hours, 7 days, 28 days, 90 days, 1 year, and 2 years. RESULTS: Of 567 patients, cumulative 2-year stroke recurrence rate was 10.8% and case fatality was 38.6%. Recurrence subtype was associated with initial stroke subtype (P<0.001). On multivariable Cox regression, hyperlipidemia (adjusted hazard ratio, 3.32; P=0.005) and prior stroke (adjusted hazard ratio, 2.92; P=0.01) were independent predictors of 2-year recurrence in 28-day survivors. CONCLUSIONS: Despite rigorous ascertainment, recurrent stroke rates were lower in current study than in earlier studies. Our data suggest that large sample sizes may be needed for future secondary prevention trials in patients treated with modern preventive medications.
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Ataque Isquêmico Transitório/diagnóstico , Ataque Isquêmico Transitório/epidemiologia , Vigilância da População , Acidente Vascular Cerebral/diagnóstico , Acidente Vascular Cerebral/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Estudos de Coortes , Feminino , Seguimentos , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Valor Preditivo dos Testes , Estudos Prospectivos , Recidiva , Resultado do TratamentoRESUMO
OBJECTIVES: Time is a fundamental component of acute stroke and transient ischaemic attack (TIA) care, thus minimising prehospital delays is a crucial part of the stroke chain of survival. COVID-19 restrictions were introduced in Ireland in response to the pandemic, which resulted in major societal changes. However, current research on the effects of the COVID-19 pandemic on prehospital care for stroke/TIA is limited to early COVID-19 waves. Thus, we aimed to investigate the effect of the COVID-19 pandemic on ambulance time intervals and suspected stroke/TIA call volume for adults with suspected stroke and TIA in Ireland, from 2018 to 2021. DESIGN: We conducted a secondary data analysis with a quasi-experimental design. SETTING: We used data from the National Ambulance Service in Ireland. We defined the COVID-19 period as '1 March 2020-31 December 2021' and the pre-COVID-19 period '1 January 2018-29 February 2020'. PRIMARY AND SECONDARY OUTCOME MEASURES: We compared five ambulance time intervals: 'allocation performance', 'mobilisation performance', 'response time', 'on scene time' and 'conveyance time' between the two periods using descriptive and regression analyses. We also compared call volume for suspected stroke/TIA between the pre-COVID-19 and COVID-19 periods using interrupted time series analysis. PARTICIPANTS: We included all suspected stroke/TIA cases ≥18 years who called the National Ambulance Service from 2018 to 2021. RESULTS: 40 004 cases were included: 19 826 in the pre-COVID-19 period and 19 731 in the COVID-19 period. All ambulance time intervals increased during the pandemic period compared with pre-COVID-19 (p<0.001). Call volume increased during the COVID-19-period compared with the pre-COVID-19 period (p<0.001). CONCLUSIONS: A 'shock' like a pandemic has a negative impact on the prehospital phase of care for time-sensitive conditions like stroke/TIA. System evaluation and public awareness campaigns are required to ensure maintenance of prehospital stroke pathways amidst future healthcare crises. Thus, this research is relevant to routine and extraordinary prehospital service planning.
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COVID-19 , Ataque Isquêmico Transitório , Acidente Vascular Cerebral , Adulto , Humanos , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/terapia , Ataque Isquêmico Transitório/complicações , Ambulâncias , Pandemias , COVID-19/epidemiologia , COVID-19/complicações , Irlanda/epidemiologia , Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Acidente Vascular Cerebral/complicaçõesRESUMO
BACKGROUND AND PURPOSE: Statins reduce stroke risk when initiated months after transient ischemic attack (TIA)/stroke and reduce early vascular events in acute coronary syndromes, possibly via pleiotropic plaque stabilization. Few data exist on acute statin use in TIA. We aimed to determine whether statin pretreatment at TIA onset modified early stroke risk in carotid stenosis. METHODS: We analyzed data from 2770 patients with TIA from 11 centers, 387 with ipsilateral carotid stenosis. ABCD2 score, abnormal diffusion weighted imaging, medication pretreatment, and early stroke were recorded. RESULTS: In patients with carotid stenosis, 7-day stroke risk was 8.3% (95% confidence interval [CI], 5.7-11.1) compared with 2.7% (CI, 2.0%-3.4%) without stenosis (P<0.0001; 90-day risks 17.8% and 5.7% [P<0.0001]). Among carotid stenosis patients, nonprocedural 7-day stroke risk was 3.8% (CI, 1.2%-9.7%) with statin treatment at TIA onset, compared with 13.2% (CI, 8.5%-19.8%) in those not statin pretreated (P=0.01; 90-day risks 8.9% versus 20.8% [P=0.01]). Statin pretreatment was associated with reduced stroke risk in patients with carotid stenosis (odds ratio for 90-day stroke, 0.37; CI, 0.17-0.82) but not nonstenosis patients (odds ratio, 1.3; CI, 0.8-2.24; P for interaction, 0.008). On multivariable logistic regression, the association remained after adjustment for ABCD2 score, smoking, antiplatelet treatment, recent TIA, and diffusion weighted imaging hyperintensity (adjusted P for interaction, 0.054). CONCLUSIONS: In acute symptomatic carotid stenosis, statin pretreatment was associated with reduced stroke risk, consistent with findings from randomized trials in acute coronary syndromes. These data support the hypothesis that statins started acutely after TIA symptom onset may also be beneficial to prevent early stroke. Randomized trials addressing this question are required.
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Isquemia Encefálica/tratamento farmacológico , Estenose das Carótidas/tratamento farmacológico , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Acidente Vascular Cerebral/prevenção & controle , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/diagnóstico por imagem , Isquemia Encefálica/fisiopatologia , Estenose das Carótidas/diagnóstico por imagem , Estenose das Carótidas/fisiopatologia , Imagem de Difusão por Ressonância Magnética/métodos , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Radiografia , Fatores de Risco , Acidente Vascular Cerebral/diagnóstico por imagem , Acidente Vascular Cerebral/fisiopatologia , Fatores de TempoRESUMO
OBJECTIVE: Symptomatic carotid stenosis is associated with a 3-fold risk of early stroke recurrence compared to other stroke subtypes. Current carotid imaging techniques rely on estimating plaque-related lumen narrowing but do not evaluate intraplaque inflammation, a key mediator of plaque rupture and thromboembolism. Using combined (18) F-fluorodeoxyglucose positron-emission tomography (FDG-PET)/computed tomography, we investigated the relation between inflammation-related FDG uptake and stroke recurrence. METHODS: Consecutive patients with a recent (median, 6.5 days; interquartile range, 4-8) stroke, transient ischemic attack (TIA), or retinal embolism and ipsilateral carotid stenosis (≥50%) were included. FDG uptake was quantified as mean standardized uptake values (SUVs, g/ml). Patients were followed prospectively for stroke recurrence. RESULTS: Sixty patients were included (25 stroke, 29 TIA, 6 retinal embolism). Twenty-two percent (13 of 60) had stroke recurrence within 90 days. FDG uptake in ipsilateral carotid plaque was greater in patients with early recurrent stroke (mean SUV, 1.85 g/ml; standard deviation [SD], 0.44 vs 1.58 g/ml; SD, 0.32, p = 0.02). On life-table analysis, 90-day recurrence rates with mean SUV greater than a 2.14 g/ml threshold were 80% (95% confidence interval [CI], 41.8-99.2) versus 22.9% (95% CI, 12.3-40.3) with SUV ≤2.14 g/ml (log-rank, p < 0.0001). In a Cox regression model including age and degree of stenosis (50-69% or ≥70%), mean plaque FDG uptake was the only independent predictor of stroke recurrence (adjusted hazard ratio, 6.1; 95% CI, 1.3-28.8; p = 0.02). INTERPRETATION: In recently symptomatic carotid stenosis, inflammation-related FDG uptake was associated with early stroke recurrence, independent of the degree of stenosis. Plaque FDG-PET may identify patients at highest risk for stroke recurrence, who may be selected for immediate revascularization or intensive medical treatment.
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Estenose das Carótidas/diagnóstico por imagem , Diagnóstico Precoce , Inflamação/diagnóstico por imagem , Placa Aterosclerótica/diagnóstico por imagem , Acidente Vascular Cerebral/diagnóstico por imagem , Idoso , Estenose das Carótidas/complicações , Feminino , Fluordesoxiglucose F18 , Humanos , Interpretação de Imagem Assistida por Computador , Inflamação/complicações , Masculino , Imagem Multimodal , Placa Aterosclerótica/complicações , Tomografia por Emissão de Pósitrons , Modelos de Riscos Proporcionais , Curva ROC , Compostos Radiofarmacêuticos , Recidiva , Sensibilidade e Especificidade , Acidente Vascular Cerebral/etiologia , Tomografia Computadorizada por Raios XRESUMO
BACKGROUND AND PURPOSE: The World Health Organization has emphasized the importance of international population-based data for unbiased surveillance of stroke incidence and outcome. To date, few such studies have been conducted using recommended gold-standard ascertainment methods. We conducted a large, population-based stroke study in Dublin, Ireland. METHODS: Using gold-standard ascertainment methods, individuals with stroke and transient ischemic attack occurring over a 12-month period (December 1, 2005-November 30, 2006) in North Dublin were identified. Disability was assessed using the modified Rankin score and stroke severity (<72 hours) by the National Institutes of Health Stroke Scale. Stroke-related deaths were confirmed by review of medical files, death certificates, pathology, and coroner's records. Crude and standardized (to European and World Health Organization standard populations) rates of incidence, risk factors, severity, and early outcome (mortality, case-fatality, disability) were calculated, assuming a Poisson distribution for the number of events. RESULTS: Seven hundred one patients with new stroke or transient ischemic attack were ascertained (485 first-ever stroke patients, 83 recurrent stroke patients, 133 first-ever transient ischemic attack patients). Crude frequency rates (all rates per 1000 person-years) were: 1.65 (95% CI, 1.5-1.79; first-ever stroke), 0.28 (95% CI, 0.22-0.35; recurrent stroke), and 0.45 (95% CI, 0.37-0.53; first-ever transient ischemic attack). Age-adjusted stroke rates were higher than those in 9 other recent population-based samples from high-income countries. High rates of subtype-specific risk factors were observed (atrial fibrillation, 31.3% and smoking, 29.1% in ischemic stroke; warfarin use, 21.2% in primary intracerebral hemorrhage; smoking, 53.9% in subarachnoid hemorrhage; P<0.01 for all compared with other subtypes). Compared with recent studies, 28-day case-fatality rates for primary intracerebral hemorrhage (41%; 95% CI, 29.2%-54.1%) and subarachnoid hemorrhage (46%; 95% CI, 28.8%-64.5%) were greater in Dublin. CONCLUSIONS: Using gold-standard methods for case ascertainment, we found high incidence rates of stroke in Dublin compared with those in similar high-income countries; this is likely explained in part by high rates of subtype-specific risk factors.
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Acidente Vascular Cerebral/epidemiologia , Acidente Vascular Cerebral/terapia , Idoso , Fibrilação Atrial/complicações , Fibrilação Atrial/epidemiologia , Isquemia Encefálica/complicações , Isquemia Encefálica/epidemiologia , Avaliação da Deficiência , Feminino , Hospitais/estatística & dados numéricos , Humanos , Hipertensão/complicações , Hipertensão/epidemiologia , Renda , Irlanda/epidemiologia , Ataque Isquêmico Transitório/epidemiologia , Ataque Isquêmico Transitório/terapia , Masculino , Projetos Piloto , Distribuição de Poisson , População , Fatores de Risco , Taxa de Sobrevida , Resultado do TratamentoRESUMO
Epilepsy is a heterogeneous group of disorders, often associated with significant comorbidity, such as intellectual disability and skin disorder. The genetic underpinnings of many epilepsies are still being elucidated, and we expect further advances over the coming 5 years, as genetic technology improves and prices fall for whole exome and whole genome sequencing. At present, there are several well-characterized complex epilepsies associated with single gene disorders; we review some of these here. They include well-recognized syndromes such as tuberous sclerosis complex, epilepsy associated with Rett syndrome, some of the progressive myoclonic epilepsies, and novel disorders such as epilepsy associated with mutations in the PCDH 19 gene. These disorders are important in informing genetic testing to confirm a diagnosis and to permit better understanding of the variability in phenotype-genotype correlation.
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Epilepsia/etiologia , Epilepsia/genética , Doenças Genéticas Inatas/complicações , Doenças Genéticas Inatas/genética , Síndrome de Angelman/complicações , Síndrome de Angelman/genética , Caderinas/genética , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/complicações , Lissencefalias Clássicas e Heterotopias Subcorticais em Banda/genética , Epilepsia/tratamento farmacológico , Doenças Genéticas Inatas/terapia , Doenças Genéticas Ligadas ao Cromossomo X/complicações , Doenças Genéticas Ligadas ao Cromossomo X/genética , Humanos , Doença de Lafora/complicações , Doença de Lafora/genética , Síndrome MERRF/complicações , Síndrome MERRF/genética , Neurofibromatoses/complicações , Neurofibromatoses/genética , Protocaderinas , Síndrome de Rett/complicações , Síndrome de Rett/genética , Esclerose Tuberosa/complicações , Esclerose Tuberosa/genética , Síndrome de Unverricht-Lundborg/complicações , Síndrome de Unverricht-Lundborg/genéticaRESUMO
Metachromatic leukodystrophy (MLD) is a rare inherited lysosomal disorder. The condition progresses relentlessly, with severe disability typically established within 6-14 years of symptom onset. There is no cure, and limited treatment options are available to slow disease progression. We describe the case of a 23-year-old woman with forgetfulness, unsteady gait, and falls. Neurologic examination revealed intermittent dystonic posturing of the right upper and lower limb when walking. The Addenbrooke's Cognitive Examination (ACE) score was 70/100. MRI sequences demonstrated frontal-predominant atrophy and extensive white matter hyperintensity. Differential diagnoses such as autoimmune, inflammatory, and neoplastic diseases were excluded, and a genetic diagnosis was considered. Lysosomal enzyme testing showed low arylsulfatase with elevated urinary sulfatides, and genetic testing revealed a homozygous pathogenic mutation in the ARSA gene securing a diagnosis of adult-onset MLD. A male sibling also had early cognitive impairment and was found to have the same mutation. Hematopoietic stem cell transplantation (HSCT) was offered after discussion with experts. The male sibling died of multiple complications after HSCT. The index patient is now 24 months after HSCT, and disease progression has halted. This case highlights the challenges in the accurate diagnosis of adult-onset leukoencephalopathies and explores potential treatment strategies. A stepwise approach to the differential diagnosis of white matter diseases is demonstrated. HSCT may be an effective treatment, but the significant complication rate needs to be carefully considered.
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Disfunção Cognitiva , Leucodistrofia Metacromática , Leucoencefalopatias , Adulto , Feminino , Humanos , Masculino , Adulto Jovem , Raciocínio Clínico , Leucodistrofia Metacromática/complicações , Leucodistrofia Metacromática/diagnóstico , Leucodistrofia Metacromática/terapia , Leucoencefalopatias/complicações , Disfunção Cognitiva/etiologia , Disfunção Cognitiva/complicações , Progressão da Doença , MarchaRESUMO
Background: The COVID-19 pandemic impacted on health service provision worldwide, including care for acute time sensitive conditions. Stroke and transient ischaemic attacks (TIA) are particularly vulnerable to pressures on healthcare delivery as they require immediate diagnosis and treatment. The global impact of the COVID-19 pandemic on prehospital emergency care for stroke/TIA is still largely unknown. Thus, the aim of this study is to conduct a systematic review and meta-analysis to investigate the impact of the COVID-19 pandemic on prehospital emergency care for stroke and TIA. Methods: Following the Preferred Reporting Items for Systematic Reviews and Meta Analyses (PRISMA) guidelines, the review is registered on PROSPERO (registration number CRD42022315260). Peer-reviewed quantitative studies comparing prehospital emergency care for adults with stroke/TIA before and during the COVID-19 pandemic will be considered for inclusion. The outcomes of interest are ambulance times and emergency call volumes for stroke/TIA. A systematic search of databases including PubMed, Embase and Scopus will be conducted. Two authors will independently screen studies for inclusion based on predetermined inclusion and exclusion criteria. Data extraction and quality assessment will be conducted by two authors. Meta-analysis will be performed to calculate overall pooled estimates of ambulance times (primary outcome) and stroke/TIA call volumes (secondary outcome), where appropriate. Where heterogeneity is low a fixed-effects model will be used and where heterogeneity is high a random-effects model will be used. Subgroup and sensitivity analyses will include location, stroke/TIA diagnosis and COVID-19 case numbers. Results: Data on primary and secondary outcomes will be provided. Results of subgroup/sensitivity analyses and quality assessment will also be presented. Conclusions: This review will identify existing evidence reporting the impact of the COVID-19 pandemic on prehospital emergency care for adult patients with stroke/TIA and provide summary estimates of effects on ambulance response times.
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BACKGROUND AND PURPOSE: Statins improve infarct volume and neurological outcome in animal stroke models. We investigated the relationship between statin therapy and ischemic stroke outcome in the North Dublin Population Stroke Study. METHODS: A population-based prospective cohort study was performed using rigorous ascertainment methods. Prestroke and acute (≤72 hours) poststroke medications were recorded. Modified Rankin score and fatality were assessed at 7, 28, and 90 days and 1 year. RESULTS: Of 448 ischemic stroke patients, statins were prescribed before stroke onset in 30.1% (134/445) and were begun acutely (≤72 hours) in an additional 42.5% (189/445). On logistic regression analysis, adjusting for age, prestroke disability (modified Rankin scale), NIHSS score, hypertension, and aspirin, new poststroke statin therapy was independently associated with improved early and late survival (compared with statin untreated patients: OR for death, 0.12; CI, 0.03-0.54 at 7 days; OR, 0.19; CI, 0.07-0.48 at 90 days; OR, 0.26; CI, 0.12-0.55 at 1 year; P≤0.006 for all). Similar findings were observed for statin therapy before stroke onset (adjusted OR for death compared with statin-untreated-patients, 0.04; CI, 0.00-0.33; P=0.003 at 7 days; OR, 0.23; CI, 0.09-0.58; P=0.002 at 90 days; OR, 0.48; CI, 0.23-1.01; P=0.05 at 1 year). CONCLUSIONS: Statin therapy at stroke onset and newly begun statins were associated with improved early and late outcomes, supporting data from experimental studies. Randomized trials of statin therapy for treatment of acute stroke are needed.
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Isquemia Encefálica/tratamento farmacológico , Isquemia Encefálica/mortalidade , Inibidores de Hidroximetilglutaril-CoA Redutases/administração & dosagem , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Idoso , Idoso de 80 Anos ou mais , Isquemia Encefálica/fisiopatologia , Colesterol/metabolismo , Estudos de Coortes , Comorbidade , Feminino , Humanos , Irlanda/epidemiologia , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Recuperação de Função Fisiológica/efeitos dos fármacos , Recuperação de Função Fisiológica/fisiologia , Acidente Vascular Cerebral/fisiopatologia , Taxa de Sobrevida/tendências , TempoRESUMO
BACKGROUND AND PURPOSE: Although therapeutic anticoagulation improves early (within 1 month) outcomes after ischemic stroke in hospital-admitted patients with atrial fibrillation, no information exists on late outcomes in unselected population-based studies, including patients with all stroke (ischemic and hemorrhagic). METHODS: We identified patients with atrial fibrillation and stroke in a prospective, population-based study in North Dublin. Clinical characteristics, stroke subtype, stroke severity (National Institutes of Health Stroke Scale), prestroke antithrombotic medication, and International Normalized Ratio (INR) at onset were documented. Modified Rankin Scale (mRS) score was measured before stroke and at 7, 28, and 90 days; 1 year; and 2 years after stroke. RESULTS: One hundred seventy-five patients had atrial fibrillation-associated stroke and medication data at stroke onset (159 ischemic, 16 hemorrhagic); 17% of those with ischemic stroke were anticoagulated before stroke (27 of 159.) On multivariable analysis, therapeutic INR was associated with improved late survival after ischemic stroke (adjusted 2-year odds ratio for death=0.08; 95% CI, 0.01 to 0.78; P=0.03). This survival benefit persisted when patients with hemorrhagic stroke were included (2-year survival; 70.5% therapeutic INR, 14.3% nontherapeutic INR; log-rank P<0.001; odds ratio for death=0.27; 95% CI, 0.09 to 0.88; P=0.03). Admission INR was inversely correlated with early and late modified Rankin Scale score (2-year Spearman ρ=-0.65; P<0.0003). An INR of 2 to 3 at ischemic stroke onset was associated with greater early (72 hours to 28 days) modified Rankin Scale score improvement (P=0.04) and good functional outcome (modified Rankin Scale score=0 to 2) at 1 year (adjusted odds ratio=4.8; 95% CI, 1.45 to 23.8; P=0.04). CONCLUSIONS: In addition to improving short-term outcome in selected hospital-treated patient groups, therapeutic anticoagulation may provide important benefits for long-term stroke outcomes in unselected populations.
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Anticoagulantes/administração & dosagem , Fibrilação Atrial/tratamento farmacológico , Fibrilação Atrial/mortalidade , Coeficiente Internacional Normatizado , Acidente Vascular Cerebral/tratamento farmacológico , Acidente Vascular Cerebral/mortalidade , Varfarina/administração & dosagem , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/efeitos adversos , Fibrilação Atrial/complicações , Intervalo Livre de Doença , Feminino , Seguimentos , Humanos , Irlanda/epidemiologia , Masculino , Estudos Prospectivos , Acidente Vascular Cerebral/etiologia , Taxa de Sobrevida , Fatores de Tempo , Varfarina/efeitos adversosRESUMO
PURPOSE OF REVIEW: The aim is to review transient ischaemic attack (TIA) clinics, other service delivery models, and current TIA management. RECENT FINDINGS: Urgent assessment of TIA patients by stroke specialist services reduces stroke risk and is cost-effective. Almost one-third of TIA patients wait more than 24 h before presenting to medical attention, with delay associated with higher stroke risk. Risk stratification following suspected TIA may be performed by clinical assessment of individual patient characteristics, combined with the validated ABCD2 score (pre-investigation), and the ABCD3-I score (postinvestigation) in secondary care settings. Brain MRI and transcranial Doppler ultrasound add information related to vascular territory, TIA mechanism, and prognosis. Variability in systolic blood pressure in treated and untreated patients is an important predictor of stroke risk, independently of mean blood pressure. SUMMARY: Daily specialist-provided TIA services delivered in clinic or inpatient settings have proven efficacy for stroke prevention. In addition, a rapid-access, clinic-based service is associated with cost savings and reduced hospital bed-day utilization after TIA.