RESUMO
BACKGROUND: Chronic subdural haematoma is a common surgically treated intracranial emergency. Burr-hole drainage surgery, to evacuate chronic subdural haematoma, involves three elements: creation of a burr hole for access, irrigation of the subdural space, and insertion of a subdural drain. Although the subdural drain has been established as beneficial, the therapeutic effect of subdural irrigation has not been addressed. METHODS: The FINISH trial was an investigator-initiated, pragmatic, multicentre, nationwide, randomised, controlled, parallel-group, non-inferiority trial in five neurosurgical units in Finland that enrolled adults aged 18 years or older with a chronic subdural haematoma requiring burr-hole drainage. Patients were randomly assigned (1:1) by computer-generated block randomisation with block sizes of four, six, or eight, stratified by site, to burr-hole drainage either with or without subdural irrigation. All patients and staff were masked to treatment assignment apart from the neurosurgeon and operating room staff. A burr hole was drilled at the site of maximum haematoma thickness in both groups, and the subdural space was either irrigated or not irrigated before inserting a subdural drain, which remained in place for 48 h. Reoperations, functional outcome, mortality, and adverse events were recorded for 6 months after surgery. The primary outcome was the reoperation rate within 6 months. The non-inferiority margin was set at 7·5%. Key secondary outcomes that were also required to conclude non-inferiority were the proportion of participants with unfavourable functional outcomes (ie, modified Rankin Scale score of 4-6, where 0 indicates no symptoms and 6 indicates death) and mortality rate at 6 months. The primary and key secondary analyses were done in both the intention-to-treat and per-protocol populations. The trial was registered with ClinicalTrials.gov (NCT04203550) and is completed. FINDINGS: From Jan 1, 2020, to Aug 17, 2022, we assessed 1644 patients for eligibility and 589 (36%) patients were randomly assigned to a treatment group and treated (294 assigned to drainage with irrigation and 295 assigned to drainage without irrigation; 165 [28%] women and 424 [72%] men). The 6-month follow-up period extended until Feb 14, 2023. In the intention-to-treat analysis, 54 (18·3%) of 295 participants required reoperation in the group assigned to receive no irrigation versus 37 (12·6%) of 294 in the group assigned to receive irrigation (difference of 6·0 percentage points, 95% CI 0·2-11·7; p=0·30; adjusted for study site). There were no significant between-group differences in the proportion of people with modified Rankin Scale score of 4-6 (37 [13·1%] of 283 in the no-irrigation group vs 36 [12·6%] of 285 in the irrigation group; p=0·89) or mortality rate (18 [6·1%] of 295 in the no-irrigation group vs 21 [7·1%] of 294 in the irrigation group; p=0·58). The findings of the primary intention-to-treat analysis were not materially altered in the per-protocol analysis. There were no significant between-group differences in the number of adverse events, and the most frequent severe adverse events were systemic infections (26 [8·8%] of 295 participants who did not receive irrigation vs 22 [7·5%] of 294 participants who received irrigation), intracranial haemorrhage (13 [4·4%] vs seven [2·4%]), and epileptic seizures (five [1·7%] vs nine [3·1%]). INTERPRETATION: We could not conclude non-inferiority of burr-hole drainage without irrigation. The reoperation rate was 6·0 percentage points higher after burr-hole drainage without subdural irrigation than with subdural irrigation. Considering that there were no differences in functional outcome or mortality between the groups, the trial favours the use of subdural irrigation. FUNDING: State Fund for University Level Health Research (Helsinki University Hospital), Finska Läkaresällskapet, Medicinska Understödsföreningen Liv och Hälsa, and Svenska Kulturfonden.
Assuntos
Drenagem , Hematoma Subdural Crônico , Irrigação Terapêutica , Adulto , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Drenagem/métodos , Finlândia/epidemiologia , Hematoma Subdural Crônico/cirurgia , Hematoma Subdural Crônico/terapia , Irrigação Terapêutica/métodos , Resultado do Tratamento , Trepanação/métodosRESUMO
BACKGROUND: Forty percent of patients with aneurysmatic subarachnoid hemorrhage (aSAH) develop acute hydrocephalus requiring treatment with cerebrospinal fluid (CSF) drainage. CSF cell parameters are used in the diagnosis of nosocomial infections but also reflect sterile inflammation after aSAH. We aimed to study the temporal changes in CSF parameters and compare external ventricular drain (EVD)-derived and lumbar spinal drain-derived samples. METHODS: We retrospectively identified consecutive patients with aSAH treated at our neurointensive care unit between January 2014 and May 2019. We mapped the temporal changes in CSF leucocyte count, erythrocyte count, cell ratio, and cell index during the first 19 days after aSAH separately for EVD-derived and spinal drain-derived samples. We compared the sample sources using a linear mixed model, controlling for repeated sampling. RESULTS: We included 1360 CSF samples from 197 patients in the analyses. In EVD-derived samples, the CSF leucocyte count peaked at days 4-5 after aSAH, reaching a median of 225 × 106 (interquartile range [IQR] 64-618 × 106). The cell ratio and index peaked at 8-9 days (0.90% [IQR 0.35-1.98%] and 2.71 [IQR 1.25-6.73], respectively). In spinal drain-derived samples, the leucocyte count peaked at days 6-7, reaching a median of 238 × 106 (IQR 60-396 × 106). The cell ratio and index peaked at 14-15 days (4.12% [IQR 0.63-10.61%]) and 12-13 days after aSAH (8.84 [IQR 3.73-18.84]), respectively. Compared to EVD-derived samples, the leucocyte count was significantly higher in spinal drain-derived samples at days 6-17, and the cell ratio as well as the cell index was significantly higher in spinal drain-derived samples compared to EVD samples at days 10-15. CONCLUSIONS: CSF cell parameters undergo dynamic temporal changes after aSAH. CSF samples from different CSF compartments are not comparable.
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Drenagem , Hidrocefalia , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/líquido cefalorraquidiano , Masculino , Feminino , Pessoa de Meia-Idade , Estudos Retrospectivos , Contagem de Leucócitos , Idoso , Hidrocefalia/cirurgia , Hidrocefalia/líquido cefalorraquidiano , Hidrocefalia/etiologia , Adulto , Contagem de Eritrócitos , Líquido Cefalorraquidiano/citologia , Fatores de TempoRESUMO
BACKGROUND: The role of coagulopathy in patients with traumatic brain injury has remained elusive. In the present study, we aim to assess the prevalence of coagulopathy in patients with traumatic intracranial hemorrhage, their clinical features, and the effect of coagulopathy on treatment and mortality. METHODS: An observational, retrospective single-center cohort of consecutive patients with traumatic intracranial hemorrhage treated at Helsinki University Hospital between 01 January and 31 December 2010. We compared clinical and radiological parameters in patients with and without coagulopathy defined as drug- or disease-induced, i.e., antiplatelet or anticoagulant medication at a therapeutic dose, thrombocytopenia (platelet count < 100 E9/L), international normalized ratio > 1.2, or thromboplastin time < 60%. Primary outcome was 30-day all-cause mortality. Logistic regression analysis allowed to assess for factors associated with coagulopathy and mortality. RESULTS: Of our 505 patients (median age 61 years, 65.5% male), 206 (40.8%) had coagulopathy. Compared to non-coagulopathy patients, coagulopathy patients had larger hemorrhage volumes (mean 140.0 mL vs. 98.4 mL, p < 0.001) and higher 30-day mortality (18.9% vs. 9.7%, p = 0.003). In multivariable analysis, older age, lower admission Glasgow Coma Scale score, larger hemorrhage volume, and conservative treatment were independently associated with mortality. Surgical treatment was associated with lower mortality in both patients with and without coagulopathy. CONCLUSIONS: Coagulopathy was more frequent in patients with traumatic intracranial hemorrhage presenting larger hemorrhage volumes compared to non-coagulopathy patients but was not independently associated with higher 30-day mortality. Hematoma evacuation, in turn, was associated with lower mortality irrespective of coagulopathy.
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Transtornos da Coagulação Sanguínea/complicações , Hemorragia Intracraniana Traumática/tratamento farmacológico , Hemorragia Intracraniana Traumática/mortalidade , Idoso , Idoso de 80 Anos ou mais , Anticoagulantes/uso terapêutico , Transtornos da Coagulação Sanguínea/epidemiologia , Feminino , Escala de Coma de Glasgow , Humanos , Hemorragia Intracraniana Traumática/complicações , Modelos Logísticos , Masculino , Pessoa de Meia-Idade , Análise Multivariada , Estudos RetrospectivosRESUMO
BACKGROUND: The mean age of actively treated subarachnoid hemorrhage (SAH) patients is increasing. We aimed to compare outcomes and prognostic factors between older and younger SAH patients. METHODS: A retrospective single-center analysis of aneurysmal SAH patients admitted to a neuro-ICU during 2014-2019. We defined older patients as ≥70 years and younger patients as <70 years. For every older patient, we identified three younger patients with the same World Federation of Neurological Surgeons (WFNS) grade. We only included patients receiving active aneurysm treatment. Favorable functional outcome, defined as a Glasgow Outcome Scale (GOS) of 4-5 at 12 months, was our primary outcome. We used logistic regression to compare prognostic factors between the groups. RESULTS: Ninety-five (85%) of 112 older patients and 317 (94%) of 336 younger patients received aneurysm treatment. Of the younger patients, 91% with a good-grade SAH (WFNS I-III) had a favorable outcome compared to 52% in the older good-grade SAH group. In poor-grade patients (WFNS IV-V), favorable outcome was seen in 51% of younger patients, compared to 24% of older patients. Acute hydrocephalus and intracerebral hemorrhage were associated with unfavorable outcome in the younger (OR 4.7, 95% CI 2.6-8.4, and OR 3.7, 95% CI 2.1-6.4), but not in the older patients (OR 1.8, 95% CI 0.8-4.2, and OR 1.3, 95% CI 0.5-3.1, respectively). CONCLUSIONS: In actively treated SAH patients, age was a major determinant of outcome. Factors reflecting increases in intracranial pressure associated with outcome only among younger patients.
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Aneurisma Intracraniano/epidemiologia , Hemorragia Subaracnóidea/epidemiologia , Adulto , Fatores Etários , Idoso , Escala de Resultado de Glasgow , Humanos , Hidrocefalia/epidemiologia , Aneurisma Intracraniano/patologia , Aneurisma Intracraniano/terapia , Masculino , Pessoa de Meia-Idade , Hemorragia Subaracnóidea/patologia , Hemorragia Subaracnóidea/terapia , Resultado do TratamentoRESUMO
BACKGROUND: To ensure adequate intensive care unit (ICU) capacity for SARS-CoV-2 patients, elective neurosurgery and neurosurgical ICU capacity were reduced. Further, the Finnish government enforced strict restrictions to reduce the spread. Our objective was to assess changes in ICU admissions and prognosis of traumatic brain injury (TBI) and aneurysmal subarachnoid hemorrhage (SAH) during the Covid-19 pandemic. METHODS: Retrospective review of all consecutive patients with TBI and aneurysmal SAH admitted to the neurosurgical ICU in Helsinki from January to May of 2019 and the same months of 2020. The pre-pandemic time was defined as weeks 1-11, and the pandemic time was defined as weeks 12-22. The number of admissions and standardized mortality rates (SMRs) were compared to assess the effect of the Covid-19 pandemic on these. Standardized mortality rates were adjusted for case mix. RESULTS: Two hundred twenty-four patients were included (TBI n = 123, SAH n = 101). There were no notable differences in case mix between TBI and SAH patients admitted during the Covid-19 pandemic compared with before the pandemic. No notable difference in TBI or SAH ICU admissions during the pandemic was noted in comparison with early 2020 or 2019. SMRs were no higher during the pandemic than before. CONCLUSION: In the area of Helsinki, Finland, there were no changes in the number of ICU admissions or in prognosis of patients with TBI or SAH during the Covid-19 pandemic.
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Lesões Encefálicas Traumáticas/epidemiologia , Infecções por Coronavirus , Hospitalização/estatística & dados numéricos , Pandemias , Pneumonia Viral , Hemorragia Subaracnóidea/epidemiologia , Adulto , Idoso , Betacoronavirus , Lesões Encefálicas Traumáticas/mortalidade , COVID-19 , Cuidados Críticos , Feminino , Finlândia/epidemiologia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Neurocirurgia , Procedimentos Neurocirúrgicos , Prognóstico , Estudos Retrospectivos , SARS-CoV-2 , Hemorragia Subaracnóidea/mortalidadeRESUMO
BACKGROUND: The benefits of early surgery in cases of superficial supratentorial spontaneous intracerebral hemorrhage (ICH) are unclear. This study aimed to assess the association between early ICH surgery and outcome, as well as the cost-effectiveness of early ICH surgery. METHODS: We conducted a retrospective, register-based multicenter study that included all patients who had been treated for supratentorial spontaneous ICH in four tertiary intensive care units in Finland between 2003 and 2013. To be included, patients needed to have experienced supratentorial ICHs that were 10-100 cm3 and located within 10 mm of the cortex. We used a multivariable analysis, adjusting for the severity of the illness and the probability of surgical treatment, to assess the independent association between early ICH surgery (≤ 1 day), 12-month mortality rates, and the probability of survival without permanent disability. In addition, we assessed the cost-effectiveness of ICH surgery by examining the effective cost per 1-year survivor (ECPS) and per independent survivor (ECPIS). RESULTS: Of 254 patients, 27% were in the early surgery group. Overall 12-month mortality was 39%, while 29% survived without a permanent disability. According to our multivariable analysis, early ICH surgery was associated with lower 12-month mortality rates (odds ratio [OR] 0.22, 95% confidence intervals [CI] 0.10-0.51), but not with a higher probability of survival without permanent disability (OR 1.23, 95% CI 0.59-2.56). For the early surgical group, the ECPS and ECPIS were 111,409 and 334,227, respectively. For the non-surgical cohort, the ECPS and ECPIS were 76,074 and 141,471, respectively. CONCLUSIONS: Early surgery for superficial ICH is associated with a lower 12-month mortality risk but not with a higher probability of survival without a permanent disability. Further, costs were higher and cost-effectiveness was, thus, worse for the early surgical cohort.
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Hemorragia Cerebral/cirurgia , Idoso , Análise Custo-Benefício , Cuidados Críticos/economia , Feminino , Finlândia , Humanos , Unidades de Terapia Intensiva , Masculino , Pessoa de Meia-Idade , Estudos RetrospectivosRESUMO
BACKGROUND: Diffuse intrinsic pontine gliomas (DIPGs) have a dismal prognosis. Previously, diagnosis was based on a typical clinical presentation and magnetic resonance imaging findings. After the start of the era of biopsies, DIPGs bearing H3 K27 mutations have been reclassified into a novel entity, diffuse midline glioma, based on the presence of this molecular alteration. However, it is not well established how clinically diagnosed DIPG overlap with H3 K27-mutated diffuse midline gliomas, and whether rare long-term survivors also belong to this group. METHODS: We studied tumor samples obtained at diagnosis or upon autopsy from 23 children, including two long-term survivors. Based on clinical, radiological, and histological findings, all tumors were previously diagnosed as DIPGs. All samples were analyzed for genetic alterations by next-generation sequencing (NGS) and for protein expression by immunohistochemistry (IHC). RESULTS: H3 K27 was mutated in NGS or IHC in 20 patients, excluding both long-term survivors. One of these long-term survivors harbored a mutation in IDH1, formerly considered to be an alteration absent in pediatric diffuse brainstem gliomas. Other altered genes in NGS included TP53 (10 patients), MET and PDGFRA (3 patients each), VEGFR and SMARCA4 (2 patients each), and PPARγ, PTEN and EGFR in 1 patient, respectively. IHC revealed cMYC expression in 15 of 24 (63%) of all samples, exclusively in the biopsies. CONCLUSIONS: Eighty-seven percent of the tumors formerly diagnosed as DIPGs could be reclassified as H3 K27-mutated diffuse midline gliomas. Both long-term survivors lacked this alteration. Contrary to former conceptions, IDH1 mutations may occur also in pediatric brainstem gliomas.
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Regulação Neoplásica da Expressão Gênica , Glioma , Sequenciamento de Nucleotídeos em Larga Escala , Proteínas de Neoplasias , Proteínas do Tecido Nervoso , Adolescente , Biópsia , Neoplasias do Tronco Encefálico/genética , Neoplasias do Tronco Encefálico/metabolismo , Neoplasias do Tronco Encefálico/patologia , Criança , Pré-Escolar , Feminino , Glioma/genética , Glioma/metabolismo , Glioma/patologia , Humanos , Masculino , Proteínas de Neoplasias/biossíntese , Proteínas de Neoplasias/genética , Proteínas do Tecido Nervoso/biossíntese , Proteínas do Tecido Nervoso/genéticaRESUMO
BACKGROUND AND PURPOSE: Patient and radiological characteristics of intracerebral hemorrhage (ICH), surgical treatment, and outcome after ICH are interrelated. Our purpose was to define whether these characteristics or surgical treatment correlate with mortality among young adults. METHODS: We retrospectively reviewed clinical and imaging data of all first-ever nontraumatic patients with ICH between 16 and 49 years of age treated in our hospital between January 2000 and March 2010 and linked these data with national causes of death registry. A logistic regression analysis of factors associated with 3-month mortality and a propensity score comparison between patients treated conservatively and operatively was performed. RESULTS: Among the 325 eligible patients (59.4% men), factors associated with 3-month mortality included higher National Institutes of Health Stroke Scale score, infratentorial location, hydrocephalus, herniation, and multiple hemorrhages. Adjusted for these factors, as well as demographics, ICH volume, and the underlying cause, surgical evacuation was associated with lower 3-month mortality (odds ratio, 0.06; 95% confidence interval, 0.02-0.21). In propensity score-matched analysis, 3-month case fatality rates were 3-fold in those treated conservatively (27.5% versus 7.8%; P<0.001). CONCLUSIONS: The predictors of short-term case fatality are alike in young and elderly patients with ICH. However, initial hematoma evacuation was associated with lower 3-month case fatality in our young patients with ICH.
Assuntos
Hemorragia Cerebral/mortalidade , Adolescente , Adulto , Hemorragia Cerebral/etiologia , Feminino , Mortalidade Hospitalar , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Estudos Retrospectivos , Fatores de Risco , Resultado do Tratamento , Adulto JovemRESUMO
BACKGROUND AND PURPOSE: Seizures are a common complication of intracerebral hemorrhage (ICH). We developed a novel tool to quantify this risk in individual patients. METHODS: Retrospective analysis of the observational Helsinki ICH Study (n=993; median follow-up, 2.7 years) and the Lille Prognosis of InTra-Cerebral Hemorrhage (n=325; 2.2 years) cohorts of consecutive ICH patients admitted between 2004 and 2010. Helsinki ICH Study patients' province-wide electronic records were evaluated for early seizures occurring within 7 days of ICH and among 7-day survivors (n=764) for late seizures (LSs) occurring >7 days from ICH. A Cox regression model estimating risk of LSs was used to derive a prognostic score, validated in the Prognosis of InTra-Cerebral Hemorrhage cohort. RESULTS: Of the Helsinki ICH Study patients, 109 (11.0%) had early seizures within 7 days of ICH. Among the 7-day survivors, 70 (9.2%) patients developed LSs. The cumulative risk of LSs was 7.1%, 10.0%, 10.2%, 11.0%, and 11.8% at 1 to 5 years after ICH, respectively. We created the CAVE score (0-4 points) to estimate the risk of LSs, with 1 point for each of cortical involvement, age<65 years, volume>10 mL, and early seizures within 7 days of ICH. The risk of LSs was 0.6%, 3.6%, 9.8%, 34.8%, and 46.2% for CAVE scores 0 to 4, respectively. The c-statistic was 0.81 (0.76-0.86) and 0.69 (0.59-0.78) in the validation cohort. CONCLUSIONS: One in 10 patients will develop seizures after ICH. The risk of this adverse outcome can be estimated by a simple score based on baseline variables.
Assuntos
Hemorragia Cerebral/epidemiologia , Convulsões/epidemiologia , Índice de Gravidade de Doença , Idoso , Hemorragia Cerebral/complicações , Hemorragia Cerebral/mortalidade , Feminino , Finlândia/epidemiologia , Humanos , Masculino , Pessoa de Meia-Idade , Avaliação de Resultados da Assistência ao Paciente , Valor Preditivo dos Testes , Prognóstico , Modelos de Riscos Proporcionais , Estudos Retrospectivos , Risco , Convulsões/etiologia , Convulsões/mortalidade , Fatores de TempoRESUMO
BACKGROUND AND OBJECTIVES: Delayed cerebral ischemia (DCI) is one of the main contributing factors to poor clinical outcome after aneurysmal subarachnoid hemorrhage (SAH). Unsuccessful treatment can cause irreversible brain injury in the form of DCI-related infarction. We aimed to assess the association between the location, distribution, and size of DCI-related infarction in relation to clinical outcome. METHODS: Consecutive patients with SAH treated at 2 university hospitals between 2014 and 2019 (Helsinki, Finland) and between 2006 and 2020 (Aachen, Germany) were included. Size of DCI-related infarction was quantitatively measured as absolute volume (in milliliters). In a semiquantitative fashion, infarction in 14 regions of interest (ROIs) according to a modified Alberta Stroke Program Early CT Score (ASPECTS) was noted. The association of infarction in these ROIs along predefined regions of eloquent brain, with clinical outcome, was assessed. For this purpose, 1-year outcome was measured by the Glasgow Outcome Scale (GOS) and dichotomized into favorable (GOS 4-5) and unfavorable (GOS 1-3). RESULTS: Of 1,190 consecutive patients with SAH, 155 (13%) developed DCI-related infarction. One-year outcome data were available for 148 (96%) patients. A median overall infarct volume of 103 mL (interquartile range 31-237) was measured. DCI-related infarction was significantly associated with 1-year unfavorable outcome (odds ratio [OR] 4.89, 95% CI 3.36-7.34, p < 0.001). In patients with 1-year unfavorable outcome, vascular territories more frequently affected were left middle cerebral artery (affected in 49% of patients with unfavorable outcome vs in 30% of patients with favorable outcome; p = 0.029), as well as left (44% vs 18%; p = 0.003) and right (52% vs 14%; p < 0.001) anterior cerebral artery supply areas. According to the ASPECTS model, the right M3 (OR 8.52, 95% CI 1.41-51.34, p = 0.013) and right A2 (OR 7.84, 95% CI 1.97-31.15, p = 0.003) regions were independently associated with unfavorable outcome. DISCUSSION: DCI-related infarction was associated with a 5-fold increase in the odds of unfavorable outcome, after 1 year. Ischemic lesions in specific anatomical regions are more likely to contribute to unfavorable outcome. TRIAL REGISTRATION INFORMATION: Data collection in Aachen was registered in the German Clinical Trial Register (DRKS00030505); on January 3, 2023.
Assuntos
Infarto Cerebral , Hemorragia Subaracnóidea , Humanos , Hemorragia Subaracnóidea/diagnóstico por imagem , Hemorragia Subaracnóidea/complicações , Feminino , Masculino , Pessoa de Meia-Idade , Idoso , Infarto Cerebral/diagnóstico por imagem , Infarto Cerebral/etiologia , Escala de Resultado de Glasgow , Resultado do Tratamento , AdultoRESUMO
BACKGROUND AND OBJECTIVES: Large-scale genome-wide studies of chronic hydrocephalus have been lacking. We conducted a genome-wide association study (GWAS) in normal pressure hydrocephalus (NPH). METHODS: We used a case-control study design implementing FinnGen data containing 473,691 Finns with genotypes and nationwide health records. Patients with NPH were selected based on ICD-10 G91.2 diagnosis. To select patients with idiopathic NPH (iNPH) for sensitivity analysis, we excluded patients with a potentially known etiology of the condition using an algorithm on their disease history. The controls were the remaining non-hydrocephalic participants. For a replication analysis, the NPH cohort from UK Biobank (UKBB) was used. RESULTS: We included 1,522 patients with NPH (mean age 72.2 years, 53% women) and 451,091 controls (mean age 60.5 years, 44% women). In the GWAS comparing patients with NPH with the controls, we identified 6 gene regions significantly (p < 5.0e-8) associated with NPH that replicated in a meta-analysis with UKBB (NPH n = 173). The top loci near the following genes were rs7962263, SLCO1A2 (odds ratio [OR] 0.71, 95% CI 0.65-0.78, p = 1.0e-14); rs798495, AMZ1/GNA12 (OR 1.29, 95% CI 1.20-1.39, p = 2.9e-12); rs10828247, MLLT10 (OR 0.77, 95% CI 0.71-0.83, p = 1.5e-11); rs561699566 and rs371919113, CDCA2 (OR 0.76, 95% CI 0.70-0.82, p = 1.5e-11); rs56023709, C16orf95 (OR 1.24, 95% CI 1.16-1.33, p = 3.0e-9); and rs62434144, PLEKHG1 (OR 1.23, 95% CI 1.14-1.32, p = 1.4e-8). In the sensitivity analysis comparing only patients with iNPH (n = 1,055) with the controls (n = 451,091), 4 top loci near the following genes remained significant: rs7962263, SLCO1A2 (OR 0.70, 95% CI 0.63-0.78, p = 2.1e-11); rs10828247, MLLT10 (OR 0.74, 95% CI 0.62-0.82, p = 4.6e-10); rs798511, AMZ1/GNA12 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8); and rs56023709, C16orf95 (OR 1.28, 95% CI 1.17-1.39, p = 1.7e-8). DISCUSSION: We identified 6 loci significantly associated with NPH in the thus far largest GWAS in chronic hydrocephalus. The genes near the top loci have previously been associated with blood-brain barrier and blood-CSF barrier function and with increased lateral brain ventricle volume. The effect sizes and allele frequencies remained similar in NPH and iNPH cohorts, indicating the identified loci are risk determinants for iNPH and likely not explained by associations with other etiologies. However, the exact role of these loci is still unknown, warranting further studies.
Assuntos
Estudo de Associação Genômica Ampla , Hidrocefalia de Pressão Normal , Humanos , Hidrocefalia de Pressão Normal/genética , Feminino , Idoso , Masculino , Estudos de Casos e Controles , Pessoa de Meia-Idade , Predisposição Genética para Doença/genética , Finlândia , Estudos de Coortes , Polimorfismo de Nucleotídeo Único , Idoso de 80 Anos ou maisRESUMO
Objective-Direct oral anticoagulants (DOAC) are replacing vitamin K antagonists (VKA) for the prevention of ischemic stroke and venous thromboembolism. We set out to assess the effect of prior treatment with DOAC and VKA in patients with aneurysmal subarachnoid hemorrhage (SAH). Methods-Consecutive SAH patients treated at two (Aachen, Germany and Helsinki, Finland) university hospitals were considered for inclusion. To assess the association between anticoagulant treatments on SAH severity measure by modified Fisher grading (mFisher) and outcome as measured by the Glasgow outcome scale (GOS, 6 months), DOAC- and VKA-treated patients were compared against age- and sex-matched SAH controls without anticoagulants. Results-During the inclusion timeframes, 964 SAH patients were treated in both centers. At the time point of aneurysm rupture, nine patients (0.93%) were on DOAC treatment, and 15 (1.6%) patients were on VKA. These were matched to 34 and 55 SAH age- and sex-matched controls, re-spectively. Overall, 55.6% of DOAC-treated patients suffered poor-grade (WFNS4-5) SAH compared to 38.2% among their respective controls (p = 0.35); 53.3% of patients on VKA suffered poor-grade SAH compared to 36.4% in their respective controls (p = 0.23). Neither treatment with DOAC (aOR 2.70, 95%CI 0.30 to 24.23; p = 0.38), nor VKA (aOR 2.78, 95%CI 0.63 to 12.23; p = 0.18) were inde-pendently associated with unfavorable outcome (GOS1-3) after 12 months. Conclusions-Iatrogenic coagulopathy caused by DOAC or VKA was not associated with more severe radiological or clinical subarachnoid hemorrhage or worse clinical outcome in hospitalized SAH patients.
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BACKGROUND AND PURPOSE: The purpose of this study was to provide a simple and practical clinical classification for the etiology of intracerebral hemorrhage (ICH). METHODS: We performed a retrospective chart review of consecutive patients with ICH treated at the Helsinki University Central Hospital, January 2005 to March 2010 (n=1013). We classified ICH etiology by predefined criteria as structural vascular lesions (S), medication (M), amyloid angiopathy (A), systemic disease (S), hypertension (H), or undetermined (U). Clinical and radiological features and mortality by SMASH-U (Structural lesion, Medication, Amyloid angiopathy, Systemic/other disease, Hypertension, Undetermined) etiology were analyzed. RESULTS: Structural lesions, namely cavernomas and arteriovenous malformations, caused 5% of the ICH, anticoagulation 14%, and systemic disease 5% (23 liver cirrhosis, 8 thrombocytopenia, and 17 various rare conditions). Amyloid angiopathy (20%) and hypertensive angiopathy (35%) were common, but etiology remained undetermined in 21%. Interrater agreement in classifying cases was high (κ, 0.89; 95% CI, 0.82-0.96). Patients with structural lesions had the smallest hemorrhages (median volume, 2.8 mL) and best prognosis (3-month mortality 4%), whereas anticoagulation-related ICHs were largest (13.4 mL) and most often fatal (54%). Overall, median ICH survival was 5½ years, varying strongly by etiology (P<0.001). After adjustment for baseline characteristics, patients with structural lesions had the lowest 3-month mortality rates (OR, 0.06; 95% CI, 0.01-0.37) and those with anticoagulation (OR, 1.9; 1.0-3.6) or other systemic cause (OR, 4.0; 1.6-10.1) the highest. CONCLUSIONS: In our patients, performing the SMASH-U classification was feasible and interrater agreement excellent. A plausible etiology was determined in most patients but remained elusive in one in 5. In this series, SMASH-U based etiology was strongly associated with survival.
Assuntos
Hemorragia Cerebral/classificação , Hemorragia Cerebral/etiologia , Classificação/métodos , Adulto , Idoso , Idoso de 80 Anos ou mais , Angiopatia Amiloide Cerebral/complicações , Hemorragia Cerebral/mortalidade , Feminino , Humanos , Hipertensão/complicações , Masculino , Pessoa de Meia-Idade , Prognóstico , Reprodutibilidade dos Testes , Estudos Retrospectivos , Taxa de Sobrevida , Doenças Vasculares/complicaçõesRESUMO
INTRODUCTION: Endoscopic third ventriculostomy (ETV) is becoming an increasingly widespread treatment for hydrocephalus, but research is primarily based on paediatric populations. In 2009, Kulkarni et al created the ETV Success score to predict the outcome of ETV in children. The purpose of this study is to create a prognostic model to predict the success of ETV for adult patients with hydrocephalus. The ability to predict who will benefit from an ETV will allow better primary patient selection both for ETV and shunting. This would reduce additional second procedures due to primary treatment failure. A success score specific for adults could also be used as a communication tool to provide better information and guidance to patients. METHODS AND ANALYSIS: The study will adhere to the Transparent Reporting of a multivariable prediction model for Individual Prognosis Or Diagnosis reporting guidelines and conducted as a retrospective chart review of all patients≥18 years of age treated with ETV at the participating centres between 1 January 2010 and 31 December 2018. Data collection is conducted locally in a standardised database. Univariate analysis will be used to identify several strong predictors to be included in a multivariate logistic regression model. The model will be validated using K-fold cross validation. Discrimination will be assessed using area under the receiver operating characteristic curve (AUROC) and calibration with calibration belt plots. ETHICS AND DISSEMINATION: The study is approved by appropriate ethics or patient safety boards in all participating countries. TRIAL REGISTRATION NUMBER: NCT04773938; Pre-results.
Assuntos
Hidrocefalia , Terceiro Ventrículo , Adulto , Criança , Humanos , Hidrocefalia/cirurgia , Lactente , Estudos Multicêntricos como Assunto , Prognóstico , Estudos Retrospectivos , Terceiro Ventrículo/cirurgia , Resultado do Tratamento , Ventriculostomia/métodosRESUMO
BACKGROUND: The number of elderly patients with aneurysmal subarachnoid hemorrhage (aSAH) admitted to intensive care units (ICUs) has increased. We aimed to analyze the characteristics and outcomes of such patients in a tertiary university hospital during a 5-year period. METHODS: A retrospective single-center analysis was performed of patients with aSAH ≥70 years old admitted to a tertiary neuro-ICU during January 2014-May 2019 based on medical records and computed tomography scans. The primary outcome was functional outcome at 12 months. We used multivariable logistic regression to assess factors associated with unfavorable outcome (Glasgow Outcome Scale score 1-3 and institutionalized). RESULTS: Of 117 included patients, 49% had a favorable outcome at 12 months, and mortality was 41%. In multivariable analysis, poor-grade aSAH and intraventricular hemorrhage were predictors of poor outcome (odds ratio, 4.7, 95% confidence interval, 1.7-12.5 and odds ratio, 2.8, 95% confidence interval, 1.1-7.2, respectively). None of the patients with a Glasgow Coma Scale (GCS) motor score of 1-3 three days after admission was alive at 12 months. In contrast, 65% of those with a GCS motor score 6 had favorable outcome. CONCLUSIONS: Half of elderly patients with aSAH admitted to a neuro-ICU were able to live at home after 12 months. Mortality was significant, but the number of severely disabled patients was low. Clinical status at admission was the strongest predictor of outcome, whereas intraventricular hemorrhage increased the risk of poor outcome as well. GCS motor score 3 days after admission seemed to predict mortality and outcome.
Assuntos
Admissão do Paciente/tendências , Hemorragia Subaracnóidea/mortalidade , Hemorragia Subaracnóidea/cirurgia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Feminino , Humanos , Masculino , Estudos Retrospectivos , Hemorragia Subaracnóidea/diagnóstico por imagem , Fatores de Tempo , Resultado do TratamentoRESUMO
INTRODUCTION: Chronic subdural haematomas (CSDHs) are one of the most common neurosurgical conditions. The goal of surgery is to alleviate symptoms and minimise the risk of symptomatic recurrences. In the past, reoperation rates as high as 20%-30% were described for CSDH recurrences. However, following the introduction of subdural drainage, reoperation rates dropped to approximately 10%. The standard surgical technique includes burr-hole craniostomy, followed by intraoperative irrigation and placement of subdural drainage. Yet, the role of intraoperative irrigation has not been established. If there is no difference in recurrence rates between intraoperative irrigation and no irrigation, CSDH surgery could be carried out faster and more safely by omitting the step of irrigation. The aim of this multicentre randomised controlled trial is to study whether no intraoperative irrigation and subdural drainage results in non-inferior outcome compared with intraoperative irrigation and subdural drainage following burr-hole craniostomy of CSDH. METHODS AND ANALYSIS: This is a prospective, randomised, controlled, parallel group, non-inferiority multicentre trial comparing single burr-hole evacuation of CSDH with intraoperative irrigation and evacuation of CSDH without irrigation. In both groups, a passive subdural drain is used for 48 hours as a standard of treatment. The primary outcome is symptomatic CSDH recurrence requiring reoperation within 6 months. The predefined non-inferiority margin for the primary outcome is 7.5%. To achieve a 2.5% level of significance and 80% power, we will randomise 270 patients per group. Secondary outcomes include modified Rankin Scale, rate of mortality, duration of operation, length of hospital stay, adverse events and change in volume of CSDH. ETHICS AND DISSEMINATION: The study was approved by the institutional review board of the Helsinki and Uusimaa Hospital District (HUS/3035/2019 §238) and duly registered at ClinicalTrials.gov. We will disseminate the findings of this study through peer-reviewed publications and conference presentations. TRIAL REGISTRATION NUMBER: NCT04203550.
Assuntos
Drenagem , Hematoma Subdural Crônico/terapia , Ensaios Clínicos Controlados Aleatórios como Assunto , Irrigação Terapêutica , Finlândia , Humanos , Cuidados Intraoperatórios , Estudos Multicêntricos como Assunto , Estudos Prospectivos , Projetos de PesquisaRESUMO
BACKGROUND AND AIMS: We evaluated the accuracy of 19 published prognostic scores to find the best tool for predicting mortality after intracerebral hemorrhage (ICH). METHODS: A retrospective single-center analysis of consecutive patients with ICH (n=1013). After excluding patients with missing data (n=131), we analyzed 882 patients for 3-month (primary outcome), in-hospital, and 12-month mortality. We analyzed the strength of the individual score components and calculated the c-statistics, Youden index, sensitivity, specificity, negative and positive predictive value (NPV and PPV) for the scores. Finally, we included every score component in a multivariable model to analyze the maximum predictive value of the data elements combined. RESULTS: Observed in-hospital mortality was 23.6%, 3-month mortality was 31.0%, and 12-month mortality was 35.3%. For in-hospital mortality, the National Institutes of Health Stroke Scale (NIHSS) performed equally good as the best score for the other outcomes, the ICH Functional Outcome Score (ICH-FOS). The c-statistics of the scores varied from 0.6293 (95% CI 0.587-0.672) to 0.8802 (0.855-0.906). With all variables from all the scores in a multivariable regression model, the c-statistics did not improve, being 0.89 (0.867-0.913). Using the Youden index cutoff for the ICH-FOS score, the sensitivity (73%), specificity (90%), PPV (76%), and NPV (88%) for the primary outcome were good. CONCLUSIONS: A plethora of scores exists to help clinicians estimate the prognosis of an acute ICH patient. The NIHSS can be used to quantify the risk of in-hospital death while the ICH-FOS performed best for the other outcomes.
Assuntos
Hemorragia Cerebral/diagnóstico , Hemorragia Cerebral/mortalidade , Mortalidade Hospitalar/tendências , Índice de Gravidade de Doença , Feminino , Humanos , Masculino , Prognóstico , Estudos Retrospectivos , Fatores de RiscoRESUMO
BACKGROUND: Intracerebellar haemorrhage constitutes around 10% of all spontaneous, non-aneurysmal intracerebral haemorrhages (ICHs) and often carries a grim prognosis. In symptomatic patients, surgical evacuation is usually regarded the standard treatment. Our objective was to compare the in-hospital mortality and functional outcome at hospital discharge in either medically or surgically treated patients, and the impact of either treatment on long-term mortality after a cerebellar ICH. METHODS: An observational, retrospective, single-centre consecutive series of 114 patients with cerebellar ICH. We assessed the effect of different demographic factors on functional outcome and in-hospital mortality using logistic regression. We also divided the patients in medical and surgical treatment groups based on how they had been treated and compared the clinical and radiological parameters, in-hospital, and long-term mortality in the different groups. RESULTS: In our series, 38 patients (33.3%) underwent haematoma evacuation and 76 (66.7%) received medical treatment. Glasgow coma scale <8, blocked quadrigeminal cistern, and severe hydrocephalus were associated with in-hospital death or poor functional outcome at discharge (modified Rankin scale 4-6). Surgically treated patients were younger, had larger haematomas both in volume and diameter, were in a worse clinical condition, and suffered more from hydrocephalus and brainstem compression. There were no statistically significant differences in in-hospital or long-term mortality. However, the surgically treated patients remained in a poor clinical condition. CONCLUSIONS: Surgical treatment of cerebellar ICH can be life-saving but often leads to a poor functional outcome. New studies are needed on long-term functional outcome after a cerebellar ICH.
RESUMO
Background. Frequency and impact of medical complications on short-term mortality in young patients with intracerebral hemorrhage (ICH) have gone unstudied. Methods. We reviewed data of all first-ever nontraumatic ICH patients between 16 and 49 years of age treated in our hospital between January 2000 and March 2010 to identify medical complications suffered. Logistic regression adjusted for known ICH prognosticators was used to identify medical complications associated with mortality. Results. Among the 325 eligible patients (59% males, median age 42 [interquartile range 34-47] years), infections were discovered in 90 (28%), venous thrombotic events in 13 (4%), cardiac complications in 4 (1%), renal failure in 59 (18%), hypoglycemia in 15 (5%), hyperglycemia in 165 (51%), hyponatremia in 146 (45%), hypernatremia in 91 (28%), hypopotassemia in 104 (32%), and hyperpotassemia in 27 (8%). Adjusted for known ICH prognosticators and diabetes, the only independent complication associated with 3-month mortality was hyperglycemia (plasma glucose >8.0 mmol/L) (odds ratio: 5.90, 95% confidence interval: 2.25-15.48, P < 0.001). Three or more separate complications suffered also associated with increased mortality (7.76, 1.42-42.49, P = 0.018). Conclusions. Hyperglycemia is a frequent complication of ICH in young adults and is independently associated with increased mortality. However, multiple separate complications increase mortality even further.