The association between hyponatraemia and long-term functional outcome in patients with aneurysmal subarachnoid haemorrhage: A single centre prospective cohort study

To assess the association between hyponatraemia and long-term functional outcome and other relevant outcomes in patients with aneurysmal subarachnoid haemorrhage (aSAH) we conducted a prospective cohort study in a Neurosciences Intensive Care Unit (ICU) in Sydney, Australia. The primary exposure variable was hyponatraemia (Na⁺ <135 mmol/L). The primary outcome was favourable outcome, a score of 5–8 on the extended Glasgow Outcome Score (GOSe) at 12 months. We also measured mortality, the incidence of delayed cerebral ischaemia (DCI) and cerebral arterial vasospasm and duration of ICU and hospital admission. There were 200 participants, 111 (56%) developed hyponatraemia. Hyponatraemia was not associated with favourable outcome at 12 months (unadjusted odds ratio [OR] OR 1.31, 95% confidence interval [CI] 0.65–2.65, p = 0.56). The result was similar after adjustment for baseline covariates (adjusted OR 0.60, 95% CI 0.16–1.99, p = 0.43). There was no association between hyponatraemia and the incidence of DCI (OR 0.95, 95% CI 0.46 to 2.0, p > 0.99) nor cerebral arterial vasospasm (OR 1.4, 95% CI 0.8 to 2.5, p = 0.27). Those who developed hyponatraemia had a longer median duration of ICU admission (17 days, interquartile range [IQR] 12 to 20, compared to 13 days, IQR 8–21, p = 0.02) and longer median duration of hospital admission (24 days, IQR 21–30, compared to 22 days IQR 14–31, p = 0.05). While hyponatraemia is common following aSAH, it is not associated with worse long-term functional outcome, increased rate of DCI, nor cerebral arterial vasospasm. Hyponatraemia in patients with aSAH was associated with longer duration of ICU and hospital admission.     

Aneurysmal subarachnoid hemorrhage in patients with migraine and tension headache: A cohort comparison study

Migraine headache is a common condition with an estimated lifetime prevalence of greater than 20%. While it is a well-established risk factor for cardiovascular disease and ischemic stroke, its association with subarachnoid hemorrhage is largely unexplored. We sought to compare the incidence of aneurysmal subarachnoid hemorrhage in a cohort of migraine patients with a cohort of patients with tension headache. A cohort comparison study utilizing the MarketScan insurance claims database compared patients diagnosed with migraine who were undergoing treatment with abortive or prophylactic pharmacotherapy (treatment cohort) and patients diagnosed with tension headache who had never been diagnosed with a migraine and who were naïve to migraine pharmacotherapy (control cohort). Patients with major pre-existing risk factors for aSAH were excluded from the study, and minor risk factors such as smoking status and hypertension were accounted for using coarsened exact matching (CEM) and subsequent cox proportional-hazards (CPH) regression. More than 679,000 patients (~125,000 treatment and ~ 550,000 control) with an average follow-up of more than three years were analyzed for aneurysmal subarachnoid hemorrhage. CPH regression on matched data showed that treated migraine patients had a significantly lower hazard of aneurysmal subarachnoid hemorrhage compared with tension headache patients (HR = 0.40, 95% CI: 0.19 – 0.86, p = 0.02). This large cohort comparison study, analyzing more than 679,000 patients, demonstrated that migraine patients undergoing pharmacologic treatment had a lower hazard of aneurysmal subarachnoid hemorrhage than patients diagnosed with tension headaches. Future work specifically focusing on migraine medications may identify the mechanisms underlying this association.     

Tick‐borne encephalitis in Poland in years 1993–2008 – epidemiology and clinical presentation. A retrospective study of 687 patients

Background and purpose: Tick‐borne encephalitis (TBE) is an emerging disease in Europe as in Poland, especially in north‐eastern part of the country. The aim of the study was to characterize the epidemiology and clinical features of TBE in this region. Methods: Clinical and epidemiological data of 687 patients hospitalized between 1993 and 2008 at the Department of Infectious Diseases and Neuroinfections with the diagnosis of TBE were analysed. Results: In the case of 59 patients (9.5%), the disease was job related (forestry workers, farmers). In the examined group, TBE presented with meningitis in 282 cases (41%), with meningoencephalitis in 353 cases (51.3%) and with meningoencephalomyelitis in 52 cases (7.6%). The most common neurological abnormalities were ataxia in 88 cases (14.17%) and pareses in 53 cases (8.53%). Four patients (0.6%) died, 144 patients (23.2%) were discharged with neurological sequelae of TBE. Two hundred and seventy‐two patients (43.8%) required further psychiatric treatment. At least 38 patients (6.1%) developed long‐term sequelae and required further hospitalizations. Dexamethasone in the dosage of 6–32 mg was administered in 407 patients for 1–64 days. Conclusions: The diagnosis of TBE sometimes is difficult as the disease symptoms may be non‐characteristic. Therefore, a detailed anamnesis is very important in the process of TBE diagnosis and may alone justify lumbar puncture conduction. Despite usually mild course of the disease, patients may develop neurological and psychiatrical sequelae.     

High prevalence of rare ryanodine receptor type 1 variants in patients suffering from aneurysmatic subarachnoid hemorrhage: A pilot study

Subarachnoid hemorrhage (SAH) remains a challenging neurosurgical disease. The ryanodine receptor type 1 Ca2+ channel (RyR1) plays a crucial role in vasoconstriction and hemostasis. Mutations of the encoding gene, RYR1, are known to cause susceptibility to malignant hyperthermia (MH). Recently, a RYR1 mutation was found to be associated with abnormal bleeding times. Therefore, an assessment of the RYR1 gene might be of high relevance in patients with aneurysmatic SAH. In the presented pilot study, we screened 10 patients suffering from SAH for RYR1 variants and, for the first time in SAH, performed an assessment of pathogenicity of these variants using protein prediction software. Four of the patients showed a RYR1 variant. For three of the variants, p.Glu79Lys, p.Arg885C, p.Glu2635 Val, all three programs predicted pathogenicity. Their prevalence in the general population is very low i.e. under 0.005%. For the fourth variant, p.Pro4501Leu (RS73933023), the results of the prediction programs were discrepant and the prevalence in the general population was high, i.e. almost 0.5%, which is too frequent to be associated with the rare SAH phenotype. Clinical evaluation revealed that no differences concerning neurological outcome, presence of vasospasm, ischemic deficits and mean hospital stay between patients with and without variants were found. However, in our series SAH patients have an increased frequency of rare RYR1 variants. Hence, potentially contributing to the pathogenesis of SAH. Further data is needed to confirm this preliminary result.     

Six-month mortality and functional outcomes in aneurysmal sub-arachnoid haemorrhage patients admitted to intensive care units in Australia and New Zealand: A prospective cohort study

Historical studies suggest survivors of aneurysmal sub-arachnoid haemorrhage (SAH) have at least a moderate burden of functional impairment. However, there is a paucity of modern data concerning these outcomes in those admitted to the intensive care unit (ICU). Accordingly, the aim of this multicentre prospective observational cohort study was to provide contemporary epidemiological data concerning 6-month outcomes of adult aneurysmal SAH patients admitted to ICU in Australia and New Zealand (ANZ). Between March 2016 and June 2018 (inclusive), 357 patients requiring ICU admission were enrolled into the study, from eleven (n = 11) neurosurgical centres in ANZ. The majority of patients were female (n = 242, 68%), the median [IQR] age was 57 [49, 67] years, and almost all were living independently prior to their SAH (n = 337, 94%). 38% (n = 134) suffered a high-grade (WFNS 4–5) SAH. The median index ICU and hospital lengths of stay (LOS) were 9 [4–14], and 20 [13–29] days, respectively. In-hospital mortality was 22% (n = 77). Of the evaluable cohort (n = 348), a further nine (n = 9) patients had died by 6-months, yielding an all cause mortality of 25% (n = 86). Moreover, 35% (n = 114) of assessable patients were ‘dead or disabled’ (modified Rankin scale ≥4) at 6-months, and there was significant variation between sites, independent of SAH severity. Overall, these patients consumed substantial healthcare resources, and given the burden of mortality and morbidity, in addition to the variability between institutions, there may be opportunity to improve patient outcomes.     

Relation between brain lesion location and clinical outcome in patients with severe traumatic brain injury: A diffusion tensor imaging study using voxel‐based approaches

The early prediction of consciousness recovery from traumatic brain injury (TBI) is crucial to make decisions about the appropriate use of prolonged intensive care. Diffusion tensor imaging (DTI) has been proposed as a biomarker of white matter injury that could be used in a classification purpose. Instead of region‐of‐interest‐based approach, we applied voxel‐based approaches (voxel‐based DTI and tract‐based spatial statistics) on 30 patients with TBI to identify, without any prior, the brain regions that were specifically damaged in unfavorable 1‐year outcome group compared to the favorable one. DTI were acquired at mean 23 days (5–53 days) and two DTI‐derived indices, fractional anisotropy (FA) and apparent diffusion coefficient (ADC), were tested. Our results showed that (1) ADC is not a relevant biomarker for early 1‐year outcome prognosis; (2) FA measured in inferior longitudinal fasciculus, in cerebral peduncle, in posterior limb of the internal capsule, and in posterior corpus callosum is specifically decreased in unfavorable outcome group compare to the favorable one; (3) a linear discriminant analysis using the FA measured in these four regions showed good classification performance (sensitivity = 86% and specificity = 86%). These findings confirm the relevance of the use of DTI as biomarkers for consciousness recovery after TBI and support the possible use of these biomarkers for early classification of patients. Hum Brain Mapp, 2009. © 2009 Wiley‐Liss, Inc.     

The associations of APP , PSEN1 , and PSEN2 genes with Alzheimer's disease: A large case–control study in Chinese population

AimThe associations of non‐pathogenic variants of APP, PSEN1, and PSEN2 with Alzheimer''s disease (AD) remain unclear. This study is aimed at determining the role of these variants in AD.MethodsOur study recruited 1154 AD patients and 2403 controls. APP, PSEN1, PSEN2, and APOE were sequenced using a targeted panel. Variants were classified into common or rare variants with the minor allele frequencies (MAF) cutoff of 0.01. Common variant (MAF≥0.01)‐based association test was performed by PLINK 1.9, and gene‐based (MAF <0.01) association analysis was conducted using Sequence Kernel Association Test‐Optimal (SKAT‐O test). Additionally, using PLINK 1.9, we performed AD endophenotypes association studies.ResultsA common variant, PSEN2 rs11405, was suggestively associated with AD risk (p = 1.08 × 10⁻²). The gene‐based association analysis revealed that the APP gene exhibited a significant association with AD (p = 1.43 × 10⁻²). In the AD endophenotypes association studies, APP rs459543 was nominally correlated with CSF Aβ42 level (p = 7.91 × 10⁻³).ConclusionOur study indicated that non‐pathogenic variants in PSEN2 and APP may be involved in AD pathogenesis in the Chinese population.