Monique H M Vlak

Trigger Factors and Their Attributable Risk for Rupture of Intracranial Aneurysms: A Case-Crossover Study

Background and Purpose— Little is known about activities that trigger rupture of an intracranial aneurysm. Knowledge on what triggers aneurysmal rupture increases insight into the pathophysiology and facilitates development of prevention strategies. We therefore aimed to identify and quantify trigger factors for aneurysmal rupture and to gain insight into the pathophysiology. Methods— During a 3-year period, 250 patients with aneurysmal subarachnoid hemorrhage completed a structured questionnaire regarding exposure to 30 potential trigger factors in the period soon before subarachnoid hemorrhage (hazard period) and for usual frequency and intensity of exposure. We assessed relative risks (RR) of rupture after exposure to triggers with the case-crossover design comparing exposure in the hazard period with the usual frequency of exposure. Additionally, we calculated population-attributable risks. Results— Eight triggers increased the risk for subarachnoid hemorrhage: coffee consumption (RR, 1.7; 95% CI, 1.2–2.4), cola consumption (RR, 3.4; 95% CI,1.5–7.9), anger (RR, 6.3; 95% CI, 4.6–25), startling (RR, 23.3; 95% CI, 4.2–128), straining for defecation (RR, 7.3; 95% CI, 2.9–19), sexual intercourse (RR, 11.2; 95% CI, 5.3–24), nose blowing (RR, 2.4; 95% CI, 1.3–4.5), and vigorous physical exercise (RR, 2.4; 95% CI, 1.2–4.2). The highest population-attributable risks were found for coffee consumption (10.6%) and vigorous physical exercise (7.9%). Conclusions— We identified and quantified 8 trigger factors for aneurysmal rupture. All triggers induce a sudden and short increase in blood pressure, which seems a possible common cause for aneurysmal rupture. Some triggers are modifiable, and further studies should assess whether reduction of exposure to these factors or measures preventing sudden increase in blood pressure decrease the risk of rupture in patients known to have an intracranial aneurysm.

Independent Risk Factors for Intracranial Aneurysms and Their Joint Effect A Case-Control Study

Background and Purpose— Three percent of the population has an unruptured intracranial aneurysm (UIA). We aimed to identify independent risk factors from lifestyle and medical history for the presence of UIAs and to investigate the combined effect of well-established risk factors. Methods— We studied 206 patients with an UIA who never had a subarachnoid hemorrhage and 574 controls who were randomly retrieved from general practitioner files. All participants filled in a questionnaire on potential risk factors for UIAs. With logistic regression analysis, we identified independent risk factors for UIA and assessed their combined effect. Results— Independent risk factors were current smoking (odds ratio [OR], 3.0; 95% confidence interval [CI], 2.0–4.5), hypertension (OR, 2.9; 95% CI, 1.9–4.6), family history of stroke other than subarachnoid hemorrhage (OR, 1.6; 95% CI, 1.0–2.5), hypercholesterolemia (OR, 0.5; 95% CI, 0.3–0.9), and regular physical exercise (OR, 0.6; 95% CI, 0.3–0.9). The joint risk of smoking and hypertension was higher (OR, 8.3; 95% CI, 4.5–15.2) than the sum of the risks independently. Conclusions— Current smoking, hypertension, and family history of stroke increase the risk of UIA, with smoking and hypertension having an additive effect, whereas hypercholesterolemia and regular physical exercise decrease this risk. A healthy lifestyle probably reduces the risk of UIA and thereby possibly also that of aneurysmal subarachnoid hemorrhage. Whether smoking and hypertension increase the risk of aneurysmal subarachnoid hemorrhage only through an increased risk of aneurysm formation or also through an increased risk of rupture remains to be established.

Risk of Rupture of an Intracranial Aneurysm Based on Patient Characteristics A Case–Control Study

Background and Purpose— Knowledge about risk factors contributes to understanding the pathophysiological mechanisms that cause intracranial aneurysm rupture and helps to develop possible treatment strategies. We aimed to study lifestyle and personal characteristics as risk factors for the rupture of intracranial aneurysms. Methods— We performed a case–control study with 250 patients with an aneurysmal subarachnoid hemorrhage and 206 patients with an unruptured intracranial aneurysm. All patients with an aneurysmal subarachnoid hemorrhage and patients with a unruptured intracranial aneurysm were asked to fill in a structured questionnaire about their lifestyle and medical history. For patients with an unruptured intracranial aneurysm, we also collected data on the indication for imaging. With logistic regression analysis, we identified independent risk factors for aneurysmal rupture. Results— Reasons for imaging in patients with an unruptured intracranial aneurysm were atherosclerotic disease (23%), positive family history (18%), headache (8%), preventive screening (3%), and other (46%). Factors that increased risk for aneurysmal rupture were smoking (odds ratio, 1.9; 95% confidence interval, 1.2–3.0) and migraine (2.4; 1.1–5.1); hypercholesterolemia decreased this risk (0.4; 0.2–1.0), whereas a history of hypertension did not independently influence the risk. Conclusions— Smoking, migraine and, inversely, hypercholesterolemia are independent risk factors for aneurysmal rupture. Data from the questionnaire are insufficient to conclude whether hypercholesterolemia or its treatment with statins exerts a risk-reducing effect. The pathophysiological mechanisms through which smoking and migraine increase the risk of aneurysmal rupture should be investigated in further studies. Although a history of hypertension does not increase risk of rupture, a sudden rise in blood pressure might still trigger aneurysmal rupture.

Novel PRKCG/SCA14 mutation in a Dutch spinocerebellar ataxia family : expanding the phenotype

We report on a family with an autosomal dominant cerebellar ataxia in which we identified a novel mutation in exon 5 of the PRKCG/SCA14 gene that results in a Val138Glu substitution in the encoded protein PKCγ. While most affected subjects displayed a late‐onset uncomplicated form of spinocerebellar ataxia with occasional mild extrapyramidal features (such as postural tremor), one patient presented with a very mild nonprogressive ataxia since the age of 3 years and predominant multifocal myoclonus.

Lifetime risks for aneurysmal subarachnoid haemorrhage: multivariable risk stratification

Objective The overall incidence of aneurysmal subarachnoid haemorrhage (aSAH) in western populations is around 9 per 100 000 person-years, which confers to a lifetime risk of around half per cent. Risk factors for aSAH are usually expressed as relative risks and suggest that absolute risks vary considerably according to risk factor profiles, but such estimates are lacking. We aimed to estimate incidence and lifetime risks of aSAH according to risk factor profiles. Methods We used data from 250 patients admitted with aSAH and 574 sex-matched and age-matched controls, who were randomly retrieved from general practitioners files. We determined independent prognostic factors with multivariable logistic regression analyses and assessed discriminatory performance using the area under the receiver operating characteristic curve. Based on the prognostic model we predicted incidences and lifetime risks of aSAH for different risk factor profiles. Results The four strongest independent predictors for aSAH, namely current smoking (OR 6.0; 95% CI 4.1 to 8.6), a positive family history for aSAH (4.0; 95% CI 2.3 to 7.0), hypertension (2.4; 95% CI 1.5 to 3.8) and hypercholesterolaemia (0.2; 95% CI 0.1 to 0.4), were used in the final prediction model. This model had an area under the receiver operating characteristic curve of 0.73 (95% CI 0.69 to 0.76). Depending on sex, age and the four predictors, the incidence of aSAH ranged from 0.4/100 000 to 298/100 000 person-years and lifetime risk between 0.02% and 7.2%. Conclusions The incidence and lifetime risk of aSAH in the general population varies widely according to risk factor profiles. Whether persons with high risks benefit from screening should be assessed in cost-effectiveness studies.

Exome sequencing and network analysis identifies shared mechanisms underlying spinocerebellar ataxia.

The autosomal dominant cerebellar ataxias, referred to as spinocerebellar ataxias in genetic nomenclature, are a rare group of progressive neurodegenerative disorders characterized by loss of balance and coordination. Despite the identification of numerous disease genes, a substantial number of cases still remain without a genetic diagnosis. Here, we report five novel spinocerebellar ataxia genes, FAT2, PLD3, KIF26B, EP300, and FAT1, identified through a combination of exome sequencing in genetically undiagnosed families and targeted resequencing of exome candidates in a cohort of singletons. We validated almost all genes genetically, assessed damaging effects of the gene variants in cell models and further consolidated a role for several of these genes in the aetiology of spinocerebellar ataxia through network analysis. Our work links spinocerebellar ataxia to alterations in synaptic transmission and transcription regulation, and identifies these as the main shared mechanisms underlying the genetically diverse spinocerebellar ataxia types.

Comparison of patient and proxy responses on risk factors for stroke.

Capelle LG, Vlak MHM, Algra A, Rinkel GJE. Comparison of patient and proxy responses on risk factors for stroke.
Acta Neurol Scand: 2011: 123: 160–166.
© 2010 John Wiley & Sons A/S.

Risk factors in patients with perimesencephalic hemorrhage

Smoking and hypertension are risk factors for aneurysmal subarachnoid hemorrhage (aSAH), whilst excessive alcohol consumption is less consistently linked with aSAH. Perimesencephalic hemorrhage (PMH) is a benign subset of non‐aneurysmal subarachnoid hemorrhage. The exact cause of PMH is unknown, and its risk factor profile may help to elucidate the pathogenesis. The influence of smoking, hypertension and excessive alcohol consumption on the occurrence of PMH was studied.

Difference in Aneurysm Characteristics between Patients with Familial and Sporadic Aneurysmal Subarachnoid Haemorrhage.

Object Patients with familial intracranial aneurysms (IA) have a higher risk of rupture than patients with sporadic IA. We compared geometric and morphological risk factors for aneurysmal rupture between patients with familial and sporadic aneurysmal subarachnoid hemorrhage (aSAH) to analyse if these risk factors contribute to the increased rupture rate of familial IA. Methods Geometric and morphological aneurysm characteristics were studied on CT-angiography in a prospectively collected series of patients with familial and sporadic aSAH, admitted between September 2006 and September 2009, and additional patients with familial aSAH retrieved from the prospectively collected database of familial IA patients of our center. Odds ratios (OR) with corresponding 95% confidence intervals (95% CI) were calculated to compare the aneurysm characteristics between patients with familial and sporadic aSAH. Results We studied 67 patients with familial and 184 with sporadic aSAH. OR’s for familial compared with sporadic aSAH were for oval shape 1.16(95%CI:0.65–2.09), oblong shape 0.26(95%CI:0.03–2.13), irregular shape 0.83(95%CI:0.47–1.49), aspect ratio ≥ 1.6 0.94(95%CI:0.54–1.66), contact with the perianeurysmal environment (PAE) 1.15(95%CI:0.56–2.40), deformation by the PAE 1.05(95%CI:0.47–2.35) and for dominance of the posterior communicating artery (PCoA) in case of PCoA aneurysms 1.97(95% CI:0.50–7.83). Conclusions The geometric and morphological risk factors for aneurysm rupture do not have a higher prevalence in familial than in sporadic aSAH and thus do not explain the increased risk of IA rupture in patients with familial IA. We recommend further search for other potential risk factors for rupture of familial IA, such as genetic factors.

Migraine prevalence in patients with unruptured intracranial aneurysms: A case–control study

Migraine is a suggested risk factor for aneurysmal subarachnoid hemorrhage (aSAH). An increased risk of aSAH in migraineurs may be explained by an increased prevalence of unruptured intracranial aneurysms (UIA). We performed a case–control study to compare lifetime migraine prevalence in patients with UIA, patients with a history of transient ischemic attact (TIA) or ischemic stroke and controls without a history of aSAH, TIA or ischemic stroke.