Bo Kristensen

Epidemiology and Etiology of Ischemic Stroke in Young Adults Aged 18 to 44 Years in Northern Sweden

BACKGROUND AND PURPOSE The aim of this study was to conduct a population-based epidemiological survey among young adults aged 18 to 44 years in Northern Sweden and furthermore to gain further insight into the etiology of ischemic stroke in this age group. METHODS Two studies were done. In the first part, epidemiological data were collected to calculate incidence and mortality from 1991 through 1994. This was based on the World Health Organization Northern Sweden MONICA register of acute stroke events. Eighty-eight first-ever ischemic stroke patients were identified during that period. In the second part, 107 consecutive patients aged 18 to 44 years with ischemic stroke referred to a university hospital were studied prospectively during a 5-year period and were extensively evaluated according to a standardized protocol. On the basis of modified Trial of ORG 10172 in Acute Stroke Treatment (TOAST) criteria, the patients were classified into eight subtypes of ischemic stroke. RESULTS The average population-based annual incidence rate for ischemic stroke (cases per 100,000 per year) was 11.3 (95% confidence interval, 6.7 to 16.1). The case-fatality rate was 5.7%. According to the modified TOAST criteria, a probable cause of ischemic stroke was identified in 36% and remained unexplained in 21% of cases. Spontaneous cervical arterial dissection was the leading probable etiology (13%). Patent foramen ovale or atrial septal aneurysm was a possible cause of stroke in 28% of cases. The percentages of ischemic stroke attributed to IgG anticardiolipin antibodies (4.7%), atherothrombotic vasculopathy (3.7%), oral contraceptive use (7%), and migraine (1%) were lower than reported in recent clinical series. CONCLUSIONS The incidence rate for ischemic stroke was higher than previously reported from most countries in Western Europe. The higher incidence was not explained by a higher prevalence of premature atherosclerotic vasculopathy. Without the additional diagnostic information derived from advanced cardiac imaging, the proportion of indeterminate cases would have constituted 37% of the patients.

Cognitive impairment in young adults with infratentorial infarcts

Objective: To describe cognitive functions and functional outcome in young patients with isolated infratentorial infarcts. Background: Contemporary knowledge implies a cerebellar contribution to cognitive behavior. Neuropsychological examination of patients with selective cerebellar lesions provides an opportunity to document the existence and nature of clinically relevant cognitive manifestations from lesions of the cerebellum. Methods: Prospective case series. The patients were assessed acutely and at 4 and 12 months after onset. Twenty-four patients from a consecutive series of 105 patients aged 18 to 44 years with cerebral infarction had a brain stem or cerebellar infarction. Fourteen age-matched controls were used for neuropsychological comparisons. Evaluation included MRI, angiography, and transesophageal echocardiography. Disability and neurologic dysfunction were assessed by the modified Rankin scale, NIH stroke scale, and maximal working capacity. A comprehensive neuropsychological battery was performed at baseline in 20 of the 24 patients. Results: Eighteen patients had a cerebellar infarct. Two patients had lateral medullary infarcts, and two isolated pontine infarcts. Twenty-two patients had a favorable outcome according to the modified Rankin scale (grade 0-2) and the NIH scale. In contrast, 12 patients were granted full or partial sick leave at the 4 months follow-up, and 10 patients at 12 months. Patients generally performed worse than controls in various aspects of cognitive function, especially in tasks concerning working memory, the temporary storage of complex information, and cognitive flexibility. Measures of verbal IQ (r = -0.74) and performance IQ (r = -0.78) were related to the size of the infarct. The block design task performance in the early poststroke period predicted maximal working capacity at 12 months. Conclusions: Cerebellar damage impairs central aspects of attention and visuospatial skills. In contrast, intelligence and episodic memory remain unchanged. When the lesion involves large portions of the cerebellar hemispheres, changes concerning broad areas of intelligence may occur. The prognosis is favorable for neurologic dysfunction, but cognitive deficits may prevent return to work.

Regional cerebral blood flow, white matter abnormalities, and cerebrospinal fluid hydrodynamics in patients with idiopathic adult hydrocephalus syndrome.

OBJECTIVES--(1) to evaluate regional cerebral blood flow (rCBF) with single photon emission computed tomography and 99mTc-hexamethylpropyleneamine oxime in patients with the idiopathic adult hydrocephalus syndrome (IAHS); (2) to examine regional cerebral blood flow (rCBF), gait, and psychometric functions before and after CSF removal (CSF tap test); (3) to assess abnormalities in subcortical white matter by MRI. METHODS--Thirty one patients fulfilling the criteria for IAHS (according to history and clinical and neuroradiological examination) were studied. Quantified gait measurements, psychometric testing, and rCBF before and after removal of CSF were obtained. Pressure of CSF and CSF outflow conductance were investigated with a constant pressure infusion method. Brain MRI was used to quantify the severity of white matter lesions and periventricular hyperintensities. In IAHS a widespread rCBF hypoperfusion pattern was depicted, with a caudal frontal and temporal grey matter and subcortical white matter reduction of rCBF as the dominant feature. Removal of CSF was not accompanied by a concomitant increase in rCBF. Significant white matter lesions were detected only in a minority of patients by MRI. An altered CSF hydrodynamic state with a higher CSF pressure and lower conductance was confirmed. IAHS is characterised by an abnormal CSF hydrodynamic state, associated with a widespread rCBF reduction with preference for subcortical white matter and frontal-temporal cortical regions. Furthermore in most patients MRI did not show white matter changes suggestive of a coexistent subcortical arteriosclerotic encephalopathy. At least in the idiopathic group of patients with AHS, measurements of rCBF before and after temporary relief of the CSF hydrodynamic disturbance will not provide additional information that would be helpful in the preoperative evaluation but is suggestive of a preserved autoregulation of rCBF.

Three-year survival and functional outcome of patients with idiopathic adult hydrocephalus syndrome

Article abstract The functional outcome of 42 patients with idiopathic adult hydrocephalus syndrome (IAHS) was followed over a 3-year period after shunting. Survival curves were compared with those of age-matched healthy elderly subjects and patients with first-ever ischemic stroke. Twenty-seven patients with IAHS were improved 3 months after the operation and 11 remained improved at the 3-year follow-up. The case fatality in patients with stroke and those with IAHS was similar (32% versus 28%), but the relative risk of death among IAHS patients compared to a general elderly population was 3.3.

CSF hydrodynamics in idiopathic intracranial hypertension A long‐term study

To examine CSF hydrodynamics, we studied 16 patients with idiopathic intracranial hypertension and 45 control subjects with a constant-pressure infusion method. Fifteen patients had 155 examinations up to 15 years after the onset of disease. In most patients, the disturbances of CSF hydrodynamics persisted for many years. We identified at least two mechanisms for the development of the increased CSF pressure: a rise of sagittal sinus pressure, probably explained by extracellular edema causing partial compression of the major venous sinus (type 1), or a low conductance with a compensatory increase in CSF pressure in order to sustain the bulk flow (type 2).

Hyperhomocysteinemia and Hypofibrinolysis in Young Adults With Ischemic Stroke

BACKGROUND AND PURPOSE Data from epidemiological and case-control studies suggest that increased total homocysteine (tHcy) levels are associated with increased risk for thromboembolic disease. The mechanisms by which hyperhomocysteinemia contributes to thrombogenesis are incompletely understood. The main objectives of this study of young ischemic stroke patients were (1) to examine fasting and post-methionine load levels of tHcy, (2) to ascertain the genotype frequency of the C677CT mutation in the methylenetetrahydrofolate reductase gene (TT genotype), and (3) to study the possible interaction between plasma tHcy levels and fibrinolytic factors. METHODS This case-control study was based on 80 consecutive patients aged 18 to 44 years admitted between January 1992 and May 1996 as a result of a first-ever ischemic stroke. Forty-one healthy control subjects were recruited. Measurement of fasting tHcy and post-methionine load levels and evaluation of the fibrinolytic system were undertaken at least 3 months (mean, 5.1+/-1. 9 months) after admission. Genotyping of the methylenetetrahydrofolate reductase gene was performed. RESULTS Although the increase after methionine loading (ie, postload tHcy minus fasting-level tHcy) was significantly higher among patients, there was no difference in fasting and postload tHcy levels. After adjustment for conventional risk factors, elevated postload increase tHcy levels were associated with a 4.8-fold increased risk of ischemic stroke. There was no difference between patients and control subjects in either TT genotype frequency or T allele frequency. Abnormal response to methionine loading was associated with higher tissue plasminogen activator (tPA) mass concentration, higher plasminogen activator inhibitor-1 levels, and lower tPA activity. After adjustment for age, sex, body mass index, serum cholesterol, and triglycerides, an abnormal increase in postload tHcy levels remained significantly associated with tPA mass concentration levels (P=0.03). CONCLUSIONS A moderately elevated increase in tHcy levels after methionine loading was associated with an increased risk for ischemic stroke in young adults. In contrast, fasting tHcy levels did not differ between patients and controls. A moderately elevated increase in tHcy after methionine loading may provide a additional thrombogenic risk mediated in part by interactions with the fibrinolytic system. In young stroke patients, a methionine loading test to detect hyperhomocysteinemia should always be considered in the convalescent phase of the disease.

Increased Fibrinogen Levels and Acquired Hypofibrinolysis in Young Adults With Ischemic Stroke

BACKGROUND AND PURPOSE Elevated fibrinogen levels and abnormalities in the fibrinolytic system are related to the occurrence of cardiovascular events. However, the role of these factors in the evolution of cerebrovascular disease has received less attention, in particular in young stroke patients. The aim of this study was to evaluate possible abnormalities in plasma fibrinogen levels and the state of the fibrinolytic system in young adults with a first-ever ischemic stroke. METHODS This study is based on 102 consecutive patients aged 18 to 44 years admitted between January 1991 and May 1996 as a result of a first ischemic stroke. Forty-one healthy controls were recruited. Evaluations of anthropometric/metabolic variables, plasma fibrinogen levels, and the fibrinolytic system were undertaken >/=3 months (mean, 5.4+/-2.0 months) after admission. RESULTS Patients had lower tissue plasminogen activator activity and increased plasminogen activator inhibitor type 1 activity at baseline, as well as increased tissue plasminogen activator mass concentration both at baseline and after a venous occlusion test. Overall, there were no significant differences between the main etiologic subgroups regarding plasma fibrinogen levels and fibrinolytic variables. Baseline fibrinolytic variables were strongly correlated with body mass index, serum triglycerides, and cholesterol levels. After adjustments in multivariate models, fibrinogen levels and tissue plasminogen activator mass concentration both at baseline and after venous occlusion test remained significantly increased in patients. Logistic multiple regression analyses indicated that plasma fibrinogen was a strong predictor of ischemic stroke (odds ratio, 11.25; 95% CI, 3.27 to 38. 69). CONCLUSIONS Increased fibrinogen levels and tissue plasminogen activator mass concentration are independently associated with ischemic stroke in young adults. Metabolic perturbations are closely interrelated with aberrations in tissue plasminogen activator and plasminogen activator inhibitor type 1 activity in these patients, findings consistent with an acquired hypofibrinolysis.

CSF hydrodynamics in superior sagittal sinus thrombosis.

Cerebrospinal fluid hydrodynamics were investigated with a constant pressure infusion method in patients with superior sagittal sinus thrombosis. Ten patients were studied with serial examinations up to 15 years after the onset of the disease. A total of 70 CSF hydrodynamic examinations were performed. A clear increase in intracranial pressure due to raised pressure in the major dural sinus was seen in all patients. A striking feature was the persistent intracranial pressure increase that declined only gradually. This had no obvious clinical impact. Change in CSF resorption facility played only a minor role in the intracranial pressure elevation. None of the patients developed hydrocephalus.

Lateral sinus thrombosis after untreated otitis media. A clinical problem--again?

Abstract Antimicrobial agents have greatly reduced the incidence of intracranial complications of infections of the middle ear and mastoid. Too many prescriptions and overconsumption of antibiotics when otitis media is suspected has caused resistance to many antibiotics, leading to a pronounced and justifiable desire to reduce the widespread excessive use of antibiotics. The possible untoward consequences of a too restricted antibiotic policy, however, is illustrated by the following case of a 14-year-old boy who, after non-treatment of an ear infection, fell ill with one-sided headache and vomiting caused by a lateral sinus thrombosis. After intravenous treatment with antibiotics, anticoagulants and ventilation of the middle ear, the infection was cured without complications. This case calls attention to the symptoms of otitic complications arising outside the temporal bone. The physician must always bear in mind the possibility of an unusual event. The general treatment of endocranial complications is outlined, giving details of the treatment given in this special case. We stress that one should not be too cautious in prescribing antibiotics in otitis media.

Effects of transient and persistent cerebrospinal fluid drainage on sleep disordered breathing in patients with idiopathic adult hydrocephalus syndrome

OBJECTIVES To examine sleep disordered breathing including obstructive sleep apnoea in patients with idiopathic adult hydrocephalus syndrome (IAHS) and to study the effects of CSF drainage and shunting procedure on sleep disordered breathing. METHODS In 17 patients with IAHS polysomnographic investigations were performed before and after lumbar CSF drainage and after shunt operation. RESULTS Baseline investigations documented a high prevalence of sleep related obstructive respiratory events (respiratory disturbance index >10 in 65% of the patients) and impaired sleep structure. There was no correlation between respiratory disturbance index and CSF pressure. Minimum oxygen saturation was highly correlated with cognitive function. Neither lumbar CSF drainage nor shunting alleviated the respiratory disturbance index. REM and delta sleep increased initially after shunting but there was no sustained effect on sleep quality. CONCLUSIONS Sleep disordered breathing is a prevalent finding in patients with IAHS. The shortcoming of CSF drainage to improve sleep disordered breathing either transiently or permanently implies that sleep disordered breathing is a coexistent condition, or an irreversible consequence of the hydrocephalus, with a potential of causing additional dysfunction in IAHS.