Biomedical subjects
Publications and source records attributed to J van Gijn.
An 11-year-old girl had a one-day history of nausea and vomiting for which her family physician prescribed 4 suppositories of prochlorperazine 25 mg. Five hours after the last dose she developed dystonic posturing; she recovered rapidly after intramuscular injection of 40 mg orphenadrine.
OBJECTIVE: To assess the time course of secondary ischemia and first rebleeding and the relation between the timing of operation and the time course of secondary ischemia in a consecutive series of patients with aneurysmal subarachnoid hemorrhage (SAH). METHODS: Life table methods were used to assess the daily rates of ischemia and of rebleeding on day 0, day 1 to 3, day 4 to 10, day 11 to 14, and day 15 to 21. The authors compared the time course of secondary ischemia between patients operated within 4 days of SAH and those operated after 10 days. RESULTS: Of 346 patients included, 220 were operated, 131 within 4 days and 74 after 10 days. The rebleed rate was highest on the day of the initial hemorrhage, then diminished, and increased slightly again during the second week. The rate of secondary ischemia was highest on day 4, diminished after day 10, but peaked again from day 14 to 18 for patients who were operated later than 10 days after aneurysmal rupture. The peak rate of ischemia was much higher after early than after late operation. Although patients with early operation were in a better clinical condition on admission, with a relatively low risk of secondary ischemia, the overall rate of secondary ischemia was as high as in patients with delayed operation. From day 11 to 21 the rebleed rate was higher than the rate of secondary ischemia. CONCLUSIONS: These results indicate that operation is a risk factor for ischemia, especially when performed early. If operation is postponed, it should be planned soon after day 10, because of the relatively high rebleed rate from day 11 to 21.
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BACKGROUND: Cerebral white matter lesions are often observed on MRI scans of elderly nondemented and demented persons. Their pathogenesis is not fully understood but cerebral hypoperfusion may be involved. Atrial fibrillation is a common finding in elderly subjects and may lead to a reduced cardiac output with cerebral hypoperfusion. The authors investigated the association between atrial fibrillation and the presence of white matter lesions. METHODS: From 1995 through 1996, the authors randomly sampled 1077 subjects from two ongoing prospective population-based studies. From each participant, an electrocardiogram (ECG) was recorded; atrial fibrillation and left ventricular hypertrophy were diagnosed with a computer program. For one of the two groups (553 subjects), earlier ECGs were available (mean follow-up 4.7 years). All subjects underwent 1.5-T MRI scanning; white matter lesions were separately rated for the periventricular and subcortical regions. RESULTS: The prevalence of atrial fibrillation was 1.9% among subjects younger than 75 years and 5.5% in subjects older than 75 years. The total number of subjects with atrial fibrillation was 28. Subjects with atrial fibrillation had severe periventricular white matter lesions more than twice as often as subjects who did not (RR 2.2; 95% CI 1.0 to 5.2) but had no increased risk of subcortical white matter lesions (RR 1.1; 95% CI 0.4 to 2.6). For seven subjects with atrial fibrillation both at baseline and at follow up, these relative risks were 6.3 (95% CI 1.1 to 37.1) and 0.7 (95% CI 0.1 to 3.7). CONCLUSIONS: Atrial fibrillation is associated with periventricular white matter lesions, but not with subcortical white matter lesions.
Every physician encounters patients with physical symptoms that remain unexplained, despite appropriate investigations. Medical curricula and textbooks fail to provide guidance about the management of such problems. Particularly specialists tend to feel helpless; this often leads to more referrals and unnecessary operations. Three patients, referred to a neurologist for a second opinion, had chronic, unexplained, crippling pains: a woman aged 53 with low back pain radiating to the right leg for 27 years, a man aged 31 with neck pain for 3 years and a woman aged 31 with pain in the left arm for 1.5 years. They had no recognisable features of depression. Their illness behaviour reversed after the neurologist reassured the patients and advised them to embark upon a strict programme of gradually increasing activities. In two of the patients, the scheme was supervised by the general practitioner. A follow-up interview (after a median interval of 3 years) of 27 similar patients referred for a second opinion showed some success with this approach in about half of them. In retrospect no predictive factors at baseline could be identified other than age and duration of symptoms. An indispensable first step in patients with unexplained, chronic pain is unqualified recognition of the symptoms, reassurance, and an explanation that avoids the mind-body division.
OBJECTIVE: To assess the safety and feasibility of a clinical trial on the effectiveness of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH). BACKGROUND: Several studies have indicated that increased platelet activity might be involved in the pathogenesis of delayed cerebral ischemia (DCI) after SAH. METHOD: Fifty patients who had early surgery (< or =4 days) for a ruptured aneurysm were enrolled in this randomized, double-blind, placebo-controlled trial. Trial medication, consisting of suppositories with 100 mg ASA versus placebo, was started immediately after surgical clipping of the aneurysm and continued for 21 days. End points were functional outcome and quality of life at 4 months, clinical deterioration after operation, development of DCI, hypodense lesion on postoperative CT, and hemorrhagic complications. RESULTS: One-third of all patients with aneurysmal SAH were eligible for the trial. Fifteen of 26 patients receiving placebo deteriorated clinically versus 10 of 24 patients receiving ASA; 4 patients in each group deteriorated from DCI. Postoperative hypodensities on CT were observed in 27 patients, distributed equally in both groups. Functional outcome and quality-of-life scores were slightly in favor of patients who had received ASA, but not to a significant degree (p = 0.22). Two patients in the ASA group had an asymptomatic hemorrhagic complication, and one patient in the placebo group had a fatal and another a symptomatic hemorrhagic complication. CONCLUSION: This pilot study shows that a clinical trial of acetylsalicylic acid (ASA) in subarachnoid hemorrhage (SAH) is feasible and probably safe. The effectiveness of ASA on functional outcome and delayed cerebral ischemia has to be studied in a larger trial.
The round figure for the current year has stirred people's minds in anticipation. Numbers have acquired great significance also in today's medical science. The Paris physician Pierre Charles Alexandre Louis (1787-1872) is considered the founding father of the numerical method in medicine. At first the principle of aggregating data from different individuals aroused much resistance and even disgust: Claude Bernard was a leading figure among those who warned that one will never find a mean in nature, and that grouping findings together obscures the true relationship between biological phenomena. True enough, statistical significance is not a characteristic of nature itself. Significant differences or risk reductions do not necessarily imply clinical relevance, and results obtained in a group of patients are rarely applicable to an individual patient in the consultation room. Likewise, the health of a human being cannot be captured in biochemical, radiological or other technical measures, nor in disease-specific scales that reduce well-being to one or two digits. The editors of this journal will remain keen on publishing numerical studies that contribute to evidence-based medicine, but at the same time they will continue to foster the art of reporting illness from the point of view of the sick person.
BACKGROUND: Rupture of an intracranial aneurysm causes bleeding into the subarachnoid space, which may lead to spasm of the cerebral arteries and ischaemic damage to the brain. Prophylactic use of calcium antagonists in patients with ruptured intracranial aneurysms might reduce the risk of ischaemic damage. OBJECTIVES: This review aimed to determine whether calcium antagonists improve outcome in patients with aneurysmal subarachnoid haemorrhage (SAH). SEARCH STRATEGY: The Cochrane Stroke Group trials register (last searched: March 1999) plus hand searching and personal contacts with trialists and pharmaceutical companies marketing calcium antagonists. SELECTION CRITERIA: All completed, unconfounded, truly randomised controlled trials comparing any calcium antagonist with control, within ten days of SAH onset. Eleven trials that met the inclusion criteria were included in the overview. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: We analysed 11 trials totalling 2804 randomized patients with subarachnoid haemorrhage (1376 in the treatment and 1428 in the control group). The drugs analyzed were: nimodipine (eight trials, 1574 patients), nicardipine (two trials, 954 patients), and AT877 (one trial, 276 patients). In 92% of the patients aneurysms were confirmed by angiography or autopsy. Overall, calcium antagonists significantly reduce the risk of poor outcome after subarachnoid haemorrhage: relative risk (RR) 0.82 (95% CI 0. 72-0.93); the absolute risk reduction was 5.1%, the corresponding number of patients needed to treat to prevent a single poor outcome event is 20. For oral nimodipine alone the RR was 0.69 (0.58-0.84). The RR of death on treatment with calcium antagonists was 0.94 (95% CI 0.80-1.10), that of ischaemic neurological deficits 0.67 (95% CI 0.59-0.76), and that of CT-scan documented cerebral infarction 0.80 (95% CI 0.71-0.89). REVIEWER'S CONCLUSIONS: Calcium antagonists reduce the proportion of patients with poor outcome and ischemic neurological deficits after aneurysmal SAH; the risk reduction for case fatality alone is not statistically significant. The results for 'poor outcome' are statistically robust, but depend mainly on trials with oral nimodipine; the evidence for nicardipine and AT877 is inconclusive. The intermediate factors through which nimodipine exerts its beneficial effect after aneurysmal SAH remain uncertain.
BACKGROUND: Patients with subarachnoid haemorrhage who develop spasm of the cerebral arteries may suffer from delayed cerebral ischaemia. This may be exacerbated by reduced circulatory volume. Intravenous fluid therapy to expand the circulating volume might reduce the risk of delayed cerebral ischaemia and so reduce the risk of neurological disability. OBJECTIVES: The object of this review was to determine whether there is evidence that volume expansion therapy improves outcome in patients with aneurysmal subarachnoid haemorrhage. SEARCH STRATEGY: The Cochrane Stroke Group's Specialised Register was searched for trials relevant to this review (last searched: March 1999). Trialists were also contacted. SELECTION CRITERIA: All randomized controlled trials of volume expansion therapy in patients with aneurysmal subarachnoid haemorrhage. DATA COLLECTION AND ANALYSIS: Two reviewers independently extracted the data and assessed trial quality. Trialists were contacted to obtain missing information. MAIN RESULTS: Two trials were identified. For one trial the decision about inclusion is pending because clinical data on follow up have not been provided yet. In the other trial, outcome assessment was done at the day of operation (7 to 10 days after subarachnoid haemorrhage); data on longer follow up have not been collected. REVIEWER'S CONCLUSIONS: The effects of volume expansion therapy have not been studied properly in patients with aneurysmal subarachnoid haemorrhage. At present, there is no sound evidence for or against the use of volume expansion therapy in patients with aneurysmal subarachnoid haemorrhage.
BACKGROUND: Re-bleeding is an important cause of death and disability in people with aneurysmal subarachnoid haemorrhage. This is probably due to dissolution of the clot by natural fibrinolytic activity. OBJECTIVES: The objective of this review was to assess the effect of antifibrinolytic treatment in patients with aneurysmal subarachnoid haemorrhage. SEARCH STRATEGY: We searched the Cochrane Stroke Group trials register and reference lists of articles. We also contacted drug companies. SELECTION CRITERIA: Randomised trials comparing oral or intravenous antifibrinolytic drugs (tranexamic acid, epsilon amino-caproic acid or an equivalent) with control in people with confirmed subarachnoid haemorrhage. DATA COLLECTION AND ANALYSIS: Two reviewers independently selected trials for inclusion and extracted the data. All five reviewers assessed trial quality. MAIN RESULTS: Eight trials involving 937 patients were included. Based on 579 patients in two trials, antifibrinolytic treatment did not show any benefit for poor outcome (death, vegetative state or severe disability) with an odds ratio of 1.05, 95% confidence interval 0.76 to 1.46. Death from all causes was not significantly influenced by treatment across all eight trials (odds ratio 0.96, 95% confidence interval 0.72 to 1.26). Antifibrinolytic treatment reduced the risk of re-bleeding reported at the end of follow-up, with some heterogeneity between the trials (odds ratio 0.59, 95% confidence interval 0.42 to 0.81). Treatment increased the risk of cerebral ischaemia in four trials (odds ratio 2.03, 95% confidence interval 1.40 to 2.94). Antifibrinolytic treatment showed no effect on the reported rate of hydrocephalus in four trials (odds ratio 1. 05, 95% confidence interval 0.71 to 1.56). REVIEWER'S CONCLUSIONS: Antifibrinolytic treatment does not appear to benefit people with aneurysmal subarachnoid haemorrhage. However, the trials were all done more than 10 years ago. New strategies may counteract the ischaemia-inducing potential of antifibrinolytic treatment and lead to improved outcome. A trial of combined antifibrinolytic and anti-ischaemia treatment is underway.
Cerebral white matter lesions (WMLs) have been associated with cognitive dysfunction. Whether periventricular or subcortical WMLs relate differently to cognitive function is still uncertain. In addition, it is unclear whether WMLs are related to specific cognitive domains such as memory or psychomotor speed. We examined the relationship between periventricular and subcortical WMLs and cognitive functioning in 1,077 elderly subjects randomly sampled from the general population. Quantification of WMLs was assessed by means of an extensive rating scale on 1.5-T magnetic resonance imaging scans. Cognitive function was assessed by using multiple neuropsychological tests from which we constructed compound scores for psychomotor speed, memory performance, and global cognitive function. When analyzed separately, both periventricular and subcortical WMLs were related to all neuropsychological measures. When periventricular WMLs were analyzed conditional on subcortical WMLs and vice versa, the relationship between periventricular WMLs and global cognitive function remained unaltered whereas the relationship with subcortical WMLs disappeared. Subjects with most severe periventricular WMLs performed nearly 1 SD below average on tasks involving psychomotor speed, and more than 0.5 SD below average for global cognitive function. Tasks that involve speed of cognitive processes appear to be more affected by WMLs than memory tasks.
In many patients with subarachnoid hemorrhage (SAH) there is a delay between the onset of symptoms and admission to hospital. An important cause for the delay is an initially erroneous diagnosis. The goal of this study was to determine the frequency of acute confusional state (ACS) as a presenting symptom of SAH and to describe the clinical and radiological characteristics of these patients. We studied all 717 patients registered from January 1989 to July 1997 in the SAH database of the University Medical Center Utrecht. For patients who presented with ACS we reviewed the computed tomography scans for baseline characteristics: the amount of cisternal blood, intraventricular or intracerebral hemorrhage, and hydrocephalus. Details about features of onset were known for 646 patients. Nine patients (1.4%) presented with ACS. In five patients ACS was either preceded by a period of loss of consciousness or accompanied by severe headache. Subtle focal deficits were found at initial neurological examination in four patients. Computed tomography demonstrated a frontal hematoma in three patients and hydrocephalus in four. The site of the ruptured aneurysm was at the anterior communicating artery in four patients, at the internal carotid artery in two, and at the basilar artery in two. In our series, one per 70 patients with SAH presents with ACS. Keys to early diagnosis of SAH in patients presenting with ACS are a preceding period of loss of consciousness and severe headache on neurological assessment.
"Quality of life" (QOL) measurement reflects the impact of a disease on the daily life of a patient, and this can be used as an outcome measure in clinical trials. QOL measurements are rarely used in patients with neuromuscular disease. The aim of this study was to determine whether QOL is reduced in chronic polyneuropathy, whether there is a relationship between QOL and objective measures of disease severity, and whether measuring QOL is a useful addition to the assessment of severity of polyneuropathy. We measured QOL in 90 patients with chronic axonal polyneuropathy (33 with hereditary motor and sensory neuropathy type II and 57 with chronic idiopathic axonal polyneuropathy) using the RAND 36-item Health Survey questionnaire (RAND-36). We compared the results with the QOL of a reference population, with summed motor and sensory scores, and with the Rankin scale for handicap. Patients had worse scores than the reference population on seven of eight areas of the RAND-36. Patients with both low motor and low sensory scores rated lower in physical and emotional areas than less impaired patients. A low Rankin score was related only to physical domains. We conclude that in patients with chronic axonal polyneuropathy the severity of disease can be assessed with a general QOL instrument, and that this provides additional information, particularly on areas related to emotional and social functioning.
Cerebral white matter lesions are frequently observed on magnetic resonance imaging of elderly, nondemented persons. There is evidence that white matter lesions are involved in the pathophysiology of cognitive decline and dementia. White matter lesions can be divided into those in the periventricular and those in the subcortical region. Pathological and epidemiological studies suggest that atherosclerosis is involved in the pathogenesis of these lesions. Our study reports on the association between atherosclerosis in the carotid arteries and white matter lesions in a population-based study among 1077 elderly subjects. We randomly sampled 1077 subjects aged between 60-90 years from two prospective population-based studies. All subjects underwent ultrasonography of the carotid artery. In addition, 1.5 T magnetic resonance imaging was performed; white matter lesions in the subcortical and periventricular regions were rated separately. With increasing number of plaques in the carotid artery the severity of periventricular white matter lesions increased (Ptrend = 0.03), but not the severity of subcortical white matter lesions (Ptrend = 0.19). In addition, an increase in intima media thickness was borderline significantly associated with an increased severity of periventricular white matter lesions (Ptrend = 0.09), but not of subcortical white matter lesions (Ptrend = 0.68). These findings suggest that partly dissimilar pathogenetic mechanisms are involved in the etiology of periventricular and subcortical white matter lesions.
OBJECTIVES: to assess whether the risk of recurrent ischaemic stroke in patients with symptomatic internal carotid artery (ICA) occlusion has changed over the past decades, to determine risk factors for the occurrence of ischaemic stroke and to assess the risk of endarterectomy (CEA) of a severe contralateral ICA stenosis. DESIGN: retrospective cohort study. PATIENTS AND METHODS: patients with symptomatic ICA occlusion were identified from duplex registry files between 1991 and 1995. Information was obtained on vascular risk factors, performance of CEA for a contralateral ICA stenosis and on recurrence of ischaemic stroke. The rate of complications occurring within 30 days after CEA of the contralateral ICA in patients with symptomatic ICA occlusion was compared with the risk of CEA in patients with asymptomatic ICA occlusion and severe contralateral ICA stenosis (symptomatic or asymptomatic). RESULTS: ninety-seven patients were identified. Mean follow-up time was 26 months. The annual risk of (non-)fatal stroke was 5.3% for all strokes (95% CI 2. 9%-9.6%) and 3.8% for ipsilateral stroke (95% CI 1.9%-7.7%). Hyperlipidaemia and severe stenosis of the contralateral ICA were independent risk factors. Twenty-two of 32 patients with a severe stenosis of the contralateral ICA underwent CEA, of which one patient died and three suffered a minor ischaemic stroke. The perioperative risk of CEA in the control group of 20 patients with asymptomatic contralateral ICA occlusion was 0% (0 of 20). CONCLUSIONS: outcome in patients with symptomatic ICA occlusion has not substantially improved over the years. CEA for severe stenosis of the contralateral ICA carried a relatively high risk in our series, but deserves to be studied in a controlled design.
OBJECTIVE: Often patients with subarachnoid haemorrhage (SAH) recall a recent episode of acute severe headache, usually interpreted as a "warning headache" or first SAH. An alternative explanation is recall bias. The clinical and radiological features of patients with SAH were studied in relation to previous headaches or later rebleeding. METHODS: Patients with either a previous headache episode or a subsequent rebleed were selected from the SAH database in Utrecht within 1 month of the index SAH. The clinical condition was graded on the World Federation of Neurological Surgeons (WFNS) scale. The CT was reviewed and the amounts of subarachnoid blood, hydrocephalus, and intraventricular, intracerebral, and subdural blood were rated. Proportions were compared by unpaired or paired t test. RESULTS: Forty four of 390 patients (11%) had had a severe headache before their index SAH (11 of these had a subsequent rebleed); 31 other patients had a rebleed in hospital but no preceding headache. Patients with and without preceding headache did not differ in level of consciousness (14 of 44 v 11 of 31 were comatose), nor in any of the radiological features. After rebleeding (42 patients), 37 of 42 patients were comatose (v 11 of 42 before), and CT showed higher proportions of intracerebral haemorrhage (17%), intraventricular haemorrhage, (27%), and hydrocephalus (12%) than baseline scans. Intraventricular haemorrhage was twice as frequent after rebleeding than at baseline. CONCLUSIONS: The clinical and radiological features of patients admitted with SAH after a preceding bout of headache did not differ from those without such an episode, and are clearly dissimilar from those after documented rebleeds. The findings challenge the existence of minor "warning headaches".
BACKGROUND AND PURPOSE: The method of choice for detecting or excluding a vertebrobasilar aneurysm still is a matter of debate in patients with a characteristically perimesencephalic pattern of subarachnoid hemorrhage (SAH) on CT. We used decision analysis to compare possible diagnostic strategies in these patients. METHODS: A decision analytic model was developed to evaluate the effect of 4 different diagnostic strategies following a perimesencephalic pattern of SAH on CT: 1, no further investigation; 2, digital subtraction angiography (DSA) by catheter; 3, CT angiography as initial modality, not followed by DSA if negative; and 4, CT angiography as initial modality, followed by DSA. We used a 4% prevalence of a vertebrobasilar aneurysm given a perimesencephalic pattern of hemorrhage, a 97% sensitivity and specificity of CT angiography, and a 99.5% sensitivity and 100% specificity of DSA. In a prospectively collected series, the complication rate from DSA in patients with a perimesencephalic pattern of hemorrhage was 2.6%. We calculated the expected utility of each of the 4 diagnostic options and used sensitivity analyses to examine the influence of the plausible ranges of the various estimates used. RESULTS: The expected utilities were 99.09 for CT angiography only, 98.96 for no further investigation, 98.22 for DSA, and 96.34 for CT angiography plus DSA. The results of the sensitivity analysis indicate that over a wide range of assumptions, CT angiography only is the most beneficial option. Only when the complication rate of catheter angiography is <0.2% is DSA the preferred strategy. CONCLUSIONS: Our decision analysis shows that in patients with a perimesencephalic pattern of hemorrhage on CT, CT angiography only is the best diagnostic strategy. DSA can be omitted in patients with a perimesencephalic pattern of hemorrhage and a negative CT angiogram.
BACKGROUND AND PURPOSE: We sought to assess whether MRI, MR angiography, or (1)H MR spectroscopy can be used to identify patients with symptomatic carotid artery occlusion (CAO) who are at high risk of recurrent ipsilateral cerebral ischemic events. METHODS: In 115 consecutive patients with transient or moderately disabling symptoms of cerebral or retinal ischemia and ipsilateral CAO, we studied the prognostic value of (1) presence of a border-zone infarct; (2) quantitative flow in the middle cerebral artery (MCA) ipsilateral to the CAO; and (3) metabolic ratios in the centrum semiovale ipsilateral to the CAO. RESULTS: Presence of a border-zone infarct and the rate of flow in the MCA did not have a significant relationship with recurrence of cerebral ischemic events. Patients with a low N:-acetyl aspartate (NAA)/choline ratio had an annual risk of recurrent, ipsilateral, cerebral ischemic events of 16.0% (95% CI, 9.5 to 27.0), whereas this risk was 4.2% (95% CI, 2.2 to 8.0) in those with a normal NAA/choline ratio (hazard ratio, 0. 43; 95% CI, 0.19 to 1.00). Patients who on entry had had only retinal symptoms had on average a higher NAA/choline ratio (mean difference, 0.25; 95% CI, 0.13 to 0.37) and a lower risk of recurrent cerebral ischemic events (odds ratio, 0.0; 95% CI, 0.0 to 0.6) than those with cerebral ischemic symptoms. CONCLUSIONS: NAA/choline ratio measured by (1)H MRS, but not the presence of a border-zone infarct or the amount of flow in the MCA, can identify patients with symptomatic CAO who are at risk of future ipsilateral cerebral ischemic events.