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Biomedical subjects

J Stam

Publications and source records attributed to J Stam.

At least 19 recordsLinked to original sources

Clinical features and prognostic factors of cerebral venous sinus thrombosis in a prospective series of 59 patients. For The Cerebral Venous Sinus Thrombosis Study Group.

The prognosis of cerebral venous sinus thrombosis (CVST) is variable, and outcome may range from complete recovery to death. Prognostic factors to predict outcome in the acute phase of CVST have not been analysed in a prospective study. Prognostic factors in patients enrolled in a clinical treatment trial were prospectively investigated. Poor outcome after 12 weeks, defined as death or dependency (Oxford handicap score > or =3), was used as the principle outcome measure. Univariate relations between possible prognostic factors and outcome at 12 weeks were analyzed with chi(2) tests. Treatment and all factors associated with prognosis (p< or = 0.25) were forced into a logistic regression model with a forward selection procedure. Fifty nine patients (50 women, nine men) were studied, with a mean age of 37 years (range 18 to 80 years). After 12 weeks 10 patients (17%) had a poor outcome. The univariate identified factors related to poor outcome were papilloedema, altered consciousness, coma, age older than 33 years, diagnostic delay < or =10 days, intracerebral haemorrhage, and involvement of the straight sinus. Isolated intracranial hypertension and a delta sign on CT were associated with good outcome. In the multivariate analysis coma and cerebral haemorrhage were significantly associated with a poor outcome, with odds ratios of 8.2 (95% confidence interval (95% CI) 1. 3-50.1) and 20.7 (95% CI 1.6-264.3) respectively. Involvement of the straight sinus was also weakly, but not significantly, associated with poor outcome. In conclusion, coma and intracerebral haemorrhage are independent predictors for poor outcome of CVST.

Adolescent↗

[Neuroradiologic intervention in two patients with cerebral sinus thrombosis].

Two patients with cerebral sinus thrombosis were successfully treated with neuroradiological intervention procedures, one with local thrombolysis and the other with mechanical thrombosuction using a hydrolyser catheter. The first patient, a 20-year-old woman, was treated with asparaginase for acute lymphatic leukaemia. She lapsed into coma with extensor posturing due to superior sagittal and right transverse sinus thrombosis. She recovered completely after local thrombolysis with 2,940,000 units urokinase, administered over a period of 40 hours. The second patient was a 29-year-old man who presented with clinical deterioration after seizures due to superior sagittal, left transverse and straight sinus thrombosis. A CT-scan demonstrated bilateral haemorrhagic cerebral infarctions. Since the risk of haemorrhage during thrombolysis with urokinase was considered to be high, mechanical thrombosuction with a hydrolyser catheter was performed. This procedure took only 4 hours. The patient recovered completely in two weeks. These cases add further evidence to the effectiveness of thrombolysis and thrombosuction in selected patients with severe cerebral sinus thrombosis.

Adult↗

[Thrombolytic therapy of brain infarct: the end of beginning].

Thrombolysis by intravenous application of thrombolytic drugs may improve the outcome of patients with a brain infarct, but it also entails risks. The effect of recombinant tissue plasminogen activator (rtPA) was compared with placebo in three medium-sized randomized controlled clinical trials. One study, performed in North America, showed a clear benefit of rtPA administered within 3 hours after the onset of symptoms. Two European trials showed a less strong effect, but the number of patients who were independent after 3 months' follow-up was also larger after treatment with rtPA within 6 hours. A meta-analysis of all three trials demonstrates a significant advantage of rtPA over placebo for all the usual outcome measures, without significant excess mortality in the rtPA group. The chance of being able to live independently increases by about 8% after treatment with rtPA. In conclusion there is now sufficient evidence to start with thrombolytic treatment for cerebral infarcts in hospitals with a stroke unit, if a number of additional quality standards for the acute diagnosis and treatment of stroke patients are met.

Acute Disease↗

Long-term outcome of cognition and functional health after cerebral venous sinus thrombosis.

The authors examined cognition and functional health of 57 patients with sinus thrombosis 1 year or more after enrollment in a randomized trial of anticoagulant treatment or placebo. Eight patients died and two declined participation. Of the remaining 47 patients, 16 (35%) had cognitive impairments, 3 (6%) were dependent, 19 (40%) had symptoms that led to restrictions in lifestyle, and 19 (40%) could not resume their previous level of economic activity. Outcome after sinus thrombosis may be less favorable than reported previously, and was not significantly influenced by treatment.

Adult↗

Thyrotoxicosis as a predisposing factor for cerebral venous thrombosis.

Thyroid storm is a rare and life-threatening complication of untreated thyrotoxicosis. A number of neurological complications have been described in association with thyrotoxicosis. We report the case of a 28-year-old woman with a thyroid storm on the basis of Graves' disease and probably triggered by a surgical procedure. She developed cerebral venous thrombosis (CVT) of the left transverse and rectus sinus with a venous infarction of the left thalamus. Except for an increased factor VIII clotting activity there were no thrombophilic abnormalities. Similar cases have been described in the literature and the reported incidence of the combination of CVT and thyrotoxicosis is significantly higher than expected by chance alone (0.1 x 10(-6) per year vs. 0.0032 x 10(-6)/year). This case is consistent with the assumption that thyrotoxicosis, probably through a factor VIII-mediated hypercoagulability, may be a predisposing factor for the development of CVT.

Adult↗

[Creative mathematics with clopidogrel; exaggeration of the preventive effect by manufacturer].

A number of Dutch medical journals recently carried an advertisement stating that clopidogrel treatment reduced the number of ischaemic complications with 26%, compared with aspirin treatment. This is a miscalculation: the actual reduction is 0.51% in absolute rates, and 8.7% in relative terms. The error by Sanofi-Synthelabo arose by comparison of the event rates for clopidogrel (5.32%) as well as for aspirin (5.83%) with that in an imaginary placebo group (7.77%), yielding a reduction of ischaemic complications of 2.45% and 1.94% respectively; erroneous comparison of these two numbers leads to a difference of 26%.

Advertising↗

[Physical diagnostics--tendon reflexes].

Clinical examination of the tendon reflexes is helpful in localising lesions in the nervous system, which is an important step in the diagnosis of neurological disorders. The large intra- and interindividual variations of reflex amplitudes make interpretation difficult. Published interobserver agreement studies provide conflicting results. The diagnostic specificity of unequivocally abnormal reflexes is moderate to good (70-95%, decreasing with increasing age), but the sensitivity is lower (50-70%), both for peripheral and for central lesions. This implies that the finding of a clearly abnormal reflex pattern is often helpful, but the finding of normal reflexes usually does not exclude a neurological lesion.

Brain Diseases↗

Spinal xanthomatosis: a variant of cerebrotendinous xanthomatosis.

We describe seven Dutch patients from six families with a slowly progressive, mainly spinal cord syndrome that remained for many years the sole expression of cerebrotendinous xanthomatosis (CTX). MRI demonstrated white matter abnormalities in the lateral and dorsal columns of the spinal cord. Post-mortem examination of one of the patients showed extensive myelin loss in these columns. An array of genotypes was found in these patients. We conclude that 'spinal xanthomatosis' is a clinical and radiological separate entity of CTX that should be included in the differential diagnosis of 'chronic myelopathy'.

Adult↗

Randomized, placebo-controlled trial of anticoagulant treatment with low-molecular-weight heparin for cerebral sinus thrombosis.

BACKGROUND AND PURPOSE: Treatment of cerebral sinus thrombosis with heparin is controversial. We conducted a double-blind, placebo-controlled multicenter trial to examine whether anticoagulant treatment improves outcome in patients with sinus thrombosis. METHODS: Patients were randomized between body weight-adjusted subcutaneous nadroparin (180 anti-factor Xa units/kg per 24 hours) and matching placebo for 3 weeks (double-blind part of trial), followed by 3 months of oral anticoagulants for patients allocated nadroparin (open part). Patients with cerebral hemorrhage caused by sinus thrombosis were also included. RESULTS: Sixty patients were enrolled, and none were lost to follow-up. In 1 patient the diagnosis proved wrong after randomization. After 3 weeks, 6 of 30 patients (20%) in the nadroparin group and 7 of 29 patients (24%) in the placebo group had a poor outcome, defined as death or Barthel Index score of <15 (risk difference, -4%; 95% CI, -25 to 17%; NS). After 12 weeks, 4 of 30 patients (13%) in the nadroparin group and 6 of 29 (21%) in the placebo group had a poor outcome, defined as death or Oxford Handicap Score of >/=3 (risk difference, -7%; 95% CI, -26% to 12%; NS). There were no new symptomatic cerebral hemorrhages. One patient in the nadroparin group had a major gastrointestinal hemorrhage, and 1 patient in the placebo group died from clinically suspected pulmonary embolism. CONCLUSIONS: Patients with cerebral sinus thrombosis treated with anticoagulants (low-molecular-weight heparin followed by oral anticoagulation) had a favorable outcome more often than controls, but the difference was not statistically significant. Anticoagulation proved to be safe, even in patients with cerebral hemorrhage.

Adolescent↗

Case-control study of risk of cerebral sinus thrombosis in oral contraceptive users and in [correction of who are] carriers of hereditary prothrombotic conditions. The Cerebral Venous Sinus Thrombosis Study Group.

OBJECTIVE: To investigate whether users of oral contraceptives and in [corrected] carriers of a hereditary prothrombotic condition (factor V Leiden mutation, protein C, S, or antithrombin deficiency) have an increased risk of cerebral sinus thrombosis. DESIGN: Comparison of a prospective series of cases of cerebral sinus thrombosis with population data. SETTING: Neurological teaching hospitals from different regions in the Netherlands (cases) and a representative sample of the non-institutionalised Dutch population (controls). SUBJECTS: 40 women aged 18-54 years with cerebral sinus thrombosis (cases) and 2248 women aged 18-49 years (controls). MAIN OUTCOME MEASURE: Current use of oral contraceptives at the time of the thrombosis (cases) or at the time of the questionnaire (controls). Prevalences of a hereditary prothrombotic condition in patients and in the population with odds ratios. RESULTS: 34 of 40 (85%) women with cerebral sinus thrombosis used oral contraceptives, versus 1007 of 2248 (45%) of the control women; the age adjusted odds ratio was 13 (95% confidence interval 5 to 37). Seven of 36 patients (19%) had a prothrombotic deficiency, versus 7% expected in the population; this corresponds to a threefold to fourfold increase in risk. In women who used oral contraceptives and also carried a prothrombotic defect, the odds ratio for cerebral sinus thrombosis was about 30 relative to women who had neither risk factor. CONCLUSION: The use of oral contraceptives and being a carrier of a hereditary prothrombotic condition increase the risk of and interact in a multiplicative way in the development of cerebral sinus thrombosis.

Adolescent↗

Silent intracerebral microhemorrhages in patients with ischemic stroke. Amsterdam Vascular Medicine Group.

We compared the frequencies of signs of old intracerebral hemorrhages on brain magnetic resonance imaging scans in 66 patients with ischemic stroke, 69 with myocardial infarction, and 86 with peripheral arterial disease (a total of 221 patients). Magnetic resonance imaging scans were independently assessed by two investigators without knowledge of clinical or laboratory data. In 31 patients (14%) we found local cerebral hemosiderin deposits. In 24 patients they were clinically silent. Hemosiderin deposits were significantly more frequent in patients with ischemic stroke (26%) than in patients with myocardial infarction (4%) or peripheral arterial disease (13%). Hemosiderin deposits were associated with cerebral white matter lesions (odds ratio, 5.3; 95% confidence interval, 2.5-12.4). The odds ratios were higher in patients with severe cerebral white matter lesions. Our findings support the hypothesis that cerebral vessels of patients with ischemic stroke are more prone to rupture than those of patients with other manifestations of atherosclerotic disease, which may explain the higher incidence of intracerebral hemorrhages when these patients are treated with oral anticoagulants. The microhemorrhages were associated with cerebral white matter lesions, which suggests that they are another manifestation of cerebral small-vessel disease.

Aged↗

Involvement of amino acid residues 423-429 of human protein S in binding to C4b-binding protein.

Human protein S binds to C4b-binding protein (C4BP) both in plasma and in a system using purified proteins. Amino acid residues 420-434 of the first disulfide loop of the sex hormone binding globulinlike domain of protein S are involved in the interaction of protein S with C4BP. To define the involvement of specific polar amino acids within residues 420-434, we studied in parallel synthetic protein S peptides and recombinant protein S variants containing the same amino acid replacements, K423E, E424K, Q427E and K429E. Synthetic peptide analogs of peptide PSP-420 (residues 420-434) were assayed for binding C4BP and as inhibitors of complex formation. The PSP-420 peptide and the analogous peptide with the substitution E424K, but not the peptides containing the substitutions K423E and K429E, were able to bind C4BP. Recombinant proteins with mutations of K423E, Q427E and K429E showed reduced affinity for C4BP compared to plasma protein S, recombinant wild type protein S, or E424K-protein S. These results suggest that Lys-423, Gln-427 and Lys-429 of protein S are important for normal binding to C4BP. The anti-protein S monoclonal antibody LJ-56, raised against peptide PSP-420, recognizes only free protein S and inhibits complex formation with C4BP. Antibody LJ-56 recognized the E424K and Q427E peptides but not the K423E or K429E peptides. Similarly, the E424K and Q427E protein S mutants were recognized by LJ-56, whereas the K423E and K429E protein S mutants were not recognized. This suggests that both in the peptide PSP-420 and in protein S, Lys-423 and Lys-429 significantly contribute to binding to antibody LJ-56. These results demonstrate that protein S residues 423, 427 and 429, but not residue 424, are involved in binding to both the antibody LJ-56 and to C4BP. When peptides PSP 420 and SL-6 (residues 447-460) with carboxyterminal amide or carboxylate moieties were compared to their ability to inhibit C4BP-protein S complexation, PSP-420-amide was the most potent. This finding together with the other results described here supports the hypothesis that the residues 420 and 434 in protein S provides a major binding site for C4BP.

Amino Acid Sequence↗

Disequilibrium in patients with atherosclerosis: relevance of pontine ischemic rarefaction. Amsterdam Vascular Medicine Group.

OBJECTIVE: To examine the clinical relevance of isolated pontine hyperintense lesions (PHLs) on MRI in patients with atherosclerosis. METHODS: Seventeen atherosclerotic patients with isolated PHL on MRI were compared with 17 patients without PHL and were matched for age, sex, and initial manifestation of atherosclerosis. Subjects and observer were blinded to the MRI findings. We assessed symptoms, impairment, and disability with a structured interview and neurologic examination as well as disability scales. RESULTS: On all items, patients with PHL scored worse than did their controls. We found the largest differences in frequencies of symptoms of disequilibrium, difficulties with speech or swallowing, the Timed Walking Test, and the body care and movement subscale of the Sickness Impact Profile. Except for disequilibrium (p = 0.04), these differences did not reach statistical significance. Abnormal tandem-walking tests were more frequent in patients than they were in controls. Pyramidal signs were equally distributed. CONCLUSIONS: We propose PHL as a cause of symptoms of disequilibrium in patients with atherosclerosis. Symptoms are probably elicited by dysfunction of the corticopontine fibers, the pontocerebellar fibers, or the pontine nuclei.

Aged↗

T2-weighted hyperintense MRI lesions in the pons in patients with atherosclerosis. Amsterdam Vascular Medicine Group.

BACKGROUND AND PURPOSE: Pontine hyperintense lesions (PHL) on T2-weighted MRI have been recognized recently. Histopathological findings resemble periventricular leukoaraiosis, and a vascular etiology has been suggested. We studied the frequency and the associated factors of PHL in patients with symptomatic atherosclerosis. METHODS: Two independent observers assessed brain MRIs in a prospective cohort of patients with symptomatic atherosclerosis. Only patients in whom both observers scored PHL on T2- and proton density-weighted images, but not on T1-weighted images, were considered to have the lesion. RESULTS: We studied 229 patients 31% presenting with ischemic stroke, 31% with myocardial infarction, and 38% with peripheral artery disease. Both observers scored PHL in 23% of all patients. Patients with PHL were significantly older and had more lacunar infarcts and periventricular leukoaraiosis than patients without PHL. There were more women, more hypercholesterolemic and diabetic patients, and more cortical infarcts on MRI (P = NS). After logistic regression the presence of leukoaraiosis (odds ratio, 2.4; 95% confidence interval, 1.6 to 3.4) and lacunar infarcts (odds ratio, 2.2, 95% confidence interval, 1.5 to 3.1) remained independently associated with PHL. PHL was more common in patients with ischemic strokes (39%) than in patients with myocardial infarctions (11%) or peripheral artery disease (19%) (P < .001). CONCLUSIONS: We found that PHL on T2- and proton density-weighted MR images are often found in patients with symptomatic atherosclerosis. The association with periventricular leukoaraiosis and lacunar infarcts suggests that PHL is a variant of leukoaraiosis, with possibly the same pathophysiology. The clinical symptoms and consequences of PHL, however, are not yet clear.

Age Distribution↗