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Mark A van Buchem

Publications and source records attributed to Mark A van Buchem.

12 recordsLinked to original sources
PubMed2003

Operational definitions for the NINDS-AIREN criteria for vascular dementia: an interobserver study.

BACKGROUND AND PURPOSE: Vascular dementia (VaD) is thought to be the most common cause of dementia after Alzheimer's disease. The commonly used International Workshop of the National Institute of Neurological Disorders and Stroke (NINDS) and the Association Internationale pour la Recherche et l'Enseignement en Neurosciences (AIREN) criteria for VaD necessitate evidence of vascular disease on CT or MRI of the brain. The purposes of our study were to operationalize the radiological part of the NINDS-AIREN criteria and to assess the effect of this operationalization on interobserver agreement. METHODS: Six experienced and 4 inexperienced observers rated a set of 40 MRI studies of patients with clinically suspected VaD twice using the NINDS-AIREN set of radiological criteria. After the first reading session, operational definitions were conceived, which were subsequently used in the second reading session. Interobserver reproducibility was measured by Cohen's kappa. RESULTS: Overall agreement at the first reading session was poor (kappa=0.29) and improved slightly after application of the additional definitions (kappa=0.38). Raters in the experienced group improved their agreement from almost moderate (kappa=0.39) to good (0.62). The inexperienced group started out with poor agreement (kappa=0.17) and did not improve (kappa=0.18). The experienced group improved in both the large- and small-vessel categories, whereas the inexperienced group improved generally in the extensive white matter hyperintensities categories. CONCLUSIONS: Considerable interobserver variability exists for the assessment of the radiological part of the NINDS-AIREN criteria. Use of operational definitions improves agreement but only for already experienced observers.

Brain↗
PubMed2003

Evaluation of diagnostic NOTCH3 immunostaining in CADASIL.

CADASIL is caused by mutations in the NOTCH3 gene. Although increasingly recognized as a disease entity, the diagnostic confirmation can be lengthy or inconclusive. Recently, NOTCH3 immunostaining of skin biopsy specimens has been introduced as a new diagnostic test. The aim of this study was to independently assess the diagnostic value of NOTCH3 immunostaining, and determine whether the degree of immunostaining correlates with other disease parameters. We determined NOTCH3 mutation carrier status in 62 symptomatic and asymptomatic individuals from 15 CADASIL families. Skin biopsy specimens of these individuals, as well as of a disease control group, were immunostained with NOTCH3 antibody and blindly analyzed by two independent observers to determine sensitivity and specificity. A semiquantitative NOTCH3 immunostaining score was correlated with clinical, genetic and MRI parameters. The sensitivity was 90.2% and 85.4%, respectively, for the two observers, the specificity 95.2% and 100%; both lower than previously reported. Certain NOTCH3 mutations may underlie false-negative results. False-positive results were found in a non-mutated control, and also in one disease control. There was no difference in immunostaining between symptomatic and asymptomatic NOTCH3 mutated individuals. Furthermore, the NOTCH3 immunostaining score did not correlate with clinical or MRI parameters. NOTCH3 immunostaining is a supportive, but not definitive, CADASIL diagnostic test, and should be interpreted in the context of clinical and radiological data. Confirmation by DNA analysis is requisite for positive results, and when there exists high clinical suspicion, also for negative results.

Adult↗
PubMed2003

Voxel-based morphometry in hypocretin-deficient narcolepsy.

STUDY OBJECTIVES: Recent studies suggest that narcolepsy is caused by degeneration of hypocretin (orexin) producing neurons. To find evidence for this hypothesis, we aimed to detect structural changes in the hypothalamus and/or hypocretin projection areas of patients with narcolepsy. DESIGN: We used voxel-based morphometry (VBM), an unbiased MRI morphometric method with a high sensitivity for subtle changes in gray and white matter volumes. SETTING: Image acquisition was carried out in the department of Radiology at Leiden University Medical Center; image post-processing was performed in the Wellcome Department of Cognitive Neurology, London. PARTICIPANTS: Fifteen narcoleptic patients were studied, all having cataplexy and typical findings on Multiple Sleep Latency Testing. All patients were HLA-DQB1*0602 positive and hypocretin-1 deficient. The control group consisted of 15 age and sex matched healthy subjects. MEASUREMENTS AND RESULTS: We found no differences in global gray or white matter volumes between patients and controls. Furthermore, regional gray or white matter volumes in the hypothalamus and hypocretin projection areas did not differ between patients and controls. CONCLUSIONS: VBM failed to show structural changes in the brains of patients with narcolepsy. This suggests that narcolepsy either is associated with microscopic changes undetectable by VBM or that functional abnormalities of hypocretin neurons are not associated with structural correlates.

Adult↗
PubMed2003

Incipient CADASIL.

BACKGROUND: Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is caused by mutations in the NOTCH3 gene. Knowledge of disease expression in young adult NOTCH3 mutation carriers (MCs) is limited. OBJECTIVE: To characterize clinical, neuropsychological, and radiological status in NOTCH3 MCs younger than 35 years. DESIGN: Clinical characterization and blinded survey comparing MCs with non-MCs. SETTING: Referral center. PARTICIPANTS: Individuals younger than 35 years who were at a 50% risk of a NOTCH3 mutation, from our CADASIL database. Thirteen individuals, from 8 families, met the criteria. METHODS: Comprehensive clinical, genetic, neuropsychological, and radiological investigations. Magnetic resonance images were scored according to a standardized white matter hyperintensities rating scale. RESULTS: Six individuals, from 5 families, were MCs. Clinical symptoms consisted of migraine (with aura), stroke, and stroke-like episodes. We did not find evidence for psychiatric disturbances, functional disability, or cognitive dysfunction, compared with non-MCs. Radiologically, a characteristic magnetic resonance imaging lesion pattern emerged for all MCs. This comprised white matter hyperintensities in the anterior temporal lobes, the frontal lobes, and the periventricular frontal caps. CONCLUSIONS: Migraine (with aura) and stroke can present in NOTCH3 MCs younger than 35 years; however, more importantly, physical function and cognition are intact. Possible subtle cognitive dysfunction needs to be assessed in a larger study. White matter hyperintensities on magnetic resonance imaging are characteristic, and are consistently visualized from the age of 21 years and onward. Awareness of the clinical and radiological features of CADASIL in those younger than 35 years should increase early diagnosis and allow for customized counseling of young adults from families with CADASIL.

Adult↗
PubMed2003

Cerebral hemodynamics and white matter hyperintensities in CADASIL.

Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL) is a hereditary small-vessel disease caused by mutations in the NOTCH3 gene on chromosome 19. On magnetic resonance imaging (MRI), subcortical white matter hyperintensities and lacunar infarcts are visualized. It is unknown whether a decrease in cerebral blood flow or cerebrovascular reactivity is primarily responsible for the development of white matter hyperintensities and lacunar infarcts. The authors used phase-contrast MRI in 40 NOTCH3 mutation carriers (mean age 45 +/- 10 years) and 22 nonmutated family members (mean age 39 +/- 12 years), to assess baseline total cerebral blood flow (TCBF) and cerebrovascular reactivity after acetazolamide. Mean baseline TCBF was significantly decreased in NOTCH3 mutation carriers. In young subjects, baseline TCBF was significantly lower than in nonmutation carriers (mean difference 124 mL/min). Furthermore, baseline TCBF did not differ significantly between mutation carriers with minimal and mutation carriers with moderate or severe white matter hyperintensities. No significant difference in mean cerebrovascular reactivity was found between mutation carriers and nonmutation carriers. This study suggests that a decrease in baseline TCBF in NOTCH3 mutation carriers precedes the development of white matter hyperintensities.

Adult↗
PubMed2002

Magnetization transfer imaging in normal aging, mild cognitive impairment, and Alzheimer's disease.

The purpose of this study was to assess whether structural brain damage as detected by volumetric magnetization transfer imaging (MTI) is present in mild cognitive impairment (MCI) and Alzheimer's disease (AD) and, if so, whether these abnormalities are global in character or restricted to the temporal lobe. Volumetric MTI analysis of the whole brain and temporal and frontal lobes was performed in 25 patients with probable AD, in 13 patients with MCI, and in 28 controls. Magnetization transfer ratio (MTR) histograms were produced, from which we derived measures for structural brain damage and atrophy. The peak heights of the MTR histograms of MCI and AD patients were lower than those of controls for the whole brain and temporal and frontal lobes, reflecting structural brain damage. AD patients had more atrophy than controls in all regions that were studied. MCI patients differed from controls for temporal lobe atrophy only. Volumetric MTI demonstrates structural changes that are related to cognitive decline in large parts of the brain of AD patients. Moreover, structural changes also were observed in MCI patients, indicating that widespread brain damage can be demonstrated before patients are clinically demented.

Aged↗
PubMed2002

Reproducibility of total cerebral blood flow measurements using phase contrast magnetic resonance imaging.

PURPOSE: To evaluate reproducibility of total cerebral blood flow (CBF) measurements with phase contrast magnetic resonance imaging (pcMRI). MATERIALS AND METHODS: We repeated total CBF measurements in 15 healthy volunteers with and without cardiac triggering, and with and without repositioning. In eight volunteers measurements were performed at two different occasions. In addition, measurement of flow in a phantom was performed to validate MR measurements. RESULTS: A difference of 40.4 ml/minute was found between CBF measurements performed with and without triggering (P < 0.05). For repeated triggered measurements, the coefficient of variation (CV) was 7.1%, and for nontriggered measurements 10.3%. For repeated measurements with repositioning, the CV was 7.1% with and 11.2% without triggering. Repeated measurements at different occasions showed a CV of 8.8%. Comparing measured with real flow in the phantom, the triggered differed 4.9% and the nontriggered 8.3%. CONCLUSION: The findings of this study demonstrate that pcMRI is a reliable method to measure total CBF in terms of both accuracy and reproducibility.

Adult↗
PubMed2002

MR assessment of cerebral vascular response: a comparison of two methods.

PURPOSE: To compare the results and reproducibility of two MR-based methods of measuring the cerebrovascular response (CVR). MATERIALS AND METHODS: In eight volunteers, CVR was assessed with two MR-based methods upon a challenge with acetazolamide. CVR was assessed by measuring changes in total cerebral blood flow (TCBF) using phase contrast (PC) MRI, and by measuring perfusion MRI. To assess reproducibility the measurements were repeated after 1 week. RESULTS: The average CVR with the PC-MRI method was 46% (SD = 16%), and for perfusion MR the measured CVR was 44% (SD = 16%). The coefficient of variation (COV) for PC-MRI was 28%, while perfusion MR had a COV of 26%. The limits of agreement between the two methods were -49% and 45%, demonstrating a lack of agreement between the two methods in terms of CVR estimation. CONCLUSION: CVR estimates based on PC-MRI and perfusion MRI showed reproducibility but a lack of agreement in healthy volunteers. This lack of agreement can be attributed to the different aspects of the CVR reflected by these methods: TCBF reflects changes in CBF, whereas our perfusion MRI method reflects cerebral blood volume (CBV).

Acetazolamide↗
PubMed2002

Production of IL-1beta and IL-1Ra as risk factors for susceptibility and progression of relapse-onset multiple sclerosis.

Interleukin-1beta (IL-1beta) is present in multiple sclerosis (MS) lesions. Interleukin-1 receptor antagonist (IL-1Ra) moderates the induction of experimental autoimmune encephalomyelitis (EAE). Here, we show that families that are characterized by high IL-1beta over IL-1Ra production ratio are at 2.2-fold (95% CI, 1.0-4.8; p=0.05) increased risk to have a patient relative with relapse-onset MS than families with a low ratio. It is also related to the reduction of volumetric magnetization transfer ratio (MTR) histogram height, a measure of parenchymal integrity (p=0.04). Those families who combine a high IL-1beta over IL-1Ra ratio with a high tumor necrosis factor (TNF) over IL-10 production ratio have a 6.2-fold (95% CI, 1.8-21; p=0.002) increased risk. Innate production of IL-1beta and IL-1Ra is not related to the outcome of primary progressive MS. Taq1 polymorphism in the IL-1beta gene and the variable number of tandem repeats (VNTR) polymorphism of 86-base pairs within the IL-1Ra gene cannot explain these findings.

Adult↗
PubMed2002

Chronic sinusitis in severe asthma is related to sputum eosinophilia.

BACKGROUND: Chronic rhinosinusitis and asthma are conditions that frequently coexist, particularly in severe asthma. The precise mechanism of the relationship between upper and lower airway inflammation is still a matter of debate. We hypothesized that the extent of inflammation in the nasal mucosa is related to lung function and inflammation in the bronchial mucosa in patients with severe asthma. OBJECTIVE: We sought to investigate the relationship between sinonasal inflammation as assessed on computed tomography (CT) scanning, lung function, sputum eosinophilia, and nitric oxide (NO) in exhaled air in patients with severe asthma. METHODS: Eighty-nine nonsmoking outpatients with severe asthma (29 men and 60 women; mean age 45 years; age range, 18-74 years) were included in this study. CT scans were scored (0-30) by a blinded investigator using a validated method. Lung function, NO in exhaled air, and sputum eosinophils were measured by using standard procedures. RESULTS: CT scans showed abnormalities in 84% of patients. Extensive sinus disease (score 12-30) was found in 24% of patients. There was a significant positive correlation between CT scores and eosinophils in peripheral blood (R(s) = 0.46) and induced sputum (R(s) = 0.40) and level of exhaled NO (R(s) = 0.45, P <.01). CT scores were also positively related to functional residual capacity and inversely related to diffusion capacity, particularly in patients with adult-onset asthma (R(s) = 0.47 and R(s) = -0.53, respectively). CONCLUSIONS: The results of this study show a direct relationship between sinonasal mucosa thickness and bronchial inflammation in severe asthma, particularly in patients with adult-onset disease. Whether sinus disease directly affects the intensity of bronchial inflammation is still an unanswered question.

Adult↗
PubMed2002

Subcortical lacunar lesions: an MR imaging finding in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy.

PURPOSE: To assess the prevalence and distribution of subcortical lacunar lesions (SLLs) in patients with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), to determine whether SLLs are an abnormal finding by studying their prevalence in healthy subjects, and to assess whether SLLs occur in other conditions associated with small vessel disease and white matter areas of high signal intensity (WMH). MATERIALS AND METHODS: The presence of SLLs, their location, and their relation to other abnormalities were assessed on magnetic resonance (MR) images (T1-weighted, T2-weighted, and fluid-attenuated inversion-recovery) obtained in 34 CADASIL patients and 20 healthy family members. Three additional control groups of healthy volunteers, elderly patients with vascular risk factors, and patients with another hereditary small vessel disease were also screened for the presence and location of SLLs. Sensitivity and specificity of the presence of SLLs for the diagnosis of CADASIL were assessed. RESULTS: SLLs were found in 20 (59%) of CADASIL patients. Incidence of SLLs increased with age (20%, <30 years; 50%, 30-50 years; 80%, >50 years). SLLs invariably occurred in the anterior temporal lobes and in areas where diffuse WMH expanded into arcuate fibers. From the anterior temporal lobe, the lesions could extend dorsally into the temporal lobes and rostrally into the frontal lobes. Lesions were not found in the parietal and occipital lobes. None of the control subjects had SLLs. Specificity and sensitivity of SLLs for CADASIL were 100% and 59%, respectively. CONCLUSION: SLLs are an abnormal finding at MR imaging that frequently occur in CADASIL patients.

Adult↗