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Biomedical subjects

P Scheltens

Publications and source records attributed to P Scheltens.

At least 127 records · Page 7Linked to original sources
PubMed1995

A four-generation Dutch family with cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL), linked to chromosome 19p13.

We describe a four-generation Dutch family suffering from cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). Of twenty affected family members, ten are still alive. Age at onset of the strokes was between 29 and 52 years, with a mean of 41.8 years. This family has the typical clinical and radiological features of CADASIL (except for the occurrence of ischemic heart disease at a relatively young age in some subjects), and is linked to chromosome 19p13. This disease has so far been described in families from Finland, France, Germany, Italy, Japan, Spain and the United Kingdom, and there is a remarkable clinical and genetical homogeneity among all families reported, including this Dutch family.

Adult↗
PubMed1995

Medial temporal lobe atrophy in an open population of very old persons: cognitive, brain atrophy, and sociomedical correlates.

Medial temporal lobe structures may be important for memory. We examined the cognitive, brain atrophy, and sociomedical correlates of medial temporal lobe atrophy (MTA) in 59 individuals (79.2 +/- 4.6 years old) randomly selected from a population-based study within strata of age and severity of clinically assessed DSM-III-R dementia (45 clinically normal and 14 mild/severely demented). MTA was qualitatively assessed on coronal T-1-weighted MRI. Thirty-three percent of the sample showed MTA, which was associated with dementia severity (p < 0.01), and cortical and white matter atrophy. MTA was not associated with age, education, sex, depressive symptoms, or presence of infarction. Controlling for age, education, and associated brain atrophy, those with MTA performed more poorly on a general test of cognitive function (the neuropsychological test component of the Cambridge Examination for Mental Disorders of the Elderly; p < 0.04) and its subtests of memory function (p < 0.02) and memory-related functions, including perception, fluency, and orientation (p < 0.05). In the clinically normal subsample, those with MTA performed more poorly on the memory function (p < 0.05) subtests. We conclude that MTA is common among very old persons, is associated with other brain abnormalities implicated in cognitive function, but may specifically contribute to memory dysfunction in the general population of very old persons.

Aged↗
PubMed1995

Histopathologic correlates of white matter changes on MRI in Alzheimer's disease and normal aging.

We investigated the histopathologic correlates of white matter changes in Alzheimer's disease (AD) patients (n = 6) and controls (n = 9) using postmortem MRI. White matter changes were rated on a 0 to 3 scale in 51 regions. Histopathologically, we subjectively rated the loss of myelinated axons in the deep and periventricular white matter, denudation of the ventricular ependyma, gliosis, width of the perivascular spaces, and leptomeningeal congophilic angiopathy; we measured structural changes in the walls of the blood vessels in the white matter in micrometers. The AD brains displayed significantly more white matter hyperintensities on MRI than controls. Histopathologically, the denudation of the ventricular ependyma and the gliosis were significantly more severe in AD than in controls, and there was a trend toward more loss of myelinated axons in the deep white matter in the AD brains (p = 0.07). The MRI abnormalities correlated with the loss of myelinated axons in the deep white matter (r' = 0.37; p < 0.01) and with the denudation of the ventricular lining (r' = 0.54; p < 0.01). We could not find any evidence for arteriolosclerosis, but the mean thickness of the adventitia of the arteries of the deep white matter in AD almost doubled the value in control brains (p = 0.0009). We conclude that white matter abnormalities in AD patients and controls consist of loss of myelinated axons, probably caused by arterial changes and breakdown of the ventricular lining. Since imaging/histopathologic correlation was similar in AD patients and controls, these changes probably represent some form of accelerated aging.

Aged↗
PubMed1994

Limited duration of the effect of methylprednisolone on changes on MRI in multiple sclerosis.

Treatment with methylprednisolone reduces the duration and severity of clinical relapses in multiple sclerosis (MS), while reducing the number of gadolinium-enhancing lesions on T1-weighted MRI. We performed serial MRI imaging after methylprednisolone treatment to see whether suppression of enhancement persists and whether related abnormalities on T2-weighted images disappear at follow-up. Thirteen patients with definite MS received a total of 31 courses of methylprednisolone over an average period of 50 weeks. Gadolinium-enhanced MRI was obtained before and after treatment, then at monthly intervals, using a standardised repositioning and imaging protocol. Two experienced readers in conference defined the number of active (gadolinium-enhancing and new or enlarging nonenhancing) lesions. We detected 609 active lesions on 195 examinations. Directly after treatment the reduction in the number of enhancing lesions was 78%, indicating restoration of the BBB and suppression of inflammation. It was uncommon for a lesion which stopped enhancing to show enhancement on a subsequent examination. No beneficial effect was observed on the rate of disappearance of related abnormalities on T2-weighted images, indicating persistent change such as oedema, cellular infiltration or demyelination. Moreover, in 89% of cases, an increase in the number of active lesions was observed before new clinical activity, if any, was observed (on average 52% earlier). MRI enabled us to demonstrate that the duration of the effect of methylprednisolone treatment is temporary (on average 9.7 weeks).

Adult↗
PubMed1994

Cerebrospinal fluid ferritin levels of patients with Parkinson's disease, Alzheimer's disease, and multiple system atrophy.

Iron is believed to play a role in the pathogenesis of both Parkinson's disease (PD) and Alzheimer's disease (AD). We measured ferritin, which is considered to be the iron storage protein, in CSF of patients with PD, AD, and multiple system atrophy (MSA) as well as control subjects. We found a significant increase in CSF ferritin in AD compared with both PD and age-matched controls. No significant differences were found between PD patients with dementia (PDD) and non-demented PD patients. For non-demented PD patients a positive correlation between CSF ferritin and age was found. Our results may indicate that iron has a role in the pathophysiology of AD.

Age Distribution↗
PubMed1994

Clinically silent dysfunction of dorsal columns and dorsal spinocerebellar tracts in hereditary spastic paraparesis.

Hereditary spastic paraparesis (HSP) is a neurodegenerative disorder, of which progressive spastic paraparesis is the clinical hallmark. Given the neuropathological evidence of degeneration of pyramidal tracts, dorsal columns, and dorsal spinocerebellar tracts, it is surprising that sensory symptoms are so indistinct compared to motor symptoms. We investigated the involvement of peripheral conduction and spinal proprioceptive pathways by nerve conduction studies, somatosensory evoked potentials of the median and tibial nerves, and quantitative assessment of the vibration perception thresholds of the hands and feet respectively in 32 patients suffering from HSP and healthy control groups. We did not find peripheral conduction abnormalities in HSP patients. Log-transformed vibration perception thresholds of the feet were abnormal in 13/32 HSP patients and in 0/64 controls (p < 0.00001), while tibial nerve somatosensory evoked potentials were abnormal in 20/32 patients and in 1/17 controls (p = 0.00001). The values for the upper extremities were within normal limits for nearly all subjects. In the HSP group, the neurophysiological disturbances did not correlate significantly with duration or severity of the disease, when age was controlled for, except for median nerve SSEP latency, which was affected by severity (p = 0.0072). We conclude that neurophysiological methods detected proprioceptive, subclinical abnormalities in several HSP patients, which may reflect degeneration of the dorsal columns, and/or dorsal spinocerebellar tracts. Since we found no correlation with several disease variables, the fact that not all HSP patients displayed these abnormalities may be caused by anatomical variations in proprioceptive pathways, rather than by phenotypical heterogeneity.

Action Potentials↗
PubMed1994

Decreased cerebrospinal fluid nitrate levels in Parkinson's disease, Alzheimer's disease and multiple system atrophy patients.

Nitric oxide (NO) is a recently discovered endogenous mediator of vasodilatation, neurotransmission, and macrophage cytotoxicity. NO is thought to have a function in memory and in long-term potentiation. At high concentrations NO is neurotoxic and may play a role in neurodegeneration. NO is formed from L-arginine by the enzyme NO synthase (NOS), for which tetrahydrobiopterin (BH4) is a necessary co-factor. Alzheimer's disease (AD) and, to a lesser degree, Parkinson's disease (PD) are thought to be associated with increased microglial activity, suggesting that NO production may be increased. Alternatively, in circumstances of reduced levels of intracellular L-arginine or BH4, NO production is diminished and neurotoxic oxygen radicals may be produced. Since BH4 is decreased in AD and PD brains, these diseases may be associated with decreased NO production. We investigated these two alternatives by measuring the NO degradation products nitrite and nitrate in cerebrospinal fluid (CSF) of PD (n = 103), AD (n = 13), and multiple system atrophy (MSA; n = 14) patients and controls (n = 20). We found for all patient groups, compared with controls, significantly decreased levels of nitrate, but not nitrite. This finding seems to indicate a decreased NO production of the central nervous system (CNS) in these neurodegenerative disorders.

Aged↗
PubMed1994

[Contribution of morphological imaging in the diagnosis of dementia. I--Alzheimer disease].

In patients with Alzheimer's disease, morphological neuroimaging techniques usually reveal signs of global cerebral atrophy which gradually worsen over time and depends on age and severity of the cognitive decline. Because of the lack of artifacts and of a more appropriate angle, magnetic resonance imaging scans may visualize a prominent atrophy of the medial temporal lobes, including hippocampal structures. Hippocampal atrophy is relatively specific of Alzheimer's disease before 65 and is related to the severity of memory disorders. White matter changes in patients without cerebrovascular risk factors are not more severe in patients with presenile Alzheimer's disease than in age-matched controls. They are, however, more severe in patients with senile onset than in age-matched controls. These findings suggest that white matter changes in patients with senile onset are consistent with a diagnosis of Alzheimer's disease.

Alzheimer Disease↗
PubMed1994

Evidence for atrophy of the corpus callosum in Alzheimer's disease.

Patients with late-onset Alzheimer's disease (AD) have more white matter changes on magnetic resonance imaging (MRI) than controls. To test the hypothesis that AD patients might have also atrophy of the corpus callosum (CC), we compared the CC thickness on MRI from 20 AD patients and 21 controls. We found a significant reduction in the CC thickness in AD compared with age-matched controls (p < 0.01). We demonstrated that atrophy of the CC depends mainly on the diagnosis of senile dementia of the Alzheimer type and at a lower degree on the diagnosis of presenile AD but neither on age nor on ventricle enlargement. This result suggests that beside the greater severity of white matter involvement in late-onset AD, atrophy of the CC may also be present.

Aged↗
PubMed1994

Pathologic findings in a case of primary progressive aphasia.

We report the histopathologic and immunohistochemical findings of a patient who suffered from primary progressive aphasia for 13 years. During the course of his illness, he was diagnosed as having Pick's disease, based on gradually progressive mild personality changes and MRI findings of severe bilateral temporal lobe atrophy. There was severe neuronal loss in the temporal gyri, intense gliosis throughout the cortex, and mild gliosis of the temporal white matter, without any changes typical for Alzheimer's disease or Pick's disease. Using the antibody Alz-50, we found many Alz-50-positive neurons that exhibited a granular or diffuse cytoplasmic stain without fibrous structures in the temporal and parietal cortex, but no ubiquitin or beta (A4) protein-reactive cells, nor spongiform changes. Staining for Alz-50 and ubiquitin did not reveal the presence of Pick bodies or Lewy bodies. We consider this case to be an example of nonspecific cortical degeneration. Our findings stress the need for histopathologic verification of the primary progressive aphasia syndrome.

Amyloid beta-Peptides↗
PubMed1994

Phase-contrast cine MR imaging of normal aqueductal CSF flow. Effect of aging and relation to CSF void on modulus MR.

Cine phase-contrast MR imaging was used to study pulsatile CSF flow in the aqueduct in 11 young controls (mean age 30 years) and 9 old controls (mean age 69 years). A high-resolution gradient echo technique and an oblique imaging plane, perpendicular to the aqueduct, was used to avoid volume averaging. Phantom studies confirmed that the technique was accurate. Aqueductal velocity and flux in old controls was higher than in young controls, but the differences were not significant. For all controls together, the averaged peak velocity was 4.2 +/- 1.5 cm/s in rostral and -7.8 +/- 4.9 cm/s in caudal direction; for the flux it was 0.16 +/- 0.10 cm3/s in rostral and -0.29 +/- 0.19 cm3/s in caudal direction. Phase-contrast measurements were significantly related to flow-void on modulus MR images, but not with ventricular size or cortical atrophy. The present technique avoids underestimation of aqueductal flow, and therefore reveals higher aqueductal velocity and flux values than previous studies. Factors other than age or atrophy seem to determine aqueductal CSF flow.

Adult↗
PubMed1993

SPECT, CT and MRI in a Turkish family with Huntington's disease.

A Turkish family with Huntington's disease documented on CT, MRI and SPECT is reported. Whereas in clinically definite cases CT and MRI are of limited value and SPECT does not add anything of value, in one asymptomatic subject SPECT showed moderate caudate nucleus hypoperfusion, underlining the hypothesis that SPECT may have a role in predicting Huntington's disease.

Adult↗
PubMed1993

Methotrexate induced brain necrosis and severe leukoencephalopathy due to disconnection of an Ommaya device.

A 63-year old woman with breast carcinoma developed leucoencephalopathy and local brain necrosis after intraparenchymal infusion of methotrexate. This iatrogenic condition was caused by drain disconnection of the Ommaya device (bore hole type). The diagnosis of this rare complication of an Ommaya device was based on multiplanar MR-imaging. The case is discussed with regard to the complications of intraventricular chemotherapy by means of an Ommaya reservoir.

Brain↗
PubMed1993

Serum alpha 1-antichymotrypsin is not a useful marker for Alzheimer's disease or dementia in Parkinson's disease.

We measured serum alpha 1-antichymotrypsin (ACT) levels in patients with Alzheimer's disease (AD), Parkinson's disease (PD), Multiple System Atrophy (MSA) and age-matched controls to evaluate whether serum ACT levels in AD patients were elevated and whether ACT levels in PD patients with dementia differed from those in PD or AD. None of the patient groups displayed an increase in ACT levels. We conclude that serum ACT is not useful as a marker, nor in AD nor in dementia in PD.

Aged↗
PubMed1993

A semiquantative rating scale for the assessment of signal hyperintensities on magnetic resonance imaging.

Differences in grading signal hyperintensities on magnetic resonance imaging may explain earlier reported conflicting results in studies of normal aging and dementia. We designed a new rating scale in which periventricular and white matter signal hyperintensities as well as basal ganglia and infratentorial signal hyperintensities are rated separately in a semiquantative way. In this study we compared the inter- and intra-observer agreements of this scale to the widely used rating scale of Fazekas. We confirmed the poor to reasonable intra- and inter-observer agreements of the Fazekas scale. The new scale, although more elaborate, provided good agreements with respect to the white matter, basal ganglia and infratentorial signal hyperintensities. In rating periventricular hyperintensities this scale yielded no advantage. It is concluded that this scale may be of use in studies especially focussing on deep white matter pathology on MRI, because it provides more detailed information, with good intra- and inter-observer reliability.

Aged↗