E.Ch. Wolters

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

Article abstract—We investigated the histopathologic correlates of white matter changes in Alzheimers disease (AD) patients (n = 6) and controls (n = 9) using postmortem MRT. 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 con-gophilic 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 imaginghistopathologic correlation was similar in AD patients and controls, these changes probably represent some form of accelerated aging.

Loss of olfaction in de novo and treated Parkinson's disease: Possible implications for early diagnosis

Olfactory dysfunction is a common finding in patients with Parkinsons disease (PD). As most studies reported on odor identification in more advanced and treated PD, we administered an odor detection, discrimination, and identification test to a heterogeneous, partly de novo, group of patients. Forty‐one non‐demented PD patients, 24 of whom had untreated early PD, and 18 healthy controls, were examined. Odor identification and discrimination data were corrected for odor detection scores. PD patients scored significantly lower on all olfactory tests. Interestingly, the subgroup of de novo patients with early PD also showed significant olfactory disturbances compared with healthy subjects. Within the PD group, using multiple regression analysis, we found a significant, negative correlation between odor discrimination measures and disease severity.

Clozapine in the treatment of parkinsonian patients with dopaminomimetic psychosis

In a double-blind placebo-controlled study, we evaluated the effects of clozapine (75 to 250 mg/day, mean 170.8) on dopaminomimetic psychosis and parkinsonian disability. Clozapine prevented deterioration of psychosis during the increase of dopaminomimetics in the 3 patients who completed the study. Worsening of parkinsonism occurred in 3 of the 6 patients. In the dosage used, clozapines usefulness was limited by its propensity to produce sedation, confusion, and increased parkinsonism.

[123I]FP-CIT SPECT is a useful method to monitor the rate of dopaminergic degeneration in early-stage Parkinson's disease

Summary. We investigated the applicability [123I]FP-CIT SPECT for the assessment of the rate of dopaminergic degeneration in PD. Twenty early-stage PD patients (age range 43–73 yr; mean age 55.4) were examined twice, a mean of 12 months apart. The mean annual change in the ratio of specific to nonspecific [123I]FP-CIT binding to the striatum was used as the outcome measure. The mean annual decrease in striatal [123I]FP-CIT binding ratios was found to be about 8% (of the baseline mean). In order to demonstrate a significant effect (p < 0.05) of putative neuroprotective agent with 0.80 power and 50% of predicted protection within 2 years, 36 patients are required in each group, when the effects are measured by means of changes in [123I]FP-CIT binding ratios in whole striatum. Our findings indicate that [123I]FP-CIT SPECT seems to be a useful tool to investigate the progression of dopaminergic degeneration in PD and may provide an objective method of measuring the effectiveness of neuroprotective therapies.

Intrinsic and extrinsic psychosis in Parkinson's disease

Abstract Direct and indirect signs and symptoms of Parkinsons disease are a major cause of disability in the elderly. Intrinsic symptoms comprise not only the well-known clinical hallmarks of this disease with motor behavioral abnormalities, such as bradykinesia, hypokinesia, rigidity and tremor, but also autonomic failure with orthostatic hypotension, urinal incontinence and impotence as well as non-motor behavioral abnormalities: mental dysfunction characterized by mood disorders, cognitive dysfunction and, sporadically, delusions and hallucinations. These symptoms are caused by a progressive abnormal degeneration of the dopamine (DA) producing cells in the substantia nigra (SN) and ventral tegmentum area (VTA) in combination with an interindividual fluctuating degree of decay in the noradrenergic (locus coeruleus), cholinergic forebrain (nucleus basalis of Meynert) and serotoninergic (dorsal raphe nuclei) systems. Extrinsic symptoms, induced by pharmacotherapy, mainly manifest with (un)predictable motor response fluctuations and dopaminomimetic psychosis. Psychological and psychiatric symptoms in Parkinsons disease (PD) are important predictors of the patients quality of life. As these symptoms are potentially treatable, identification is of major clinical importance both for the patients and their caregivers and may enable to maintain Parkinsons disease patients at home for a longer period.

SLEEP APNEA SYNDROME PRESENTING WITH COGNITIVE IMPAIRMENT

We report a patient in whom cognitive disturbances led to the discovery of a sleep apnea syndrome. To our knowledge, this sequence of events has not been reported before

Evaluation of [123I]β-CIT binding with SPECT in controls, early and late Parkinson's disease

The main neuropathological feature in Parkinsons disease (PD) is a severe degeneration of the dopaminergic neurons in the substantia nigra resulting in a loss of dopamine in the striatum. Recently, a new radioligand (beta-CIT) for single photon emission computed tomography (SPECT) became available for in vivo imaging of the dopamine transporter on nerve endings of dopaminergic neurons in the striatum. The present results demonstrate that [123I]-beta-CIT SPECT allows a discrimination between early and late PD patients. In our opinion, these preliminary data suggest that [123I]-beta-CIT SPECT should be used from now on in longitudinal studies (such as the DATATOP study) in which the effects of (putative) neuroprotective interventions in PD are monitored.

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

SummaryIron is believed to play a role in the pathogenesis of both Parkinsons disease (PD) and Alzheimers 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.

Normal cerebrospinal fluid glutathione concentrations in Parkinson's disease, Alzheimer's disease and multiple system atrophy

We measured total glutathione concentrations in the cerebrospinal fluid (CSF) of non-demented Parkinsons disease patients (PD; n=71), demented PD patients (PDD; n=13), multiple system atrophy patients (MSA; n=10), Alzheimers disease patients (AD; n=17) and age-matched controls (n=21). No statistically significant differences in the mean total CSF glutathione concentrations were found between groups and dopaminomimetic treatment was not found to have any effect on total CSF glutathione levels. Our main conclusion is that total glutathione is not useful as a CSF marker for assumed oxidative stress in patients with PD, MSA or AD.

Sneddon's syndrome: case report and literature review

Diagnostic and therapeutic problems of Sneddons syndrome are reviewed on the basis of the observation of a pregnant 36-year-old female. She had had Hodgkins disease stage I, curatively treated when she was 23 years old. She developed cerebral ischemic events, initially ascribed to isolated cerebral angiitis, associated with progressive dermatological lesions (generalised livedo racemosa). A temporal artery biopsy did not reveal giant cell angiitis, while the cutaneous arterioles in a biopsy showed marked intimal proliferation without inflammatory cell infiltration. The literature on Sneddons syndrome is reviewed.