M. A. Kuiper

L-glutamate, L-arginine and L-citrulline levels in cerebrospinal fluid of Parkinson's disease, multiple system atrophy, and Alzheimer's disease patients

Summary. Alterations in neuronal nitric oxide (NO) production may play a role in the pathophysiology of Parkinsons disease (PD) Alzheimers disease (AD), and multiple system atrophy (MSA). The biosynthesis of NO is dependent on the availability of L-arginine, the substrate for NO-synthase (NOS), and on L-glutamate, which stimulates NO synthesis via the NMDA receptor. In this process L-citrulline is formed. We measured the levels of these amino acids in cerebrospinal fluid (CSF) of 108 PD patients, 12 AD patients, 15 MSA patients and 21 healthy subjects. A slight but statistically significant elevation of CSF L-citrulline was found in MSA patients, while CSF L-glutamate was found to be significantly decreased in AD patients. We found no significant changes in L-arginine levels. Although the relation between the CSF levels of these amino acids and neuronal NO production is still unclear, our findings suggest that AD is associated with a decrease in NO synthesis.

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.

Serum α1-antichymotrypsin is not a useful marker for Alzheimer's disease or dementia in Parkinson's disease

SummaryWe measured serum α1-antichymotrypsin (ACT) levels in patients with Alzheimers disease (AD), Parkinsons 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.

Investigating associations between ICU level and quality of care in the Netherlands: reporting only SMRs is not the whole story

Dear Editor, With interest we read the paper by Kluge et al. [1] in which they compared standardized mortality ratios (SMRs) in different levels of intensive care in the Netherlands. They clearly showed that the SMR was equally low in all levels of intensive care, suggesting an overall good performance of the Dutch intensive care system [2]. This, however, does not necessarily mean that the different levels of intensive care perform the same and, therefore, they should not conclude that their finding ‘is in contrast with some earlier studies suggesting a volume–outcome relationship’. Kluge et al. [1] found very different case-mixes in the three levels of intensive care, with sicker patients being more prevalent in higher-level intensive care units (ICUs) than in lower-level ones. SMRs can be confounded by case-mix differences since the SMR is calculated using a logistic regression model, and a wellknown and previously reported serious problem of this model is that it underestimates mortality in the more sick patient and overestimates mortality in the less sick patient [2]. Furthermore, notwithstanding the fact that these authors did take 90-day mortality into account, the transfer of patients must have contaminated their findings. Thus, we suggest that at best Kluge et al. [1] can conclude that SMRs are similar in different levels of intensive care in the Netherlands when the data are not corrected for important differences in case-mix and not corrected for the effects of patients who were transferred from ICUs providing a lower level of care to those providing a higher level of care. Obviously, a case–control design study in which patient groups are matched and transferred patients excluded is preferred. As highlighted very recently, performance assessment requires better case-mix adjustment than is currently available in the APACHE IV model, especially given the growing role of outcomes in driving prospective payment patient referral and public reporting [3]. This is not to say that SMR is invalid per se. Indeed, large differences in SMRs should prompt discussions between ICUs as part of their quality improvement cycles. However, we regret that Kluge et al. [1] over-interpreted—or possibly misinterpreted—their findings, which should be corrected.

Drug-induced psychosis in Parkinson's disease (I): manifestations and therapy

In this first part of a review on drug-induced psychosis in Parkinsons disease, the etiology, the clinical features and the therapeutic strategies will be discussed. The drugs used in the therapy of Parkinsons disease may lead to non-motor complications, such as delirium or hallucinations. Especially anti-cholinergics, respectivily dopaminometics, play an important role. Lowering the dose or even discontinuing the medication is the main therapeutic measure. The use of an atypical antipsychotic drug (clozapine) may be indicated.