Q10 therapy in patients with idiopathic Parkinson's disease.

A 3-month open-label trial was performed to evaluate the efficacy of 200 mg Q10 daily in 10 patients with Parkinson's disease. Motor performance was assessed with UPDRS and motor tests. There was no significant effect on the clinical ratings.

Decreased striatal dopamine-receptor binding in sporadic ALS: glutamate hyperactivity?

The pathogenesis of ALS may be related to increased glutamatergic excitotoxicity. The striatum receives massive glutamatergic input. Animal studies suggest that glutamate decreases striatal D2-receptor synthesis. In drug-naive, sporadic ALS patients we demonstrated decreased striatal D2-receptor binding in vivo that could be partially reversed by the glutamatergic transmission blocker riluzole. Our findings support the glutamatergic excitotoxicity hypothesis in sporadic ALS.

Clinical and pathologic abnormalities in a family with parkinsonism and parkin gene mutations.

A Dutch family with autosomal recessive early-onset parkinsonism showed a heterozygous missense mutation in combination with a heterozygous exon deletion in the parkin gene. Although the main clinical syndrome consisted of parkinsonism, the proband clinically had additional mild gait ataxia and pathologically showed neuronal loss in parts of the spinocerebellar system, in addition to selective loss of dopaminergic neurons in the substantia nigra pars compacta. Lewy bodies and neurofibrillary tangles were absent, but tau pathology was found.

MRI in patients with suspected vascular parkinsonism.

To determine whether MRI can reveal more vascular lesions in patients clinically suspected of having vascular parkinsonism, we compared 15 such patients with 15 patients who had idiopathic Parkinson's disease and 10 hypertensive controls. Patients with suspected vascular parkinsonism had significantly more subcortical lesions than those with Parkinson's disease or hypertension. The cutoff point that best distinguished patients with suspected vascular parkinsonism from patients with Parkinson's disease was a 0.6% level of lesioned brain tissue volume. There were two types of vascular parkinsonism: one had an acute onset and lesions located in the subcortical gray nuclei (striatum, globus pallidus, thalamus); the other had an insidious onset and lesions diffusely distributed in the watershed areas.

Impaired cognitive shifting in parkinsonian patients on anticholinergic therapy.

In this study we established that cognitive shifting, an ability that is known to be affected in PD, is more impaired in PD patients, treated with anticholinergics, than in de novo patients. Eleven PD patients on anticholinergic monotherapy were compared with 30 de novo patients. The groups did not differ with respect to age, duration and severity of PD, and depression, nor with respect to general intelligence or attention. We assessed cognitive shifting with three different card-sorting tests. The patients on anticholinergics showed a poorer performance on all card-sorting tests than the de novo patients did. The patients on anticholinergics needed significantly more trials in two card-sorting tests and discovered significantly less categories in total. There was also a significant difference in memory performance, but memory performance did not correlate with any score on the card-sorting tests. This indicates that the performance on card-sorting tests and the memory performance were independent.

Memory performance under varying cueing conditions in patients with Parkinson's disease.

The present study is a continuation of a previous study in memory performance which showed that Parkinson's disease (PD) patients increasingly relied on explicit cues which prompt the external strategy of serial clustering, in comparison to control subjects (CS), who profited increasingly from implicit cues which prompt the internal and more effective strategy of semantic clustering. In this study, we investigated whether the recall of PD patients can be affected by adding or removing explicit cues. We manipulated the California Verbal Learning Test in two ways. First, we told the subjects under study in advance from which categories the items to be recalled were derived, thus making the implicit cue to cluster semantically explicit (explicit condition). Next, we permuted the sequence of the items in each trial, thus preventing the subjects from adhering to the serial order, i.e. to explicit cues (permuted condition). We included the data of our previous study (mixed condition) in the analysis of memory and learning performance in the three conditions. Learning of PD patients, as reflected in the semantic ratio, proved to be more affected by the cueing conditions than that of CS. Total performance and the serial ratios did not show a significant interaction between group and cueing condition. The results are discussed in terms of external and internal generation of problem-solving strategies.

Executive functions and disease characteristics in Parkinson's disease.

In the present study, we investigated the association of two executive functions with disease characteristics in Parkinson's disease (PD), especially with severity of motor symptoms. We operationalized two executive functions, viz. fluency and cognitive shifting, each in a number of tests with heterogeneous materials, but with an identical format. We calculated the correlations between test performance and disease characteristics, including the factor scores of the Unified Parkinson's Disease Rating Scale (UPDRS). The results of this study show that only cognitive shifting was consistently associated with the severity of motor symptoms in PD, in particular with rigidity. None of the fluency tests had a significant association with severity of motor symptoms. The present study indicates that PD, as reflected by the severity of motor symptoms, is not associated with a general decrease in executive function. In spite of the fact that both are executive functions and both require generation of items, fluency and cognitive shifting are differentially related to PD.

Haloperidol and cognitive shifting.

In this study haloperidol appeared to affect the performance on a selected category of cognitive tasks considered to represent shifting aptitude. A pretest--post-test design was used with two groups of subjects: 17 patients suffering from idiopathic spasmodic torticollis, and 17 controls who were matched for age and intelligence. The results are discussed in relation to previous findings on haloperidol and cognition, shifting disorder in Parkinson's disease and changes in behavioural organization found in animals with an experimentally induced dopaminergic hypoactivity.

Memory and learning strategies in patients with Parkinson's disease.

Parkinson's disease patients (PD) do not differ from control subjects (CS) when they have to execute a problem solving task in which external cues for solving the problem are given. However, when PD have to solve a problem by means of an internally generated strategy, they show a serious decrease in performance. We hypothesised that this distinction may also apply to the way PD and CS organize recall. In order to test our hypothesis the California Verbal Learning Test (CVLT) was administered to 59 PD and 30 CS. The test consists of five learning trials using a 16-word target list, composed of four items from each of four semantic categories. The fact that the word list was built on this implicit organization was not divulged in advance. The sequence in which the words were read is fixed; each subsequent word belongs to a category being different from the category to which the preceding word belongs. The organization in recall according to the semantic categories is considered to be the result of an unprompted, internally generated strategy. Recall according to the sequence in which the words are read by the experimenter, is viewed as an externally offered strategy. The results prove to be in line with our hypothesis: unlike CS who appeared to rely mainly and increasingly on an internally generated semantic organization, PD showed evidence of gradually adhering more to the externally imposed serial sequence.

Stimulation of growth-hormone release with clonidine does not distinguish individual cases of idiopathic Parkinson's disease from those with striatonigral degeneration.

Multiple System Atrophy (MSA) and idiopathic Parkinson's disease (PD) can be difficult to distinguish. There is an ongoing debate about the diagnostic value of the growth-hormone response to clonidine (CGH-test) in PD and MSA. We investigated whether the CGH-test can identify individual patients in the early stages of PD (n = 21) and Striatonigral Degeneration (SND, n = 11), a particular variety of MSA. Patients were diagnosed on the basis of clinical criteria and IBZM-SPECT. Clonidine induced a greater total serum growth-hormone production in PD than in SND (p = 0.01). However, taking the difference in prevalence of PD and SND into account, and because of the low likelihood ratios of the test, an increase of GH after clonidine increases the pre-test probability for PD by about only 5 %, while an absent response of GH also increases the pre-test probability for SND by about 5 %. We conclude that the CGH-test discriminates between groups of patients with PD and SND, but has little practical diagnostic value for identifying individual patients.

Spasmodic torticollis: the problem of pathophysiology and assessment.

In 17 patients with idiopathic spasmodic torticollis (ST) quantitative indices for both signs (extent and direction of the head deflexions) and complaints (of deflexion, shaking and pain) were collected. In the literature deflexion in the horizontal plane is most frequently considered, but analysis of the data shows that deflexion in the coronal and sagittal planes is also important. Furthermore, it is found that especially the deflexions in the coronal and sagittal plane covariate with the patients' complaints, but not with horizontal deflexion. On the basis of these and related data, it is suggested that we are dealing with at least two subtypes of ST. Finally, the patient's neuroticism and depression scale values are within the normal range and do not show significant correlations with ST duration. The present study provides no evidence that ST is a psychogenic disorder. ST should be regarded as a central nervous system disorder of unknown aetiology.

MR volume estimation of subcortical brain lesions and ventricular cerebrospinal fluid: a simple and accurate stereologic method.

PURPOSE: To describe an MR imaging quantification method for estimation of total volumes of both white and gray matter subcortical lesions and ventricular cerebrospinal fluid (CSF) in the living human brain, and to determine the method's reliability. METHODS: In 12 subjects, total subcortical lesion and ventricular CSF volumes were estimated using systematic sampling. Systematic sampling was performed on equidistant MR sections using a counting grid with systematically ordered intersection points. The grid was randomly positioned on each consecutive MR section. Each grid intersection point hitting the structure of interest represents a fixed known volume dependent on grid intersection point distance and the sum of the section thickness and section gap. RESULTS: Total volume estimation of subcortical lesion and ventricular CSF takes 15 and 5 minutes per subject, respectively. Coefficients of error of the individual volume estimates ranged from .01 to .13 and are negligible to the coefficients of the group mean (range, .70 to .89). For subcortical lesion volume, the random intraobserver error yielded .04 and for ventricular CSF .02; the random interobserver error amounted to .11 and .04, respectively; and the systematic interobserver error was .15 and .04, respectively. CONCLUSION: The method described here for subcortical lesion and ventricular CSF volume estimation is accurate, reliable, valid, and fast.

Decreased striatal dopamine D2 receptor binding in amyotrophic lateral sclerosis (ALS) and multiple system atrophy (MSA): D2 receptor down-regulation versus striatal cell degeneration.

Recently, decreased striatal dopamine D2-receptor binding was demonstrated in vivo in amyotrophic lateral sclerosis (ALS). To further elucidate the pathogenetic mechanism underlying this D2-receptor deficit, a multi-level comparison was made between 30 sporadic ALS subjects and 24 patients with multiple system atrophy (MSA), a disorder clinically characterized by bradykinesia, neuroradiologically by severe D2-receptor loss, and neuropathologically by degenerating striatal cells. The extent of D2-deficit in ALS and MSA were within the same range, but extrapyramidal signs and symptoms were virtually absent in our ALS patients. Striatal cell loss in general or competitive D2-receptor occupancy could be considered unlikely in ALS. The striatum receives massive glutamatergic input and the pathogenesis of ALS may be related to increased glutamatergic excitotoxicity. As other mechanisms (cell loss, receptor occupancy) could be ruled out, and as animal studies suggest that (excess of) glutamate decreases striatal D2-receptor synthesis, the striatal D2-receptor deficit in ALS is most likely to be caused by a receptor down-regulation.

Movement-related potential measures of different modes of movement selection in Parkinson's disease.

Movement-related potentials were recorded preceding self-paced voluntary movements in patients with Parkinson's disease and in healthy subjects of the same age group. We compared the Readiness Potential preceding joystick movements in a fixed direction and preceding joystick movements in freely selected directions. In normal subjects the Readiness Potential amplitude was higher preceding freely selected movements than preceding movements in a fixed direction. The Readiness Potential in Parkinson patients failed to be modified by the different modes of movement selection. The modulation of the Readiness Potential by different ways of preparing for movement might be due to the supplementary motor area (SMA) being more strongly engaged by tasks requiring internal control of movements than by tasks that are externally structured. The results suggest that this task-dependent variation of SMA activity is reduced in Parkinson's disease. A failing capacity to adapt SMA activity to different task demands has previously been suggested by evidence from positron emission tomography studies using similar tasks.

Erythrocyte anion transporter and antibrain immunoreactivity in chorea-acanthocytosis. A contribution to etiology, genetics, and diagnosis.

Novel structural and functional alterations in the erythrocyte anion transporter band 3 are described in one patient with definite, and in two patients with symptoms compatible with chorea-acanthocytosis, but without acanthocytes. Immunoblotting analysis shows increased fragmentation of band 3, and sulfate flux measurements indicate that anion transport activity is reduced in the erythrocytes of these patients. These changes are similar, but not identical to those observed during normal erythrocyte aging. In addition, distinct antibrain immunoreactivity was present in the plasma of these patients. A family study indicates that abnormal erythrocyte band 3 structure and function and antibrain immunoreactivity may be phenotypes of two independent, genetically determined factors, that are part of the heterogenic defect of chorea-acanthocytosis. The findings in the patients without acanthocytes indicate that the biochemical abnormalities may be related to a chorea-acanthocytosis-like, amyotrophic extrapyramidal movement disorder with axonal neuropathy. Measurement of erythrocyte sulfate transport and plasma antibrain immunoreactivity could be of use in establishing the diagnosis and further unravelling the genetic background of chorea-acanthocytosis and related syndromes.

The Symptom Checklist-90 Revised questionnaire: no psychological profiles in complex regional pain syndrome-dystonia.

Complex regional pain syndrome (CRPS) is a syndrome usually localized in the extremities, mostly occurring after a preceding trauma or operation. Dystonia is present in a minority of CRPS patients, but, when present, leads to severe disability. Various pathological factors have been postulated to present in CRPS-dystonia, such as involvement of the sympathetic system, reorganization of the central nervous system, and psychological distress. In the present study, we investigated the involvement of psychological distress in CRPS-dystonia with the aid of the Symptom Checklist-90 Revised (SCL-90R) questionnaire. The SCL-90R is a multidimensional self-report inventory covering various dimensions of psychological distress. In a population of 1006 CRPS patients, we analyzed the SCL-90R scores of 27 patients with CRPS-dystonia (23 female and 4 male) and compared the scores to sample scores of a control female (n = 577) and a control rehabilitation population (n = 56). Insomnia scored significantly higher in the female CRPS-dystonia population, as compared to the control female population (P < 0.001), and in the total CRPS-dystonia population, as compared to the rehabilitation population (P < 0.01). Remarkable was the significantly higher score of somatization in the rehabilitation population, as compared to the CRPS-dystonia population (P = 0.006). For the other dimensions of psychological distress of the SCL-90R, the scores of the CRPS-dystonia and control populations were similar. With regard to the SCL-90R scores, we conclude that specific psychological profiles are not present in CRPS-dystonia.

Effects of female sex steroids on Parkinson's disease in postmenopausal women.

There are conflicting reports about estrogen modulating the activity of nigrostriatal dopaminergic neurons. Furthermore, modulation may be influenced by progesterone levels. Therefore, the clinical effects of sex steroids on parkinsonian symptoms in postmenopausal women with Parkinson's disease (PD) were analyzed in the present study. Patients (n = 12) were under the age of 80, able to perform the motor function tests, and showed no contraindications for estrogen suppletion. Motor function was assessed using the Unified Parkinson's Disease Rating Scale (UPDRS) and a patient interview on subjective changes. In a placebo-controlled, randomized, double-blind trial lasting 8 weeks, no significant dopaminergic effect of estradiol (E2) could be demonstrated, whereas in an open trial phase lasting 2 weeks, progesterone seemed to have an antidopaminergic effect. Several mechanisms are discussed that can account for the fact that we found no effect of E2 on motor functioning in our patients with PD.

Short-term memory in Parkinson's disease after withdrawal of long-term anticholinergic therapy.

We assessed the short-term memory (STM) using the Visual Paired Associates and the Verbal Paired Associates test, and the motor status at the end of 7.8 +/- 3.7 years of anticholinergic therapy in 22 nondemented patients with Parkinson's disease (PD). Eighteen patients managed to stop anticholinergic therapy. During anticholinergic therapy, STM in PD is significantly worse than in normal controls (CS). Two months after the withdrawal of anticholinergic drugs, the STM retest gain is significantly greater in PD than in CS, and at that time STM in PD did equal CS levels. After withdrawal of anticholinergic therapy, thirteen patients noticed a deterioration of motor function; the dose of levodopa had to be increased in seven patients. We conclude that in nondemented PD patients, long-term anticholinergic therapy probably does not result in irreversible damage to STM, and withdrawal of long-term anticholinergic therapy is feasible in the majority of PD patients.

Cognitive shifting as a predictor of progress in social understanding in high-functioning adolescents with autism: a prospective study.

Although striking and pervasive failure of social understanding is commonly viewed as a major defining characteristic of people with autism, few follow-up reports were published that have focused on improvement of social intelligence. In this prospective study in which 17 high-functioning adolescents with autism were involved, cognitive shifting as measured by card sorting tests, unlike overall intelligence, was shown to be the only significant factor in predicting progress in social understanding as assessed by social comprehension tests. A pretest-posttest design was used. During the 2-year follow-up all the subjects were in residential care and enrolled in educational curricula focusing on the development of social intelligence, living, and vocational skills.

Problems of levodopa treatment.

This article reviews the side-effects of levodopa therapy in Parkinson's disease. First the pharmacokinetic aspects of levodopa are dealt with. Then the side-effects are successively discussed. Finally the therapeutic possibilities for the side-effects will be covered. An attempt has been made to give both proponents and opponents of a certain therapy their due to make it clear to the reader that for the time being uniform therapeutic recommendations are not always possible. The typical characteristics and circumstances of every individual patient should be considered before any advice can be given.