Peter Klotz

The motor performance test series in Parkinson's disease is influenced by depression

SummaryThe Motor Performance Test Series (MPTS) is widely used for treatment control in Parkinsons disease (PD). To elucidate the possible influence of depression on the fine motor skills in PD, 54 patients with idiopathic PD were investigated with the MPTS. 27 patients with major intensity of depression were compared to 27 age and motor disability matched patients with minor symptoms of depression, evaluated by the Zung depression scale. As determined by the subtest aiming, a significant lower ability for precise, quick complex arm-hand movements in depressed Parkinsonian patients was found. This result may be explained partly by motivation deficits in depressed patients with PD. On the other hand impairment of special motor loops including frontal lobe projections to specific thalamic subnuclei or to the caudate nucleus may cause disturbances of the subtest aiming in depressed Parkinsonian patients. On the basis of these findings impaired aiming may be explained by diminished ability for complex, semivoluntary movements in depressive Parkinsonian patients. The influence of psychiatric comorbidity on MPTS subtest aiming has to be considered in further therapy studies using evaluation of motor deficits by MPTS.

Disturbance of colour perception in Parkinson's disease

SummaryA computer-aided method for the determination of colour fusion time (CFT) was developed. CFT indicates the acuity of the perception of monochromatic contours. CFT was determined in 36 patients with Parkinsons disease (PD) and compared with a group of 36 age- and sexmatched controls. Patients with PD generally had a shortened fusion time, especially for dark-green, light-blue and dark-red stimuli. The results give evidence to the hypothesis of a colour peception disorder in PD. The physiological and pathoanatomical basis of this phenomenon is unknown, but a functional deficit of cortical neurons may be a probable cause.

Hepatic mitochondrial dysfunction in manifest and premanifest Huntington disease

Objective: In this cross-sectional study, we investigated whether there is evidence for hepatic mitochondrial dysfunction in manifest and/or premanifest Huntington disease (HD) by using the 13C-methionine breath test. Methods: The 13C-methionine breath test was performed within a group of 21 patients with early manifest HD without medication, 30 premanifest mutation carriers, as well as 36 healthy controls. Premanifest mutation carriers were stratified into the 2 groups preHD-A (further from predicted onset) and preHD-B (nearer) based on a calculation of the probability of estimated disease onset within 5 years. The 13C-methionine breath test was performed after an overnight fasting, breath samples were analyzed by nondispersive isotope-selective infrared spectroscopy, and results expressed as percentage dose recovered after 90 minutes of testing time. Statistical analyses comprised analysis of covariance and post hoc t tests. Results: Patients with manifest HD and mutation carriers from our preHD-B group revealed a lower amount of exhaled 13CO2 compared with healthy controls (p < 0.001 and p = 0.017, respectively). In a stepwise linear regression model, breath test results correlate to functional and cognitive scores of the Unified Huntingtons Disease Rating Scale in manifest and also in premanifest HD. For all mutation carriers together, there was a weak but significant correlation of breath test results to ratio caudate volume/total intracranial volume. Conclusion: This study demonstrates for the first time in vivo a subclinical, hepatic involvement in manifest and premanifest HD.

Progressive hepatic mitochondrial dysfunction in premanifest Huntington's disease

A subclinical, hepatic involvement in manifest and premanifest Huntingtons disease (HD) was recently demonstrated by using the 13C‐methionine breath test (MeBT). In this longitudinal pilot study, we investigated whether there is evidence for progressive hepatic mitochondrial dysfunction in premanifest HD.

Instrumental methods and scoring in extrapyramidal disorders

Theoretical Basics of Rating Scales.- The Hoehn and Yahr Rating Scale for Parkinsons Disease.- A Rational Basis for a New Scoring System Measuring Disability in Parkinsons Disease.- Depression Inventories in Parkinsons Disease.- Selecting Neurologic Function Tests for Parkinsons Disease: A Primer.- Measurement of Muscle Tone - Demarcation Between Spasticity and Rigidity.- Instrumental Assessment of Rigidity.- Tremor Assessment in Clinical Trials.- Frequency, Amplitude and Waveform Characteristics of Physiologic and Pathologic Tremors.- Interaction Between Voluntary and Involuntary Movements.- Long-Term Measurement of Tremor.- Kinematics of Standing Posture Associated with Aging and Parkinsons Disease.- Differential Diagnosis of Organic and Psychogenic Vertigo Using Dynamic Posturography.- Relevance of Posturographic Parameters in the Differential Diagnosis of Parkinsonism.- Quantification of Dopaminomimetic Effects on Parkinsonian Symptoms Using Automatic and Voluntary Postural Responses.- Posturography in Parkinsons Disease Patients on and off Medication.- Tracking Measures of Movement.- Kinematic Analysis of Complex Movements in Parkinsons Disease.- The Age Function of Normative Data for a Personal Computer-based Test System for the Analysis and Quantification of Manual Movement Disability.- Quantitative Clinical Evaluation of Parkinsonism Based on Visuomotor Tracking and Tracing.- Kinematic Properties of Upper Limb Movement Trajectories.- Use of Quantitative Assessment in Evaluating Patients with Neural Transplants.- Measurement of Diadochokinesia.- The Complexity Effect as an Indicator for the Parkinson Plus Syndrome.- Quantitative Assessment of Akinesia in Parkinsons Disease.- Motor Performance Test after Schoppe and Clinical Rating Scales - A Comparison.

Analysis of the course of Parkinson's disease under dopaminergic therapy: Performance of “fast tapping” is not a suitable parameter

In addition to clinical rating scales, instrumental methods are employed frequently for assessment of performance or motor deficits in Parkinsons disease (PD). Many studies have analyzed such parameters in cross‐sectional studies. We employed a battery of tests to investigate fine motor performance over a period of 4 years in 411 de novo parkinsonian patients from the Prado study. Specifically, tapping and pegboard testing (“plugging”) were evaluated and performance on these tests compared with clinical ratings. Plugging scores correlated well with tapping scores and clinical rating at each assessment timepoint. Both tests also showed significant differences to healthy controls. Nevertheless “fast tapping” was found to be less impaired than was plugging in de novo patients. Over time, it was observed that plugging scores, but not tapping scores, exhibited changes that paralleled movements in clinical score. Plugging scores exhibited a marked response to dopaminergic therapy whereas fast tapping showed no therapeutic response. Fast tapping is certainly not suitable for assessment of bradykinesia or hypokinesia, and does not respond to dopaminergic therapy.

Increase of angiotensin II type 1 receptor auto-antibodies in Huntington’s disease

BackgroundIn the recent years, a role of the immune system in Huntington’s disease (HD) is increasingly recognized. Here we investigate the presence of T cell activating auto-antibodies against angiotensin II type 1 receptors (AT1R) in all stages of the disease as compared to healthy controls and patients suffering from multiple sclerosis (MS) as a prototype neurologic autoimmune disease.ResultsAs compared to controls, MS patients show higher titers of anti-AT1R antibodies, especially in individuals with active disease. In HD, anti-AT1R antibodies are more frequent than in healthy controls or even MS and occur in 37.9% of patients with relevant titers ≥ 20 U/ml. In a correlation analysis with clinical parameters, the presence of AT1R antibodies in the sera of HD individuals inversely correlated with the age of onset and positively with the disease burden score as well as with smoking and infection.ConclusionsThese data suggest a dysfunction of the adaptive immune system in HD which may be triggered by different stimuli including autoimmune responses, infection and possibly also smoking.

Stability of cognitive functions under mitoxantrone therapy in patients with progressive multiple sclerosis: A pilot analysis

OBJECTIVE Mitoxantrone (MX) is a potent immunosuppressant that is licensed as escalation therapy for the treatment of active multiple sclerosis (MS). METHODS In an open-label, retrospective analysis, we investigated effects of MX therapy on parameters of cognitive functions in patients with progressive MS and significant disability. Twenty patients received a total of 42 mg/m(2) MX in 4 cycles. Six patients who fulfilled the criteria for MX therapy, yet did not receive this treatment, served as controls. Before initiation of therapy and after a mean observation period of 24 months, neurological examination and a neuropsychological test battery were performed. Neuropsychological analyses comprised tests for cognitive flexibility as a part of executive functioning, and verbal as well as non-verbal tests for memory and attention. Additionally, intelligence and symptoms of depression were investigated. RESULTS While there was stability of EDSS over time, there were no differences in cognitive functions before and after MX treatment. In contrast, patients not receiving MX showed a worsening of verbal short term memory and cognitive flexibility over the same time period. CONCLUSION In conclusion, this preliminary observational study points at stability of cognitive functions under MX therapy in patients with progressive multiple sclerosis.

Sustained-release of levodopa: single dose study of a new formulation.

SummaryMotor fluctuations and dyskinesias in Parkinsonian patients may be at least partially due to fluctuations of levodopa plasma concentrations. Sustained-release (SR) formulations of levodopa may present a promising, effective solution of this problem. Therefore we performed a 4-fold, crossover double-blind trial with a new SR preparation, tested in healthy volunteers (Gerlach et al., 1988) before, in 12 Parkinsonian subjects. Two different dosages of the pure new levodopa SR-preparation, a composition of 70% SR and 30% levodopa immediate release (IR) and a conventional IR levodopa preparation were compared by their pharmacokinetic behaviour and their clinical effects. The relative bioavailability of levodopa in plasma was 69% for the combination of SR and IR levodopa release, for the pure SR formulations (100mg levodopa) 54% and (200 mg levodopa) 55%, compared to the 100% of the standard form of IR release of 100 mg levodopa. In contrast to the conventional IR formulation the pharmacokinetic behaviour of the SR preparations showed no initial sharp peak, but more continuous and longer maintaining plasma concentrations of levodopa. Due to the small numbers of cases and the missing homogenity of the selected patients no statistical significant differences between the four preparations regarding the clinical response were observed. But the described pharmacokinetic behaviour gives hope, that these newly developed SR-preparations may lead to progress in the treatment of Parkinsons disease (prolongation of dosage intervals, reduction of motor fluctuations).

Neuropsychological impairment in natalizumab-associated progressive multifocal leukoencephalopathy: implications for early diagnosis

Immunocompromised patients and, recently, natalizumab (NAT)-treated patients with multiple sclerosis (MS) are at risk to develop the relatively rare but potentially fatal opportunistic central nervous system infection progressive multifocal leukoencephalopathy (PML). As rapid immune reconstitution by removal of NAT appears to determine prognosis, early diagnosis is mandatory.1 Neuropsychological symptoms are common in early stages of disease,2 yet data on neuropsychological function in NAT-PML is lacking. Few studies in HIV-associated PML have demonstrated a reduction in attention/working memory, visuospatial abilities and motor speed.3 We compare the neuropsychological performance of patients with NAT-PML with patients with relapsing–remitting (RR) MS during NAT therapy and patients with RR multiple sclerosis (RRMS) with relapse; we identify specific neuropsychological abnormalities that might support early NAT-PML diagnosis. Our monocentric retrospective analysis of data obtained during routinely performed investigations was approved by the local ethics committee (No 4566-13). Epidemiological characteristics of patients with NAT-PML (n=8, definite diagnosis4) and controls (stable NAT-treated patients, n=9; patients with RRMS with preceding relapse, n=14) are given in table 1. The time point of NAT-PML diagnosis corresponded to first detection of JC virus DNA in cerebrospinal fluid. Neuropsychological examination included Wechsler Memory Scale (digits forwards, backwards, visual reproduction I, information and general orientation), Rey Auditory Verbal Learning test, Regensburger Word Fluency Test, Shulman Clock Drawing Test and Beck Depression Inventory II. At the time point of …