[Characteristics and dynamics of inpatient treatment of patients with Parkinson's disease in Germany : Analysis of 1.5 million patient cases from 2010 to 2015]. / Charakteristika und Dynamik der stationären Behandlung von Parkinson-Patienten in Deutschland : Analyse von 1,5 Mio. Patientenfällen aus den Jahren 2010 bis 2015.

BACKGROUND: Parkinson's disease is the most common neurodegenerative movement disorder and the fastest-growing neurological disease in the world. The diagnostic spectrum, demographic characteristics, comorbidities and case number developments of inpatient treatment in Germany with resulting implications for patient care have so far been insufficiently investigated. METHODS: Data from the diagnosis-related groups (DRG) statistics were analyzed in patients with a main and secondary diagnosis of primary Parkinson's syndrome (PS), secondary PS or other degenerative disease of the basal ganglia. For the reporting years 2010-2015, the dataset comprised 1,520,366 patient cases from 413 districts/independent cities throughout Germany. RESULTS: In 2015, mostly patients with moderate and severe primary PS were hospitalized (64.7%) often exhibiting motor fluctuations as well as marked medical and psychiatric comorbidities. Vascular parkinsonism was the most frequent secondary PS (36.6%) and progressive supranuclear palsy was the leading diagnosis in the other disorders of the basal ganglia (51.9%). Primary PS as a secondary diagnosis was found in many internal medicine hospitalizations. The inpatient case numbers for primary PS increased significantly from the years 2010 to 2015 and rural regions were particularly affected. CONCLUSION: The number of inpatient cases of Parkinson's disease is greatly increasing in Germany and mainly affects patients with severe motor complications and secondary parkinsonian syndromes. Particularly in rural areas, there is a risk of overburdening the treatment infrastructure, so that both outpatient and inpatient sectors must be strengthened. A limitation of the study is the analysis of only DRG coded data, whose quality could be improved in subsequent examinations by comparison with the current diagnostic criteria of the specialist societies.

Comparison of 200 mg retarded release levodopa/carbidopa - with 150 mg levodopa/carbidopa/entacapone application: pharmacokinetics and efficacy in patients with Parkinson's disease.

The interval of line tracing performance is more associated to basal ganglia function due to the dependence on bradykinesia and rigidity. The other component of this task, the precision of execution of complex movement sequences, is more related to attention. We compared the motor response after once dosing of 200 mg retarded release LD (levodopa)/CD (carbidopa) and of 150 mg LD/CD/EN (entacapone) by rating of motor symptoms, by measurement of LD- and 3-O-methyldopa (3-OMD) plasma concentrations and by the outcomes of a line tracing task. Thirteen treated patients with Parkinson's disease (PD) took one of the two tested LD formulations on two consecutive days under randomised, double blind, identical standardised conditions. No significant differences appeared regarding rated motor response and LD plasma concentrations, but 3-OMD only significantly went up after LD/CD intake. LD/CD/EN was superior to LD/CD regarding the attention related components of line tracing probably due to a hypothetically increased dopamine occurrence at the prefrontal cortex, which guides human behaviour.

Acute levodopa administration reduces cortisol release in patients with Parkinson's disease.

Levodopa (LD) application improves motor symptoms in patients with Parkinson's disease (PD) patients. Little is known on further effects of LD, which induced lower plasma levels of cortisol and lower serotonergic activity in certain brain areas of fish. Objectives of this trial were to analyse levels of cortisol, LD and 3-O-methyldopa (3-OMD) after administration of LD/benserazide in long term treated PD patients. 12 PD patients, taken off their regular treatment for at least 12 hours, received soluble 200 mg LD/50 mg benserazide under stress free conditions. Motor symptoms improved, LD and 3-OMD levels increased, whereas cortisol concentrations started to decrease significantly 30 minutes after LD intake. This reduced cortisol release may result from an overflow of exogenous LD in the brainstem. This hypothetically causes an reduced 5-HT content in neurons projecting to the hypothalamic structures, which are involved in the partial 5-HT dependent central regulation of peripheral cortisol release.

Pharmacokinetic behaviour of levodopa and 3-O-methyldopa after repeat administration of levodopa/carbidopa with and without entacapone in patients with Parkinson's disease.

Addition of the catechol-O-methyltransferase (COMT) inhibitor entacapone (EN) prolongs plasma metabolism of levodopa (LD). Objectives were to determine the clinical response after EN addition and the plasma degradation of LD and 3-O-methyldopa [3-OMD]. Not optimum treated hospitalised patients with Parkinson's disease received the same LD dosage on the first day only with carbidopa (CD) and on the second day with CD and EN (t.i.d.) within a standardised setting. We scored motor symptoms and measured LD- and 3-OMD levels on both days at fixed moments. Motor impairment significant better improved probably due to significant higher maximum concentrations [C(max)] and computed area under the curve values of LD levels during the LD/CD/EN condition. Time to C(max) of LD was significantly delayed after the first two LD/CD/EN intakes. An impact of EN on 3-OMD levels appeared. A possibly augmented LD absorption and a prolonged LD metabolism after EN supplementation may contribute to a more continuous LD delivery to the brain.

Transdermal rivastigmine treatment does not worsen impaired performance of complex motions in patients with Alzheimer's disease.

BACKGROUND: There is a debate about the deterioration of fine motor behavior during treatment with cholinesterase inhibitors. METHODS: We used an instrumental motor test, which demands a complex motion series. Thereby we assessed motor function in patients with Alzheimer's disease (AD), in patients with mild cognitive impairment (MCI), and in controls. We also performed this task and a complex reaction time paradigm (CRT) during a six-week open-label safety study using transdermal delivery of the cholinesterase inhibitor rivastigmine. OBJECTIVES: To investigate (1) the performance of complex movements during deterioration of cognitive function and (2) the impact of rivastigmine on fine motor behavior and CRT outcomes in AD patients. RESULTS: There were significant differences in the motor test outcomes, particularly when performed with the left non-dominant hand, between controls and patients with AD and MCI. Rivastigmine did not deteriorate assessed fine motor skills and CRT results. CONCLUSION: Our study shows an impaired carrying out of complex motion series during neurodegeneration associated with cognitive dysfunction. Rivastigmine selectively inhibits the predominant cortical and hippocampal G1 cholinesterase isoform; therefore, hypothetically no deterioration of fine motor behavior appeared during transdermal rivastigmine treatment. We assume that a putative drug-induced increase in speed and attention did not offset a deterioration of motion performance because we found no significant changes in the CRT results.

Differential executive control impairments in early Parkinson's disease.

Investigations concerning cognitive functions in early PD have revealed memory and executive function deficits related to dysfunction of fronto-striatal circuitry. Despite the range of data base, many previous investigations are limited because of methodological questions and inconsistencies. Thus the pattern of executive function impairments in early PD is far from being established. In the present investigation, twenty PD patients in early stages of the disease were compared to control subjects on a comprehensive neuropsychological test battery, aiming to explore their cognitive profile across a range of executive subcomponents. Results revealed impairments with respect to initiation, reasoning and planning. In summary, the present investigation shows that PD is associated with a differential executive impairment pattern which is (partly) related to disease characteristics and affective variables.

Simple movement sequences better correlate to levodopa plasma levels than complex ones.

Instrumental assessment of movements with a computer based device reflect the clinical response of patients with Parkinson's disease (PD) to dopaminergic stimulation. We investigated associations between levodopa plasma levels, scored motor symptoms of upper limbs and instrumental test outcomes after dopaminergic stimulation. Clinical rating scores, test outcomes for simple and complex motion series significantly improved after oral application of 250 mg of a water soluble, fast absorbed levodopa/benserazide preparation, which induced a significant increase of levodopa in plasma during a two hour interval. There was a significant association between the computed area under the curve-values of levodopa plasma concentrations and test results for simple-, but not for complex movement sequences. Performance of complex motion series additionally ask for concomitant cognitive efforts with consecutive hypothetical involvement of extranigral non dopaminergic systems. In contrast, practice of simple movements is more directly associated to the predominantly dopamine regulated motor system.

Worsened motor test performance following acute apomorphine injection in previously untreated patients with Parkinson's disease.

Instrumental tests and clinical rating assess motor disability in Parkinson's disease (PD) patients. Previous long-term dopaminergic substitution influences the behaviour following acute dopaminergic stimulation. Objective of this study was to investigate the motor response following an apomorphine application in previously untreated-, treated- and before treated PD patients, who received placebo. Outcomes of instrumental tests worsened in previously untreated-, but not in before treated PD patients after apomorphine injection and in the PD subjects under the placebo condition. Generally, rating scores of motor symptoms significantly improved after apomorphine administration, whereas placebo application showed no effects. Tolerance to sedative effects of apomorphine in treated PD patients or sensitivity of employed motor tests to presynaptic dopaminergic autoreceptor mediated inhibition of endogenous dopamine release or postsynaptic dopaminergic overstimulation with resulting decreased cognitive function in previously untreated PD patients hypothetically caused this discrepancy between outcomes of subjective clinical rating and objective motor test performance.