Biomedical subjects

H Przuntek

Publications and source records attributed to H Przuntek.

At least 19 recordsLinked to original sources

PubMed2006

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.

Adult↗

PubMed2006

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.

Administration, Cutaneous↗

PubMed2006

Predictors of gastric emptying in Parkinson's disease.

Predictors of gastric emptying (GE) in patients with idiopathic Parkinson's disease (PD) of a solid and liquid meal are not well defined. For measurement of GE 80 patients with PD were randomly assigned to receive either a solid meal (250 kcal) containing 13C-octanoate (n = 40) or a liquid meal (315 kcal) with 13C-acetate (n = 40). All patient groups were off medication affecting motility and were matched for age, gender, body mass index, disease duration and severity, using Unified Parkinson's Disease Rating Scale (UPDRS). Gastric emptying was compared with a healthy control group (n = 40). Multiple regression analysis was used to determine predictors of gastric emptying. Exactly 88% and 38% of PD patients had delayed GE of solids and liquids respectively. Solid and liquid emptying was similar in women and men. There were no differences in GE in PD patients < 65 years of age when compared with patients > or = 65 years. Multiple regression analysis showed that motor handicaps such as rigour and action tremor are independent predictors of solid GE (r = 0.68, P < 0.001). The severity of motor impairment, but not any other neurological symptom, as assessed by UPDRS is associated with gastroparesis in PD and solid emptying is more likely to be delayed.

Acetates↗

PubMed2006

Repeat intrathecal triamcinolone acetonide application is beneficial in progressive MS patients.

Available immunomodulatory and conventional steroid treatment regimens provide a limited symptomatic benefit for patients with progressive multiple sclerosis (MS). We performed an open trial on the short-term efficacy of repeated intrathecal application of the sustained release steroid triamcinolone acetonide (TCA) in 27 progressive MS patients. Six TCA administrations, performed every third day, reduced the Expanded Disability Status Scale (EDSS) score [initial: 5.4+/-1.3, 3-7.5 (mean+/-SD, range); end: 4.9+/-1.1; 2.5-6.5; P<0.001] and significantly increased the walking distance and speed in particular after the fourth TCA injection. Concomitantly serially determined cerebrospinal fluid (CSF) markers of cell injury, neuron-specific enolase, total tau-protein, S-100, and beta-amyloid did not significantly change within the interval of TCA treatment. No serious side effects appeared. We conclude that repeat intrathecal injection of 40 mg TCA provides a substantial benefit in progressive MS patients with predominant spinal symptoms and does not alter CSF markers of neuronal cell injury.

Adult↗

PubMed2006

Oral fumaric acid esters for the treatment of active multiple sclerosis: an open-label, baseline-controlled pilot study.

An exploratory, prospective, open-label study of fumaric acid esters (FAE, Fumaderm(R)) was conducted in patients with relapsing-remitting multiple sclerosis (RRMS). The study consisted of the following four phases: 6-week baseline, 18-week treatment (target dose of 720 mg/day), 4-week washout, and a second 48-week treatment phase (target dose of 360 mg/day). Ten patients with an Expanded Disability Status Scale (EDSS) score of 2.0-6.0 and at least one gadolinium-enhancing (Gd+) lesion on T1-weighted magnetic resonance imaging (MRI) brain scans participated in the study. Safety was assessed by adverse events (AEs), blood chemistry/hematology, electrocardiogram, and urinalysis. The primary efficacy outcomes were number and volume of Gd+ lesions. Other clinical outcomes included EDSS score, ambulation index (AI), and nine-hole peg test (9-HPT). Effects of FAE on intracellular cytokine profiles, T-cell apoptosis, and soluble adhesion molecules were also assessed. Three patients withdrew during the first 3 weeks of the study because of side effects, non-compliance, and follow-up loss. The most common AEs were gastrointestinal symptoms and flushing; all AEs were reported as mild and reversible. FAE produced significant reductions from baseline in number (P < 0.05) and volume (P < 0.01) of Gd+ lesions after 18 weeks of treatment; this effect persisted during the second treatment phase at half the target dose after the 4-week washout period. EDSS scores, AI, and 9-HPT remained stable or slightly improved from baseline in all patients. Measures of T-cell function demonstrated alterations in cytokines and circulating tumor necrosis factor. The results of this exploratory study suggest that further studies of FAE in patients with MS are warranted.

Administration, Oral↗

PubMed2005

[Segmental dysfunction of sweating in multiple system atrophy].

There are many different causes of anhidrosis. Sweat glands can be absent, atrophic or blocked; sympathetic innervation may be disturbed, or central nervous system damage may prevent perspiration. We present a patient with multiple system atrophy ( MSA) who presented with unilateral anhidrosis of the trunk. MSA is a sporadic neurodegenerative disorder of adults involving the pyramidal, extrapyramidal, cerebellar and/or autonomic system. The findings in our patient could be explained by a depletion of catecholaminergic sympathetic neurons of the thoracic spinal neurons.

Barbiturates↗

PubMed2004

Efficacy of budipine and placebo in untreated patients with Parkinson's disease.

Previous studies demonstrated the efficacy of budipine on motor symptoms of treated patients with Parkinson's disease (PD) with rating scales. However rating procedures may be subjective and variable. Therefore additional use of instrumental motor tests are helpful to reflect therapeutic benefits. Objective was to test the efficacy of 20 mg budipine (t.i.d.) in 51 previously untreated idiopathic PD patients in a monocenter, double-blind, placebo-controlled trial with a 2:1 randomisation over a three month interval. Budipine was not superior to placebo application. However a detailed analysis of rating results shows, that budipine but not placebo treated patients significantly improved. Budipine caused significant better outcomes of motor tests with execution of complex movements, but did not change results of tasks, which demand for simple motions. Placebo significantly improved dopamine sensitive motor test results. These outcomes may result from improved non dopaminergic neurotransmission due to budipine. Placebo caused better results of dopamine sensitive tests, since placebo may release endogenous dopamine.

Adult↗

PubMed2004

L-carnitine and creatine in Friedreich's ataxia. A randomized, placebo-controlled crossover trial.

Impaired oxidative phosphorylation is a crucial factor in the pathogenesis of Friedreich's ataxia (FA). L-carnitine and creatine are natural compounds that can enhance cellular energy transduction. We performed a placebo-controlled triple-phase crossover trial of L-carnitine (3 g/d) and creatine (6.75 g/d) in 16 patients with genetically confirmed FA. Primary outcome measures were mitochondrial ATP production measured as phosphocreatine recovery by 31Phosphorus magnetic resonance spectroscopy, neurological deficits assessed by the international co-operative ataxia rating scale and cardiac hypertrophy in echocardiography. After 4 months on L-carnitine phosphocreatine recovery was improved compared to baseline (p<0.03, t-test) but comparison to placebo and creatine effects did not reach significance (p=0.06, F-test). Ataxia rating scale and echocardiographic parameters remained unchanged. Creatine had no effect in FA patients. L-carnitine is a promising substance for the treatment of FA patients, and larger trials are warranted.

Adenosine Triphosphate↗

PubMed2004

Antiapoptotic effects of budipine.

Apoptosis is one essential step for neuronal death in the nigrostriatal region in patients with Parkinson's disease. Cytotoxic tumor necrosis factor-alpha (TNF-alpha) and the proinflammatory cytokine interleukin-6 (Il-6) provide a proapoptotic environment. We investigated the influence of the antiparkinsonian compound budipine on the release of TNF-alpha and Il-6 in peripheral blood mononuclear cells (PBMC) and on the degree of cisplatin induced apoptotic cell death in SH-SY 5Y human neuroblastoma cells. 10(-7), 10(-8), 10(-9) mol/l of budipine significantly reduced release of TNF-alpha and Il-6 in PBMC and decreased apoptotic cell death after 50 hours and 74 hours in the SH-SY 5Y cells. Our results suggest, that budipine administration provides an antiapoptotic environment and slows neuronal apoptotic and inflammatory mediated loss of neurons.

Anti-Inflammatory Agents, Non-Steroidal↗

PubMed2004

Transdermal lisuride delivery in the treatment of Parkinson's disease.

Transdermal delivery of dopamine agonists (DA) is a promising therapeutic concept, which aims to ameliorate frequency and intensity of motor fluctuations in patients with Parkinson's disease (PD). We treated 8 PD patients with unpredictable on-off phenomena with lisuride patches (release: 2-5 microg lisuride base/cm2/hour in mice) in addition to their preexisting antiparkinsonian drug regime up to a period of 8 days. In order to quantify the intensity and frequency of motor fluctuations, we determined the motor changing rate (MCR), which corresponds to the patient's self rating of motor function, performed every thirty minutes, divided through the number of scored intervals minus 1. Additional lisuride patch application significantly (p = 0.023) improved the MCR compared to baseline. Relevant side effects were transient skin irritations in four patients. Our observational study demonstrates the safety, tolerability and efficacy of transdermal lisuride delivery in the treatment of motor complications.

Administration, Cutaneous↗

PubMed2004

Congruent deterioration of complex and simple movements in patients with Huntington's disease.

Rating scales and assessment of simple and complex movements may reflect severity of Huntington's disease (HD). Objectives of our study were to compare scored HD symptoms and outcomes of instrumental tests, which demand for simple (tapping) and complex (peg insertion) movement series, in controls and subjects in various HD stages and to correlate them to each other. Motor test outcomes were significantly worsened in previously untreated and treated HD patients in comparison with HD gene carriers and controls. Peg insertion- and tapping results significantly correlated with the scored HD symptoms. Significant associations appeared between both motor test results in the controls, the previously untreated- and treated HD patients. Results of both instrumental tasks represent no specific diagnostic marker of HD, but the significant associations between both motor test outcomes indicate, that a parallel progress of deterioration of complex and simple movement abilities occurs after start of HD.

Adult↗

PubMed2004

Methyltetrahydrofolate reductase polymorphism influences onset of Huntington's disease.

Onset of Huntington's disease (HD) negatively correlates with CAG repeat length of the HD gene, which encodes the protein huntingtin. This protein interacts with the homocysteine metabolizing enzyme cystathionine betasynthase (CBS). Objective of this study was to analyze the impact of CAG repeats, polymorphisms of various homocysteine metabolizing enzymes, like CBS, Methyltetrahydrofolate Reductase (MTHTR), Methionine Synthase Reductase (MSR) and methionine synthase (MS) on HD onset in 171 patients. The significant impact of CAG repeats on HD onset (chi2= 25.54, FG = 4, p<0.0001) with a significant correlation between both (R= -0.521, p=0.01) was obvious. HD patients with the homozygous MTHFR-1298-CC significantly (p = 0.024) earlier experienced HD symptoms. There was no influence demonstrable of CBS, MSR and MS. Determination of MTHFR polymorphisms and CAG repeats enables screening for subjects with putative early HD onset in order to study neuroprotective compounds in their efficacy to delay HD symptoms.

Adult↗

PubMed2004

Transcranial sonography in spinocerebellar ataxia type 3.

BACKGROUND: Transcranial sonography (TCS) identifies hyperechogenic basal ganglia in extrapyramidal disorders such as Parkinson's disease or dystonia and reveals brain atrophy reflecting the stage of degeneration in Huntington's disease. Aim of the present study was to evaluate the diagnostic potential of TCS in spinocerebellar ataxia type 3 (SCA3), a neurodegenerative disease affecting the cerebellum, multiple pontine nuclei, substantia nigra, pallidum, putamen, caudate nucleus and long spinal tracts. METHODS: 15 patients with a molecular diagnosis of SCA3 and 15 age- and sex-matched healthy control individuals were examined with TCS. Echogenicity of the substantia nigra, caudate nucleus, pallidum, putamen, dentate nucleus and cerebellar white matter were determined quantitatively (substantia nigra by measuring the area of incresed echogenicity) or semiquantitatively (0 = none, 1 = mild, 2 = marked) on both sides and compared with the echotexture of defined brain structures. Additionally, the width of the lateral ventricles, the 3rd and 4th ventricle was measured in both groups. RESULTS: SCA3 patients exhibited hyperechogenicities of the cerebellar white matter (57%), substantia nigra (40%), the dentate nucleus (54%), putamen (40%) and pallidum (40%) significantly more frequently (p <0.05) than controls (20%, 13%, 9%, 0%, and 0% in the corresponding areas). In none of the healthy individuals a marked signal increase could be observed, whereas 53% of SCA3 subjects had at least one region with marked echogenicity. Cerebellar atrophy as demonstrated by an enlarged 4th ventricle was observed in all SCA3 patients whereas this structure could not be differentiated from surrounding parenchyma due to its small size in healthy individuals. 3rd and lateral ventricles were significantly larger in SCA patients as compared to controls (p < 0.05). CONCLUSIONS: TCS is a suitable and non-invasive bed-side method to detect basal ganglia hyperechogenic lesions and posterior fossa abnormalities in SCA3 patients. The pattern of echotexture alterations and brain atrophy most likely reflects distribution and morphology of the neurodegenerative process.

Adult↗

PubMed2004

Therapeutic strategies in Friedreich's ataxia.

Friedreich's ataxia is caused by a pronounced lack of frataxin, a mitochondrial protein of not fully understood function. Lack of frataxin homologues in yeast and mice leads to increased sensitivity to oxidative stress, depletion of proteins with iron-sulfur clusters like respiratory chain complexes I-III and aconitase, and to iron accumulation in mitochondria. Similar effects have been demonstrated in human disease with increased markers of oxidative DNA damage in urine and impaired oxidative phosphorylation in in vivo exercise studies using 31 Phosphorus magnetic resonance spectroscopy (31P-MRS). Therapeutical trials mainly focus on antioxidative treatment with coenzyme Q10 or its short-chain variant idebenone. Promising effects on cardiac hypertrophy in uncontrolled preliminary studies contrast with minor effects in controlled trials and no effect of antioxidants on neurological deficits has been established. Preliminary encouraging 31P-MRS data exist for the treatment with L-carnitine but not with creatine. However, all these interventions may take effect too late in the pathogenic process. Alternative strategies aiming at an enhancement of frataxin by stem cell transplantation, gene transfer or frataxin supplementation are desirable. Additionally, more efficient biomarkers are needed to monitor treatment effects.

Animals↗

PubMed2004

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.

Aged↗

PubMed2004

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.

Adult↗

PubMed2004

Clinical effects of repetitive transcranial magnetic stimulation versus acute levodopa challenge in Parkinson's disease.

We studied the short-term clinical effects of 10-Hz repetitive transcranial magnetic stimulation (rTMS) of the motor hand area contralateral to the more affected limb in 12 non-fluctuating, for at least 12 hours drug free patients with Parkinson's disease (PD). We investigated the efficacy of rTMS in combination with a levodopa challenge test design under double-blind, placebo controlled conditions. Significant reductions of UPDRS III motor scores showed the treatment conditions: placebo/rTMS, levodopa/sham stimulation and levodopa/rTMS. A more detailed evaluation of arm symptoms contralateral to the stimulated brain region showed even more pronounced effects for the three conditions. There were significant differences between the mean response of the UPDRS III arm scores to the four test conditions. In conclusion our study demonstrates short-term beneficial effects of 10-Hz rTMS on motor symptoms in PD patients. A release of endogenous dopamine in subcortical structures, i.e. putamen, in response to rTMS is the most likely mechanism of action.

Adult↗

PubMed2004

Impact of apomorphine on BOLD signal during movement in normals.

Our group investigated modulatory effects of apomorphine on cerebral activation patterns during finger tapping movements in six healthy right-handed volunteers using an established fMRI protocol. Apomorphine application disclosed a reduction of cerebral activation to the contralateral precentral and postcentral gyrus and ipsilateral cerebellum, with a prominent net reduction of BOLD signal in cerebellar areas. These findings contradict those of similar studies performed on dopaminergic function and Parkinson's disease (PD), which predominantly found augmentation of cerebral activation patterns in normal volunteers and PD patients after dopaminergic stimulation. One conceivable explanation for our singular results would be preferred binding of apomorphine to presynaptic dopaminergic receptors, leading to inhibition of endogenous dopamine release and resultant diminished dopaminergic stimulation, reflected in diminished cerebral activation patterns. These findings warrant future consideration and further investigation of possible central inhibitory effects of dopaminergic therapy in functional imaging studies of the dopaminergic system in general and PD in particular.

Adult↗