Cerebral vasculitis with multiple infarcts caused by lyme disease.
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Adult↗
Biomedical subjects
H Reichmann
Publications and source records attributed to H Reichmann.
Switching and combining dopamine agonists.
Switching from one dopamine agonist to another is common practice in the treatment of patients with Parkinson's disease. This paper describes some ideas on the most practical way to perform switching. In addition, it describes the possibilities of combining various dopamine agonists and discusses pros and cons for doing so.
Antiparkinson Agents↗
Coenzyme Q10 reduces the toxicity of rotenone in neuronal cultures by preserving the mitochondrial membrane potential.
Defects in mitochondrial energy metabolism due to respiratory chain disorders lead to a decrease in mitochondrial membrane potential (DeltaPsim) and induce apoptosis. Since coenzyme Q10 (CoQ10) plays a dual role as an antioxidant and bioenergetic agent in the respiratory chain, it has attracted increasing attention concerning the prevention of apoptosis in mitochondrial diseases. In this study the potential of CoQ10 to antagonize the apoptosis-inducing effects of the respiratory chain inhibitor rotenone was explored by video-enhanced microscopy in SH-SY5Y neuroblastoma cells. The cationic fluorescent dye JC-1 which exhibits potential-dependent accumulation in mitochondria was used as an indicator to monitor changes in DeltaPsim. The relative changes in fluorescence intensity after incubation with rotenone for 15 minutes were calculated. Pre-treatment with CoQ10 (10 or 100 microM) for 48 h led to a significant reduction of rotenone-induced loss of DeltaPsim. These results suggest, that cytoprotection by CoQ10 may be mediated by raising cellular resistance against the initiating steps of apoptosis, namely the decrease of DeltaPsim. Whether these data may provide new directions for the development of neuroprotective strategies has to be investigated in future studies.
Antioxidants↗
Arguments for the use of dopamine receptor agonists in clinical and preclinical Parkinson's disease.
On the basis of experimental studies which have demonstrated deleterious effects of L-DOPA (L-3,4-dihydroxyphenylalanine) in vivo and in vitro, it has been suggested that L-DOPA itself may contribute to the progression of Parkinson's disease. This hypothesis is, for many clinicians, the rationale for postponing the employment of and reducing the applied dosage of L-DOPA and for beginning therapy with dopamine receptor agonists or the monoamine oxidase type B (MAO-B) inhibitor selegiline. Furthermore, clinical studies have demonstrated that early treatment with dopamine receptor agonists is associated with a lower incidence of motor fluctuations and dyskinesia. Dopamine receptor agonists exert their symptomatic effect by directly activating dopamine receptors, bypassing the presynaptic synthesis of dopamine and the degenerating nigro-striatal dopaminergic system. They can thus also be of benefit late in the therapy of the disorder. In addition, the pharmacological profile of dopamine receptor agonists suggests a possible neuroprotective effect. This paper reviews briefly the pharmacology of dopamine receptor agonists and basic knowledge concerning the dopamine receptor stimulation which underlies their therapeutic effect. Preclinical approaches for demonstrating neuroprotective effects and their clinical relevance are also discussed.
Animals↗
[New approaches to transplantation of dopamine-producing cells and stem cells].
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Animals↗
[Early detection of Parkinson syndrome].
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Arthralgia↗
Schnitzler's syndrome with neurological findings.
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Brain↗
Differentiation of parkinsonian syndromes according to differences in executive functions.
Groups of patients with Parkinson's disease (PD), striatonigral degeneration-type multiple system atrophy (MSA) or progressive supranuclear palsy (PSP) with motor disability stages II and III according to Hoehn and Yahr, and a healthy control group were compared using neuropsychological tests of executive functions. The results indicate that all three patient groups were impaired in the tests of executive functions. In comparison with healthy subjects, the three patient groups showed impaired performance regarding verbal fluency, problem solving and verbal and figural working memory. Patients with PD differed significantly from healthy subjects in a test of verbal recency, while patients with MSA or PSP were unimpaired. The comparison of patient groups revealed no differences between PD and MSA patients. However, patients with PSP showed greater impairment in both phonemic and semantic fluency than patients with PD or MSA. Using discriminant function analysis, it was found that variables derived from four verbal fluency tasks (simple and alternate semantic and phonemic fluency) discriminated among the three patient groups at a level significantly exceeding chance. Over 90% of patients with PSP were correctly classified. Patients with PD and MSA were correctly classified in over 70% of cases. These results suggest that verbal fluency tasks may be sensitive measures in the differential diagnosis of PD, MSA and PSP.
Aged↗
HLA typing and Parkinson's disease.
Idiopathic Parkinson's disease (IPD) is a neurodegenerative disorder of unknown aetiology. Several antigens have been associated with IPD using serological methods. We systematically analysed HLA class I and II alleles in 45 German Caucasian IPD patients using sequence-specific oligonucleotides and sequence-specific primer technology. Applying Bonferroni adjusted p values, we demonstrate a statistically significant increase of the DQB1*06 allele (p = 0.002) in IPD which may indicate an association between IPD and the immune system. Alternatively, HLA alleles might be in linkage disequilibrium with genes located next to the HLA locus.
Adult↗
[Pramipexole in Parkinson disease. Results of a treatment observation].
Pramipexole is a novel, internationally available selective nonergot D2 dopamine agonist. The effectiveness, tolerability, and safety of pramipexole have been extensively proven in controlled trials in patients in the early and advanced stage of Parkinson's disease as monotherapy and in combination with L dopa. These trials indicated specific activity against tremor, anhedonia, and depression. Therefore, the present prospective, multicenter postmarketing surveillance study evaluated for the first time to what extent the results from the controlled pramipexole trials could be replicated under routine conditions in neurological practice and clinics. Modern scales were applied for the assessment of tremor and mood, i.e., the Short Parkinson's Evaluation Scale (SPES), the Tremor Impact Scale (TIS), and the German version of the Snaith-Hamilton Pleasure Scale (SHAPS-D). In 298 German Centers, 657 Parkinson's patients (365 men, 292 women) in advanced disease stages were treated with pramipexole in combination with levodopa. The average ages (+/- SD) were 67 (+/- 8.9) years for men and 69 (+/- 9.4) years for females. Motor functioning, especially tremor, motor complications, depression, and activities of daily living improved highly significantly (P < 0.0005), including self-rating by the patients. The dosage of levodopa could be reduced on average by 8% (P < 0.0001). This might contribute to a slowing of the disease progression in the long run. Dropouts due to side effects were observed only in 3.5% of the patients. Using new assessment scales suitable for routine application allowed confirmation of the results from controlled clinical trials with regard to tremor, anhedonia, and depression. The average daily dosage of pramipexole prescribed was 1.05 mg and thus was definitely lower than the average daily dosages of 2.35-2.66 mg used in controlled trials. This signifies that the option to adjust dosage according to effectiveness and tolerability under routine conditions yields a considerably lower incidence of adverse effects.
Aged↗
[Entacapone for treatment of motor fluctuations in idiopathic Parkinson syndrome].
The treatment of idiopathic Parkinson's disease becomes rather difficult if levodopa-induced late complications such as motor fluctuations or dyskinesias occur. This prospective and open study shows that an add-on therapy with entacapone can significantly lower wearing-off and end-of-dose akinesia. This treatment is well tolerated and easy to perform.
Aged↗
Practical importance of neuroprotection in Parkinson's disease.
Consensus could be reached that there is overwhelming evidence of preclinical neuroprotection. However, the evidence of neuroprotection/neurorescue under clinical conditions is limited. Lessons from clinical trials designed to show neuroprotection (selegiline, amantadine, dopamine agonists) demonstrate that with the drugs available neuroprotection/neurorescue has to start as early as possible. A PET-controlled clinical trial with ropinirole shows that there seems to be a good chance for neuroprotection in the early phase of Parkinson's disease in patients treated from the very beginning of the disease while there is no such benefit in patients with a late start of a neuroprotective therapeutic strategy. Also long-term clinical neuroprotection cannot be reached. Complicating factors to demonstrate clinical neuroprotection are discussed.
Amantadine↗
Protection of dopaminergic neurons in primary culture by lisuride.
Dopamine agonists play an important role in the treatment of Parkinson's disease by reducing the administration of L-3,4-dihydroxyphenylalanine (L-DOPA). The enzymatic and non-enzymatic conversion of L-DOPA is suspected to increase oxidative stress, which leads to the degeneration of dopaminergic neurons in Parkinson's disease. In primary mouse mesencephalic cultures we show that the dopamine D1/D2 receptor agonist lisuride, in a concentration range of 0.001-1 microM, enhances the survival of dopaminergic neurons, protects against toxicity induced by L-DOPA or 1-methyl-4-phenylpyridinium ion (MPP+) and stimulates 3H-dopamine uptake. Lisuride also reduces anaerobic metabolism during incubation with L-DOPA. The present findings suggest that lisuride may have trophic/survival-promoting properties and potentially reduces oxidative stress.
1-Methyl-4-phenylpyridinium↗
Pergolide protects dopaminergic neurons in primary culture under stress conditions.
Dopamine agonists are an important therapeutic strategy in the treatment of Parkinson's disease. They postpone the necessity for and reduce the required dose of L-3,4-dihydroxyphenylalanine (L-DOPA) medication thus protecting against the development of motor complications and potential oxidative stress due to L-DOPA metabolism. In primary cultures from mouse mesencephalon we show that pergolide, a preferential D(2) agonist enhanced the survival of healthy dopaminergic neurons at low concentrations of 0.001 microM. About 100 fold higher concentrations (0.1 microM) were necessary to partially reverse the toxic effects of 10 microM 1-methyl-4-phenylpyridinium (MPP(+)). Pergolide was equally effective in preventing the reduction of dopamine uptake induced by 200 microM L-DOPA. Furthermore, between 0.001-0.1 microM it also reduced lactate production thus promoting aerobic metabolism. The present findings suggest that pergolide protects dopaminergic neurons under conditions of elevated oxidative stress.
1-Methyl-4-phenylpyridinium↗
Novel mitochondrial DNA mutations in Parkinson's disease.
Despite the recent discovery of several chromosomal gene mutations in familial Parkinson's disease (PD) the genetic background for idiopathic PD remains to be elusive. Since the discovery of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) action on dopaminergic neuronal cells and the specific decrease of mitochondrial complex I activity in substantia nigra of PD patients mitochondrial biochemistry and genetics emerged to become Pandora's box in the pathogenesis of PD. One approach was to establish the potential role of defective mitochondrial DNA (mtDNA). As complex I genes are the most vulnerable part of mtDNA we analyzed the mitochondrial MTND1 and MTND2 genes of 10 substantia nigra and 85 platelet samples from PD patients. We were uneventful to detect heteroplasmic base changes even applying techniques able to visualize mutations with low percentage of heteroplasmy but here we report novel homoplasmic base changes. These results add further evidence that there are no inherited disease specific mtDNA mutations, hence individual homoplasmic mutations or very low grade heteroplasmic mutations in the vicinity of mitochondrial metabolism and oxidative stress may contribute to selective neuronal vulnerability in PD.
Base Sequence↗
Olfactory function in idiopathic Parkinson's disease (IPD): results from cross-sectional studies in IPD patients and long-term follow-up of de-novo IPD patients.
Olfactory loss is a prominent symptom in idiopathic Parkinson's disease (IPD). Experiment 1 re-investigated the diagnostic value of psychophysical testing in the differentiation between idiopathic Parkinson disease (IPD) from non-IPD; 50 consecutive PS patients participated. In Experiment 2 five de-novo patients received 3 olfactory tests spread over a period of approximately one year. Nineteen IPD patients were anosmic, and 18 were hyposmic. All but one patient with MSA and PSP had mild/moderate hyposmia. Normosmia was found in CBD/misdiagnosed PS/psychogenic movement disorder. In Experiment 2, one of the de-novo patients was normosmic, 3 hyposmic, and 1 anosmic. Follow up investigations indicated decreased olfactory function in 3 patients while it improved in one. The normosmic patient retained olfactory abilities. This patient failed to respond to pharmacological treatment. In summary, olfactory tests differentiate IPD from non-IPD. Furthermore, tests of olfactory function may also be of interest in investigations related to treatment of PS.
Adult↗
A G468-T AMPD1 mutant allele contributes to the high incidence of myoadenylate deaminase deficiency in the Caucasian population.
Myoadenylate deaminase deficiency is the most common metabolic disorder of skeletal muscle in the Caucasian population, affecting approximately 2% of all individuals. Although most deficient subjects are asymptomatic, some suffer from exercise-induced myalgia suggesting a causal relationship between a lack of enzyme activity and muscle function. In addition, carriers of this derangement in purine nucleotide catabolism may have an adaptive advantage related to clinical outcome in heart disease. The molecular basis of myoadenylate deaminase deficiency in Caucasians has been attributed to a single mutant allele characterized by double C to T transitions at nucleotides +34 and +143 in mRNA encoded by the AMPD1 gene. Polymerase chain reaction-based strategies have been developed to specifically identify this common mutant allele and are considered highly sensitive. Consequently, some laboratories preferentially use this technique over other available diagnostic tests for myoadenylate deaminase deficiency. We previously identified a G468-T mutation in one symptomatic patient who was only heterozygous for the common AMPD1 mutant allele. In this report, nine additional individuals with this compound heterozygous genotype are revealed in a survey of 48 patients with documented deficiency of skeletal muscle adenosine monophosphate deaminase and exercise-induced myalgia. Western blot analysis of leftover biopsy material from one of these individuals does not detect any immunoreactive myoadenylate deaminase polypeptide. Baculoviral expression of the G468-T mutant allele produces a Q156H substitution enzyme exhibiting labile catalytic activity. These combined results demonstrate that the G468-T transversion is dysfunctional and further indicate that AMPD1 alleles harboring this mutation contribute to the high incidence of partial and complete myoadenylate deaminase deficiency in the Caucasian population. Consequently, genetic tests for abnormal AMPD1 expression designed to diagnose patients with metabolic myopathy, and to evaluate genetic markers for clinical outcome in heart disease should not be based solely on the detection of a single mutant allele.
AMP Deaminase↗
Olfactory function in Parkinsonian syndromes.
The study aimed to compare olfactory function in idiopathic Parkinson's disease (IPD) and nonidiopathic Parkinson's syndrome (PS). At their first visit 50 PS patients (age 38-80 years) received testing for odor threshold, olfactory discrimination and identification. All patients underwent extensive neurological diagnostics including PET scans. Patients were followed up for 6-12 months. Most of IPD patients were functionally anosmic (n=19), the remaining IPD patients had severe/moderate hyposmia (n=18). PS patients diagnosed with multiple system atrophy had less severe olfactory deficits (7 hyposmia, 1 normosmia). With the exception of 1 hyposmic patient, other PS patients had no olfactory deficits (progressive supranuclear palsy, corticobasal degeneration, psychogenic PS, essential tremor). This study added to previous findings: (1) there was no major difference betwesen olfactory function in IPD subtypes; (2) all olfactory tests differentiated IPD from nonIPD. These data suggest that olfactory probes improve the diagnostic armamentarium in IPD.
Adult↗