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G Künig

Publications and source records attributed to G Künig.

30 records · Page 2Linked to original sources
PubMed1997

Costs of treating dystonias and hemifacial spasm with botulinum toxin A.

Botulinum toxin (BTX) has become a safe and effective therapeutic tool in the treatment of a variety of neurological disorders, especially dystonias. One major disadvantage, however, is the high cost of a single injection of BTX. In this study of 835 patients, we calculated the cost of treatment with BTX serotype A (BTX-A) for different dystonias and hemifacial spasm. The annual expenditure per patient for BTX-A injections in this cohort totalled (mean +/- standard deviation) 1030 Deutschmarks (DM) [1996 values] +/- DM610 [$US570 +/- $US340; 230 +/- 130 pounds sterling (Pound)] for blepharospasm (n = 158), DM1450 +/- DM1520 ($US800 +/- $US830; 310 Pounds +/- 280 Pounds) for craniocervical dystonia (n = 148), and DM1480 +/- DM780 ($US810 +/- $US430; 330 Pounds +/- 180 Pounds) for oromandibular dystonia (n = 16), while the treatment of cervical dystonia consumed DM4590 +/- DM2060 ($US2520 +/- $US1130; 960 Pounds +/- 420 Pounds) [n = 362] per patient. In order to alleviate symptoms in patients with hemifacial spasm (n = 151), DM510 +/- DM270 ($US280 +/- $US150; 110 Pounds +/- 60 Pounds) had to be spent annually. The expenses for surgical therapy for cervical dystonia were DM10,120 +/- DM1900 (n = 54). No major differences concerning expenditure could be found in this study between the 2 available preparations of BTX. However, there appeared to be a lower rate of adverse effects with the Botox formulation, compared with the Dysport formulation, of BTX-A (this difference was statistically significant, i.e. p < 0.001). Although the cost of an individual injection is high, other cost factors also substantially contribute to the societal costs of adult-onset dystonias. Some of these costs may be attenuated with the use of BTX. The subjective and objective relief of these socially devastating and sometimes painful conditions rewards the expenditure associated with the use of BTX-A.

Adult↗
PubMed1995

Regional differences in the interaction of the excitotoxins domoate and L-beta-oxalyl-amino-alanine with [3H]kainate binding sites in human hippocampus.

The excitotoxic amino acid domoate causes anterograde amnesia and memory deficits while the excitotoxin L-beta-oxalyl-amino-alanine (L-BOAA) is considered the causative agent of the motoneurone disorder, neurolathyrism. Employing quantitative autoradiography we investigated the potency of domoate and L-BOAA to inhibit [3H]kainate binding in human hippocampus. Domoate inhibited binding of [3H]kainate with inhibition constants between 5.8 +/- 2.8 nM (deep layers of gyrus parahippocampalis) and 200.9 +/- 247.8 nM (CA1 region of hippocampus). It was about a thousandfold more potent than L-BOAA with inhibition constants between 2.1 +/- 0.5 microM (superficial layers of gyrus parahippocampalis) and 51.0 +/- 41.9 microM (CA2/3 region of hippocampus). Interestingly, L-BOAA showed lowest affinity to [3H]kainate binding sites in those regions in which domoate showed highest affinity (e.g. CA2/3) and vice versa (e.g. CA1). These data further support the notion that the neurological symptoms observed after domoate intoxication are due to an excitotoxic action at kainate receptors and provide evidence for heterogeneity of kainate receptors in human hippocampus.

Aged↗
PubMed1995

Effect of age and disease duration on parkinsonian motor scores under levodopa therapy.

One hundred and fifty patients suffering from Parkinson's disease were analysed for the expression of the motor symptoms during optimum response to levodopa therapy (subscale III of the Unified-Parkinson's Disease Rating Scale). Patients were grouped according to age (< or = 64, 65-74, > or = 75 years). Disease duration and daily levodopa dosage were similar in the three groups. Pooled residual scores for posture and gait impairment (PGI), tremor (T), rigidity (R) and distal motor impairment (DMI; hand and foot movements) increased with age (Kruskal-Wallis ANOVA). The parkinsonian scores were significantly higher than the scores of 150 age-matched normal controls (Mann-Whitney U test). The differences between the patients' scores and the scores of the age-matched controls increased with age. In spite of a significant increase in the daily levodopa dosage with disease duration (linear regression), PGI aggravated age-dependently, and DMI age-independently with symptom duration (Spearman rank correlation). In contrast, T and R did not increase with disease duration.

Adult↗
PubMed1995

Epidemiological, genetic, pharmacological, kinesiological, nuclear medical (IBZM-SPECT), standard and functional MRI studies on Parkinson's disease and related disorders and economic evaluation of Parkinson's disease therapy--clinical projects in the BMFT-research program Munich: "Parkinson's disease and other basal ganglia disorders".

The results of selected clinical research projects related to epidemiological, genetic, pharmacological, kinesiological, and neuroimaging aspects (SPECT, PET, MRI, functional MRI) of basal ganglia disorders such as Parkinson's disease, Progressive Supranuclear Palsy, Multiple System Atrophy and Wilson's disease are summarized. A retrospective pharmacoeconomic analysis of Parkinson's disease is presented. These studies are part of a nationwide research program of the German ministry of research and technology (BMFT) entitled "Parkinson's disease and other basal ganglia disorders" and were carried out at the Department of Neurology, LMU München.

Basal Ganglia Diseases↗
PubMed1994

Neurofibrillary tangles without cell loss in the lateral vestibular nucleus of patients with Alzheimer's disease.

The lateral vestibular nucleus (LVN, nucleus of Deiters) was examined in the brains of four control subjects and four patients with dementia of the Alzheimer type (DAT). Neuronal counts on sections stained with silver and a polyclonal antibody to human choline acetyltransferase (ChAT) revealed an undiminished number of LVN neurons in patients with DAT. Numerous silver-stained neurofibrillary tangles (NFTs) were found in the DAT group, some also in the LVN of controls. These findings suggest that DAT affects LVN neurons, however without causing neuronal loss.

Aged↗
PubMed1994

Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) inhibit [3H] alpha-amino-3- hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) binding in human hippocampus.

Excitotoxins L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4,6-trihydroxyphenylalanine (6-OH-DOPA) have been investigated with regard to their potency to inhibit [3H] alpha-amino-3-hydroxy-5-methyl-4- isoxazole-propionic acid (AMPA) binding in human hippocampus in a quantitative autoradiographic study. With dissociation constants (KD) of [3H]AMPA binding and inhibition concentrations (IC50) of L-BOAA, 6-OH-DOPA and L-glutamate obtained from saturation and displacement experiments inhibition constants (Ki) for the inhibition of [3H]AMPA binding in individual hippocampal subregions could be calculated. They were between 5.2 +/- 2.9 and 35.1 +/- 39.9 microM for L-BOAA and 39.1 +/- 26.8 and 59.4 +/- 44.1 microM for 6-OH-DOPA. L-BOAA was equally potent as the endogenous agonist L-glutamate with Ki's between 13.1 +/- 3.9 and 21.4 +/- 12.1 microM (n = 4, mean +/- S.D.). Limbic system symptoms like cognitive deficits, mood disturbances and vivid dreams observed in patients with the motor neuron disease neurolathyrism may thus well be mediated by agonistic action of L-BOAA at AMPA glutamate receptors in hippocampus.

Aged↗
PubMed1994

Oxidative stress: free radical production in neural degeneration.

It is not yet established whether oxidative stress is a major cause of cell death or simply a consequence of an unknown pathogenetic factor. Concerning chronic diseases, as Parkinson's and Alzheimer's disease are assumed to be, it is possible that a gradual impairment of cellular defense mechanisms leads to cell damage because of toxic substances being increasingly formed during normal cellular metabolism. This point of view brings into consideration the possibility that, besides exogenous factors, the pathogenetic process of neurodegeration is triggered by endogenous mechanisms, either by an endogenous toxin or by inherited metabolic disorders, which become progressively more evident with aging. In the following review, we focus on the oxidative stress theory of neurodegeneration, on excitotoxin-induced cell damage and on impairment of mitochondrial function as three major noxae being the most likely causes of cell death either independently or in connection with each other. First, having discussed clinical, pathophysiological, pathological and biochemical features of movement and cognitive disorders, we discuss the common features of these biochemical theories of neurodegeneration separately. Second, we attempt to evaluate possible biochemical links between them and third, we discuss experimental findings that confirm or rule out the involvement of any of these theories in neurodegeneration. Finally, we report some therapeutic strategies evolved from each of these theories.

Alzheimer Disease↗
PubMed1994

Interactions of neurotoxins with non-NMDA glutamate receptors: an autoradiographic study.

Neurotoxic substances are discussed to cause neurodegeneration by acting as excitotoxins on glutamate receptors. We investigated the properties of L-beta-oxalyl-amino-alanine (L-BOAA) and 3,4, 6-trihydroxyphenlyalanine (6-OH-Dopa) at the alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid (AMPA) glutamate receptor and that of L-BOAA and domoic acid at the kainate glutamate receptor in human hippocampus. (3H)AMPA binding in hippocampal subfields was inhibited by L-BOAA and 6-OH-Dopa with mean IC50-values in the low micromolar range. (3H)Kainate binding was inhibited by L-BOAA with similar potency as (3H)AMPA binding and by domoic acid with mean IC50-values in the low nanomolar range. These results support the notion that symptoms like anterograde amnesia and epileptic seizures seen in domoic acid intoxication and limbic symptoms, e.g. cognitive and mood impairment observed in neurolathyrism may be caused by excitotoxic action on non-NMDA receptors. The potent interaction of 6-OH-Dopa with the AMPA-receptor may point to a possible dopaminergic-glutamatergic interaction in the development of neurodegenerative diseases like Parkinson's and Huntington's disease.

Amino Acids, Diamino↗
PubMed1993

Involvement of transmitter systems in neuropsychiatric diseases.

Normal function of the central nervous system (CNS) requires intact morphology as well as neurotransmission. Diseases of the CNS can become manifest as a sensorimotor deficit or psychic alteration, or both. When observing neuropsychiatric diseases, interaction of different transmitter systems is obvious. Thus, an increase or a decrease of transmitter systems affect each other. Mechanisms of compensation can also lead to alterations in transmitter systems not involved in the pathological process. Parkinson's disease, hyperkinetic movement disorders like ballism and Huntington's chorea, epilepsy and anxiety will be used in this paper as examples of the synergistic action of dopaminergic, peptidergic, glutamatergic, GABAergic and cholinergic neurotransmission. With our knowledge of the functional balance of transmitter systems in the CNS, various pharmacological strategies have been available to intervene in the pathophysiological process. The excitatory or inhibitory quality of the transmitter systems must be considered if such strategies are to be employed. On the other hand, a functional balance between two or more transmitter systems may cause a contrary therapeutic intervention on the opposite side of the balance.

Anxiety Disorders↗
PubMed1992

Modern therapy of Parkinson's disease.

The article summarizes historical aspects and current concepts of the treatment of Parkinson's disease. Antiparkinsonian therapy varies with the progression of the disease, age and clinical subtypes. Levodopa, anticholinergic substances, direct dopamine agonists, amantadine, L-deprenyl are used to treat motor symptoms of Parkinson's disease. Novel substances and therapeutic concepts are currently investigated. Treatment of non-motor symptoms of Parkinson's disease and supportive therapies are discussed in the article.

Antiparkinson Agents↗
PubMedDate not supplied

Pramipexole, a nonergot dopamine agonist, is effective against rest tremor in intermediate to advanced Parkinson's disease.

We evaluated the efficacy of the nonergot dopamine receptor agonist pramipexole in 16 patients with advanced Parkinson's disease and marked rest tremor during an "on" period. The patients were drawn from a larger placebo-controlled, double-blind, randomized trial, which was not originally designed to investigate the effect of pramipexole on tremor. Eleven patients received pramipexole. The first effects were seen with a pramipexole dose of 0.75 mg/d with a reduction of the tremor item A of Unified Parkinson's Disease Rating Scale (UPDRS III, "on" state) by 25% and of rigidity and akinesia by 22%. Under the highest dose, 4.5 mg/d, the tremor score was improved by 61% over baseline (p < 0.0056, Wilcoxon signed rank) and the sum of rigidity and akinesia items by 66% (p < 0.0038, Wilcoxon signed rank). Five patients received placebo and did not improve. Based on this sample of patients, the nonergot dopamine receptor agonist pramipexole appears to have a potent anti-rest tremor action while being effective against akinesia and rigidity.

Aged↗