Biomedical subjects

G Künig

Publications and source records attributed to G Künig.

At least 19 recordsLinked to original sources

PubMed2007

[CERAD and NOSGER. Comparing predictive scales for dementia in a Swiss gerontopsychiatric patient population].

BACKGROUND: The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is an established screening instrument for the diagnosis of Alzheimer's disease. The Nurses Observation Scale for Geriatric Patients (NOSGER), actually developed for rating the frequency of behavioral disturbances, appears suitable for dementia screening as well. MATERIAL AND METHOD: In this retrospective study we analyze the neuropsychological data of 400 consecutive patients at our hospital with several psychiatric diagnoses and cognitive deficits. By means of logistic calculation in single and multivariable models, the predictive value of CERAD and NOSGER for dementia diagnosis was studied. RESULTS: All CERAD subtests were significant single predictors for dementia. The multivariable model with the highest prediction for probability of dementia diagnosis contained the subtests Verbal Fluency Test, Word List Recall, Constructional Practice Recall, and the Mini-Mental State Examination. However, NOSGER could not differentiate between demented and nondemented patients. CONCLUSION: In our gerontopsychiatric population, CERAD separates demented patients from nondemented ones with high predictive potency. The NOSGER does not reveal any predictive value for the diagnosis of dementia.

Aged↗

PubMed2006

Unrecognised long-lasting tramadol-induced delirium in two elderly patients. A case report.

We present the cases of two elderly patients with intermittent long-term tramadol intake against chronic back pain. Over a period of more than two years they experienced fluctuating confusional states and cognitive deficits, reversible only after discontinuation of tramadol. According to the DSM IV-criteria, an unrecognised recurrent tramadol-induced delirium can be diagnosed in both cases. Although tramadol may represent a well established safe therapy for chronic non-malignant pain in the elderly, these cases demonstrate that it should be applied with caution even in healthy subjects.

Adrenergic alpha-Antagonists↗

PubMed2002

Parkin mutations in a patient with hemiparkinsonism-hemiatrophy: a clinical-genetic and PET study.

The authors describe a 37-year-old woman with early-onset hemiparkinsonism (HP) and ipsilateral body hemiatrophy (HA). Genetic analysis revealed a missense mutation (Arg275Trp) and a duplication of exon 7 of parkin. The complementary metabolic and receptor pattern of PET ligands corresponded to that typically found in idiopathic PD, although tracer binding asymmetry was lacking. Parkin mutations should be considered in HPHA, particularly when there is a younger age at onset and dystonia is an early sign.

Adult↗

PubMed2001

Changes in brain activation associated with reward processing in smokers and nonsmokers. A positron emission tomography study.

Tobacco smoking is the most frequent form of substance abuse. Several studies have shown that the addictive action of nicotine is mediated by the mesolimbic dopamine system. This system is implicated in reward processing. In order to better understand the relationship between nicotine addiction and reward in humans, we investigated differences between smokers and nonsmokers in the activation of brain regions involved in processing reward information. Using [H2(15O)] positron emission tomography (PET), we measured regional cerebral blood flow (rCBF) in healthy smokers and nonsmokers while they performed a prelearned, pattern-recognition task. We compared two conditions involving nonmonetary reinforcement or monetary reward with a baseline condition in which nonsense feedback was presented. With monetary reward, we found activation in the frontal and orbitofrontal cortex, occipital cortex, cingulate gyrus, cerebellum, and midbrain in both groups. Additionally, monetary reward activated typical dopaminergic regions such as the striatum in nonsmokers but not in smokers. We found a similar pattern of activation associated with nonmonetary reinforcement in nonsmokers, whereas activation was found in smokers only in the cerebellum. The different patterns of activation suggest that the brains of smokers react in a different way to reward than those of nonsmokers. This difference involves in particular the regions of the dopaminergic system including the striatum. In principle these observations could be interpreted either as a consequence of tobacco use or as a primitive condition of the brain that led people to smoke. Supported by related nonimaging studies, we interpret these differences as a consequence of tobacco smoking, even if a short-term effect of smoking prior to the experiment cannot be excluded.

Adult↗

PubMed2001

The role of language areas in motor control dysfunction in Parkinson's disease.

We evaluated the differences in motor control organization between parkinsonian patients with (seven cases) and without (ten cases) gait disorder. We used positron emission tomography (O15-H2O-PET) to measure regional cerebral blood flow as a correlate for local neuronal activation. This has been assessed during repetitive joystick movements of the right hand, externally triggered using a metronome as an auditory cue. In patients with Parkinson's disease (PD) without gait disorder, the contralateral supplementary motor cortex and the bilateral cerebellum were activated, while in PD patients with gait disorder the contralateral Broca's area, the contralateral sensory motor cortex and the homolateral cerebellum were activated. Our results suggest that PD patients with gait disorder creates an internal verbal cue in order to control the output of the movement of joystick, supplying the loss of control of the supplementary motor cortex that is activated in patients without gait disorder.

Brain↗

PubMed2001

Reward mechanisms in the brain and their role in dependence: evidence from neurophysiological and neuroimaging studies.

This article reviews neuronal activity related to reward processing in primate and human brains. In the primate brain, neurophysiological methods provide a differentiated view of reward processing in a limited number of brain structures. Dopamine neurons respond to unpredictable rewards and produce a global reinforcement signal. Some neurons in the striatum also react to the expectation and detection of reward. Other striatal neurons show reward-related activities related to the preparation, initiation and execution of movement. Orbitofrontal neurons discriminate among different rewards and code reward preferences. In the human brain, regions belonging to a meso-striatal and meso-corticolimbic loop respond to reinforcement stimuli in control subjects. These observations corroborate results obtained in primates. Additionally, reward induces activation in regions specific to task performance. Our results also show a similar pattern of reward-related activation in nicotine and opiate addicts. Thus, in contrast to healthy subjects, typical reward-related regions respond in addicts to monetary reward but not to nonmonetary reinforcement. Reduced activation in performance-related regions is also observed in both groups of dependent subjects. The results of animal and human studies suggest that dopamine and dopamine-related regions are associated with the integration of motivational information and movement execution. Dopamine-related pathological disorders can be associated with movement disorders, such as Parkinson's disease or with false motivational attributions such as drug dependence.

Animals↗

PubMed2001

Changes in reward-induced brain activation in opiate addicts.

Many studies indicate a role of the cerebral dopaminergic reward system in addiction. Motivated by these findings, we examined in opiate addicts whether brain regions involved in the reward circuitry also react to human prototypical rewards. We measured regional cerebral blood flow (rCBF) with H(2)(15)O positron emission tomography (PET) during a visuo-spatial recognition task with delayed response in control subjects and in opiate addicts participating in a methadone program. Three conditions were defined by the types of feedback: nonsense feedback; nonmonetary reinforcement; or monetary reward, received by the subjects for a correct response. We found in the control subjects rCBF increases in regions associated with the meso-striatal and meso-corticolimbic circuits in response to both monetary reward and nonmonetary reinforcement. In opiate addicts, these regions were activated only in response to monetary reward. Furthermore, nonmonetary reinforcement elicited rCBF increases in limbic regions of the opiate addicts that were not activated in the control subjects. Because psychoactive drugs serve as rewards and directly affect regions of the dopaminergic system like the striatum, we conclude that the differences in rCBF increases between controls and addicts can be attributed to an adaptive consequence of the addiction process.

Adult↗

PubMed2001

Levodopa pharmacokinetic-pharmacodynamic modeling and 6-[18F]levodopa positron emission tomography in patients with Parkinson's disease.

OBJECTIVE: Parameters of a pharmacokinetic-pharmacodynamic (PK-PD) model of levodopa have been claimed to reflect the magnitude of the dopaminergic deficit in patients with Parkinson's disease. The aim of this study was to correlate such parameters with positron emission tomography (PET) with levodopa tagged with 6-fluorine 18, an established imaging method for striatal dopaminergic neurons. METHODS: Twenty-three patients in different disease stages (Hoehm and Yahr stage 2.5-5 [Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology 1967;4:427-42]; median duration, 12 years) were studied. PK-PD modeling followed a single oral dose of levodopa/benserazide. The sum score of the Columbia Rating Scale (CURSSigma) was used for clinical assessments. A nonparametric effect compartment approach assuming a sigmoidal E(max) model was applied to the PK-PD analysis of plasma levodopa concentrations and corresponding CURSSigma. Thereafter 6-[18F]levodopa PET was performed, and the influx rate constants (k(c)) for the putamen and the caudatus region were correlated with the median effective concentration (EC(50)) and the equilibrium half-life (T(eq)) of the PK-PD model. RESULTS: (1) A significant correlation was observed between PK-PD parameters or with k(c) putamen as the dependent variable and the duration of the disease as the independent variable, which explains 33% of the variability of the EC(50), 42% of the variability of T(eq), and 36% of the variability of k(c). (2) Significant correlations were observed between k(c) and either EC(50) or T(eq), yielding the closest correlation for the putamen region (r = -0.47, P <.05; and r = 0.55, P <.01; respectively). CONCLUSIONS: Our findings show that key parameters of a PK-PD model of levodopa were in fairly close agreement with imaging of dopaminergic neurons by 6-[18F]levodopa PET. However, although PK-PD modeling of levodopa has been proven as a useful investigation of approaches aimed to restore dopaminergic deficits or to monitor disease progression, this modeling cannot serve as a pathomorphologic surrogate for the loss of striatal dopaminergic neurons.

Adult↗

PubMed2000

Reduced reward processing in the brains of Parkinsonian patients.

Regional cerebral blood flow (rCBF) in healthy controls and non-demented, non-depressed Parkinsonian patients was measured using H2(15)O PET while subjects performed a prelearned pattern recognition task with delayed response. To investigate differences between the two groups in response to reward, the experimental design consisted of three reinforcement conditions: no reinforcement consisting of nonsense feedback, positive symbolic reinforcement and monetary reward. In the controls, monetary reward activated bilaterally the striatum and anterior cingulate gyrus, as well as unilaterally the left cerebellum, midbrain and medial frontal gyrus. Symbolic reinforcement revealed a similar pattern of activation, except that the striatum and left midbrain showed no activation. The Parkinsonian patients responded to monetary reward with increased activation bilaterally in the cerebellum, medial frontal gyrus, and anterior cingulate gyrus as well as unilaterally in the right fusiform gyrus and midbrain and left caudate nucleus and precentral gyrus. Symbolic reinforcement induced significantly increased rCBF in the right cerebellum only. Compared with symbolic reinforcement, monetary reward produced extended activation of temporoparietal association cortex. The pattern observed in the controls demonstrates the role in reward processing of dopaminergic mesolimbic pathways in the healthy human brain, whereas the pattern in the Parkinsonian patients suggests the involvement of compensatory cortical loops in the diseased brain.

Arousal↗

PubMed2000

Ineffective subthalamic nucleus stimulation in levodopa-resistant postischemic parkinsonism.

The authors report a patient with postischemic parkinsonism who responded neither to levodopa nor to bilateral subthalamic nucleus (STN) stimulation. MRI revealed bilateral lesions of the substantia nigra, the striatum, the external pallidum, and part of the internal pallidum. PET showed reduced striatal dopa-decarboxylase activity, D2 receptor binding, and glucose metabolism. Perioperative microrecording showed low-frequency activity of STN cells. This case suggests that parkinsonian patients who do not have a good response to levodopa or in whom a postsynaptic dopaminergic lesion can be shown may not be good candidates for STN surgery.

Antiparkinson Agents↗

PubMed2000

Bradykinesia in early Huntington's disease.

BACKGROUND: Huntington's disease (HD) is generally considered a hyperkinetic disorder, although hypokinetic features are part of the motor syndrome. Moreover, the striatum is considered to play a key role in initiating and executing motor programs and achieving optimal scheduling in response generation. Controversial results regarding the association between clinical features and markers of progression of the disease might be the result of inadequate restriction of clinical signs to the choreatic syndrome. OBJECTIVE: To determine the relationship of neurologic motor and cognitive indices in patients with HD with intrinsic neuronal loss in the striatum, as measured using raclopride C11 and PET. PATIENTS AND METHODS: A cross-sectional study was performed on 11 patients with mild HD (stages 0-2). Motor (Unified Huntington's Disease Rating Scale [UHDRS], saccadic and tapping speed) and cognitive (verbal fluency, Trail Making Test, Stroop Test, Symbol Digit Modalities Test, Conditioned Associative Learning Test, and silhouette identification and object decision of the Visual Object and Space Perception battery) scores were correlated with raclopride C11 binding. RESULTS: Bradykinesia (a summation of five items of the UHDRS motor scale) was the best predictor for stage, that is, functional capacity, and showed a highly significant relationship with putaminous D2 binding (r = -0.94) and with CAG expansion length x years of age (r = 0.96). The exclusion of two patients with a rigid-akinetic HD variant did not alter these coefficients. Chorea was less well correlated than bradykinesia with D2 binding in all striatal regions. Performance on different cognitive tests, especially in timed tasks, was highly correlated with raclopride C11 binding in caudate nucleus and ventral striatum. CONCLUSION: Loss of D2 binding in the striatum is highly correlated with the deficit in fast motor and cognitive processing in patients with early Huntington's Disease. Thus, impairment of rapid execution of adequate responses to environmental changes seems to be a common manifestation of striatal disorders.

Adult↗

PubMed2000

Benzodiazepine receptor binding in Huntington's disease: [11C]flumazenil uptake measured using positron emission tomography.

We used positron emission tomography and [11C]flumazenil to analyze the benzodiazepine receptor binding in symptomatic and asymptomatic carriers of the Huntington's disease gene. We found an inverse relationship between [11C]flumazenil and [11C]raclopride binding in the putamen of symptomatic patients, and interpret this result as GABA receptor upregulation.

Adult↗

PubMed1998

Loss of human hippocampal adenosine A1 receptors in dementia: evidence for lack of specificity.

The density of hippocampal adenosine A1 receptors was measured in autopsy samples of six patients with dementia with either Alzheimer (three) or sclerosis type pathology (three) in hippocampus and six control patients. Kinetic parameters (Bmax and KD) were determined by means of quantitative autoradiography using [3H]8-cyclopentyl-1 ,3-dipropylxanthine as a radioligand. A significant 50% reduction of CA1 adenosine A1 receptors was observed in patients with dementia independent of the specific pathology. These results suggest that loss of hippocampal adenosine A1 receptors in dementia is not specific for Alzheimer type pathology.

Aged↗

PubMed1998

D2 receptor binding in dopa-responsive dystonia.

We have studied dopamine D2 receptor binding by [11C]raclopride positron emission tomography in 14 patients with dopa-responsive dystonia (DRD). Data were compared with 16 levodopa-treated patients with Parkinson's disease (PD) and 26 healthy controls. The results revealed an elevated [11C]raclopride binding index in the putamen and caudate nucleus of DRD patients compared with controls as well as a significant elevation in the caudate nucleus compared with PD patients. The increase of [11C]raclopride binding may be interpreted either as reduced tracer displacement by endogenous dopamine, or as an alteration of the receptor features due to chronic dopamine deficiency. The difference in [11C]raclopride binding in DRD and PD patients in the caudate nucleus suggests that this structure may be of pathophysiological relevance in the presentation of the clinical features of both diseases.

Adolescent↗

PubMed1998

123I-IBZM binding compared with long-term clinical follow up in patients with de novo parkinsonism.

We performed a prospective clinical follow up (mean follow up, 36 months; range, 24-56 months) of 65 patients with de novo parkinsonism in whom imaging of dopamine D2 receptors was performed before the initiation of dopaminomimetic therapy by means of 123I-iodobenzamide-single-photon-emission computed tomography (IBZM-SPECT). The results of IBZM-SPECT were compared with the long-term response to dopaminomimetic drugs, the development of motor fluctuations, and the development of clinical signs incompatible with Parkinson's disease (PD). A total of 55 patients had normal and 10 patients had reduced IBZM binding; 45 patients showed a good response to levodopa (L-dopa), 11 showed an equivocal response, and nine did not respond; 31 patients developed a fluctuating response to dopaminomimetic drugs and seven patients developed clinical signs indicative of multiple-system atrophy (n = 5), progressive supranuclear palsy (n = 1), or corticobasal ganglionic degeneration (n = 1). Chi-squared analysis showed a significant correlation of the results of IBZM-SPECT with the long-term response to dopaminomimetic therapy (p < 0.0001) and the development of motor fluctuations (p < 0.001) or clinical signs incompatible with PD (p < 0.0001). We conclude that IBZM-SPECT can help to differentiate between patients who will show a good response to L-dopa and will develop motor fluctuations (most likely patients with PD) and those patients who will not respond to L-dopa and might develop clinical signs compatible with another hypokinetic disorder of the basal ganglia.

Adult↗

PubMed1998

Inhibition of [3H]alpha-amino-3-hydroxy-5-methyl-4-isoxazole-propionic acid [AMPA] binding by the anticonvulsant valproate in clinically relevant concentrations: an autoradiographic investigation in human hippocampus.

The interaction of the anticonvulsant valproate with AMPA glutamate receptors in human post mortem hippocampus was investigated. At concentrations of > or = 100 microM valproate decreased binding of 40 nM [3H]AMPA to 45+/-56% of control level (CA 1). Clinically effective brain concentrations for valproate are estimated at 100-200 microM. Our results thus provide evidence that the anticonvulsant effects of valproate may partially be caused by interaction with AMPA receptors.

Aged↗

PubMed1998

Facial pain in a case of cranial dystonia: a case report.

A 76-year-old man had shown sustained excruciating facial pain in the maxillary region for more than 30 years. Since he was suffering from blepharospasm, facial electromyography was performed and revealed a perioral dystonia. This possible cause of facial pain might have been overlooked had dystonia not been considered and electromyographical studies performed. Repeated intramuscular perioral injections of botulinum toxin brought about complete pain relief. This case shows that involuntary activity of facial muscles can cause a severe chronic pain syndrome. Possible mechanisms include irritation of ascending trigeminal fibers, muscle ischemia due to compression of blood -vessels, or release of pain-producing substances.

Aged↗

PubMed1998

What is the optimal dose of botulinum toxin A in the treatment of cervical dystonia? Results of a double blind, placebo controlled, dose ranging study using Dysport. German Dystonia Study Group.

OBJECTIVES: Botulinum toxin injections have become a first line therapeutic approach in cervical dystonia. Nevertheless, published dosing schedules, responder rates, and frequency of adverse events vary widely. The present prospective multicentre placebo controlled double blind dose ranging study was performed in a homogenous group of previously untreated patients with rotational torticollis to obtain objective data on dose-response relations. METHODS: Seventy five patients were randomly assigned to receive treatment with placebo or total doses of 250, 500, and 1000 Dysport units divided between one splenius capitis (0, 175, 350, 700 units) and the contralateral sternocleidomastoid (0, 75, 150, 300 units) muscle. Assessments were obtained at baseline and weeks 2, 4, and 8 after treatment and comprised a modified Tsui scale, a four point pain scale, a checklist of adverse events, global assessment of improvement, and a global rating taking into account efficacy and adverse events. At week 8 the need for retreatment was assessed and then the code was unblinded. For those still responding, there was an open follow up until retreatment to assess the duration of effect. RESULTS: Seventy nine per cent reported subjective improvement at one or more follow up visits. Decreases in the modified Tsui score were significant at week 4 for the 500 and 1000 unit groups versus placebo (p<0.05). Additionally positive dose-response relations were found for the degree of subjective improvement, duration of improvement, improvement on clinical global rating, and need for reinjection at eight weeks. A significant dose relation was also established for the number of adverse events overall and for the incidence of neck muscle weakness and voice changes. CONCLUSION: Magnitude and duration of improvement was greatest after injections of 1000 units Dysport; however, at the cost of significantly more adverse events. Therefore a lower starting dose of 500 units Dysport is recommended in patients with cervical dystonia, with upward titration at subsequent injection sessions if clinically necessary.

Adult↗