[Molecular biology in neurology].
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Gene Transfer Techniques↗
Biomedical subjects
T Gasser
Publications and source records attributed to T Gasser.
Time course of distant effects of local injections of botulinum toxin.
Botulinum toxin A (btx) is used to treat focal dystonias. From accidental intoxications it is known that btx can cause generalized pathologic single-fiber electromyography (SFEMG) findings. We monitored the onset and course of these disturbances in eight patients who received a small dose of btx (2-22 ng) for therapy of focal dystonias in the head/neck region for the first time via repeated SFEMG investigations at days 0, 3, 6, 9, 12, 28, and 56. Recordings were performed in the extensor digitorum brevis muscle, and in two patients additionally in the tibialis anterior muscle. In six of these patients we found an increase of jitter and blocking. The onset of these changes was in the range of 3-13 days after injection. Fiber density showed a tendency to increase. There was no correlation between SFEMG findings and the dose of injected btx. Possible mechanisms for these observations may be either a very efficient local uptake and retrograde axonal transport via the spinal motor neurons or a systemic distribution via the blood circulation.
Adult↗
3H-spiperone binding to lymphocytes fails in the differential diagnosis of de novo Parkinson syndromes.
In order to investigate the diagnostic value of 3H-spiperone binding capacity to lymphocytes in the differential diagnosis of de novo Parkinson's disease (idiopathic Parkinson syndrome, PD), we performed a double blind prospective study of spiperone binding capacity of 123 patients and 23 healthy control persons, belonging to different diagnostic groups (PD, Parkinsonian syndrome due to vascular lesions, multiple system atrophy [MSA], essential tremor). Diagnoses were based on medical history, clinical examination, CT or MRI scan, acute response to dopamimetic drugs, one year follow up, and long term response to L-DOPA treatment. Spiperone binding was assayed using ten different concentrations (0.03-3 nmol) in absence or presence of 1 mumol (+)-butaclamol to determine nonspecific binding. There was no significant difference in spiperone binding between patients with PD not treated with L-DOPA, and patients with other basal ganglia disorders including parkinsonian syndrome due to vascular lesions, multiple system atrophy, or progressive supranuclear palsy, and age matched controls. Binding was significantly higher in parkinsonian patients with PD treated with L-DOPA and patients with essential tremor. It is concluded that at present 3H-spiperone binding gives no further information in the differential diagnosis of de novo Parkinson's disease.
Adult↗
Quantitative EEG analysis in early onset Alzheimer's disease: a controlled study.
We report EEG findings in 15 presenile Alzheimer patients (probable Alzheimer's disease according to NINCDS-ADRDA criteria) and 15 age-matched controls. The quantitative EEG was analysed with respect to absolute power for each frequency band at each location accounting for EOG and EMG artifacts respectively. Compared to controls patients showed an increase of power in the slow frequency bands delta and theta which occurred quite uniformly over the different brain regions. In contrast, the decrease of the power of the fast frequency bands alpha 2, beta 1 and beta 2 was accentuated over temporo-parietal regions. In the fast bands patients had a rather flat topographic power profile. The alpha activity was on the average still of a rhythmic nature but the peak frequency was slowed. Differences in slow and fast frequency bands were more pronounced on the left hemisphere.
Aged↗
Psychosocial aspects of Parkinson's disease.
Although Parkinson's disease has a definite neurologic basis, patients and relatives experience a multitude of stresses, only partly related to motor symptoms. Subjective and behavioral problems may be regarded as secondary disease symptoms. In an integrated approach, patients and relatives receive psychological counseling and learn new coping strategies for everyday situations. Results show that even elderly patients can make use of structured psychological interventions and change dysfunctional behaviors and cognitions. Measures specifically adjusted to Parkinson's disease are aimed at helping patients make better use of the beneficial effects of medication and counteract the possible negative effects of social and emotional stressors. Relatives need information about the disease and training to cope adequately with difficult caring situations. Future evaluation of medical treatment of Parkinson's disease should consider the interaction of psychological factors and symptom intensity. This interaction may result in momentary changes in the effects of medication because of psychological conditions. In the early stages of the disease, medication has the most positive effect, and psychological interventions should also have the most benefit.
Aged↗
[Neurogenetics. Part 3. New developments in gene mapping and diagnosis].
In the past year, the molecular genetic analysis of hereditary neurological diseases has expanded our knowledge of these disorders considerably. Additional genes for mendelian disorders were mapped. They include a form of familial Alzheimer's disease, progressive myoclonic epilepsy of the Unverricht-Lundborg type, and limb girdle muscular dystrophy. For a number of diseases, such as myotonic dystrophy, a form of Charcot-Marie-Tooth's disease, and most recently, Huntington's disease, the causative gene itself and its mutations were identified. These advances broaden the possibilities of molecular genetic diagnosis of hereditary neurological diseases and provide new insight into the molecular pathogenesis of these disorders.
Chromosome Mapping↗
IBZM-SPECT as predictor for dopamimetic responsiveness of patients with de novo parkinsonian syndrome.
IBZM-SPECT is useful as a predictor for the responsiveness to oral L-DOPA therapy in de novo parkinsonian patients. A reduction of postsynaptic dopamine D2 receptors in de novo parkinsonian patients makes the diagnosis of Parkinson's disease rather unlikely. Normal IBZM binding does not prove the diagnosis of Parkinson's disease; however, together with a positive apomorphine test, it strongly supports the clinical diagnosis. At present the combination of IBZM-SPECT and apomorphine testing appears to be a useful procedure for selecting de novo patients for clinical trials with new anti-parkinsonian therapy.
Administration, Oral↗
Apomorphine test for dopaminergic responsiveness in patients with previously untreated Parkinson's disease.
We prospectively examined the predictive value of the apomorphine test for the therapeutic efficacy of sustained oral levodopa treatment in 62 patients with de novo Parkinson syndrome (no additional neurological deficit) who had not previously been treated with dopaminergic medication. Patients received 2 to 5 mg of apomorphine hydrochloride subcutaneously and a subsequent trial of oral levodopa of at least 3 months' duration. In three patients, response to apomorphine could not be evaluated owing to side effects experienced during the test. In the remaining 59 patients, the best predictor of response to oral levodopa was the apomorphine-induced relative decrease in the scores on the motor examination part of the Unified Parkinson Disease Rating Scale (UPDRS). At a cutoff value of 20% improvement in UPDRS scores, the test predicted the response to levodopa correctly in 50 patients (85%). The sensitivity of the test was 90%, specificity 88%. The positive predictive value was 95%. However, seven of 19 apomorphine test-negative patients experienced a good (n = 4) or partial (n = 3) improvement with levodopa therapy. Thus, the negative predictive value was only 63%. We conclude that response to apomorphine has a high predictive value for response to sustained oral levodopa treatment in most previously untreated patients, but a negative test should not preclude an adequate trial of oral levodopa.
Adult↗
Marked reduction of striatal dopamine D2 receptors as detected by 123IBZM-SPECT in a Wilson's disease patient with generalized dystonia.
[123I]iodobenzamide-single photon emission computed tomography (IBZM-SPECT) was employed to study the distribution of dopamine D2 receptors in a patient with biochemically proven Wilson's disease presenting with generalized dystonia. IBZM is a dopamine D2 receptor antagonist with high affinity and specific binding to basal ganglia detectable by SPECT. IBZM-SPECT in this patient (age, 20 years) displayed a striatum to frontal cortex ratio of 1.2 compared to 1.55 +/- 0.05 (mean +/- SD) in normal controls (n = 7; mean age, 53.3 years). In parallel with this finding, MRI with heavily T2-weighted sequences showed atrophy and low signal intensity changes of the basal ganglia. There was no improvement of dystonia after a subcutaneous injection of apomorphine. In contrast, IBZM-SPECT of a neurologically asymptomatic Wilson's disease patient (age, 21 years) displayed a striatum to frontal cortex ratio of 1.6. The MRI scan of this patient was normal. It is suggested that the observed apomorphine-unresponsive generalized dystonia in this Wilson's disease patient is related to striatal lesions proven by IBZM-SPECT and MRI.
Adult↗
Hypofrontality on topographic EEG in schizophrenia. Correlations with neuropsychological and psychopathological parameters.
Topographic EEG was performed in 17 DSM-III-R schizophrenic patients and in 15 sex- and age-matched healthy controls. Eleven patients were first-onset (neuroleptic naive) schizophrenics. EEG band power was compared with psychopathology, neuropsychology and neurological soft signs. The EEG was recorded at 14 topographic locations monopolarly and movements of the eye and of the lid were monitored by two bipolar electro-oculogram (EOG) derivations, one vertical and one horizontal. A multivariate correction of EOG artefacts was performed based on regression analysis with respect to EOG channels. Schizophrenic patients showed higher mean and median power in most bands. These differences were marked in the delta band, in the fast alpha and beta bands, in particular at left frontal sites. Delta power at F7 was by far the best separating variable between schizophrenics and controls in a discriminant analysis. Significant positive correlations were found between the Brief Psychiatric Rating Scale scores "Anxiety-depression" and "Activation" and power in the fast bands and negative ones between "Anergia" and the beta bands. Positive significant correlations emerged between the total score in the Negative Symptoms Rating Scale and the amount of delta power, predominantly over the temporal region. Impairment in the Luria-Nebraska neuropsychological scores "Rhythm" and "Memory" correlated highly significantly with EEG band power. No correlations were found between neurological soft signs and EEG band power. Our results are in line with the hypothesis of a hypofrontality in schizophrenia. It is unlikely that these findings are an artefact of prior psychiatric treatment, as they were also observed in first-onset, neuroleptic naive schizophrenics.(ABSTRACT TRUNCATED AT 250 WORDS)
Adult↗
The deleterious effect of ocular artefacts on the quantitative EEG, and a remedy.
The effect of ocular artefacts on spectral EEG parameters is assessed statistically. These artefacts are caused by movements of the eyeball and/or of the lid. Further, methods for correcting ocular artefacts are presented and evaluated. This methodological study is based on data from an investigation comparing the EEG of schizophrenic patients (n = 17) with healthy controls (n = 15). Ocular artefacts are monitored by the bipolar vertical and the bipolar horizontal electro-oculogram (EOG). It is shown that the influence of ocular artefacts on the measured electrical activity in the frontal region is larger than the cerebral potentials which the EEG is ideally intended to record. The more frequent occurrence of blinks and eye movements in schizophrenic patients may lead to an artificial enhancement of slow frequency EEG power for schizophrenics and eventually "false significances". In contrast to this, we found more significant group differences when correcting for EOG artefacts than without it. This can be attributed to a very much inflated sample variability of the uncorrected EEG, due to the individually varying EOG power. We conclude that it may not be sufficient to select visually epochs for analysis that are considered artefact-free. Rather, one should monitor EOG artefacts and apply an appropriate correction.
Artifacts↗
Folinic acid therapy fails to improve early Parkinson's disease: a two week placebo controlled clinical trial.
Folinic acid (15 mg bid, po) was administered in a two week, double-blind, placebocontrolled, cross over clinical trial in 5 patients with Parkinson's disease (Hoehn and Yahr stage I or II). 4 patients had not been on L-dopa treatment prior to entering this trial and one patient was on a small dose of L-dopa. No significant improvement could be detected in this pilot study by clinical evaluation and motor performance assessed by a computer assisted motor performance test.
Adult↗
The autosomal dominant dystonias.
Dystonia is a term used to describe a specific set of abnormal movements that can occur as a symptom of a variety of neurologic disorders, but also as a disease entity in its own right. This review focuses on the primary dystonias and delineates the genetic contribution to these disorders. Included is a description of the well recognized forms of primary dystonias which manifest autosomal dominant inheritance, especially the "classic" type of early onset, generalized torsion dystonia, but also other clinically distinct forms such as myoclonic dystonia, paroxysmal dystonia, and DOPA-responsive dystonia. Also, a summary of the molecular genetic studies pertinent to these disorders and a discussion of the implications of recent genetic research for delineating the wide spectrum of this phenotypically and genetically heterogeneous group of diseases are forthcoming.
Alleles↗
123I-iodobenzamide-SPECT predicts dopaminergic responsiveness in patients with de novo parkinsonism.
We used 123I-iodobenzamide-single photon emission computed tomography (IBZM-SPECT) in a prospective study to investigate 38 patients with parkinsonism (Hoehn and Yahr stage I to III) not previously treated with dopamimetic drugs. Thirty-four patients only showed symptoms of Parkinson's disease, and four patients showed, in addition, subtle clinical signs of progressive supranuclear palsy or multisystem atrophy. IBZM is a dopamine D2 receptor antagonist detectable by SPECT. We compared IBZM-SPECT results with clinical response to subcutaneous injections of the D1/D2 dopamine receptor agonist apomorphine (38 patients) and long-term dopamimetic therapy (31 patients). IBZM-SPECT results predicted a positive or negative response to apomorphine in 30 of 34 patients (apomorphine response in four patients was equivocal) and response to dopamimetic therapy in 27 of 31 patients. Thus, imaging of dopamine D2 receptors using readily available IBZM-SPECT seems to distinguish between L-dopa-responsive (most likely Parkinson's disease of Lewy body type) and L-dopa-unresponsive parkinsonism in patients not previously treated with dopamimetic drugs.
Adult↗
Botulinum toxin A in orthopaedic surgery.
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Botulinum Toxins↗
Analysing curves using kernel estimators.
In this paper a novel statistical method for curve fitting is described and applied to growth data for illustration. This technique, called kernel estimation, is non-parametric and belongs to the class of smoothing methods. Therefore, it does not need an a priori functional model where individual parameters are determined from the data. Functional models can only reflect features which have been incorporated into the model. Recent progress in selecting the degree of smoothing from the data makes the new method more easy to use and more objective. It applies to the curve itself or to its derivatives.
Growth↗
MICs of ciprofloxacin and trimethoprim for Escherichia coli: influence of pH, inoculum size and various body fluids.
The influence of pH, inoculum size, human urine and prostatic extract on the MICs of ciprofloxacin and trimethoprim for Escherichia coli was investigated. There was no influence by the bacterial inoculum size within wide ranges on either drug. An increase in pH had a variable influence on the MICs of trimethoprim for E. coli but lowered those of ciprofloxacin considerably. Human prostatic extract increased the trimethoprim MIC for E. coli but lowered those of ciprofloxacin as compared to Mueller Hinton broth. Human urine increased the MICs of both drugs for E. coli.
Animals↗
[Neurogenetics--the challenge for neurology. Part 1. Gene mapping and gene diagnostics].
Recent advances in gene mapping have provided distinct chromosomal locations for a number of neurological disease genes. Mapping strategies include the identification of chromosomal aberrations associated with disorders and the candidate gene approach which requires correct assumptions about the primary biochemical defect. The most successful strategy, linkage analysis, relies on family studies and allows the mapping of genes without knowledge of the molecular cause of a disorder. Once the chromosomal position for a disease gene is known, indirect DNA diagnosis becomes available, providing risk estimates for individuals in affected families. Identification of the disease gene itself allows the characterization of the protein involved and direct diagnosis at DNA and protein level, thus leading to a greater understanding of the molecular pathology of neurogenetic disorders.
Chromosome Mapping↗