The gene coding for glial cell line derived neurotrophic factor (GDNF) maps to chromosome 5p12-p13.1.
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Animals↗
Biomedical subjects
T Gasser
Publications and source records attributed to T Gasser.
Genetic linkage studies in autosomal dominant parkinsonism: evaluation of seven candidate genes.
Linkage studies were performed in three families (A, B, and C) with autosomal dominantly inherited parkinsonism affecting multiple members in three generations. Affected individuals exhibited the cardinal signs and symptoms of Parkinson's disease, with a mean age of onset of 51, 62, and 61 years in Families A, B, and C, respectively. Parkinsonian symptoms responded to L-dopa treatment, and an [18F]6-fluoro-L-dopa positron emission tomography scan in 1 affected member of Family B showed decreased striatal uptake typical of Parkinson's disease. Ancestors of all three families were traced to a small region in northern Germany and southern Denmark, suggesting the possibility of a common mutation. Linkage studies were performed with polymorphic markers associated with the following candidate genes: the genes for glutathione peroxidase (GPX1, 3q11), tyrosine hydroxylase (TH, 11p15.5), brain-derived neurotrophic factor (BDNF, 11p14), catalase (CAT, 11p13), amyloid precursor protein (APP, 21q21), copper-zinc superoxide dismutase (SOD1, 21q21), and debrisoquin 4-hydroxylase (CYP2D6, 22q13.1). Summed lod scores for all families excluded linkage to the genes GPX1, TH, APP, SOD1, and CYP2D6, as well as to the chromosomal region containing the genes CAT and BDNF. If families were analyzed individually, exclusion was possible for two (Family A), six (Family B), and five (Family C) of the seven candidate genes. There was strong evidence against linkage for the remaining loci in all families analyzed individually, except for TH, which was uninformative in Families A and B, and CYP2D6, which gave slightly positive pairwise lod scores in Family A. Our results indicate that the candidate genes investigated are not involved in the etiology of parkinsonism in these families.
Adult↗
EEG coherence in Alzheimer disease.
A novel approach is introduced to examine EEG coherence in different frequency bands of 17 locations from the 10-20 system. Fifty patients with clinically diagnosed Alzheimer's disease were compared with 42 age-approximated non-demented controls. We determined the average coherence between individual electrodes and all neighbouring electrodes. Coherence was decreased in the sample of demented patients and this effect was most pronounced in the frontal and central derivations of the theta, alpha and beta frequency bands. The results can be interpreted as the effects of neuronal loss and neocortical disconnection.
Aged↗
Quantitative EEG analysis in early onset Alzheimer's disease: correlations with severity, clinical characteristics, visual EEG and CCT.
We report EEG findings in 15 presenile Alzheimer patients (probable Alzheimer's disease according to NINCDS-ADRDA criteria) in relation to clinical characteristics. The quantitative EEG was analysed in terms of absolute band power while accounting for EOG and EMG artifacts, respectively. The degree of dementia is strongly reflected by an increase of power in the delta frequency band, accentuated on the left hemisphere, as well as decrease of alpha activity. Longer duration of disease is associated with a decrease of power in the alpha frequency band, earlier age at onset with an additional increase of power in the theta frequency band. Visual EEG evaluation correlates highly with the degree of dementia, in contrast to visually assessed CCT.
Age of Onset↗
Spontaneous perforation of the ureter: a rare complication of urolithiasis.
The spontaneous rupture of the ureter is a rare condition. A case of a girl is reported with a spontaneous perforation caused by ureteral and renal calculi. The concomitant urinoma was drained and the ureter splinted with a double-J catheter. The calculi were destroyed by extracorporal piezoelectric lithotripsy without anesthesia.
Child↗
Plasma triglycerides and three lipoprotein cholesterol fractions are independent predictors of the extent of coronary atherosclerosis.
BACKGROUND: The lipoprotein system has manifold links to atherosclerotic disease. LDL cholesterol is related to lesion formation and growth. The cholesterol of HDLs is indicative of protection against atherosclerosis. The status of triglycerides and of subfractions of high-density lipoproteins as risk factors is less certain. Also, the magnitude of the atherogenic/protective power of these factors is not known. METHODS AND RESULTS: Five hundred patients (418 men and 82 women) were enrolled in an angiographic study. A total of 1006 coronary lesions with > or = 50% narrowing were recorded as study end points. By extent of atherosclerosis, defined as the number of > or = 50% lesions, the study subjects were allocated to one of four ordered categories with 0, 1 to 3, 4 to 6, or 7 to 10 lesions, respectively. Subfractions of HDL cholesterol were determined by a dual precipitation method. By a polychotomous logistic regression model, it was found that, besides age and sex, LDL cholesterol, HDL2 cholesterol, HDL3 cholesterol, and triglycerides were independently predictive (P < .05) of the extent of coronary atherosclerosis. An increase in age by 10 years was associated with an increase of the odds ratio for falling into a higher-extent category by a factor of 1.64, and the same increase of the odds ratio was obtained by increasing LDL cholesterol by 0.92 mmol/L or triglycerides by 1.01 mmol/L and by decreasing HDL2 cholesterol by 0.20 mmol/L or HDL3 cholesterol by 0.46 mmol/L. The less sensitive coronary end point, presence of atherosclerosis (ie, observation of > or = 1 lesion of > or = 50%) depended significantly on age, sex, LDL cholesterol, and HDL2 cholesterol, but not on HDL3 cholesterol or triglycerides. CONCLUSIONS: In addition to LDL, HDL2, and HDL3 cholesterol, triglycerides also proved independently predictive of the extent of coronary atherosclerosis.
Cholesterol, HDL↗
The DYT1 gene on 9q34 is responsible for most cases of early limb-onset idiopathic torsion dystonia in non-Jews.
Idiopathic torsion dystonia (ITD) is characterized by involuntary twisting movements and postures. A gene for this disorder, DYT1, was mapped to chromosome 9q34 in 12 Ashkenazi Jewish (AJ) families and one large non-Jewish kindred. In the AJ population, strong linkage disequilibrium exists between DYT1 and adjacent markers within a 2-cM region. The associated haplotype occurs in > 90% of early limb-onset AJ cases. We examined seven non-Jewish ITD families of northern European and French Canadian descent to determine the extent to which early-onset ITD in non-Jews maps to DYT1. Results are consistent with linkage to the DYT1 region. Affected individuals in these families are clinically similar to the AJ cases; i.e., the site of onset is predominantly in the limbs and at least one individual in each pedigree had onset before age 12 years. None carries the AJ haplotype; therefore, they probably represent different mutations in the DYT1 gene. The two French Canadian families, however, display the same haplotype. Estimates of penetrance in non-Jewish families range from .40 to .75. We identified disease gene carriers and, with adjustments for age at onset, obtained a direct estimate of penetrance of .46. This is consistent with estimates of 30%-40% in the AJ population. Two other non-Jewish families with atypical ITD (later onset and/or cranial or cervical involvement) are not linked to DYT1, which indicates involvement of other genes in dystonia.
Adolescent↗
[Molecular biology in neurology].
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Gene Transfer Techniques↗
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↗