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J Dichgans

Publications and source records attributed to J Dichgans.

At least 181 records · Page 10Linked to original sources
PubMed1996

Autosomal dominant cerebellar ataxia type I clinical features and MRI in families with SCA1, SCA2 and SCA3.

Sixty-five patients suffering from autosomal dominant cerebellar ataxia-I(ADCA-1) were subjected genotype phenotype correlation analysis using molecular genetic assignment to the spinocerebellar ataxia type 1, 2 or 3 (SCA1, -2 or -3) locus, clinical examination, eye movement recording and morphometric analysis of MRIs. Pyramidal tract signs, pale discs and dysphagia were more frequent in SCA1 compared SCA2 and SCA3 patients. Saccade velocity was reduced in 56% of SCA1 and all SCA2, but only in 30% of SCA3 patients. MRIs of SCA2 patients showed atrophy changes typical of severe olivopontocerebellar atrophy (OPCA). The morphological changes in SCA1 were similar but less pronounced. In contrast, SCA3 patients had only mild cerebellar and brain stem atrophy distinct from typical OPCA. The principal finding of this study is that mutations of the SCA2 and SCA3 gene cause phenotypes which can be distinguished in vivo by recording of eye movements and morphometric MRI analysis. Correlative plotting of saccade velocity and diameter of the middle cerebellar peduncle yields a clear separation of SCA2 and SCA3. Spinocerebellar ataxia type I falls into an intermediate range that overlaps with both SCA2 and SCA3. However, the clinical syndrome observed in SCA1 patients is different from that in SCA2 and SCA3.

Adult↗
PubMed1996

Interaction of smooth pursuit and the vestibuloocular reflex in three dimensions.

1. What is the neural mechanism of vestibuloocular reflex (VOR) cancellation when a subject fixates a target moving with the head? One theory is that the moving target evokes pursuit eye movements that add to and cancel the VOR. A recent finding with implications for this theory is that eye velocity vectors of both pursuit and the VOR vary with eye position, but in different ways, because pursuit follows Listing's law whereas the VOR obeys a "half-Listing" strategy. As a result, pursuit cannot exactly cancel the VOR in most eye positions, and so the pursuit superposition theory predicts an eye-position-dependent pattern of residual eye velocities during cancellation. To test these predictions, we measured eye velocity vectors in humans during VOR, pursuit, and cancellation in response to torsional, vertical, and horizontal stimuli with the eyes in different positions. 2. For example, if a subject is rolling clockwise (CW, frequency 0.3 Hz, maximum speed 37.5 deg/s) while looking 20 deg up, the VOR generates an eye velocity that is mainly counterclockwise (CCW), but also leftward. If we then turn on a small target light, located 20 deg up and moving with the subject, then pursuit superposition predicts that the CCW component of eye velocity will shrink and the horizontal component will reverse, from leftward to rightward. This pattern was seen in all subjects. 3. Velocities depended on eye position in the predicted way; e.g., when subjects looked 20 deg down, instead of 20 deg up, during CW roll, the reversal of horizontal eye velocity went the other way, from rightward to leftward. And when gaze was 20 deg right or left, analogous reversals occurred in the vertical eye velocity, again as predicted. 4. Analogous predictions for horizontal and vertical stimulation were also borne out by the data. For example, when subjects rotated rightward while looking 20 deg up, the VOR response was leftward and CCW. When the target light switched on, the torsional component of the response reversed, becoming CW. And analogous predictions for other eye positions and for vertical stimulation also held. 5. For all axes of stimulation and all eye positions, eye velocity during cancellation was roughly parallel with the gaze line. This alignment is predicted by pursuit superposition and has the effect of reducing retinal image slip over the fovea. 6. The fact that the complex dependence of eye velocity on the stimulation axis and eye position predicted by pursuit superposition was seen in all subjects and conditions suggests strongly that the VOR indeed is canceled additively by pursuit. However, eye velocities during cancellation were consistently smaller than predicted. This shrinkage indicates that a second mechanism, besides pursuit superposition, attenuates eye velocities during cancellation. The results can be explained if VOR gain is reduced by approximately 30%, and if, in addition, pursuit is driven by retinal slip rather than reconstructed target velocity in space.

Adult↗
PubMed1996

Friedreich's ataxia with retained tendon reflexes: molecular genetics, clinical neurophysiology, and magnetic resonance imaging.

Lower limb areflexia is generally regarded as an essential criterion for the diagnosis of Friedreich's ataxia (FRDA). We describe a family with a recessive form of early-onset ataxia in which one member had a phenotype typical of FRDA whereas another, with retained tendon reflexes in the lower limbs, did not have electrophysiologic evidence of the usual severe afferent axonal neuropathy of FRDA. In contrast, somatosensory evoked potentials, eye-movement recordings, and MRI of the head and cervical cord provided results highly suggestive of FRDA in both patients. We performed genetic linkage analysis in this family, using markers tightly linked to the FRDA locus on chromosome 9. Inheritance of identical paternal and maternal genotypes by the affected members, but not by their unaffected siblings, provided supporting evidence that this disorder may result from mutation within the FRDA gene or is tightly linked to the investigated loci on chromosome 9.

Adult↗
PubMed1996

[Influence of genetic factors on multiple sclerosis].

Epidemiological studies have provided evidence for a genetic contribution to the susceptibility of multiple sclerosis (MS). One in six patients has at least one affected family member. The concordance rate is approximately 25% in monozygotic twins, and 3% in siblings, however the prevalence in adopted siblings is similar to the general population (0.1%) MS is thought to be a T cell-mediated autoimmune disease and therefore genes controlling the immune response have been studied intensively as potential susceptibility factors. The best documented association was found for genes of the human-leukocyte antigen complex. Other possible susceptibility genes may reside in the regions of the T cell receptors and the tumour necrosis factors. So far it is clear, that MS is a multifactorial disease in which several genes must be involved. Population genetics and molecular biology will help to characterise further these susceptibility factors.

Autoimmune Diseases↗
PubMed1996

[Gene therapy of neurologic diseases. Experimental approaches and clinical perspectives].

So far, it has not been possible to treat many neurological conditions causally. However, in the past few years underlying genetic defects have been characterized for a substantial number of neurodegenerative disorders. Experimental methods have been developed that allow for efficient gene transfer into defined regions of the mammalian CNS. Such techniques can be applied to deliver genes into target cells of a recipient organism or to transfer genetically modified cells into defined regions of the CNS. Candidate genes for gene therapy are those encoding for neurotrophins and neurotransmitters for symptomatic therapy and, in the case of neurodegenerative disorders with localized gene defects, the wild-type allele as a causal treatment approach. In this review article, we describe some of the most widely used strategies for gene transfer to the CNS. We also report on the results obtained with animal models for human disease, and discuss both the chances and problems of gene therapy approaches in clinical medicine.

Animals↗
PubMed1995

A defect of kinesthesia in Parkinson's disease.

Patients suffering from Parkinson's disease (PD) are more dependent on visual feedback during movement than are normals. Studying two-dimensional pointing movements, we recently found that PD patients undershoot targets when vision of their own moving hand is occluded but not when complete vision is provided or when the target is extinguished immediately before movement onset. In the absence of vision, information about position of the moving hand may originate from peripheral kinesthetic feedback and from corollary discharges derived from the efferent motor signal. To find out which of both mechanisms--kinesthetic feedback or corollary discharge--is defective in PD, we compared active movements with imposed movements in which the hand is passively moved by the experimenter, whereas vision of the hand was occluded under either condition. In agreement with our earlier findings, slow, active pointing movements of PD patients were hypometric. In addition, PD patients terminated passively imposed movements of comparable speed earlier than did normals, with the consequence that imposed movements were equally hypometric. Our results make it unlikely that disturbed corollary discharge is responsible for hypometria under nonvisual conditions. Instead, the data suggest that PD patients have a defect of kinesthesia in slowly executed movements.

Adult↗
PubMed1995

The development of goal-directed reaching in infants: hand trajectory formation and joint torque control.

Nine young infants were followed longitudinally from 4 to 15 months of age. We recorded early spontaneous movements and reaching movements to a stationary target. Time-position data of the hand (endpoint), shoulder, and elbow were collected using an optoelectronic measurement system (ELITE). We analyzed the endpoint kinematics and the intersegmental dynamics of the shoulder and elbow joint to investigate how changes in proximal torque control determined the development of hand trajectory formation. Two developmental phases of hand trajectory formation were identified: a first phase of rapid improvements between 16 and 24 weeks of age, the time of reaching onset for all infants. During that time period the number of movement units per reach and movement time decreased dramatically. In a second phase (28-64 weeks), a period of "fine-tuning" of the sensorimotor system, we saw slower, more gradual changes in the endpoint kinematics. The analysis of the underlying intersegmental joint torques revealed the following results: first, the range of muscular and motion-dependent torques (relative to body weight) did not change significantly with age. That is, early reaching was not confined by limitations in producing task-adequate levels of muscular torque. Second, improvements in the endpoint kinematics were not accomplished by minimizing amplitude of muscle and reactive torques. Third, the relative timing of muscular and motion-dependent torque peaks showed a systematic development toward an adult timing profile with increasing age. In conclusion, the development toward invariant characteristics of the hand trajectory is mirrored by concurrent changes in the control of joint forces. The acquisition of stable patterns of intersegmental coordination is not achieved by simply regulating force amplitude, but more so by modulating the correct timing of joint force production and by the system's use of reactive forces. Our findings support the view that development of reaching is a process of unsupervised learning with no external or innate teacher prescribing the desired kinematics or kinetics of the movement.

Adult↗
PubMed1995

Fixation instability and oculomotor abnormalities in Friedreich's ataxia.

Eye movements were studied in 13 patients with Friedreich's ataxia and correlated with MRI findings to investigate whether oculomotor abnormalities can be traced to cerebellar disturbances in this disease. One of the most prominent eye signs was fixation instability (square-wave jerks, SWJ.). Besides SWJ the patients showed various combinations of cerebellar, vestibular and brain-stem oculomotor signs. Our patients did not comprise a homogeneous group with regard to their oculomotor findings. There was no correlation between the severity of any of the so-called cerebellar oculomotor disturbances and the number of SWJ. We tried to correlate the extent of oculomotor disturbances with floccular atrophy and atrophy of the dorsal vermis on MRI in seven of the patients. None of the oculomotor features (including SWJ) correlated with flocculus or dorsal vermis size. Furthermore, floccular and vermal measurements on MRI were normal. Accordingly, we think it unlikely that the oculomotor disturbances, including SWJ, are attributable to cerebellar pathology per se.

Adult↗
PubMed1995

Reliability, specificity and sensitivity of long-term tremor recordings.

We have developed a method of long-term EMG recording that has proven suitable for the quantification of pathological tremor. In the present paper we show that the principal parameters of the method (tremor occurrence, tremor intensity, tremor frequency) are highly reproducible and that the method is specific and sensitive for detection of pathological tremor. Twelve patients with essential tremor (ET) and 13 patients with Parkinson's disease (PD) were recorded repeatedly on 3 successive days. For each patient group and for each parameter the intersubject variability was much larger than the intersubject variability. The intraclass correlation coefficient "R" was in the order of 0.9 for each parameter and the mean of Pearson's correlation coefficient between successive days was also approximately 0.9. Recordings from normal controls demonstrated that the method's specificity for pathological tremor is 94.1% and its sensitivity is 96%.

Adult↗
PubMed1995

Noninvasive investigation of pericarotid syndrome: role of MR angiography in the diagnosis of internal carotid dissection.

A 52-year-old man presented with unilateral left periorbital and frontotemporal pain associated with a partial ipsilateral Horner's syndrome of the postganglionic type and representing a pericarotid syndrome. MRI demonstrated a perivascular subacute hematoma at the level of the cervical portion of the left internal carotid artery with a markedly reduced flow-void signal. MR angiography confirmed the narrowed lumen of the dissected cervical internal carotid artery. There was also a right-sided precavernous carotid aneurysm. Three months later the left-sided pain had subsided, with complete resolution of the hematoma and incomplete restoration of the left carotid lumen seen on MR angiography. Dissection of the carotid wall may cause the oculosympathetic paralysis by producing a lesion of the superior cervical ganglion, the internal carotid nerve, or the perivascular sympathetic plexus. Whereas in pericarotid syndrome the most common cause is cervical carotid dissection, Raeder's syndrome additionally involving parasellar cranial nerves, may be caused by any paracavernous/cavernous lesion, including neoplasms and intracranial carotid aneurysms. The clinical distinction is useful to determine the appropriate diagnostic investigation, in view of the different pathoanatomical localization and different disease spectrum. As demonstrated in the present case, the combination of MRI and MR angiography is a reliable noninvasive tool to investigate the differential diagnosis of pericarotid syndrome, accurately depicting occlusive, stenotic or aneurysmal lesions of the carotid artery. We suggest that intraarterial angiography is no longer necessary.

Aortic Dissection↗
PubMed1995

[Classification and diagnosis of degenerative ataxias].

The degenerative ataxias comprise a wide spectrum of neurodegenerative diseases with varying clinical characteristics and heterogeneous neuropathology. Traditionally, classification of these diseases has been based on neuropathological criteria. Recently, however, clinical and genetic classifications have gained wide acceptance. These classifications distinguish between hereditary and non-hereditary ataxias. According to their mode of inheritance, the hereditary ataxias are further subdivided into autosomal-recessive and autosomal-dominant ataxias. The non-hereditary ataxias are divided into symptomatic ataxias with an identified cause and idiopathic ataxia with unknown cause. Diagnostic criteria based on history, clinical presentation and a number of laboratory tests have been defined for each category. More extensive ancillary tests are necessary to identify or exclude symptomatic causes of ataxia. Recent molecular genetic research has led to the identification of a number of gene loci and mutations responsible for certain types of hereditary ataxia.

Chromosome Aberrations↗
PubMed1995

Tremorlytic activity of budipine: a quantitative study with long-term tremor recordings.

The tremorlytic activity of the novel antiparkinson agent budipine was quantified in an open trial. Eleven patients with Parkinson's disease (PD) were treated with individual doses of budipine added to stable conventional antiparkinsonian medication. Tremor activity was measured using long-term electromyogram (EMG) recordings. Tremor intensity was reduced by 25%, tremor occurrence by 34%, and conventional "Unified Parkinson's Disease Rating Scale" (UPDRS) scores improved by 20% with this medication. There were two dropouts because of side effects. One dropout appeared not to be related to budipine. Apart from those, the drug was well tolerated by all patients. We conclude that budipine is an effective and well-tolerated tremorlytic drug and that the method of long-term EMG recording is suitable for tremor quantification in clinical studies.

Adult↗
PubMed1995

Long-term tremor recordings in parkinsonian and essential tremor.

We have recently developed a method of long-term EMG recording (Bacher et al., 1989), which has proven suitable for the quantification of pathological tremor. In the present paper we show that (1) the principal parameters of the method (tremor occurrence, tremor intensity, tremor frequency) are highly reproducible with intraclass correlation coefficients in the order of 0.9, (2) that the method has both a high specificity (87.5%) and sensitivity (96%) for detection of pathological tremor, and (3) that it can be useful for examining agonist-antagonist muscle activation under everyday conditions.

Adult↗