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Biomedical subjects

H Topka

Publications and source records attributed to H Topka.

At least 19 recordsLinked to original sources
PubMed2002

[Laboratory diagnosis of hyperkinetic movement disorders in adulthood].

Hyperkinetic movement disorders such as dystonia, chorea, ballism, myoclonus, tics, and tremor may be idiopathic or symptomatic in origin. Symptomatic movement disorders need further diagnostic testing in order to identify their etiology. In addition to clinical findings, imaging techniques, and electrophysiological testing, laboratory studies are required. Here, we review the prevalence of diseases presenting with symptomatic hyperkinetic movement disorders and discuss the diagnostic relevance of laboratory studies.

Biomarkers↗
PubMed2002

Mutations of GCH1 in Dopa-responsive dystonia.

Dopa responsive dystonia (DRD) is an autosomal dominant dystonia caused by mutations in the gene GCH1 in about 50% of cases. GCH1 codes for GTP cyclohydrolase I, a rate limiting enzyme in the synthesis of tetrahydrobiobterin (BH(4)) from GTP. There is reduced penetrance and pronounced variation in expressivity of GCH1 mutations in families with DRD. Correlations between given mutations in GCH1 and phenotypes cannot be established. Mutations in GCH1 appear to function as dominant-negatives but the exact mechanism remains unclear. Additional open questions in DRD include the molecular mechanisms resulting in highly variable expressivity of symptoms and the more likely occurrence of symptoms in a female than in a male carrier of a GCH1 mutation.

Biopterins↗
PubMed2001

Transcranial magnetic stimulation: no effect on mood with single pulse during learned helplessness.

1. Transcranial Magnetic Stimulation (TMS) is suggested to be an effective tool in the treatment of depression. However, the methodology most suitable for clinical application remains unclear. 2. The effect of TMS was tested in a double-blind and placebo-controlled setting on 18 healthy subjects. At the same time an established learned helplessness paradigm was applied to induce dysphoria, which consisted of unsolvable anagrams. 3. Sixty 0.5 Hz stimuli were administered at an intensity of 130% of the subject's motor threshold after the subjects were exposed to the learned helplessness situation. Using a vertically positioned coil, the stimuli were applied to the right or to the left frontal cortex, or on the occipital cortex as a placebo condition. 4. Although dysphoria was successfully induced by unsolvable anagrams, TMS on either of the two frontal locations did not influence mood. This lack of effect may be due to the stimulation characteristics employed here (low TMS intensity, and low frequency). On the other hand, the findings may reflect the neurobiological difference between experimentally induced sad mood and clinical depression.

Adult↗
PubMed2001

Motor thresholds in humans: a transcranial magnetic stimulation study comparing different pulse waveforms, current directions and stimulator types.

OBJECTIVES: To evaluate the stimulation effectiveness of different magnetic stimulator devices with respect to pulse waveform and current direction in the motor cortex. METHODS: In 8 normal subjects we determined motor thresholds of transcranial magnetic stimulation in a small hand muscle. We used focal figure-of-eight coils of 3 common stimulators (Dantec Magpro, Magstim 200 and Magstim Rapid) and systematically varied current direction (postero-anterior versus antero-posterior, perpendicular to the central sulcus) as well as pulse waveform (monophasic versus biphasic). The coil position was kept constant with a stereotactic positioning device. RESULTS: Motor thresholds varied consistently with changing stimulus parameters, despite substantial interindividual variability. By normalizing the values with respect to the square root of the energy of the capacitors in the different stimulators, we found a homogeneous pattern of threshold variations. The normalized Magstim threshold values were consistently higher than the normalized Dantec thresholds by a factor of 1.3. For both stimulator types the monophasic pulse was more effective if the current passed the motor cortex in a postero-anterior direction rather than antero-posterior. In contrast, the biphasic pulse was weaker with the first upstroke in the postero-anterior direction. We calculated mean factors for transforming the intensity values of a particular configuration into that of another configuration by normalizing the different threshold values of each individual subject to his lowest threshold value. CONCLUSIONS: Our transformation factors allow us to compare stimulation intensities from studies using different devices and pulse forms. The effectiveness of stimulation as a function of waveform and current direction follows the same pattern as in a peripheral nerve preparation (J Physiol (Lond) 513 (1998) 571).

Adult↗
PubMed2001

Dynamic organization of the somatosensory cortex induced by motor activity.

Intensive and long-lasting experience of altered sensory input induces permanent changes in the functional organization of the somatosensory cortex. In addition, an increasing body of evidence suggests the existence of dynamic, short-term and task-dependent adaptation of representational maps within somatosensory cortex. It is hypothesized that somatosensory maps can, not only, be acquired within a short period of time, but might also be set up during periods of training related to specific tasks and subsequently activated dynamically upon performance of that particular task. In order to test this hypothesis we studied the functional organization of somatosensory cortex for a heavily overlearned and frequently performed task for which no new acquisition of a sensory map had to be assumed. To this end, the functional organization of somatosensory cortex for handwriting was compared with the organization during rest in healthy humans. Functional organization of the somatosensory cortex was assessed using non-invasive, neuromagnetic source imaging based on tactile stimulation of the thumb (D1) and little finger (D5) during writing and rest. In different blocks, subjects wrote with their right, dominant and their left hand, respectively. During writing, D1 and D5 of the writing hand were stimulated. To test the reliability of our results all measurements were repeated after 1 week. It was found that amplitudes of somatosensory evoked magnetic fields with latencies of 45 ms were reduced during writing compared with rest. This finding is in accordance with the sensorimotor gating effect. Using source localization we could show that cortical representations of D1 and D5 are more distant during writing with either hand compared with rest. Our data suggest that somatosensory cortical maps undergo rapid modulation depending on task-specific involvement of sensory processing in daily-life overlearned movements. As it is unlikely that a new sensory map is always acquired when a frequently used task such as writing is performed, we suggest that somatosensory cortex switches between different, concurrently pre-existing maps depending on actual requirements. Task-dependent activation of pre-existing maps might be a powerful mechanism to optimize stimulus processing.

Adult↗
PubMed2000

Dopa-responsive dystonia: mutation analysis of GCH1 and analysis of therapeutic doses of L-dopa. German Dystonia Study Group.

Analysis of the gene GCH1 in 58 patients with dystonia and a positive response to L-dopa revealed mutations in 30 individuals from 22 families. Thirteen of the mutations observed were familial, three occurred de novo, and inheritance could not be determined in six cases. There was no mutation in the promoter region of GCH1 in any patient. The doses of L-dopa given to members of the two groups were not significantly different.

Adult↗
PubMed2000

Interindividual variability of the modulatory effects of repetitive transcranial magnetic stimulation on cortical excitability.

Repetitive transcranial magnetic stimulation (rTMS) appears to have effects on cortical excitability that extend beyond the train of rTMS itself. These effects may be inhibitory or facilitatory and appear to depend on the frequency, intensity, duration and intertrain interval of the rTMS. Many studies assume facilitatory effects of high-frequency rTMS and inhibitory effects of low-frequency rTMS. Nevertheless, the interindividual variability of this modulation of cortical excitability by rTMS has not been systematically investigated. In this study, we applied 240 pulses of rTMS at 90% of the subjects' motor threshold to their motor cortex at different frequencies (1, 10, 15 and 20 Hz) and examined the effects on motor evoked potentials (frequency tuning curve). Although the averaged group data showed a frequency-dependent increase in cortical excitability, each subject had a different pattern of frequency tuning curve, i.e. a different modulatory effect on cortical excitability at different rTMS frequencies. The interindividual variability of these modulatory effects was still high, though less so, when the number of rTMS pulses was increased to 1,600. These findings illustrate the degree of variability of the rTMS effects in the human brain.

Cerebral Cortex↗
PubMed2000

Management of spasticity associated pain with botulinum toxin A.

Lesions of the central nervous system often result in an upper motor neuron syndrome including spasticity, paresis with pyramidal signs, and painful spasms. Pharmacological treatment with oral antispasticity drugs is frequently associated with systemic side effects which limit their clinical use. Botulinum Toxin A (BtxA) injected in spastic muscles has been shown to be effective in reducing muscle tone, but only few studies have reported pain relief as additional benefit. Therefore, we investigated the effects of local BtxA injections in 60 patients with acute (< 12 months) and chronic spasticity and pain in a prospective multicenter study. Target muscles for BtxA were selected on the basis of clinical examination. Intramuscular BtxA injections were placed in muscles exhibiting increased muscle tone in combination with pain during passive joint movement. Patients received a mean total dose of 165.7 +/- 108.2 [30-400] units BOTOX((R)) per treatment session in a mean 3.4 +/- 1.5 muscles. Baseline and follow-up (mean 5.9 weeks) measures included a patient self-assessment of pain and function on a five-level scale, a physician's evaluation of function, and a global rating of response to BtxA. Fifty-four of sixty patients experienced improvement in pain without subjective functional improvement. The effects were comparable in acute (n = 17) and chronic (n = 43) spasticity. Physician's assessment of gain in function increased significantly (p < 0.05) only in patients with chronic spasticity. No serious adverse event was observed. Mild reversible side effects (local pain, hematoma, edema, mild weakness) were observed in four patients. In conclusion, we found that intramuscular BtxA injections are a potent, well-tolerated treatment modality to significantly reduce spasticity-related local pain. This problem may be a main indication, especially in patients with poor response or intolerable side effects to oral medication.

Adolescent↗
PubMed2000

Modulation of corticospinal excitability by repetitive transcranial magnetic stimulation.

OBJECTIVE: Repetitive transcranial magnetic stimulation (rTMS) is able to modulate the corticospinal excitability and the effects appear to last beyond the duration of the rTMS itself. Different studies, employing different rTMS parameters, report different modulation of corticospinal excitability ranging from inhibition to facilitation. Intraindividual variability of these effects and their reproducibility are unclear. METHODS: We examined the modulatory effects of rTMS to the motor cortex at various frequencies (1, 10, 20 Hz) and at different time-points in twenty healthy volunteers. RESULTS: We observed significant inhibition of MEPs following 1 Hz rTMS and significant facilitation of MEPs following 20 Hz rTMS for both day1 and day 2. Interestingly, at 1 Hz and 20 Hz rTMS, the modulatory effect produced by rTMS was greater on day 2. However, there was no significant change in corticospinal excitability following 10 Hz rTMS neither on day 1 nor day 2. CONCLUSION: Our findings raise questions as to how stimulation parameters should be determined when conducting studies applying rTMS on multiple days, and in particular, studies exploring rTMS as a treatment modality in neuropsychiatric disorders.

Adult↗
PubMed2000

Evoked potentials in multiple system atrophy (MSA).

OBJECTIVES: To study the involvement of pyramidal tracts and sensory pathways in multiple system atrophy (MSA). MATERIALS AND METHODS: Evoked potential studies were performed in 45 MSA patients suffering from either MSA of cerebellar type (MSA-C) or MSA of parkinsonian type (MSA-P). RESULTS: Motor evoked potentials were normal in all MSA patients, whereas visual and somatosensory evoked potential abnormalities were found in about 40% of the MSA patients with no significant difference between the cerebellar (MSA-C) and parkinsonian (MSA-P) subgroup. Abnormal latencies of wave III in brainstem auditory evoked potentials were significantly more frequent in MSA-C. CONCLUSIONS: Abnormalities of somatosensory, visual and auditory evoked potentials are frequent findings in MSA, whereas abnormal motor evoked potentials are not a characteristic feature of the disease.

Adult↗
PubMed2000

Nerve conduction studies in multiple system atrophy.

To study the frequency and severity of peripheral neuropathy in multiple system atrophy (MSA), we performed nerve conduction studies in 42 MSA patients suffering from either cerebellar MSA (MSA-C) or parkinsonian MSA (MSA-P). Abnormal nerve conduction was present in 24% of the patients. Abnormalities were significantly more frequent in MSA-P (43%) compared to MSA-C (14%). Motor nerve conduction velocities were reduced in 4% of the MSA-C and in 7% of the MSA-P patients. Abnormal compound muscle action potentials were more frequent in MSA-P (29% versus 7% in MSA-C) pointing to a more pronounced loss of motor axons in this subgroup. Sensory nerve conduction velocities were abnormal in 4% of the MSA-C and 14% of the MSA-P patients, and mean sensory nerve action potentials were normal in all MSA-C and reduced in 7% of the MSA-P patients. The data provide evidence that the peripheral nervous system is differentially affected in MSA-C and MSA-P.

Action Potentials↗
PubMed1999

GCH1 mutation in a patient with adult-onset oromandibular dystonia.

The authors report a mutation in exon 5 of GCH1 in a patient with adult-onset oromandibular dystonia and no obvious family history of dystonia. The patient responded positively to treatment with L-dopa. These findings demonstrate that GCH1 mutations must be considered even in patients with dystonic symptoms not typical of dopa-responsive dystonia.

Age of Onset↗
PubMed1999

Deficits in phasic muscle force generation explain insufficient compensation for interaction torque in cerebellar patients.

A simple paradigm was used to investigate how patients with cerebellar lesions cope with the need to correct for joint interactions during a multi-joint movement. Normal subjects and patients with cerebellar degeneration performed fast unconstrained elbow flexions with the instruction to voluntarily fixate the shoulder joint. Angular kinematics and inverse dynamics analyses were performed. A susceptibility index quantified how strong-concomitant shoulder-motion depended on interactions from the elbow. Amplitudes of involuntary shoulder movements increased with elbow movement speed and were generally larger in patients. Susceptibility indices were smaller in patients, indicating a more variable compensatory response, however, increased with elbow movement speed. We conclude that patients were significantly less able to 'tune' their postural stabilizing response to match interaction torques. However, the velocity dependence of this effect points to a deficit in generating normal levels of phasic torque.

Adult↗
PubMed1999

A cerebellar-like terminal and postural tremor induced in normal man by transcranial magnetic stimulation.

Trains of repetitive transcranial magnetic stimulation (TMS) at 10-30 Hz and intensities of 90-120% motor threshold were delivered through a figure of eight coil over the motor cortex while normal subjects made either rapid, self-terminated (ballistic) wrist movements or maintained the position of their wrist at a fixed angle. Movement kinematics and EMG activity in antagonistic forearm muscles were analysed. In the ballistic task, repetitive TMS had little effect on the velocity or acceleration of the initial segment of the movement, although it induced large terminal oscillations (tremor) around the target position at frequencies between 4.4 and 7.2 Hz. The likelihood that tremor would occur increased with increasing stimulus intensities or frequencies. It was maximal with stimulation over the forearm area, and decreased with stimulation over the leg area, or over parietal sites; there was no tremor during stimulation of cervical nerve roots. The frequency of the induced tremor was independent of the rate of stimulation and did not depend on the presence of excitatory and inhibitory motor responses to the stimulus. Stimulation could also induce tremor of the same frequency in the fixed task, but only during co-contraction of forearm muscles. The amplitude of tremor was proportional to the level of co-contraction. Clinically, the tremor induced by repetitive TMS appeared very similar to cerebellar tremors. In order to confirm this we investigated two cerebellar patients, one with autosomal dominant cerebellar ataxia and the other with multiple sclerosis. Both of them had a terminal tremor of 6-7 Hz in the wrist movement task. In the holding task, the amplitude of their postural tremor increased with the level of co-contraction in forearm muscles. Since the frequency of repetitive TMS-induced tremor was independent of stimulus parameters, we conclude that it represents some intrinsic property of the CNS. We suggest that the tremor is caused by disruption of cortical processes involved in terminating a voluntary movement or maintaining a posture. Similarities to cerebellar patients suggest that repetitive TMS may cause tremor by interfering with adaptive cerebellar afferent inflow to motor cortex. Repetitive TMS-induced tremor, therefore, may represent a model of some forms of cerebellar tremor in man.

Adult↗
PubMed1999

Bilateral segmental dystonia in a professional tennis player.

Dystonias occur frequently as repetitive movements, persistent elevations of muscle tone, or tonic contortions, whereby the cause is assumed to be an impairment of basal ganglia function. Focal dystonias are especially known in musicians, although little is reported on focal dystonias in athletic stress. The present case report describes the case of a 34-yr-old professional tennis player with bilateral segmental dystonia. The symptoms were expressed in involuntary movements when he intended to hit the ball and in a progredient tremor, initially in one hand, later in both, making him unable to write. The altered mobility during athletic stress was confirmed by video analysis, the altered innervation with excessive, uncoordinated impulse influx by means of electromyography during sport-type specific stress, and writing incapacity during a writing test. The symptoms abated under therapy with trihexyphenidyl-HCL, so that the patient has been able to work as a tennis coach with improved athletic performance for the past 3 yr. It is concluded that the various forms of dystonia should be included in the differential diagnosis of impaired coordinative movements under athletic exercise, especially of the upper extremities.

Adult↗
PubMed1999

Age related axonal neuropathy in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD).

To identify determinants of peripheral involvement in spinocerebellar ataxia type 3/Machado-Joseph disease (SCA3/MJD) the influence of CAG repeat length, age of onset, disease duration and age on the results of nerve conduction studies was analysed in 58 patients with SCA3/MJD. Patients with SCA3/MJD showed marked reduction of compound muscle action potential (CMAP) and sensory nerve action potential (SNAP) amplitudes indicating axonal neuropathy of both motor and sensory fibres. In addition, there was moderate slowing of nerve conduction suggestive of mild peripheral demyelination. Multivariate regression showed that CMAP and SNAP amplitudes decreased with age, but were not affected by CAG repeat length, age of onset, or disease duration. The age related decline of CMAP and SNAP amplitudes in SCA3/MJD was greater than in normal subjects. The data suggest that the degree of peripheral damage in SCA3/MJD does not depend on CAG repeat length, age of onset, or disease duration, but is mainly related to the time period over which the SCA3/MJD mutation exerts its effect.

Adult↗
PubMed1998

Motor skill learning in patients with cerebellar degeneration.

To explore the role of the cerebellum in learning a complex motor task, we studied nineteen patients with cerebellar degeneration and sixteen healthy subjects who attempted to improve their performance in generating a trajectory connecting five via points on a data tablet. Multijoint arm movements were performed at a constant total movement time, and spatial error was measured. Subjects performed 100 trials at a movement time of 3.5 s (slow movements), and another 100 trials at maximum speed (fast movements). With slow movements, patients and normal subjects reduced the error over trials to the same extent, but in patients, the rate of improvement was slightly slower. With fast movements, patients showed less improvement than normal subjects. When tested 24 h later, patients demonstrated significant retention of acquired skill and tended to improve more rapidly when performing both slow and fast movements than during the first session. We conclude that patients with cerebellar degeneration can exhibit almost normal performance in skill learning with slow movements, but with fast movements, their performance improves to a lesser extent. The problem may be difficulty in the refinement of motor execution, which is more of a requirement for fast movements than for slow ones.

Adult↗