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Biomedical subjects

H Topka

Publications and source records attributed to H Topka.

At least 19 recordsLinked to original sources
PubMed2006

Spontaneous cerebrospinal fluid hypovolaemia: a therapeutic dilemma?

Spontaneous intracranial hypotension is characterized by orthostatic headaches in conjunction with reduced cerebrospinal fluid volume (CSF) and characteristic imaging findings. We report the clinical course of six consecutive patients with spontaneous intracranial hypotension who were followed between 4 months and 2.5 years. The characteristic orthostatic headaches were present in five patients. Diffuse pachymeningeal enhancement on brain magnetic resonance imaging (MRI) was evident in all cases. CSF detected elevated protein content in three of six patients. In only two of our six patients a first epidural blood patch resulted in complete symptom resolution lasting 4 months and 1 year. Four patients received a second epidural blood patch and one patient also received a third. In four patients, follow-up brain MRI revealed re-occurrence of the typical MRI features and all of them suffered from orthostatic symptoms at this time. Only four patients are free of complaints after an average follow-up period of 10 months. Symptom relief within 7 days from an epidural blood patch is accepted to be diagnostic for spontaneous intracranial hypotension. However, our data illustrate that the clinical course of the syndrome is very unstable and the epidural blood patch is less effective than widely accepted.

Adult↗
PubMed2006

Combination of TMS and fMRI reveals a specific pattern of reorganization in M1 in patients after complete spinal cord injury.

PURPOSE: After a spinal cord injury (SCI), which was complete, deafferentation of the body representation caudal to the lesion height results in drastic changes in the cortical representation. The underlaying processes are poorly understood. METHODS: We investigated cortical representation sites of upper limb muscles using functional magnetic resonance imaging (fMRI) and transcranial magnetic stimulation (TMS) in five patients suffering from thoracic complete SCI and one with an incomplete SCI in the height of L1. RESULTS: In comparison to healthy controls fMRI demonstrated a displacement of elbow movement representations in the precentral gyrus in patients with complete SCI into the direction of the deafferented cortical thoracic representation. Changes increased with time after the incidence of SCI. TMS revealed reduced excitability and prolonged silent periods for muscles more distant to the deafferented area. CONCLUSIONS: Whereas fMRI demonstrated changes in representation sites adjacent to the deafferented area, TMS excitability changes were also observed more distant to the deafferented area and silent periods were prolonged in comparison to healthy controls. TMS changes might depend on both: the distance to the deafferented area and the time of persistence of deafferentation.

Adult↗
PubMed2005

Disturbances of grip force behaviour in focal hand dystonia: evidence for a generalised impairment of sensory-motor integration?

BACKGROUND: Focal task specific dystonia occurs preferentially during performance of a specific task. There may be an inefficiently high grip force when doing manipulative tasks other than the trigger task, possibly reflecting a generalised impairment of sensory-motor integration. OBJECTIVE: To examine how well subjects with writer's cramp (n = 4) or musician's cramp (n = 5) adapted their grip force when lifting a new object or catching a weight. METHODS: Nine patients with focal hand dystonia and 10 controls were studied. Experiments addressed different motor behaviours: (A) lifting and holding an object; (B) adjusting grip force in anticipation of or in reaction to a change in load force by catching a small weight dropped expectedly or unexpectedly into a hand held receptacle. RESULTS: In (A), patients produced a grip force overshoot during the initial lifts; force overflow was most pronounced in those with writer's cramp. Patients and controls adjusted their grip force to object weight within one or two lifts, though patients settled to a steady force level above normal. In (B), patients with focal hand dystonia and normal controls showed similar predictive grip force adjustments to expected changes in object load, suggesting that this aspect of sensory-motor integration was normal. Patients had a shorter latency of grip force response than controls after an unexpected load increase, reflecting either a greater level of preparatory motor activity or a disinhibited spinal reflex response. CONCLUSIONS: The overall increased grip force in patients with focal hand dystonia is likely to be a prelearned phenomenon rather than a primary disorder of sensory-motor integration.

Adult↗
PubMed2003

Aspirin non-responder status in patients with recurrent cerebral ischemic attacks.

BACKGROUND: Antiplatelet agents such as acetylsalicylic acid (aspirin) reduce the relative risk for cerebrovascular events in patients with cardiovascular or cerebrovascular disorders by approximately 23 %. Recent observations raise the possibility that aspirin resistance may contribute to the failure of aspirin treatment in a significant proportion of patients (aspirin non-responders). To evaluate the clinical relevance of aspirin non-responder status, we analysed platelet functions in symptomatic and asymptomatic patients treated with aspirin for secondary prevention of cardiovascular and cerebrovascular events. METHODS: A total of 53 patients on 100 mg aspirin daily for secondary prevention (mean treatment duration > 60 months) were included. Patients were categorized as asymptomatic if they were free of cerebrovascular incidents for at least 24 months (n = 18). Symptomatic patients had suffered ischemic strokes or transient ischemic attacks within the previous 3 days (n = 35). Platelet function was assessed using the PFA-100 system that allows for quantitative assessment of platelet function, reporting platelet aggregatability as the time required to close a small aperture in a biologically active membrane. RESULTS: Collagen/epinephrine closure times were significantly shorter in symptomatic patients than in asymptomatic patients (p < 0.01). Individual closing times were normal in 12 of 35 symptomatic patients (34 % non-responders) whereas all asymptomatic patients had prolonged closure times. CONCLUSIONS: Aspirin non-responder status may contribute to failure of aspirin therapy in the secondary prevention of cerebrovascular incidents in as much as 30-40 % of patients. Quantitative assessment of platelet functions may provide a means to predict aspirin treatment failure in individual patients and to re-direct therapeutic strategies.

Aged↗
PubMed2003

Comparison of representational maps using functional magnetic resonance imaging and transcranial magnetic stimulation.

OBJECTIVE: Comparison of functional magnetic resonance imaging (fMRI) representational maps, that were generated during voluntary thumb abduction, hand dorsiflexion and foot elevation to amplitude maps of motor-evoked potentials (MEPs) elicited by single transcranial magnetic stimulation (TMS) administered to cortical motor representation areas of the muscles of the thenar eminence, extensor carpi radialis and tibialis anterior muscles. METHODS: Stimulus locations that produced maximal motor-evoked potential amplitudes were compared to fMRI activation maxima in three-dimensional (3D)-space and in a 2D-projection using a novel technique that allowed fMRI activation sites to be projected onto the surface of the brain. RESULTS AND CONCLUSIONS: When analyzing pooled data from all target muscles, the location of projected fMRI and TMS activation maxima on the cortical surface differed by an average 13.9 mm. The differences in 3D distances were particularly large for representation areas of lower leg muscles. 3D distances between fMRI activation maxima and highest MEP site in TMS correlated significantly with higher TMS thresholds. These observations strongly suggest that higher TMS excitation thresholds and lower MEP amplitudes are largely due to the absolute distance between the stimulation site and the excitable cortical tissue targeting this muscle. After the projection 4 out of 5 representation sites as evaluated by TMS were located anterior to the fMRI activation maxima, an observation which may due to the orientation of the magnetic field induced by the current in the coil. The representation sites as evaluated with both methods were specific for the type of movement: distances between representation maxima of the same movements were significantly smaller than those within different movements. Nevertheless, fMRI and TMS provide complementary information, which is discussed on the basis of the functional map observed with both methods.

Adult↗
PubMed2003

Reversible segmental cerebral vasoconstriction (Call-Fleming syndrome): are calcium channel inhibitors a potential treatment option?

The Call-Fleming syndrome is characterized by sudden onset of thunderclap-like headache and focal neurological deficits. The pathophysiological correlate is a reversible segmental cerebral vasoconstriction frequently associated with focal cerebral ischaemia. The syndrome has been described in a variety of clinical conditions, and recently an association between the syndrome and exposure to vasoactive drugs was observed. Effective treatment options are not known. A 63-year-old female developed sudden 'worst ever' headache. Initial neurological examination, laboratory blood tests, CSF examination and brain magnetic resonance imaging (MRI) were normal. Previous medical history was unremarkable and she did not take vasoactive drugs. Eleven days after the onset of headache she developed visual field impairment and a right-sided hemiparesis. Brain MRI revealed bilateral posterior and left parietal ischaemic strokes. Cerebral catheter angiography showed segmental arterial vasoconstriction. A vasodilative therapy with calcium channel inhibitors was started and serial transcranial Doppler ultrasonography demonstrated resolution of cerebral arterial vasoconstriction. The present case illustrates that calcium channel inhibitors may be an effective therapy for segmental cerebral arterial vasoconstriction. However, more clinical data are needed to prove this observation.

Calcium Channel Blockers↗
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↗