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1.
Clin Neurophysiol ; 120(6): 1213-9, 2009 Jun.
Article in English | MEDLINE | ID: mdl-19447675

ABSTRACT

OBJECTIVE: To investigate whether movement-related cortical potentials (MRCP) provide a physiological correlate that indicates the response to treatment in patients with writer's cramp. METHODS: In 21 patients with writer's cramp, who underwent 4 weeks of limb immobilization followed by re-training for 8 weeks, we recorded MRCPs preceding a self-initiated brisk finger abduction movement. MRCP measurements of pre-movement activity were performed at baseline, after the end of immobilization and four and 8 weeks of re-training. We examined 12 controls, who received no intervention, twice 4 weeks apart. RESULTS: Patients benefited from the therapeutical intervention (Zeuner et al., 2008). They showed no abnormalities of the MRCPs at baseline. In controls, MRCPs did not significantly change after 4 weeks. In patients, immobilization and re-training had no effect on MRCPs. There was no correlation between the severity of dystonic symptoms or the individual treatment response and MRCPs. CONCLUSION: MRCPs are stable measures for interventional studies. However, they do not reflect clinical severity of dystonic symptoms or improvement after therapeutic interventions. SIGNIFICANCE: This is the first study to investigate MRCPs in a large cohort of patients with writer's cramp compared to a control group at different time points. These potentials do not reflect the motor control disorder in patients with writer's cramp.


Subject(s)
Contingent Negative Variation/physiology , Dystonia/physiopathology , Dystonia/therapy , Dystonic Disorders/physiopathology , Dystonic Disorders/therapy , Evoked Potentials, Motor/physiology , Movement/physiology , Adult , Aged , Case-Control Studies , Cohort Studies , Electroencephalography , Electromyography , Female , Fingers/innervation , Fingers/physiology , Humans , Male , Middle Aged , Motor Activity/physiology , Muscle Contraction/physiology , Muscle, Skeletal/innervation , Muscle, Skeletal/physiology , Restraint, Physical/methods , Restraint, Physical/physiology
2.
J Neurophysiol ; 100(5): 2515-24, 2008 Nov.
Article in English | MEDLINE | ID: mdl-18701754

ABSTRACT

We recorded resting-state neuronal activity from the human subthalamic nucleus (STN) during functional stereotactic surgeries. By inserting up to five parallel microelectrodes for single- or multiunit recordings and applying statistical spike-sorting methods, we were able to isolate a total of 351 single units in 65 patients with Parkinson's disease (PD) and 33 single units in 9 patients suffering from essential tremor (ET). Among these were 93 pairs of simultaneously recorded neurons in PD and 17 in ET, which were detected either by the same (n = 30) or neighboring microelectrodes (n = 80). Essential tremor is a movement disorder without any known basal ganglia pathology and with normal dopaminergic brain function. By comparing the neuronal activity of the STN in patients suffering from PD and ET we intended to characterize, for the first time, changes of basal ganglia activity in the human disease state that had previously been described in animal models of Parkinson's disease. We found a significant increase in the mean firing rate of STN neurons in PD and a relatively larger fraction of neurons exhibiting burstlike activity compared with ET. The overall proportion of neurons exhibiting intrinsic oscillations or interneuronal synchronization as defined by significant spectral peaks in the auto- or cross-correlations functions did not differ between PD and ET when considering the entire frequency range of 1-100 Hz. The distribution of significant oscillations across the theta (1-8 Hz), alpha (8-12 Hz), beta (12-35 Hz), and gamma band (>35 Hz), however, was uneven in ET and PD, as indicated by a trend in Fisher's exact test (P = 0.05). Oscillations and pairwise synchronizations within the 12- to 35-Hz band were a unique feature of PD. Our results confirm the predictions of the rate model of Parkinson's disease. In addition, they emphasize abnormalities in the patterning and dynamics of neuronal discharges in the parkinsonian STN, which support current concepts of abnormal motor loop oscillations in Parkinson's disease.


Subject(s)
Action Potentials/physiology , Neurons/physiology , Parkinsonian Disorders/pathology , Parkinsonian Disorders/physiopathology , Subthalamic Nucleus/pathology , Analysis of Variance , Chi-Square Distribution , Essential Tremor/pathology , Essential Tremor/physiopathology , Humans , Periodicity
3.
Neurology ; 70(16 Pt 2): 1445-51, 2008 Apr 15.
Article in English | MEDLINE | ID: mdl-18413569

ABSTRACT

BACKGROUND: Axial symptoms of Parkinson disease (PD) may result from dysfunctional basal ganglia-brainstem connections. In this study, we assessed whether modulation of basal ganglia activity by high-frequency stimulation of the subthalamic nucleus (STN-HFS) in PD had an impact on the brainstem-controlled startle system. METHODS: We assessed auditory startle responses (recorded from right orbicularis oculi, masseter, sternocleidomastoid, biceps brachii, and soleus muscle) and audiospinal facilitation (startle conditioned soleus H-reflexes at interstimulus intervals of 0-250 msec) in 24 patients with PD with chronically implanted, bilateral STN electrodes in the stimulation on (STIM ON) and off condition (STIM OFF) and 20 healthy controls. RESULTS: The mixed linear analysis of variance model revealed a significant effect for the startle onset latency in the orbicularis oculi muscle for the factors GROUP (patients with PD vs controls; p < 0.0001, F = 44.66) and STIM (nested within GROUP) (p = 0.0034, F = 8.79). Audiospinal facilitation was modulated by STN-HFS as shown by highly significant effects for STIM [GROUP] (p < 0.0001, F = 15.9), ISI [GROUP] (p < 0.0001, F = 3.5), and the interaction of ISI x STIM [GROUP] (p = 0.0085, F = 2.65) in the mixed linear model. CONCLUSION: High-frequency stimulation of the subthalamic nucleus alters the excitability of the brainstem startle system in Parkinson disease, most likely by releasing the reticular motor system from abnormal descending input of the basal ganglia via pallidotegmental pathways.


Subject(s)
Acoustic Stimulation/methods , Deep Brain Stimulation/methods , Parkinson Disease/physiopathology , Reflex, Startle/physiology , Spinal Cord/physiology , Subthalamic Nucleus/physiology , Aged , Electric Stimulation/methods , Female , H-Reflex/physiology , Humans , Male , Middle Aged , Muscle, Skeletal/physiology
4.
Acta Neurochir (Wien) ; 149(8): 749-58; discussion 758, 2007 Aug.
Article in English | MEDLINE | ID: mdl-17660940

ABSTRACT

BACKGROUND: The ventro-lateral thalamus is the stereotactic target of choice for severe intention tremor. Nevertheless, the optimal target area has remained controversial, and targeting of the subthalamic area has been suggested to be superior. PATIENTS AND METHODS: Eleven patients with disabling intention tremor of different etiology (essential tremor (n = 8), multiple sclerosis (n = 2) and one with, spinocerebellar ataxia) were implanted bilaterally with DBS electrodes targeted to the ventro-lateral thalamus using micro-recording and micro-stimulation. Among five tracks explored in parallel optimal tracks were chosen for permanent electrode implantation. Postoperative tremor suppression elicited by individual electrode contacts was quantified using a lateralised tremor rating scale at least 3 months (in most patients >1 year) after implantation. The position of electrode contacts was determined retrospectively from stereotactic X-ray exams and by correlation of pre- and postoperative MRI. RESULTS: In all patients, DBS suppressed intention tremor markedly. On average, tremor on the left and right side of the body was improved by 68% (+/-19; standard deviation) and 73% (+/-21), respectively. In most patients, distal electrode contacts located in the subthalamic area proved to be more effective than proximal contacts in the ventro-lateral thalamus. In stereotactic coordinates, the optimal site was located 12.7 mm (+/-1.4; mean +/- standard deviation) lateral, 7.0 (+/-1.6) mm posterior, and 1.5 (+/-2.0) mm ventral to the mid-commissural point. In general, the best contacts could be selected for permanent stimulation. Nevertheless, in some instances, more proximal contacts had to be chosen because of adverse effects (paraesthesiae, dysarthria, gait ataxia) which were more pronounced with bilateral stimulation resulting in slightly less tremor suppression on the left and right side of body (63 +/- 18 and 68 +/- 19%, respectively). CONCLUSION: Direct comparison of different stimulation sites in individual patients revealed that DBS in the subthalamic area is more effective in suppressing pharmacoresistant intention tremor than the ventro-lateral thalamus proper. Anatomical structures possibly involved in tremor suppression include cerebello-thalamic projections, the prelemniscal radiation, and the zona incerta.


Subject(s)
Deep Brain Stimulation/methods , Dominance, Cerebral/physiology , Subthalamic Nucleus/physiopathology , Tremor/therapy , Ventral Thalamic Nuclei/physiopathology , Aged , Electrodes, Implanted , Female , Follow-Up Studies , Humans , Magnetic Resonance Imaging , Male , Microelectrodes , Middle Aged , Multiple Sclerosis/physiopathology , Multiple Sclerosis/therapy , Neurons , Retrospective Studies , Spinocerebellar Ataxias/physiopathology , Spinocerebellar Ataxias/therapy , Stereotaxic Techniques , Treatment Outcome , Tremor/etiology , Tremor/physiopathology
5.
J Neural Transm (Vienna) ; 112(12): 1677-86, 2005 Dec.
Article in English | MEDLINE | ID: mdl-16049636

ABSTRACT

Introduction. The European Multiple System Atrophy-Study Group (EMSA-SG) is an academic network comprising 23 centers across Europe and Israel that has constituted itself already in January 1999. This international forum of established experts under the guidance of the University Hospital of Innsbruck as coordinating center is supported by the 5th framework program of the European Union since March 2001 (QLK6-CT-2000-00661). Objectives. Primary goals of the network include (1) a central Registry for European multiple system atrophy (MSA) patients, (2) a decentralized DNA Bank, (3) the development and validation of the novel Unified MSA Rating Scale (UMSARS), (4) the conduction of a Natural History Study (NHS), and (5) the planning or implementation of interventional therapeutic trials. Methods. The EMSA-SG Registry is a computerized data bank localized at the coordinating centre in Innsbruck collecting diagnostic and therapeutic data of MSA patients. Blood samples of patients and controls are recruited into the DNA Bank. The UMSARS is a novel specific rating instrument that has been developed and validated by the EMSA-SG. The NHS comprises assessments of basic anthropometric data as well as a range of scales including the UMSARS, Unified Parkinson's Disease Rating Scale (UPDRS), measures of global disability, Red Flag list, MMSE (Mini Mental State Examination), quality of live measures, i.e. EuroQoL 5D (EQ-5D) and Medical Outcome Study Short Form (SF-36) as well as the Beck Depression Inventory (BDI). In a subgroup of patients dysautonomic features are recorded in detail using the Queen Square Cardiovascular Autonomic Function Test Battery, the Composite Autonomic Symptom Scale (COMPASS) and measurements of residual urinary volume. Most of these measures are repeated at 6-monthly follow up visits for a total study period of 24 months. Surrogate markers of the disease progression are identified by the EMSA-SG using magnetic resonance and diffusion weighted imaging (MRI and DWI, respectively). Results. 412 patients have been recruited into the Registry so far. Probable MSA-P was the most common diagnosis (49% of cases). 507 patients donated DNA for research. 131 patients have been recruited into the NHS. There was a rapid deterioration of the motor disorder (in particular akinesia) by 26.1% of the UMSARS II, and - to a lesser degree - of activities of daily living by 16.8% of the UMSARS I in relation to the respective baseline scores. Motor progression was associated with low motor or global disability as well as low akinesia or cerebellar subscores at baseline. Mental function did not deteriorate during this short follow up period. Conclusion. For the first time, prospective data concerning disease progression are available. Such data about the natural history and prognosis of MSA as well as surrogate markers of disease process allow planning and implementation of multi-centre phase II/III neuroprotective intervention trials within the next years more effectively. Indeed, a trial on growth hormone in MSA has just been completed, and another on minocycline will be completed by the end of this year.


Subject(s)
Multicenter Studies as Topic/methods , Multiple System Atrophy/classification , Multiple System Atrophy/epidemiology , Animals , Clinical Trials as Topic/methods , Databases, Factual , Europe , Humans , Internationality , Israel , Registries
6.
Neurosci Lett ; 386(3): 156-9, 2005 Oct 07.
Article in English | MEDLINE | ID: mdl-16024174

ABSTRACT

We present the results of continuous microelectrode recordings from individual pallidal neurons in patients with idiopathic torsion dystonia under different levels of propofol anesthesia. Neither the estimated plasma concentration of propofol nor the level of consciousness had a consistent effect on abnormally low neuronal firing rates. Our data support the pathophysiological model of a decreased basal ganglia output in dystonia and argue against a possible pharmacological artifact.


Subject(s)
Action Potentials/drug effects , Dystonia Musculorum Deformans/physiopathology , Globus Pallidus/drug effects , Globus Pallidus/physiopathology , Neurons/drug effects , Propofol/pharmacology , Action Potentials/physiology , Adolescent , Adult , Anesthetics, Intravenous/blood , Anesthetics, Intravenous/pharmacology , Artifacts , Consciousness/drug effects , Consciousness/physiology , Electrodiagnosis/methods , Electrophysiology/methods , Humans , Microelectrodes , Middle Aged , Neural Inhibition/drug effects , Neural Inhibition/physiology , Neurons/physiology , Propofol/blood
8.
Neurology ; 63(5): 812-5, 2004 Sep 14.
Article in English | MEDLINE | ID: mdl-15365128

ABSTRACT

BACKGROUND: The pathophysiologic mechanism underlying psychogenic tremor is not clear. Continuous voluntary production of tremor may be uncovered by a positive entrainment of tremor in different limbs. But some patients have tremor ongoing during their waking time which is unlikely to be produced voluntarily. Therefore, nonvoluntary physiologic oscillatory mechanisms must be considered. METHODS: Fifteen patients with psychogenic tremor manifesting in both hands, who were diagnosed using established criteria, were examined. Postural tremor was recorded with accelerometry and electromyography (EMG) while the hands were held against gravity. Power spectral peak frequencies and accelerometric total power as a measure of amplitude were determined. Coherency spectra between the EMG signals from the right and left arm were calculated. RESULTS: Seven of 15 patients showed a significant coherency between the two hands; the remaining 8 patients maintained independent oscillations. Clinical presentation, tremor frequencies, and amplitudes were not significantly different between the two groups. CONCLUSIONS: Two different pathogenetic mechanisms may play a role in psychogenic tremor. Bilateral voluntary movements are typically coherent. Thus, coherent psychogenic tremor would be in keeping with voluntarily produced oscillations. Absent coherence is an indication of another, possibly nonvoluntary mechanism like clonus or enhanced physiologic tremor.


Subject(s)
Psychophysiologic Disorders/physiopathology , Tremor/physiopathology , Adult , Electromyography/methods , Female , Hand/physiopathology , Humans , Isometric Contraction , Male , Middle Aged , Models, Neurological , Signal Processing, Computer-Assisted , Tremor/psychology , Volition
9.
J Neurol ; 251(5): 571-8, 2004 May.
Article in English | MEDLINE | ID: mdl-15164190

ABSTRACT

OBJECTIVES: Sporadic (SSP) and hereditary spastic paraplegias (HSP) are clinically and genetically heterogeneous disorders, which are characterised by a slowly progressive spastic paraparesis. Initial symptoms and the rate of progression are variable even among members of the same family. Spastic paraparesis is the major and most disabling clinical symptom and was assessed with gait analysis using a three-dimensional infrared movement analysis system. METHODS AND RESULTS: 22 patients with clinically and/or genetically confirmed SSP/HSP were compared with age-matched control subjects. Significantly lower values were found for gait velocity, stride length, step height and the range of motion of the knee-angle. The gait pattern is characterised by a severe spasticity of both legs with only mild paresis. The balance-related gait parameters show a broad-based gait without inwardly rotated feet. No correlation was found between disease duration and the severity of the gait disorder and the central motor conduction time to the leg muscles and the abnormal gait parameters. The gait pattern did not differ between the 7 SSP cases and the 15 HSP cases. CONCLUSIONS: We conclude that three-dimensional gait analysis can uncover specific features of such rare gait disorders, and may be used as an objective tool to quantify the impairment of gait parameters in patients with SSP/HSP and thus can be used to monitor disease progression and the effect of therapeutic interventions.


Subject(s)
Gait/physiology , Paraparesis, Spastic/physiopathology , Spastic Paraplegia, Hereditary/physiopathology , Adult , Case-Control Studies , Electric Stimulation/methods , Exercise Test/methods , Female , Humans , Infrared Rays , Locomotion/physiology , Lower Extremity/physiopathology , Magnetics , Male , Middle Aged , Muscle, Skeletal/physiopathology , Muscle, Skeletal/radiation effects , Neurologic Examination , Reaction Time/physiology , Spastic Paraplegia, Hereditary/diagnosis
10.
Neurology ; 62(2): 208-11, 2004 Jan 27.
Article in English | MEDLINE | ID: mdl-14745055

ABSTRACT

OBJECTIVE: To assess the relative contribution of genetic and environmental factors for the etiology of essential tremor (ET) and to explore the effect of different diagnostic criteria. METHODS: A total of 2,448 twins of the Danish twin registry aged 70 years or more were screened for ET by an interview and an Archimedes spiral test. All twin pairs (n = 162) with a positive screening test of at least one of the twins were recontacted and 218 individuals (109 pairs) were interviewed and examined by a movement disorder specialist. The consensus criteria of the Tremor Investigation Group were applied to diagnose ET. RESULTS: Twenty-nine twins fulfilled the criteria of definite, 7 of probable, and 56 of possible ET. The probandwise concordance rate for the broadest definition of ET was 77% for monozygotic twins (MZ) and 59% for dizygotic twins (DZ). However, in an analysis restricted to cases of probable and definite ET, the concordance rates were 93% and 29%. The heritability for the liability to ET ranged from 93% to 99% using a general population prevalence of 1.2% for white 70+-year-olds. The inclusion of probable and exclusion of possible cases in the diagnosis of ET produced the highest concordance rates. CONCLUSION: The high concordance among MZ twins of very old age in this first population-based twin study of ET suggests that a disease phenotype consisting of definite and probable ET has a high heritability and hence is a good candidate for a phenotype to be used in linkage studies.


Subject(s)
Diseases in Twins/epidemiology , Essential Tremor/epidemiology , Twins, Monozygotic , Age Factors , Aged , Aged, 80 and over , Denmark/epidemiology , Essential Tremor/genetics , Humans , Longitudinal Studies , Neurologic Examination , Phenotype , Twins, Dizygotic
11.
J Neurol ; 250 Suppl 1: I43-6, 2003 Feb.
Article in English | MEDLINE | ID: mdl-12761636

ABSTRACT

DBS of the STN is one of the most promising new therapies for the treatment of PD. However - like many other therapies for PD - the present stage of the scientific assessment does not yet suffice the rigid criteria of evidence-based medicine. Further studies should specifically address the questions of efficacy and side effects as well as the impact on quality of life.


Subject(s)
Electric Stimulation Therapy/methods , Evidence-Based Medicine/methods , Parkinson Disease/therapy , Subthalamic Nucleus/surgery , Dyskinesias/therapy , Electric Stimulation , Humans , Patient Selection
12.
Pain ; 84(2-3): 331-8, 2000 Feb.
Article in English | MEDLINE | ID: mdl-10666538

ABSTRACT

BACKGROUND: Complex regional pain syndromes (causalgia and RSD) can be relieved by blockade of the sympathetic efferent activity. The mechanisms of sympathetically maintained pain (SMP) are unclear. So far an adrenergic interaction between sympathetic vasoconstrictor neurons and nociceptors has been proposed. Alternatively, a cholinergic coupling of sympathetic sudomotor neurons and nociceptors is possible. OBJECTIVE: To determine the effect of cutaneous sympathetic sudomotor activity on pain induced by primary afferent C-nociceptor activation with capsaicin in humans. METHODS: In 10 healthy volunteers capsaicin was injected into the forearm skin to induce ongoing pain and dynamic and punctate mechanical hyperalgesia. Intensity of pain and hyperalgesia and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of low and high sympathetic sudomotor skin activity induced by whole-body temperature changes with a thermal suit. By altering whole-body temperature from a moderately warm to an intensely warm state, sympathetic sudomotor activity is modulated selectively in the widest range that can be achieved physiologically while sympathetic vasoconstrictor activity is continuously inhibited. The degree of sudomotor discharge was monitored by measuring cutaneous sweat production at the forearm with the colour indicator ponso-red. The inhibition of vasocontrictor discharge was monitored by measuring cutaneous blood flow at the index finger with laser Doppler flowmetry. RESULTS: The intensity and spatial distribution of capsaicin-evoked ongoing pain and dynamic and punctate mechanical hyperalgesia were not significantly different during the presence of high and low sympathetic sudomotor discharge. CONCLUSIONS: Cutaneous sympathetic sudomotor activity does not influence capsaicin induced pain and mechanical hyperalgesia.


Subject(s)
Hyperalgesia/physiopathology , Pain/physiopathology , Sweat Glands/physiopathology , Sympathetic Nervous System/physiopathology , Adult , Capsaicin , Female , Hot Temperature , Humans , Hyperalgesia/chemically induced , Male , Pain/chemically induced , Physical Stimulation , Skin/innervation , Skin/physiopathology , Skin Temperature
13.
Neurology ; 52(5): 923-32, 1999 Mar 23.
Article in English | MEDLINE | ID: mdl-10102407

ABSTRACT

BACKGROUND: Painful nerve and tissue injuries can be exacerbated by activity in sympathetic neurons. The mechanisms of sympathetically maintained pain (SMP) are unclear. OBJECTIVE: To determine the effect of cutaneous sympathetic activity on pain induced by primary afferent C-nociceptor sensitization with capsaicin in humans. METHODS: In healthy volunteers capsaicin was applied topically (n = 12) or injected into the forearm skin (n = 10) to induce spontaneous pain, dynamic and punctate mechanical hyperalgesia, and antidromic (axon reflex) vasodilatation (flare). Intensity of pain and hyperalgesia, axon reflex vasodilatation (laser Doppler), and flare size and area of hyperalgesia (planimetry) were assessed. The local skin temperature at the application and measurement sites was kept constant at 35 degrees C. In each individual the analyses were performed during the presence of high and low sympathetic skin activity induced by whole-body cooling and warming with a thermal suit. By this method sympathetic vasoconstrictor activity is modulated in the widest range that can be achieved physiologically. The degree of vasoconstrictor discharge was monitored by measuring skin blood flow (laser Doppler) and temperature (infrared thermometry) at the index finger. RESULTS: The intensity and spatial distribution of capsaicin-evoked spontaneous pain and dynamic and punctate mechanical hyperalgesia were identical during the presence of high and low sympathetic discharge. Antidromic vasodilatation and flare size were significantly diminished when sympathetic vasoconstrictor neurons were excited. CONCLUSIONS: Cutaneous sympathetic vasoconstrictor activity does not influence spontaneous pain and mechanical hyperalgesia after capsaicin-induced C-nociceptor sensitization. When using physiologic stimulation of sympathetic activity, the capsaicin model is not useful for elucidating mechanisms of SMP. In neuropathic pain states with SMP, different mechanisms may be present.


Subject(s)
Capsaicin/adverse effects , Hyperalgesia/physiopathology , Pain/physiopathology , Sympathetic Nervous System/physiopathology , Vasodilation/physiology , Adult , Body Temperature/physiology , Female , Humans , Male , Pain/chemically induced , Regional Blood Flow , Skin/blood supply , Skin/physiopathology
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