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ABSTRACT: Writer's cramp patients show poor force regulation during handwriting, but also in other experimental tasks requiring fine motor control. Botulinum neurotoxin (BoNT) treatment is clinically effective in a substantial portion of writer's cramp patients, but the full mechanism of action remains enigmatic. BoNT possibly influences α- and γ-motoneurons through chemodenervation not only of extra-, but also intrafusal muscle fibres and might thus influence muscle spindle afferents. Hence, BoNT weakens injected muscles, but may also modulate sensory aspects of force control. Ten patients and 18 controls pressed their index finger on a force sensor tracking two visual targets: The first target consisted of five plateaus with successively higher force levels and alternated with ascending ramps. In the second target condition the same successive plateaus were to be reached by abrupt jumps. The generated force displayed as a time dependant curve. Root mean square of the difference between target and produced force level was calculated for each plateau/ramp/jump. Patients were treated with BoNT at week 4 and measured at baseline, weeks 2, 4, 6 and 8. Disturbed force regulation in patients for the plateaus and the second jump at baseline resolved after BoNT treatment, and the root mean square of force deviation decreased for the ramps. Fine force control was within the 95% confidence interval of the control group after treatment. In conclusion, force regulation was disturbed in patients and improved after BoNT treatment. This is not compatible with a simple muscle weakening and might thus reflect improved sensorimotor integration.
Parkinsonism & Related Disorders 03/2013; · 3.80 Impact Factor
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ABSTRACT: This review describes the most recent advances in epidemiology, classification, genetics, pathology and treatment of essential tremor. In addition, recent advances in more rare forms of tremor are summarized.
Clinical, biochemical, pathological and imaging studies suggest an abnormal functioning of the cerebellum in essential tremor. Minor changes of cognition and personality may be due to secondary effects. Dementia and possible shortened life span seem to be limited to late-onset essential tremor. Many of these issues are not yet finally settled and need confirmation in further studies. The current essential tremor classification seems not to reflect the variety of phenotypic expressions. Regarding treatment, there is now a level B evidence for topiramate. Levetiracetam may induce a positive response in Holmes tremor, but is ineffective in orthostatic tremor.
These findings have extended our knowledge about essential tremor. It appears that a new, more distinct classification system is required. Recent treatments have remained unchanged.
Current opinion in neurology 08/2012; 25(4):475-82. · 5.43 Impact Factor
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ABSTRACT: From longitudinal voxel-based morphometry (VBM) studies we know that relatively short periods of training can increase regional grey matter volume in trained cortical areas. In 14 right-handed patients with writer's cramp, we employed VBM to test whether suppression (i.e., immobilization) or enhancement (i.e., training) of manual activity lead to opposing changes in grey matter in the contralateral primary motor hand area (M1(HAND)). We additionally used transcranial magnetic stimulation (TMS) to evaluate concurrent changes in regional excitability. Patients were recruited from a clinical trial which was designed to improve handwriting-associated dystonia. Initially the dystonic hand was immobilized for 4 weeks with the intention to reverse faulty plasticity. After immobilization, patients accomplished a motor re-training for 8 weeks. T1-weighted MRIs of the whole brain and single-pulse TMS measurements of the resting motor threshold (RMT) were performed every 4 weeks. Immobilization of the right hand resulted in a relative grey matter decrease in the contralateral left M1(HAND) along with a decrease in corticomotor excitability as indexed by an increase in RMT. Subsequent training reversed the effects of immobilization, causing an increase in regional grey matter density and excitability of left M1(HAND). The relative changes in grey matter correlated with the relative shifts in RMT. This prospective within-subject VBM study in task-specific hand dystonia shows that the grey matter density of M1(HAND) is dynamically shaped by the level of manual activity. This bi-directional structural plasticity is functionally relevant as local grey matter changes are mirrored by changes in regional excitability.
NeuroImage 01/2011; 54(1):32-41. · 5.89 Impact Factor
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ABSTRACT: Associative high-frequency electrical stimulation (HFS) of the supraorbital nerve in five healthy individuals induced long-term potentiation (LTP)-like or depression (LTD)-like changes in the human blink reflex circuit according to the rules of spike timing-dependent plasticity (Mao and Evinger, 2001). HFS given at the onset of the R2 component of the blink reflex (HFS(LTP)) produced a lasting facilitation of the R2, whereas HFS given shortly before R2 (HFS(LTD)) caused a lasting suppression of the R2. In patients with benign essential blepharospasm (BEB), a focal dystonia affecting the orbicularis oculi muscles, HFS(LTP) induced excessive LTP-like associative plasticity relative to healthy controls, which was normalized after botulinum toxin (BTX) injections (Quartarone et al, 2006).
We used HFS conditioning of the supraorbital nerve to study homeostatic metaplasticity of the blink reflex circuit in healthy subjects and dystonic patients. On separate days, we tested the conditioning effects on the R2 response and paired-pulse R2 inhibition after (i) HFS(LTP), (ii) HFS(LTP) followed by HFS(LTP), and (iii) HFS(LTP) followed by HFS(LTD). Controls also received (iv) HFS(LTD) alone and (v) a non-intervention protocol. In BEB patients, HFS(LTP) followed by HFS(LTD) was given before and after BTX treatment. We were not able to replicate the bidirectional timing-dependent effects of HFS(LTP) and HFS(LTD) alone. All HFS protocols produced a non-specific reduction of the R2 response and a relative decrease in paired-pulse inhibition. These R2 changes also occurred in controls when no HFS was applied. There was also no trace of a homeostatic response pattern in BEB patients before or after BTX treatment.
Our data challenge the efficacy of associative HFS to produce bidirectional plasticity in the human blink reflex circuit. The non-specific decrease of the R2 response might indicate habituation of the blink reflex following repeated electrical supraorbital stimulation. The increase of inhibition after paired pulse stimulation might reflect homeostatic behaviour to prevent further down regulation of the R2 response to preserve the protection of this adverse-effects reflex.
PLoS ONE 01/2010; 5(10):e13602. · 4.09 Impact Factor
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ABSTRACT: Previous studies showed a beneficial effect of motor re-training in task-specific hand dystonia. Here we examined whether re-training needs to specifically focus on the task affected by dystonia. 21 patients with writer's cramp were randomly assigned to two types of re-training: One group of patients trained drawing and writing movements using a pen attached to the bottom of a finger splint. The second group used therapeutic putty to train finger movements without exercises of drawing and writing movements. Training lasted for 8 weeks. Before re-training, affected hand and forearm were immobilized for 4 weeks to facilitate the responsiveness to re-training. Dystonia was assessed during handwriting using the Writer's Cramp Rating Scale. Although no clinical improvement was observed immediately after immobilization, 8 weeks of re-training improved task-specific dystonia relative to baseline (P = 0.005). Both training modalities were equally effective. More severely affected patients benefited most. There was no correlation between disease duration and the individual treatment response. Re-training also improved hand function as indexed by the Arm Dystonia Disability Scale (P = 0.008). Kinematic handwriting analysis showed that re-training lowered vertical force level and enhanced the fluency of handwriting. We conclude that re-training does not need to specifically focus on the task affected by dystonia to be clinically effective.
Movement Disorders 10/2008; 23(16):2319-27. · 4.51 Impact Factor
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ABSTRACT: The cortex is involved in rhythmic hand movements. The cortical contribution to rhythmic motor patterns of the feet, however, has never been evaluated in humans. In this study we investigated EEG activity related to rhythmic stepping and tapping movements in 10 healthy subjects. Subjects performed self-paced fast bilateral anti-phase, in-phase and unilateral rhythmic foot movements as well as an isometric cocontraction of the calf muscles, while being seated as relaxed as possible. Surface EMG from the anterior tibial muscles was recorded in parallel with a 64 channel EEG. Power spectra, corticomuscular coherence and corticomuscular delay were calculated. All subjects showed corticomuscular coherence at the stepping frequencies in the central midline region that extended further to the frontal mesial area. The magnitude and the topography of this coherence were equal for the right and left anterior tibial muscle and all movement conditions. During cocontraction there was coherence in the 15-30 Hz range which was refined to the central midline area. EEG-EMG delays were significant in 9 subjects with values between 14 and 26 ms, EMG-EEG feedback was only found in 6 subjects with delays between 25 and 40 ms. We conclude that rhythmic motor patterns of the feet are represented in the cortex, transmitted to the muscles with delays compatible with fast corticospinal transmission and fed back to the cortex. A similar cortical contribution may be important also for gait control in humans.
Brain Research 08/2008; 1236:79-84. · 2.73 Impact Factor
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ABSTRACT: Classical Parkinsonian rest tremor typically fluctuates over time and can be provoked by stressful situations. We quantified and compared the influence of different provocation methods on classical rest tremor severity. The effect of counting backwards from 100, tapping of the contralateral foot and a Stroop test on the Unified Parkinson's Disease Rating Scale (UPDRS) III rest tremor scores and the accelerometrically measured tremor amplitudes (total power) were analyzed in 18 patients with Parkinson's disease and a Type I tremor. Each of the three provocation methods increased the UPDRS III rest tremor score by 1-2 and the total power by 1-2 orders of magnitude compared with baseline (P < 0.001). The maximal effect was reached on average after 2-3 minutes of provocation. The effects were not significantly different. Provocations clearly influence the result of clinical rest tremor ratings, with the kind of provocation being of minor importance. We therefore suggest that each assessment of Parkinsonian rest tremor should include a systematic provocation and this should be formally included in future versions of the UPDRS.
Movement Disorders 06/2008; 23(7):1019-23. · 4.51 Impact Factor
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ABSTRACT: Writer's cramp is a task-specific hand dystonia affecting handwriting. Clinical scores such as the Arm Dystonia Disability Scale (ADDS) or Writer's Cramp Rating Scale (WCRS) as well as kinematic analysis of handwriting movements have been used to assess functional impairment in affected patients. In 21 patients with writer's cramp and healthy controls, we analyzed the kinematics of writing and cyclic drawing movements. We rated the severity of dystonia using the ADDS and WCRS and correlated the clinical scores with movement kinematics. Mean stroke frequency was significantly reduced in dystonic patients. Drawing movements showed more frequently a decrease in stroke frequency than handwriting movements. During circle drawing, mean vertical peak velocity was more variable in patients relative to controls, indicating an impaired ability to reproduce the same kinematic pattern over time. An increase in vertical writing pressure was only observed during handwriting but not during circle drawing and may reflect a compensatory effort to stabilize the pencil. Kinematic measures and individual ADDS and WCRS scores did not correlate with each other. The lack of correlation is not surprising as ADDS, WCRS, and kinematic analysis probe different aspects of motor impairment. The ADDS characterizes how dystonia affects a set of fine manual tasks, whereas the WCRS scores the manifestation of dystonia during handwriting. Therefore, the clinical scores and kinematic analysis of handwriting provide complementary insights into motor impairment. Future studies need to address which combination of clinical scores and kinematic measures are most appropriate to quantify impairment in writer's cramp.
Movement Disorders 07/2007; 22(8):1102-9. · 4.51 Impact Factor
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ABSTRACT: Focal hand dystonia may arise as a result of aberrant plasticity from excessive repetitive use. Improvement might be possible with appropriate motor training. Focusing on trying to decrease abnormal overflow of movement to fingers not involved in a task, we developed a motor training program for individualized finger movements. Ten patients with writer's cramp participated in the motor training program. Evaluation was done with the Fahn dystonia scale, kinematic analysis of handwriting, transcranial magnetic stimulation (TMS), and electroencephalography (EEG). Clinical improvement of dystonia was significant using the Fahn dystonia scale, and 6 patients reported an improvement in writing. The handwriting analysis showed a trend for improvement after training in simple exercises. There were no changes in cortical excitability measured by TMS and EEG. Whereas this method of motor training for 4 weeks led to mild subjective improvement and some improvement in handwriting, it is not sufficient to reverse motor cortex abnormalities measured by TMS and EEG.
Movement Disorders 04/2005; 20(3):335-41. · 4.51 Impact Factor
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ABSTRACT: We investigated the effects of ethanol and diazepam on the central, mechanical, and mechanical reflex components of tremor in patients with essential tremor (ET). A double-blind crossover study (ethanol or diazepam) was conducted on 2 separate days. Dose of ethanol or diazepam was calculated in each individual according to height, weight, and age in 10 patients with ET. The postural tremor amplitude at the wrist was recorded using a three-dimensional accelerometer placed on the dorsum of the hand. Electromyogram (EMG) was recorded with surface electrodes placed on the forearm extensors and flexors. To separate central and mechanical (reflex) components, a 500-g weight was placed on the dorsum of the hand during a second tremor measurement. Tremor recordings were done at baseline and 30, 60, 90, and 120 minutes after drug ingestion. Ethanol and diazepam blood levels were measured at baseline and after 20, 40, 80, and 120 minutes. Blood ethanol and diazepam levels were highest after 40 and 80 minutes. The amplitude of the central component 60 minutes after ingestion of ethanol was decreased significantly (P = 0.029) compared with diazepam. Our findings suggest that the improvement in tremor after ethanol ingestion was due, at least in part, to an effect on a central oscillator.
Movement Disorders 12/2003; 18(11):1280-5. · 4.51 Impact Factor
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ABSTRACT: In a prior study, 10 patients with focal hand dystonia learned braille reading as sensory training for 8 weeks. Practice time was 30 to 60 minutes daily. They improved both their spatial acuity using the Grating Orientation Discrimination Task (GOT) and their dystonia using the Fahn scale. Three patients continued training for 1 year. Patients showed further improvement in the GOT, writing a standard paragraph, and self-rating scales. Sensory training lasting longer than 8 weeks may lead to continued improvement.
Movement Disorders 10/2003; 18(9):1044-7. · 4.51 Impact Factor
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ABSTRACT: Acute deafferentation of a limb results in bilateral cortical reorganization, but the behavioral consequences of this phenomenon are unknown. Here we found rapid improvements in tactile spatial acuity and changes in cortical processing for the left hand during cutaneous anesthesia of the right hand. The site-specific improvement in tactile spatial acuity may represent a behavioral compensatory gain.
Nature Neuroscience 11/2002; 5(10):936-8. · 15.53 Impact Factor
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ABSTRACT: Some patients with focal hand dystonia have impaired sensory perception. Abnormal sensory processing may lead to problems with fine motor control. For patients with focal hand dystonia who demonstrate sensory dysfunction, sensory training may reverse sensory impairment and dystonic symptoms. We studied the efficacy of learning to read braille as a method of sensory training for patients with focal hand dystonia. Sensory spatial discrimination was evaluated in 10 patients who had focal hand dystonia and 10 age- and gender-matched controls with a spatial acuity test (JVP domes were used in this test). Clinical dystonia evaluation included the Fahn dystonia scale and time needed to write a standard paragraph. Each individual was trained in braille reading at the grade 1 level for 8 weeks, between 30 and 60 minutes daily, and was monitored closely to ensure that reading was done regularly. Both controls and patients demonstrated improvement on the spatial acuity test. Patients showed a significant mean difference from baseline to 8 weeks on the Fahn dystonia scale. Sixty percent of the patients shortened the time they needed to write a standard paragraph. Improved sensory perception correlated positively with improvement on the Fahn dystonia scale. We conclude that training in braille reading improves deficits in spatial discrimination and decreases disability in patients with focal hand dystonia.
Annals of Neurology 06/2002; 51(5):593-8. · 11.09 Impact Factor
