Effects of transcutaneous electrical nerve stimulation on motor cortex excitability in writer's cramp: neurophysiological and clinical correlations.

We recently reported that transcutaneous electrical nerve stimulation (TENS) applied over forearm flexor muscles, a paradigm producing in physiological conditions transient changes in corticomotoneuronal excitability of forearm muscles, may improve motor symptoms in writer's cramp (WC). In the present study, we explored the possibility that one or repeated sessions of TENS might have beneficial effects on handwriting in WC by remodulating cortical excitability of forearm agonist and antagonist muscles. Motor evoked potentials (MEPs) after transcranial magnetic stimulation of the left motor cortex were recorded from the right flexor carpi radialis (FCR) and extensor carpi radialis (ECR) muscles, before and after 1 and 15 sessions of TENS applied over flexor muscles in patients and in a control group. One session of TENS induced a significant smaller reduction of MEPs from the FCR and a smaller increase of the MEPs from the ECR in patients than in normal subjects. In WC, repeated sessions of TENS had the effect to decrease MEP amplitude in the FCR and to increase it in the ECR. This modulation was paralleled by a handwriting improvement. In conclusion, repeated TENS sessions may have the effect to re-modulate excitability of the motor cortex in WC and this modulation might partially play a role in temporarily improving the handwriting.     

EMG-EMG coherence in writer's cramp.

We investigated the extent to which oscillatory drives to muscle, believed to arise mainly from the motor cortex, are exaggerated and/or fail to react normally to peripheral stimulation in writer's cramp. We used the coherence between active forearm flexor and intrinsic hand muscles as our index of such drives before and after digital nerve stimulation of the dominant hand. The results in 8 patients with writer's cramp were compared with those in eight age- and sex-matched healthy subjects. We found no significant difference in either the strength of intermuscular coherence or its modulation by cutaneous stimulation between patients and healthy subjects during voluntary flexion of the wrist and extension-abduction of the fingers. Therefore, we were unable to provide evidence for a pervasive disturbance of oscillatory cortical motor outflow in writer's cramp.     

Cooling improves the writing performance of patients with writer's cramp.

Cooling of hand and forearm muscles by immersion in 15 degrees C cold water for 5 minutes improved the writing performance of patients with writer's cramp. Since abnormal processing of muscle spindle afferent discharges contributes to the pathology of writer's cramp, this effect might result from a reduction in muscle spindle activity by lowering muscle temperature. Cooling is a simple, cheap, and safe procedure, providing temporary relief for patients with writer's cramp.     

Three brothers with a very-late-onset writer's cramp.

Writer's cramp (WC) is a form of focal task-specific dystonia, which is brought on by writing. Although most cases are sporadic, a positive family history is present in 5% to 20% of cases. To date, WC has been reported in several families with primary torsion dystonia, including DYT7, a pure focal dystonia, and in the mixed dystonias, DYT1, DYT6, and DYT13. We describe a family of Bulgarian descent with three brothers presenting with a very-late-onset dystonic WC, compatible with linkage to chromosome 18p.     

Botulinum toxin therapy of writer's cramp

The pathophysiology and management of writer's cramp is one of the most challenging amongst the various forms of focal dystonias. Frequently, the dystonic postures are confounded by compensatory muscle activity. Correct identification of target muscles for botulinum toxin (BT) injections determines the treatment success. The dosages of different preparations vary, with 1 unit of Botox® roughly equalling 3.5 units of Dysport®. Electromyographic guided injections yield better results and may also decrease the amount of toxin required. Weakness of target muscles interfering with other non‐writing activities is a frequently encountered adverse effect. Studies have shown that BT is a safe long‐term therapy option.     

Basal ganglia–premotor dysfunction during movement imagination in writer's cramp

The pathophysiology of idiopathic focal hand dystonia (writer's cramp) is characterized by deficient inhibitory basal ganglia function and altered cortical sensorimotor processing. To explore if this is already a primary finding in dystonia for internal movement simulation independent of dystonic motor output or abnormal sensory input, we investigated the neural correlates of movement imagination and observation in patients with writer's cramp. Event‐related fMRI was applied during kinesthetic motor imagery of drawing simple geometric figures (imagination task) and passively observing videos of hands drawing identical figures (observation task). Compared with healthy controls, patients with writer's cramp showed deficient activation of the left primary sensorimotor cortex, mesial and left dorsal premotor cortex, bilateral putamen, and bilateral thalamus during motor imagery. No significant signal differences between both groups were found during the observation task. We conclude that internal movement simulation and planning as tested during imagination of hand movements appear to be dysfunctional in patients with writer's cramp, whereas visual signal processing and observation‐induced activation are unaffected. Deficient basal ganglia–premotor activation could be a correlate of impaired basal ganglia inhibition and focusing during the selection of motor programs in dystonia. This finding seems to be an intrinsic deficit, as it is found during motor imagery in the absence of dystonic symptoms. © 2012 Movement Disorder Society     

How to assess motor impairment in writer's cramp.

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.     

Abnormal plasticity of the sensorimotor cortex to slow repetitive transcranial magnetic stimulation in patients with writer's cramp.

Previous studies demonstrated functional abnormalities in the somatosensory system, including a distorted functional organization of the somatosensory cortex (S1) in patients with writer's cramp. We tested the hypothesis that these functional alterations render S1 of these patients more susceptible to the "inhibitory" effects of subthreshold 1 Hz repetitive transcranial magnetic stimulation (rTMS) given to S1. Seven patients with writer's cramp and eight healthy subjects were studied. Patients also received rTMS to the motor cortex hand area (M1). As an outcome measure, short-latency afferent inhibition (SAI) was tested. SAI was studied in the relaxed first dorsal interosseous muscle using conditioning electrical stimulation of the index finger and TMS pulses over the contralateral M1. Baseline SAI did not differ between groups. S1 but not M1 rTMS reduced SAI in patients. rTMS had no effects on SAI in healthy subjects. Because SAI is mediated predominantly at a cortical level in the sensorimotor cortex, we conclude that there is an abnormal responsiveness of this area to 1 Hz rTMS in writer's cramp, which may represent a trait toward maladaptive plasticity in the sensorimotor system in these patients.     

Bilateral mirror writing movements (mirror dystonia) in a patient with writer's cramp: functional correlates.

A recent prospective analysis on writer's cramp showed that up to 44.6% of patients in a series of 65 presented mirror dystonia, defined as involuntary movements of the resting hand, abnormal posture, tremor, and jerks occurring while writing with the opposite hand. A clinical case is presented, with videotape evidence of right-handed writer's cramp, with mirror movements elicited while writing using either hand. Functional magnetic resonance imaging studies are compared both to those of a normal patient and to those from a patient with writer's cramp but lacking mirror dystonia. Widespread bilateral activation of cortical motor areas contralateral to the mirror movements in patients with writer's cramp and mirror movements suggests, that bilateral activation of the primary motor cortex may account for the appearance of these mirror movements. Further studies need to be conducted to determine whether mirror movements in dystonic patients appear as a result of loss of intra- and/or interhemispheric cortical inhibition or are simply a consequence of the sustained effort these patients need to exert while writing using a dystonic hand.     

Corticospinal excitability during motor imagery is diminished by continuous repetition-induced fatigue

Application of continuous repetition of motor imagery can improve the performance of exercise tasks. However, there is a lack of more detailed neurophysiological evidence to support the formulation of clear standards for interventions using motor imagery. Moreover, identification of motor imagery intervention time is necessary because it exhibits possible central fatigue. Therefore, the purpose of this study was to elucidate the development of fatigue during continuous repetition of motor imagery through objective and subjective evaluation. The study involved two experiments. In experiment 1, 14 healthy young volunteers were required to imagine grasping and lifting a 1.5-L plastic bottle using the whole hand. Each participant performed the motor imagery task 100 times under each condition with 48 hours interval between two conditions: 500 mL or 1500 mL of water in the bottle during the demonstration phase. Mental fatigue and a decrease in pinch power appeared under the 1500-mL condition. There were changes in concentration ability or corticospinal excitability, as assessed by motor evoked potentials, between each set with continuous repetition of motor imagery also under the 1500-mL condition. Therefore, in experiment 2, 12 healthy volunteers were required to perform the motor imagery task 200 times under the 1500-mL condition. Both concentration ability and corticospinal excitability decreased. This is the first study to show that continuous repetition of motor imagery can decrease corticospinal excitability in addition to producing mental fatigue. This study was approved by the Institutional Ethics Committee at the Nagasaki University Graduate School of Biomedical and Health Sciences(approval No. 18121302) on January 30, 2019.     

Spinocerebellar ataxia type 3 presenting with writer's cramp without ataxia

Aim of the study: Spinocerebellar ataxia type 3 is the most common cause of autosomal dominant inherited ataxia worldwide.

Material and methods: Clinically, it exhibits wide phenotypic variability. Presentation as isolated dystonia is exceptional.

Results: Here, the case of a woman with writers cramp without ataxia is presented as a paucisymptomatic manifestation of this disease.

Conclusions: This association has not been described to date and extends the clinical variability of the disease.     

Unusual familial presentation of epsilon‐sarcoglycan gene mutation with falls and writer's cramp

Inherited myoclonus dystonia (M‐D, DYT11) is an autosomal dominant dystonia‐plus syndrome, which in many families is caused by mutations in the SGCE/ (epsilon‐sarcoglycan gene. We present a family with M‐D, with an unusual presentation characterized by infantile onset with falls in two sisters and adult‐onset writer's cramp in their father. Myoclonus dystonia is typically characterized by a variable mixture of alcohol‐sensitive myoclonic jerks and dystonia classically affecting mainly the proximal arms and neck. Leg involvement is less frequent, and to our knowledge, initial presentation with falls has not previously been described. The unusual phenotype of the family is discussed. © 2008 Movement Disorder Society.     

Changes in resting-state brain networks in writer's cramp

Objectives:

Writer's cramp (WC) is characterized by excessive cocontractions of agonist and antagonist hand and forearm muscles during writing. Changes in functional magnetic resonance imaging activation patterns in such conditions can be ambiguous as they might either reflect some aspect of the primary pathophysiological mechanism or, alternatively, may be the result of adaptive actions during task execution. To circumvent this problem, we examined WC patients during rest, i.e., without a task, using independent component analysis (ICA) applied to the blood oxygen level‐dependent time series.

Methods:

Functionally connected brain networks during rest were defined by ICA to assess differences between WC patients (n = 16) and healthy controls (n = 16). Analysis was carried out using FMRIB's Software Library.

Results:

Two functional networks showed between‐group differences, the sensorimotor network and the default‐mode network. In WC patients, the connectivity was reduced in the left postcentral area and increased in basal ganglia in contrast to healthy controls. These changes were not reversed after treatment with botulinum toxin.

Conclusions:

In line with other studies, the results show a dysfunction in cortico‐subcortical circuits in WC involving somatosensory cortex, areas interfacing the sensory and motor systems, and putamen contralateral to symptomatic hand. Hum Brain Mapp, 2012. © 2011 Wiley Periodicals, Inc.

     

Focal enhancement of motor cortex excitability during motor imagery: a transcranial magnetic stimulation study

OBJECTIVES: In order to learn more about the physiology of the motor cortex during motor imagery, we evaluated the changes in excitability of two different hand muscle representations in the primary motor cortex (M1) of both hemispheres during two imagery conditions. MATERIALS AND METHODS: We applied focal transcranial magnetic stimulation (TMS) over each M1, recording motor evoked potentials (MEPs) from the contralateral abductor pollicis brevis (APB) and first dorsal interosseus (FDI) muscles during rest, imagery of contralateral thumb abduction (C-APB), and imagery of ipsilateral thumb abduction (I-APB). We obtained measures of motor threshold (MT), MEP recruitment curve (MEP-rc) and F waves. RESULTS: Motor imagery compared with rest significantly decreased the MT and increased MEPs amplitude at stimulation intensities clearly above MT in condition C-APB, but not in condition I-APB. These effects were not significantly different between right and left hemisphere. MEPs simultaneously recorded from the FDI, which was not involved in the task, did not show facilitatory effects. There were no significant changes in F wave amplitude during motor imagery compared with rest. CONCLUSIONS: Imagery of unilateral simple movements is associated with increased excitability only of a highly specific representation in the contralateral M1 and does not differ between hemispheres.     

The modulation of motor cortex excitability during motor imagery depends on imagery quality

Motor imagery (MI) increases corticomotor excitability and modulates intracortical inhibition. This study aimed to relate these neurophysiological mechanisms to imagery quality. Twenty-three healthy adults participated. First, the ability to vividly and accurately imagine performing a finger-to-thumb opposition task was evaluated by calculating a MI index (MII) based on psychological, behavioural and psychophysiological measurements. These scores were used to distinguish good from poor imagers. Transcranial magnetic stimulation was then used to assess modulation of corticomotor excitability, short-interval intracortical inhibition (sICI) and short-interval intracortical facilitation (sICF). Participants imagined abduction of their right thumb paced by a 1-Hz metronome. Single and paired magnetic stimuli were delivered at rest, while listening to the metronome, and during or between imagined movements. Corticomotor excitability was facilitated in the right opponens pollicis for good and poor imagers during MI, and this was positively correlated to the MII score. Poor imagers also facilitated corticomotor excitability of the right abductor digiti minimi, which was not involved in the movement. No interactions were found with sICI and sICF for good imagers, whereas poor imagers recruited intracortical facilitation while imagining. Accurate MI performance was characterised by muscle-specific temporal modulation of corticomotor excitability.     

Screening for dystonia genes DYT1, 11 and 16 in patients with writer's cramp

Task‐specific focal upper limb dystonia can be part of the phenotypic spectrum of different types of hereditary dystonia. We investigated whether writer's cramp as presenting symptom is associated with mutations in DYT11, DYT16, or with the DYT1 GAG deletion in 43 patients. No DYT11 and DYT16 mutations were identified. One patient carried the GAG deletion in the DYT1 gene. In our cohort, writer's cramp as presenting symptom is not associated with mutations in DYT11, DYT16, but it can be the sole manifestation of DYT1 GAG deletion mutation carriers. © 2009 Movement Disorder Society     

Reduced parietal connectivity with a premotor writing area in writer's cramp

Writer's cramp is a task‐specific form of dystonia with symptoms characterized by abnormal movements and postures of the hand and arm evident only during writing. Its pathophysiology has been related to faulty sensorimotor integration, abnormal sensory processing, and impaired motor planning. Its symptoms might appear when the computational load of writing pushes a tonically altered circuit outside its operational range. Using resting‐state fMRI, we tested whether writer's cramp patients have altered intrinsic functional connectivity in the premotor–parietal circuit. Sixteen patients with right‐sided writer's cramp and 19 control subjects were studied. We show that writer's cramp patients have reduced connectivity between the superior parietal lobule and a dorsal precentral region that controls writing movements. This difference between patients and controls occurred in the absence of writing and only in the hemisphere contralateral to the affected hand. This finding adds a novel element to the pathophysiological substrate for writer's cramp, namely, task‐independent alterations within a writing‐related circuit. © 2012 Movement Disorder Society     

Nonlinear sensory cortex response to simultaneous tactile stimuli in writer's cramp.

Writer's cramp is a task-specific dystonia that leads to involuntary hand postures during writing. Abnormalities of sensory processing may play a pathophysiological role in this disorder. Electrophysiology studies in a monkey model of focal dystonia have revealed de-differentiation of sensory maps and the existence of single cells in hand regions of area 3b with enlarged receptive fields that extend to the surfaces of more than one digit. These changes may lead to abnormal processing of simultaneous sensory inputs. To study abnormal processing of simultaneous sensory information in adult humans with writer's cramp, we used functional magnetic resonance imaging to compare the response in primary sensory cortex with simultaneous tactile stimulation of the index and middle finger, with the response to stimulation of each finger alone. We tested five patients with writer's cramp and seven unaffected (normal) subjects. In the normal subjects, a linear combination of the activation patterns for individual finger stimulation predicts the pattern of activity for combined stimulation with 12% error. In writer's cramp patients, the linear combination predicted the combined stimulation pattern with 30% error. Results indicate a nonlinear interaction between the sensory cortical response to individual finger stimulation in writer's cramp. This altered interaction may contribute to the motor abnormalities.