Lack of inhibitory interaction between somatosensory afferent inputs and intracortical inhibitory interneurons in focal hand dystonia.

We looked for an impaired interaction in the primary motor cortex between intracortical inhibitory circuits and circuits fed by somatosensory inputs in patients with writer's cramp. Short-interval intracortical inhibition (sICI) to wrist extensor carpi radialis muscle (ECR) was conditioned by stimulation of antagonist muscle afferents and sICI to first dorsal interosseus (FDI) muscle by homotopic cutaneous afferents stimulation. sICI was assessed at rest and during a tonic contraction of the target muscle. Eighteen patients with writer's cramp (10 having a wrist dystonic posture in flexion during writing and 8 in extension) were compared to 14 control subjects. Peripheral inputs decreased sICI in control subjects. This decrease was lost in patients in both FDI and ECR, regardless of the wrist dystonic posture. By contrast, contraction-induced depression of sICI appeared dependant on the dystonic status of the muscle: depression of sICI to ECR was abolished in patients with wrist dystonic posture in flexion, but not in patients with dystonic posture in extension, sICI even giving way to motor-evoked potential facilitation. Loss of interaction between interneurons mediating sICI and peripheral inputs probably belongs to the initial abnormalities underlying dystonia. Lack of peripherally induced sICI modulation may oppose wrist and/or hand muscles synergies.     

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.     

Transient improvement of writing tremor by holding breath in volition: a case report]

We report a 76-year-old Japanese woman who had tremor of her hand during writing. Her past and family histories were unremarkable. On neurological examination, there was no abnormal finding except the writing tremor and the postural tremor of her lips and jaw. Surface EMG studies revealed that regular grouped discharges, at a frequency of about 5 Hz, appeared in the wrist flexor and extensor muscles soon after she start writing; these grouped discharges were inhibited while holding breath. Her postural tremor improved after consumption of a small amount of alcohol, suggesting that she had essential tremor. Thus, she may be diagnosed as having a variant of essential tremor. On the other hand, this tremor may be interpreted as a variant of writer's cramp, since her writing tremor transiently improved when she hold breath, just like a trick. In patients with dystonia, it is well known that dystonic symptoms can be temporally ameliorated by geste movement like a "trick". Although the pathophysiological relationship between primary writing tremor and writer's cramp are unclear, the unique characters of this tremor may suggest that a focal task-specific tremor and essential tremor can co-exist.     

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.     

Neurophysiological investigations in patients with primary writing tremor.

The pathophysiology of primary writing tremor (PWT) is still unknown: it has been classified as a focal form of essential tremor and as a tremulous form of writer's cramp. We studied cortical and spinal excitability in patients with PWT and compared the results with published data of patients with essential tremor, and writer's cramp. We used electrical stimulation of median and radial nerve to study reciprocal inhibition of forearm antagonist muscles and paired transcranial magnetic stimulation at short and long interstimulus intervals (ISIs) to assess intracortical excitability. Both studies were conducted on patients with PWT and on control subjects. The early (presynaptic) and late (disynaptic) phases of reciprocal inhibition were normal as was intracortical excitability at short and long ISIs. Our study suggests that the pathophysiology of PWT is different from that of writer's cramp and partially also from that of essential tremor.     

Prospective clinical study of writer's cramp.

Sixty-five consecutive patients with writer's cramp were studied prospectively to evaluate clinical and demographic features, the number of writing hours per day at dystonia onset, and the existence of trigger events. Assessment of writing and drawing was done on a standardized test using categorical scales. The importance of subjective handicap and pain, of postural and action tremor, the abnormal features of hand grip and the occurrence of mirror dystonia (dystonia occurring in the dominant hand when writing with the other hand) were studied. Thirty-two patients had simple writer's cramp, whereas the others had complex writer's cramp with several activities other than writing involved. No significant differences were seen in age of onset, legibility, pain, and handicap in these two groups. Seven patients had a family history of focal dystonia and six of them had a complex form of writer's cramp. Mirror dystonia was seen in 29 patients and in some it appeared useful to distinguish dystonic movements from secondary compensatory strategies.     

Tonic vibration reflex and muscle afferent block in writer's cramp

Patients with focal dystonia take advantage of certain cutaneous or proprioceptive sensory inputs to alleviate their symptoms (“sensory trick”). We examined the effects of increasing muscle spindle activity by the tonic vibration reflex maneuver and Decemberreasing it by intramuscular injection of lidocaine. The vibration was applied to the palm or the tendon of forearm muscles in 15 patients with writer's cramp and 15 age-matched normal subjects. In 11 patients, the vibration induced dystonic postures or movements typical of those seen during writing. Normal subjects showed either no response to the vibration or a gradually developing tonic vibration reflex only in the wrist and finger flexors, which produced visible movements with a significantly longer latency (12.5 ± 6.7 seconds [mean ± standard deviation]) than what was observed in the patients (2.7 ± 2.5 seconds, p < 0.0001). Local injection of lidocaine (0.5%, 5–40 ml/muscle) attenuated the tendon reflex with relatively little effect on the M response. Injection into muscles with increased activity produced Marchked reduction of dystonic movements and significant clinical improvement in 13 patients, whereas injection into the other muscles had no effect. The clinical benefit lasted for 1 to 24 hours after injection. In 13 patients who had additional injections of 10% ethanol, which blocks sodium channels for a longer period than does lidocaine, the duration of action was prolonged to 5 to 21 days. These findings suggest that muscles causing dystonic movements have abnormal sensitivities to vibration at rest and that muscle afferents may play a pivotal role in producing dystonic movements. Local injection of lidocaine or ethanol reduces the effectiveness of muscle spindle afferent and may provide a means of treating patients with writer's cramp without causing unwanted weakness.     

Primary writing tremor and myoclonic writer's cramp

Four patients with primary writing tremor had a focal, task-specific tremor that responded to anticholinergic drugs. Physiologic features included EMG activity alternating in antagonist muscles, 5- to 20-microV cerebral potentials evoked by stretch of pronator teres, and no C-reflexes. Another patient had myoclonic jerks of the forearm on attempts to write ("myoclonic writer's cramp") that also responded to anticholinergic drugs; EMG activity appeared synchronously or alternating in antagonist muscles. These disorders have features of dystonia and enlarge the spectrum of writer's cramp.     

Impaired modulation of motor cortex excitability by homonymous and heteronymous muscle afferents in focal hand dystonia.

A decrease of heteronymous median nerve-evoked inhibition of corticospinal projections to forearm extensor muscles was reported in a group of 10 dystonic patients by Bertolasi and colleagues in 2003. Here we tested the excitability of corticomotoneuronal connections to both wrist extensor (ECR) and flexor (FCR) muscles after conditioning stimulation of median and also radial nerve at rest in a group of 25 patients with focal hand dystonia compared to 20 healthy subjects. We also investigated the effect of the wrist dystonic posture, either in flexion or in extension, on the afferent modulation of ECR and FCR motor evolved potentials (MEPs). The heteronymous (median-induced) but also homonymous (radial-induced) inhibitions (interstimuli intervals 13-21 ms) of ECR MEP size observed in healthy subjects were decreased in patients. In addition, homonymous (median-induced) facilitation of FCR MEP size was also decreased in patients while heteronymous inhibition (radial-induced) was not. Neither the involvement of the target muscle in the dystonic posture nor the origin of the afferent volley (from a dystonic muscle) influenced the degree of impairment of afferent modulation of the MEP. These findings support the view that a global abnormal somatosensory coupling in focal hand dystonia may contribute to an inadequate motor command to wrist muscles.     

Abnormal postexcitatory and interhemispheric motor cortex inhibition in writer's cramp

Focal transcranial magnetic stimulation (TMS) of the motor cortex was used to study excitatory and inhibitory stimulation effects in 25 patients with writer's cramp and 25 healthy volunteers. We investigated excitatory and inhibitory corticospinally mediated motor effects in muscles contralateral to the stimulation side as well as interhemispheric inhibition of tonic motor activity in muscles ipsilateral to stimulation. Motor evoked potentials (MEPs) were recorded from both first dorsal interosseus muscles. Motor thresholds at rest and amplitudes and latencies of MEPs obtained during maximal contraction were always bilaterally normal. The duration of postexcitatory inhibition was significantly shortened (168±55 vs. 198±39 ms in normal subjects, P=0.001) and the duration of interhemispheric inhibition prolonged (30.3±6.6 vs. 26±3.9 ms in normal subjects, P < 0.001). Both observations would be compatible with a decreased inhibition of corticospinal and transcallosal outputs of the motor cortex. The results were not influenced by fatigue effects. Abnormal motor cortex inhibition seems to be a generalized phenomenon in writer's cramp since it was detected in both hemispheres and during a simple isometric motor task which did not evoke dystonic symptoms. Received: 28 February 2000 / Received in revised form: 29 June 2000 / Accepted: 1 August 2000     

Hand orthosis as a writing aid in writer's cramp.

Writer's cramp is a focal, task-specific dystonia of the hand and wrist. It primarily affects people who do a significant amount of writing, and causes difficulties in writing. We present five cases with writer's cramp who showed improvement in their writing ability with an applied hand orthosis.     

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.     

Hand cramps: clinical features and electromyographic patterns in a focal dystonia

We studied 19 patients with hand cramps, including writer's cramp, typist's cramp, piano, and guitar player's cramp. EMGs were recorded while patients performed the task triggering the cramps. Ten patients with dystonic cramps had EMGs with generalized muscle spasms with co-contraction of agonist and antagonist muscles. In three patients with simple cramps that involved one to three fingers, specific muscle groups showed co-contracting bursts that lasted longer than normal. The physiological abnormalities support the interpretation that hand cramp is a focal dystonia, characterized by both excessive muscle activity and defective fine motor control.     

Cerebral activation patterns in patients with writer's cramp: a functional magnetic resonance imaging study

Functional MRI (fMRI), visualizing changes in cerebral blood oxygenation, has to date not been performed either in patients with writer's cramp or in healthy subjects during writing. We compared the cerebral and cerebellar activation pattern of 12 patients with writer's cramp during writing with a group of 10 healthy subjects performing the same tasks over 30-s periods of rest or writing. Sixty echo planar imaging multi-slice datasets were analysed using SPM96 software. Data were analysed for each subject individually and groupwise for patients vs. controls. Healthy subjects showed a significant activation of the ipsilateral dentate nucleus, contralateral cerebellar hemisphere, contralateral primary sensorimotor cortex, and contralateral precentral gyrus during writing. Patients with writer's cramp showed significantly greater activation of the ipsilateral cerebellar hemisphere than controls. Also the activation in the primary sensorimotor cortex extended further caudally and anteriorly towards the premotor association area. Activation was observed in the thalamus during writing only among the patients. Our results indicate an increased basal ganglia output via the thalamus to the motor and premotor cortical areas in dystonia patients and support the notion of disinhibition of the motor cortex leading to coconcentrations and dystonic postures. Received: 10 November 1999 / Received in revised form: 4 April 2000 / Accepted: 26 April 2000     

Disturbed sensorimotor processing during control of precision grip in patients with writer's cramp.

The aim of the study was to investigate force regulation in patients with writer's cramp when performing a drawer-opening task using the precision grip. Experimental conditions included intervening load pulses and vibratory manipulations for examining grip force responses to sensory disturbances. The data revealed that grip force was increased in patients with writer's cramp compared with normal subjects, with a stronger modulation in the symptomatic compared with the asymptomatic hand. This denotes a change in force scaling capabilities and most notably for the preferred hand used in manipulative activities. Vibratory stimulation of the extrinsic hand/finger muscles resulted in an increased grip force of both hands in the patients with writer's cramp. The latter was not observed in normal subjects and supports a bilateral dysfunction in sensorimotor integration resulting from focal dystonia. In conclusion, the disturbed regulation of the precision grip during a drawer-opening task is illustrative for the inability of patients with writer's cramp to efficiently control the force output during manipulative activities.     

Writer's cramp syndrome treated successfully by thalamotomy

In the literature the prevalent until now opinion was that writer's cramp was a disturbance of psychic origin or an occupational neurosis. However, the authors treated successfully three cases of this syndrome with thalamotomy in the years 1976-1982. Two cases were in subject with right-handedness who had graphospasm with evidence of increasing difficulty in writing until complete impossibility of further writing, after several years postural and intentional tremor appeared, and dystonic symptoms developed in the right foot. The third cases had a history of 16 years of writer's cramp and after years symptoms of right-sided dystonia with involuntary movements of the right upper extremity and continuous tics and spams of the facial muscles. After thalamotomy in all cases writer's cramp, tremors and involuntary movements disappeared, writing became again possible and the efficiency of right extremities returned. The described cases of writer's clamp were focal forms of dystonia which became generalized after years. The indications to stereotaxic treatment in these syndromes should be established much earlier.     

Does abnormal interhemispheric inhibition play a role in mirror dystonia?

The presence of mirror dystonia (dystonic movement induced by a specific task performed by the unaffected hand) in the dominant hand of writer's cramp patients when the nondominant hand is moved suggests an abnormal interaction between the 2 hemispheres. In this study we compare the level of interhemispheric inhibition (IHI) in 2 groups of patients with writer's cramp, one with the presence of a mirror dystonia and the other without as well as a control group. The level of bidirectional IHI was measured in wrist muscles with dual‐site transcranial magnetic stimulation with a 10‐millisecond (short IHI) and a 40‐millisecond (long IHI) interstimulus interval during rest and while holding a pen in 9 patients with mirror dystonia 7 without mirror dystonia, and 13 controls. The group of patients without mirror dystonia did not differ from the controls in their IHI level. In contrast, IHI was significantly decreased in the group of patients with mirror dystonia in comparison with the group without mirror dystonia and the controls in both wrist muscles of both the dystonic and unaffected hand whatever the resting or active condition (P = 0.001). The decrease of IHI level in the group of patients with mirror dystonia was negatively correlated with the severity and the duration of the disease: the weaker the level of IHI, the more severe was the disease and the longer its duration. Interhemispheric inhibition disturbances are most likely involved in the occurrence of mirror dystonia. This bilateral deficient inhibition further suggests the involvement of the unaffected hemisphere in the pathophysiology of unilateral dystonia. © 2013 International Parkinson and 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.     

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.     

Corticospinal excitability during motor imagery of a simple tonic finger movement in patients with writer's cramp.

Motor imagery (MI) is the mental rehearsal of a motor act without overt movement. Using transcranial magnetic stimulation (TMS), we tested the effect of MI on corticospinal excitability in patients with writer's cramp. In 10 patients with writer's cramp and 10 healthy controls, we applied focal TMS over each primary motor area and recorded motor evoked potentials (MEPs) from contralateral hand and arm muscles while participants imagined a tonic abduction of the index finger contralateral to the stimulated hemisphere. In healthy controls and patients, the MEP amplitude in the relaxed first dorsal interosseus muscle (FDI) showed a muscle-specific increase during MI; however, the increase was less pronounced in patients than in healthy controls. In addition, in patients but not in controls, the MEP amplitude also increased in hand and forearm muscles not involved in the imagined movement. This abnormal spread of facilitation was observed in the affected and unaffected upper limb. MI of simple hand movements is less efficient and less focussed in patients with writer's cramp than it is in normal subjects.