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     

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 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.     

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.     

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.     

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.     

Abnormal spinal interactions from hand afferents to forearm muscles in writer's cramp.

OBJECTIVE: Spinal reflexes from hand to wrist muscles were investigated in writer's cramp. METHODS: Stimulus-triggered rectified EMG averages after ulnar nerve and cutaneous stimulation, in wrist flexors and extensors during tonic contraction, were compared in 18 controls and 19 patients. RESULTS: On the patient dystonic side, ulnar-induced EMG suppression was decreased in wrist extensors, and facilitation in wrist flexors modified dependent on the dystonic wrist posture during writing. No change was found on the patient non-dystonic side. Cutaneous stimulation increased wrist flexor EMG on both sides of the patients with normal wrist posture during writing, but had no effect in controls and patients with abnormal wrist posture. CONCLUSIONS: Comparison between cutaneous and mixed nerve stimuli suggests that spindle afferents from intrinsic hand muscles may mediate patients' ulnar-induced EMG modulations. Abnormal proprioceptive control was only observed on dystonic side, while bilateral unusual cutaneous control was found in patients. Changes in spinal transmission were partly related to the dystonic wrist posture, suggesting that systems involved in sensory processing can be differentially altered in writer's cramp. SIGNIFICANCE: Changes in spinal transmission, probably related to peripheral and/or cortical inputs, might either take part in primary or adaptive mechanisms underlying writer's cramp.     

A positron emission tomography study of essential tremor: Evidence for overactivity of cerebellar connections

The origin of essential tremor is unknown. Animal models have suggested that the inferior olivary nucleus may act as a tremor generator. We used positron emission tomography to study changes in regional cerebral blood flow associated with involuntary postural tremor and passive wrist oscillation in patients with essential tremor. Activation due to voluntary wrist oscillation and arm extension without tremor was studied in normal control subjects. The essential tremor group had bilaterally increased cerebellar blood flow at rest (without tremor) compared with the control group. Involuntary postural tremor was associated with further bilateral cerebellar activation, and also contralateral striatal, thalamic, and sensorimotor cortex activation. Voluntary wrist oscillation, maintained arm extension without tremor, and passive wrist oscillation were all associated with significant ipsilateral rather than bilateral cerebellar activation. We conclude that essential tremor is associated with increased bilateral cerebellar activity both at rest and during tremor.     

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.     

Primary writing tremor: motor cortex reorganisation and disinhibition.

BACKGROUND: Primary writing tremor (PWT) is a task-specific tremor of uncertain origin. There has been debate as to whether PWT represents a variant of essential tremor or a tremulous form of focal dystonia related to writer's cramp. In writer's cramp there is evidence of changes in intracortical inhibition (ICI), as well as cortical motor reorganisation. OBJECTIVE: To study corticomotor organisation and short-latency ICI in a patient with typical task-specific PWT. METHODS: Transcranial magnetic stimulation mapping of the corticomotor representation of the hand and studies of ICI using paired-pulse stimulation were performed in a 47-year-old right-handed woman with a pure task-specific writing tremor. RESULTS: The motor maps for the hand were displaced posteriorly on both sides and reverted to a normal position after treatment with botulinum toxin. Short-latency ICI was reduced for the dominant hand. CONCLUSION: The findings indicate reorganisation and disinhibition of the corticomotor projection to the hand and point to the participation of cortical centres in the origin of PWT.     

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     

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.     

Writing tremor myoclonus

A patient with a 9-year history of primary writing tremor is described. Spontaneous postural tonic abduction and tremor of the right index finger was also present. Atypical features included unidirectionality of the tremor, writing-associated and independent, bilateral proximal upper limb myoclonus. No clinical response was obtained after intravenous benztropine and subtotal lidocaine infiltration of the right first dorsal interosseous muscle motor point. There was no dystonia present. This case illustrates the sporadic occurrence of writing tremor of the primary type in the absence of dystonia, otherwise a common feature of writer's cramp.     

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.     

Increased co-activation of the upper limb muscles in writer''s cramp.

Eleven patients with writer's cramp were studied during the performance of a series of writing and non-writing tasks. Their performance in the tasks and the intensity of contraction in the flexor and extensor muscles of the fingers and elbow (recorded electromyographically) were compared with the results from a group of matched normal controls. The patients showed highly significant increases in muscle activation especially in the triceps muscle which was overactive in all but one of the tasks undertaken. Psychometric testing showed no difference between patients and controls. The results support the view that writer's cramp is a form of focal dystonia in which the disorder of motor control is not confined to writing activities.     

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.     

123I-IPT brain SPECT study in essential tremor and Parkinson's disease

OBJECTIVE: To investigate nigral neuronal damage in patients with isolated postural tremor and those with postural and rest tremor without parkinsonism. METHODS: Using [123I]-N-(3-iodopropen-2-yl)-2 -carbomethoxy-3beta-(4-chlorophenyl) tropane SPECT, we measured the basal ganglia-occipital cortex/occipital cortex ([BG-OCC]/OCC) uptake ratios in 21 control subjects and patients with isolated postural tremor (n = 9), postural and rest tremor (n = 6), and PD (n = 11). RESULTS: In the patients with PD, the means (+/-SD) of the (BG-OCC)/OCC ratios of the ipsilateral (2.35+/-0.37) and the contralateral (1.97+/-0.33) sides to the more severely affected limbs were significantly lower than the mean of the bilateral (BG-OCC)/OCC ratios of the age-matched control subjects (3.83+/-0.66). The mean (+/-SD) of the bilateral (BG-OCC)/OCC ratios of the patients with isolated postural tremor (3.60+/-0.83) was comparable with that of the age-matched control subjects. However, the mean (+/-SD) of the bilateral (BG-OCC)/OCC ratios of the patients with postural and rest tremor (2.61+/-0.18) was lower than that of the control subjects (p < 0.05). The mean of the bilateral (BG-OCC)/OCC ratios of the patients with postural and rest tremor was comparable with that of the side ipsilateral to the severely affected limbs of the patients with PD. However, it was higher than that of the side contralateral to the limbs more severely affected by PD. Four of the six patients with postural and rest tremor had (BG-OCC)/OCC ratios lower than 2 standard deviations from the mean of the age-matched control subjects. CONCLUSIONS: Later in their clinical courses, some patients with postural tremor may acquire rest tremor in association with mild substantia nigra neuronal loss.     

Low-frequency repetitive transcranial magnetic stimulation of the motor cortex in writer's cramp

OBJECTIVE: To study the short-term effects of slow repetitive transcranial magnetic stimulation (rTMS) of the motor cortex on cortical excitability and handwriting in patients with writer's cramp. BACKGROUND: Cortical excitability of the primary motor cortex is abnormally enhanced in patients with writer's cramp. Therefore, reducing cortical excitability by low-frequency rTMS of the motor cortex might result in beneficial effects on handwriting in writer's cramp. DESIGN/METHODS: We studied the effects of subthreshold 1-Hz rTMS on motor threshold and cortico-cortical excitability using the paired-pulse technique in seven patients and seven controls. In another 16 patients and 11 age-matched controls we evaluated changes in cortical excitability by measuring the stimulus-response curve and the postexcitatory silent period before and after subthreshold 1-Hz rTMS. In addition, we analyzed the handwriting before and 20 minutes after 1-Hz rTMS. RESULTS: In the first experiment, low-frequency rTMS resulted in a normalization of the deficient cortico-cortical inhibition in the patients without affecting motor threshold. In the second experiment, 1-Hz rTMS resulted in a significant prolongation of the postexcitatory silent period without affecting the stimulus-response curve in the patient group. Moreover, the dystonic patients showed a significant reduction of mean writing pressure after subthreshold 1-Hz rTMS that was associated with clear but transient improvement in six patients. CONCLUSIONS: In some patients 1-Hz rTMS can reinforce deficient intracortical inhibition and may improve handwriting temporarily. Our data support the notion that reduced intracortical inhibition plays a part in the pathophysiology of focal dystonia.     

Sensorimotor organization in double cortex syndrome

Subcortical band heterotopia is a diffuse malformation of cortical development related to pharmacologically intractable epilepsy. On magnetic resonance imaging (MRI), patients with "double cortex" syndrome (DCS) present with a band of heterotopic gray matter separated from the overlying cortex by a layer of white matter. The function and connectivity of the subcortical heterotopic band in humans is only partially understood. We studied six DCS patients with bilateral subcortical band heterotopias and six healthy controls using functional MRI (fMRI). In controls, simple motor task elicited contralateral activation of the primary motor cortex (M1) and ipsilateral activation of the cerebellum and left supplementary motor area (SMA). All DCS patients showed task-related contralateral activation of both M1 and the underlying heterotopic band. Ipsilateral motor activation was seen in 4/6 DCS patients. Furthermore, there were additional activations of nonprimary normotopic cortical areas. The sensory stimulus resulted in activation of the contralateral primary sensory cortex (SI) and the thalamus in all healthy subjects. The left sensory task also induced a contralateral activation of the insular cortex. Sensory activation of the contralateral SI was seen in all DCS patients and secondary somatosensory areas in 5/6. The heterotopic band beneath SI became activated in 3/6 DCS patients. Activations were also seen in subcortical structures for both paradigms. In DCS, motor and sensory tasks induce an activation of the subcortical heterotopic band. The recruitment of bilateral primary areas and higher-order association normotopic cortices indicates the need for a widespread network to perform simple tasks.     

Evolution of functional reorganization in hemiplegic stroke: a serial positron emission tomographic activation study

We used serial positron emission tomography (PET) to study the evolution of functional brain activity within 12 weeks after a first subcortical stroke. Six hemiplegic stroke patients and three normal subjects were scanned twice (PET 1 and PET 2) by using passive elbow movements as an activation paradigm. Increases of regional cerebral blood flow comparing passive movements and rest and differences of regional cerebral blood flow between PET 1 and PET 2 in patients and normal subjects were assessed by using statistical parametric mapping. In controls, activation was found in the contralateral sensorimotor cortex, supplementary motor area, and bilaterally in the inferior parietal cortex with no differences between PET 1 and PET 2. In stroke patients, at PET 1, activation was observed in the bilateral inferior parietal cortex, contralateral sensorimotor cortex, and ipsilateral dorsolateral prefrontal cortex, supplementary motor area, and cingulate cortex. At PET 2, significant increases of regional cerebral blood flow were found in the contralateral sensorimotor cortex and bilateral inferior parietal cortex. A region that was activated at PET 2 only was found in the ipsilateral premotor area. Recovery from hemiplegia is accompanied by changes of brain activation in sensory and motor systems. These alterations of cerebral activity may be critical for the restoration of motor function.