Writer's Cramp Research Articles

POMD06 Utility of visual, tactile and mixed tasks in the determination of temporal discrimination thresholds in adult-onset primary torsion dystonia

Adult-onset primary torsion dystonia (AOPTD) is autosomal dominant with reduced penetrance. Sensory abnormalities in unaffected relatives may indicate nonmanifesting gene carriage—an ideal endophenotype being present in all patients and 50%...

Corticospinal excitability during action observation in task-specific dystonia: a transcranial magnetic stimulation study

Observation of actions performed by other individuals activates the onlooker's motor system in a way similar to real movement execution. The functioning of this mechanism in the pathological domain is not clear yet. The aim of this study was to explore whether action observation activates the motor system of patients affected by a task-specific form of dystonia, such as writer's cramp. Transcranial magnetic stimulation was applied over the primary motor cortex and motor evoked potentials were recorded from hand (FDI and ADM) and forearm (FCR) muscles at baseline and during observation of actions (grasping and writing) or images. Writing actions could be performed with healthy or dystonic movement patterns. Results showed a highly specific and reversed pattern of activation in the FDI muscle of the two groups. Differences between the two writing conditions were significantly opposite in the two groups: control subjects had higher activation during observation of the dystonic compared to the healthy action, whereas in patients observation of the healthy writing led to higher activation than the dystonic writing. This opposite corticospinal modulation might be explained by a different self-attribution of the observed actions in the two groups.

Manual activity shapes structure and function in contralateral human motor hand area

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 (M1HAND). 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 4weeks with the intention to reverse faulty plasticity. After immobilization, patients accomplished a motor re-training for 8weeks. T1-weighted MRIs of the whole brain and single-pulse TMS measurements of the resting motor threshold (RMT) were performed every 4weeks. Immobilization of the right hand resulted in a relative grey matter decrease in the contralateral left M1HAND 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 M1HAND. 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 M1HAND 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.

Impaired interhemispheric inhibition in writer's cramp

Reduced cortical inhibition is a feature of focal hand dystonia and this likely contributes to excessive muscle contractions. Inhibition from the opposite hemisphere, known as interhemispheric inhibition (IHI), was studied bidirectionally in 7 right-handed patients with writer's cramp (WC) and age-matched healthy controls in a cross-sectional physiologic study. IHI was measured with paired transcranial magnetic stimulation with the conditioning stimulus applied to the motor cortex and the test stimulus applied to the contralateral motor cortex. Surface EMG was measured in right and left first dorsal interosseous muscles during rest, and while holding a pen between the thumb and index finger at 20% maximum voluntary contraction with the right dystonia-affected hand. The time course and magnitude of IHI was studied at interstimulus intervals of 6, 8, 10, 12, 30, 40, and 50 msec between the conditioning stimulus and test stimulus. In WC at rest, IHI was significantly reduced in the dystonia-affected right hand (IHI from right to left motor cortex) at both short (SIHI, 10-12 msec) and long (LIHI, 30-40 msec) intervals compared to the unaffected hand. Compared to controls, SIHI and LIHI were reduced in the dystonia-affected hand only. There was no difference in IHI between controls and WC during the task of holding a pen. In WC, both SIHI and LIHI are reduced in the dystonia-affected hand compared to the unaffected hand and to healthy controls. Impaired IHI may contribute to excessive muscle contraction in WC.

TENS is harmful in primary writing tremor

Objective It is unclear whether primary writing tremor (PWT) is a tremulous form of dystonia or a tremor per se. Transcutaneous electrical nerve stimulation (TENS) at 50 Hz applied for 2 weeks was reported to improve the writing capabilities of patients with writer’s cramp (WC). We explored whether such a beneficial effect can be obtained in patients with a PWT. Methods In a cross-over, double-blinded randomized study we tested whether 2-week periods of 5, 25 or 50 Hz TENS applied to wrist flexor muscles, improved the score of the Fahn–Tolosa–Marin scale of nine patients with PWT. Excitability of neurons and of various intracortical circuits in the motor cortex were also tested before and after TENS by using transcranial magnetic stimulation. Results TENS at 5 and 25 Hz did not have any effect while TENS at 50 Hz worsened the clinical condition and the cortical excitability. Conclusions TENS is not a new treatment alternative for PWT. Significance The beneficial effect in WC and the harmful one in PWT of TENS stresses that the two disorders are likely different nosological entities.

Paroxysmal exercise-induced dyskinesia, writer's cramp, migraine with aura and absence epilepsy in twin brothers with a novel SLC2A1 missense mutation

We report two monochorionic twins that progressively developed, between ages 5 and 10, a combination of episodic neurological disorders including paroxysmal exercise-induced dyskinesia, migraine without or with aura, absence seizures and writer's cramp. CSF/serum glucose ratio was moderately decreased in both patients. Mutational analysis of SLC2A1 gene identified a de novo heterozygous missense mutation in exon 4. This novel mutation has been previously showed to disrupt glucose transport in vitro. Both patients showed immediate and near-complete response to ketogenic diet. This clinical observation suggests that a high index of suspicion for GLUT1 deficiency syndrome is warranted in evaluating patients with multiple neurological paroxysmal events.

Writing kinematics and pen forces in Writer’s Cramp: Effects of task and clinical subtype

Objective Writer’s Cramp (WC) is defined as a task-specific form of focal-hand-dystonia generating hypertonic muscle co-contractions resulting in impaired handwriting. Little is known about kinematic and dynamic characteristics in handwriting in the different subtypes of WC. Methods In this study, kinematic and force analyses were used to compare handwriting capacity of 14 simple, 13 dystonic WC-patients and 14 healthy subjects. The effect of task-complexity was investigated using a simple repetitive writing-task, writing pairs of letters, a sentence and copying a text. Results In general, patients showed significant deficits in kinematic and force parameters during writing, but no consistent differences between the two subtypes of WC were found. The complexity of writing material modulated writing parameters in all groups, but less complex material did not ameliorate the patients’ deficits relative to control subjects. Conclusions The similarity of deficits in patients with simple and dystonic WC does not support the concept of a unitary progression of deficits causing a switch from simple to dystonic WC. Dystonic WC seems to be characterized by a spread of symptoms independent of severity. Obviously, the deficits concern elementary aspects of writing and are not modulated by more complex aspects. Significance Quantification of writing deficits by simple and short phrases with kinematic and force parameters can substantially improve the characterization of WC.

Restoration of motor inhibition through an abnormal premotor‐motor connection in dystonia

To clarify the rationale for using rTMS of dorsal premotor cortex (PMd) to treat dystonia, we examined how the motor system reacts to an inhibitory form of rTMS applied to the PMd in healthy subjects and in a group of patients with focal hand dystonia and DYT1 gene carriers. Continuous theta burst transcranial magnetic stimulation (cTBS) with 300 and 600 pulses (cTBS300 and cTBS600) was applied to PMd, and its after-effects were quantified by measuring the amplitude of MEPs evoked by single pulse transcranial magnetic stimulation (TMS) over the primary motor cortex (M1), short interval intracortical inhibition/facilitation (SICI/ICF) within M1, the third phase of spinal reciprocal inhibition (RI), and writing tests. In addition, in DYT1 gene carriers, the effects of cTBS300 over M1 and PMd on MEPs were studied in separate experiments. In healthy subjects, cTBS300 and cTBS600 over PMd suppressed MEPs for 30 min or more and cTBS600 decreased SICI and RI. In contrast, neither form of cTBS over PMd had any significant effect on MEPs, while cTBS600 increased effectiveness of SICI and RI and improved writing in patients with writer's cramp. NMDYT1 had a normal response to cTBS300 over left PMd. We suggest that the reduced PMd to M1 interaction in dystonic patients is likely to be due to reduced excitability of PMd-M1 connections. The possible therapeutic effects of premotor rTMS may therefore involve indirect effects of PMd on SICI and RI, which this study has shown can be normalised by cTBS.

Writer's cramp: A potential early feature of Huntington's disease

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How psychogenic is dystonia? views from past to present

In the last few centuries, there has been a constant sway between organic and psychogenic explanations for dystonia. In the current study, we investigate this history, assuming the perspective of a spectrum from organic to psychogenic, between which ideas were moving. We have focussed on (i) primary generalized dystonia, (ii) cervical dystonia, (iii) writer's cramp and (iv) fixed dystonia related to complex regional pain syndrome. We have studied medical texts published since the 19th century and their references. Jean-Martin Charcot advocated the concept of hysteria, disorders in which, besides predisposition, environmental factors were involved in their pathogenesis. Sigmund Freud introduced psychoanalysis as an explanatory therapy for psychic disorders. Previous theories, together with the lack of an organic substrate for dystonia, made a strong case for psychogenic explanations. Consequently, many dystonia patients were told that they suffered from psychological conflicts and were treated for them. However, after the description of new hereditary cases in the 1950s, the limited efficacy of psychotherapy in torsion dystonia, the effects of surgical treatments and the lesion studies in the 1960s, more physicians became convinced of the organic nature. The culminating point was the discovery of the DYT1 gene in 1997. In the meantime, experts had already convinced the neurological community that cervical dystonia and writer's cramp were focal dystonias, i.e. minor forms of generalized dystonia, and therefore organic disorders. In contrast, the pathophysiology of fixed dystonia related to complex regional pain syndrome remained controversial. Knowledge of this history, which played on the border between neurology and psychiatry, is instructive and reflects the difficulty in discriminating between them. Today, new insights from functional imaging and neurophysiological studies again challenge the interpretation of these disorders, while the border between psychogenic and organic has become more blurred. Abnormalities of sensorimotor integration and cortical excitability that are currently supposed to be the underlying cause of dystonia bring us back to Sherringtonian physiology. We suggest that this may lead to a common explanation of the four afflictions of which we have traced the history.

Prise en charge de la crampe de l’écrivain : 14 ans d’expérience de la toxine botulique

Writer's cramp is a focal dystonia; treatment remains disappointing. We report our 14-year experience with a population of 119 patients aged between 18 and 85 years (average age 43 years). Treatment was based on botulinum toxin injections (Dysport) and physiotherapy. Patients were reviewed every four to six months with clinical and video evaluation by three different observers and subjective analysis of the treatment efficiency by the patient (score of 1 to 3). The post-injection deficit, if present, was also quantified. In the group treated with toxin and physiotherapy, cramps improved (score 2 and 3) in 61.6% of patients; a majority of patients (n=14) reported they were moderately satisfied (score 2). In the group treated with toxin alone, 37.9% of patients were improved (score 2 and 3) with a majority (n=18) very satisfied reporting normal writing (score 3). Age was not a predictor of therapeutic response. Good results were obtained with injections of the flexor carpi radialis followed by flexor digitorum profundus II and III and the flexor pollicis longus. Seventy-one per cent of injections caused moderate muscle weakness, minimally disabling compared to the benefit of injections. Twenty-seven patients were followed for more than two years and three patients, who had achieved score 3 with excellent response, were followed for 14 years with very efficient repeated injections. If the injections were not effective the first time, we re-assessed the situation and adjusted the injections; we considered that toxin treatment was unsuccessful after three injections without benefit. The choice treatment for writer's cramp remains well-targeted injections of botulinum toxin. Physiotherapy is useful when the toxin injections are ineffective in completely improving writing. This requires close cooperation between the injector, the physiotherapist and the patient.

Table tennis dystonia

Focal task-specific dystonia (FTSD) occurs exclusively during a specific activity that usually involves a highly skilled movement. Classical FTSD dystonias include writer's cramp and musician's dystonia. Few cases of sport-related dystonia have been reported. We describe the first four cases of FTSD related to table tennis (TT), two involving professional international competitors. We also systematically analyzed the literature for reports of sport-related dystonia including detailed clinical descriptions. We collected a total of 13 cases of sport-related dystonia, including our four TT players. Before onset, all the patients had trained for many years, for a large number of hours per week. Practice time had frequently increased significantly in the year preceding onset. As TT is characterized by highly skilled hand/forearm movements acquired through repetitive exercises, it may carry a higher risk of FTSD than other sports. Intensive training may result in maladaptive responses and overwhelm homeostatic mechanisms that regulate cortical plasticity in vulnerable individuals. Our findings support the importance of environmental risk factors in sport-related FTSD, as also suggested in classical FTSD, and have important implications for clinical practice.

Expertise with pathological actions modulates a viewer's motor system

Brain mechanisms for action understanding rely on matching the observed actions into the viewer's motor system. Health professionals, who treat patients affected by movement disorders as dystonia, frequently see hyperkinetic action patterns characterized by an overflow of muscle co-contractions. To avert an overload of the motor system during observation of those actions, they might need to look at dystonic motor symptoms in a cool, detached way. To investigate whether visual expertise about atypical movement kinematics influences the viewer's motor system, we applied transcranial magnetic stimulation to clinicians and to naive subjects, while they observed handwriting actions performed with two different kinematics: fluent and non-fluent. Crucially, the latter movement pattern was easily recognized by the clinicians as a typical expression of writer's cramp, whereas it was unknown to the naive subjects. Results showed that clinicians had similar corticospinal activation during observation of dystonic and healthy writings, whereas naive subjects were hyper-activated during observation of dystonic movements. Hyper-activation was selective for the muscles directly involved in the dystonic co-contractions and inversely correlated with subjective movement fluency scores, hinting at a fine-tuned association between the breakdown of observed movement fluency and corticospinal activation. These findings suggest that observation of unusual pathological actions differently modulates the viewer's motor system, depending on knowledge, visual expertise, and ability in recognizing suboptimal movement kinematics.

Functional magnetic resonance imaging in primary writing tremor and writer's cramp: A pilot study.

Objectives:The precise pathophysiology of primary writing tremor (PWT) and writer’s cramp (WC) is not known. The aim of this study is to compare the cerebral activation patterns in patients of PWT, WC and healthy controls, during a task of signing on paper, using functional magnetic resonance imaging (fMRI).Materials and Methods:Six subjects with PWT, three with WC and six healthy volunteers were examined using a 1.5-Tesla scanner. The paradigm consisted of three times repetition of a set of period of rest and activity. Each set consisted of 10 blood oxygen level dependent (BOLD) echo-planar imaging (EPI) acquisitions at rest followed by 10 BOLD EPI acquisitions while signing their names on paper using the dominant right hand. Entire brain was covered. SPM99 analysis was done.Results:In comparison to the healthy controls, the following differences in cerebral activation were noted in the patients: (a) primary and supplementary motor areas showed overactivation in patients of PWT and underactivation in patients of WC, (b) the cingulate motor area showed underactivation in patients of PWT and overactivation in patients of WC and (c) the cerebellar activity was reduced in both WC and PWT.Conclusion:Our preliminary findings suggest that the cerebral and cerebellar activation patterns in PWT and WC during signing on paper are distinct from each other and from healthy controls. There may be cerebellar dysfunction in addition to motor dysfunctions in the pathogenesis of these disorders.

Mutation screening of the DYT6/THAP1 gene in Italy

Mutations in the THAP1 gene on chromosome 8p21-p22 (DYT6 locus) have been recently reported as causative of autosomal dominant primary torsion dystonia (PTD) in four Amish-Mennonite families and in 12 additional probands of different ancestry. We sequenced the THAP1 gene in 158 patients with DYT1-negative PTD who had onset of symptoms below 30 years and/or positive family history. One sporadic Greek male patient, aged 57 years, was found to carry a novel heterozygous missense variant in THAP1 exon 3 (p.Cys170Arg), of likely pathogenic significance. This subject first presented with right writer's cramp at age of 10 years and, subsequently, developed left arm dystonia and an extremely severe left laterocollis, without further spreading to other body districts. Our findings expand the genotypic spectrum of THAP1 and strengthen the association with upper body involvement, including the cranial and cervical districts that are usually spared in DYT1-PTD.

P1.061 Interoceptive mirroring to guide assessment of writer's cramp

P1.061 Interoceptive mirroring to guide assessment of writer's cramp

Paramedical treatment in primary dystonia: A systematic review

Dystonia is a disabling movement disorder with a significant impact on quality of life. The current therapeutic armamentarium includes various drugs, botulinum toxin injections, and occasionally (neuro)surgery. In addition, many patients are referred for paramedical (including allied health care) interventions. An enormous variation in the paramedical treatment is provided, largely because evidence-based, accepted treatment regimes are not available. We have conducted a systematic review of studies that explored the effect of various paramedical interventions in primary dystonia. Only studies that have used clinical outcome measures were included. There were no class A1 or A2 studies and therefore, level 1 or 2 practice recommendations for a specific intervention could not be deducted. Many papers were case reports, mostly with a very limited number of patients and a clear publication bias for beneficial effects of a particular paramedical intervention. Some potentially interesting interventions come from class B studies, which include physical therapy in addition to botulinum toxin injections (BoNT-A) in cervical dystonia; sensorimotor training and transcutaneous electrical nerve stimulation (TENS) in writer's cramp; and speech therapy added to BoNT-A injections in laryngeal dystonia. Good quality clinical studies are therefore warranted, which should have the aim to be generally applicable. A design in which the paramedical intervention is added to a current gold standard, for example, BoNT-A injections in cervical dystonia, is recommended.

Digit‐specific aberrations in the primary somatosensory cortex in Writer's cramp

One approach to the treatment of focal hand dystonia (FHD) is via sensory-based training regimes. It is known that FHD patients demonstrate a reduced distance between the representations of digits 1 and 5 and also digits 2 and 5 in primary somatosensory cortex. However, we lack information on the spatial relationships among digits, such as reduced inter-digit spacing or shifts of representations within the cortical areas, and whether aberrations are specific to symptomatic digits. Our aim was to characterize the spatial relationships among individual digits to determine the types of aberrations that exist and whether these are specific to symptomatic digits only. Using high-resolution fMRI over a limited volume and surface-based mapping techniques, the cortical representations of all digits of the dystonia-affected hand within the sub-regions of the postcentral gyrus were mapped in patients with task-specific Writer's cramp (WC). In area 3b, digits directly involved in writing (D1, D2 and D3) show reduced inter-digit separation, reversals, and overlapping activation. The thumb representation occupies territory normally occupied by digit 2 in controls. Asymptomatic digits 4 and 5 preserve their inter-digit separation yet shift towards the D1/D2/D3 cluster, suggesting that reduced spacing, not simply digit shifts, are associated with dystonia symptoms. Area 3a was less responsive to sensory input in WC patients providing evidence of reduced afferent drive or top-down modulation to this sub-region. Therapeutic regimes aimed at facilitating inter-digit separation of digits 1, 2 and 3 may promote beneficial plasticity in WC patients.

Pathophysiology of dystonia

In the past 18 months, several important studies in neuroimaging, epidemiology of dystonia and animal models have been published. Moreover, new advances in genetics have broadened the spectrum of dystonia. Here, we discuss these findings and their implication in the pathophysiology of dystonia. From neurophysiological studies and animal models, converging arguments support the role of combined corticostriatal, cerebellar and dopaminergic dysfunctions in the pathophysiology of dystonia. A large study in epidemiology identified several risk factors associated with writer's cramp (time spent handwriting each day and the additional burden of an abrupt increase in the writing time in the year before onset). Important studies on the abnormal structure-function relationship in hereditary and sporadic dystonia explored the relationship between genotype, phenotype and endophenotype. Different pathophysiological mechanisms may underlie similar phenotypes whereas different genotypes may share similar functional abnormalities. The respective roles of corticostriatal-cortical and cerebellar loops remain to be clarified as the original causative process (either degenerative or developmental) is accompanied by functional reorganization.

Embouchure dystonia—Portrait of a task‐specific cranial dystonia

Focal task-specific dystonia (FTSD) is an unusual disorder of motor control, which typically affects the hand but may also involve the face, jaw, and tongue. We report 89 musicians with dystonia of the embouchure (ED), the muscles of the lower face, jaw, and tongue used to control the flow of air into the mouthpiece of a woodwind or brass instrument. Symptoms of ED began at an average age of 36, were typically painless and only rarely were preceded by trauma. Specific musical techniques commonly triggered dystonia, often in one instrumental register. Task-specific embouchure tremor and lip-pulling ED phenotypes were common among high-register brass players (trumpet and French horn), whereas lip-locking occurred exclusively in low-register brass players (trombone and tuba). Jaw and tongue ED phenotypes occurred predominantly in woodwind players, and once present, frequently spread to speaking or eating. Six percent of all ED patients had coincident writer's cramp, suggesting a possible genetic predisposition to develop dystonia. We assessed two-point sensory discrimination in the upper lip, lower lip, and hand in ED patients, normal musicians, and nonmusician age-matched controls--there were no differences between groups. Once present, symptoms of ED did not remit and often disrupted careers and livelihoods. Better treatments are urgently needed for this unusual disorder of oral motor control.