Botulinum neurotoxin for writer’s cramp: A systematic review and illustrated guide

Divyani Garg; Suvorit S Bhowmick; Jacky Ganguly; Shivam O Mittal; Rupam Borgohain; Prashanth L Kukkle

doi:10.4103/AOMD.AOMD_27_22

REVIEW ARTICLE

Year : 2022 | Volume : 5 | Issue : 3 | Page : 159-177

Botulinum neurotoxin for writer’s cramp: A systematic review and illustrated guide

Divyani Garg¹, Suvorit S Bhowmick², Jacky Ganguly³, Shivam O Mittal⁴, Rupam Borgohain⁵, Prashanth L Kukkle⁶
¹ Department of Neurology, Vardhman Mahavir Medical College and Safdarjung Hospital, New Delhi, India
² Movement Disorders Clinic, Vadodara Institute of Neurological Sciences, Vadodara, Gujarat, India
³ Movement Disorders Clinic, University of Western Ontario, London, Ontario, Canada
⁴ Movement Disorders Clinic, Cleveland Clinic, Abu Dhabi, United Arab Emirates
⁵ Department of Neurology, Nizam’s Institute of Medical Sciences (NIMS), Hyderabad, Telangana, India
⁶ Center for Parkinson’s Disease and Movement Disorders, Manipal Hospital, Bengaluru, Karnataka, India; Parkinson’s Disease and Movement Disorders Clinic, Bengaluru, Karnataka, India

Date of Submission	12-Jun-2022
Date of Decision	01-Jul-2022
Date of Acceptance	01-Aug-2022
Date of Web Publication	14-Dec-2022

Correspondence Address:
Prashanth L Kukkle
Center for Parkinson’s Disease and Movement Disorders, Manipal Hospital, Millers’ Road, Bengaluru, Karnataka
India

Source of Support: None, Conflict of Interest: None

DOI: 10.4103/AOMD.AOMD_27_22

Abstract

Writer’s cramp (WC) is a focal task-specific dystonia that affects the fingers, hands, and forearms. It interferes with an individual’s ability to write, causing professional disability. In this systematic review, we discuss the epidemiology, pathophysiology, clinical features, and management of WC. In accordance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines, we included publications until February 5, 2022, from the PubMed database. In addition, we elaborate on the clinical assessment and selection of appropriate muscles for botulinum neurotoxin therapy through pictorial illustrations. The prevalence of WC is underestimated because medical attention is only sought by those with professional disability. The clinical presentation of WC is heterogeneous. In some patients, dystonia is manifested only during writing tasks (simple WC), while in others, several manual tasks are affected in addition to writing (complex WC). Some patients have semirhythmic movements of the hand with no apparent postural abnormality during writing (writing tremor). The assessment of the pattern of dystonia is confounded by the compensatory movements a patient adopts while writing. There are several pharmacological, nonpharmacological, and surgical options for the management of WC. However, there are no randomized controlled trials supporting the efficacy of oral medications. The efficacy of physiotherapy, occupational therapy, and noninvasive brain stimulation is debatable. Neurosurgical procedures, although reportedly effective, are seldom justified in focal task-specific dystonia. Botulinum neurotoxin is considered an effective treatment option based on several prospective studies and few randomized controlled trials. However, WC may be the most challenging indication for this therapy because writing is a complex manual task. Furthermore, given the heterogeneity, clinicians often face difficulties in discerning the exact abnormality and selecting the appropriate muscles for treatment.

Keywords: botulinum toxin, systematic review, task-specific dystonia, writer’s cramp

How to cite this article:
Garg D, Bhowmick SS, Ganguly J, Mittal SO, Borgohain R, Kukkle PL. Botulinum neurotoxin for writer’s cramp: A systematic review and illustrated guide. Ann Mov Disord 2022;5:159-77

How to cite this URL:
Garg D, Bhowmick SS, Ganguly J, Mittal SO, Borgohain R, Kukkle PL. Botulinum neurotoxin for writer’s cramp: A systematic review and illustrated guide. Ann Mov Disord [serial online] 2022 [cited 2023 May 30];5:159-77. Available from: https://www.aomd.in/text.asp?2022/5/3/159/363464

Divyani Garg and Suvorit S. Bhowmick both are Equal contributors

Introduction

Writer’s cramp (WC) is a focal task-specific dystonia (FTSD) characterized by involuntary and excessive contractions of the muscles of the upper extremities, resulting in abnormal movements or postures of the fingers, hands, forearms, and arms (in some patients), when attempting to write.^[1] In the first section, we provide an overview of the history, epidemiology, pathophysiology, clinical features, and management of WC. Our emphasis is on the treatment of WC with botulinum neurotoxin (BoNT). The subsequent sections address its administration, with illustrations.

Search Methodology

A systematic search of the PubMed database was conducted and publications until February 5, 2022, were included in our study. Our study follows the Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines for transparent and complete reporting of systematic reviews. Separate searches were independently conducted by two authors (JG and PLK) using the keywords “Writer’s Cramp” [tiab] OR “Writer Cramp” [tiab] OR “Writers Cramp” [tiab]. Publications in English and involving human patients were shortlisted. All types of publications such as case reports, case series, observational studies, retrospective studies, prospective studies, controlled trials (randomized/nonrandomized), and consensus statements or guidelines were included. Additional relevant articles from cross-references were included. Studies on animal models or other medical disorders, non-English articles, and reviews were excluded. The studies individually narrowed down by each author (JG and PLK) were downloaded into the Zotero bibliographic software, following which both authors screened the titles or abstracts of the publications together to select appropriate articles. Any discordance between the two authors regarding the inclusion of studies was resolved by the other authors (DG and SSB). A total of 214 articles were shortlisted and individually reviewed ([Figure 1], [Supplement 1]).

Figure 1: Preferred Reporting Items for Systematic Reviews and Meta-Analyses flowchart

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Writer’s cramp: Review

Historical recap

Although the term “dystonia” was first used by Oppenheim in 1911, the clinical phenomenon was noted at least two centuries earlier. Ramazzini is accredited with providing the first account of WC in the revised edition of his seminal work on occupational medicine, De Morbis Artificum Diatriba (Diseases of Workers, 1713); he deduced that scribes and notaries were affected by constant writing.^[2] WC was reportedly prevalent among the brush writers of ancient China.^[3] While reporting on an epidemic of WC among the British Civil Service clerks, in 1830, Bell provided an apt description of the condition as we presently recognize. The increasing prevalence of WC was attributed to the advent of the steel nib, which replaced the quill. In the 19th century, similar features in the upper extremities were identified in several occupations; they were grouped as occupation neuroses or craft palsies. In the early 20th century, several physicians considered craft palsies as psychogenic disorders. For example, Pai^[4] classified WC as tremulous, ataxic or jerky, and paralytic in 171 patients with abnormal handwriting among 1880 patients with neuropsychiatric symptoms. He concluded that paralytic WC, characterized by slovenly and illegible writing, was a manifestation of organic disorders of the central nervous system, and the remaining cases had a psychogenic basis.^[4] Through the efforts of Marsden, the psychogenic notion was quelled and WC was established as a type of focal dystonia.^[5],[6]

Epidemiology

Systematic epidemiological studies on WC are not available, and most of the data is either from specialized clinics or published case series. WC is underreported as medical attention is only sought by those with professional disabilities. Approximately, half of the patients with WC report writing as an essential part of their profession.^[7] The pooled prevalence of WC from several service-based studies was 16.5 per 100,000.^[8] The crude prevalence of WC in a community survey of isolated dystonia in Kolkata, India, was 21.0 per 100,000.^[9] WC is commonly reported by men. Soland et al.^[10] reported a male:female ratio of 2:1. The onset of symptoms usually occurs in the fourth decade ([Table 1]).

Table 1: Demographic and clinical profile of writer's cramp

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Pathophysiology

The pathophysiological process and postulation of WC is based upon decreased inhibition, maladaptive plasticity, aberrant somatotopy, impaired sensory processing, impaired sensory–motor integration, and motor network abnormalities in the central nervous system [Figure 2]. Genetic susceptibility possibly nurtures this fertile background in individuals who spend considerable time writing.^[11]

Figure 2: Schematic diagram showing the pathophysiology of writer's cramp

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Loss of inhibition

Transcranial magnetic stimulation (TMS) studies showed reduced short-interval intracortical inhibition and a shortened cortical silent period in WC.^[12],[13] The lack of surround inhibition leads to loss of selectivity in muscle recruitment for a particular task (e.g., writing) and unnecessary activation of the neighboring muscles. Impaired reciprocal inhibition manifests as co-contraction of antagonist muscles.^[14],[15]

Maladaptive plasticity and aberrant somatotopy

Abnormal neuroplastic responses in the motor and sensory cortices were noted in conditioning protocols using TMS. Patients with WC exhibited abnormal responses to paired associative stimulation of the median nerve and primary motor cortex, with increased facilitation that included the non-median nerve innervated muscles.^[16] Functional neuroimaging and somatotopic mapping showed abnormal cortical representation of the digits (unilateral or bilateral) and reorganization of the sensory homunculus in FTSD.^[17],[18] Repetitive sensory input from writing possibly results in enlargement of the tactile receptive field, and consequently, motor dysfunction.^[11],[19]

Impaired sensory–motor integration

Magnetoencephalographic recordings in FTSD showed uncoupling of the primary sensory and motor areas, resulting in inefficient sensory–motor control during motor execution.^[20] Abnormal sensory processing in WC can interfere with proper recruitment of the motor program. Abnormalities in movement preparation such as planning and processing lead to the generation of a “faulty motor program” in FTSD.^[21],[22] On switching the task to the opposite (unaffected) hand, intact sensory feedback initially counteracts the faulty program. With sustained activity and the resulting limb-specific refinement of the program, dystonic posturing during writing may appear in the initially unaffected hand. Furthermore, abnormal activation of the brain postural system possibly plays an important role in FTSD.^[23] Tasks such as writing require coordination and fine-tuning of several individual movements to achieve maximum speed and precision. Errors in the motor program can trigger overactivation of the “movement-controlling postural signals,” leading to the “excessive dynamic postures” of WC.^[22] In addition, patients with WC are unable to correctly predict the temporal characteristics of the writing movement.^[21] Abnormal processing of the time-dependent components of the movement may be responsible for this inability.

Abnormal motor network

Abnormalities in the motor network involving the basal ganglia and cerebellum are implicated in FTSD.^[24] Some authors have noted that the availability of dopamine receptors and dopamine release is decreased in the striatum during task activation in WC. There is evidence of abnormal cerebellar activation in patients with WC.^[25],[26] It has been proposed that the representation and reproduction of motor skills are deranged in WC due to compensatory mechanisms of a healthy motor system.^[27]

Genetic susceptibility

Family history of dystonia is reported in up to 10% of the affected individuals. In the pediatric age group, WC can be a presenting feature of inherited dystonia. Because of reduced penetrance and occurrence of de novo mutations, there is often no family history. Patients with mutations in the TOR1A (DYT1), SGCE (DYT11), GCH1 (DYT5), PRRT2 (DYT10), PRKRA (DYT16), CACNA1H, ATXN3 (SCA3), CACNA1A (SCA6), and ADCK3 genes may manifest WC.^{[28],[29],[30],[31],[32],[33],[34],[35],[36],[37]} DYT1 should be suspected, if patients with early-onset WC have spread of dystonia, and if patients have combined dystonia myoclonus, DYT11 should be considered.^[30] If combined WC and ataxia is present, coenzyme Q¹⁰ deficiency (autosomal recessive cerebellar ataxia type 2) from biallelic pathogenic variants in the ADCK3 gene should be investigated, irrespective of age of onset, especially if there is familial clustering of WC.^[37] WC was reported in familial dystonia with a hitherto unknown specific gene abnormality, such as DYT7 and DYT13.^[38],[39]

Clinical features

The clinical description of WC emanates from several large observational studies summarized in [Table 1].^{[1],[4],[7],[10],[40],[41],[42],[43],[44],[45]} However, many smaller case series and case reports are available in the literature [Supplement 2]. Affected individuals usually present with insidious onset and progressive cramp, ache, or stiffness of the fingers and hand while writing. In addition, the forearm and arm may be involved. Some patients complain of struggle while writing, clumsiness, freezing, tremor, deterioration in neatness or speed of writing, or difficulty in holding a pen. Examination often shows difficulty in holding a pen and dystonic posturing of the hand. The posturing usually increases as the patient continues writing and may spread to proximal parts of the upper extremity. Besides distorted posture, there is slowing and loss of normal fluidity of movement. In some patients, posturing is subtle and difficult to identify by careful inspection.^[7]

WC can be classified as flexor, extensor, or combined pattern; focal or generalized; and simple or complex. Flexor and extensor WC refer to involvement of the flexor and extensor muscles, respectively. Focal or localized WC indicates involvement of up to three fingers of the same hand, whereas generalized or nonlocalized WC indicates involvement of more than three fingers of the same hand or both hands.^[42],[46] WC is classified as simple when dystonia affects only the writing task and complex when patients experience difficulty predominantly in writing as well as additional activities, such as typing, shaving, eating, etc. “Complex WC” is preferred over the former term “dystonic WC,” which may imply that the nature of simple WC is not dystonic.^[1],[7] While some patients report clear progression of WC from simple to complex (progressive WC), several others do not recall if writing and other tasks were simultaneously affected.^[1],[7] Impairment of legibility and quality of drawing is similar in patients with simple and complex WC.^[7] Dystonia may spread to the neck or the opposite upper extremity; thus, it becomes segmental dystonia in some patients. WC may precede or follow other dystonic features. Furthermore, it may be a component of multifocal or generalized dystonia. Finally, some patients exhibit rhythmic or semirhythmic movements of the hand and forearm during writing (primary writing tremor) with no apparent postural abnormality. It is debated whether these abnormal movements should be classified as a subtype of dystonia (e.g., dystonic tremor), essential tremor, or a completely distinct entity.^[47] Thus, WC has a heterogeneous clinical presentation.

Approximately, 25% of the patients develop WC in the nondominant hand when they learn to write with it. In patients with WC, the abnormal posture may be due to dystonia or compensatory movements adopted by the patient. Mirror dystonia is helpful in differentiating between the two (see section Botulinum Neurotoxin Injection: An Illustrated Guide), although they are observed in only approximately 50% of the patients.^[7] Borgohain et al.^[48] highlighted the concept of concordant and discordant mirror dystonia, which Singer et al.^[49] corroborated subsequently. When mirror movements yield the same dystonic posture as primarily observed, they are called concordant. When mirror dystonic movements yield a different posture, they are called discordant. Rama Raju et al.^[50] investigated electrophysiological differences in patients with concordant and discordant mirror dystonia. Among the 12 patients evaluated, they noted remarkable quantifiable differences in electromyography (EMG) signals in these groups. The authors speculated that the discordant group had a compensatory force, which overcame the dystonic force, resulting in the final abnormal posture.

Evaluation

Evaluation of WC includes appropriate history, thorough clinical examination, and certain auxiliary techniques (see section Botulinum Neurotoxin Injection: An Illustrated Guide and [Video 1 [Additional file 1]]. Several scales are used to assess the severity of WC, including the Writer’s Cramp Rating Scale (WCRS), Arm Dystonia Disability Scale (ADDS), and Burke–Fahn–Marsden dystonia and disability scale.^[51]

Therapeutic strategies

Pharmacological options

Oral medications

To date, no randomized clinical trial (RCT) has evaluated the efficacy of oral medications for WC. The response to treatment is variable and ranges from 10% to 20% for anticholinergic agents. The following medications are commonly used: trihexyphenidyl (anticholinergic, 6–100 mg/day), baclofen (GABA_B receptor agonist, 30–120 mg/day), clonazepam (GABA_A receptor agonist, 1–6 mg/day), and tetrabenazine (dopamine depleting agent, 25–100 mg/day). The maximum dose of these medications is limited by their adverse effects.^[52]

Botulinum neurotoxin therapy

BoNT injection is the mainstay in the treatment of WC.^[53],[54] Several early case reports and case series, followed by open-label studies, and few placebo-controlled RCTs have demonstrated an improvement in legibility, speed of writing, and pain in patients treated with BoNT ([Table 2]). For example, Borgohain et al.^[55] reported functional improvement in 94% (marked or striking in 47%) of the patients with WC (n = 33) in an open-label study. However, the lack of reliable and reproducible objective scales, the subjective nature of the assessment, variable injection dose and patterns, and heterogenous study populations in different studies make prediction of the outcome difficult. Approximately, 50-75% of the patients with WC respond favorably to BoNT; however, the response rate is low compared to blepharospasm and cervical dystonia. The response is usually better after subsequent injections as the initial dose is purposefully kept low to avoid hand weakness, by several injectors. Long-term follow-up data are limited. In an open-label extension of a double-blind placebo-controlled RCT, 20 out of 39 patients (51%) were receiving BoNT therapy, with positive results at the 1-year follow-up.^[56] Karp et al.^[57] followed-up 37 patients with focal hand dystonia for more than 2 years to study its long-term effects. Approximately, one-third of the patients (12 with WC) continued to receive injections with good-to-excellent benefits for a mean of 3 years (range, 2–6 years). Despite the benefits, five patients could not pursue the treatment because of inaccessibility or cost. Others discontinued the injections because of inadequate response or loss of response. Lungu et al.^[58] reported the longest follow-up of BoNT therapy in patients with focal hand dystonia. Approximately, 9% of the patients (20 out of 214, majority with WC) continued BoNT therapy for 10 years. None of them developed immunity to the toxin. The inter-injection interval was variable because the patients often timed the injections based on their anticipated activities. Approximately, two-third of the patients discontinued injections due to insufficient response.

Table 2: Summary of studies on botulinum neurotoxin for the treatment of writer's cramp

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It is not uncommon for a patient to be dissatisfied with the degree of benefit because BoNT injection does not provide relief from all the symptoms of dystonia, especially loss of speed and coordination.^[59] The long duration of the illness, progressive dystonia, secondary dystonia, and dystonic tremor are considered poor prognostic indicators of therapy.^[60] Weakness of the fingers or hand is a common, albeit temporary, side effect.

There are several commercially available BoNT formulations for patients with WC. Data on their efficacy and safety are available for onabotulinumtoxinA and abobotulinumtoxinA. However, there are no trials comparing the efficacy of these two formulations. In addition, there is limited published data on incobotulinumtoxinA and rimabotulinumtoxinB for WC.^{[53],[54],[61],[62]}

Non-pharmacological options

Sensory training

Sensory training presumably improves spatial discrimination, which enables the patients to selectively engage their muscles during the writing task. A study (n = 10) showed that daily sessions of braille reading improved the Fahn dystonia scale scores and time taken to write a paragraph after 8 weeks.^[63] Three patients who continued braille training for 1 year had further improvement in paragraph writing and self-reported scale scores.^[64]

Motor training

Some studies have demonstrated the benefit of retraining of the finger movements in WC through exercise, which could be task-specific or otherwise.^[65],[66] A study (n = 21) showed that both putty-based finger exercises and tasks involving writing or drawing with a pen attached to a finger splint led to remarkable improvement in the WCRS scores after 8 weeks.^[66] Task-specific retraining is demanding and requires occupational therapists; moreover, the margin of improvement is questionable. An RCT (n = 12) did not show improvement in the subjective scale at 20 weeks, with occupational therapy in addition to the BoNT therapy.^[67]

Detraining

Limb immobilization is based on the suggestion that inactivity may stimulate neuroplasticity, attenuating overactive cortical regions. However, modest benefit in dystonia rating scores was counteracted by undesirable side-effects such as joint pain, edema, and hand weakness.^[68],[69]

Ergonomic alterations in writing

Patients often change their grip on pens or use thicker pens to alleviate discomfort.

Surgical options

Neurosurgical procedures for WC are rarely justified, given the limited disability and potential risks. Nevertheless, contralateral thalamotomy, pallidotomy, and thalamic or pallidal deep brain stimulation (DBS) are therapeutic options for patients with refractory WC and marked occupational disability.^{[70],[71],[72],[73]} The preferred target for ablation or stimulation is the ventro-oral (Vo) thalamic nucleus complex, comprising the ventralis oralis anterior and posterior nuclei of the thalamus in the pallidothalamic and cerebellothalamic pathways, respectively.^[74] The choice of surgical procedure is debatable, particularly in young patients in whom the risk of permanent side effects needs to be balanced with long-term implant management, battery replacement, hardware complications, and cost.

Stereotactic lesioning

Horisawa et al.^[75] reported the long-term efficacy of Vo thalamotomy in 171 patients with FTSD (92 patients with WC). The task-specific focal hand dystonia scale was remarkably better in 72 patients who were followed-up for approximately 4 years. Permanent (3.5%) or temporary (16.4%) adverse events included dysarthria, weakness, dysesthesia, and impaired verbal recall.^[75],[76]

Deep brain stimulation

Unlike ablative procedures, DBS does not create irreversible lesions. Vo and the ventral intermediate thalamic nuclei, as well as the globus pallidus interna, were successful DBS targets in few patients with WC.^[77],[78]

Magnetic resonance-guided focused ultrasound (MRgFUS) thalamotomy

Horisawa et al.^[79] recently reported improvement in dystonia rating scales at 12 months in a pilot study of WC (n = 9) treated by MRgFUS thalamotomy. The WCRS and ADDS scores improved from 6.3 ± 2.7 and 58.7% ± 14.3% at baseline to 1.6 ± 3.1 (p = 0.011) and 81.6% ± 22.9% (p = 0.0229), respectively. Adverse events included transient facial palsy (n = 2), transient dysarthria (n = 3), and persistent dysarthria (n = 1). MRgFUS is a less invasive procedure than lesioning. If long-term efficacy and safety are established, it may be an asset in the management of WC.

Non-invasive brain stimulation

Repetitive transcranial magnetic stimulation (rTMS)

Low frequency (<1 Hz) rTMS decreases cortical excitability, driving investigators to study its short-term effect on WC.^[80] In an open-label study (n = 16), half of the patients reported moderate-to-marked improvement in handwriting, lasting at least 3 hours following a single session of biphasic 1-Hz rTMS over the contralateral motor cortex.^[81] There was remarkable reduction in the mean writing pressure. Electrophysiological evaluation showed normalization of the deficient corticocortical inhibition and prolongation of the silent period. In a single-blind sham-controlled trial (n = 9), remarkable improvement was observed in handwriting (tracking error and pen pressure) and prolongation of the silent period with 0.2-Hz monophasic rTMS over the contralateral premotor cortex but not the motor cortex.^[82] Subsequent studies using different parameters showed that the premotor cortex could be a promising target for rTMS.^[83],[84] In a double-blind crossover study, subjective and objective improvement was observed in writing at 2 weeks with 1-Hz rTMS over the sensory cortex for 5 days.^[85] Despite these positive findings, the duration of therapy needed to sustain notable clinical benefit remains unknown.

Transcranial direct current stimulation (tDCS)

Few studies that explored the therapeutic efficacy of short-term tDCS did not find changes in neurophysiology that may lead to clinical benefits.^[86] In a randomized sham-controlled trial (n = 12), no improvement was observed in ADDS and kinetic parameters of writing with 2-mA cathodal tDCS of the contralateral motor cortex.^[87] Moreover, subjective worsening noticed by some patients led to premature termination of the trial. While previous studies showed that weak cathodal tDCS decreases excitability of the motor cortex, there was no modulation of short-interval intracortical inhibition through stimulation. Cerebellar stimulation appeared to be promising as it could reduce plasticity responses of the motor cortex and increase cerebellar brain inhibition. However, studies utilizing 2-mA anodal tDCS of the cerebellum failed to demonstrate any clinical benefit. In a double-blind sham-controlled crossover trial (n = 10), no improvement was observed in the WCRS scores, timed writing, and subjective rating.^[88] The plasticity responses to paired associative stimulation were variable in the patients. Subsequently, a double-blind cross-over trial (n = 8) showed improvement in some kinematic measures; however, there was no correlation between the change in cerebellar brain inhibition and improvement.^[89]

Botulinum Neurotoxin Injection: An Illustrated Guide

Assessment of a patient with writer’s cramp

It is often difficult to determine the movements that are dystonic and those that are part of the normal writing pattern. Meticulous clinical assessment is indispensable to appropriate muscle selection for BoNT injection. The salient points are mentioned below.

History

In addition to noting the duration of the symptoms, precipitating events such as trauma or emotional stress, and family history of dystonia or other movement disorders, the clinician should ask the patient to describe the abnormal movements or postures in detail. Furthermore, the clinician should be mindful of task specificity, noticeable differences with the type of pen, surface, or writing style, and maneuvers (e.g., sensory tricks) to alleviate the abnormal movements or posture. The patient may be able to convey the direction of the movement distortion and perceived area of involvement.^[90] In addition, it should be noted that patients with overuse syndrome (due to tenosynovitis) and ulnar or median entrapment neuropathy may complain of discomfort while writing.^[59]

Clinical examination

The patient should be positioned in a standard manner: seated on a chair placed close to a table, and a paper should be placed on the table. This prevents the patient from adopting a compensatory position while writing ([Video 1], [Figure 3], [Supplement 3] [Supplement video 1). The clinician should observe the predominant pattern of WC (flexor, extensor, or combined) and classify it as simple or complex and focal or generalized. It is helpful to examine the posture of the fingers and hand at rest, while outstretched, while holding a pen, and while writing and note if tremor is present in these postures. The presence of tremor while hovering over an “X” mark on the paper indicates wrist flexion dystonic tremor, and inability to keep touching the “X” mark indicates wrist extension dystonic tremor. Muscles that contract abnormally are often painful. As a result, writing is interrupted to relieve the pain or to enable repositioning of the grip. The patient should be instructed to write a standard paragraph continuously. For example, “Swami and his Friends” by RK Narayan (Malgudi Days, introductory paragraph) was used in the dissertation of Sivadasan A.^[91] This paragraph contains some words that are not easy to comprehend and may initiate psychological stress in patients with WC and aggravate the disability. Several studies have used standard sentences such as “Today is a bright and sunny day,” and sentences in the local dialect. A standard paragraph in a language easily comprehensible by the patient is suitable for assessment. Use of excessive pressure on the paper suggests flexor pattern, whereas light pressure or faint writing suggests extensor pattern dystonia. Sensory tricks may be employed to improve the flow of writing. These may be implement-based, such as the use of a thicker pen or a different nib shape, holding the pen in a particular posture, changing the angle of the paper, and touching the hand or the forearm.

Figure 3: A sample writer's cramp assessment sheet

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The wrist is usually slightly flexed at the beginning of a sentence and then extends as the hand moves across the paper in a right-handed individual. In contrast, the wrist is more flexed at the beginning of a sentence in a left-handed individual. The writing hand should be observed from several angles to understand the abnormal posture. The clinician should note the presence of pronation or supination of the forearm, in addition to deviation of the wrist and fingers.^[90]

A major challenge for the clinician is determining if the abnormal posture exhibited by the patient while writing is true dystonia or a compensatory posture. Compensatory movements or postures involving the wrist, elbow, shoulder, and/or the trunk are voluntary to facilitate the writing task; therefore, muscles responsible for such movements should not be injected. For example, a patient with flexor WC may abduct the shoulder to write. The patient should be instructed to avoid compensatory postures so that the actual dystonia can be revealed. Another method is to check mirror movements of the affected hand while writing with the unaffected one.^[7],[49] For example, if the affected hand that initially assumes a flexed posture while writing clearly extends while observing mirror dystonic movements (discordance), then the pattern of WC should be labeled as extensor. In a series of 27 patients (published as an abstract), Borgohain et al.^[48] found that discordant mirror dystonia was predominantly observed in wrist flexor-type (90.1%) WC, while concordant mirror dystonia was observed in both wrist flexor-type (37.5%) and extensor-type (50.0%) WC (p = 0.0017). There was no difference in outcome between the patients with concordant and discordant movements when muscles were injected based on mirror dystonic movements. Therefore, this maneuver is useful in unmasking true dystonia.

Finally, the clinician should note the involvement of the opposite hand, abnormal posture, or tremor during other tasks such as holding a glass or cup-pouring tasks. In addition, he should note whether the dystonia is truly focal or segmental (e.g., neck or laryngeal involvement along with the upper limbs).

Auxiliary assessment

Wire EMG may be helpful if BoNT therapy fails or if the abnormal movements are difficult to interpret. EMG records from customized wires inserted into multiple muscles during the activation of dystonia provides additional information on the involvement of muscles not obvious on clinical examination.^[57],[90] It may be possible for the clinician to tailor the injection patterns using supplementary information from kinematic analysis of hand movements during writing.^[92],[93] Multisensor-based kinematic analysis records finger and wrist forces along with deviation angles at the wrist, elbow, and shoulder while patients perform a series of standardized tasks, such as hovering the pen over a fixed dot for 30 seconds, small and large counterclockwise spiral drawing, small and large clockwise spiral drawing, writing a standard sentence (“today is a bright and sunny day”), and left-to-right sinusoid tracing (low frequency, high amplitude; high frequency, high amplitude; low frequency, low amplitude; high frequency, and low amplitude). Temporary improvement with intramuscular lidocaine has the potential of guiding muscle selection.^[94] At present, there is no evidence whether muscle selection based on these methods results in better outcomes.

Injection technique

BoNT may be injected with the knowledge of anatomical landmarks and palpation of muscles. However, this technique has less reliability and higher risk of causing hand weakness than guided techniques because muscles in the forearm are in proximity to each other. Inaccuracy of muscle localization without EMG was demonstrated in a study, in which the needle reached the intended target in only 37% of the attempts.^[95] Ultrasound, EMG, and electrical stimulation may be utilized to guide needle placement in the intended muscle. EMG guidance is the preferred technique by most clinicians as ultrasound requires additional expertise and equipment. Electrical stimulation is helpful in isolating the individual finger flexors. There is no evidence on the superiority of a guidance technique; a trial comparing guidance techniques in focal dystonia (Clinical Trials identifier NCT02334683) is ongoing.

Treatment with BoNT relies on recognizing the muscles that are responsible for different patterns of dystonia and thorough knowledge of the anatomy of the upper extremities. Injecting all the muscles that contribute to the abnormal posture may not be necessary. The main muscles are injected in the first session. Muscle selection is refined in the subsequent sessions based on benefit, patient satisfaction, and adverse effects.^[90] Information on individual muscles and injection techniques is shown in [Table 3] and [Figure 4][Figure 5][Figure 6][Figure 7].

Table 3: Muscles injected for the treatment of writer's cramp

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Figure 4: Patterns of writer's cramp: (a) focal flexor pattern, (b) wrist and finger flexor pattern, (c) focal extensor pattern, (d) wrist extensor pattern

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Figure 5: Injection technique for the finger and wrist flexors: (a) flexor pollicis longus and brevis, (b) flexor pollicis longus injection technique, (c) flexor digitorum superficialis,
(d) flexor digitorum superficialis injection technique, (e) flexor digitorum profundus, (f, g) flexor digitorum profundus injection techniques, (h) flexor carpi ulnaris and radialis, (i)
flexor carpi ulnaris injection technique, (j) flexor carpi radialis injection technique

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Figure 6: Injection technique for the finger and wrist extensors and the forearm pronators and supinator: (a) extensor indicis proprius; (b) extensor indicis proprius injection
technique; (c) extensor digitorum communis; (d) extensor digitorum communis injection technique; (e) extensor carpi ulnaris; (f) extensor carpi ulnaris injection technique; (g)
extensor carpi radialis longus and brevis; (h) extensor carpi radialis longus injection technique; (i) pronator teres, pronator quadratus, and supinator; (j) pronator teres injection
technique; (k) pronator quadratus injection technique; (l) supinator injection technique

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Figure 7: Injection technique for the thumb abductors and extensors: (a) abductor pollicis longus, (b) abductor pollicis longus injection technique, (c) abductor pollicis brevis,
(d) abductor pollicis brevis injection technique, (e) extensor pollicis longus and brevis, (f) extensor pollicis longus injection technique

Click here to view

Flexor pattern

Focal flexor pattern

There is abnormal flexion of the thumb or index finger or both while writing ([Figure 4a]). The flexor pollicis longus (FPL) and brevis are involved in thumb flexion. Individual fascicles of the flexor digitorum superficialis (FDS) and profundus are responsible for proximal and distal finger flexion, respectively.

Generalized flexor pattern

The patient’s wrist tends to flex while writing ([Figure 4b]). The flexor carpi radialis and flexor carpi ulnaris are involved in radial and ulnar deviation, respectively, of the wrist in addition to flexion. Usually, there is abnormal flexion of the digits. There may be pronation of the forearm.

Extensor pattern

Focal extensor pattern

In this pattern, dystonia is usually restricted to a single extensor muscle ([Figure 4c]). This pattern is usually due to the involvement of the extensor indicis proprius (EIP) and extensor pollicis longus.

Generalized extensor pattern

In this pattern, the entire hand extends on writing ([Figure 4d]). Compensatory actions include flexion of the fingers to maintain pen grip and adduction of the proximal arm.

Botulinum Neurotoxin Dosage for Muscles

The dosage of BoNT for WC is highly variable. A wide range of doses is effective for similar muscles in different patients ([Table 4]). There appears to be no correlation between the dose injected and the extent of benefit. Some patients with excellent outcomes respond to an onabotulinumtoxinA dose as low as 2.5 U, whereas others have minimal or no response to a dose as high as 80 U. Similarly, there is no correlation between the dose used and the duration of benefit.^[57] In general, men may need a higher dose of BoNT compared to women. The number of muscles injected is usually two per session, but it may range from 1–4 muscles.^[96]

Table 4: Dosage of botulinum neurotoxin in different
muscles

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Rivest et al.^[97] reported that the degree of weakness needed to control dystonic spasms in a given muscle remarkably varied among patients. In this study (n = 12), the mean abobotulinumtoxinA dose for the finger flexors, finger extensors, wrist flexors, and wrist extensors was 69.2 U (range, 40–180 U), 56.6 U (range, 40–80 U), 110.0 U (range, 80–120 U), and 104.0 U (range, 80–120, U), respectively ([Table 2]). Karp et al.^[57] reported that the mean onabotulinumtoxinA dose required to achieve a moderate or excellent outcome was lower in women (16 ± 3 U) than in men (30 ± 5 U). Most of the patients had two muscles injected per session in this study (n = 53; WC, 32; musician dystonia, 19), with a mean dose of 26 ± 2 U (range, 2.5–160 U). Therefore, the BoNT dose should be decided based on the bulk of the muscles.

Wissel et al.^[96] conducted a study (n = 31) on abobotulinumtoxinA for WC, where the mean dose injected per session was 133.2 U (range, 40–240 U), divided between 1–4 muscles ([Table 2]). The most commonly injected muscles were the flexor carpi ulnaris (n = 57) and flexor carpi radialis (n = 30), FDS II and III (n = 49), FPL (n = 28), and the extensor carpi ulnaris (n = 32). Patients in the active arm (n = 20) of an RCT received a mean abobotulinumtoxinA dose of 102 U (range, 30–220 U). The patients were given an additional 75 U (range, 0–240 U) at 1 month, if the response was not satisfactory. The most commonly injected muscles included FPL, flexor digitorum profundus, and EIP.^[56]

Tricks and Pitfalls of Botulinum Neurotoxin Therapy

Injectors should be aware of the tricks and pitfalls of BoNT therapy to avoid its side effects. EMG guidance is essential for accurate BoNT injection in the forearm. A double concentration (1:2 dilution) of BoNT is preferred in some centers to avoid the spread of the toxin to the neighboring muscles.^[98] Finger drop is a common side effect of forearm injection. The supinator is a deep muscle wrapping the radius, and it requires the needle to go deep and reach the bone. If injected superficially, it may result in finger drop due to weakness of the extensor digitorum communis. Some muscles on the extensor surface are in the radio-ulnar groove but on the ulnar aspect, and from distal to proximal, they are EIP, extensor pollicis brevis, extensor pollics longus, and abductor pollicis longus. Accurate anatomical landmarking for these muscles (as discussed in this review) is important to avoid finger drop. It is important to accurately inject FDS because of its anatomical complexity. FDS fibers for the third and fourth fingers are proximal and superficial (see [Table 3] and [Figure 5]). FDS for the fifth finger is deeper. FDS for the second finger is bit distal and lateral. FDS for the fifth finger is in the same spot but deeper. In contrast, FDS for the second finger is distal and lateral to that spot. In WC, injecting individual fibers of FDS, depending on the finger involved, improves efficacy and avoids unnecessary weakness of the other fingers. While injecting the long flexors and extensors of the fingers, clinicians should target the main muscle belly where neuromuscular junctions are abundant and not the tendinous part. However, after several sessions of injections, muscle atrophy can occur. Therefore, the injector should be extremely cautious in selecting the right spot with EMG guidance.

Conclusions

There are several knowledge gaps in WC, such as the influence of primary written language and excessive use of devices such as mobile phones, touchpads, and laptops. In addition, differentiating between dystonic and compensatory movements the pattern and dose of BoNT, utility of kinematics, EMG, mirror dystonic movements in guiding muscle selection for BoNT, long-term benefits of noninvasive brain stimulation and choice of surgical therapy in refractory cases should be explored. WC often limits work and causes pain, embarrassment, and low self-esteem. Several patients prefer to remain untreated, because the treatment is not satisfactory or cost-effective. Furthermore, despite the challenges, writing may still be possible or they develop alternative methods of communication. BoNT should be considered for WC because several patients may benefit from the therapy. Muscle selection and the technique of injection are considered important determinants of symptom relief; therefore, it is imperative that the clinician accurately identifies the muscles involved in WC. While EMG is extremely useful for muscle localization, the clinician should have sound knowledge of anatomical landmarks. Acquiring the skill of ultrasound guidance may further aid in injecting deeper forearm muscles.

Acknowledgments

None.

Author contribution

Research project: A. Conception, B. Organization, C. Execution

Statistical analysis: A. Design, B. Execution

Review and Critique: A. Manuscript preparation: B. Writing of the first draft, C. Review and Critique.

Divyani Garg: 1B, 1C, 2B, 3A, 3B, 3C

Suvorit Bhowmick: 1B, 1C, 2B, 3A, 3B, 3C

Jacky Ganguly: 1C, 2A, 2B, 3A, 3B, 3C

Shivam Om Mittal: 1C, 3B

Rupam Borgohain: 3C

Prashanth LK: 1A, 1B, 1C, 2A, 3A, 3B, 3C

Ethical compliance statement

The manuscript adheres to the journal ethical requirements. As this is an review, ethics clearance from institute boards was not required.

Financial support and sponsorship

Nil.

Conflicts of interest

There are no conflicts of interest.

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