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A Pilot Study of Botulinum Toxin for Jerky, Position-Specific, Upper Limb Action Tremor


Tabish A. Saifee,

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London, GB
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Tiago Teodoro,

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London; Department of Cardiovascular and Cell Sciences, St George’s University of London, London, UK; Instituto de Medicina Molecular, Faculdade de Medicina, Universidade de Lisboa, Lisboa; Serviço de Neurologia, Hospital de Santa Maria, Lisboa, PT
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Roberto Erro,

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London; Dipartimento di Scienze Neurologiche e del Movimento, Universitàdi Verona, Verona, IT
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Mark J. Edwards,

Sobell Department of Motor Neuroscience and Movement Disorders, UCL Institute of Neurology, London; Department of Cardiovascular and Cell Sciences, St George’s University of London, London, GB
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Carla Cordivari

Department of Clinical Neurophysiology, National Hospital for Neurology and Neurosurgery, London, GB
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Background: We aimed to investigate the efficacy and safety of botulinum toxin (BT) injections for jerky action tremor of the upper limb.

Methods: We performed an uncontrolled, prospective study of electromyography (EMG)-guided BT injections for jerky, position-specific, upper limb action tremor. The primary outcome was clinical global impression at 3–6 weeks after baseline.

Results: Eight patients with jerky, position-specific action tremor involving the upper limb were consecutively recruited. After a median follow-up of 4.4 weeks (interquartile range [IQR] 3.6–6 weeks), four of them rated themselves as ‘‘improved’’ and two as ‘‘much improved.’’ Five of these six subjects reported improvements in specific activities of daily living (bringing liquids to mouth, feeding, shaving, and dressing). Upper limb subscore of the Fahn–Tolosa–Marin Tremor Rating Scale (FTM) significantly decreased from 4.5 (4–6) to 3 (2–5) (p=0.01).

Discussion: This pilot, prospective cohort study suggests that EMG-guided BT injections may improve jerky, position-specific, upper limb action tremor. Placebocontrolled studies evaluating larger samples of patients are warranted to confirm these findings.

How to Cite: Saifee TA, Teodoro T, Erro R, Edwards MJ, Cordivari C. A Pilot Study of Botulinum Toxin for Jerky, Position-Specific, Upper Limb Action Tremor. Tremor and Other Hyperkinetic Movements. 2016;6:406. DOI:
  Published on 29 Sep 2016
 Accepted on 24 Aug 2016            Submitted on 19 May 2016


The efficacy of pharmacological treatment for upper limb tremors is often disappointing. In this context, use of botulinum toxin (BT) injections has had mixed results. Some studies have described significant improvement of both tremor and function,1,2 but others have failed to confirm those benefits.35

More recently, a retrospective study of open-label BT injections for proximal upper limb tremor reported moderate or marked subjective benefit in 63% patients.6 These encouraging results were related to the application of an individualized injection strategy in accordance with tremor characteristics. However, no details were provided about BT doses and injection sites.

Here we report a pilot, uncontrolled, prospective cohort study investigating the efficacy and safety of BT for jerky, position-specific, upper limb action tremor.


We recruited consecutive patients presenting with jerky, position-specific, postural and kinetic tremor of the upper limb to a botulinum toxin clinic at the National Hospital for Neurology and Neurosurgery (London), during a period of 10 months. Here we use the term “position-specific” to describe tremor appearance or exacerbation in particular positions of the upper limbs (e.g. tremor worsening while slowly supinating or pronating the forearms with the upper limbs flexed at the elbow). Tremor involved the proximal (i.e. shoulder abduction/adduction or internal/external rotation) and/or distal upper limb (forearm pronation/supination or hand tremor). Participants were naïve to BT and refractory or intolerant to drug therapy, or preferred a trial of BT to trials of medication after balancing the risks and benefits against the alternatives. Non-significant tremor severity and general contraindications to BT were exclusion criteria.

Our primary outcome measure was clinical global impression (CGI) at the follow-up visit (i.e. “much worse,” 1; “worse,” 2; “no change,” 3; “improved,” 4; “much improved,” 5; as rated by the patient). Secondary outcomes were change in the upper limb tremor subscore of the Fahn–Tolosa–Marin Tremor Rating Scale (FTM),7 improvement of specific activities of daily living (ADL) (patients were asked specifically about feeding, bringing liquids to mouth, hygiene, dressing, writing and working), and occurrence of adverse events (particularly weakness).

The injection strategy, including muscle selection and dosages, was individualized according to tremor characteristics. Utilization of electromyography (EMG) guidance increased the likelihood of injecting tremulous muscles and sparing non-tremulous ones, thus maximizing efficacy while avoiding muscle weakness as a side effect. Abobotulinum toxin A (Dysport®) was used, in a concentration of 20 units (U) per 0.1 mL. All BT injections were performed by C.C.

Clinical and demographic information was collected during initial assessment by T.A.S. The follow-up visits were performed 3–6 weeks after baseline by T.A.S. and C.C. Baseline and follow-up upper limb FTM subscores were rated by T.T., who analyzed video records blinded for the time point. Ethics approval and the participant’s written informed consent were obtained.

Outcome measures were continuous variables, and were expressed as medians (interquartile range). Differences among those variables, before and after treatment, were analyzed using Wilcoxon signed-rank test. The statistical package was STATA version 13 software, and p<0.05 was considered significant.


We recruited eight patients with predominantly postural and kinetic, upper limb tremor (five males, three females), with a median age of 70 years (IQR 56–73 years) (Table 1). Tremor was also present at rest in three patients. Tremor was unilateral or asymmetric in all participants. Proximal tremor was predominant, but the shoulder and forearm were involved in most subjects. Tremor was jerky in character in all participants. Moreover, tremor also showed position-specificity in all subjects. Indeed, we observed significant tremor worsening when we asked the patients to slowly supinate or pronate the forearms with the upper limbs flexed at the elbow. Four subjects were non-responsive and/or intolerant to previous drug treatments and another four were treatment naïve. Two patients had head tremor and one had mild cervical dystonia as additional neurological features.

Table 1

Clinical Characteristics

ID Sex Age P. Hand UL Involvement by Tremor Other Previous Treatments/Response Injection Strategy
Side (R/L) Segments Affected Rest (R), Postural (P), Kinetic (K) Muscles/Dose Total Dose
1 F 71 L L S, A, H R, P, K Head tremor; unsteady gait (stable) PRO, TPM, GBP, PMD/NR, IT Left: T min 80, Infraspin 80, L dorsi 80 240
2 M 76 R R S, A, F P, K Nil Nil Right: Infraspin 80, Sup 30, ECR 30, P teres 40, Deltoid 20 200
3 M 71 R L>R S, A, F P, K Nil Unknown/NR Right: Infraspin 50, P teres 50, Sup 50, P quadratus 50 200
Left: Infraspin 50, P major 50, Subscapularis 100, P teres 50, P quadratus 50, Sup 50 350
4 F 69 R L>R S, A>F P, K Nil Unknown/NR Right: Infraspin 100, P major 100, Trapezius 100 300
Left: Infraspin 100, P major 100, Trapezius 100 300
5 M 61 R R>L S, A, F R, P, K Head tremor PRO/NR, IT Right: P quadratus 20, Supraspin 40, T major 100, P teres 50 210
6 M 51 R R>L F>H, A, S P, K Nil Nil Right: P teres 60, P quadratus 40, Sup 40 140
7 M 43 R R = L H, F>S, A R, P, K Nil Nil Right: FC ulnaris: 120, EC radialis 40 160
8 F 75 R R F>S, A P, K Mild cervical dystonia Nil Right: Sup 40, P teres 30, P quadratus 40, Infraspin 80 190
Median (IQR) 70 (56–73) 205 (190–300)

Abbreviations: A, Arm; ECR, Extensor Carpi Radialis; F, Forearm; FC ulnaris, Flexor Carpi Ulnaris; GBP, Gabapentin; H, Hand; Infraspin, Infraspinatus; IT, Intolerance; L dorsi, Latissimus Dorsi; NR, Non-response; Other, Other Neurological Problems; PRM, Primidone; PRO, Propranolol; P. hand, Preferred Hand; P major, Pectoralis Major; P quadratus, Pronator Quadratus; P teres, Pronator Teres; S, Shoulder; Sup, Supinator; Supraspin, Supraspinatus; T min, Teres Minor; TPM, Topiramate; UL, Upper Limb.

Dosage is in units of Dysport®.

A total of 10 upper limbs were treated, and 14 individual muscles injected. Our approach was to inject, in an individualized fashion, the following muscles according to the clinical presentation: shoulder abduction movement, deltoid (one) and supraspinatus (one); shoulder adduction, pectoralis major (one) and teres major (one) (also arm internal rotation); scapular rotation, trapezius (one); shoulder external rotation, infraspinatus (five) and teres minor (one); arm internal rotation, latissimus dorsi (one) and subscapularis (one); forearm supination, supinator (five); forearm pronation, pronator teres (five) and pronator quadratus (five); wrist extension/abduction, extensor carpi radialis (two); wrist flexion/adduction, flexor carpi ulnaris (one) (Table 1). The median total dosage per participant of Dysport® was 205 IU (190–300 IU) (Table 2).

Table 2


ID Follow-up (weeks) Side Global Clinical Impression Upper Limb CRS for Tremor Subscore Improvement in Specific Activities of Daily Living Adverse events
1 3.7 L 3 5 5 None Marked shoulder weakness
2 3 R 4 2 0 BLM Mild shoulder weakness
3 6 R 4 5 3 BLM (mild) None
L 6 6
4 6 R 5 3 1 Feeding and BLM Mild weakness
L 6 5
5 5 R 5 6 3 Feeding, BLM, shaving, dressing None
6 3.6 R 4 4 2 Feeding (mild) None
7 3.6 R 3 4 4 None None
8 6 R 4 4 2 None None
Median (IQR) 4.4 (3.6–6) 4 (3.5–4.5) 4.5 (4–6) 3 (2–5)

Abbreviations: B, Baseline; BLM, Bringing Liquids to Mouth; CRS, Clinical Rating Scale; F, Follow-up; IQR, Interquartile Range; L, Left; R, Right.

Clinical global impression: much improved (5), improved (4), no change (3), worse (2), much worse (1).

After a median follow-up of 4.4 weeks (IQR 3.6–6 weeks), four of the eight participants reported themselves to be “improved” and two “much improved.” The two other subjects reported no change in tremor. Importantly, five of the six subjects who reported improvement also described functional benefit in specific ADL, including bringing liquids to the mouth (four), feeding (three), dressing (one), shaving (one). FTM upper limb subscores (possible range 0–12) significantly decreased from a median of 4.5 (4–6) to 3 (2–5) (p = 0.01, Wilcoxon signed-rank test).

Three subjects experienced muscle weakness following injections, but this was only clinically significant in one participant whose weakness affected the shoulder (Table 2). Our sample is too small to correlate efficacy and safety with specific clinical patterns or injection strategies.


In this pilot, prospective cohort study we investigated EMG-guided BT injections for jerky, position-specific, upper limb action tremor. Six out of the eight patients reported a beneficial effect. In five of these, it included improvement in one or more ADL, for example bringing liquids to the mouth and feeding. Efficacy was further supported by a significant decrease in the FTM upper limb subscore.

Importantly, BT was well tolerated in our cohort, with significant weakness in only one patient. EMG guidance and an individualized treatment likely contributed to there being limited adverse effects.

Despite the small sample size and the open-label, uncontrolled administration of BT, these results are encouraging. Significantly, this is the first prospective study evaluating BT for jerky, postural, and kinetic tremor of the upper limb. Moreover, our sample included medication-refractory patients with proximal “wing-beating” tremor, which can be very disabling by interfering with bringing food or liquids to the mouth.6

BT injections have a fairly accepted role in managing head tremor, tremulous spasmodic dysphonia, and primary writing tremor.8,9 However, studies of the effect of BT on other upper limb tremor types have had heterogeneous results in terms of functional disability. Although a placebo-controlled trial in multiple sclerosis-associated tremor1 and a case report in anti-MAG neuropathy-related tremor2 described significant improvement of both tremor and function, other studies of BT in essential or parkinsonian tremor failed to demonstrate functional improvement3,4 and/or to show change in objective tremor measures.5

More recently, a retrospective, open-label study of BT for proximal upper limb tremor reported moderate or marked benefit in 63% of 19 patients.6 The adoption of an individualized injection strategy was most likely to be related to this better outcome.6 Similarly, we applied an individualized strategy of BT injection, in accordance with tremor characteristics.

Dystonia was present in only one patient in our cohort, and did not affect the upper limb (Table 1). However, upper limb tremor in study participants had clinical characteristics akin to dystonic tremor/tremor associated with dystonia.10 Tremor was “jerky” in character, position specific, predominantly postural/kinetic, and unilateral/asymmetric. Although dystonic tremor is classically defined by the coexistence of dystonia in the same body part,11 recent studies suggest that patients can have isolated tremor with dystonic features but without overt dystonia12,13 and develop dystonia only later in life.14 In the absence of reliable biomarkers for dystonic tremor, we adopted a descriptive label of “jerky, position-specific, upper limb action tremor,” but highlighting the phenomenological similarities between dystonic tremor10 and that of the patients described here. This is relevant because evidence to guide treatment of dystonic tremor is scarce, and the efficacy of drug treatment generally disappointing.8 Interestingly, in a previous retrospective study of individually tailored BT injections for upper limb tremor, significant improvements were observed in four out of six patients with dystonic tremor.6

We acknowledge that our study has significant methodological limitations. These include a small sample size, the absence of a control group and the open-label nature of the intervention.

Nevertheless, the existence of a common trend among the follow-up clinical global impression of the patients, blinded tremor rating scale scores, and modification of ADL hints at a genuine beneficial effect.

In conclusion, this small, open-label and uncontrolled prospective cohort study suggests that individualized EMG-guided BT injections may reduce tremor and improve function in patients with jerky, position-specific, upper limb action tremor, with few side effects. We believe that these findings should encourage further investigation about the role of individualized BT treatment for upper limb action tremor, through the performance of randomized, controlled, well-powered clinical trials.


1 Funding: Tiago Teodoro receives funding from the grant “SFRH/SINTD/95267/2013”, awarded by “Fundação para a Ciência e a Tecnologia”. 

2 Financial Disclosures: Roberto Erro received consultancies from Zambon. Mark J Edwards receives royalties from the Oxford University Press for the Oxford Handbook of Parkinson’s disease and other movement disorders, honoraria from UCB for speaking engagements, and grant funding from NIHR and the Medical Research Council. 

3 Conflict of Interest: Tiago Teodoro has received travel grants from Ipsen®. 

4 Ethics Statement: This study was performed in accordance with the ethical standards detailed in the Declaration of Helsinki. The authors’ institutional ethics committee has approved this study and all patients have provided written informed consent. All patients that appear on video have provided written informed consent; authorization for the videotaping and for publication of the videotape was provided. 


  1. Van Der Walt, A Sung, S Spelman, T et al. (2012). A double-blind, randomized, controlled study of botulinum toxin type A in MS-related tremor. Neurology 79: 92–99. [PubMed]  

  2. Latino, P, Pellicano, C, Pontieri, FE and Giovannelli, M (2015). Treatment with botulinum toxin for anti-MAG neuropathy-related arm tremor. Neurol Sci 36: 333–334. doi: 10.1007/s10072-014-1890-6. [PubMed]  

  3. Brin, MF Lyons, KE Doucette, J et al. (2001). A randomized, double masked, controlled trial of botulinum toxin type A in essential hand tremor. Neurology 56: 1523–1528. doi: 10.1212/WNL.56.11.1523. [PubMed]  

  4. Jankovic, J, Schwartz, K, Clemence, W, Aswad, A and Mordaunt, J (1996). A randomized, double-blind, placebo-controlled study to evaluate botulinum toxin type A in essential hand tremor. Mov Disord 11: 250–256. doi: 10.1002/mds.870110306. [PubMed]  

  5. Trosch, RM and Pullman, SL (1994). Botulinum toxin A injections for the treatment of hand tremors. Mov Disord 9: 601–609. doi: 10.1002/mds.870090604. [PubMed]  

  6. Kim, SD, Yiannikas, C, Mahant, N, Vucic, S and Fung, VSC (2014). Treatment of proximal upper limb tremor with botulinum toxin therapy. Mov Disord 29: 835–838. doi: 10.1002/mds.25739. [PubMed]  

  7. Pahwa, R Lyons, K Hubble, JP et al. (1998). Double-blind controlled trial of gabapentin in essential tremor. Mov Disord 13: 465–467. doi: 10.1002/mds.870130315. [PubMed]  

  8. Fasano, A, Bove, F and Lang, AE (2014). The treatment of dystonic tremor: a systematic review. J Neurol Neurosurg Psychiatry 85: 759–769. doi: 10.1136/jnnp-2013-305532. [PubMed]  

  9. Papapetropoulos, S and Singer, C (2006). Treatment of primary writing tremor with botulinum toxin type a injections: report of a case series. Clin Neuropharmacol 29: 364–367. doi: 10.1097/01.WNF.0000236765.00785.9C. [PubMed]  

  10. Erro, R Rubio-Agusti, I Saifee, TA et al. (2014). Rest and other types of tremor in adult-onset primary dystonia. J Neurol Neurosurg Psychiatry 85: 965–968. doi: 10.1136/jnnp-2013-305876. [PubMed]  

  11. Deuschl, G, Bain, P and Brin, M (1998). Consensus statement of the Movement Disorder Society on Tremor. Ad Hoc Scientific Committee. Mov Disord 13(Suppl. 3): 2–23. doi: 10.1002/mds.870131303. 

  12. Stamelou, M Charlesworth, G Cordivari, C et al. (2014). The phenotypic spectrum of DYT24 due to ANO3 mutations. Mov Disord 29: 928–934. doi: 10.1002/mds.25802. [PubMed]  

  13. Gövert, F and Deuschl, G (2015). Tremor entities and their classification: an update. Curr Opin Neurol 28: 393–9. doi: 10.1097/WCO.0000000000000211. [PubMed]  

  14. Münchau, A Schrag, A Chuang, C et al. (2001). Arm tremor in cervical dystonia differs from essential tremor and can be classified by onset age and spread of symptoms. Brain J Neurol 124((Pt 9)): 1765–1776. doi: 10.1093/brain/124.9.1765. 

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