Table 6.
Studies with botulinum toxin A (BTX A) for the treatment of severe ET.
| Tremor Location | Author; Year [Ref] | Study Design | Main Results | |
|---|---|---|---|---|
| UPPER LIMBS | Trosch & Pullman, 1994 [174] | Open-label study involving 12 ET patients. Identification of target muscles by clinical evaluation and tremor analysis including EMG activity. Infiltration of 10-25 Units of BTX A in ECU; ECR; FCR and FCU in all patients; and 75 Units in biceps and triceps and 20 Units in FDD in some patients). Evaluation at 6-weeks. | Five patients reported subjective moderate to marked improvement; only 3 showed an objective major reduction in tremor amplitude, and tremor severity scales showed mild but statistically significant improvement. | |
| Henderson et al., 1996 [175] | Single-blind placebo-controlled study with placebo given first. Infiltration of 25 Units ob BTX A divided into several muscles including EIP and FDP. Only 3 of the 17 patients involved were diagnosed with “pure” ET | Improvement of postural tremor in the pool of patients included with “pure ET” or ET associated with other conditions was twice with BTX A than with placebo | ||
| Jankovic et al., 1996 [176] | Randomized-double blind; placebo-controlled study. Infiltration of 15 Units of BTX A or placebo in FCU and FCR and 10 in ECR brevis and ECR longus and in ECU in the dominant hand. A second injection of 30 Units in FCU and FCU and 20 in ECR and ECU was administered at 4-weeks if there was no improvement. The final evaluation was done at 16 weeks. | Mild to moderate subjective improvement of tremor in 75% of patients treated with BTX A and 27% with placebo. A non-significant trend towards improvement in tremor scales. Reduction in tremor amplitude (postural accelerometry) in 75% of BTX A-treated patients vs 8.3% of placebo-treated. Mild finger weakness in all BTX A treated patients | ||
| Pullman et al., 1996 [177] | Open-label prospective study involving 187 patients with several limb disorders (14 with essential tremor) during an 8-year period | 25% reduction in tremor amplitude. Mild transient weakness as a frequent side effect | ||
| Pacchetti et al., 2000 [178] | Open-label study involving 20 ET patients. Recording of activity in ECR; ECU; FCR; FCU; brachioradialis; PT; biceps and triceps of the right arm and infiltration of BTX A in muscles showing tremor at 2 postures avoiding ECR or ECU if possible. Measurement of tremor amplitude with accelerometry. | Significant reduction in severity and functional rating scales scores and of tremor amplitude as measured with accelerometry and EMG. Mild transient 3rd finger weakness in 15% of patients. | ||
| Brin et al., 2001 [179] | Randomized; multicenter; double-masked clinical trial with three treatment groups: low-dose botulinum toxin type A (50 U); high dose BTX A (100 U); and vehicle placebo involving 133 patients with ET; injected into the wrist flexors and extensors. Follow-up for 16; Assessment with clinical rating scales; measures of motor tasks and functional disability; and global assessment of treatment. | Significant improvement of postural but not of kinetic tremor. Lack of improvement in the measures of motor tasks and functional disability. Dose-dependent hand weakness as the main side effect. | ||
| Samotus et al., 2016 [180] | 38-week open-label study involving 24 ET patients injected with incobotulinumtoxinA using guiding muscle selection. Assessment with clinical scales of severity and quality of life, and objective kinematic assessments | Significant improvement of tremor severity and quality of life in clinical scales; and a significant reduction in tremor amplitude in the wrist and shoulder joints. Mild weakness in injected muscles without interference in arm function in 40% of patients | ||
| Samotus et al., 2017 [181] | 96-week open-label study involving 24 ET patients injected with incobotulinumtoxinA using guiding muscle selection. Assessment with clinical scales of severity and quality of life, and objective kinematic assessments | Significant improvement of tremor severity and quality of life in clinical scales; and a significant reduction in tremor amplitude in the wrist and shoulder joints. Mild weakness in injected muscles without interference in arm function in 40% of patients | ||
| Samotus et al., 2018 [182] | 96-week open-label study involving 10 ET patients (drug naïve for incobotulinumtoxin A and oral drugs) injected with incobotulinumtoxinA using guiding muscle selection. Assessment with clinical scales of severity and quality of life, and objective kinematic assessments | Significant improvement of tremor severity and quality of life in clinical scales; and a significant reduction in tremor amplitude in the wrist and shoulder joints. 44.6% (p <0.0005) non-dose-dependent reduction in maximal grip strength; but only 2 participants complained of mild weakness | ||
| Tremor Location | Author; Year [Ref] | Study Design | Main Results | |
| Mittal et al., 2018 [183] | 28-week; double-blind; placebo-controlled; crossover trial involving 33 ET patients injected with 80–120 units of IncoA into 8–14 hand and forearm muscles using a customized approach and selection by needle EMG. Assessment with clinical scales of tremor and measurement of muscle strength by an ergometer | Significantly higher improvement in clinical tremor scales and subjective improvement for IncoA than for placebo. Non-significant differences in developing mild transient hand weakness between the two groups | ||
| Niemann & Jankovic, 2018 [184] | Retrospective review of a database of patients treated with onaBoNT-A for hand tremor evaluated between 2010 and 2018 in at least 2 sessions with follow-up (53 of them diagnosed with ET; most of them injected in FCR and FCU). | 80.2%-85.7% reported moderate or marked improvement at their first and last follow-up visit; respectively. Total dose injected increased significantly between the first and the last visit. Only 12.2% developed transient weakness of pain | ||
| Samotus et al., 2019 [185] | 30-weeks open-label study; with follow-ups six-weeks post-treatment; involving 31 ET participants who received three bilateral-arm BoNT-A injection cycles. Assessment with clinical scales of severity and quality of life, and objective kinematic assessments | Significant improvement of tremor severity and quality of life in clinical scales; and a significant reduction in tremor amplitude (47.7%) in both arms that persisted from weeks 18-30. Maximum grip strength reduced at week 6 (p = 0.001) but without functional impairment | ||
| HEAD | Pahwa et al., 1995 [186] | Double-blind; placebo-controlled study involving 10 patients with ET affecting the head. Infiltrations with 40 U of BTX A into each sternocleidomastoid muscle and 60 U into each splenius capitis using EMG guidance. Clinical and accelerometric evaluation at baseline; and at 2; 4; and 8 weeks after injection | Non-significant differences in subjective assessments; clinical ratings; and tremor amplitude between BTX A and placebo. Mild transient weakness in 70% of patients with BTX A and in 10% with placebo. | |
| Wissel et al., 1997 [187] | Open-label study of 43 patients with head tremor (29 with dystonic tremor and 14 with ET head tremor). Selection of muscles by EMG. Patients with ET head tremor received 400 U of BTX A (Dysport) divided into the two splenius capitis. | Significant improvement in tremor amplitude measured by accelerometry. mild and transient side effects (local pain; neck weakness; and dysphagia) reported by 40% | ||
| VOICE (EVT) | Warrick et al., 2000 [188] | Prospective open-label crossover study using BTX A involving 10 patients with EVT (bilateral 2.5-U or unilateral 15-U EMG-guided injection); followed by the alternative injection 16 to 18 weeks later. Evaluation with subjective judgment; and acoustic; aerodynamic; and nasopharyngoscopic data at 2; 6; 10; and 16 weeks after each injection. | Objective reduction in tremor severity in 3/10 patients with bilateral injection; and 2/9 with unilateral injection. Eight/10 wished to be re-injected at the conclusion of the study. Reduction in the vocal effort and in laryngeal airway resistance. Breathiness; coughing/choking and swallowing problems as side effects (one with pneumonia 2 to 4 weeks after unilateral injection). Side effects more severe with unilateral injection | |
| Hertegård S et al., 2000 [189] | Open-label study involving 15 patients with EVT. Injections of BTX A (1.25-2.5 U) to the thyroarytenoid muscles (in some cases cricothyroid or thyrohyoid muscles as well). Evaluations with subjective judgments by the patients; and perceptual and acoustic analysis of voice recordings. | Subjective beneficial effect in 67% of the patients. Significant decrease in voice tremor during connected speech (p <0.05); and in fundamental frequency during sustained vowel phonation (p <0.01); and nearly significant decrease in the fundamental frequency variations (p = 0.06). |
||
| Adler et al., 2004 [190] | Open-label randomized study involving 13 patients with EVT using 3 doses of BTX A (1.25 U; 2.5 U; or 3.75 U in each vocal cord). Evaluations at baseline and postinjection at weeks 2; 4; and 6. | Significant improvement with the 3 doses used in tremor severity scale scores; measures of functional disability; measures of the effect of injection; independent ratings of videotaped speech; and acoustic measures of tremor. Transient breathiness (11 patients) and dysphagia (3 patients) as the main adverse effects at all doses. | ||
| Justicz et al., 2016 [191] | Individual prospective cohort study involving 18 EVT patients. Assessments at baseline 2 weeks after propranolol therapy (maximum 60-90 mg/day) and 4 weeks after BTX A injection (average dose 3.18 UI in the thyroarytenoid/lateral cricoarytenoid complex; unilateral in 2 patients and bilateral in 16). | Both treatments get improvement in a Voice-Related Quality-Of-Life (VRQOL) questionnaire; in a Quality of life in Essential Tremor questionnaire; and in a blinded perceptual voice assessment; but only BTX A treatment showed significant changes with respect to baseline. | ||
| Tremor Location | Author; Year [Ref] | Study Design | Main Results | |
| Estes et al., 2018 [192] | Prospective crossover study involving 7 EVT patients injected with BTX A (15 U of Dysport in the left thyroaritenoid muscle) or a buffered hydrogel in laryngeal adductor muscles; with evaluation at 30 days after the procedure. Assessment with Vocal Tremor Scoring System (VTSS); and acoustic and aerodynamic measures. | Both treatments get improvement when compared with baseline, but there were non-significant differences between them. | ||
| Guglielmino et al., 2018 [193] | Randomized crossover study involving 5 EVT patients injected with BTX A (mean dose 1.26 U) or treated with oral propranolol 80 mg/day. Assessment with perceptual and acoustic measures before and after the administration of the two treatments. | Non-significant improvement of perceptual and acoustic measures; both with BTX A and propranolol. | ||
ECR: extensor carpi radialis; ECU: extensor carpi ulnaris; FCR: flexor carpi radialis; FCU: flexor carpi ulnaris; FDC: flexor digitorum comunis; PT pronator teres; EIP: extensor indicir proprius; FDP: flexor digitorum profundus; EMG electromyography; ET essential tremor; EVT: essential voice tremor.