Botulinum toxin versus trihexyphenidyl in cervical dystonia: a prospective, randomized, double-blind controlled trial. Botulinum toxin type B: a double-blind, placebo-controlled, safety and efficacy study in cervical dystonia. Quantitative EMG in botulinum toxin treatment of cervical dystonia. A double-blind, placebo-controlled study.
Botulinum toxin type A (BTA) is replacing trihexyphenidyl as the treatment of choice for idiopathic cervical dystonia (ICD), but there has never been a direct comparative study.
                This trial compares the effectiveness of BTA with that of trihexyphenidyl in a prospective, randomized, double-blind design. Sixty-six consecutive patients with ICD were randomized to treatment with trihexyphenidyl tablets plus placebo injection or placebo tablets plus BTA injections. Tablets were administered daily according to a fixed schedule. Dysport or saline was injected under EMG guidance at study entry and again after 8 weeks. Patients were assessed for efficacy at baseline and after 12 weeks by different clinical rating scales.
                Sixty-four patients completed the study, 32 in each group. Mean dose of BTA was 292 mouse units (first session) and 262 mouse units (second session). Mean dose of trihexyphenidyl was 16.25 mg. The changes on the Disability section of the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS-Disability) (primary outcome), Tsui Scale, and the General Health Perception Subscale were significantly in favor of BTA. More patients treated with BTA had an improvement of at least three points on the TWSTRS-Disability (14 versus 6) and on the Tsui Scale (23 versus 12). Adverse effects were significantly less frequent in the BTA group.
                BTA is significantly more effective in the treatment of ICD, with less adverse effects. We enrolled and treated 122 patients with idiopathic cervical dystonia in a double-blind, placebo-controlled safety and efficacy study of botulinum toxin type B (BotB). Both A-responsive and A-resistant patients were enrolled. Patients received intramuscular injections of either BotB (2,500 U, 5,000 U, or 10,000 U) or placebo. The primary outcome measure of efficacy was the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-Total score at 4 weeks following study drug administration. Secondary measures of efficacy were TWSTRS-Severity, -Disability, and -Pain subscale scores, and Analog Pain Assessment, Investigator Global Assessment, Patient Global Assessment, and Sickness Impact Profile scores. Duration of effect was estimated with an intent-to-treat analysis of responders. Safety measures included clinical parameters, laboratory tests, and adverse events. The primary and most of the secondary analyses indicated a statistically significant treatment effect and a dose response. BotB is safe, well tolerated, and efficacious in the treatment of cervical dystonia at the doses tested. We used turns-amplitude analysis of the EMG as a guidance for botulinum toxin (BT) treatment in 19 patients with cervical dystonia. At the first examination, muscles showing abnormal activity (> 100 turns/sec at rest) were given BT 75 units (10 patients) or placebo (9 patients). At subsequent examinations, about 6, 12 and 18 weeks after the start, BT 75 units were given to all hyperactive muscles. Six weeks after the first BT treatment the sternocleidomastoid muscle contralateral to the involuntary head rotation and the ipsilateral and contralateral posterior neck muscles (PNM) showed a reduction of involuntary activity, as indicated by reduced turns/sec and mean amplitude at rest. Similar changes were seen when comparing BT treatment with placebo. The reduction was greater in the contralateral sternocleidomastoid muscle than in PNM, suggesting that PNM need higher doses of BT. At maximal voluntary contraction, BT treated muscles showed unchanged turns/sec (5/6 tests), decreased mean amplitude and increased ratio (turns/amplitude). This may reflect a functional random loss of muscle fibres, combined with inability to activate all motor units. A high (89%) clinical success rate with BT therapy was obtained, and it is concluded that quantitative EMG is a useful tool for the precise identification of hyperactive muscles, for optimal placing of the injection cannula and for unbiased monitoring of the treatment effect.
A single injection of BtB was effective and safe for treating cervical dystonia. Long-term uncontrolled studies suggested that further injection cycles continue to work for most patients. 
Future research should explore technical factors such as the optimum treatment intervals and use of image or electromyographic guidance for administration. Other issues include service delivery, quality of life, long-term efficacy and safety, and the relative indications for BtA, BtB and other treatments such as deep brain stimulation