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We conducted a single-dose, placebo-controlled, double-blind, dose-response study of NerBloc®(rimabotulinumtoxinB) in patients with cervical dystonia (placebo, 2,500 U, 5,000 U, 10,000 U). The primary endpoint, the change in Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS)-total score at 4 weeks post dose from baseline, showed a significant improvement in all treatment groups (2,500 U, 5,000 U, 10,000 U) compared with the placebo group. As for the secondary endpoints, the change of TWSTRS subscales, severity, disability and pain scores, at 4 weeks post dose in 10,000 U group, showed a significant improvement compared with the placebo group, however, no significant differences were observed between 2,500 U or 5,000 U and placebo group. The subject's and physician's global assessments (visual analog scale; VAS) at 4 weeks post dose also showed significant improvement in all treatment groups relative to the placebo group, whereas subject's pain assessment (VAS) at 4 weeks post dose did not show significant improvement in any of treatment groups. The incidence rate of adverse events was not substantially different between the placebo group and 2,500 or 5,000 U group, but significantly higher in 10,000 U group than in the placebo group. Adverse events frequently observed in active drug groups included dry mouth/thirst and dysphagia, all of which were mild in severity. There were no adverse events that led to death, serious disorders or study discontinuations. The incidence rate of abnormal laboratory values did not show significant difference in any of parameters between the placebo group and any of treatment groups. NerBloc® possessing muscle relaxing effect is expected to be a potential treatment to improve symptoms of cervical dystonia. Clinically recommended dose will range from 2,500 U to 10,000 U. In this study, 10,000 U group was the most effective and the effect lasted the longest. The efficacy and safety profile of NerBloc ® in this study was similar to that in AN072-009 study conducted in the US.

We examined the inter-rater reliability for the evaluation of patients with cervical dystonia by using the Toronto Western Spasmodic Torticollis Rating Scale (TWSTRS) (translated into Japanese). The TWSTRS is a rating scale that assesses patients with cervical dystonia by grading their symptoms on a subscale of severity, disability, and pain. This study used to TWSTRS-severity scores to examine the inter-rater reliability among 27 evaluators (neurologists) by using videotaped images of 2 patients. Along with the total-severity score on the TWSTRS, the intra-class correlation (ICC) and the lower limit of the 95% confidence interval were calculated as indices of inter-rater reliability. A high ICC of 0.745 was obtained. The ICC obtained from another study conducted outside Japan was 0.763, which is almost equivalent to the result of our study. Thus, the TWSTRS has a favorable inter-rater reliability which suggests that this scale was sufficiently reliable to be used as an accurate and easily available rating tool during the treatment of cervical dystonia.

Stiff-person syndrome, a relatively rare disease with a poor prognosis, presents as muscle stiffness, rigidity, and spasm. We reported a patient with this syndrome who was treated successfully. The patient was a 56-year-old Japanese man with respiratory infection-like prodromal symptoms. Episodes of painful spasm in both legs on extension and lordosis occurred spontaneously or were triggered with touch or pinprick stimuli at or below spinal level C3, and progressed subacutely. Tendon reflexes were hyperactive, Babinski's sign was positive, and vibration sense was reduced in the legs. Episodes of spasm were alleviated using diazepam. Even after discontinuing diazepam, these symptoms did not exacerbate. In this patient, although anti-glutamic acid decarboxylase (GAD) antibody was negative, anti-EB virus antibody was positive. No previous reports have described stiff-person syndrome with EB virus infection. However, a few cases of this syndrome associated with viral infection were recently reported and viral gene mimicity with GAD has been postulated. Viral infection might be considered as a probable cause of this syndrome.

The goal of medical therapy for primary dystonia is conservative. While botulinum toxin (BTX) therapy is a first choice for blepharospasm and cervical dystonia, medical therapy is selected as such for other types of dystonia. As oral medications, trihexyphenidyl and benzodiazepines are most frequently used. Muscle relaxants are also commonly used, but dopamine antagonists are not recommended because of the risk of inducing tardive dyskinesia. For childhood-onset generalized dystonia, levodopa should be considered to rule out levodopa-responsive dystonia. Mexiletine is reported to be effective not only for bleharospasm and cervical dystonia but for focal limb dystonia. To improve the therapeutic performance of BTX therapy for blepharospasm, it is recommended that corrugator supercilii and procerus muscles, as well as orbicularis oculi muscle, be added as target muscles. To improve the therapeutic performance of BTX therapy for cervical dystonia, it is recommended that this therapy be started as early as possible, especially within one year of illness, and that levator scapulae muscle be added as target if necessary. To improve usefulness of medical therapy for dystonia, its strategy must be standardized, and more useful therapies must be positively adopted. Algorithm for treatment of dystonia must also be established and generalized.