Abstracts / Toxicon 123 (2016) S2eS90
cholinergic neurons of the mouse intestine. PLoS Pathog. 2012; 8: e1002583. Couesnon A, Shimizu T, Popoff MR. Differential entry of botulinum neurotoxin A into neuronal and intestinal cells. Cell Microbiol. 2009;11:289-308. 184. TREATMENT OF HOLMES TREMOR WITH BOTULINUM TOXIN ~o*, Vasco Salgado, Mariana Fernandes, Patrícia Pita Leonor Reborda Lobo, Cristina Costa. Neurology Department, Hospital Prof. Doutor Fernando Fonseca, Amadora, Sintra, Portugal * Corresponding author: Neurology Department, Hospital Prof. Doutor Fernando Fonseca, IC 19, 2720-276 Amadora, Portugal. E-mail address:[email protected]
Introduction and Objectives: Holmes tremor is a low-frequency rest and intentional tremor, sometimes postural, with irregular amplitude that frequently affects the upper limb. It develops from weeks to months after a lesion of the brainstem, cerebellum or, less often, the thalamus. We report a patient with Holmes tremor secondary to multiple sclerosis treated with botulinum toxin. Methods and Results: The patient was a 62-year-old, right-handed woman with a history of bipolar disease and remitting-relapsing type multiple sclerosis, currently treated with teriﬂunomide. She displayed a low-frequency tremor in her right hand, present at rest and increasing with sustained postures, ultimately leading to limitation of daily activities, namely writing. A brain MRI showed multiple demyelinating lesions, including one in the left thalamus. Levodopa was not effective. Neurological examination showed postural tremor, a pronation and supination tremor pattern of the forearm. Botulinum toxin (Dysport®, Ipsen) was administered under ultrasound guidance to the muscles pronator teres (30 U), supinator (20 U), biceps (50 U) and brachioradialis (50 U). There was signiﬁcant improvement in tremor amplitude and severity along with a functional gain in the upper limb, namely in writing ability, without adverse effects. In the second treatment the muscles ﬂexor carpi radialis (15 U) and ulnaris (20 U), extensor carpi radialis (20 U) and ulnaris (20 U) were added, with increased beneﬁt. GAS change was 27,27 after the 1st treatment and 13,64 after the 2nd treatment, implying a signiﬁcant gain of function. Conclusions: Holmes tremor is an uncommon, disabling neurological condition and responds poorly to medical therapy. Botulinum toxin may be a useful and safe treatment option to consider in patients affected by this type of tremor. Keywords: Botulinum toxin; Holmes tremor; Multiple sclerosis 185. AN INTERNATIONAL, MULTICENTER, PROSPECTIVE, RANDOMIZED, EVALUATOR-BLINDED STUDY COMPARING DIFFERENT BOTULINUM TOXIN INJECTION STRATEGIES FOR TREATMENT OF UPPER LIMB SPASTICITY Tiina Rekand a, *, Bo Biering-Sørensen b, Jun He c, Ole Jakob Vilholm d, Peter € rn Stro € m g, Peter Brøgger Christensen e, Trandur Ulfarsson f, Torbjo Myrenfors g, Pascal Maisonobe h, Roger Belusa g, Torben Dalager i. a Department of Neurology, Haukeland Unversity Hospital, Bergen, Norway; b Department of Neurology, Glostrup Hospital, Glostrup, Denmark; c Department of Neurology, University Hospital of Copenhagen, Roskilde Hospital, Denmark; d Department of Neurology, Vejle Hospital, Vejle, Denmark; e Department of Neurology, Aarhus University Hospital, Denmark; f Department of Rehabilitation Medicine, Sahlgrenska University Hospital, Gothenburg, Sweden; g Institut Produits Synth ese (Ipsen AB), Stockholm, Sweden; h Ipsen Pharma, Boulogne, France; i Dystonia Clinic, Bispebjerg Hospital, Copenhagen, Denmark * Corresponding author: Department of Neurology, Haukeland University Hospital, 5020 Bergen, Norway. E-mail address:[email protected]
Introduction and objectives: To evaluate noninferiority between two injection strategies incorporating different numbers of injection sites and concentrations/volumes of abobotulinumtoxinA (ABO, Dysport®).
Methods: Patients who had previously received 2 cycles of ABO with satisfactory efﬁcacy (per investigator’s judgment) were randomized (1:1) to two groups. Total dose administered at Visit 1 (baseline) was per investigator’s judgment and remained unchanged from the run-in period (max dose 800 U). G1: 2 injection sites per muscle, 0.1-0.7 mL per muscle (ABO concentration 300 U/mL), G2: 1 injection site per muscle, 0.4-2.0 mL per muscle (ABO concentration 100 U/mL) according to a predeﬁned neuromuscular junction targeting technique. Electromyography or ultrasound was used to guide injections. The primary endpoint (PE) was percentage of patients with at least 1 level improvement in MAS at elbow ﬂexors 4 weeks post Visit 1 injection. Results: The study was closed before full recruitment due to slow recruitment. The study was planned to include 272 patients. Noninferiority in PE was not shown in the intention-to-treat (ITT) (n¼88) or in the per protocol (PP) (n¼54) population. ABO units administered (mean±SD [standard deviation]) were 537.8±130.2 for G1 and 579.4±180.5 for G2. The ITT population displayed a numerical preponderance toward G1 (72.7 vs 56.8%, P¼0.0986) based on the primary endpoint. The proportion of patients with at least 1 level decrease in MAS in PP was 69% for G1 and 68% for G2. Injection pain (VAS±SD) was not statistically different between the groups (G1: 30.68±27.33 vs G2: 25.67±25.37). Overall the treatment was well tolerated. Conclusions: In the PP population similar efﬁcacy was observed while the ITT population indicated a slight trend favoring G1 with multiple injection sites per muscle. However, since the study had to be closed before full recruitment, noninferiority could not be demonstrated. Keywords: Botulinum toxin; Injection; Neuromuscular junction; Spasticity 186. LONG-TERM EFFECTS OF HIGH DOSES OF INCOBOTULINUMTOXINA (XEOMIN) FOR TREATMENT OF SPASTICITY Tiina Rekand*, Tori Lunde. Department of Neurology, Haukeland University Hospital, Bergen, Norway * Corresponding author: Department of Neurology, Haukeland University Hospital, Jonas Lies vei 65, 5053 Bergen, Norway. E-mail address:[email protected]
Introduction and objectives: The TOWER study (NCT01603459) assessed the safety and efﬁcacy of escalating incobotulinumtoxinA (Xeomin) doses in patients with spasticity of the upper and lower limb due to cerebral causes (stroke and nonstroke). Study participants were treated with 400800 U incobotulinumtoxinA after receiving considerably lower doses of botulinum toxin prior to the study. Methods: At the end of the TOWER study, all participants at the Spasticity Management Clinic in Haukeland University Hospital were given a choice to continue with the doses used in the study or to reduce doses to the prestudy level. Patients who continued high-dose therapy received at least 6 further incobotulinumtoxinA treatments at intervals of 90-100 days. Efﬁcacy evaluation was based on clinical assessments and patient interviews. Results: Of the 7 TOWER study participants at Haukeland University Hospital, 6 continued with high-dose therapy (50% male; median age, 54.5 years); 1 patient was not followed up further. Spasticity was related to stroke (n¼5) and to surgery for a brain tumor (n¼1). Prior to the TOWER study, patients had received a mean dose of 385 U incobotulinumtoxinA. During TOWER, patients received total doses of 400 U-780 U incobotulinumtoxinA into both the upper and lower limb (3 patients), or the upper limb only (3 patients). After TOWER, patients received total doses of 500 U780 U (mean 620 U) incobotulinumtoxinA per treatment cycle over an observation period of 3-5 cycles. The mean dose increase from before to after the study was 41%. Patients reported sustained effects of high-dose treatments on functionality. One patient experienced loss of grasping; hence, the dose was reduced to 600 U. No patient reported side effects. Conclusions: High doses of incobotulinumtoxinA (up to 780 U) were well tolerated and allowed optimization of botulinum toxin therapy to achieve long-lasting effects. No side effects occurred. Editorial support funded by Merz Pharmaceuticals. Keywords: Botulinum toxin A; IncobotulinumtoxinA; Long-lasting effects; Spasticity