Objective To study the effect of botulinum neurotoxin (BoNT) treatment in jerky and tremulous functional movement disorders (FMD).Methods Patients with invalidating, chronic (>1 year) symptoms... Show moreObjective To study the effect of botulinum neurotoxin (BoNT) treatment in jerky and tremulous functional movement disorders (FMD).Methods Patients with invalidating, chronic (>1 year) symptoms were randomly assigned to two subsequent treatments with BoNT or placebo every 3 months with stratification according to symptom localisation. Improvement on the dichotomised Clinical Global Impression-Improvement scale (CGI-I) (improvement vs no change or worsening) at 4 months, assessed by investigators blinded to the allocated treatment was the primary outcome. Subsequently all patients were treated with BoNT in a ten month open-label phase.Results Between January 2011 and February 2015 a total of 239 patients were screened for eligibility of whom 48 patients were included. No difference was found on the primary outcome (BoNT 16 of 25 (64.0%) vs Placebo 13 of 23 patients (56.5%); proportional difference 0.075 (95% CI -0.189 to 0.327; p=0.77). Secondary outcomes (symptom severity, disease burden, disability, quality of life and psychiatric symptoms) showed no between-group differences. The open-label phase showed improvement on the CGI-I in 19/43 (44.2%) of remaining patients, with a total of 35/43 (81.4%) improvement compared with baseline.Conclusions In this double-blind randomised controlled trial of BoNT for chronic jerky and tremulous FMD, we found no evidence of improved outcomes compared with placebo. Motor symptoms improved in a large proportion in both groups which was sustained in the open-label phase. This study underlines the substantial potential of chronic jerky and tremulous FMD patients to recover and may stimulate further exploration of placebo-therapies in these patients. Show less
Contarino, M.F.; Dool, J. van den; Balash, Y.; Bhatia, K.; Giladi, N.; Koelman, J.H.; ... ; Tijssen, M.A.J. 2017
BackgroundSubthalamic nucleus (STN) deep brain stimulation effectively improves parkinsonian symptoms. It is hypothesized that distinct functional territories with different neurophysiologic... Show moreBackgroundSubthalamic nucleus (STN) deep brain stimulation effectively improves parkinsonian symptoms. It is hypothesized that distinct functional territories with different neurophysiologic activity within the STN relate to different symptoms.ObjectiveThe aim of the study was to identify distinctive characteristics of STN neuronal activity related to tremor by directly comparing tremor sides with no-tremor sides. In addition, we studied the spatial pattern of frequency distributions within the STN in more detail.MethodsWe analyzed intraoperative STN single/multiunit recordings from 33 tremor sides and 23 no-tremor sides. STN tracks were normalized to a length of 1 and subdivided into eight successive layers. The power spectral density was split into six frequency bands: theta (3-8 Hz), alpha (9-12 Hz), lower beta (13-20 Hz), upper beta (21-30 Hz), lower gamma (31-59 Hz), and upper gamma (60-100 Hz).ResultsTremor sides presented predominant theta frequency oscillations in the most dorsal layers of the STN, whereas in no-tremor sides beta frequencies predominated. Oscillatory activity was stronger in the dorsal STN than in the ventral, and this pattern was specific for frequencies in the theta, alpha, and beta bands, but not in the gamma bands.ConclusionsOur study supports the hypothesis that the presence of tremor is associated with a distinctive neuronal oscillations pattern. In particular, we demonstrate the specificity of the association of theta frequencies in the dorsal STN with tremor. Identification of symptom-specific characteristics of intraoperative microrecordings in the STN may lead to refinement of targeting for each patient, tailored to the specific clinical presentation. (C) 2012 Elsevier Inc. All rights reserved. Show less
Groen, J.L.; Ritz, K.; Contarino, M.F.; Warrenburg, B.P. van de; Aramideh, M.; Foncke, E.M.; ... ; Tijssen, M.A. 2010
Mutations in THAP1, a gene encoding a nuclear pro-apoptotic protein, have been associated with DYT6 dystonia. First reports on the phenotype of DYT6 dystonia show an early onset dystonia with... Show moreMutations in THAP1, a gene encoding a nuclear pro-apoptotic protein, have been associated with DYT6 dystonia. First reports on the phenotype of DYT6 dystonia show an early onset dystonia with predominant cranio-cervical and laryngeal involvement. Here we assessed the frequency and phenotype of THAP1 mutation carriers in a large Dutch cohort of adult-onset >= 26 years) dystonia (n = 388) and early-onset dystonia (n = 67) patients. We describe the phenotype of DYT6 dystonia patients and their response on GPi DBS. Overall, 3 nonsynonymous heterozygous mutations were detected in the early-onset group (4.5%). Two DYT6 families were identified, showing a heterozygous phenotype. All patients had segmental or generalized dystonia, often associated with profound oromandibular and laryngeal involvement. No nonsynonymous mutations were found in patients with adult-onset focal dystonia. Rare synonymous variants were identified in conserved regions of THAP1, two in the adult-onset cervical dystonia group and one in the control group. Four DYT6 dystonia patients were treated with GPi DBS with moderate to good response on motor function but marginal benefit on speech. (C) 2010 Movement Disorder Society Show less
