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The Effect of Botulinum Toxin on Network Connectivity in Cervical Dystonia: Lessons from Magnetoencephalography

Background: Pharmacological management of cervical dystonia (CD) is considered to be symptomatic in effect, rather than targeting the underlying pathophysiology of the disease. Magnetoencephalography (MEG), a direct measure of neuronal activity, while accepted as a modality for pre-surgical mapping in epilepsy, has never been used to explore the effect of pharmacotherapy in movement disorders.

Methods: Resting state MEG data were collected from patients with CD, pre- and post-botulinum toxin injections. All of these patients exhibited good clinical benefit with botulinum toxin. Resting state MEG data from four age- and gender-matched healthy controls with no neurological disorders were also collected.

Results: Our exploratory study reveals a difference in coherence between controls and patients in the following regions: fronto-striatal, occipito-striatal, parieto-striatal, and striato-temporal networks. In these regions there is an increase after botulinum toxin. Specifically, increased coherence in the left putamen and right superior parietal gyrus was noticeable. Both intrahemispheric and interhemispheric networks were affected.

Discussion: This is the first attempt to directly assess changes in functional connectivity with pharmacotherapy using MEG. Botulinum toxin might affect sensorimotor integration, leading to clinical benefit. The presence of increased interhemispheric coherence and intrahemispheric coherence points to the importance of global and local networks in the pathophysiology of dystonia.

Publication type: 
Author: 
Abhimanyu Mahajan
Abdullah Alshammaa
Andrew Zillgitt
Susan M. Bowyer
Peter LeWitt
Patricia Kaminski
Christos Sidiropoulos
Subjects: 
Magnetoencephalography
Dystonia
Botulinum toxin--Therapeutic use
Sensorimotor integration
Neurosciences
Title string: 
The Effect of Botulinum Toxin on Network Connectivity in Cervical Dystonia: Lessons from Magnetoencephalography
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:3tx95x69px

The Inter-rater Variability of Clinical Assessment in Post-anoxic Myoclonus

Background: Acute post-anoxic myoclonus (PAM) can be divided into an unfavorable (generalized/subcortical) and more favorable ((multi)focal/cortical) outcome group that could support prognostication in post-anoxic encephalopathy; however, the inter-rater variability of clinically assessing these PAM subtypes is unknown.

Methods: We prospectively examined PAM patients using a standardized video protocol. Videos were rated by three neurologists who classified PAM phenotype (generalized/(multi)focal), stimulus sensitivity, localization (proximal/distal/both), and severity (Clinical Global Impression-Severity Scale (CGI-S) and Unified Myoclonus Rating Scale (UMRS)).

Results: Poor inter-rater agreement was found for phenotype and stimulus sensitivity (κ = –0.05), moderate agreement for localization (κ = 0.46). Substantial agreement was obtained for the CGI-S (intraclass correlation coefficient (ICC) = 0.64) and almost perfect agreement for the UMRS (ICC = 0.82).

Discussion: Clinical assessment of PAM is not reproducible between physicians, and should therefore not be used for prognostication. PAM severity measured by the UMRS appears to be reliable; however, the relation between PAM severity and outcome is unknown.

Topic: 
Publication type: 
Author: 
van Jonathan C. Zijl
Martijn Beudel
Jan Elting-Willem J.
de Bauke M. Jong
van der Joukje Naalt
van den Walter M. Bergh
Andrea O. Rossetti
Marina A. J. Tijssen
Janneke Horn
Subjects: 
Neurology
Myoclonus
Prognosis
Title string: 
The Inter-rater Variability of Clinical Assessment in Post-anoxic Myoclonus
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:7sqv9s4mxh

Supplemental File: The Interrater Variability of Clinical Assessment in Post-anoxic Myoclonus

Background: Acute post-anoxic myoclonus (PAM) can be divided into an unfavorable (generalized/subcortical) and more favorable ((multi)focal/cortical) outcome group which could support prognostication in post-anoxic encephalopathy, however the interrater variability of clinically assessing these PAM subtypes is unknown.
Methods: We prospectively examined PAM patients using a standardized video protocol. Videos were rated by three neurologists who classified PAM phenotype (generalized/(multi)focal), stimulus sensitivity, localization (proximal/distal/both), and severity (Clinical Global Impression-Severity scale (CGI-S) and Unified Myoclonus Rating Scale (UMRS)).
Results: Poor interrater agreement was found for phenotype and stimulus sensitivity
(κ=-0.05), moderate agreement for localization (κ=0.46). Substantial agreement was obtained for the CGI-S (intraclass correlation coefficient (ICC)=0.64) and almost perfect agreement for the UMRS (ICC=0.82).
Discussion: Clinical assessment of PAM is not reproducible between physicians, and should therefore not be used for prognostication. PAM severity measured by the UMRS appears to be reliable, however the relation between PAM severity and outcome is unknown.

Topic: 
Author: 
van Jonathan C. Zijl
Martijn Beudel
Jan Elting-Willem J.
de Bauke M. Jong
van der Joukje Naalt
van den Walter M. Bergh
Andrea O. Rossetti
Marina A. J. Tijssen
Janneke Horn
Subjects: 
Myoclonus
Diagnosis
Clinical medicine
Title string: 
Supplemental File: The Interrater Variability of Clinical Assessment in Post-anoxic Myoclonus
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:5x69p8cz9q

A Comparison Study of Cognitive and Neuropsychiatric Features of Essential Tremor and Parkinson’s Disease

Background: Essential tremor (ET) and Parkinson’s disease (PD) are two of the most common movement disorders. Leaving aside their motor features, these two conditions share several non-motor features, including cognitive dysfunction and personality changes. However, there are few data comparing the cognitive and personality profiles of ET with PD. Here we compare the cognitive and personality profiles of the two diseases.

Methods: Thirty-two consecutive non-demented ET patients (13 females and 19 males) (67.7±9.8 years), 32 non-demented PD patients (13 females and 19 males) (67.7±9.5 years), and 32 healthy matched controls (14 females and 18 males) (67.9±10.1 years) underwent a neuropsychological test battery, including a global cognitive assessment and tests of attention, executive function, memory, language, and visuospatial function, as well as the Personality Assessment Inventory. Multivariable linear regression analyses were performed, adjusted for age, sex, years of education, medications that potentially affect cognitive function, number of medications, and the 17-item Hamilton Depression Rating Scale Total Score.

Results: Neuropsychological scores were similar in PD and ET patients, but patients with disease performed more poorly than control subjects in cognitive tasks such as attention, executive function, memory, and naming.

Discussion: ET and PD exhibited similar deficits in specific aspects of neuropsychological functioning, particularly those thought to rely on the integrity of the prefrontal cortex, and this suggests involvement of frontocerebellar circuits. These findings further challenge the traditional view of ET as a benign and monosymptomatic disorder.

Publication type: 
Author: 
Puertas-MartíVer nónica
FernáSara ndez-Guinea
Alberto Villarejo-Galende
Elan D. Louis
Juan Pablo Romero
Benito-LeóJuli nán
Subjects: 
Tremor
Parkinson's disease
Neuropsychology
Movement disorders
Neurosciences
Medicine
Title string: 
A Comparison Study of Cognitive and Neuropsychiatric Features of Essential Tremor and Parkinson’s Disease
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:205956

Deutetrabenazine in Tics Associated with Tourette Syndrome

Background: Deutetrabenazine, an inhibitor of vesicular monoamine transporter type 2 (VMAT2) depletes presynaptic dopamine and is useful in the treatment of hyperkinetic movement disorders. This study explored the safety, tolerability, and preliminary efficacy of deutetrabenazine in adolescents with moderate-to-severe tics associated with Tourette syndrome (TS).

Methods: In this open-label study of 12–18-year-old patients with TS-related tics, deutetrabenazine was titrated up to 36 mg/day over 6 weeks to adequately suppress tics without bothersome adverse effects (AEs), followed by maintenance at optimal dose for 2 weeks. An independent blinded rater assessed tic severity using the Yale Global Tic Severity Scale (YGTSS), which was the primary outcome measure. Secondary outcome measures included the TS Clinical Global Impression (TS-CGI) and TS Patient Global Impression of Change (TS-PGIC).

Results: Twenty-three enrolled patients received deutetrabenazine and had at least 1 post-baseline YGTSS assessment. The mean (SD [standard deviation]) baseline YGTSS Total Tic Severity Score (TTS) was 31.6 (7.9) and had decreased by 11.6 (8.2) points at week 8, a 37.6% reduction in tic severity (p<0.0001). The TS-CGI score improved by 1.2 (0.81) points (p<0.0001) and the TS-PGIC results at week 8 indicated that 76% of patients were much improved or very much improved compared with baseline. The mean (SD) daily deutetrabenazine dose at week 8 was 32.1 (6.6) mg (range 18–36 mg). One week after withdrawal of deutetrabenazine, the TTS scores increased by 5.6 (8.4) points, providing confirmation of the drug effect. No serious or severe adverse events were reported.

Discussion: The results of this open-label 8-week study suggest that deutetrabenazine is safe and associated with improvement in tic severity in adolescents with TS and troublesome tics.

Publication type: 
Author: 
Joseph Jankovic
Joohi Jimenez-Shahed
Cathy Budman
Barbara Coffey
Tanya Murphy
David Shprecher
David Stamler
Subjects: 
Tic disorders
Movement disorders
Movement disorders--Treatment
Tourette syndrome
Neurosciences
Medicine
Title string: 
Deutetrabenazine in Tics Associated with Tourette Syndrome
GUID update: 
https://academiccommons.columbia.edu/catalog/ac:205926

Occurrence of Dysphagia Following Botulinum Toxin Injection in Parkinsonism-related Cervical Dystonia: A Retrospective Study

Background: The aim was to compare the occurrence of post-injection dysphagia in parkinsonism-related cervical dystonia (PRCD) versus cervical dystonia (CD) of other etiologies (non-PRCD). A secondary objective was to explore potential clinical differences between PRCD and non-PRCD and their respective responses to botulinum toxin (BoNT).

Methods: A cross-sectional chart review was carried out of patients treated for CD with Onabotulinumtoxin A at the University of Florida. We collected demographic information, dose of BoNT injected, patient-reported presence of dysphagia as a side effect, patient-perceived duration of benefit and efficacy according to the Clinical Global Impression Scale (CGIS).

Results: Of the 144 patients included, 24 patients were diagnosed with PRCD and 120 were diagnosed as non-PRCD. Data analysis showed no significant differences in number of weeks of benefit from BoNT (PRCD 9.1±3.7 versus non-PRCD 9.4±3.7 weeks, p = 0.830), BoNT dosage (PRCD 235.0±95.6 versus non-PRCD 263.7±101.3 units, p = 0.181), median CGIS score (median = 2 or “much improved” for both groups, p = 0.88), or the presence of dysphagia after BoNT (PRCD 17% versus non-PRCD 19 %, p = 0.753, n = 132). In a subgroup analysis of the non-PRCD group, patients who experienced dysphagia were older than those who did not (63.9±8.9 years versus 58.1±14.4 years, p = 0.02).

Discussion: Despite an increased baseline risk of dysphagia in patients with PRCD, BoNT appears to be equally safe and equally beneficial in PRCD and non-PRCD patients.

Publication type: 
Author: 
Addie Patterson
Leonardo Almeida
Christopher W. Hess
Daniel Martinez-Ramirez
Michael S. Okun
Ramon L. Rodriguez
Valerie Rundle-Gonzalez
Aparna Wagle Shukla
Irene A. Malaty
Subjects: 
Medicine
Neurosciences
Title string: 
Occurrence of Dysphagia Following Botulinum Toxin Injection in Parkinsonism-related Cervical Dystonia: A Retrospective Study
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:204145

A Pilot Study of Botulinum Toxin for Jerky, Position-Specific, Upper Limb Action Tremor

Background: We aimed to investigate the efficacy and safety of botulinum toxin (BT) injections for jerky action tremor of the upper limb.

Methods: We performed an uncontrolled, prospective study of electromyography (EMG)-guided BT injections for jerky, position-specific, upper limb action tremor. The primary outcome was clinical global impression at 3–6 weeks after baseline.

Results: Eight patients with jerky, position-specific action tremor involving the upper limb were consecutively recruited. After a median follow-up of 4.4 weeks (interquartile range [IQR] 3.6–6 weeks), four of them rated themselves as “improved” and two as “much improved.” Five of these six subjects reported improvements in specific activities of daily living (bringing liquids to mouth, feeding, shaving, and dressing). Upper limb subscore of the Fahn–Tolosa–Marin Tremor Rating Scale (FTM) significantly decreased from 4.5 (4–6) to 3 (2–5) (p = 0.01).

Discussion: This pilot, prospective cohort study suggests that EMG-guided BT injections may improve jerky, position-specific, upper limb action tremor. Placebo-controlled studies evaluating larger samples of patients are warranted to confirm these findings.

Publication type: 
Author: 
Tabish A. Saifee
Tiago Teodoro
Roberto Erro
Carla Cordivari
Mark J. Edwards
Subjects: 
Medicine
Neurosciences
Toxicology
Title string: 
A Pilot Study of Botulinum Toxin for Jerky, Position-Specific, Upper Limb Action Tremor
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:204136

Ethosuximide for Essential Tremor: An Open-Label Trial

Background: T-type calcium channel activation has been postulated to underlie rhythmicity in the olivo-cerebellar system that is implicated in ET. Ethosuximide reduces T-type calcium currents and can suppress tremor in two animal models of ET. We explored the effects of ethosuximide in subjects with ET in an open-label trial using both clinical scales and accelerometric recordings measures. We initially planned to conduct the trial with 15 patients, but due to lack of efficacy and a high incidence of adverse effects, the trial was stopped after seven patients had participated.

Methods: Seven patients diagnosed with ET were included in the study. The ethosuximide dose was 500 mg daily (BID). The main outcome measures were: 1) tremor clinical rating scale (TCRS) score, 2) accelerometric recordings, and 3) self-reported disability scale score.

Results: Five patients completed the study, and two dropped out due to adverse effects. There were no significant changes in clinical scores in motor task performance (TCRS 1+2), daily living activities (TCRS 3), or in the patients’ subjective assessment (TCRS 4) and global appraisal. There were no differences observed for accelerometry data or disability scale scores. Anxiety, nervousness, headache, and dizziness were reported by two patients while on ethosuximide, causing them to stop the trial. No patient preferred to continue ethosuximide treatment.

Discussion: The results of our exploratory study suggest that ethosuximide is not an effective treatment for ET.

Topic: 
Publication type: 
Author: 
Alexandre Gironell
Juan Marin-Lahoz
Subjects: 
Medicine
Pharmacology
Title string: 
Ethosuximide for Essential Tremor: An Open-Label Trial
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:204019

Effective Management of Upper Limb Parkinsonian Tremor by IncobotulinumtoxinA Injections Using Sensor-based Biomechanical Patterns

Background: Focal treatment of Parkinson’s disease tremor by botulinum toxin type A incobotulinumtoxinA (BoNT-A) injections has been inadequately investigated and at best provides modest relief with significant muscle weakness. Complexity of multi-joint tremulous movements results in non-individualized dosing regimens. This 38-week open-label study used kinematic technology to guide muscle selection and improve efficacy of incobotulinumtoxinA (BoNT-A) injections for Parkinson’s disease tremor. Methods: Participants (n=28) attended study visits at weeks 0, 6, 16, 22, 32, and 38, and were injected with BoNT-A at weeks 0, 16, and 32. During each visit, clinical tremor scales, the Unified Parkinson’s Disease Rating Scale (UPDRS) and the Fahn–Tolosa–Marin (FTM), and kinematic assessments were conducted. Participants performed rest and postural scripted tasks with motion sensors placed over the wrist, elbow, and shoulder joints where tremor was quantified by angular root mean square (RMS) amplitude in multiple degrees of freedom at each joint. Injection parameters were determined using the clinician’s interpretation of which muscles would contribute to the upper limb tremor biomechanics analyzed kinematically. Results: Kinematic measures of tremor amplitude allowed detailed segmentation of tremor into directional components at each arm joint permitting a statistically significant decrease in mean UPDRS item 20 (rest tremor) at week 16 (p=0.006) and at week 32 (p=0.014), and in FTM tremor severity scores at week 6 (p=0.024). Ten participants perceived mild muscle weakness following the third treatment, which did not interfere with performing activities of daily living. Discussion: Kinematics is a simple method for standardizing assessments and treatment of upper limb Parkinson’s disease tremor, thereby personalizing tremor therapy and optimizing the effect of BoNT-A injections for Parkinson’s disease tremor.

Publication type: 
Author: 
Fariborz Rahimi
Olivia Samotus
Jack Lee
Mandar Jog
Subjects: 
Health sciences
Neurosciences
Medicine
Movement disorders
Botulinum toxin
Parkinson's disease--Treatment
Biomechanics
Title string: 
Effective Management of Upper Limb Parkinsonian Tremor by IncobotulinumtoxinA Injections Using Sensor-based Biomechanical Patterns
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:193448

Sources of Disability in Tourette Syndrome: Children vs. Adults

Background: Tourette syndrome (TS) is a neurodevelopmental disorder characterized by tics and neuropsychiatric co-morbidities like Obsessive Compulsive Disorder (OCD) and Attention Deficit Disorder (ADHD), among others. In many instances tics get better with age but this is not always true regarding the psychiatric co-morbidities. Methods: This manuscript reviews the disease-specific Quality of Life (QOL) instruments used to measure disability in TS and the existing literature on sources of functional impairment in children and adults with TS. Results: Traditionally, disability in TS has been recorded using objective measures. In recent years there has been a development of disease-specific instruments to measure subjectively the impact of the different aspects of TS on the patient's daily function. The differential impact of tics vs. the psychiatric co-morbidities in children with TS is an issue of debate in the existing literature. In adults with TS, the literature is scant, therefore the sources of disability in this group are even less defined compared to children. Discussion: As clinicians, we need to focus on determining the sources of disability in children and adults with TS so we can target our interventions successfully.

Publication type: 
Author: 
Katie Kompoliti
Subjects: 
Health sciences
Neurosciences
Medicine
Tourette syndrome
Quality of life--Measurement
Tourette syndrome in children
People with disabilities
Title string: 
Sources of Disability in Tourette Syndrome: Children vs. Adults
GUID update: 
http://academiccommons.columbia.edu/catalog/ac:193469

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