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Article ; Online: Safety and real-world dosing of onabotulinumtoxinA for the treatment of adult spasticity: post hoc analysis of the Adult Spasticity International Registry study.

Bavikatte, Ganesh / Esquenazi, Alberto / Dimyan, Michael A / Dashtipour, Khashayar / Feng, Wuwei / Mayadev, Angeli / Fanning, Kristina / Musacchio, Tiziana / Zuzek, Aleksej / Francisco, Gerard E

American journal of physical medicine & rehabilitation

2024

Abstract: Objective: To evaluate the safety of onabotulinumtoxinA treatment for spasticity across dose ranges in real-world practice.: Design: Adult Spasticity International Registry (ASPIRE) was a multicenter, prospective, observational study (NCT01930786) of ...

Abstract	Objective: To evaluate the safety of onabotulinumtoxinA treatment for spasticity across dose ranges in real-world practice. Design: Adult Spasticity International Registry (ASPIRE) was a multicenter, prospective, observational study (NCT01930786) of onabotulinumtoxinA treatment for adult spasticity over 2 years. Adverse events (AEs), serious AEs (SAEs), treatment-related AEs (TRAEs), and TRSAEs were sorted into 5 categories (≤200 U, 201-400 U, 401-600 U, 601-800 U, ≥801 U) based on cumulative dose per session. Results: In 3103 treatment sessions (T), 730 patients received ≥1 dose of onabotulinumtoxinA. Dose categories included: ≤200 U (n = 312; t = 811), 201-400 U (n = 446, t = 1366), 401-600 U (n = 244, t = 716), 601-800 U (n = 69, t = 149), ≥801 U (n = 29, t = 61). Of these patients, 261 reported 827 AEs, 94 reported 195 SAEs, 20 reported 23 TRAEs, and 2 patients treated with 201-400 U onabotulinumtoxinA reported 3 TRSAEs. TRAEs reported: ≤200 U (8 TRAEs/811, 0.9%); 201-400 U (7/1366, 0.5%); 401-600 U (6/716, 0.8%); 601-800 U (1/149, 0.7%); ≥801 U (1/61, 1.6%). Conclusions: In this post hoc analysis, most treatment sessions were performed with 201-400 U onabotulinumtoxinA. Patients treated with 201-400 U onabotulinumtoxinA had an AE profile consistent with onabotulinumtoxinA package inserts globally (eg, United States, European Union, United Kingdom, Canada). No new safety signals were identified.
Language	English
Publishing date	2024-01-03
Publishing country	United States
Document type	Journal Article
ZDB-ID	219390-5
ISSN	1537-7385 ; 0002-9491 ; 0894-9115
ISSN (online)	1537-7385
ISSN	0002-9491 ; 0894-9115
DOI	10.1097/PHM.0000000000002410
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Article ; Online: How do the physiology and transcallosal effects of the unaffected hemisphere change during inpatient rehabilitation after stroke?

Wittenberg, George F / Dimyan, Michael A

Clinical neurophysiology : official journal of the International Federation of Clinical Neurophysiology

2014 Volume 125, Issue 10, Page(s) 1932–1933

MeSH term(s)	Evoked Potentials, Motor/physiology ; Female ; Humans ; Male ; Motor Cortex/physiopathology ; Neural Inhibition/physiology ; Recovery of Function/physiology ; Stroke/physiopathology
Language	English
Publishing date	2014-02-28
Publishing country	Netherlands
Document type	Editorial ; Comment
ZDB-ID	1463630-x
ISSN	1872-8952 ; 0921-884X ; 1388-2457
ISSN (online)	1872-8952
ISSN	0921-884X ; 1388-2457
DOI	10.1016/j.clinph.2014.02.016
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Article ; Online: Baseline Predictors of Response to Repetitive Task Practice in Chronic Stroke.

Dimyan, Michael A / Harcum, Stacey / Ermer, Elsa / Boos, Amy F / Conroy, Susan S / Liu, Fang / Horn, Linda B / Xu, Huichun / Zhan, Min / Chen, Hegang / Whitall, Jill / Wittenberg, George F

Neurorehabilitation and neural repair

2022 Volume 36, Issue 7, Page(s) 426–436

Abstract: Background: Repetitive task practice reduces mean upper extremity motor impairment in : Objectives: To identify prognostic factors and better understand the biological substrate for reductions in arm impairment in response to repetitive task practice ...

Abstract	Background: Repetitive task practice reduces mean upper extremity motor impairment in Objectives: To identify prognostic factors and better understand the biological substrate for reductions in arm impairment in response to repetitive task practice among patients with chronic (≥6 months) post-stroke hemiparesis. Methods: The intervention is a form of repetitive task practice using a combination of robot-assisted therapy and functional arm use in real-world tasks. Baseline measures include the Fugl-Meyer Assessment, Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, MRI, transcranial magnetic stimulation, kinematics, accelerometry, and genomic testing. Results: Mean increase in FM-UE was 4.6 ± 1.0 SE, median 2.5. Approximately one-third of participants had a clinically meaningful response to the intervention, defined as an increase in FM ≥ 5. The selected logistic regression model had a receiver operating curve with AUC = .988 (Std Error = .011, 95% Wald confidence limits: .967-1) showed little evidence of overfitting. Six variables that predicted response represented impairment, functional, and genomic measures. Conclusion: A simple weighted sum of 6 baseline factors can accurately predict clinically meaningful impairment reduction after outpatient intensive practice intervention in chronic stroke. Reduction of impairment may be a critical first step to functional improvement. Further validation and generalization of this model will increase its utility in clinical decision-making.
MeSH term(s)	Humans ; Paresis ; Recovery of Function ; Stroke ; Stroke Rehabilitation/methods ; Transcranial Magnetic Stimulation/methods ; Upper Extremity
Language	English
Publishing date	2022-05-26
Publishing country	United States
Document type	Journal Article ; Research Support, U.S. Gov't, Non-P.H.S.
ZDB-ID	1491637-x
ISSN	1552-6844 ; 1545-9683 ; 0888-4390
ISSN (online)	1552-6844
ISSN	1545-9683 ; 0888-4390
DOI	10.1177/15459683221095171
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Article: Contraction Phase and Force Differentially Change Motor Evoked Potential Recruitment Slope and Interhemispheric Inhibition in Young Versus Old.

Ermer, Elsa / Harcum, Stacey / Lush, Jaime / Magder, Laurence S / Whitall, Jill / Wittenberg, George F / Dimyan, Michael A

Frontiers in human neuroscience

2020 Volume 14, Page(s) 581008

Abstract: Interhemispheric interactions are important for arm coordination and hemispheric specialization. Unilateral voluntary static contraction is known to increase bilateral corticospinal motor evoked potential (MEP) amplitude. It is unknown how increasing and ...

Abstract	Interhemispheric interactions are important for arm coordination and hemispheric specialization. Unilateral voluntary static contraction is known to increase bilateral corticospinal motor evoked potential (MEP) amplitude. It is unknown how increasing and decreasing contraction affect the opposite limb. Since dynamic muscle contraction is more ecologically relevant to daily activities, we studied MEP recruitment using a novel method and short interval interhemispheric inhibition (IHI) from active to resting hemisphere at 4 phases of contralateral ECR contraction: Rest, Ramp Up [increasing at 25% of maximum voluntary contraction (MVC)], Execution (tonic at 50% MVC), and Ramp Down (relaxation at 25% MVC) in 42 healthy adults. We analyzed the linear portion of resting extensor carpi radialis (ECR) MEP recruitment by stimulating at multiple intensities and comparing slopes, expressed as mV per TMS stimulation level, via linear mixed modeling. In younger participants (age ≤ 30), resting ECR MEP recruitment slopes were significantly and equally larger both at Ramp Up (slope increase = 0.047,
Language	English
Publishing date	2020-10-06
Publishing country	Switzerland
Document type	Journal Article
ZDB-ID	2425477-0
ISSN	1662-5161
ISSN	1662-5161
DOI	10.3389/fnhum.2020.581008
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Article ; Online: Neuroplasticity in the context of motor rehabilitation after stroke.

Dimyan, Michael A / Cohen, Leonardo G

Nature reviews. Neurology

2011 Volume 7, Issue 2, Page(s) 76–85

Abstract: Approximately one-third of patients with stroke exhibit persistent disability after the initial cerebrovascular episode, with motor impairments accounting for most poststroke disability. Exercise and training have long been used to restore motor function ...

Abstract	Approximately one-third of patients with stroke exhibit persistent disability after the initial cerebrovascular episode, with motor impairments accounting for most poststroke disability. Exercise and training have long been used to restore motor function after stroke. Better training strategies and therapies to enhance the effects of these rehabilitative protocols are currently being developed for poststroke disability. The advancement of our understanding of the neuroplastic changes associated with poststroke motor impairment and the innate mechanisms of repair is crucial to this endeavor. Pharmaceutical, biological and electrophysiological treatments that augment neuroplasticity are being explored to further extend the boundaries of poststroke rehabilitation. Potential motor rehabilitation therapies, such as stem cell therapy, exogenous tissue engineering and brain-computer interface technologies, could be integral in helping patients with stroke regain motor control. As the methods for providing motor rehabilitation change, the primary goals of poststroke rehabilitation will be driven by the activity and quality of life needs of individual patients. This Review aims to provide a focused overview of neuroplasticity associated with poststroke motor impairment, and the latest experimental interventions being developed to manipulate neuroplasticity to enhance motor rehabilitation.
MeSH term(s)	Disabled Persons/rehabilitation ; Exercise Therapy/methods ; Humans ; Motor Activity/physiology ; Neuronal Plasticity/physiology ; Recovery of Function/physiology ; Stroke/physiopathology ; Stroke Rehabilitation
Language	English
Publishing date	2011-01-18
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	2491514-2
ISSN	1759-4766 ; 1759-4758
ISSN (online)	1759-4766
ISSN	1759-4758
DOI	10.1038/nrneurol.2010.200
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Article ; Online: Contribution of transcranial magnetic stimulation to the understanding of functional recovery mechanisms after stroke.

Dimyan, Michael A / Cohen, Leonardo G

Neurorehabilitation and neural repair

2009 Volume 24, Issue 2, Page(s) 125–135

Abstract: Motor impairments are a major cause of morbidity and disability after stroke. This article reviews evidence obtained using transcranial magnetic stimulation (TMS) that provides new insight into mechanisms of impaired motor control and disability. They ... ...

Abstract	Motor impairments are a major cause of morbidity and disability after stroke. This article reviews evidence obtained using transcranial magnetic stimulation (TMS) that provides new insight into mechanisms of impaired motor control and disability. They briefly discuss the use of TMS in the diagnosis, prognosis, and therapy of poststroke motor disability. Particular emphasis is placed on TMS as a tool to explore mechanisms of neuroplasticity during spontaneous and treatment-induced recovery of motor function to develop more rational and clinically useful interventions for stroke rehabilitation.
MeSH term(s)	Evoked Potentials, Motor/physiology ; Humans ; Models, Neurological ; Movement Disorders/diagnosis ; Movement Disorders/etiology ; Movement Disorders/rehabilitation ; Neural Pathways/physiology ; Neuronal Plasticity/physiology ; Recovery of Function/physiology ; Stroke/complications ; Stroke/therapy ; Transcranial Magnetic Stimulation
Language	English
Publishing date	2009-09-18
Publishing country	United States
Document type	Journal Article ; Research Support, N.I.H., Intramural ; Review
ZDB-ID	1491637-x
ISSN	1552-6844 ; 1545-9683 ; 0888-4390
ISSN (online)	1552-6844
ISSN	1545-9683 ; 0888-4390
DOI	10.1177/1545968309345270
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Article ; Online: Modification of existing human motor memories is enabled by primary cortical processing during memory reactivation.

Censor, Nitzan / Dimyan, Michael A / Cohen, Leonardo G

Current biology : CB

2010 Volume 20, Issue 17, Page(s) 1545–1549

Abstract: One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in ... ...

Abstract	One of the most challenging tasks of the brain is to constantly update the internal neural representations of existing memories. Animal studies have used invasive methods such as direct microfusion of protein inhibitors to designated brain areas, in order to study the neural mechanisms underlying modification of already existing memories after their reactivation during recall [1-4]. Because such interventions are not possible in humans, it is not known how these neural processes operate in the human brain. In a series of experiments we show here that when an existing human motor memory is reactivated during recall, modification of the memory is blocked by virtual lesion [5] of the related primary cortical human brain area. The virtual lesion was induced by noninvasive repetitive transcranial magnetic stimulation guided by a frameless stereotactic brain navigation system and each subject's brain image. The results demonstrate that primary cortical processing in the human brain interacting with pre-existing reactivated memory traces is critical for successful modification of the existing related memory. Modulation of reactivated memories by noninvasive cortical stimulation may have important implications for human memory research and have far-reaching clinical applications.
MeSH term(s)	Brain/physiology ; Humans ; Memory ; Psychomotor Performance
Language	English
Publishing date	2010-09-02
Publishing country	England
Document type	Journal Article ; Research Support, N.I.H., Intramural
ZDB-ID	1071731-6
ISSN	1879-0445 ; 0960-9822
ISSN (online)	1879-0445
ISSN	0960-9822
DOI	10.1016/j.cub.2010.07.047
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Article ; Online: Methods for an Investigation of Neurophysiological and Kinematic Predictors of Response to Upper Extremity Repetitive Task Practice in Chronic Stroke.

Harcum, Stacey / Conroy, Susan S / Boos, Amy / Ermer, Elsa / Xu, Huichun / Zhan, Min / Chen, Hegang / Whitall, Jill / Dimyan, Michael A / Wittenberg, George F

Archives of rehabilitation research and clinical translation

2019 Volume 1, Issue 3-4

Abstract: Objective: To demonstrate the feasibility of algorithmic prediction using a model of baseline arm movement, genetic factors, demographic characteristics, and multimodal assessment of the structure and function of motor pathways. To identify prognostic ... ...

Abstract	Objective: To demonstrate the feasibility of algorithmic prediction using a model of baseline arm movement, genetic factors, demographic characteristics, and multimodal assessment of the structure and function of motor pathways. To identify prognostic factors and the biological substrate for reductions in arm impairment in response to repetitive task practice. Design: This prospective single-group interventional study seeks to predict response to a repetitive task practice program using an intent-to-treat paradigm. Response is measured as a change of ≥5 points on the Upper Extremity Fugl-Meyer from baseline to final evaluation (at the end of training). Setting: General community. Participants: Anticipated enrollment of community-dwelling adults with chronic stroke (N = 96; onset≥6mo) and moderate to severe residual hemiparesis of the upper limb as defined by a score of 10-45 points on the Upper Extremity Fugl-Meyer. Intervention: The intervention is a form of repetitive task practice using a combination of robot-assisted therapy coupled with functional arm use in real-world tasks administered over 12 weeks. Main outcome measures: Upper Extremity Fugl-Meyer Assessment (primary outcome), Wolf Motor Function Test, Action Research Arm Test, Stroke Impact Scale, questionnaires on pain and expectancy, magnetic resonance imaging, transcranial magnetic stimulation, arm kinematics, accelerometry, and a saliva sample for genetic testing. Results: Methods for this trial are outlined, and an illustration of interindividual variability is provided by example of 2 participants who present similarly at baseline but achieve markedly different outcomes. Conclusion: This article presents the design, methodology, and rationale of an ongoing study to develop a predictive model of response to a standardized therapy for stroke survivors with chronic hemiparesis. Applying concepts from precision medicine to neurorehabilitation is practicable and needed to establish realistic rehabilitation goals and to effectively allocate resources.
Language	English
Publishing date	2019-09-10
Publishing country	United States
Document type	Journal Article
ISSN	2590-1095
ISSN (online)	2590-1095
DOI	10.1016/j.arrct.2019.100024
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Article ; Online: Nonparetic arm force does not overinhibit the paretic arm in chronic poststroke hemiparesis.

Dimyan, Michael A / Perez, Monica A / Auh, Sungyoung / Tarula, Erick / Wilson, Matthew / Cohen, Leonardo G

Archives of physical medicine and rehabilitation

2014 Volume 95, Issue 5, Page(s) 849–856

Abstract: Objective: To determine whether nonparetic arm force overinhibits the paretic arm in patients with chronic unilateral poststroke hemiparesis.: Design: Case-control neurophysiological and behavioral study of patients with chronic stroke.: Setting: ... ...

Abstract	Objective: To determine whether nonparetic arm force overinhibits the paretic arm in patients with chronic unilateral poststroke hemiparesis. Design: Case-control neurophysiological and behavioral study of patients with chronic stroke. Setting: Research institution. Participants: Eighty-six referred patients were screened to enroll 9 participants (N=9) with a >6 month history of 1 unilateral ischemic infarct that resulted in arm hemiparesis with residual ability to produce 1Nm of wrist flexion torque and without contraindication to transcranial magnetic stimulation. Eight age- and handedness-matched healthy volunteers without neurologic diagnosis were studied for comparison. Interventions: Not applicable. Main outcome measure: Change in interhemispheric inhibition targeting the ipsilesional primary motor cortex (M1) during nonparetic arm force. We hypothesized that interhemispheric inhibition would increase more in healthy controls than in patients with hemiparesis. Results: Healthy age-matched controls had significantly greater increases in inhibition from their active to resting M1 than patients with stroke from their active contralesional to resting ipsilesional M1 in the same scenario (20%±7% vs -1%±4%, F1,12=6.61, P=.025). Patients with greater increases in contralesional to ipsilesional inhibition were better performers on the 9-hole peg test of paretic arm function. Conclusions: Our findings reveal that producing force with the nonparetic arm does not necessarily overinhibit the paretic arm. Though our study is limited in generalizability by the small sample size, we found that greater active contralesional to resting ipsilesional M1 inhibition was related with better recovery in this subset of patients with chronic poststroke.
MeSH term(s)	Aged ; Aged, 80 and over ; Arm/physiopathology ; Chronic Disease ; Exercise Therapy/methods ; Female ; Follow-Up Studies ; Hand Strength/physiology ; Humans ; Male ; Middle Aged ; Motor Cortex/physiopathology ; Motor Skills/physiology ; Paresis/etiology ; Paresis/physiopathology ; Paresis/rehabilitation ; Recovery of Function ; Retrospective Studies ; Stroke/complications ; Stroke/physiopathology ; Stroke Rehabilitation ; Task Performance and Analysis ; Treatment Outcome
Language	English
Publishing date	2014-01-16
Publishing country	United States
Document type	Comparative Study ; Journal Article ; Randomized Controlled Trial ; Research Support, N.I.H., Extramural ; Research Support, N.I.H., Intramural
ZDB-ID	80057-0
ISSN	1532-821X ; 0003-9993
ISSN (online)	1532-821X
ISSN	0003-9993
DOI	10.1016/j.apmr.2013.12.023
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Article ; Online: Emerging subspecialties: neurorehabilitation: training neurologists to retrain the brain.

Dimyan, Michael A / Dobkin, Bruce H / Cohen, Leonardo G

Neurology

2008 Volume 70, Issue 16, Page(s) e52–4

MeSH term(s)	Brain/physiology ; Humans ; Medicine/methods ; Medicine/trends ; Nervous System Diseases/rehabilitation ; Neurology/methods ; Neurology/trends ; Physicians/trends ; Rehabilitation/methods ; Rehabilitation/trends ; Specialization
Language	English
Publishing date	2008-04-14
Publishing country	United States
Document type	Journal Article ; Review
ZDB-ID	207147-2
ISSN	1526-632X ; 0028-3878
ISSN (online)	1526-632X
ISSN	0028-3878
DOI	10.1212/01.wnl.0000309216.81257.3f
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