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November 05, 2019; 93 (19) Article

Clinical and neural responses to cognitive behavioral therapy for functional tremor

View ORCID ProfileAlberto J. Espay, View ORCID ProfileScott Ries, Thomas Maloney, Jennifer Vannest, Erin Neefus, Alok K. Dwivedi, Jane B. Allendorfer, Lawson R. Wulsin, View ORCID ProfileW. Curt LaFrance, View ORCID ProfileAnthony E. Lang, Jerzy P. Szaflarski
First published October 4, 2019, DOI: https://doi.org/10.1212/WNL.0000000000008442
Alberto J. Espay
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Scott Ries
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Thomas Maloney
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Jennifer Vannest
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Erin Neefus
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Alok K. Dwivedi
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Jane B. Allendorfer
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Lawson R. Wulsin
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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W. Curt LaFrance
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Anthony E. Lang
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Jerzy P. Szaflarski
From the Gardner Family Center for Parkinson's Disease and Movement Disorders (A.J.E., E.N.); Mood Disorders Center (S.R., L.R.W.), University of Cincinnati Gardner Neuroscience Institute; Pediatric Neuroimaging Research Consortium (T.M., J.V.), Cincinnati Children's Hospital; Department of Pediatrics (J.V.), University of Cincinnati College of Medicine, OH; Department of Biomedical Sciences (A.K.D.), Paul L. Foster School of Medicine, Texas Tech University Health Sciences Center, El Paso; Department of Neurology (J.B.A., J.P.S.), University of Alabama at Birmingham; Division of Neuropsychiatry and Behavioral Neurology (W.C.L.), Rhode Island Hospital, Providence; and Edmond J. Safra Program in Parkinson's Disease and Morton and Gloria Shulman Movement Disorders Clinic (A.E.L.), Toronto Western Hospital, University of Toronto, Ontario, Canada.
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Clinical and neural responses to cognitive behavioral therapy for functional tremor
Alberto J. Espay, Scott Ries, Thomas Maloney, Jennifer Vannest, Erin Neefus, Alok K. Dwivedi, Jane B. Allendorfer, Lawson R. Wulsin, W. Curt LaFrance, Anthony E. Lang, Jerzy P. Szaflarski
Neurology Nov 2019, 93 (19) e1787-e1798; DOI: 10.1212/WNL.0000000000008442

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This article has corrections. Please see:

  • Clinical and neural responses to cognitive behavioral therapy for functional tremor - March 10, 2020
  • Clinical and neural responses to cognitive behavioral therapy for functional tremor - November 10, 2020
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Abstract

Objectives To evaluate changes in tremor severity and motor/emotion-processing circuits in response to cognitive behavioral therapy (CBT) delivered as treatment for functional tremor (FT), the most common functional movement disorder in adults.

Methods Fifteen patients with FT underwent fMRI with motor, basic-emotion, and intense-emotion tasks before and after 12 weeks of CBT. Baseline fMRI was compared to those of 25 healthy controls (HCs). The main clinical endpoint was the tremor score (sum of severity, duration, and incapacitation subscores) adapted from the Rating Scale for Psychogenic Movement Disorders (PMDRS) assessed by a blinded clinician. CBT responders were defined as those with PMDRS score reduction >75%. Anatomic and functional brain images were obtained with a 4T MRI system. Generalized linear model and region-of-interest analyses were used to evaluate before-versus-after treatment-related changes in brain activation.

Results CBT markedly reduced tremor severity (p < 0.01) with remission/near remission achieved in 73.3% of the cohort. Compared to HCs, in those with FT, a functionally defined fMRI region of interest in the anterior cingulate/paracingulate cortex showed increased activation at baseline and decreased activation after CBT during basic-emotion processing (p = 0.012 for CBT responders). Among CBT responders, the change in anterior cingulate/paracingulate was more significant in those with more severe baseline depression (r = 0.75, p < 0.01).

Conclusions Tremor severity improved significantly after CBT. The improvement was associated with changes in the anterior cingulate/paracingulate activity, which may represent a marker of emotional dysregulation in FT and a predictor of treatment response.

Classification of evidence This study provides Class III evidence that CBT significantly improves tremor severity in patients with functional tremor.

Glossary

AFNI=
Analysis of Functional Neuroimages;
CBT=
cognitive behavioral therapy;
DSM-IV=
Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
FSL=
FMRIB Software Library;
FT=
functional tremor;
HAM-A=
Hamilton Anxiety Scale;
HAM-D=
Hamilton Depression Scale;
HC=
healthy control;
ICD-10=
International Classification of Diseases, 10th revision;
MINI=
Mini International Neuropsychiatric Interview;
PMDRS=
Rating Scale for Psychogenic Movement Disorders;
PNES=
psychogenic nonepileptic seizures;
ROI=
region of interest;
TFCE=
threshold-free cluster enhancement

Footnotes

  • Go to Neurology.org/N for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Editorial, page 825

  • Class of Evidence: NPub.org/coe

  • CME Course: NPub.org/cmelist

  • Received March 6, 2019.
  • Accepted in final form June 19, 2019.
  • © 2019 American Academy of Neurology
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