Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion

Meng Wang¹, Tolulope Sajobi¹, Francesca Morgante^{2

3}, Charles Adler⁴, Pinky Agarwal⁵, Tobias Bäumer⁶, Alfredo Berardelli^{7

8}, Brian D Berman⁹, Joel Blumin¹⁰, Max Borsche¹¹, Allison Brashear¹², Andres Deik¹³, Kevin Duque¹⁴, Alberto J Espay¹⁴, Gina Ferrazzano⁷, Jeanne Feuerstein¹⁵, Susan Fox¹⁶, Samuel Frank¹⁷, Mark Hallett¹⁸, Joseph Jankovic¹⁹, Mark S LeDoux²⁰, Julie Leegwater-Kim²¹, Abhimanyu Mahajan²², Irene A Malaty²³, William Ondo^{24

25}, Alexander Pantelyat²⁶, Sarah Pirio-Richardson²⁷, Emmanuel Roze²⁸, Rachel Saunders-Pullman²⁹, Oksana Suchowersky³⁰, Daniel Truong^{31

32}, Marie Vidailhet²⁸, Aparna Wagle Shukla²³, Joel S Perlmutter³³, Hyder A Jinnah³⁴, Davide Martino³⁵

Affiliations

¹ Department of Community Health Sciences, Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
² Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK.
³ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
⁴ Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA.
⁵ Booth Gardner Parkinson's Center, Evergreen Health, Kirkland, Washington, USA.
⁶ Institute of Systems Motor Science, Center for Rare Diseases, University Medical Hospital Schleswig-Holstein, University of Lübeck, Lübeck, Germany.
⁷ Department of Human Neurosciences, University of Rome "La Sapienza", Rome, Italy.
⁸ IRCCS Neuromed, Pozzilli, Italy.
⁹ Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, USA.
¹⁰ Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹¹ Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
¹² Department of Neurology, University of California, Davis, Sacramento, California, USA.
¹³ Disease and Movement Disorders Center, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁴ Department of Neurology and Rehabilitation Medicine, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA.
¹⁵ Department of Neurology, University of Colorado, Aurora, Colorado, USA.
¹⁶ Movement Disorder Clinic, Edmond J Safra Program in Parkinson Disease, Toronto Western Hospital, and Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
¹⁷ Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
¹⁸ Human Motor Control Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA.
¹⁹ Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.
²⁰ Department of Psychology and School of Health Sciences, University of Memphis, and Veracity Neuroscience, Memphis, Tennessee, USA.
²¹ Lahey Hospital and Medical Center, Tufts University School of Medicine, Burlington, Massachusetts, USA.
²² Rush Parkinson's disease and movement disorders program, Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
²³ Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA.
²⁴ Houston Methodist Hospital, Houston, Texas, USA.
²⁵ Weill Cornell Medical School, New York, New York, USA.
²⁶ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁷ Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
²⁸ Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Salpetriere, Paris, France.
²⁹ Department of Neurology, Icahn School of Medicine at Mount Sinai and Mount Sinai Beth Israel, New York, New York, USA.
³⁰ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
³¹ Department of Neurosciences, UC Riverside, Riverside, California, USA.
³² The Parkinson and Movement Disorder Institute, Fountain Valley, California, USA.
³³ Departments of Neurology, Psychiatry, Radiology, Neurobiology, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St. Louis, Missouri, USA.
³⁴ Departments of Neurology, Human Genetics, and Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
³⁵ Department of Clinical Neurosciences & Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

PMID: 34296504
PMCID: PMC9100858
DOI: 10.1111/ene.15031

Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion

Meng Wang et al. Eur J Neurol. 2021 Dec.

. 2021 Dec;28(12):3999-4009.

doi: 10.1111/ene.15031. Epub 2021 Aug 4.

Authors

Affiliations

¹ Department of Community Health Sciences, Department of Clinical Neurosciences and Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.
² Neurosciences Research Centre, Molecular and Clinical Sciences Research Institute, St. George's, University of London, London, UK.
³ Department of Clinical and Experimental Medicine, University of Messina, Messina, Italy.
⁴ Department of Neurology, Mayo Clinic College of Medicine, Mayo Clinic Arizona, Scottsdale, Arizona, USA.
⁵ Booth Gardner Parkinson's Center, Evergreen Health, Kirkland, Washington, USA.
⁶ Institute of Systems Motor Science, Center for Rare Diseases, University Medical Hospital Schleswig-Holstein, University of Lübeck, Lübeck, Germany.
⁷ Department of Human Neurosciences, University of Rome "La Sapienza", Rome, Italy.
⁸ IRCCS Neuromed, Pozzilli, Italy.
⁹ Department of Neurology, Virginia Commonwealth University, Richmond, Virginia, USA.
¹⁰ Department of Otolaryngology & Communication Sciences, Medical College of Wisconsin, Milwaukee, Wisconsin, USA.
¹¹ Institute of Neurogenetics, University of Lübeck, Lübeck, Germany.
¹² Department of Neurology, University of California, Davis, Sacramento, California, USA.
¹³ Disease and Movement Disorders Center, Department of Neurology, University of Pennsylvania, Philadelphia, Pennsylvania, USA.
¹⁴ Department of Neurology and Rehabilitation Medicine, Gardner Family Center for Parkinson's Disease and Movement Disorders, University of Cincinnati, Cincinnati, Ohio, USA.
¹⁵ Department of Neurology, University of Colorado, Aurora, Colorado, USA.
¹⁶ Movement Disorder Clinic, Edmond J Safra Program in Parkinson Disease, Toronto Western Hospital, and Division of Neurology, University of Toronto, Toronto, Ontario, Canada.
¹⁷ Beth Israel Deaconess Medical Center, Boston, Massachusetts, USA.
¹⁸ Human Motor Control Section, National Institute of Neurological Disorders and Stroke, NIH, Bethesda, Maryland, USA.
¹⁹ Parkinson's Disease Center and Movement Disorders Clinic, Department of Neurology, Baylor College of Medicine, Houston, Texas, USA.
²⁰ Department of Psychology and School of Health Sciences, University of Memphis, and Veracity Neuroscience, Memphis, Tennessee, USA.
²¹ Lahey Hospital and Medical Center, Tufts University School of Medicine, Burlington, Massachusetts, USA.
²² Rush Parkinson's disease and movement disorders program, Department of Neurological Sciences, Rush University Medical Center, Chicago, Illinois, USA.
²³ Department of Neurology, Fixel Institute for Neurological Diseases, University of Florida, Gainesville, Florida, USA.
²⁴ Houston Methodist Hospital, Houston, Texas, USA.
²⁵ Weill Cornell Medical School, New York, New York, USA.
²⁶ Department of Neurology, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
²⁷ Department of Neurology, University of New Mexico Health Sciences Center, Albuquerque, New Mexico, USA.
²⁸ Sorbonne Université, Institut du Cerveau - Paris Brain Institute - ICM, Inserm, CNRS, AP-HP, Hôpital Salpetriere, Paris, France.
²⁹ Department of Neurology, Icahn School of Medicine at Mount Sinai and Mount Sinai Beth Israel, New York, New York, USA.
³⁰ Department of Medicine, University of Alberta, Edmonton, Alberta, Canada.
³¹ Department of Neurosciences, UC Riverside, Riverside, California, USA.
³² The Parkinson and Movement Disorder Institute, Fountain Valley, California, USA.
³³ Departments of Neurology, Psychiatry, Radiology, Neurobiology, Physical Therapy and Occupational Therapy, Washington University School of Medicine, St. Louis, Missouri, USA.
³⁴ Departments of Neurology, Human Genetics, and Pediatrics, Emory University School of Medicine, Atlanta, Georgia, USA.
³⁵ Department of Clinical Neurosciences & Hotchkiss Brain Institute, University of Calgary, Calgary, Alberta, Canada.

PMID: 34296504
PMCID: PMC9100858
DOI: 10.1111/ene.15031

Abstract

Background and purpose: Several clinical and demographic factors relate to anatomic spread of adult-onset isolated dystonia, but a predictive model is still lacking. The aims of this study were: (i) to develop and validate a predictive model of anatomic spread of adult-onset isolated dystonia; and (ii) to evaluate whether presence of tremor associated with dystonia influences model predictions of spread.

Methods: Adult-onset isolated dystonia participants with focal onset from the Dystonia Coalition Natural History Project database were included. We developed two prediction models, one with dystonia as sole disease manifestation ("dystonia-only") and one accepting dystonia OR tremor in any body part as disease manifestations ("dystonia OR tremor"). Demographic and clinical predictors were selected based on previous evidence, clinical plausibility of association with spread, or both. We used logistic regressions and evaluated model discrimination and calibration. Internal validation was carried out based on bootstrapping.

Results: Both predictive models showed an area under the curve of 0.65 (95% confidence intervals 0.62-0.70 and 0.62-0.69, respectively) and good calibration after internal validation. In both models, onset of dystonia in body regions other than the neck, older age, depression and history of neck trauma were predictors of spread.

Conclusions: This predictive modeling of spread in adult-onset isolated dystonia based on accessible predictors (demographic and clinical) can be easily implemented to inform individuals' risk of spread. Because tremor did not influence prediction of spread, our results support the argument that tremor is a part of the dystonia syndrome, and not an independent or coincidental disorder.

Keywords: isolated dystonia; neurological diseases; predictive models; spread; tremor.

PubMed Disclaimer

Conflict of interest statement

CONFLICT OF INTEREST

All authors report no disclosures related to the content of this research.

Figures

**FIGURE 1**
Calibration plots from the internal validation procedure (bootstrapping-corrected overfitting)

**FIGURE 2**
(a) Nomogram that allows calculation of the value of a cumulative predictive index (“Total Points”) of spread for each individual, based on the “dystonia-only” predictive model. The index score (“Total Points”) is calculated summing the points for each of the predictive variable, which can be measured graphically connecting through a perpendicular line the point on the metric scale for each variable to the metric scale for Points. A higher index score indicates higher predicted risk of spread. For example, a 70-year-old female with depression, cranial dystonia onset, no history of neck trauma, with family history, 10 years of disease duration, and no history of dystonia dominated by tremor will score as follows: 58 (on age) + 7 (on sex) + 33 (on depression) + 32 (on family history) + 0 (no on history of neck trauma) + 100 (on site of onset) + 8 (on disease duration) + 0 (on dystonia dominated by tremor) = 238, which will correspond to a 80% risk of spread. (b) Similar nomogram, but based on the “dystonia OR tremor” predictive model. Using this second nomogram, the same patient (without neck trauma) will score a cumulative predictive index of (71 + 0 + 28 + 57 + 11 + 0 + 0 + 0) =167, which will correspond to approximately 75% risk of spread

See this image and copyright information in PMC

References

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Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion

Affiliations

Predictive modeling of spread in adult-onset isolated dystonia: Key properties and effect of tremor inclusion

Authors

Affiliations

Abstract

Conflict of interest statement

Figures

References

Publication types

MeSH terms

Grants and funding

LinkOut - more resources

Full Text Sources

Medical