Functional brain networks in DYT1 dystonia

David Eidelberg, James R. Moeller, Angelo Antonini, Ken Kazumata, Toshitaka Nakamura, Vijay Dhawan, Phoebe Spetsieris, Deborah DeLeon, Susan B. Bressman, Stanley Fahn

Research output: Contribution to journalArticle

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Abstract

Early-onset idiopathic torsion dystonia (ITD) is an autosomal dominant hyperkinetic movement disorder with incomplete penetrance, associated with a 3 base-pair deletion in the DYT1 gene on chromosome 9q34. To determine the metabolic substrates of brain dysfunction in DYT1 dystonia, we scanned 7 nonmanifesting and 10 affected DYT1 carriers and 14 normal volunteers with [18F]fluorodeoxyglucose and positron emission tomography. We found that DYT1 dystonia is mediated by the expression of two independent regional metabolic covariance patterns. The first pattern, identified in an analysis of nonmanifesting gene carriers was designated movement free (MF). This abnormal pattern was characterized by increased metabolic activity in the lentiform nuclei, cerebellum, and supplementary motor areas. The MF pattern was present in DYT1 carriers with and without clinical manifestations and persisted in DYT1 dystonia patients in whom involuntary movements were suppressed by sleep. The second pattern, identified in an analysis of affected gene carders with sustained contractions at rest, was designated movement related (MR). This pattern was characterized by increased metabolic activity in the midbrain, cerebellum, and thalamus. The expression of the MR pattern was increased in waking DYT1 patients with sustained dystonia, compared with DYT1 carriers who were unaffected or who had dystonia only on action, as well as normal controls. MR subject scores declined significantly with sleep in affected DYT1 patients but not in normal controls. These findings indicate the penetrance of the DYT1 gene is considerably greater than previously assumed. ITD is mediated through the interaction of functional brain networks relating separately to gene status and to abnormal movement.

Original languageEnglish
Pages (from-to)303-312
Number of pages10
JournalAnnals of Neurology
Volume44
Issue number3
DOIs
Publication statusPublished - Sep 1998

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Dystonia
Dystonia Musculorum Deformans
Brain
Penetrance
Genes
Dyskinesias
Cerebellum
Sleep
Hyperkinesis
Corpus Striatum
Fluorodeoxyglucose F18
Movement Disorders
Motor Cortex
Mesencephalon
Thalamus
Base Pairing
Positron-Emission Tomography
Healthy Volunteers
Chromosomes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Eidelberg, D., Moeller, J. R., Antonini, A., Kazumata, K., Nakamura, T., Dhawan, V., ... Fahn, S. (1998). Functional brain networks in DYT1 dystonia. Annals of Neurology, 44(3), 303-312. https://doi.org/10.1002/ana.410440304

Functional brain networks in DYT1 dystonia. / Eidelberg, David; Moeller, James R.; Antonini, Angelo; Kazumata, Ken; Nakamura, Toshitaka; Dhawan, Vijay; Spetsieris, Phoebe; DeLeon, Deborah; Bressman, Susan B.; Fahn, Stanley.

In: Annals of Neurology, Vol. 44, No. 3, 09.1998, p. 303-312.

Research output: Contribution to journalArticle

Eidelberg, D, Moeller, JR, Antonini, A, Kazumata, K, Nakamura, T, Dhawan, V, Spetsieris, P, DeLeon, D, Bressman, SB & Fahn, S 1998, 'Functional brain networks in DYT1 dystonia', Annals of Neurology, vol. 44, no. 3, pp. 303-312. https://doi.org/10.1002/ana.410440304
Eidelberg D, Moeller JR, Antonini A, Kazumata K, Nakamura T, Dhawan V et al. Functional brain networks in DYT1 dystonia. Annals of Neurology. 1998 Sep;44(3):303-312. https://doi.org/10.1002/ana.410440304
Eidelberg, David ; Moeller, James R. ; Antonini, Angelo ; Kazumata, Ken ; Nakamura, Toshitaka ; Dhawan, Vijay ; Spetsieris, Phoebe ; DeLeon, Deborah ; Bressman, Susan B. ; Fahn, Stanley. / Functional brain networks in DYT1 dystonia. In: Annals of Neurology. 1998 ; Vol. 44, No. 3. pp. 303-312.
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