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Mov Disord. 2018 May;33(5):827-834. doi: 10.1002/mds.27358. Epub 2018 Mar 6.

Pedunculopontine Nucleus Cholinergic Deficiency in Cervical Dystonia.

Author information

Human Motor Control Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
Louis Stokes Cleveland Veterans Affairs Medical Center, Cleveland, Ohio, USA.
Neuropathology Unit, Surgical Neurology Branch, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Maryland, USA.
David Geffen School of Medicine, University of California Los Angeles, Los Angeles, California, USA.
Charles R. Drew University of Medicine and Science, Los Angeles, California, USA.
Neuropathology Core and Brain Tissue Repository, Center for Neuroscience and Regenerative Medicine, Uniform Services University, Bethesda, Maryland, USA.
Departments of Neurology and Pathology, F. Edward Hébert School of Medicine, Uniformed Services University, Bethesda, Maryland, USA.
The Henry M. Jackson Foundation for the Advancement of Military Research, Bethesda, Maryland, USA.
Hospital Israelita Albert Einstein, Instituto do Cérebro, São Paulo, Brazil.
Department of Radiology, Faculdade de Medicina da Universidade de São Paulo, Instituto de Radiologia, São Paulo, Brazil.
Department of Pathology, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Department of Neurology, Faculdade de Medicina da Universidade de São Paulo, Divisão de Neurocirurgia Funcional do Instituto de Psiquiatria-Hospital das Clinicas de Faculdade de Medicina da Universidade de Sao Paulo (HCFMUSP), São Paulo, Brazil.



The etiology of cervical dystonia is unknown. Cholinergic abnormalities have been identified in dystonia animal models and human imaging studies. Some animal models have cholinergic neuronal loss in the striatum and increased acetylcholinesterase activity in the pedunculopontine nucleus.


The objective of this study was to determine the presence of cholinergic abnormalities in the putamen and pedunculopontine nucleus in cervical dystonia human brain donors.


Formalin-fixed brain tissues were obtained from 8 cervical dystonia and 7 age-matched control brains (controls). Pedunculopontine nucleus was available in only 6 cervical dystonia and 5 controls. Neurodegeneration was evaluated pathologically in the putamen, pedunculopontine nucleus, and other regions. Cholinergic neurons were detected using choline acetyltransferase immunohistochemistry in the putamen and pedunculopontine nucleus. Putaminal cholinergic neurons were quantified. A total of 6 cervical dystonia patients and 6 age-matched healthy controls underwent diffusion tensor imaging to determine if there were white matter microstructural abnormalities around the pedunculopontine nucleus.


Decreased or absent choline acetyltransferase staining was identified in all 6 pedunculopontine nucleus samples in cervical dystonia. In contrast, strong choline acetyltransferase staining was present in 4 of 5 pedunculopontine nucleus controls. There were no differences in pedunculopontine nucleus diffusion tensor imaging between cervical dystonia and healthy controls. There was no difference in numbers of putaminal cholinergic neurons between cervical dystonia and controls.


Our findings suggest that pedunculopontine nucleus choline acetyltransferase deficiency represents a functional cholinergic deficit in cervical dystonia. Structural lesions and confounding neurodegenerative processes were excluded by absence of neuronal loss, gliosis, diffusion tensor imaging abnormalities, and beta-amyloid, tau, and alpha-synuclein pathologies. © 2018 International Parkinson and Movement Disorder Society.


MRI; acetylcholine; cervical dystonia; diffusion tensor imaging; neuropathology

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