What is the role of the pyramidal and extrapyramidal systems in the pathophysiology of tardive dyskinesia (TD)?

Answer

The pyramidal system, controlling voluntary movements, includes precise anatomic pathways from the cortex to muscle. Voluntary movements through the pyramidal systems are visible. An example of a classic disorder of the pyramidal system is a stroke, resulting in paralysis of an extremity.

Corticospinal lesions above the pyramidal decussation typically result in paralysis of volitional movements of the contralateral half of the body and a fixed posture with flexion of the upper extremity and extension of the lower extremity. Bilateral corticospinal lesions of the upper pons and midbrain typically cause extension of all 4 extremities and decerebrate rigidity with dorsiflexion of the cervical and thoracolumbar spine. Unilateral lesions of the upper pons and midbrain often result in extension of the ipsilateral arm and leg.

By contrast, extrapyramidal motor activities result in automatic movement and static, postural movement activities that are not noticeable (see Table 1 below). The extrapyramidal system includes theorized connections within the basal ganglia, the striatopallidonigral system, and other structures of the central nervous system that contribute to the regulation of movement, including related brainstem nuclei and the cerebellum.

Table 1. Classic Characterization of Pyramidal and Extrapyramidal Systems (Open Table in a new window)

Characteristic	Pyramidal	Extrapyramidal
Anatomy	Precisely demarcated pathways from cortex to muscle	Hypothesized pathways among basal ganglia and other structures of the central nervous system
Physiologic movements	Voluntary	Involuntary
Pathologic movements	Paralysis, paresis, hyperreflexia, and spasticity	Akathisia, athetosis, ballismus, chorea, dystonia, myoclonus, stereotypy, tic, and tremor

Classic disorders of the extrapyramidal system include a variety of involuntary movement disorders. Some of these movement disorders include dyskinesias such as akathisia, chorea, dystonia, myoclonus, stereotypy, tic, and tremor.

The pathophysiology of extrapyramidal disorders has been disputed on the grounds that some of these disorders may not involve lesions of the basal ganglia and, in addition, may not be involuntary. Because of the problems inherent in the concept of the extrapyramidal system, caution must be exercised in the classification of movement disorders as EPSs, and new approaches to the classification of movement disorders may be helpful.

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Diagnostic criteria for neuroleptic-induced tardive dyskinesia.
Tardive dyskinesia. Venn diagram of the classification of movement disorders.

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James Robert Brasic, MD, MPH Assistant Professor, Russell H Morgan Department of Radiology and Radiological Science and Neurology, Division of Nuclear Medicine and Molecular Imaging, Johns Hopkins University School of Medicine

James Robert Brasic, MD, MPH is a member of the following medical societies: American Academy of Child and Adolescent Psychiatry, American Academy of Neurology, International Parkinson and Movement Disorder Society, Society for Neuroscience

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Johns Hopkins University School of Medicine Received research grant from: National Institutes of Health, Johns Hopkins University School of Medicine, Intellectual & Developmental Disabilities Research Center (U54 HD079123) at the Kennedy Krieger Institute Received income in an amount equal to or greater than $250 from: Brand Institute, Inc. Received royalty from Medscape for other; Received royalty from Neuroscience-Net, LLC for other; Received grant/research funds from National Institutes of Health for other.

Chief Editor

Selim R Benbadis, MD Professor, Director of Comprehensive Epilepsy Program, Departments of Neurology and Neurosurgery, Tampa General Hospital, University of South Florida Morsani College of Medicine

Selim R Benbadis, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, American Clinical Neurophysiology Society, American Epilepsy Society, American Medical Association

Disclosure: Serve(d) as a director, officer, partner, employee, advisor, consultant or trustee for: Ceribell, Eisai, Greenwich, Growhealthy, LivaNova, Neuropace, SK biopharmaceuticals, Sunovion Serve(d) as a speaker or a member of a speakers bureau for: Eisai, Greenwich, LivaNova, Sunovion Received research grant from: Cavion, LivaNova, Greenwich, Sunovion, SK biopharmaceuticals, Takeda, UCB.

Acknowledgements

Brian Bronson, MD Staff Physician, Department of Psychiatry, New York University Medical Center

Disclosure: Nothing to disclose.

Tristen T Chun Division of Nuclear Medicine, Russell H Morgan Department of Radiology and Radiological Science, Johns Hopkins University School of Medicine

Disclosure: Nothing to disclose.

Nestor Galvez-Jimenez, MD, MSc, MHA Chairman, Department of Neurology, Program Director, Movement Disorders, Department of Neurology, Division of Medicine, Cleveland Clinic Florida

Nestor Galvez-Jimenez, MD, MSc, MHA is a member of the following medical societies: American Academy of Neurology, American College of Physicians, and Movement Disorders Society

Disclosure: Nothing to disclose.

Daniel H Jacobs MD, FAAN, Associate Professor of Neurology, University of Florida College of Medicine; Director for Stroke Services, Orlando Regional Medical Center

Daniel H Jacobs is a member of the following medical societies: American Academy of Neurology, American Society of Neurorehabilitation, and Society for Neuroscience

Disclosure: Teva Pharmaceutical Grant/research funds Consulting; Biogen Idex Grant/research funds Independent contractor; Serono EMD Royalty Speaking and teaching; Pfizer Royalty Speaking and teaching; Berlex Royalty Speaking and teaching

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Medscape Salary Employment

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