Approach Considerations

Lab studies used in the diagnosis and evaluation of dopamine-responsive dystonia (DRD) include the following:

Complete blood count (CBC) with peripheral smear examination - To rule out acanthocytosis
Serum studies for blood urea nitrogen (BUN), creatinine, liver function, copper, and ceruloplasmin
Cerebrospinal fluid (CSF) studies
Ceruloplasm

CSF examination is not performed routinely, but some subjects may show significant reductions in CSF levels of neopterin and biopterin.^[34]

Measuring CSF pterins^[17]may be useful in distinguishing the 3 disorders that are responsive to levodopa: GTPCH-deficient DRD (decreased biopterin and neopterin), TH-deficient DRD (normal biopterin and neopterin), and early-onset parkinsonism (reduced biopterin and normal neopterin).

Polysomnography

Polysomnography in DRD shows a decreased number of twitch movements during REM sleep (approximately 20% of normal). The ratio does not decrease with age, and it does not follow the decremental age variation and incremental nocturnal variation of healthy subjects.^[35]

Phenylalanine loading test

Abnormality in phenylalanine metabolism has been useful in diagnosing DRD for most (50% of patients), but not all, patients.^{[36, 37, 38]}The basis for this test is that BH4 is required as a cofactor in the breakdown of phenylalanine to tyrosine. In DRD, BH4 deficiency results in accumulation of phenylalanine.

Molecular biology

This can confirm the diagnosis in some cases.^[39]

Histology

In one autopsy case, the only neuropathologic finding was a decrease in melanin-pigmented neurons in the pars compacta of the substantia nigra. TH immunoreactivity in the substantia nigra was normal, no inclusion bodies or gliosis was noted, and no evidence of a degenerative process in the striatum was observed.^[40]

MRI

Brain magnetic resonance imaging (MRI) may show abnormalities in the basal ganglia, suggesting Wilson disease or Hallervorden-Spatz disease.

PET scanning

PET scan uptake of [¹⁸ F]dopamine may be reduced in early onset Parkinson disease, but it is normal in DRD.^{[41, 42, 43]}

A multitracer PET study has shown that the availability of the striatal dopamine D2 receptors is increased in DRD, whereas dopamine D1 receptors and dopamine transporter ligand binding are unchanged. The pattern of changes in the striatal dopaminergic system in DRD is different from that reported in juvenile Parkinson disease. The increased D2 receptor availability may be due to reduced competition by endogenous dopamine and/or compensatory response to dopamine deficiency.^[44]

SPECT scanning

Single-photon emission computed tomography (SPECT) scanning with iodine-123 (¹²³ I) 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (b-CIT) can differentiate DRD (normal) from early onset Parkinson disease (reduced).^[45]

Treatment & Management

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Author

Nirjal K Nikhar, MD, FRCP Private Practice

Nirjal K Nikhar, MD, FRCP is a member of the following medical societies: American Academy of Neurology

Disclosure: Nothing to disclose.

Coauthor(s)

Haresh Mani, MD Assistant Professor, Department of Pathology, Milton S Hershey Medical Center, Pennsylvania State University College of Medicine

Disclosure: Nothing to disclose.

Syed M S Ahmed, MD Neurologist and Sleep Specialist, Capital Neurology and Sleep Medicine; Staff Attending in Neurology and Sleep Medicine, Montgomery General Hospital; Staff Attending in Neurology and Sleep Medicine, Suburban Hospital

Syed M S Ahmed, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Sleep Medicine, Maryland State Medical Society

Disclosure: Nothing to disclose.

Chief Editor

Amy Kao, MD Attending Neurologist, Children's National Medical Center

Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Epilepsy Society, Child Neurology Society

Disclosure: Have stock (managed by a financial services company) in healthcare companies including Allergan, Cellectar Biosciences, CVS Health, Danaher Corp, Johnson & Johnson.

Acknowledgements

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.

Ann M Neumeyer, MD Clinic Director, Instructor, Departments of Neurology and Pediatrics, Massachusetts General Hospital, Harvard Medical School

Ann M Neumeyer, MD is a member of the following medical societies: American Academy of Neurology, Child Neurology Society, and Massachusetts Medical Society

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

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