eMedicine Specialties > Neurology > Pediatric Neurology

Dopamine-Responsive Dystonia: Differential Diagnoses & Workup

Author: N K Nikhar, MD, MRCP, Assistant Professor, Department of Neurology, George Washington University School of Medicine
Coauthor(s): Haresh Mani, MD,, Associate Medical Director, Pulmonary and Mediastinal Pathology, American International Pathology Laboratories
Contributor Information and Disclosures

Updated: Jul 10, 2009

Differential Diagnoses

Ataxia with Identified Genetic and Biochemical Defects
Parkinson-Plus Syndromes
Cerebral Palsy
Progressive Supranuclear Palsy
Parkinson Disease
Spasticity
Parkinson Disease in Young Adults
Torticollis

Other Problems to Be Considered

Primarily dystonic juvenile parkinsonism (DJP) and autosomal-recessive early-onset parkinsonism with diurnal fluctuation (AREPDF)

  • Dystonia predominates in DJP and AREPDF. Parkinsonism (in addition to dystonia) is apparent in DRD.22 DJP presents in the first half of the second decade23 with stumbling, pes equinovarus, and upper limb involvement that is typically asymmetrical. Forward bending of the head and trunk appear later.
  • Symptoms vary diurnally, with aggravation during activity and improvement with sleep. Long-term levodopa benefit is limited.24
  • Sustained response to levodopa without adverse effects of long-term treatment distinguishes DRD from early-onset parkinsonism with dystonia.

Early-onset idiopathic parkinsonism

  • This presents in the fourth decade, whereas DRD presents in childhood. Positron emission tomography (PET) studies show normal striatal fluorodopa uptake in DRD, whereas patients with Parkinson disease have reduced uptake. Patients with DRD presenting in infancy or early childhood may be misdiagnosed with cerebral palsy or spastic diplegia. Extrapyramidal signs may occur later; disappearance of spasticity and extrapyramidal signs following levodopa therapy confirms the diagnosis of DRD.25
  • A case report of spinocerebellar ataxia type 3 and adult-onset spastic paraplegia have been shown to clinically present as DRD.
  • In early-onset dystonia, Wilson disease, Hallervorden-Spatz disease, and neuroacanthocytosis should be considered.
  • The variations in presentation (eg, spasmodic torticollis, oromandibular dystonia, writer's cramp) should be differentiated from idiopathic (ie, dopamine-nonresponsive) focal dystonias. A therapeutic trial with levodopa is the definitive way to establish the diagnosis.

Oromandibular dystonia
Focal dystonia
Cerebral palsy
Dystonia musculorum deformans
Dyspeptic dystonia with hiatal hernia (Sandifer syndrome)
Medication reactions (eg, phenothiazines, butyrophenones)
Metabolic diseases (eg, GM2 gangliosidosis, phenylketonuria, hypothyroidism, Leigh disease)

Workup

Laboratory Studies

  • CBC with peripheral smear examination - to rule out acanthocytosis
  • Serum for BUN, creatinine, liver function tests, copper, and ceruloplasmin
  • Cerebrospinal fluid
    • Cerebrospinal fluid (CSF) examination is not performed routinely, but some subjects may show significant reductions in CSF levels of neopterin and biopterin.26
    • Measuring CSF pterins6 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).

Imaging Studies

  • Brain MRI may show abnormalities in the basal ganglia, suggesting Wilson disease or Hallervorden-Spatz disease.
  • No specific abnormalities are seen in dopamine-responsive dystonia (DRD).
  • PET scan uptake of [18 F]dopamine may be reduced in early-onset Parkinson disease, but is normal in DRD.27,28
  • Single-photon emission computed tomography (SPECT) with iodine I 123 2beta-carbomethoxy-3beta-(4-iodophenyl)tropane (b-CIT) can differentiate DRD (normal) from early-onset Parkinson disease (reduced).29
  • A multi-tracer PET study has shown that striatal dopamine D2 receptors availability is increased in DRD, whereas dopamine D1 receptors and dopamine transporter ligand binding is unchanged. The pattern of changes in striatal dopaminergic system in DRD is different from that reported in juvenile Parkinson's disease. The increased D2 receptor availability may be due to reduced competition by endogenous dopamine and/or compensatory response to dopamine deficiency.30

Other Tests

  • Polysomnography in DRD shows a decreased number of twitch movements during REM sleep (~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.31
  • Phenylalanine loading test: Abnormality in phenylalanine metabolism has been useful in diagnosing DRD for most (50% of patients) but not all patients.32,33
    • 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.34

Histologic Findings

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.35

More on Dopamine-Responsive Dystonia

Overview: Dopamine-Responsive Dystonia
Differential Diagnoses & Workup: Dopamine-Responsive Dystonia
Treatment & Medication: Dopamine-Responsive Dystonia
Follow-up: Dopamine-Responsive Dystonia
References
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Further Reading

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Keywords

dopamine-responsive dystonia, hereditary progressive dystonia with diurnal fluctuation, HPD, Segawa's disease, Segawa disease, DRD, dopa-responsive dystonia, inherited dystonia, mild parkinsonian features

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Contributor Information and Disclosures

Author

N K Nikhar, MD, MRCP, Assistant Professor, Department of Neurology, George Washington University School of Medicine
N K Nikhar, MD, MRCP is a member of the following medical societies: American Academy of Neurology
Disclosure: Nothing to disclose.

Coauthor(s)

Haresh Mani, MD,, Associate Medical Director, Pulmonary and Mediastinal Pathology, American International Pathology Laboratories
Disclosure: Nothing to disclose.

Medical Editor

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
Disclosure: Nothing to disclose.

Pharmacy Editor

Francisco Talavera, PharmD, PhD, Senior Pharmacy Editor, eMedicine
Disclosure: eMedicine Salary Employment

Managing Editor

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.

Chief Editor

Amy Kao, MD, Assistant Professor, Department of Pediatrics, Division of Pediatric Neurology, Department of Neurology, Oregon Health and Science University; Consulting Staff, Shriners Hospital for Children
Amy Kao, MD is a member of the following medical societies: American Academy of Neurology, American Academy of Pediatrics, American Epilepsy Society, and Child Neurology Society
Disclosure: Nothing to disclose.

 
 
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