Dopamine-Responsive Dystonia Differential Diagnoses

Updated: Mar 25, 2019
  • Author: Nirjal K Nikhar, MD, FRCP; Chief Editor: Amy Kao, MD  more...
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Diagnostic Considerations

Primarily dystonic juvenile parkinsonism and AREPDF

Dystonia predominates in dystonic juvenile parkinsonism (DJP) and autosomal-recessive early onset parkinsonism with diurnal fluctuation (AREPDF). Parkinsonism (in addition to dystonia) is apparent in dopamine-responsive dystonia (DRD). [30]

DJP presents in the first half of the second decade [31] 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. The long-term levodopa benefit is limited. [32]

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) scan 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. [33]

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 of DRD (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.

Additional considerations

Conditions to consider in the differential diagnosis of DRD also include the following:

  • 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

Differential Diagnoses