Dystonia

INDEX

Distinguishing the dominant movement disorder in younger patients presenting with dystonia or Parkinson disease can be extremely difficult, and both conditions may be characterized by some degree of overlap.  It is unclear from the current knowledge of their pathophysiological changes in the basal ganglia how dystonia and parkinsonism can co-occur, and why they can both respond to lesion/DBS surgery.  To further emphasize how unclear the underlying mechanisms may be, chronic GPi DBS stimulation can sometimes paradoxically lead to parkinsonism in patients treated for dystonia21.

Dystonia-parkinsonism syndromes encompass both common and rare conditions. Of particular importance are the following:

In some patients, parkinsonism dominates, whereas in others, dystonia prevails, particularly in the legs:

Dystonic Disorders with Parkinsonism

Parkinsonism, with partial responsiveness to levodopa, is commonly seen with mutations in the genes listed below, which therefore all correspond to some form of dopa-responsive dystonia.  The response of early dystonia to the introduction of dopamine replacement therapy (levodopa, dopamine agonists) is also variable; it can worsen, improve or remain unchanged ; some have suggested a better response to dopamine agonists but this benefit is inconsistent21.

Those involved in the dopamine synthesis pathway

DYT-PARK-GCH1 (DYT5a) (Dopa-responsive dystonia)

DYT-PARK-TH (DYT5b) (Dopa-responsive dystonia)

Other forms:

DYT-PARK-TAF1 (DYT3)

DYT-PARK-ATP1A3 (DYT12) (Rapid-onset dystonia parkinsonism)

DYT-PARK-PRKRA (DYT16) (Dystonia with mild parkinsonism)

Parkinsonian Disorders with associated dystonia.

Dystonia can be observed as part of the PD spectrum (e.g., blepharospasm and eyelid apraxia) and also following dopaminergic treatment or subthalamic nucleus stimulation.

Dystonia affects more than half of patients in sporadic early onset Parkinson’s disease, 20% of patients with onset at age <55 years, and another 10% within two years of onset. Although, in most cases, parkinsonism will dominate, dystonia of the legs or exercise-induced dystonia can be the presenting symptom of early onset PD, especially in autosomal recessive genetic parkinsonism such as PARK-Parkin (PARK2).

Early dystonia in PD can have a variety of focal and segmental distributions, particularly involving the lower limb.  Dystonia in young-onset PD most commonly involves the foot, typically taking onset as exercise-induced cramp-like discomfort, first noticed in the toes and later evolving into inversion of the affected foot.  This has been called kinesigenic foot dystonia, and is induced by exercise of progressively less intensity. Its finding in a young individual should raise the suspicion of young-onset PD. Patients can demonstrate a “pseudo-foot drop gait” secondary to the action dystonia of the plantar flexors and the foot invertors triggered while walking.

Hand and neck dystonia, as well as hemidystonia, have also been reported.  Dystonia of the upper limb in PD can be task specific although non-task specific dystonia is more common. Both musician’s dystonia and task- specific writing tremor preceding the development of overt Parkinson’s disease have been described. Patients can also develop fixed painless contractures of limbs, which are also thought to be dystonic. Dystonia can precede the development of parkinsonism from anywhere between 1 to 25 years.

The following forms of dystonia are seen in PD:

Focal dystonias

Axial dystonia