Risk of Spread of Focal Dystonia

Abstract & Commentary

By Claire Henchcliffe, MD, DPhil, Assistant Professor, Department of Neurology, Weill Medical College, Cornell University. Dr. Henchcliffe is on the speaker's bureau for GlaxoSmithKline, Teva/Eisai, and Boehringer Ingelheim.

Synopsis: This retrospective study of 602 primary focal dystonia patients finds that site of onset affects rate and spread of symptoms to other body parts, with spread highest in those with isolated blepharospasm at onset.

Source: Weiss EM, et al. Relative Risk of Spread of Symptoms Among the Focal Onset Primary Dystonias. Mov Disord. 2006. May 3; (Epub ahead of print) PMID: 16673404

This is a retrospective investigation of the spread patterns of focal dystonia in individuals observed over a mean of 8-13 years at an academic movement disorders center. Of 1158 dystonia patients seen for the first visit from 1995-2005, 602 met criteria for primary dystonia (ie, no underlying identified cause, such as stroke, tardive syndrome, brain injury). Those who were levodopa-responsive or had symptoms of parkinsonism were excluded. The final cohort comprised 17 with childhood onset, 60 with juvenile onset, and 525 with adult-onset dystonia. Of the 584 with a single site of onset, initial symptoms affected neck (45%), larynx (20%), upper extremities (16%), eyelids (13%), lower face (3%), and lower extremities (1.5%). A positive family history, present in 12%, did not predict a particular site of onset. Mean age at time of onset varied from 24 ± 23 years for lower extremity dystonia, to 52 ± 13 years for blepharospasm. Isolated blepharospasm in 78 was followed by spread of dystonia in 58% (lower face: 26%; neck/lower face: 28%; other: 4%; mean time to spread 3.5 ± 5.5 years). However, other sites of focal onset were less commonly followed by spread to other regions. In 264 with focal cervical dystonia, 12% experienced spread (upper extremities: 8%; lower face: 3%; eyelids: 3%; larynx: 2%; other: 2%; mean time to spread 5.9 ± 6.2 years). Of 117 with spasmodic dysphonia, spread occurred in 9% (neck: 5%; upper extremities: 5%; lower face, lids and lower extremities: 2% each site; mean time to spread: 5.6 ± 4.8 years). From 96 with upper extremity onset, 16% experienced symptom spread (neck: 8%; lower face: 5%; opposite upper extremity, lower extremities or lids: 3% each site; other: 3%; mean time to spread: 7.8 ± 1.8 years). Analysis of data for the lower extremities was limited by small numbers, as only 11 patients fell into this category, but 4/5 had symptoms spread to the arms and 2/5 to the neck.

Commentary

Primary focal dystonia is estimated to account for up to 50% of all dystonias, yet data on its natural history is limited. The present study adds considerably to our understanding of the course of focal dystonia, and represents the largest published cohort of these patients to date, with carefully characterized movement disorder phenomenology. It provides valuable data upon which to base patient counseling regarding prognosis, keeping in mind possible referral bias to the academic center represented in his study. One intriguing finding is that frequency, rate, and pattern of spread are influenced by the initial site of dystonia symptoms: blepharospasm, in particular, stands out as faster and more likely to spread to other sites than the other focal dystonias. This may be a clue that underlying physiologies differ between at least some of these groups.

The pathophysiology of focal dystonia is poorly understood. However, a role for the basal ganglia has been consistently demonstrated, and positron emission tomography has demonstrated hypermetabolism in the lentiform nucleus, thalamus, pre-motor/motor cortices, and cerebellum, as well as decreased putaminal dopamine D2 receptor binding. Cortical involvement has also been observed in patients with focal hand dystonia who have abnormal sensory cortical responses to finger stimulation, with abnormal representation of the homunculus in the primary somatosensory cortex. It is not clear, as yet, how each of these sites act and interact with each other, as dystonic symptoms develop and migrate. A better understanding of the process, however, would open the way to improved therapeutics.