Risk of spread in adult-onset isolated focal dystonia: a prospective international cohort study

Abstract

ObjectiveIsolated focal dystonia can spread to muscles beyond the initially affected body region, but risk of spread has not been evaluated in a prospective manner. Furthermore, body regions at risk for spread and the clinical factors associated with spread risk are not well characterised. We sought here to prospectively characterise risk of spread in recently diagnosed adult-onset isolated focal dystonia patients.MethodsPatients enrolled in the Dystonia Coalition with isolated dystonia affecting only the neck, upper face, hand or larynx at onset of symptoms were included. Timing of follow-up visits was based on a sliding scale depending on symptom onset and ranged from 1 to 4 years. Descriptive statistics, Kaplan-Meier survival curves and Cox proportional hazard regression models were used to assess clinical characteristics associated with dystonia spread.Results487 enrolled participants (68.3% women; mean age: 55.6±12.2 years) met our inclusion/exclusion criteria. Spread was observed in 50% of blepharospasm, 8% of cervical dystonia, 17% of hand dystonia and 16% of laryngeal dystonia cases. Most common regions for first spread were the oromandibular region (42.2%) and neck (22.4%) for blepharospasm, hand (3.5%) for cervical dystonia and neck for hand (12.8%) and laryngeal (15.8%) dystonia. Increased spread risk was associated with a positive family history (HR=2.18, p=0.012) and self-reported alcohol responsiveness (HR=2.59, p=0.009).ConclusionsInitial body region affected in isolated focal dystonia has differential risk and patterns of spread. Genetic factors likely influence the risk of spread. These findings can aid clinical prognostication and inform future investigations into potential disease-modifying treatments.

Idiopathic Non‐task‐Specific Upper Limb Dystonia, a Neglected Form of Dystonia

“…The late age of onset and the relatively high tendency to spread of non-task-specific ULD are clinical features similar to those also reported in blepharospasm and differ from those reported in cervical dystonia and task-specific ULD. 10,16 The presence of dystonic tremor in non-task-specific and task-specific ULD supports the observation that tremor is a phenotypic feature of dystonia. 17 Although we did not have data on the time of appearance of tremor and dystonia, the higher frequency of tremor among non-task-specific patients may reflect the greater frequency of segmental dystonia in this group, supporting previous reports that suggest that dystonia spreads more commonly in patients with tremor.…”

“…Likewise, there is no relationship between age of onset and tremor frequency 17,18 or between age of onset and tendency to spread in patients with different focal adult-onset dystonias. 10,16 The findings of the present study also introduce the possibility that non-taskspecific and task-specific ULD are distinct clinical subtypes. In a previous article, we reported that patients with different forms of focal adult-onset dystonia show differences in several clinical, demographic, and neurophysiological features.…”

“…1,5 Since Marsden's 4 original observation about 40 years ago that WC may be a task-specific form of adult-onset dystonia, only a few studies have investigated the demographic and clinical features of idiopathic ULD. [6][7][8][9][10][11] Most reports have included a relatively small number of patients with upper limb dystonia or they have focused on specific subtypes, such as WC 6 or musician's dystonia. 12 No studies have specifically examined the clinical features of idiopathic non-task-specific dystonia or the possible differences between non-task-specific and task-specific ULD.…”

Clinical and Demographic Characteristics of Upper Limb Dystonia

“…13,[15][16][17][18][19][20] In fact, prospective analysis in a relatively small adult-onset component of the current data set demonstrated a relationship between initial body region affected (including hand) and risk of spread. 21 Thus, clinical and demographic features are critical for understanding important subtypes of ULD. Such clinical characteristics are essential for design and implementation of future studies that aim to test symptomatic or disease-modifying interventions in isolated limb dystonia.…”

“…Such clinical characteristics are essential for design and implementation of future studies that aim to test symptomatic or disease-modifying interventions in isolated limb dystonia. 21,22 The primary aim of this report is to characterize clinical features and demographics of isolated ULD where the upper limb was involved at onset. Data are derived from the Dystonia Coalition database, the largest standardized, multicenter cohort ever assembled.…”