Sensorimotor Integration in Childhood Dystonia and Dystonic Cerebral Palsy-A Developmental Perspective

Abstract

Dystonia is a disorder of sensorimotor integration, involving dysfunction within the basal ganglia, cortex, cerebellum, or their inter-connections as part of the sensorimotor network. Some forms of dystonia are also characterized by maladaptive or exaggerated plasticity. Development of the neuronal processes underlying sensorimotor integration is incompletely understood but involves activity-dependent modeling and refining of sensorimotor circuits through processes that are already taking place in utero and which continue through infancy, childhood, and into adolescence. Several genetic dystonias have clinical onset in early childhood, but there is evidence that sensorimotor circuit development may already be disrupted prenatally in these conditions. Dystonic cerebral palsy (DCP) is a form of acquired dystonia with perinatal onset during a period of rapid neurodevelopment and activity-dependent refinement of sensorimotor networks. However, physiological studies of children with dystonia are sparse. This discussion paper addresses the role of neuroplasticity in the development of sensorimotor integration with particular focus on the relevance of these mechanisms for understanding childhood dystonia, DCP, and implications for therapy selection, including neuromodulation and timing of intervention.

Keywords: children; critical windows; dystonia; dystonic cerebral palsy; neurodevelopment; neuromodulation; plasticity; sensorimotor integration.

Figure 1

Normal development, dystonia, and role for activity-dependent plasticity. [Top (L-R)]: Thirty-five week gestation fetus; typically developing 6 month old infant; 7 year old girl with DYT-1 dystonia (2); Red Rectangle: (A) Example of activity-dependent synaptic plasticity. The two synchronously firing neurons (1 and 2) are retained by a “retrograde messenger” from the post-synaptic receptors shown in (B) while the asynchronously firing neuronal connection (3) is lost. From Penn and Shatz (3) annotated from DO Hebb 1949: “The Organisation of Behaviour”. [Lower (L-R)]: Adolescent with generalized DYT-1 Dystonia attempting to eat; Adolescent in status dystonicus due to Pantothenate Kinase associate Neurodegeneration (PKAN); Clinical cases courtesy J-P Lin.

Figure 2

DYT-1 dystonia and intrusive “ballerina postures” and improvements with Deep Brain Stimulation (DBS). Video frames over time before and after DBS. Onset age 6.0 years with rapid progression to wheel-chair mobility by age 6.5 years. (Top) “Ballerina posturing” of the right leg interferes with lying and sitting (see also Figure 1C). [Lower (left-right)]: unable to stand or walk; head and chest X-ray post ACTIVA RC rechargeable DBS implant, age 7 years; standing unsupported within days of DBS; walking unsupported 3 months post DBS with a left circumducting gait; fully recovered at 3 years post-DBS. Courtesy J-P Lin.

Figure 3

Developmental sequence of event-related changes in EEG power in relation to a proprioceptive stimulus in typically developing children and children with dystonia. Results from a study in which changes in sensorimotor cortex EEG were recorded in response to proprioceptive stimuli in 30 young people with dystonia and 22 controls (20). Participants sat at a table with their arm positioned in the arm-rest of a robotic wrist interface which delivered controlled passive wrist extension movements, resulting in brief stretches of the wrist flexors, with rise-time of 240 ms, and a target of 12° from the neutral position. Up to 160 wrist extension movements were recorded for each hand. Scalp EEG was recorded using a BrainVision system (BrainAmp MR Plus) and stimulus timing was synchronized with the EEG recordings via an electrical marker designating the movement onset. Offline, data were segmented into epochs comprising 1 s pre-stimulus and 3.5 s post-stimulus. After artifact rejection, remaining epochs were averaged to produce a stretch evoked potential for each hand in each subject. EEG power was calculated in 1 Hz bins from 5 to 40 Hz using the continuous Morlet wavelet transform with eight wavelet cycles. Relative changes in post-stimulus EEG power with respect to the pre-stimulus period were calculated. The figure shows pooled time-frequency plots across subjects showing the response over the contralateral hemisphere to stretch of the dominant hand wrist flexors i.e., right sensorimotor cortex for left hand movement, left sensorimotor cortex for right hand movement for controls (A–C), and individuals with dystonia (D–F), grouped by age. Left column: Young age group (5–9 years, n = 10), middle column: Intermediate age group (10–14 years, n = 6), right column: Older age group (15–19 years, n = 6). x-axis shows time in ms after the stimulus (dashed vertical line), y-axis shows frequency, color scale shows relative power at each frequency with respect to the pre-stimulus period, such that dark blue indicates event-related desynchronisation (ERD) and yellow-orange indicates event-related synchronization (ERS). The sharp increase in power with respect to baseline at time zero, extending up to 40 Hz, and the brief, early increase in theta range (4–7 Hz) power from 0 to 300 ms are likely to reflect movement artifact and a contribution from the stretch evoked potential, respectively. Figure adapted from McClelland et al. (20).