Recognizing the Common Origins of Dystonia and the Development of Human Movement: A Manifesto of Unmet Needs in Isolated Childhood Dystonias

Abstract

Dystonia in childhood may be severely disabling and often unremitting and unrecognized. Considered a rare disorder, dystonic symptoms in childhood are pervasive in many conditions including disorders of developmental delay, cerebral palsy (CP), autism, neurometabolic, neuroinflammatory, and neurogenetic disorders. Collectively, there is a need to recognize the role of early postures and movements which characterize phases of normal fetal, infant, and child development as a backdrop to the many facets of dystonia in early childhood neurological disorders and to be aware of the developmental context of dystonic symptoms. The role of cocontraction is explored throughout infancy, childhood, young adulthood, and in the elderly. Under-recognition of pervasive dystonic disorders of childhood, including within CP is reviewed. Original descriptions of CP by Gowers are reviewed and contemporary physiological demonstrations are used to illustrate support for an interpretation of the tonic labyrinthine response as a manifestation of dystonia. Early recognition and molecular diagnosis of childhood dystonia where possible are desirable for appropriate clinical stratification and future precision medicine and functional neurosurgery where appropriate. A developmental neurobiological perspective could also be useful in exploring new clinical strategies for adult-onset dystonia disorders focusing on environmental and molecular interactions and systems behaviors.

Keywords: Gowers; cerebral palsy; cocontraction; developmental dystonia; dystonia; genetic heterogeneity; phenotypic pleiotropy; tonic labyrinthine response.

Figure 1

Fetal, infantile and pathological ballerina posturing dystonia. Ballerina posture in 35-week gestation fetus with absent corpus callosum and subsequently normal development (A), healthy 6-month old infant (B), and a 7-year old girl with typical-onset isolated monogenic dystonia secondary to the DYT-1 mutation for the past 11 months (C). The dystonia began in the left leg, spread to the right leg enforcing wheel-chair mobility after 6 months then spread to the arms: note shoulders hunched, arms extended to write, and left leg extension under the table with “ballerina” right leg posturing associated with equinovarus posturing at the right ankle. These pictures illustrate that “ballerina posturing” is common in infancy but pathological after the first year of life. The dystonia posturing may be considered a release of formerly dominant movements and postures of the legs before independent floor locomotion, standing, and walking. It is noteworthy that the ballerina posturing of the right leg was abolished as soon as the 7-year old girl regained independent standing 1 month after DBS. This reinforces the link between dystonic postures and functional levels. In this case, a transient regression to infantile posturing is brought about by dystonia.

Figure 2

Scissoring in cerebral palsy by Gowers (46).

Figure 3

Tonic labyrinthine responses (TLRs). Provoked by supine and vertical suspension. Abolished body inversion (held upside down) and by sleep. Three-year old ex-preterm child with shunted hydrocephalus. See figures for explanation. The TLR is what produces “scissoring” in many children and young people with CP. Although often considered a feature of the “spastic syndrome,” the TLR shares more in common with dystonia since it is associated with bilateral spontaneous extensor great toes also known as the “Striatal Toe” being a hallmark of dystonia. When the Babinski manoeuver is performed (stroking the sole of the foot firmly), the great toes flex. The TLR is also associated with cocontraction of agonist–antagonist muscles and this is abolished by sleep, another features of dystonia. Operational definitions of the TLR: Vertical suspension (top left) and supine lying (top right) bring out scissoring of the legs [adduction of the hips, extension of the knees, equinus foot posturing at the ankle, and spontaneous extensor (striatal) toes] (top panels). The legs cannot be passively separated (3rd panels from top) and move “en bloc.” Inverting the child produces abduction and flexion at the hips with flexion of the knees and reduced ankle equinus (4th panels from top). Sleep abolishes the scissoring of the TLR in the supine posture (bottom left) and the muscles are completely at rest as measured by surface electromyography (bottom right): the legs are completely relaxed and offer no resistance to passive movements. Adapted from Dr. J.-P. Lin “Motor Assessment in Children with Cerebral Palsy” Ph.D. thesis, 1998, Edinburgh.

Figure 4

Developmental model of physiological and pathological dystonia in young and elderly. (A) Model of akinesia, kinesia, and hyperkinesia according to relative balance of selective control (SC) and surround inhibition (SI) with rise in cocontraction. (B) Increasing SC as increasing surround inhibition (SI) “prunes” excessive movements in childhood from age 3 to 6 years, respectively. (C) The onset of pathological dystonia is associated with reduced surround inhibition (SI) and reduced SC. (D) The elderly experience reduced SC and reduced surround inhibition (SI) with consequent loss of skilled performance. Adapted from Lin et al. (30), Mink (53), Tedroff et al. (35), and Graziaido et al. (36).

Figure 4

Developmental model of physiological and pathological dystonia in young and elderly. (A) Model of akinesia, kinesia, and hyperkinesia according to relative balance of selective control (SC) and surround inhibition (SI) with rise in cocontraction. (B) Increasing SC as increasing surround inhibition (SI) “prunes” excessive movements in childhood from age 3 to 6 years, respectively. (C) The onset of pathological dystonia is associated with reduced surround inhibition (SI) and reduced SC. (D) The elderly experience reduced SC and reduced surround inhibition (SI) with consequent loss of skilled performance. Adapted from Lin et al. (30), Mink (53), Tedroff et al. (35), and Graziaido et al. (36).