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.

Pharmacological and neurosurgical interventions for managing dystonia in cerebral palsy: a systematic review

“…7 Nevertheless, dystonia in childhood CP remains underdiagnosed. 8,9 Dystonia may be associated with basal ganglia and cortical/subcortical lesions typically arising late in gestation or around birth. 10 On neurological examination of individuals with CP, dystonia is characterized by the presence of fluctuating hypertonia and/or involuntary postures and movements triggered by arousal, such as wakening from sleep, tiredness, and lack of sleep; cognitive tasks; emotional state; and physiological phenomena, such as hunger and temperature, tactile stimulation, or voluntary movement.…”

The neurological phenotype of developmental motor patterns during early childhood

“…These processes will result in the elimination of inefficient synaptic connections, preserving the most efficient neural networks (Edelman, 1993;Nishiyori, Bisconti, Meehan, & Ulrich, 2016). This organization concurs with a gradual change in the quality of motor behavior, changing from a clumsy pattern with co-contractions, into fluent, precise, and wellcoordinated motor performances (Hempel, 1993a(Hempel, , 1993bJovanovic & Schwarzer, 2017;Largo, Fischer, & Rousson, 2003;Lin & Nardocci, 2016;Nishiyori et al, 2016).…”

“…During the acquisition of new motor patterns, the healthy motor system explores different strategies, resulting in variable motor output of optimal complexity (Dusing, Thacker, Stergiou, & Galloway, 2013). This organization concurs with a gradual change in the quality of motor behavior, changing from a clumsy pattern with co-contractions, into fluent, precise, and wellcoordinated motor performances (Hempel, 1993a(Hempel, , 1993bJovanovic & Schwarzer, 2017;Largo, Fischer, & Rousson, 2003;Lin & Nardocci, 2016;Nishiyori et al, 2016). These processes will result in the elimination of inefficient synaptic connections, preserving the most efficient neural networks (Edelman, 1993;Nishiyori, Bisconti, Meehan, & Ulrich, 2016).…”

“…Green boxes indicate the normal age-related presence of early neonatal movement patterns, primitive reflexes, and voluntary motor milestones. Due to the redundancy of neurons and synaptic connections in early childhood, inefficient activation of muscles may induce co-contractions and dystonic overflow movements (Fog & Fog, 1963;Kuiper et al, 2016;Largo et al, 2007;Lin & Nardocci, 2016;Nishiyori et al, 2016). Orange boxes indicate the maturation (determined by a peak in gray matter on MRI (Gogtay et al, 2004)) of developing motor centers.…”

“…Although speculative, the early presence of dystonic features, the prolonged continuation and the gradual disappearance (before adulthood), could be attributed to the continuous development and maturation of the basal ganglia and the connecting networks. Due to the redundancy of neurons and synaptic connections in early childhood, inefficient activation of muscles may induce co-contractions and dystonic overflow movements (Fog & Fog, 1963;Kuiper et al, 2016;Largo et al, 2007;Lin & Nardocci, 2016;Nishiyori et al, 2016).…”