Pediatric Movement Disorders - Bradykinesia

Mechanism

Parkinsonism and its components, including bradykinesia, tremor, and rigidity, are probably caused by decreased activity of the neurotransmitter dopamine within the striatum of the basal ganglia. The basal ganglia are a set of structures buried deep within the brain that are involved with the control and sequencing of movement. The striatum is the part of the basal ganglia that receives connections from the motor areas of the cortex that are responsible for organizing movement commands. The striatum also receives connections from the dopamine-producing cells at the base of the brain where it connects to the spinal cord (brainstem). This particular part of the brainstem, which produces dopamine, is known as the substantia nigra. The cells of the substantia nigra connect to the striatum where they release dopamine. The released dopamine probably affects the size and speed of movements and may be involved with the selection of components of movements or the sequencing of multi-step movements (see Anatomy of the basal ganglia). In Parkinson's disease, the dopamine-producing cells of the substantia nigra degenerate, leading to decreased dopamine in the striatum.

Damage to the basal ganglia may produce different movement disorders, including dystonia, chorea, athetosis, or parkinsonism. Loss of dopamine activity seems to "turn down the volume" on the basal ganglia, so that movements become slow and difficult to initiate. The performance of rapidly sequenced or repetitive movements may be particularly difficult.

In the most severe cases, the child is unable to initiate any movement and becomes frozen in place. A remarkable feature of parkinsonism is that often a sensory stimulus, such as a line on the ground that must be stepped over or a ball that must be caught, may lead to the very rapid and appropriate initiation of movement. Therefore, the primary problem in parkinsonism seems to be with self-generated, voluntary movements and children may move faster when they are responding to something in the environment outside themselves.

In the adult and juvenile forms of Parkinson's disease (PD), cells in the substantia nigra start to die. These two disorders probably have many causes. In some cases, the adult form of PD has been linked to a dominant mutation in the gene for alpha-synuclein. The juvenile form has been linked to recessive mutations in the parkin genes. In both cases, these lead to a progressive decrease of dopamine in the striatum of the basal ganglia. Symptoms do not occur until substantial portions of the cells have died; in some studies, up to 70% of these cells die before the onset of symptoms. In adults, parkinsonism is sometimes caused by strokes in the substantia nigra or striatum; this would be a very unusual in a child.

Other Forms of Parkinsonism
There are many other causes of adult parkinsonism that do not occur in children, including multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and corticobasal degeneration (CBD). However, many childhood degenerative diseases, including the spino-cerebellar ataxias, can lead to progressive worsening. Parkinsonism may be caused by metabolic disorders that interfere with the cells' ability to produce dopamine. The most common of these disorders is dopa-responsive-dystonia or DRD. In children with DRD, a mutation in the GTP-cyclohydrolase 1 gene leads to defective production of biopterin, cofactor for one step needed to synthesize dopamine. DRD, also called Segawa's disease or dystonia with diurnal variation, usually produces dystonia in addition to parkinsonism. Neuroleptic medications (including haloperidol, risperidal, pimozide, olanzapine, and quetiapine) commonly used to treat tic disorders or psychiatric disorders may lead to symptoms of parkinsonism in some children. Parkinsonism may also be caused by destruction of the striatum itself from toxins, lack of oxygen, stroke, or tumors.