Movement Disorders in Children

Introduction

The production of normal movement is a complex phenomenon, dependent on a multitude of structures and sensory feedback systems. In the cortex, these structures include not only the primary motor cortex (M1), but also the premotor and supplementary motor regions (Brodmann's area 6) anterior to the M1, as well as the parietal cortex (Brodmann's areas 5 and 7). The parietal cortex appears to encode information about the spatial orientation of objects in head- or shoulder-centered coordinates, as well as information about the current and desired arm positions in ballistic movements. This region has a role in the integration of visual and proprio-ceptive information into coordinate frames that can be used to generate movements. The premotor cortex appears to process sensory cues for intended movements, while the more superior and medial supplementary motor cortex has a role in the sequencing of movements.

Subcortical structures that are essential for normal movement include the cerebellum and the basal ganglia, which both receive and project fibers to all of these cortical regions. Both of these areas receive error signals from the olive and the substantia nigra, respectively. The olive encodes differences in observed and expected movements, while the substantia nigra and pars compacta encode differences in observed and expected rewards. The basal ganglia and the cerebellum appear to use these error signals to weight their processing of cortical inputs. They then project principally to the lateral thalamus (the basal ganglia to Va and VL, the "pallidal receiving area"; the cerebellum to VL and VPL, the "cerebellar receiving area"), which projects back to cortex (Fig. 1). Other projections are sent from the basal ganglia to brainstem nuclei, which are responsible for the production of complex, stereotyped movement patterns. The basal ganglia and cerebellum appear to incorporate information about errors in movement or goal-orientation and process them through various mechanisms to modulate motor output.

Brainstem centers responsible for executing complex, stereotyped movements include the superior colliculus (ballistic eye movements), the pedunculopontine nucleus (gait entrainment) and the vestibular and red nuclei (mediators of posture via modulation of extension and flexion). These centers act via regulation of the alpha motor neuron in the anterior horn, which is itself regulated by feedback from afferents from the muscle spindle and Golgi tendon organ. Information from spindles and Golgi tendon organs, encoding the velocity of muscle contraction and muscle

Pediatric Neurosurgery, edited by David Frim and Nalin Gupta. ©2006 Landes Bioscience.

G Pi and SNr )

\ I To brainstem and spinal cord

Figure 1. The BG are part of a loop circuit involving the cortex and thalamus. The open arrows reflect excitatory pathways and the dark arrows inhibitory pathways. The striatum is the source of BG input while the GPi is the major source of BG output. The BG have two major intrinsic pathways: direct and indirect. The GPe and STN are in the indirect path. The GPi is the endpoint of both indirect and direct pathways. The STN has a strong excitatory effect on GPi, which in turn inhibits the thalamus. Dopamine from the striatum excites the direct pathway and suppresses the indirect pathway. Overall, the direct pathway facilitates movement and the indirect inhibits movement. (BG = basal ganglia; GPe = globus pallidus externa; GPi = globus pallidus interna; STN = subthalamic nucleus; SNc, SNr = substantia nigra compacta and reticulata.)

length, provides baseline inputs to the alpha and gamma motor neurons. These inputs, together with the cortical and brainstem descending signals to the alpha and gamma motor neurons, contribute to a baseline efferent signal from the ventral horn, which determines muscle tone.

Disturbance of any of these pathways can produce disordered movement, which can assume a wide variety of forms. The terminology used to describe these disorders is complex, and descriptions of some common terms are given in Table 1.

Spasticity

Spasticity is a condition in which there is a velocity-dependent increase in resistance of the muscle group to passive stretch with a "clasp-knife" type component. It is associated with hyperactive deep-tendon reflexes, the Babinski sign, clonus and reduced range of joint motion. Spasticity affects both children and adults and results from a variety of neurological disorders, such as cerebral palsy

Table 1. Common definitions used to describe movement disorders

Term

Etymology

Clinical Definition

Dystonia

Chorea

Athetosis

Spasticity

Rigidity

Akathisia

Myoclonus Dyskinesia Ballismus

Syndrome of sustained muscle contractions, usually agonists and antagonists, leading to twisting, repetitive movements, or abnormal postures

[G. choreia, a choral dance] Syndrome of quick irregular movements, that can interfere with normal movements

[G. athetos, without position or place]

[G. spastikos, a drawing in]

[L. rigidus, inflexible]

[G. ballismos, a jumping about]

A constant succession of slow, writhing movements of fingers and hands, sometimes toes and feet

A velocity-dependent increase in muscle tone

Stiffness, inflexibility (not velocity-dependent)

A syndrome characterized by by an inability to remain in a sitting posture, with motor restlessness and a feeling of muscular quivering

Clonic spasm or twitching of a muscle or group of muscles

Stereotyped, automatic movements that cease during sleep

Lively jerking or shaking movements

(CP), multiple sclerosis, spinal cord or head trauma and ischemic or hypoxic brain injury. Cerebral palsy (CP) is one of the most common disorders resulting in spasticity. Spasticity occurs in approximately 60% of patients with CP, thus affecting at least 300,000 children in the United States. Spasticity is commonly treated with oral and intrathecal medications, local intramuscular injections and neuro-surgical procedures.

Neurosurgical interventions reduce spasticity by interrupting the stretch reflex at various sites along the spinal reflex arc, or by increasing the centrally-mediated inhibitory influence on the anterior horn motor neuron pool. Surgical interventions for spasticity can be classified into ablative peripheral procedures, such as rhizotomy or peripheral neurectomy, or central procedures, such as cordectomy, myelotomy, or stereotactic lesioning. Nonablative procedures include peripheral-nerve or motor-point blocks, the implantation of intrathecal catheters for infusion of drugs

to enhance inhibitory activity, and the implantation of spinal or cerebellar stimulators. Selective posterior rhizotomies and intrathecal baclofen pumps have emerged as the predominant neurosurgical procedures for treating spasticity in children. Orthopedic procedures, such as tendon release, transfer and lengthening, and myo-tomy are also performed for advanced stages of spasticity to correct deformities, release contractures and prevent skeletal complications. In general, the main goals of spasticity treatment, whether medical or surgical, are to improve function, facilitate care and reduce or prevent pain and muscle contractures.

The Stretch Reflex and Mechanisms of Spasticity

Competing excitatory impulses (glutamate- and aspartate-mediated from Ia muscle spindles) and descending inhibitory influences (gamma-amniobutyric acid (GABA)-mediated from basal ganglia and cerebellum) modulate alpha motor neuron output from the ventral horn of the spinal cord, and thus, skeletal muscle tone. Muscle spindles are specialized muscle fibers within skeletal muscle that respond to stretch by discharging through type Ia and type II afferent fibers. The stretch reflex system includes the stretch receptor within the skeletal muscle spindle, and its afferent (Ia) fiber running in the posterior nerve root, and the alpha motor neurons of the spinal cord segment innervating a particular muscle, its synergists, and its antagonists. The Ia afferent fiber directly excites the stretched muscle, whereas the inhibitory Ia interneuron, modulated by descending corticospinal tracts, inhibits the antagonistic muscle.

Reduction in GABA-mediated presynaptic inhibition of Ia afferents has been suggested as a possible contributing mechanism of spasticity. Presynaptic inhibition depresses the monosynaptic stretch reflex by reducing transmission in the Ia fiber prior to its synapse with the alpha motor neuron. Most proposed mechanisms of spasticity include a loss of inhibitory control, such as presynaptic inhibition, recurrent (Renshaw) inhibition, reciprocal Ia inhibition (leading to abnormal coactivation of antagonist muscle groups), group II afferent inhibition and Golgi tendon organ inhibition. The exact types of inhibition lost in clinical spasticity are not clearly defined and most likely vary among patient populations.

Pharmacological Treatment of Spasticity

General

The major oral agents used to treat spasticity are baclofen (Lioresal), benzodiazepines (diazepam-Valium), dantrolene (Dantrium) and tizanidine (Zanaflex). Baclofen is a GABAB agonist that produces inhibition via a bicuculline-resistant GABA receptor. It has a half-life of about 3 hours and crosses the blood-brain barrier poorly, requiring systemic doses of 20 to 90 mg/day (usually divided TID). Side effects include drowsiness, confusion and ataxia.

The benzodiazepines appear to act at the spinal cord by enhancing the postsyn-aptic effects of GABA to increase presynaptic inhibition. Diazepam is the most common benzodiazepine used for spasticity. It has a half-life of 36 hours. Typical doses range from 0.1 to 1 mg/kg day divided TID. Tolerance often develops, and lethargy is a common and undesirable side effect. Dependency may develop. Rapid withdrawal should be avoided.

Dantrolene acts site by suppressing calcium influx from the sarcoplasmic reticulum in skeletal muscle fibers, interfering with muscular contraction, and thus producing proportional increases in motor weakness and decreases in spasticity. Dantrolene has a half-life of 3 to 9 hours. The oral dose is about 12 mg/kg/day divided QID. Weakness is the main side effect, and dantrolene has been occasionally reported to cause severe hepatotoxicity.

Tizanidine is an alpha-2 agonist that modulates excitatory neurotransmitter release from interneurons and afferent terminals. Its effectiveness in adults is similar to baclofen's, but has not been tested in children in clinical trials. It has a half-life of 2 to 3 hours, and typical doses range from 8 to 24 mg/day divided QID. Side effects include lethargy, dizziness and hypotension.

Local Injections

Local treatments for spasticity utilize neuromuscular blockade to weaken muscular contractions, and thus spasticity. The agents used are botulinum toxin (Botox, types A to G), alcohol and phenol. Botox is injected intramuscularly and acts at the motor end-plate to prevent acetylcholine release, resulting in temporary muscle weakness (up to 4 months). Injections may be repeated as needed. Doses are dependent upon the size of the muscle group to be injected, ranging from 5 to 50 units/ injection site with a maximal recommended dose of 10 units/kg. Alcohol and phenol can be injected intramuscularly, intraneurally or perineurally. However, because pain and dysesthesias commonly result, these injections are not frequently performed.

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