Pediatric Movement Disorders and Ataxia

Introduction

Movement disorders are clinically defined by the inability to execute skilled motor plans due to deficient targeting and/or timing. They are dynamic disorders, shifting in severity or distribution over time, distinguished from paresis, spasticity, other sequelae of corticospinal tract injury. Classically thought to arise from basal ganglia (BG) injury, now appreciated that lesion of any node within the motor control network (BG, cortex, internal capsule, thalamus, brainstem, cerebellum)¹ can produce a movement disorder. The concept of a lesion to a network, rather than to a discrete anatomical site, now informs much of the current understanding of the origins of movement disorders.

Taxonomy

Childhood movement disorders are diverse in appearance, timing, etiology, treatment, and prognosis; a systematic approach is required. Essential clues to diagnosis:

DISTRIBUTION: (1) Focal: Only one body part/region. (2) Segmental: ≥2 contiguous regions. (3) Multifocal: ≥2 noncontiguous regions. (4) Generalized: Legs, trunk, and ≥1 other region.

TIMING: Paroxysmal vs. static, progressive, characteristic ages of onset, rate of progression.

NATURE OF MOVEMENT: Hyperkinetic, hypokinetic, or ataxic.

ELLICITING/EXACERBATING FACTORS: Arise from rest, standing, with all movement, or only with skilled movement? Time of day? Worsened or improved with alcohol, caffeine, meds? (see Table 16.1.)

Chorea

Pathophysiology

Injury to basal ganglia, especially the striatal indirect pathway, is a common anatomic precipitant for many cases of chorea. The neurophysiology underlying chorea remains a mystery.

TABLE 16.1 Tips in Evaluating a Child with Abnormal Movements

1. If a picture is worth a 1,000 words a video is worth a million.

2. Many movement disorders are coexpressed with other movement disorders. Focus on each type of movement in turn describing it first in isolation. Look for interactions among the movements—e.g., tremor only in a dystonic limb or myoclonus of such severity that it masquerades as ataxia.

3. Watch for abnormal behaviors that are used to mask abnormal movements— incorporation into normal movements strange postures sensory tricks sitting on hands with chorea or akathisia.

Causes

Static injury: Kernicterus, hypoxic-ischemic insult, toxin (ethanol, methanol, toluene, bismuth, manganese, thallium, mercury), infections (mycoplasma, Lyme, legionella, toxo, HIV, HSV, measles, mumps, varicella, parvovirus B19), trauma, midline CNS malformation disorders. Autoimmune/inflammatory: Sydenham chorea (see below), SLE, anti-phospholipid antibody syndrome (APLS), Behçet syndrome, ADEM, CNS vasculitis, Rasmussen encephalitis, MS (rare symptom), acute necrotizing encephalopathy (late finding). Endocrine/nutritional: Hyper/hypoglycemia, hyper/hyponatremia, hyperthyroidism, hypoparathyroidism, hypoMg, B₁₂ deficiency in infancy, chorea gravidarum. Medications: DA agonists, DA antagonists, AEDs (phenytoin, carbamazepine, PHB), calcium channel blockers (CCBs), anticholinergics, antihistamines, OCPs, lithium. Neurodegenerative: Huntington disease (HD), Wilson disease (WD) (see below), neuroacanthocytosis, Lesch-Nyhan, ataxia telangiectasia, mitochondrial disease (Leigh syndrome), PKAN, SCA, DRPLA, Fahr syndrome, leukodystrophy (Pelizaeus-Merzbacher disease). Metabolic syndromes: Glutaric acidemia, propionic acidemia, homocystinuria, PKU, Costeff syndrome (3-methylglutaconic aciduria), cerebral folate deficiency, sulfite oxidase deficiency, pyruvate carboxylase deficiency, biotinidase deficiency. Structural lesions: Tumor, CNS lymphoma, abscess, AVM, cavernous hemangioma. Paroxysmal dyskinesias: See later in this chapter.

Diagnosis

Signs of motor impersistence are most reliable: milkmaid’s grip, touchdown sign (arms upright, palms in), harlequin tongue. Distinguish from akathisia (inner restlessness) and tics (repetitive, internal drive). MRI: Often indicated, especially in hemichorea or with focal neurologic signs. Labs: ASLO, anti-DNAse B, helpful in establishing a diagnosis of Sydenham chorea, but unreliable at predicting duration, progression, or recurrence. Chorea can herald a treatable disorder (e.g., the antiphospholipid antibody syndrome), offering opportunity to prevent later disease progression.

Primary Chorea

Isolated chorea independent of a predisposing injury or toxic exposure; presumed to be genetic. Multigenerational family history is essential.

BENIGN HEREDITARY CHOREA (BHC): Occurs in normally developing children, 1st 5 y of life, nonprogressive after 1st decade. Generally improves (but not resolved) in adulthood. Does not impact intellect/behavior. Dominantly inherited, intra-familial heterogeneity; some carriers display athetosis, myoclonus or dystonia ± chorea.

HUNTINGTON DISEASE (HD): Most common genetic cause of chorea. Genetics: Dominantly inherited, anticipation secondary to CAG repeat expansion. Pathology: Degeneration of striatal medium spiny neurons. Juvenile HD: In <10% of cases (˜1:10⁵). Onset age <20 y, with school failure, depression, and attention deficits before chorea. Few teens, but most children <10 y develop the Westphal variant: dementia, parkinsonism, seizures, and dystonia as primary features. Children with HD progress much faster than adults. Most juvenile HD inherited through paternal lineage. May become symptomatic before fathers in cases of unusually large repeat expansion (see HD under “Parkinsonism” later in the chapter.)

Secondary Chorea

Resulting from outside injury. Five “I’s” can lead to acute or semi-acute chorea or predispose to development of chorea months/years later: injury, infarction, infection, inflammation, and infiltrative processes.

SYDENHAM CHOREA (SC): Major criterion for rheumatic fever (RF) may be 1st/only manifestation, self-limited. Pathophysiology: Autoimmune, anti-basal ganglia antibodies follow group A β-hemolytic strep infection. Epidemiology: Most common acute chorea in children, almost never below 5 y, uncommon beyond puberty, F > M. 20% kids with RF get SC. Now rare in North America/Europe, given widespread antibiotic use. Diagnosed at pediatric centers 5 to 10 times/y. Presentation: SC can follow strep infection by up to 6 mo, often asymmetric, signs of motor impersistence (spooning of fingers, harlequin tongue, milkmaid’s grip, touchdown sign) indistinct from other choreas. Important distinguishing features of SC are age and rapidonset over hours/few days. Other neurologic signs less severe but common: hypotonia, akathisia, dysarthria, gait disturbance, personality change, emotional lability. ˜20% develop attention deficits and/or OCD. Diagnosis: Clinical dx—does not require supportive testing. MRI indicated to rule out mass lesions, may have increased volume & T2 signal in basal ganglia. Throat cultures, ESR, CRP, ASLO, anti-DNAse B all have low sensitivity/specificity and may be negative at onset (since may be 6 mo s/p strep infection); sometimes useful if dx uncertain. Trending values does not improve diagnosis/predictive value. Management: Prevent recurrent SC with antibiotic prophylaxis, thorough screening for other RF sx. Treatment for mild SC debated since natural history is fluctuating improvement. Immunosuppression likely shortens course (prednisone if mild, IVIG if moderate-severe). Suppress chorea with benzodiazepines or valproate. Prognosis: Chorea resolves <6 mo in 50%; can take up to 2 y; permanent in rare cases. Recurs with subsequent strep infection in 1/3. 75% women with SC as child have recurrence with pregnancy or OCPs. Mild executive function deficits and bradykinesia are common into adulthood even if chorea resolved.

LUPUS-ASSOCIATED CHOREA: Uncommon complication of SLE, associated with anti-cardiolipin Ab or ischemia.² Chorea is 1st manifestation in majority of SLE with chorea. Consider in DDX of any new-onset chorea. Early diagnosis and treatment critical to limiting scope of disease.

POST-PUMP CHOREA: Very small fractions of patients develop persistent chorea after cardiac bypass or resuscitation. Epidemiology: Most common in patients <1 y but reported throughout the life span. Predictors: Longer hypothermia, esophageal temp <20°C, use of pH-labile intraoperative management, preop developmental delays. Pathology: Loss of neurons & myelinated axons essentially restricted to the globus pallidus. Long-term sequelae: Substantial—50% with persistent dyskinetic movements, all suffer cognitive impairment,³ less common with improving cardiac anesthesia/bypass techniques.

Tremor

Pathophysiology

Can arise from cortex, basal ganglia, brainstem, cerebellum, or periphery— each location associated with distinct tremor distributions, frequencies, and eliciting factors (see Table 16.2). At least 3 distinct mechanisms: (1) Focal weakness with imbalance of agonist-antagonist muscles; (2) failure at finetuning a movement (with impaired cerebellar compare-and-correct functions); (3) dominance of nuclei that discharge in rhythmic patterns as part of normal mode of operation (thalamus, inferior olive, portions of basal ganglia, “central oscillators” that underlie orthostatic tremor), many of which are defined functionally but not yet anatomically.

TABLE 16.2 Types of Tremor

Tremor Type		Description	Anatomical Origin
Rest tremor		Attenuates or resolves with movement or antigravity strength. Worsens with agitation or inattention.	Basal ganglia, especially substantia nigra
Action tremor		Elicited by initiating movement or increasing force generated. Four subtypes.
	1. Kinetic tremor	Occurs relatively uniformly with all types of volitional movement.
	2. Intention tremor	May emerge or worsen as the movement approaches completion—the stage at which finest tuning is required. Finger-nose-finger task demonstrates this tremor.	Cerebellum, rarely parietal, or their connections
	3. Isometric tremor	Produced by increasing force against a fixed target, without movement.
	4. Postural tremor	Occurs when holding a body part in a fixed position, resisting gravity.	Cerebello-olivary system
Rubral tremor		Coarse, jerky, irregular, large amplitude, low frequency. Combines rest and intention tremor (Holmes tremor or midbrain tremor).	Upper brainstem, thalamus, cerebellum
Physiologic tremor		Enhancement of normal motor oscillations with stressors. Nonpathologic. Seen only with particular situational challenges, e.g., stress, caffeine, fatigue.
Psychogenic tremor		Variability in tremor frequency, amplitude, distribution, and direction. Usually acute in onset but nonprogressive. Frequently distractable and demonstrates entrainment. The most common type of psychogenic movement disorder in both children and adults.

Demographics

10% to 20% of children referred to movement disorders clinics. Frequent inpatient consult—often emerges in systemically ill or heavily medicated child, usually as one of many symptoms.

Primary Tremor

Few conditions may produce tremor or tremor-like phenomena in children without other neurological symptoms. Many have self-limited, developmental conditions not requiring treatment; others are lifelong with predictable course.

DEVLOPMENTAL CONDITIONS: Developing motor control network occasionally produces paroxysmal and rhythmic benign movements. FH and exam are normal. Clinical diagnosis, but capturing events on EEG often provides reassurance for parent/physician. Resolution with normal neurodevelopment expected. Jitteriness: Symmetric, rhythmic oscillations involving arms, legs, or both. Occurs in 50% term infants in 1st wk of life. May reflect immaturity of spinal inhibitory pathways. Varies with arousal, often exacerbated by stimulation or crying, typically resolves in quietly awake state, suppressible with gentle pressure, passive manipulation of limb. Seen in normal and neurologically injured children. Shuddering attacks: Appear similar to shivering, last a few seconds, occur many times a day without provocation. Typically involve body above the diaphragm; onset 3 mo to 4 y, most common between 6 and 18 mo, duration typically few months to few years. Spasmus nutans (SN): 1 to 3 Hz oscillation of the head, either horizontal or vertical plane, onset between 6 and 12 mo, coexists with high-frequency pendular nystagmus. Postulated that head movements are compensatory for nystagmus. Head movements typically resolve within few months. Subclinical nystagmus persists several years, usually resolves. Rarely, SN-like pattern of head movement seen in patients with vision compromise, congenital nystagmus, or intracranial mass lesion—close observation and ophthalmologic evaluation are indicated.

ESSENTIAL TREMOR (ET): Epidemiology: Most common movement disorder in adults, ˜4% of all adults at 40 y. Childhood onset (mean, 6-7 y). Two peaks of referral: school-age children: tremor produces anxiety in parents; late adolescence: tremor leads to social or sports-related anxiety. M = F in adults, M > F in childhood. Genetics: Dominantly inherited, variable severity and age of onset within family. Penetrance is 100% by 60 y. Presentation/Clinical course: In children, typically mixed postural and action tremor affecting hands >> legs, neck, or voice.⁴ Always bilateral, may be moderately asymmetric, elicited, or exacerbated by stress, very slowly progressive (years to decades). Support diagnosis: Strong FH, adult family members report relief with moderate alcohol ingestion, normal development, and otherwise normal neurologic exam. Question diagnosis: Tremor sufficient to produce disability, presence of any other neurologic diagnosis or sign, progression within 1 to 2 y observation period.

Secondary Tremor

Very common neurologic symptom, consequence of many systemic diseases/CNS insults,⁴ tremor unlikely to contribute substantially to diagnosis. Tremor
that is progressive in distribution/severity, or which causes substantial disability, is likely secondary to degenerative disease or injury and requires MRI.

POSTTRAUMATIC: Tremor occurs in >50% survivors of severe head trauma in children, may present immediately after injury or develop many months later, well into rehab. Resolves spontaneously in >50%.

BOBBLE-HEAD DOLL SYNDROME: 2 to 3 Hz bobbing of the head, usually in vertical plane (“yes-yes”), occasionally in horizontal plane (“no-no”); voluntarily suppressible, often accentuated by rhythmic motor activity (e.g., walking). Typical onset 2 to 5 y. Can be associated with mass lesions in 3rd ventricle or cerebral aqueduct with hydrocephalus. Occasionally seen in children with cerebellar malformations but no mass or hydrocephalus.

DRUG-INDUCED: Tremor not likely a late effect—consider new/changed medications first. Culprits: Stimulants, bronchodilators, thyroid hormone, corticosteroids. Dopamine depleting/blocking agents can produce rest tremor and parkinsonism. Valproate, lithium, SSRIs, tricyclic antidepressants, and cyclosporine can produce variable (commonly intention) tremor.

Tics

Though tics have been regarded to be the most common movement disorder in children, this is a misconception, as the abnormality is the intense drive or impulse to act, not the movement itself. Historically they have been managed by general or behavioral neurology (see Chapter 15).

Myoclonus

DEFINITION: Brief, involuntary muscle jerk, nonsuppressible and generally no premonitory features, may be isolated finding or symptom of many diseases. Uncommon as isolated movement disorder in children—should always prompt evaluation for epileptic myoclonus.

Diagnosis

Considerations in evaluation.

EPILEPTIC VS. NONEPILEPTIC: Suggestive of epileptic myoclonus (see Chapter 5 for details): adolescent-onset, occurs just after waking; onset at 2 to 3 y with rapid evolution of multiple seizure types; onset in neonatal period; any alteration of consciousness with episodes. EEG is reasonable but nonobligatory. EMG of great value if uncertain etiology—distinguishes myoclonus vs. myoclonic seizures, negative myoclonus vs. astatic seizures, psychogenic vs. organically generated.

PRIMARY VS. SECONDARY: Myoclonus in isolation: Rare, suggests small/distinct DDX. Secondary: Follows traumatic or hypoxic CNS injury, or as part of larger cognitive/functional decline. Metabolic encephalopathies: Hepatic failure, uremia, metabolic alkalosis, hypercarbia, hyperglycemia. Toxins: Licorice, antacids, carbon monoxide, lithium, lead, mercury, bismuth, tetanus, acetone, toluene, organophosphate pesticides.

COINCIDENT WITH OTHER NEURO DISORDERS: Feature of neurodegenerative disorders and epilepsy syndromes. Prognosis/treatment based on unifying diagnosis, not on myoclonus.

ANATOMIC ORIGIN: Very useful for diagnosis and treatment, imaging sometimes helpful, careful exam more likely to localize. (1) Cortical: Most common, originates from sensorimotor cortex. Focal, distal, arrhythmic, affects arms > legs or trunk, spontaneous or induced by reflex or action. Examples:

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