The Basal Ganglia

Five subcortical gray-matter macroscopic nuclei (Figs 18-1 and 18-2) constitute the basal ganglia:

FIGURE 18-1 A, This axial view, the one used in computed tomography and magnetic resonance imaging studies, shows the basal ganglia in relation to other brain structures. The heads of the caudate nuclei (C) indent the lateral undersurface of the anterior horns of the lateral ventricles. The caudate and putamen (P) constitute the striatum. The globus pallidus (G), which has internal and external segments, and the putamen form the lenticular nucleus, named for its resemblance to an old-fashioned lens (see Fig. 18-1, C). The posterior limb of the internal capsule (IC) separates the lenticular nucleus from the thalamus (T), which is not a member of the basal ganglia family. B, In this coronal view of the diencephalon, the substantia nigra (SN), as well as the subthalamic nuclei (STN), sits below the thalamus. The substantia nigra, because of its characteristic shape and pigmentation, serves as a landmark. The lateral ventricles are bounded laterally by the heads of the caudate nuclei (C) and superiorly by the corpus callosum (CC). This myelin stain has blackened the heavily myelinated fibers of the internal capsule (IC) and corpus callosum (CC). C, A coronal view shows extrapyramidal circuits. The putamen sends a direct and an indirect dopamine tract to the internal segment of the globus pallidus (GPi). Dopaminergic neurons in the substantia nigra project to the putamen, where neurons with D₁ receptors project directly to the GPi. Putaminal neurons with D₂ receptors project through the globus pallidus external segment (GPe) and subthalamic nucleus and thence to GPi. The GPi innervates the ventrolateral nucleus of the thalamus, which projects to the motor cortex. The cortex, completing a circuit, innervates the putamen.

FIGURE 18-2 This computer-generated rendition of the midbrain should be compared to a photograph (see Fig. 2-9), functional drawings (see Figs 4-5 and 4-9), and an idealized sketch (see Fig. 21-1). The lower third of the midbrain, which lies just caudal to the diencephalon, contains the pair of horizontal but gently curved, elongated, pigmented nuclei – the substantia nigra. In Parkinson disease, the substantia nigra and other pigmented nuclei lose their pigment and, compared to normal, thus appear blanched. The midbrain also houses the prominent aqueduct of Sylvius, which is the dorsal heart-shaped hole surrounded by the periaqueductal gray matter. Cerebrospinal fluid passes from the third ventricle, through the aqueduct, to the fourth ventricle.

Neuroanatomical tracts, of spaghetti-like complexity, link the basal ganglia to each other and to the thalamus, conjugate oculomotor circuits, and the frontal lobe. Projections from the basal ganglia constitute the extrapyramidal tract, which complements the pyramidal (corticospinal) tract. The extrapyramidal tract modulates the corticospinal tract. It promotes, inhibits, and sequences movement. In addition, it maintains appropriate muscle tone and adjusts posture.

Although the extrapyramidal tract seems to play merely a supportive role – indirectly influencing the corticospinal tract by acting on thalamocortical connections and projecting only within the brain – it comprises several clinically important tracts. The most important one, from a clinical viewpoint, is the nigrostriatal tract, which, as its name suggests, extends from the substantia nigra to the striatum (Fig. 18-3). This tract provides dopamine innervation directly and indirectly, via the subthalamic nucleus, to the globus pallidus’ internal segment (GPi).

FIGURE 18-3 A succession of enzymes normally converts tyrosine to dopamine in the presynaptic nigrostriatal neuron. In Parkinson disease, the nigrostriatal tract degenerates, but the postsynaptic dopamine receptors remain intact. As a result of the degeneration, an absence of tyrosine hydroxylase leads to insufficient dopa and then markedly reduced synthesis of dopamine. L-dopa, which is a standard oral medication for Parkinson disease, penetrates the blood–brain barrier and substitutes for the deficient endogenous dopa in dopamine synthesis. D-dopa, the dextro-isomer, does not cross the blood–brain barrier and cannot enter the synthetic pathway. It is therefore useless as a treatment for Parkinson disease.

Dopamine agonists, such as pramipexole (Mirapex) and ropinirole (Requip), act directly on the D₂ receptor and, to a lesser extent, other postsynaptic dopamine receptors. Although dopamine agonists treat Parkinson disease, especially after the nigrostriatal neurons can no longer synthesize or store dopamine, they produce a less powerful effect than L-dopa.

Because reserpine and tetrabenazine deplete dopamine from its presynaptic sites, each reduces hyperkinesia in chorea, tardive dyskinesia, and Tourette disorder. However, presumably because these drugs create a dopamine deficiency state, they produce lethargy, parkinsonism, and depression.

The globus pallidus is essentially an inhibitory, gamma-aminobutyric acid (GABA)-based nucleus. In contrast, the subthalamic nucleus is essentially an excitatory, glutamate-based nucleus.

One of the main differences between dopamine receptors is that, in the striatum, dopamine binding to dopamine 1 (D₁) receptors stimulates adenyl cyclase activity, but dopamine binding to dopamine 2 (D₂) receptors inhibits adenyl cyclase activity (see Table 21-1).

Physical or biochemical injuries of the basal ganglia typically produce hypokinesia (too little movement) and, when patients move, bradykinesia or akinesia (slow or absent movement), rigidity, and impaired postural reflexes. Alternatively, such injuries may produce a hyperkinesia (excessive movement), which takes the form of tremor, athetosis, chorea, hemiballismus, or dystonia. Neurologists often refer to each of these movements as a dyskinesia. Sometimes the injuries even produce combinations of too little and too much movement. For example, Parkinson disease creates akinesia and tremor.

As with other injuries of the brain – except for those in the cerebellum – unilateral injuries of the basal ganglia induce clinical abnormalities in the contralateral side of the body. When illnesses affect only the extrapyramidal tracts, patients have no signs of pyramidal (corticospinal) tract damage, such as paresis, spasticity, hyperactive reflexes, and Babinski signs. Similarly, they have no signs of cerebral cortex damage, such as dementia and seizures.

General Considerations

The involuntary movement disorders share several clinical features. Anxiety, exertion, fatigue, and stimulants (including caffeine) increase the movements, but willful concentration and sometimes biofeedback may suppress them, at least transiently. Most movements disappear during sleep. The exceptions – hemifacial spasm, myoclonus, palatal tremor, tics, and specific sleep-related disorders, such as restless legs syndrome (RLS) and periodic movements – persist without regard to sleep stage (see Chapter 17).

Neurologists typically measure four parameters of involuntary movements:

The diagnosis of patients with involuntary movement disorders is fraught with at least two potential errors. Although possibly debilitated by uncontrollable movements and inarticulate speech, patients may remain fully alert, intelligent, and, possibly by resorting to unconventional techniques, able to communicate. Unless physicians are astute, they may misdiagnose these individuals as having Intellectual Developmental Disorder, the diagnosis from the preliminary Diagnostic and Statistical Manual of Mental Disorders, 5th edition (DSM-5) that replaces mental retardation, or dementia.

Another error may occur when patients, at first glance, appear to have a psychogenic movement disorder (see later and Chapter 3). In many situations, the lack of a definitive confirmatory laboratory test forces neurologists to rely exclusively on their clinical judgment.

Parkinson Disease

Essential tremor and RLS are more frequently occurring, but Parkinson disease remains the quintessential movement disorder. Parkinson disease has three cardinal features:

The initial and ultimately most disabling physical feature of Parkinson disease is usually bradykinesia or, in the extreme, akinesia. Slow or absent movement produces the classic masked face (Fig. 18-4), paucity of trunk and limb movement (Figs 18-5 and 18-6), and impairment of activities of daily living. Parkinson patients sometimes liken their slow movements to slogging through hip-deep mud, wearing lead clothing, or driving a car with an engaged emergency brake.

FIGURE 18-4 Compared to normal individuals of the same age, Parkinson disease patients blink less frequently, offer fewer facial expressions, and less often move their head. Neurologists have called patients’ facial appearance a “stare” or “masked facies” (Latin, face or countenance), but now they usually describe the face as masked. Even when subtle, the masked face gives the appearance of apathy or depression.

FIGURE 18-5 Parkinson disease patients typically sit motionless with their legs uncrossed and their feet flat. Their arms remain on the chair or in their lap and rarely participate in normal gestures or repositioning movements. In contrast to normal individuals and especially those with chorea, Parkinson disease patients do not shift their weight from one hip to another or make any unnecessary movements.

FIGURE 18-6 Patients with akinesia and rigidity cannot rapidly flex their spine, hips, or knees. When sitting, they tend to fall slowly and solidly backward into a chair. Unable to bend rapidly, their feet rise several inches off the floor. Sitting and turning en bloc signal early parkinsonism.

Rigidity typically accompanies bradykinesia (Fig. 18-7). Although rigidity is one of the cardinal features of Parkinson disease, it often appears as a manifestation of other extrapyramidal disorders. No matter the context, physicians should not confuse rigidity with spasticity, which signals corticospinal tract disease (see Chapter 2).

FIGURE 18-7 Physicians typically elicit rigidity by rotating the patient’s wrist. When present, rigidity causes an increased tone in all directions of movement. A superimposed tremor adds a ratchet-like, cogwheel rigidity resistance.

Tremor is often the most conspicuous feature of Parkinson disease; however, it is the least specific sign, least debilitating symptom, and least associated with dementia and depression. In Parkinson disease, the affected body part usually oscillates in a single plane with a regular rate, although with a variable amplitude. It primarily involves the hands. Even more characteristically, the tremor appears when patients rest quietly with their arms supported. Neurologists call it a resting tremor (Fig. 18-8) and can show that it differs from cerebellar and essential tremors. When patients have tremor as their primary symptom, neurologists refer to them as having “tremor-predominant” Parkinson disease.

FIGURE 18-8 The resting tremor – a cardinal feature of Parkinson disease – consists of a relatively slow (4–6-Hz) to-and-fro flexion movement of the wrist, hand, thumb, and fingers most apparent when patients sit comfortably. Its similarity to shaking pills in a cupped hand gave rise to the description “pill-rolling” tremor. The tremor is exaggerated or sometimes apparent only when patients are anxious. However, voluntary movement or intense concentration may momentarily reduce the tremor, and sleep abolishes it. Rigidity and akinesia almost always accompany the Parkinson disease resting tremor.

These cardinal features, in contrast to signs of most other movement disorders, typically first develop in an asymmetric or unilateral pattern. Even as Parkinson disease progresses to involve both sides of the body, its manifestations continue to predominate on the side initially involved.

Another important feature of Parkinson disease consists of the cardinal features’ response to levodopa (L-dopa) treatment in almost 80% of cases. In the absence of a definitive laboratory test for the illness, a positive response to L-dopa confirms the diagnosis for most neurologists. Likewise, failure to respond prompts them to consider alternative diagnoses, such as medication-induced parkinsonism, progressive supranuclear palsy, and Wilson disease (see later).

Additional symptoms and signs may emerge as Parkinson disease advances. Patients lose their postural reflexes, which are neurologic compensatory mechanisms that adjust muscle tone in response to change in position. Loss of these reflexes, in combination with akinesia and rigidity, results in a characteristic gait impairment, marche à petit pas or festinating gait, which consists of a tendency to lean forward and accelerate the pace (Fig. 18-9, A). In a test of postural reflexes, the pull test, the examiner pulls the patient from the shoulders (Fig. 18-9, B). Normal individuals merely sway. Patients who have mild impairment of their postural reflexes take a few steps back, i.e., have retropulsion. More severely affected ones rock stiffly backwards without flexion or other compensatory movement and topple, en bloc, into the examiner’s arms.

FIGURE 18-9 A, Parkinson disease often produces a festinating gait, in which patients take short, shuffling steps and accelerate their pace. Their neck and lower spine are typically flexed. When walking, they fail to swing their arms, look about, or have other normal accessory movements. Likewise, while turning en bloc, they simultaneously move their head, trunk, and legs. B, The pull test consists of the physician gently but rapidly pulling the patient’s shoulders. Unaffected individuals will compensate by taking one or two steps backward. Parkinson patients, who generally have impaired postural reflexes, will take many steps backward (i.e., have retropulsion), because they are unable to stop through reflexly weight-shifting compensatory maneuvers. In pronounced cases, as the one pictured here, patients unable to alter their posture will tilt backwards en bloc and fall into the physician’s arms. (Progressive supranuclear palsy patients have similar bradykinesia, lack of accessory movements, and a positive pull test, but their posture is extended or erect rather than flexed [see Fig. 7-7].)

Parkinson disease patients’ gait abnormality and impaired postural reflexes prevent them from walking safely. Many fall and fracture a hip. These disabilities eventually confine them to bed and prove fatal.

Even at the onset of the illness, patients’ handwriting deteriorates to a small and tremulous script, micrographia (Fig. 18-10). In a parallel fashion, their voice loses both volume and normal fluctuations in pitch and cadence, i.e., their speech becomes hypophonic and monotonous. Also, because of their illness or the medications used to treat it, Parkinson disease patients develop sleep disturbances, characteristically rapid eye movement sleep behavior disorder (see Chapter 17).

FIGURE 18-10 The handwriting in this sample from a Parkinson disease patient shows progressive decrease in height (micrographia) and a superimposed tremor. These abnormalities in signatures, such as those on checks, can often date the onset of Parkinson disease. Although essential tremor may also cause tremor in handwriting samples, micrographia indicates that the underlying illness is Parkinson disease.

After several years of disease, inadequate buffering, storage, release, and reuptake of dopamine – from both endogenous and exogenous sources – may cause fluctuating symptoms, termed “on-off.” During “on periods,” patients remain well treated and asymptomatic, but during “off periods,” which last 30 minutes to 2 hours, they are impaired by rigidity and bradykinesia. Even if patients reach a state of complete rigidity resembling catatonia in their off periods, they have no change in their level of consciousness or electroencephalogram (EEG).

Nonmotor physical problems also emerge. For example, Parkinson patients characteristically lose their sense of smell. The anosmia, which also occurs in Alzheimer disease, reflects the neurodegenerative nature of these illnesses (see Chapters 4 and 7). They also routinely develop problems with their autonomic nervous system, including dysphagia, constipation, urinary incontinence, and abnormal sweating.

Therapy of Parkinson Disease

Medications

L-Dopa.

Treatments for Parkinson disease alleviate motor symptoms for many years, but do not reverse the neurodegeneration. Medicines maintain normal dopamine activity by enhancing dopamine synthesis, retarding its metabolism, or acting as agonists at dopamine receptors. Enhancing dopamine synthesis, usually the initial treatment, consists of substituting orally administered L-dopa for endogenous but deficient DOPA in the synthetic pathway (Fig. 18-3).

To bypass the tyrosine hydroxylase deficiency, L-dopa penetrates the blood–brain barrier and inserts itself into the synthetic chain where it substitutes for DOPA. Acting as endogenous DOPA, L-dopa undergoes decarboxylation to form dopamine:

L-dopa remains effective until almost all the nigrostriatal tract neurons degenerate and the remaining ones can no longer synthesize, store, and appropriately release dopamine.

In contrast to the degenerating presynaptic neurons, the postsynaptic nigrostriatal neurons, which are coated with the dopamine receptors, remain intact. These receptors respond to dopamine agonists as well as to naturally synthesized and L-dopa-derived dopamine.

Prescribing L-dopa, in the “precursor replacement strategy,” is highly effective and maintains most patients’ functional status for approximately the first 5 years of the illness. During that time, enough nigrostriatal neurons remain intact to synthesize, store, and release the L-dopa-derived-dopamine. This strategy provides the most powerful, easiest to use, and least complicated symptomatic treatment. Neurologists typically prescribe L-dopa as a therapeutic trial and then for treatment until deterioration requires supplement with a dopamine agonist.

Dopa- and Dopamine-Preserving Medications

Several medications increase nigrostriatal dopa by inhibiting two enzymes – dopa decarboxylase and catechol-O-methyltransferase (COMT) – that metabolize it in the systemic circulation (Fig. 18-11). With a relative increase in nigrostriatal dopa, nigrostriatal dopamine concentration increases.

FIGURE 18-11 Medicines that inhibit catechol-O-methyltransferase (COMT), such as entacapone, and those that inhibit decarboxylase, such as carbidopa, slow the metabolism of L-dopa. Because of the blood–brain barrier, they do not affect dopamine synthesis in the nigrostriatal tract. These enzymes, combined with L-dopa, permit smaller L-dopa doses, which minimizes systemic side effects.

These enzyme-inhibiting medications cannot, in any significant concentration, cross the blood–brain barrier. Because the blood–brain barrier essentially excludes them from the nigrostriatal tract, they do not interfere with the normal nigrostriatal metabolism of L-dopa to dopamine. They act outside the brain to prevent the metabolism of L-dopa to dopamine or other metabolite within the systemic circulation.

One enzyme-inhibiting medication, carbidopa, inactivates dopa decarboxylase. Pharmaceutical firms have marketed fixed combinations of carbidopa and L-dopa as Sinemet. Another enzyme-inhibiting medication, entacapone (Comtan), inhibits COMT. A commercial preparation, Stalevo, combines both enzyme inhibitors – carbidopa and entacapone – with L-dopa.

These dopa-preserving medications maintain cerebral dopamine concentrations while allowing a reduced L-dopa dosage. They allow patients to avoid systemic side effects, particularly nausea, vomiting, cardiac arrhythmias, and hypotension. Some of the most troublesome side effects, nausea and vomiting, result from high doses of dopamine stimulating the emesis (vomiting) center in the medulla, which is one of the few areas of the brain not protected by the blood–brain barrier. The L-dopa and carbidopa commercial combination, Sinemet (Latin, sine without, em vomiting), almost completely eliminates that problem.

A complementary therapeutic strategy consists of blocking MAO-B, one of the main enzymes responsible for metabolizing and thus deactivating nigrostriatal dopamine. Selegiline and rasagiline (Azilect) – MAO-B inhibitors – preserve dopamine activity because they impair the oxidation of both endogenous and medically derived dopamine. As an added benefit of selegiline, its own metabolism produces minute amounts of methamphetamine and amphetamine, which provide a small but definite antidepressant effect. At least on a theoretical level, MAO-B inhibitors may also confer some neuroprotection by providing an antioxidant effect and reducing free radical formation.

On the other hand, although they ameliorate some symptoms and provide a modicum of antidepressant effect, antiparkinson MAO-B inhibitors carry a caveat. At high doses, they inhibit MAO-A as well as MAO-B. Because MAO-A is important in both serotonin and catecholamine metabolism, MAO-B inhibitors place patients in a position where they are vulnerable to the serotonin syndrome or a hypertensive crisis (see previously and Chapters 6, 9, and 21).

Dopamine Agonists

As an initial medication or when dopamine production eventually falls to inadequate levels, dopamine agonists – pramipexole and ropinirole – provide stimulation of postsynaptic dopamine receptors (see Fig. 18-3). Bypassing degenerated presynaptic neurons, dopamine agonists act directly on D₂ and, to a lesser extent, on other postsynaptic dopamine receptors.

One dopamine agonist – injectable apomorphine – rescues Parkinson disease patients from a sudden loss of dopamine activity. More important, it also rapidly reverses dopamine activity deficiency in NMS.

Problems with These Dopaminergic Medicines

Even though dopamine precursors and agonists miraculously reverse the rigidity and bradykinesia in at least the early stages of Parkinson disease, they often fail to alleviate these symptoms in its latter stages and cannot, at any time, alleviate others. In particular, these dopaminergic medicines do not alleviate dysarthria, dysphagia, gait freezing, tendency to fall, dementia, hallucinations, depression, or other psychiatric comorbidities – symptoms that often most reduce the quality of life.

In addition to failing to help certain symptoms, the dopaminergics may cause dyskinesias, sleep disturbances, visual hallucinations, thought disorders, and other mental status changes. The dyskinesias consist of oral-buccal-lingual movements, chorea, akathisia, dystonic postures, and rocking. Most of the dyskinesias are transient and do not inhibit patients’ function; however, sometimes they cause gait impairment or resemble tardive dyskinesia (see later). Despite most patients’ problems with dyskinesias, they prefer overactivity, which allows them to walk and care for themselves, to understimulation, with its rigidity and immobility.

Other Medications

Coenzyme Q10 plays a vital role in the mitochondrial respiratory chain. Presumably because of its antioxidant effect, pretreatment with coenzyme Q10 greatly reduces the Parkinson-producing potential of MPTP. Preliminary studies suggest that it may slow the progression of Parkinson disease.

Alpha tocopherol (vitamin E), another antioxidant and free radical scavenger, should protect dopamine from destruction by free radicals and other toxins. Despite that solid rationale, a major study in Parkinson disease showed that tocopherol, either alone or in combination with selegiline, failed to slow progression of the illness.

Anticholinergics reduce tremor in Parkinson disease and other forms of parkinsonism. By reducing cholinergic activity, these medicines seem to act by maintaining the balance with the diminished dopamine activity (Fig. 18-12). On the other hand, anticholinergics routinely produce mental and physical side effects, especially in the elderly.

FIGURE 18-12 In a classic but limited model, dopamine and acetylcholine (cholinergic) activity normally balance each other. When Parkinson disease reduces dopamine activity, the left side of the scale rises. Dopamine precursors, dopamine agonists, and anticholinergics – Parkinson disease treatments – restore the balance. Conditions characterized by excessive dopamine activity, such as chorea, push the left side downward. Substances that either antagonize or deplete dopamine, or enhance cholinergic activity, restore the balance.

Amantadine enhances dopamine activity by acting on presynaptic neurons to facilitate dopamine release and inhibit its reuptake. Amantadine provides a temporary, modest improvement in rigidity and bradykinesia. It may also ameliorate L-dopa-induced dyskinesias. Unless the patient has underlying dementia, amantadine rarely produces confusion or hallucinations.

Deep Brain Stimulation

Studies have not yet established the ideal location for the electrodes, the parameters of stimulation, or even its mechanism of action, but DBS has unequivocally raised the quality of life of patients with Parkinson disease, dystonia, and essential tremor. It also has clearly helped in many cases of Tourette disorder, spasmodic torticollis, tardive dyskinesias, chronic pain, and certain psychiatric conditions, including treatment-resistant depression and obsessive-compulsive disorder (OCD: see later).

To implant DBS in Parkinson disease patients, neurosurgeons insert tiny electrodes in the subthalamic nucleus or GPi. They then connect the electrodes to a pacemaker-like device inserted into the subcutaneous tissues of the chest. For a procedure that involves a neurosurgeon’s inserting a probe deeply into each side of the brain, DBS is relatively safe.

DBS allows Parkinson disease patients to reduce their medication regimen and maintain their mobility with a great reduction in dyskinesias. It also helps patients beset by constant on-off episodes. However, DBS does not ameliorate gait impairment, postural instability, cognitive impairment, or depression. In fact, depending on the target, postoperative dopaminergic medication regimen, and other postoperative factors, several percent of Parkinson patients have developed or have had worsening of depression, approximately 0.5–1.0% had suicide ideation or attempts, and a larger proportion showed apathy. Of course, in many of these cases the symptoms were mild, transient, or amenable to treatment. Moreover, DBS does not hasten cognitive deterioration.

Athetosis

Athetosis consists of involuntary slow, continually changing, twisting movements predominantly affecting the face, neck, and distal limbs (Fig. 18-13). It sits at the beginning of a sequence – athetosis, choreoathetosis, chorea, and hemiballismus – of progressively larger and more irregular involuntary movements. In a potentially confusing aspect, additional involuntary movements may coexist with athetosis. For example, rapid jerks of chorea may punctuate slow movements of athetosis, and powerful twists of dystonia may interrupt and override athetosis’ slow fluctuations.

FIGURE 18-13 In athetosis, the face grimaces incessantly. Fragments of smiles alternate with frowns. Pulling of one or the other side distorts the entire appearance. In addition, neck muscles contract and rotate the head. Laryngeal contractions and irregular chest and diaphragm muscle movements cause an irregular speech cadence, nasal pitch, and dysarthria. Fingers writhe constantly and tend to assume hyperextension postures. At the same time, wrists rotate, flex, and extend. Involuntary limb activity prevents writing, buttoning, and other fine tasks, but it usually allows deliberate, larger-scale shoulder, trunk, and hip movement.

Usually encountered as a variety of cerebral palsy (see Chapter 13), athetosis is usually not apparent until early childhood. Most often athetosis results from combinations of perinatal hyperbilirubinemia (kernicterus), hypoxia, and prematurity. Genetic factors are unimportant.

Because athetosis originates in brain injuries that occur during the first 30 days after birth as well as in utero, which neurologists consider congenital brain injuries, seizures and mental retardation frequently accompany this movement disorder. However, with damage confined to the basal ganglia, as in many cases of athetosis, patients have normal intelligence despite disabling movements and garbled speech. Physicians, schoolteachers, family members, and friends should recognize that these patients retain cognitive and emotional capacities despite devastating physical neurologic disabilities.*

Dopamine antagonists may suppress athetosis, but their long-term use may lead to complications. Paradoxically, neurologists often offer an empiric trial of L-dopa to children with athetosis for the possibility that the movements do not represent cerebral palsy but a different illness, dopa-responsive dystonia (see later). According to preliminary reports, DBS may also reduce athetosis. Injections of one of the varieties of botulinum toxin, onabotulinumtoxinA (Botox), abobotulinumtoxinA (Dysport), rimabotulinumtoxinB (Myobloc) or incobotulinumtoxin (Xeomin), may offer several months of reduced particularly troublesome movement or coexistent spasticity. (This book refers to all these medicines as “botulinum” or “botulinum toxin.”) When neurologists inject botulinum for spasticity, dystonia, or other reason (see below), it may induce temporary weakness. Moreover, because the affected neurons reconstitute themselves, neurologists must repeat the injections – usually every 3 months.

Chorea