Circuitry

In basal ganglia circuitry, all of cerebral cortex projects to the striatum (i.e., the caudate nucleus, putamen, and nucleus accumbens), which then projects to the globus pallidus (external and internal segments), through the thalamus, and finally back to the cerebral cortex. Dopaminergic projections from the substantia nigra pars compacta (motor) and nearby ventral tegmental area (limbic) play an important role. Because this feedback loop ultimately affects movement through pyramidal neurons’ output through the spinal cord, “extrapyramidal symptoms” (EPS) is not an entirely accurate term for basal ganglia problems. However, it is entrenched in clinical usage. The subthalamic nucleus, too, has an important modifying influence. Hypokinetic disorders usually stem from damage to the direct pathway through the internal globus pallidus; hyperkinetic movements result from damage to the indirect pathway through the external globus pallidus and subthalamic nucleus. These pathways control affect and cognition, as well as movement.

Cerebellar problems, such as ataxia, and primary motor (pyramidal) symptoms such as paralysis (complete inability to voluntarily use a muscle), paresis (partial paralysis), or spasticity, are not, by convention, movement disorders, because they do not stem from damage to the basal ganglia. However, they will be covered briefly here, because their effects on movement may easily be mistaken for basal ganglia symptoms.

Pharmacology

Dopamine is the best-understood neurotransmitter related to basal ganglia function.² Its receptors fall into two classes, the D₁ class, of which D₁ is mostly found in the striatum and D₅ extrastriatal, and the D₂ class, of which D₂ is primarily striatal whereas D₃ and D₄ are mostly extrastriatal. Its release in the motor control areas of the striatum seems to facilitate limb movement via D₂ receptors, and to inhibit movement via D₁ receptors. Medications most commonly used to affect dopamine neurotransmission are antagonists (such as haloperidol), precursors (such as levodopa), receptor agonists (such as pramipexole), and inhibitors of dopamine metabolism (such as entacapone [a catechol-O-methyltransferase (COMT) inhibitor] and selegiline [a monoamine oxidase-B (MAO-B) inhibitor, at least at low doses]). Acetylcholine is also important in the basal ganglia, particularly in striatal and nucleus accumbens’ control of motivation and memory. To a first approximation cholinergic effects counteract those of dopamine, making anticholinergics (such as benztropine) useful in the treatment of patients with drug-induced parkinsonism. Gamma-aminobutyric acid (GABA) and glutamate are the predominant neurotransmitters in basal ganglia circuitry, but their ubiquity makes them bad targets for pharmacological interventions.

Electrophysiology

As an alternative to the pharmacological targeting of specific neurotransmitter systems, anatomically targeted interventions (such as deep brain stimulation [DBS]) have become increasingly popular. DBS electrodes in the thalamus and globus pallidus can control tremor and dystonia, respectively. The pallidal site may also benefit TD. DBS in the subthalamic nucleus can help Parkinson’s disease. Subthalamic stimulation may also trigger psychiatric changes (including disinhibition and agitation). Most recently, DBS has been used in the anterior cingulate and internal capsule to manage treatment-resistant depression and obsessive-compulsive disorder (OCD). DBS’s mechanisms are complicated, but standard DBS stimulation seems to inhibit, not stimulate, gray matter around the electrode. It may jam normal neural transmission. The stimulator thus makes a reversible brain lesion, one whose size can be adjusted by changing electrode voltage or other parameters.

Patient History

Most movement disorders are diagnosed by history and the physical examination, not by laboratory tests. The first priority is to determine the frequency and nature of falling, as falls are the most immediate health risk. The second most immediate health risk is dysphagia causing aspiration, so it is important to ask whether the patient has had trouble swallowing pills, or coughs after drinking liquids. One should ask about what daily tasks are difficult—for example, “Does the tremor interfere with using a spoon (usually an action tremor) or holding a newspaper (usually a rest tremor)?” Drug use, especially use of neuroleptics, but also use of sleeping pills and alcohol, is important.

In characterizing memory loss, distinguishing between attentional and subcortical deficits (in which clues and to-do lists can help) and cortical, Alzheimer’s-type deficits (in which there are prominent language problems and compensatory strategies) is of little help. Hallucinations in basal ganglia disorders are much more often visual than auditory. Clinicians should ask the patient about early signs (such as vivid dreams, seeing dust particles or a webbing over the visual field, and transiently misidentifying objects as animate).

Physical Observation

Much of the physical examination of a patient with a movement disorder can proceed through observation without direct physical contact (e.g., “Does the patient enter the room quickly or slowly?”), and can thus be carried out during a psychiatric interview. Once seated, one can assess whether the patient is restless or immobile. Facial immobility might be a consequence of depression—or it might be a side effect of antipsychotics.

Symptoms of movement disorders are summarized in Table 80-1. They range from hypokinetic to hyperkinetic, and from feeling involuntary to voluntary. Unfortunately, it is not easy to distinguish movement disorders through written descriptions of symptoms, and descriptions in this chapter are no exception. Web-based or published patient videos are the best way to learn this crucial distinction.³ Many are available online (e.g., www.psychiatrist.com/supplenet/v65s09/ovi.pdf).

Table 80-1 Symptoms, Causes, and Treatment of Movement Disorders, with a Focus on Causes Common in Adult Psychiatric Patients

Hypokinetic Signs

Rigidity.

Rigidity is the cardinal hypokinetic sign. While rigidity is characteristic of parkinsonism, it is sometimes present even in hyperkinetic conditions, such as Tourette’s syndrome. Rigidity produces a constant “lead pipe” resistance to movement along the whole range of the joint. It can quickly be assessed without touching the patient, by asking the patient to rapidly rotate the wrist back and forth, as if trying to screw in a lightbulb. Cogwheel rigidity is simply a tremor superimposed on rigidity, although the tremor is not always apparent visually. Patients sometimes complain of an inner tremor not visible to others. Their complaint may be mistaken for somatization or delusion, but it is more commonly evidence for parkinsonism. Rigidity makes movements low-amplitude, and they rapidly decrease in size. Handwriting almost always demonstrates this, and is another simple, noninvasive test (Figure 80-2).

Figure 80-2 Handwriting and spiral drawing reflects tremor type. A, The large scrawl of essential tremor. B, Cramped, parkinsonian writing and spiral shows little of the tremor—writing is an action.

Rigidity is different from spasticity, the jerky “clasp-knife” phenomenon seen after stroke-induced paralysis or paresis. The presence of hyperreflexia, muscle atrophy, flexor spasms, and toe-walking helps distinguish spasticity from rigidity.

Although patients with hypokinetic movement disorders often say they feel weak, they usually have normal muscle bulk and can exert considerable strength if given enough time to fully engage their muscles. In this, basal ganglia movement disorders differ notably from the paralytic weakness of cortical strokes or peripheral nerve injuries.

Bradykinesia.

Bradykinesia (slower movements) and akinesia (fewer movements) may culminate in freezing, a sudden inability to move that most often occurs when the patient tries to initiate a movement. Freezing is related to the psychiatric syndrome of catatonia (see Chapter 55). Freezing, like many basal ganglia symptoms, is more a problem with internally motivated behaviors than with ones that are responses to environmental cues. Patients can sometimes break freezes with sensory tricks (such as stepping over a line on the floor, or hearing marching music). This can incorrectly appear to be evidence for a somatoform disorder.

Hyperkinetic Signs

Chorea and Athetosis.

Apart from the briefest, most ballistic movements, most hyperkinetic movements feel semipurposive, and the patient can usually suppress them for brief periods. For this reason the abnormal movements may mistakenly seem psychogenic. Athetosis, a slow, writhing, nearly dystonic movement, rarely needs to be distinguished from the quicker movements of chorea and dyskinesias, as their causes and treatment are similar. Choreoathetosis is often described as dance-like, but it is rarely so. Rhythmic chorea was common in Charcot’s day, when the most common cause was tertiary syphilis or the hysterical chorea that imitated it (Figure 80-3). Common modern causes include lupus, pregnancy, Huntington’s disease, Wilson’s disease, and use of oral contraceptives or neuroleptics. Typical neuroleptics (such as haloperidol) generally suppress choreoathetosis, but may eventually cause a tardive worsening of the hyperkinesis.

Figure 80-3 Choreoathetotic arm posturing in Picasso’s Le Fol (1904). At the time of his painting, the most common causes of chorea were tertiary syphilis and hysteria.

Dyskinesia.

Dyskinesia looks much like chorea. The distinction between them is largely a convention, with “dyskinesia” usually reserved for drug-related reactions. The two major types are parkinsonian dyskinesia (from the administration of dopamine agonists to patients with chronically low endogenous dopamine) and TD (from long-term exposure to dopamine antagonists). Both are probably the result of dopamine receptor hypersensitivity. Dyskinesia’s large movements usually look aimless but they may feel semivoluntary, as when a bipolar patient with orobuccal TD describes moving her tongue to rid herself of an unpleasant mouth feeling.

Akathisia.

Akathisia may also be caused by use of dopamine antagonists, but it usually occurs acutely, rather than after chronic exposure. Its movements both feel and look voluntary—they are low amplitude and look restless. It is similar in look and feel to the fidgetiness of mania, or of boredom. It is of great clinical importance because it is triggered by a highly uncomfortable desire to move constantly, a desire that may even drive violent action. Treating akathisia often requires discontinuation of the neuroleptic. While akathisia in some ways resembles restless leg syndrome, the latter is usually not drug-induced, happens primarily when the patient relaxes before sleep, and has a more distinctly sensory trigger—such as a feeling of limb “creepiness.”

Tics.

Tics are more intermittent than are the hyperkinetic movements described so far. They are multifocal, usually stereotyped, and repetitive. They are typically driven by a conscious urge to move or by a premonitory sensation, and can often be suppressed briefly. Complex tics include gestures and vocalizations that may feel meaningful and goal-directed. Complex tics exist on a continuum with the compulsive behaviors of OCD, but people with tics often report a drive toward some sensory satisfaction rather than a drive away from a feared event. Simple tics (such as winks, sniffs, and shrugs) are common in the general population. The simplest tics (e.g., arm jerks) may feel involuntary and look myoclonic.

Myoclonus.

Myoclonus is an intermittent, ballistic jerk caused by a single muscle group, which promptly relaxes; it is involuntary. Myoclonus during sleep is normal, and may be generated from a source outside the basal ganglia. Asterixis is negative myoclonus, that is, a sudden lapse of tone with quick recovery. Both can be seen in encephalopathy, drug intoxication (especially with opiates), and neurodegenerative diseases. Hemiballism, a repetitive flinging movement of a limb, is quite rare; it usually arises after a subthalamic nucleus lesion.

Gait

Apart from neuroleptic malignant syndrome (NMS), the most dangerous movement disorders are those that affect gait and increase the risk of falls. Gait disorders are often multifactorial.⁴

Table 80-1 describes movement disorders that are typically seen in psychiatric patients, and Table 80-2 describes types of gait disorders. Balance is often impaired by hypokinetic movement disorders, in large part because patients cannot correct their posture quickly enough when they make a misstep. This is quite different from ataxia, the poor balance caused by cerebellar lesions or anticonvulsant toxicity. Ataxia can give a wildly swaying gait, yet it paradoxically causes fewer falls. It is often associated with spinning vertigo, distinct from the light-headedness caused by a variety of medications, anxiety, and depression. One cause of gait disorder that surgery may—occasionally—cure is normal pressure hydrocephalus (NPH). Its cardinal symptoms include a parkinsonian gait, incontinence, and, eventually, dementia. Radiographically, NPH causes dilated ventricles with normal sulci, in distinction to the global atrophy more commonly seen with dementia (Figure 80-4). By the time dementia develops, symptoms are hardly ever reversible. In the absence of parkinsonism, incontinence, and the characteristic radiographic findings, dementia is virtually never caused by NPH.

Table 80-2 Types of Gait Disorder

Figure 80-4 Imaging of hydrocephalus and atrophy. In hydrocephalus, whether obstruc-tive or normal pressure, ventricular volume increases out of proportion to volume of the sulci. The largest width of the frontal horns (FH) should be greater than half of the internal skull diameter (ID) in true hydrocephalus.