Hyperkinetic movement disorders (hyperkinesias, hyperkinetic dyskinesias) are characterized by excessive, unwanted, involuntary movements, and are classified according to their phenomenology. The form of the movement can assist in diagnosis and may be rhythmic or arrhythmic, generalized or focal, unilateral or bilateral, fast or slow, brief or sustained, repetitive or nonrepetitive, small or large in amplitude, proximal or distal, complex or simple, suppressible or nonsupressible, positional or nonpositional, synchronous or asynchronous, paroxysmal or nonparoxysmal, and occurring while awake or asleep. Some movement disorders appear to be bizarre and are sometimes misdiagnosed as psychiatric disorders, for example, dystonia. Although an overgeneralization, Table 10.1 indicates candidate movement disorders based on their properties.

Hyperkinetic movement forms include rhythmic movements, which generally represent tremor, whereas most other movement disorders are nonrhythmic. Generalized movements usually suggest chorea, childhood-onset dystonia, myoclonus, tics, and akathisia, whereas more focal movements are typical of adult-onset dystonia and some types of myoclonus, tics, tremors, and hemifacial spasm (HFS). Unilateral movements may indicate parkinsonian tremor, secondary dystonia, or chorea due to a focal lesion, hemiballismus, and HFS. Most hyperkinesias

are fast and of brief duration, but slow and sustained movements can betray dystonia and some forms of tics. Repetitive movements may represent dystonia, myoclonus, tics, akathisia, HFS and, of course, tremor, but nonrepetitive movements are typical of chorea. Large amplitude violent movements signal ballismus, severe akathisia, and less commonly dystonia, tics, and severe chorea, whereas small amplitude movements are more typical of chorea, dystonia, myoclonus, tremor, and HFS. Proximal joint excursions usually indicate ballismus and sometimes dystonia, whereas distal movements usually suggest chorea and tremor. Complex movements may signal complex tics or dystonia, whereas simple movements suggest chorea, myoclonus, simple tics, and tremor. Suppressible movements are generally tics, but other movements may be minimally suppressible, especially in the context of “trick” maneuvers that patients with dystonia and tremor acquire. Some movements such as tremor, myoclonus, and dystonia may be positional and myoclonus can be synchronous or asynchronous.

Table 10.2 lists the prevalences of the more common hyperkinesias.

The etiologies of movement disorders are beyond the scope of this manual. Aside from multiple mutations in many of the primary movement disorders, there are multiple etiologies (including genetic) of secondary movement disorders. The genetics of movement disorders are evolving so rapidly that texts are outdated before they are even printed. A search of contemporary journals is the only way to track the panoply of mutations associated with certain movement disorders. Although movement disorders are usually not purely localizable to lesions of a single structure, chorea is most often associated with caudate, dystonia with putamen, and ballismus with subthalamic nucleus lesions.

Although the pathophysiologies are significantly complex, the rudiments are provided for each disorder in the subsequent text.
In contrast to Parkinson disease, where there is reduced activation of the supplementary motor cortex (SMA), it is believed that the cortex is overactivated in the hyperkinesias.

Hyperkinesias include other less common dyskinesias that are outside the scope of this manual and are considered elsewhere.¹

Tremors are rhythmically repetitive movements.

The pathophysiology of tremors has been linked to the thalamic nucleus ventralis intermedius as a final common pathway, with inputs from the globus pallidus and cerebellum.

Tremors are classified by whether their peak amplitude occurs when the affected limb is in repose, or during activity (see Table 10.3). Those most apparent in repose and attenuating with activity are resting tremors, generally involving the hand in a side-to-side alternating movement of 4 to 6 Hz. Rabbit tremor is a focal perioral rest tremor resembling the rapid sniffing movements of a rabbit. Most tremors, however, reach peak amplitude with activity and are further classified by the type of activity that provokes maximal amplitude. Those activating only with specific limb postures, such as sustention of the arms, are postural tremors (also called positional tremors). Orthostatic tremor is
a postural tremor of the legs and trunk of 12 to 20 Hz evident when the patient is standing. Tremors that activate consistently throughout the range of a movement, such as the finger-to-nose examination, are action tremors, often presenting as an up-and-down movement of the distal fingers of 8 to 12 Hz when the arms are extended and further intensifying with action. Essential tremor is an autosomal dominant action–postural tremor. Tremors reaching peak amplitude only at the end of the movement, such as when nearing the target finger or nose, constitute terminal kinetic tremor (also called intention tremor or cerebellar intention tremor). Tremors occurring only during selective tasks, such as when playing only certain notes on a musical instrument represent focal task-specific tremor. Physiologic tremor is an action–postural tremor evident in normal individuals and is brought out by conditions of stress, anxiety, or caffeine. Rubral tremor usually combines the features of resting, postural, action, and terminal kinetic tremors. On rare occasions, rhythmic myoclonus and polyminimyoclonus involving distal fingers occur and can be mistaken for tremor.

There are many etiologies of various tremors.¹ Resting and rabbit tremors are seen in Parkinson disease (see Chapter 10) and in drug-induced parkinsonism related to dopamine D₂ receptor antagonist drugs. Most tremors are action–postural tremors and there are many causes of these (e.g., essential tremor, toxins, lithium, valproate, β agonists, stimulants, antihistamines, hypoglycemia, thyrotoxicosis, pheochromocytoma, steroids, cyclosporin, interferon, other movement disorders, amyotrophic lateral sclerosis [ALS], and peripheral injury). Essential tremor is familial and has been linked to ETM and FET1 mutations. Terminal kinetic (intention) tremor generally occurs with cerebellar systems disease. Task-specific tremor may represent a form of dystonia. Physiologic tremor in normal individuals is made apparent by stress, anxiety, or caffeine. Rubral tremor is seen with midbrain lesions in the vicinity of the red nucleus, accounting for the term rubral. Prognosis of each tremor generally depends on the underlying cause.

The treatment of tremor first involves addressing the underlying cause. After that, treatment is symptomatic. Resting tremor is ameliorated with anticholinergics or dopamine agonists (levodopa or direct acting agonists), action–postural and orthostatic tremors with β-blockers, clonazepam, or gabapentin, rubral tremor by treating resting and action components, and task-specific tremor with botulinum toxin. For essential tremor, propranolol and primidone are effective for limb tremor and second-line treatments include alprazolam, atenolol, gabapentin, sotalol, and topiramate; propranolol is useful for head tremor and botulinum toxin A has been used for hand tremor and vocal tremor in essential tremor.² No satisfying treatments have been found for terminal kinetic tremors. Botulinum toxin, deep brain stimulation (DBS) of the Vim thalamus, internal pallidum, or
subthalamic nucleus and thalamotomy are sometimes useful for some intractable tremors.

The neuropsychiatric features of tremor are presently ill defined and are otherwise those of the underlying etiology and its treatment.

Choreoathetosis ranges from fast dance-like chorea to slower writhing movements termed athetosis. Choreatic movements generally flow freely from limb to limb, are arrhythmic, and are difficult to suppress.

The pathophysiology of chorea generally reflects striatal disease leading to disinhibition of the external globus pallidus, producing a direct γ-aminobutyric acid (GABA)-mediated overinhibition and indirect (through the subthalamic nucleus) glutamatergic understimulation of the internal globus pallidus. This in turn disinhibits glutamatergic thalamocortical stimulatory activity projecting to the SMA and other loci.

Chorea can be diagnosed by certain features. It can be activated or facilitated by having the patient walk or perform other maneuvers, such as the finger-to-nose examination or finger tapping. The Abnormal Involuntary Movement Scale (AIMS) examination used to diagnose tardive dyskinesia (TD) (TD usually involves choreiform movements) is an appropriate procedure for evaluating chorea: Observe the patient at rest with wrists supported by the knees and hands hanging down, then provoke movements with facilitatory maneuvers, then observe the patient when standing, followed by walking. Observe for activation with facilitation and on walking. So-called piano-playing movements may be apparent in the fingers. Facial and orolingual movements may be apparent, as may limb chorea, truncal movements, and a choreic gait. Patients may attempt to make the movements look as though they were intended by incorporating a choreic excursion into some other sequence of movement, termed a parakinesia, such as voluntarily running their hand through their hair. Chorea is associated with motor impersistence, manifest in fixation instability, tongue protrusion, and milkmaid’s grip. In fixation instability, the patient is generally unable to fixate their gaze on a target for more than 30 seconds without breaking off the target, called a saccadic intrusion. These can also be apparent on testing extraocular movements, where the eyes suddenly break off the target because of a saccadic intrusion. Motor impersistence is also manifest in the patient’s inability to maintain tongue protrusion for more than a 30-second interval. Milkmaid’s grip refers to involuntary relaxations and sudden compensatory contractions when asked to grip the examiner’s fingers, with the patient producing a grip similar to milking a cow. Paroxysmal kinesigenic and nonkinesigenic choreas are paroxysmal choreic events that occur either with or without exercise.¹

The etiologies of chorea are legion (see Table 10.4). The chorea of Huntington disease (HD) and Sydenham chorea represent two of the best-known choreic disorders (see section IC4a and IC4b). Choreic primary etiologies include hereditary (including HD, benign familial chorea and a diversity of neurologic or systemic diseases), drug induced (e.g., dopaminergic agents, stimulants, anticonvulsants, steroids, opiates, antihistamines, and digoxin), metabolic (e.g., sodium, hypocalcemia, hypomagnesemia, glucose, hepatic, renal, propionic acidemia, glutaric aciduria, GM1 gangliosidosis, and kernicterus), endocrinologic (e.g, hyperthyroidism, parathyroid, pseudohypoparathyroidism, hypocortisolemia, and pregnancy), nutritional (e.g., niacin, thiamine, Vitamin B₁₂, and D deficiencies), infectious/immunologic (e.g., human immunodeficiency virus (HIV), Sydenham chorea, bacterial, tubercular, viral), cerebrovascular (e.g., infarct, transient ischemic attack [TIA], migraine, arteriovenous malformation [AVM], polycythemia vera, and lupus), traumatic, neurodegenerative (e.g., Pick disease, thalamic centrum medianum nucleus degeneration), and physiologic (e.g., senile essential chorea, and physiologic chorea of infancy). There are a number of genetic mutations associated with non-HD choreas (e.g., HDL1, HDL2, CHAC, a 4p.15.3 autosomal recessive gene, a 14q autosomal dominant gene, etc.). In TD, usually developing after at least 3 months of antipsychotic administration, the movements are most commonly oral-buccal-lingual in distribution, but involvement of the extremities and trunk is also seen in more severe cases.