of the direct pathway leads to disinhibition of the gabaergic neurons of the gpi/snr, ultimately resulting in activation of thalamic neurons and excitation of cortical neurons. in contrast, activation of the indirect pathway stimulates the inhibitory striatal gaba/enkephalin projection, resulting in suppression of gabaergic neuronal activity. this, in turn, causes disinhibition of the stn excitatory outputs, thus triggering the gpi/snr inhibitory projections to the thalamus and decreased activation of cortical neurons. while deregulation of either of these pathways can disturb motor output, hyperkinesia is thought to result from overactivity of the direct pathway and decreased activity from the indirect pathway. hyperkinesia occurs when dopamine receptors, and norepinephrine receptors to a lesser extent, within the cortex and the brainstem are more sensitive to dopamine or when the dopaminergic receptors/neurons are hyperactive. hyperkinesia can be caused by a large number of different diseases including metabolic disorders, endocrine disorders, heritable disorders, vascular disorders, or traumatic disorders. other causes include toxins within the brain, autoimmune disease, and infections, which include meningitis. since the basal ganglia often have many connections with the frontal lobe of the brain, hyperkinesia can be associated with neurobehavioral or neuropsychiatric disorders such as mood changes, psychosis, anxiety, disinhibition, cognitive impairments, and inappropriate behavior. in children, primary dystonia is usually inherited genetically. secondary dystonia, however, is most commonly caused by dyskinetic cerebral palsy, due to hypoxic or ischemic injury to the basal ganglia, brainstem, cerebellum, and thalamus during the prenatal or infantile stages of development. chorea and ballism can be caused by damage to the subthalamic nucleus. chorea can be secondary to hyperthyroidism. athetosis can be secondary to sensory loss in the distal limbs; this is called pseudoathetosis in adults but is not yet proven in children. diagnosis definition there are various terms which refer to specific movement mechanisms that contribute to the differential diagnoses of hyperkinetic disorders. as defined by hogan and sternad, "posture" is a nonzero time period during which bodily movement is minimal. when a movement is called "discrete," it means that a new posture is assumed without any other postures interrupting the process. "rhythmic" movements are those that occur in cycles of similar movements. "repetitive," "recurrent," and "reciprocal" movements feature a certain bodily or joint position that occur more than once in a period, but not necessarily in a cyclic manner. overflow refers to unwanted movements that occur during a desired movement. it may occur in situations where the individual's motor intention spreads to either nearby or distant muscles, taking away from the original goal of the movement. overflow is often associated with dystonic movements and may be due to a poor focusing of muscle activity and inability to suppress unwanted muscle movement. co-contraction refers to a voluntary movement performed to suppress the involuntary movement, such as forcing one's wrist toward the body to stop it from involuntarily moving away from the body. in evaluating these signs and symptoms, one must consider the frequency of repetition, whether or not the movements can be suppressed voluntarily (either by cognitive decisions, restraint, or sensory tricks), the awareness of the affected individual during the movement events, any urges to make the movements, and if the affected individual feels rewarded after having completed the movement. the context of the movement should also be noted; this means that a movement could be triggered in a certain posture, while at rest, during action, or during a specific task. the movement's quality can also be described in observing whether or not the movement can be categorized as a normal movement by an unaffected individual, or one that is not normally made on a daily basis by unaffected individuals. differential diagnosis diseases that feature one or more hyperkinetic movements as prominent symptoms include: huntington's disease hyperkinesia, more specifically chorea, is the hallmark symptom of huntington's disease, formerly referred to as huntington's chorea. appropriately, chorea is derived from the greek word, khoros, meaning "dance." the extent of the hyperkinesia exhibited in the disease can vary from solely the little finger to the entire body, resembling purposeful movements but occurring involuntarily. in children, rigidity and seizures are also symptoms. other hyperkinetic symptoms include: head turning to shift eye position facial movements, including grimaces slow, uncontrolled movements quick, sudden, sometimes wild jerking movements of the arms, legs, face, and other body parts unsteady gait abnormal reflexes "prancing," or a wide walk the disease is characterized further by the gradual onset of defects in behavior and cognition, including dementia and speech impediments, beginning in the fourth or fifth decades of life. death usually occurs within 10–20 years after a progressive worsening of symptoms. caused by the huntington gene, the disease eventually contributes to selective atrophy of the caudate nucleus and putamen, especially of gabaergic and acetylcholinergic neurons, with some additional degeneration of the frontal and temporal cortices of the brain. the disrupted signaling in the basal ganglia network is thought to cause the hyperkinesia. there is no known cure for huntington's disease, yet there is treatment available to minimize the hyperkinetic movements. dopamine blockers, such as haloperidol, tetrabenazine, and amantadine, are often effective in this regard. wilson's disease samuel alexander kinnier wilson, the neurologist most known for his description of what came to be known as wilson's disease. wilson's disease (wd) is a rare inherited disorder in which patients have a problem metabolizing copper. in patients with wd, copper accumulates in the liver and other parts of the body, particularly the brain, eyes and kidneys. upon accumulation in the brain, patients may experience speech problems, incoordination, swallowing problems, and prominent hyperkinetic symptoms including tremor, dystonia, and gait difficulties. psychiatric disturbances such as irritability, impulsiveness, aggressiveness, and mood disturbances are also common. restless leg syndrome restless leg syndrome is a disorder in which patients feel uncomfortable or unpleasant sensations in the legs. these sensations usually occur in the evening, while the patient is sitting or lying down and relaxing. patients feel like they have to move their legs to relieve the sensations, and walking generally makes the symptoms disappear. in many patients, this can lead to insomnia and excessive daytime sleepiness. this is a very common problem and can occur at any age. similarly, the syndrome akathisia ranges from mildly compulsive movement usually in the legs to intense frenzied motion. these movements are partly voluntary, and the individual typically has the ability to suppress them for short amounts of time. like restless leg syndrome, relief results from movement. post-stroke repercussions a multitude of movement disorders have been observed after either ischemic or hemorrhagic stroke. some examples include athetosis, chorea with or without hemiballismus, tremor, dystonia, and segmental or focal myoclonus, although the prevalence of these manifestations after stroke is quite low. the amount of time that passes between stroke event and presentation of hyperkinesia depends on the type of hyperkinetic movement since their pathologies slightly differ. chorea tends to affect older stroke survivors while dystonia tends to affect younger ones. men and women have an equal chance of developing the hyperkinetic movements after stroke. strokes causing small, deep lesions in the basal ganglia, brain stem and thalamus are those most likely to be associated with post-stroke hyperkinesia. dentatorubral-pallidoluysian atrophy drpla is a rare trinucleotide repeat disorder (polyglutamine disease) that can be juvenile-onset (< 20 years), early adult-onset (20–40 years), or late adult-onset (> 40 years). late adult-onset drpla is characterized by ataxia, choreoathetosis and dementia. early adult-onset drpla also includes seizures and myoclonus. juvenile-onset drpla presents with ataxia and symptoms consistent with progressive myoclonus epilepsy (myoclonus, multiple seizure types and dementia). other symptoms that have been described include cervical dystonia, corneal endothelial degeneration autism, and surgery-resistant obstructive sleep apnea. management athetosis, chorea and hemiballismus before prescribing medication for these conditions which often resolve spontaneously, recommendations have pointed to improved skin hygiene, good hydration via fluids, good nutrition, and installation of padded bed rails with use of proper mattresses. pharmacological treatments include the typical neuroleptic agents such as fluphenazine, pimozide, haloperidol and perphenazine which block dopamine receptors; these are the first line of treatment for hemiballismus. quetiapine, sulpiride and olanzapine, the atypical neuroleptic agents, are less likely to yield drug-induced parkinsonism and tardive dyskinesia. tetrabenazine works by depleting presynaptic dopamine and blocking postsynaptic dopamine receptors, while reserpine depletes the presynaptic catecholamine and serotonin stores; both of these drugs treat hemiballismus successfully but may cause depression, hypotension and parkinsonism. sodium valproate and clonazepam have been successful in a limited number of cases. stereotactic ventral intermediate thalamotomy and use of a thalamic stimulator have been shown to be effective in treating these conditions. essential tremor the medical treatment of essential tremor at the movement disorders clinic at baylor college of medicine begins with minimizing stress and tremorgenic drugs along with recommending a restricted intake of beverages containing caffeine as a precaution, although caffeine has not been shown to significantly intensify the presentation of essential tremor. alcohol amounting to a blood concentration of only 0.3% has been shown to reduce the amplitude of essential tremor in two-thirds of patients; for this reason it may be used as a prophylactic treatment before events during which one would be embarrassed by the tremor presenting itself. using alcohol regularly and/or in excess to treat tremors is highly inadvisable, as there is a purported correlation between tremor and alcoholism. alcohol is thought to stabilize neuronal membranes via potentiation of gaba receptor-mediated chloride influx. it has been demonstrated in essential tremor animal models that the food additive 1-octanol suppresses tremors induced by harmaline, and decreases the amplitude of essential tremor for about 90 minutes. two of the most valuable drug treatments for essential tremor are propranolol, a beta blocker, and primidone, an anticonvulsant. propranolol is much more effective for hand tremor than head and voice tremor. some beta-adrenergic blockers (beta blockers) are not lipid-soluble and therefore cannot cross the blood–brain barrier (propranolol being an exception), but can still act against tremors; this indicates that this drug's mechanism of therapy may be influenced by peripheral beta-adrenergic receptors. primidone's mechanism of tremor prevention has been shown significantly in controlled clinical studies. the benzodiazepine drugs such as diazepam and barbiturates have been shown to reduce presentation of several types of tremor, including the essential variety. controlled clinical trials of gabapentin yielded mixed results in efficacy against essential tremor while topiramate was shown to be effective in a larger double-blind controlled study, resulting in both lower fahn-tolosa-marin tremor scale ratings and better function and disability as compared to placebo. it has been shown in two double-blind controlled studies that injection of botulinum toxin into muscles used to produce oscillatory movements of essential tremors, such as forearm, wrist and finger flexors, may decrease the amplitude of hand tremor for approximately three months and that injections of the toxin may reduce essential tremor presenting in the head and voice. the toxin also may help tremor causing difficulty in writing, although properly adapted writing devices may be more efficient. due to high incidence of side effects, use of botulinum toxin has only received a c level of support from the scientific community. deep brain stimulation toward the ventral intermediate nucleus of the thalamus and potentially the subthalamic nucleus and caudal zona incerta nucleus have been shown to reduce tremor in numerous studies. that toward the ventral intermediate nucleus of the thalamus has been shown to reduce contralateral and some ipsilateral tremor along with tremors of the cerebellar outflow, head, resting state and those related to hand tasks; however, the treatment has been shown to induce difficulty articulating thoughts (dysarthria), and loss of coordination and balance in long-term studies. motor cortex stimulation is another option shown to be viable in numerous clinical trials. dystonia treatment of primary dystonia is aimed at reducing symptoms such as involuntary movements, pain, contracture, embarrassment, and to restore normal posture and improve the patient's function. this treatment is therefore not neuroprotective. according to the european federation of neurological sciences and movement disorder society, there is no evidence-based recommendation for treating primary dystonia with antidopaminergic or anticholinergic drugs although recommendations have been based on empirical evidence. anticholinergic drugs prove to be most effective in treating generalized and segmental dystonia, especially if dose starts out low and increases gradually. generalized dystonia has also been treated with such muscle relaxants as the benzodiazepines. another muscle relaxant, baclofen, can help reduce spasticity seen in