Hyperkinesis
Encyclopedia
Hyperkinesia, also known as hyperkinesis, refers to an increase in muscular activity that can result in excessive abnormal movements, excessive normal movements, or a combination of both. The word hyperkinesis comes from the Greek hyper, meaning "increased," and kinein, meaning "to move." Hyperkinesia is a state of excessive restlessness which is featured in a large variety of disorders that affect the ability to control motor movement, such as Huntington’s disease. It is the opposite of hypokinesia
, which refers to decreased bodily movement, as commonly manifested in Parkinson's disease
. Many hyperkinetic movements are the result of improper regulation of the basal ganglia-thalamocortical circuitry. Overactivity of a direct pathway combined with decreased activity of an indirect pathway results in activation of thalamic neurons and excitation of cortical neurons, resulting in increased motor output. Often, hyperkinesia is paired with hypotonia
, a decrease in muscle tone. Many hyperkinetic disorders are psychological in nature and are typically prominent in childhood. Depending on the specific type of hyperkinetic movement, there are different treatment options available to minimize the symptoms, including different medical and surgical therapies.
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.
and negative signs, which are also typically involved in such disorders. Several prominent forms of hyperkinetic movements include:
refers to a group of progressive neurological diseases that alter coordination and balance. Ataxias are often characterized by poor coordination of hand and eye movements, speech problems, and a wide-set, unsteady gait. Possible causes of ataxias may include stroke, tumor, infection, trauma, or degenerative changes in the cerebellum. These types of hyperkinetic movements can be further classified into two groups. The first group, hereditary ataxias, affect the cerebellum and spinal cord and are passed from one generation to the next through a defective gene. A common hereditary ataxia is Friedreich's ataxia. in contrast, sporadic ataxias occur spontaneously in individuals with no known family history of such movement disorders.
is defined as a slow, continuous, involuntary writhing movement that prevents the individual from maintaining a stable posture. These are smooth, nonrhythmic movements that appear random and are not composed of any recognizable sub-movements. They mainly involve the distal extremities, but can also involve the face, neck, and trunk. Athetosis can occur in the resting state, as well as in conjunction with chorea and dystonia
. When combined with chorea, as in cerebral palsy
, the term "choreoathetosis" is frequently used.
, cerebral cortex
, thalamus
, and cerebellum
. It has also been associated with encephalitis
, hyperthyroidism
, anticholinergic toxicity, and other genetic and metabolic disorders. Chorea is also the prominent movement featured in Huntington's Disease
.
is a movement disorder in which involuntarily sustained or intermittent muscle contractions cause twisting or repetitive movements, abnormal postures, or both. Such abnormal postures include foot inversion, wrist ulnar deviation, or lordotic trunk twisting. They can be localized to specific parts of the body or be generalized to many different muscle groups. These postures are often sustained for long periods of time and can be combined in time. Dystonic movements can augment hyperkinetic movements, especially when linked to voluntary movements.
Blepharospasm
is a type of dystonia characterized by involuntary contraction of the muscles controlling the eyelids. Symptoms can range from a simple increased frequency of blinking to constant, painful eye closure leading to functional blindness.
Oromandibular dystonia
is a type of dystonia marked by forceful contractions of the lower face, which causes the mouth to open or close. Chewing motions and unusual tongue movements may also occur with this type of dystonia.
Laryngeal dystonia or spasmodic dysphonia
results from abnormal contraction of muscles in the voice box, resulting in altered voice production. Patients may have a strained-strangled quality to their voice or, in some cases, a whispering or breathy quality.
Cervical dystonia (CD) or spasmodic torticollis
is characterized by muscle spasms of the head and neck, which may be painful and cause the neck to twist into unusual positions or postures.
Writer's cramp
and musician’s cramp is a task-specific dystonia, meaning that it only occurs when performing certain tasks. Writer’s cramp is a contraction of hand and/or arm muscles that happens only when a patient is writing. It does not occur in other situations, such as when a patient is typing or eating. Musician’s cramp occurs only when a musician plays an instrument, and the type of cramp experienced is specific to the instrument. For example, pianists may experience cramping of their hands when playing, while brass players may have cramping or contractions of their mouth muscles.
movements are nonrhythmic, rapid, nonsuppressible, and violent. They usually occur in an isolated body part, such as the proximal arm.
(HFS) is characterized by involuntary contraction of facial muscles, typically occurring only on one side of the face. Like blepharospasm, the frequency of contractions in hemifacial spasm may range from intermittent to frequent and constant. The unilateral blepharospasm of HFS may interfere with routine tasks such as driving. In addition to medication, patients may respond well to treatment with Botox. HFS may be due to vascular compression of the nerves going to the muscles of the face. For these patients, surgical decompression may be a viable option for the improvement of symptoms.
is defined as a sequence of repeated, often nonrhythmic, brief, shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. These movements may be asynchronous, in which several muscles contract variably in time, synchronous, in which muscles contract simultaneously, or spreading, in which several muscles contract sequentially. It is characterized by a sudden, unidirectional movement due to muscle contraction, followed by a relaxation period in which the muscle is no longer contracted. However, when this relaxation phase is decreased, as when muscle contractions become faster, a myoclonic tremor results. Myoclonus can often be associated with seizures, delirium
, dementia
, and other signs of neurological disease and gray matter
damage.
disorders. Stereotypies are quite common in preschool-aged children and for this reason are not necessarily indicative of neurological pathology on their own.
or tardive dystonia, both referred to as "TD," refers to a wide variety of involuntary stereotypical movements caused by the prolonged use of dopamine receptor-blocking agents. The most common types of these agents are antipsychotics and anti-nausea agents. The classic form of TD refers to stereotypic movements of the mouth, which resemble chewing. However, TD can also appear as other involuntary movements such as chorea, dystonia
, or tics.
can be defined as a repeated, individually recognizable, intermittent movement or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. These abnormal movements occur with intervening periods of normal movement. These movements are predictable, often triggered by stress, excitement, suggestion, or brief voluntary suppressibility. Many children say that the onset of tics can stem from the strong urge to move. Tics can be either muscular (alter normal motor function) or vocal (alter normal speech) in nature and most commonly involve the face, mouth, eyes, head, neck or shoulder muscles. Tics can also be classified as simple motor tics (a single brief stereotyped movement or movement fragment), complex motor tics (a more complex or sequential movement involving multiple muscle
groups), or phonic tics (including simple, brief phonations or vocalizations).
When both motor and vocal tics are present and persist for more than one year, a diagnosis of Tourette syndrome
(TS) is likely. TS is an inherited neurobehavioral disorder characterized by both motor and vocal tics. Many individuals with TS may also develop obsessions, compulsions, inattention and hyperactivity. TS usually begins in childhood. Up to 5% of the population suffers from tics, but at least 20% of boys will have developed tics at some point in their lifetimes.
can be defined as a rhythmic, back and forth or oscillating involuntary movement about a joint axis. Tremors are symmetric about a midpoint within the movement, and both portions of the movement occur at the same speed. Unlike the other hyperkinetic movements, tremors lack both the jerking associated movements and posturing.
Essential tremor
(ET), also known as benign essential tremor, or familial tremor, is the most common movement disorder. It is estimated that 5 percent of people worldwide suffer from this condition, affecting those of all ages but typically staying within families. ET typically affects the hands and arms but can also affect the head, voice, chin, trunk and legs. Both sides of the body tend to be equally affected. The tremor is called an action tremor, becoming noticeable in the arms when they are being used. Patients often report that alcohol helps lessen the symptoms. Primary medical treatments for ET are usually beta-blockers. For patients who fail to respond sufficiently to medication, deep brain stimulation
and thalamotomy
can be highly effective.
A “flapping tremor,” or asterixis
, is characterized by irregular flapping-hand movement, which appears most often with outstretched arms and wrist extension. Individuals with this condition resemble birds flapping their wings.
Other hyperkinetic symptoms include:
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 Huntingtin
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 amantidine, are often effective in this regard.
, dystonia, and gait difficulties. Psychiatric disturbances such as irritability, impulsiveness, aggressiveness, and mood disturbances are also common.
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.
The causes of the majority of the above hyperkinetic movements can be traced to improper modulation of the basal ganglia
by the subthalamic nucleus. In many cases, the excitatory output of the subthalamic nucleus is reduced, leading to a reduced inhibitory outflow of the basal ganglia. Without the normal restraining influence of the basal ganglia, upper motor neurons of the circuit tend to become more readily activated by inappropriate signals, resulting in the characteristic abnormal movements.
There are two pathways involving basal ganglia-thalamocortical circuitry, both of which originate in the neostriatum. The direct pathway projects to the internal globus pallidus (GPi
) and to the substantia nigra pars reticulata (SNr). These projections are inhibitory and have been found to utilize both GABA
and substance P
. The indirect pathway, which projects to the globus pallidus external (GPe), is also inhibitory and uses GABA and enkephalin
. The GPe projects to the subthalamic nucleus
(STN), which then projects back to the GPi and GPe via excitatory, glutaminergic pathways. Excitation 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 GABAerigc 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.
, 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.
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 unadvisable, 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. Beta-adrenergic blockers (beta blockers) are not lipid soluble and therefore cannot cross the blood-brain barrier
, 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.
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 cerebral palsy
such as dystonia in the leg and trunk. Treatment of secondary dystonia by administering levodopa in dopamine-responsive dystonia
, copper chelation
in Wilson’s disease, or stopping the administration of drugs that may induce dystonia have been proven effective in a small number of cases. Physical therapy has been used to improve posture and prevent contractures via braces and casting, although in some cases, immobilization of limbs can induce dystonia, which is by definition known as peripherally induced dystonia. There are not many clinical trials that show significant efficacy for particular drugs, so medical of dystonia must be planned on a case-by-case basis. Botulinum toxin B, or Myobloc, has been approved by the US Food and Drug Administration to treat cervical dystonia due to level A evidential support by the scientific community. Surgery known as GPi DBS (Globus Pallidus Pars Interna Deep Brain Stimulation) has come to be popular in treating phasic forms of dystonia, although cases involving posturing and tonic contractions have improved to a lesser extent with this surgery. A follow-up study has found that movement score improvements observed one year after the surgery was maintained after three years in 58% of the cases. It has also been proven effective in treating cervical and cranial-cervical dystonia.
or radiculopathy
. Surgical treatment for disabling Tourette’s syndrome has been proven effective in cases presenting with self-injury. Deep Brain Stimulation surgery targeting the globus pallidus, thalamus and other areas of the brain may be effective in treating involuntary and possibly life-threatening tics.
noticed that the corpus striatum was typically discolored, shrinkened, and abnormally softened in the cadavers of people who had died from paralysis. The view that the corpus striatum played such a large role in motor functions was the most prominent one until the 19th century when electrophysiologic stimulation studies began to be performed. For example, Gustav Fritsch
and Eduard Hitzig
performed them on dog cerebral cortices in 1870, while David Ferrier
performed them, along with ablation studies, on cerebral cortices of dogs, rabbits, cats, and primates in 1876. During the same year, John Hughlings Jackson
posited that the motor cortex was more relevant to motor function than the corpus striatum after carrying out clinical-pathologic experiments in humans. Soon it would be discovered that the theory about the corpus striatum would not be completely incorrect.
By the late 19th century, a few hyperkinesias such as Huntington’s chorea, post-hemiplegic choreoathetosis, Tourette’s syndrome, and some forms of both tremor and dystonia were described in a clinical orientation. However, the common pathology was still a mystery. British neurologist William Richard Gowers
called these disorders “general and functional diseases of the nervous system” in his 1888 publication entitled A Manual of Diseases of the Nervous System. It was not until the late 1980s and 1990s that sufficient animal models and human clinical trials were utilized to discover the specific involvement of the basal ganglia in the hyperkinesia pathology. In 1998, Wichmann and Delong made the conclusion that hyperkinesia is associated with decreased output from the basal ganglia, and in contrast, hypokinesia is associated with increased output from the basal ganglia. This generalization, however, still leaves a need for more complex models to distinguish the more nuanced pathologies of the numerous diverse hyperkinesias which are still being studied today.
In the 2nd century, Galen
was the first to define tremor as “involuntary alternating up-and-down motion of the limbs.” Further classification of hyperkinetic movements came in the 17th and 18th centuries by Franciscus Sylvius
and Gerard van Swieten
. Parkinson’s disease was one of the first disorders to be named as a result of the recent classification of its featured hyperkinetic tremor. The subsequent naming of other disorders involving abnormal motions soon followed.
to trace skeletal muscle activity in some hyperkinetic disorders. The electromyogram (EMG) of dystonia sometimes shows rapid rhythmic bursts, but these patterns can almost always be produced intentionally. In the myoclonus EMG, there are typically brief, and sometimes rhythmic, bursts or pauses in the recording pattern. When the bursts last for 50 milliseconds or less they are indicative of cortical myoclonus, but when they last up to 200 milliseconds, they are indicative of spinal or brainstem myoclonus. Such bursts can occur in multiple muscles simultaneously quite quickly, but high time resolution must be used in the EMG trace to clearly record them. The bursts recorded for tremor tend to be longer in duration than those of myoclonus, although some types can last for durations within the range for those of myoclonus. Future studies would have to examine the EMGs for tics, athetosis, stereotypies and chorea as there are minimal recordings done for those movements. However, it may be predicted that the EMG for chorea would include bursts varying in duration, timing, and amplitude, while that for tics and stereotypies would take on patterns of voluntary movements.
In general, research for treatment of hyperkinesia has most recently been focusing on ameliorating symptoms rather than attempting to correct the pathogenesis of the disease. Therefore, now and in the future it may be beneficial to inform the learning of the disease's pathology through carefully controlled, long-term, observation-based studies. As therapies are supported by proven effectiveness that can be repeated in multiple studies, they are useful, but the clinician may also consider that the best treatments for patients can only be evaluated on a case-by-case basis. It is the interplay of these two facets of neurology and medicine that may bring about significant progress in this field.
Hypokinesia
Hypokinesia refers to decreased bodily movement. It is associated with basal ganglia diseases , mental health disorders and prolonged inactivity due to illness, amongst other diseases.Hypokinesia describes a spectrum of disorders:...
, which refers to decreased bodily movement, as commonly manifested in Parkinson's disease
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. Many hyperkinetic movements are the result of improper regulation of the basal ganglia-thalamocortical circuitry. Overactivity of a direct pathway combined with decreased activity of an indirect pathway results in activation of thalamic neurons and excitation of cortical neurons, resulting in increased motor output. Often, hyperkinesia is paired with hypotonia
Hypotonia
Hypotonia is a state of low muscle tone , often involving reduced muscle strength. Hypotonia is not a specific medical disorder, but a potential manifestation of many different diseases and disorders that affect motor nerve control by the brain or muscle strength...
, a decrease in muscle tone. Many hyperkinetic disorders are psychological in nature and are typically prominent in childhood. Depending on the specific type of hyperkinetic movement, there are different treatment options available to minimize the symptoms, including different medical and surgical therapies.
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.
Classification
Basic hyperkinetic movements can be defined as any unwanted, excess movement. Such abnormal movements can be distinguished from each other on the basis of whether or not, or to what degree they are, rhythmic, discrete, repeated, and random. In evaluating the individual with a suspected form of hyperkinesia, the physician will record a thorough medical history including a clear description of the movements in question, medications prescribed in the past and present, family history of similar diseases, medical history including past infections, and any past exposure to toxic chemicals. Hyperkinesia is a defining feature of many childhood movement disorders, yet distinctly differs from both hypertoniaHypertonia
Hypertonia a condition marked by an abnormal increase in muscle tension and a reduced ability of a muscle to stretch. It is caused by lesions to upper motor neurons in the central nervous system, which carry information from the central nervous system to the muscles and control posture, muscle...
and negative signs, which are also typically involved in such disorders. Several prominent forms of hyperkinetic movements include:
Ataxia
The term ataxiaAtaxia
Ataxia is a neurological sign and symptom that consists of gross lack of coordination of muscle movements. Ataxia is a non-specific clinical manifestation implying dysfunction of the parts of the nervous system that coordinate movement, such as the cerebellum...
refers to a group of progressive neurological diseases that alter coordination and balance. Ataxias are often characterized by poor coordination of hand and eye movements, speech problems, and a wide-set, unsteady gait. Possible causes of ataxias may include stroke, tumor, infection, trauma, or degenerative changes in the cerebellum. These types of hyperkinetic movements can be further classified into two groups. The first group, hereditary ataxias, affect the cerebellum and spinal cord and are passed from one generation to the next through a defective gene. A common hereditary ataxia is Friedreich's ataxia. in contrast, sporadic ataxias occur spontaneously in individuals with no known family history of such movement disorders.
Athetosis
AthetosisAthetosis
Athetosis is a symptom characterized by involuntary convoluted, writhing movements of the fingers, arms, legs, and neck. Movements typical of athetosis are sometimes called athetoid movements. Lesions to the brain are most often the direct cause of the symptoms, particularly to thecorpus striatum...
is defined as a slow, continuous, involuntary writhing movement that prevents the individual from maintaining a stable posture. These are smooth, nonrhythmic movements that appear random and are not composed of any recognizable sub-movements. They mainly involve the distal extremities, but can also involve the face, neck, and trunk. Athetosis can occur in the resting state, as well as in conjunction with chorea and dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
. When combined with chorea, as in cerebral palsy
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....
, the term "choreoathetosis" is frequently used.
Chorea
Chorea is a continuous, random-appearing sequence of one or more discrete involuntary movements or movement fragments. Although chorea consists of discrete movements, many are often strung together in time, thus making it difficult to identify each movement's start and end point. These movements can involve the face, trunk, neck, tongue, and extremities. Unlike dystonic movements, chorea-associated movements are often more rapid, random and unpredictable. Movements are repeated, but not rhythmic in nature. Children with chorea appear fidgety and will often try to disguise the random movements by voluntarily turning the involuntary, abnormal movement into a seemingly more normal, purposeful motion. Chorea may result specifically from disorders of the basal gangliaBasal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
, cerebral cortex
Cerebral cortex
The cerebral cortex is a sheet of neural tissue that is outermost to the cerebrum of the mammalian brain. It plays a key role in memory, attention, perceptual awareness, thought, language, and consciousness. It is constituted of up to six horizontal layers, each of which has a different...
, thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
, and cerebellum
Cerebellum
The cerebellum is a region of the brain that plays an important role in motor control. It may also be involved in some cognitive functions such as attention and language, and in regulating fear and pleasure responses, but its movement-related functions are the most solidly established...
. It has also been associated with encephalitis
Encephalitis
Encephalitis is an acute inflammation of the brain. Encephalitis with meningitis is known as meningoencephalitis. Symptoms include headache, fever, confusion, drowsiness, and fatigue...
, hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
, anticholinergic toxicity, and other genetic and metabolic disorders. Chorea is also the prominent movement featured in Huntington's Disease
Huntington's disease
Huntington's disease, chorea, or disorder , is a neurodegenerative genetic disorder that affects muscle coordination and leads to cognitive decline and dementia. It typically becomes noticeable in middle age. HD is the most common genetic cause of abnormal involuntary writhing movements called chorea...
.
Dystonia
DystoniaDystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
is a movement disorder in which involuntarily sustained or intermittent muscle contractions cause twisting or repetitive movements, abnormal postures, or both. Such abnormal postures include foot inversion, wrist ulnar deviation, or lordotic trunk twisting. They can be localized to specific parts of the body or be generalized to many different muscle groups. These postures are often sustained for long periods of time and can be combined in time. Dystonic movements can augment hyperkinetic movements, especially when linked to voluntary movements.
Blepharospasm
Blepharospasm
A blepharospasm , is any abnormal contraction or twitch of the eyelid....
is a type of dystonia characterized by involuntary contraction of the muscles controlling the eyelids. Symptoms can range from a simple increased frequency of blinking to constant, painful eye closure leading to functional blindness.
Oromandibular dystonia
Oromandibular dystonia
Oromandibular dystonia is a form of focal dystonia affecting the mouth, jaw, and tongue.Botulinum toxin has been used in treatment....
is a type of dystonia marked by forceful contractions of the lower face, which causes the mouth to open or close. Chewing motions and unusual tongue movements may also occur with this type of dystonia.
Laryngeal dystonia or spasmodic dysphonia
Spasmodic dysphonia
Spasmodic dysphonia is a voice disorder characterized by involuntary movements of one or more muscles of the larynx during speech.- Types of spasmodic dysphonia :...
results from abnormal contraction of muscles in the voice box, resulting in altered voice production. Patients may have a strained-strangled quality to their voice or, in some cases, a whispering or breathy quality.
Cervical dystonia (CD) or spasmodic torticollis
Spasmodic torticollis
Spasmodic torticollis is a chronic neurological movement disorder causing the neck to involuntarily turn to the left, right, upwards, and/or downwards. The condition is also referred to as "cervical dystonia". Both agonist and antagonist muscle contract simultaneously during dystonic...
is characterized by muscle spasms of the head and neck, which may be painful and cause the neck to twist into unusual positions or postures.
Writer's cramp
Writer's cramp
Writer's cramp, also called mogigraphia and scrivener's palsy, causes a cramp or spasm affecting certain muscles of the hand and/or fingers. Writer's cramp is a task-specific focal dystonia of the hand...
and musician’s cramp is a task-specific dystonia, meaning that it only occurs when performing certain tasks. Writer’s cramp is a contraction of hand and/or arm muscles that happens only when a patient is writing. It does not occur in other situations, such as when a patient is typing or eating. Musician’s cramp occurs only when a musician plays an instrument, and the type of cramp experienced is specific to the instrument. For example, pianists may experience cramping of their hands when playing, while brass players may have cramping or contractions of their mouth muscles.
Hemiballismus
Typically caused by damage to the subthalamic nucleus or nuclei, hemiballismusHemiballismus
Hemiballismus is a very rare movement disorder. It is 500 times rarer than Parkinson's disease. Its effects can sometimes be severe enough to prevent patients from being able to perform daily functions. It is usually associated with structural brain lesions but can occur with metabolic abnormalities...
movements are nonrhythmic, rapid, nonsuppressible, and violent. They usually occur in an isolated body part, such as the proximal arm.
Hemifacial spasm
Hemifacial spasmHemifacial spasm
Hemifacial spasm or HFS is a neurological disorder in which blood vessels constrict the seventh cranial nerve and cause varying degrees of facial spasm, typically originating around the eye of the afflicted side of the face...
(HFS) is characterized by involuntary contraction of facial muscles, typically occurring only on one side of the face. Like blepharospasm, the frequency of contractions in hemifacial spasm may range from intermittent to frequent and constant. The unilateral blepharospasm of HFS may interfere with routine tasks such as driving. In addition to medication, patients may respond well to treatment with Botox. HFS may be due to vascular compression of the nerves going to the muscles of the face. For these patients, surgical decompression may be a viable option for the improvement of symptoms.
Myoclonus
MyoclonusMyoclonus
Myoclonus is brief, involuntary twitching of a muscle or a group of muscles. It describes a medical sign and, generally, is not a diagnosis of a disease. Brief twitches are perfectly normal. The myoclonic twitches are usually caused by sudden muscle contractions; they also can result from brief...
is defined as a sequence of repeated, often nonrhythmic, brief, shock-like jerks due to sudden involuntary contraction or relaxation of one or more muscles. These movements may be asynchronous, in which several muscles contract variably in time, synchronous, in which muscles contract simultaneously, or spreading, in which several muscles contract sequentially. It is characterized by a sudden, unidirectional movement due to muscle contraction, followed by a relaxation period in which the muscle is no longer contracted. However, when this relaxation phase is decreased, as when muscle contractions become faster, a myoclonic tremor results. Myoclonus can often be associated with seizures, delirium
Delirium
Delirium or acute confusional state is a common and severe neuropsychiatric syndrome with core features of acute onset and fluctuating course, attentional deficits and generalized severe disorganization of behavior...
, dementia
Dementia
Dementia is a serious loss of cognitive ability in a previously unimpaired person, beyond what might be expected from normal aging...
, and other signs of neurological disease and gray matter
Gray Matter
"Gray Matter" is a short story by Stephen King, first published in the October 1973 issue of Cavalier magazine, and later collected in King's 1978 collection Night Shift. It is set in the same area as King's novel Dreamcatcher.-Setting:...
damage.
Stereotypies
Stereotypies are repetitive, rhythmic, simple movements that can be voluntarily suppressed. Like tremors, they are typically back and forth movements, and most commonly occur bilaterally. They often involve fingers, wrists, or proximal portions of the upper extremities. Although, like tics, they can stem from stress and excitement, there is no underlying urge to move associated with stereotypies and these movements can be stopped with distraction. When aware of the movements, the child can also suppress them voluntarily. Stereotypies are often associated with developmental syndromes, including the autism spectrumAutism spectrum
The term "autism spectrum" is often used to describe disorders that are currently classified as pervasive developmental disorders. Pervasive developmental disorders include autism, Asperger syndrome, Childhood disintegrative disorder, Rett syndrome and Pervasive Developmental Disorder Not Otherwise...
disorders. Stereotypies are quite common in preschool-aged children and for this reason are not necessarily indicative of neurological pathology on their own.
Tardive dyskinesia / tardive dystonia
Tardive dyskinesiaTardive dyskinesia
Tardive dyskinesia is a difficult-to-treat form of dyskinesia that can be tardive...
or tardive dystonia, both referred to as "TD," refers to a wide variety of involuntary stereotypical movements caused by the prolonged use of dopamine receptor-blocking agents. The most common types of these agents are antipsychotics and anti-nausea agents. The classic form of TD refers to stereotypic movements of the mouth, which resemble chewing. However, TD can also appear as other involuntary movements such as chorea, dystonia
Dystonia
Dystonia is a neurological movement disorder, in which sustained muscle contractions cause twisting and repetitive movements or abnormal postures. The disorder may be hereditary or caused by other factors such as birth-related or other physical trauma, infection, poisoning or reaction to...
, or tics.
Tics
A ticTic
A tic is a sudden, repetitive, nonrhythmic, stereotyped motor movement or vocalization involving discrete muscle groups. Tics can be invisible to the observer, such as abdominal tensing or toe crunching. Common motor and phonic tics are, respectively, eye blinking and throat clearing...
can be defined as a repeated, individually recognizable, intermittent movement or movement fragments that are almost always briefly suppressible and are usually associated with awareness of an urge to perform the movement. These abnormal movements occur with intervening periods of normal movement. These movements are predictable, often triggered by stress, excitement, suggestion, or brief voluntary suppressibility. Many children say that the onset of tics can stem from the strong urge to move. Tics can be either muscular (alter normal motor function) or vocal (alter normal speech) in nature and most commonly involve the face, mouth, eyes, head, neck or shoulder muscles. Tics can also be classified as simple motor tics (a single brief stereotyped movement or movement fragment), complex motor tics (a more complex or sequential movement involving multiple muscle
groups), or phonic tics (including simple, brief phonations or vocalizations).
When both motor and vocal tics are present and persist for more than one year, a diagnosis of Tourette syndrome
Tourette syndrome
Tourette syndrome is an inherited neuropsychiatric disorder with onset in childhood, characterized by multiple physical tics and at least one vocal tic; these tics characteristically wax and wane...
(TS) is likely. TS is an inherited neurobehavioral disorder characterized by both motor and vocal tics. Many individuals with TS may also develop obsessions, compulsions, inattention and hyperactivity. TS usually begins in childhood. Up to 5% of the population suffers from tics, but at least 20% of boys will have developed tics at some point in their lifetimes.
Tremor
A tremorTremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
can be defined as a rhythmic, back and forth or oscillating involuntary movement about a joint axis. Tremors are symmetric about a midpoint within the movement, and both portions of the movement occur at the same speed. Unlike the other hyperkinetic movements, tremors lack both the jerking associated movements and posturing.
Essential tremor
Essential tremor
Essential tremor is a slowly progressive neurological disorder whose most recognizable feature is a tremor of the arms that is apparent during voluntary movements such as eating and writing...
(ET), also known as benign essential tremor, or familial tremor, is the most common movement disorder. It is estimated that 5 percent of people worldwide suffer from this condition, affecting those of all ages but typically staying within families. ET typically affects the hands and arms but can also affect the head, voice, chin, trunk and legs. Both sides of the body tend to be equally affected. The tremor is called an action tremor, becoming noticeable in the arms when they are being used. Patients often report that alcohol helps lessen the symptoms. Primary medical treatments for ET are usually beta-blockers. For patients who fail to respond sufficiently to medication, deep brain stimulation
Deep brain stimulation
Deep brain stimulation is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain...
and thalamotomy
Thalamotomy
First introduced in the 1950s, thalamotomy is an invasive procedure, primarily effective for tremors such as those associated with Parkinson's Disease , where a selected portion of the thalamus is surgically destroyed...
can be highly effective.
A “flapping tremor,” or asterixis
Asterixis
Asterixis is a tremor of the wrist when the wrist is extended , sometimes said to resemble a bird flapping its wings. This motor disorder is characterized by jerking movements and is associated with various encephalopathies due especially to faulty metabolism...
, is characterized by irregular flapping-hand movement, which appears most often with outstretched arms and wrist extension. Individuals with this condition resemble birds flapping their wings.
Volitional hyperkinesia
Volitional hyperkinesia refers to any type of involuntary movement described above that interrupts an intended voluntary muscular movement. These movements tend to be jolts that present suddenly during an otherwise smoothly coordinated action of skeletal muscle.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 Huntingtin
Huntingtin
The Huntingtin gene, also called HTT or HD gene, is the IT15 gene which codes for a protein called the huntingtin protein...
gene, the disease eventually contributes to selective atrophy of the Caudate nucleus
Caudate nucleus
The caudate nucleus is a nucleus located within the basal ganglia of the brains of many animal species. The caudate nucleus is an important part of the brain's learning and memory system.-Anatomy:...
and Putamen
Putamen
The putamen is a round structure located at the base of the forebrain . The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that comprises the basal ganglia. Through various pathways, the putamen is connected to the substantia nigra and globus pallidus...
, 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
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
, tetrabenazine
Tetrabenazine
Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorder and is marketed under the trade names Nitoman in Canada and Xenazine in New Zealand and some parts of Europe, and is also available in the USA as an orphan drug. On August 15, 2008 the U.S...
, and amantidine, are often effective in this regard.
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 tremorTremor
A tremor is an involuntary, somewhat rhythmic, muscle contraction and relaxation involving to-and-fro movements of one or more body parts. It is the most common of all involuntary movements and can affect the hands, arms, eyes, face, head, vocal folds, trunk, and legs. Most tremors occur in the...
, 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 insomniaInsomnia
Insomnia is most often defined by an individual's report of sleeping difficulties. While the term is sometimes used in sleep literature to describe a disorder demonstrated by polysomnographic evidence of disturbed sleep, insomnia is often defined as a positive response to either of two questions:...
and excessive daytime sleepiness. This is a very common problem and can occur at any age.
Similarly, the syndrome akathisia
Akathisia
Akathisia, or acathisia, is a syndrome characterized by unpleasant sensations of inner restlessness that manifests itself with an inability to sit still or remain motionless...
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 victims 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.Pathophysiology
Basal ganglia
The basal ganglia are a group of nuclei of varied origin in the brains of vertebrates that act as a cohesive functional unit. They are situated at the base of the forebrain and are strongly connected with the cerebral cortex, thalamus and other brain areas...
by the subthalamic nucleus. In many cases, the excitatory output of the subthalamic nucleus is reduced, leading to a reduced inhibitory outflow of the basal ganglia. Without the normal restraining influence of the basal ganglia, upper motor neurons of the circuit tend to become more readily activated by inappropriate signals, resulting in the characteristic abnormal movements.
There are two pathways involving basal ganglia-thalamocortical circuitry, both of which originate in the neostriatum. The direct pathway projects to the internal globus pallidus (GPi
GPI
GPI may refer to:* Alpha GPI, a Brazilian submachine gun.* Greenfield Park International, a primary school in Greenfield Park, Quebec, Canada.* Gas Petroleum&Properties Investments, LLC...
) and to the substantia nigra pars reticulata (SNr). These projections are inhibitory and have been found to utilize both GABA
Gabâ
Gabâ or gabaa, for the people in many parts of the Philippines), is the concept of a non-human and non-divine, imminent retribution. A sort of negative karma, it is generally seen as an evil effect on a person because of their wrongdoings or transgressions...
and substance P
Substance P
In the field of neuroscience, substance P is a neuropeptide: an undecapeptide that functions as a neurotransmitter and as a neuromodulator. It belongs to the tachykinin neuropeptide family. Substance P and its closely related neuropeptide neurokinin A are produced from a polyprotein precursor...
. The indirect pathway, which projects to the globus pallidus external (GPe), is also inhibitory and uses GABA and enkephalin
Enkephalin
An enkephalin is a pentapeptide involved in regulating nociception in the body. The enkephalins are termed endogenous ligands, or specifically endorphins, as they are internally derived and bind to the body's opioid receptors. Discovered in 1975, two forms of enkephalin were revealed, one...
. The GPe projects to the subthalamic nucleus
Subthalamic nucleus
The subthalamic nucleus is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. Anatomically, it is the major part of subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also...
(STN), which then projects back to the GPi and GPe via excitatory, glutaminergic pathways. Excitation 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 GABAerigc 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
Autoimmune disease
Autoimmune diseases arise from an overactive immune response of the body against substances and tissues normally present in the body. In other words, the body actually attacks its own cells. The immune system mistakes some part of the body as a pathogen and attacks it. This may be restricted to...
, and infections, which include meningitis
Meningitis
Meningitis is inflammation of the protective membranes covering the brain and spinal cord, known collectively as the meninges. The inflammation may be caused by infection with viruses, bacteria, or other microorganisms, and less commonly by certain drugs...
.
Since the basal ganglia often have many connections with the frontal lobe
Frontal lobe
The frontal lobe is an area in the brain of humans and other mammals, located at the front of each cerebral hemisphere and positioned anterior to the parietal lobe and superior and anterior to the temporal lobes...
of the brain, hyperkinesia can be associated with neurobehavioral or neuropsychiatric disorders such as mood changes, psychosis
Psychosis
Psychosis means abnormal condition of the mind, and is a generic psychiatric term for a mental state often described as involving a "loss of contact with reality"...
, 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
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....
, due to hypoxic
Hypoxia (medical)
Hypoxia, or hypoxiation, is a pathological condition in which the body as a whole or a region of the body is deprived of adequate oxygen supply. Variations in arterial oxygen concentrations can be part of the normal physiology, for example, during strenuous physical exercise...
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
Subthalamic nucleus
The subthalamic nucleus is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. Anatomically, it is the major part of subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also...
. Chorea can be secondary to hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
. Athetosis can be secondary to sensory loss in the distal limbs; this is called pseudoathetosis in adults but is not yet proven in children.
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 fluphenazineFluphenazine
Fluphenazine is a typical antipsychotic drug used for the treatment of psychoses such as schizophrenia and acute manic phases of bipolar disorder. It belongs to the piperazine class of phenothiazines....
, pimozide
Pimozide
Pimozide is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine . On a weight basis it is even more potent than haloperidol. It also has special neurologic indications for Tourette syndrome...
, haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
and perphenazine
Perphenazine
Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. It has been in clinical use for decades....
which block dopamine receptors; these are the first line of treatment for hemiballismus. Quetiapine
Quetiapine
Quetiapine , is an atypical antipsychotic approved for the treatment of schizophrenia, and bipolar disorder....
, sulpiride
Sulpiride
Sulpiride is an...
and olanzapine
Olanzapine
Olanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...
, the atypical neuroleptic agents, are less likely to yield drug-induced parkinsonism
Parkinsonism
Parkinsonism is a neurological syndrome characterized by tremor, hypokinesia, rigidity, and postural instability. The underlying causes of parkinsonism are numerous, and diagnosis can be complex...
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
Thalamic stimulator
A thalamic stimulator is a relatively new medical device that can suppress tremors, such as those caused by Parkinson's Disease or essential tremor. It was approved for use by the Food and Drug Administration on August 4, 1997. Installation is invasive, so it is typically only used when the...
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 MedicineBaylor College of Medicine
Baylor College of Medicine, located in the Texas Medical Center in Houston, Texas, USA, is a highly regarded medical school and leading center for biomedical research and clinical care...
begins with minimizing stress and tremorgenic drugs along with recommending a restricted intake of beverages containing caffeine
Caffeine
Caffeine is a bitter, white crystalline xanthine alkaloid that acts as a stimulant drug. Caffeine is found in varying quantities in the seeds, leaves, and fruit of some plants, where it acts as a natural pesticide that paralyzes and kills certain insects feeding on the plants...
as a precaution, although caffeine has not been shown to significantly intensify the presentation of essential tremor. Alcohol
Alcohol
In chemistry, an alcohol is an organic compound in which the hydroxy functional group is bound to a carbon atom. In particular, this carbon center should be saturated, having single bonds to three other atoms....
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 unadvisable, as there is a purported correlation between tremor and alcoholism. Alcohol is thought to stabilize neuronal membranes via potentiation of GABA receptor
GABA receptor
The GABA receptors are a class of receptors that respond to the neurotransmitter gamma-aminobutyric acid , the chief inhibitory neurotransmitter in the vertebrate central nervous system...
-mediated chloride influx. It has been demonstrated in essential tremor animal models that the food additive 1-octanol
Octanol
Octanol is a straight chain fatty alcohol with eight carbon atoms and the molecular formula CH37OH. Although the term octanol usually refers exclusively to the primary alcohol 1-octanol, there are other less common isomers of octanol such as the secondary alcohols 2-octanol, 3-octanol and...
suppresses tremors induced by harmaline
Harmaline
Harmaline is a fluorescent psychoactive indole alkaloid from the group of harmala alkaloids and beta-carbolines. It is the reduced hydrogenated form of harmine.-Occurrence in nature:...
, 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
Beta blocker
Beta blockers or beta-adrenergic blocking agents, beta-adrenergic antagonists, beta-adrenoreceptor antagonists or beta antagonists, are a class of drugs used for various indications. They are particularly for the management of cardiac arrhythmias, cardioprotection after myocardial infarction ,...
, and primidone
Primidone
Primidone is an anticonvulsant of the pyrimidinedione class, the active metabolites of which, phenobarbital and phenylethylmalonamide , are also anticonvulsants...
, an anticonvulsant
Anticonvulsant
The anticonvulsants are a diverse group of pharmaceuticals used in the treatment of epileptic seizures. Anticonvulsants are also increasingly being used in the treatment of bipolar disorder, since many seem to act as mood stabilizers, and in the treatment of neuropathic pain. The goal of an...
. Propranolol is much more effective for hand tremor than head and voice tremor. Beta-adrenergic blockers (beta blockers) are not lipid soluble and therefore cannot cross the blood-brain barrier
Blood-brain barrier
The blood–brain barrier is a separation of circulating blood and the brain extracellular fluid in the central nervous system . It occurs along all capillaries and consists of tight junctions around the capillaries that do not exist in normal circulation. Endothelial cells restrict the diffusion...
, 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
Benzodiazepine
A benzodiazepine is a psychoactive drug whose core chemical structure is the fusion of a benzene ring and a diazepine ring...
drugs such as diazepam
Diazepam
Diazepam , first marketed as Valium by Hoffmann-La Roche is a benzodiazepine drug. Diazepam is also marketed in Australia as Antenex. It is commonly used for treating anxiety, insomnia, seizures including status epilepticus, muscle spasms , restless legs syndrome, alcohol withdrawal,...
and barbiturates have been shown to reduce presentation of several types of tremor, including the essential variety. Controlled clinical trials of gabapentin
Gabapentin
Gabapentin is a pharmaceutical drug, specifically a GABA analogue. It was originally developed for the treatment of epilepsy, and currently is also used to relieve neuropathic pain...
yielded mixed results in efficacy against essential tremor while topiramate
Topiramate
Topiramate is an anticonvulsant drug. It was originally produced by Ortho-McNeil Neurologics and Noramco, Inc., both divisions of the Johnson & Johnson Corporation. This medication was discovered in 1979 by Bruce E. Maryanoff and Joseph F. Gardocki during their research work at McNeil...
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
Botulinum toxin
Botulinum toxin is a protein produced by the bacterium Clostridium botulinum, and is considered the most powerful neurotoxin ever discovered. Botulinum toxin causes Botulism poisoning, a serious and life-threatening illness in humans and animals...
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
Deep brain stimulation
Deep brain stimulation is a surgical treatment involving the implantation of a medical device called a brain pacemaker, which sends electrical impulses to specific parts of the brain...
toward the ventral intermediate nucleus of the thalamus
Thalamus
The thalamus is a midline paired symmetrical structure within the brains of vertebrates, including humans. It is situated between the cerebral cortex and midbrain, both in terms of location and neurological connections...
and potentially the subthalamic nucleus
Subthalamic nucleus
The subthalamic nucleus is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. Anatomically, it is the major part of subthalamus. As suggested by its name, the subthalamic nucleus is located ventral to the thalamus. It is also...
and caudal zona incerta
Zona incerta
The zona incerta is a horizontally elongated region of gray matter cells in the subthalamus below the thalamus. Its connections project extensively over the brain from the cerebral cortex down into the spinal cord....
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
Dysarthria
Dysarthria is a motor speech disorder resulting from neurological injury of the motor component of the motor-speech system and is characterized by poor articulation of phonemes...
), 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 anticholinergicAnticholinergic
An anticholinergic agent is a substance that blocks the neurotransmitter acetylcholine in the central and the peripheral nervous system. An example of an anticholinergic is dicycloverine, and the classic example is atropine....
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
Baclofen
Baclofen is a derivative of gamma-aminobutyric acid . It is primarily used to treat spasticity and is under investigation for the treatment of alcoholism....
, can help reduce spasticity
Spasticity
Spasticity is a feature of altered skeletal muscle performance in muscle tone involving hypertonia, which is also referred to as an unusual "tightness" of muscles...
seen in cerebral palsy
Cerebral palsy
Cerebral palsy is an umbrella term encompassing a group of non-progressive, non-contagious motor conditions that cause physical disability in human development, chiefly in the various areas of body movement....
such as dystonia in the leg and trunk. Treatment of secondary dystonia by administering levodopa in dopamine-responsive dystonia
Dopamine-responsive dystonia
Dopamine-responsive dystonia , also known as hereditary progressive dystonia with diurnal fluctuation, Segawa's disease, or Segawa's dystonia, is a genetic movement disorder which usually manifests itself during early childhood at around ages 5–8 years .Characteristic symptoms are increased muscle...
, copper chelation
Chelation
Chelation is the formation or presence of two or more separate coordinate bonds between apolydentate ligand and a single central atom....
in Wilson’s disease, or stopping the administration of drugs that may induce dystonia have been proven effective in a small number of cases. Physical therapy has been used to improve posture and prevent contractures via braces and casting, although in some cases, immobilization of limbs can induce dystonia, which is by definition known as peripherally induced dystonia. There are not many clinical trials that show significant efficacy for particular drugs, so medical of dystonia must be planned on a case-by-case basis. Botulinum toxin B, or Myobloc, has been approved by the US Food and Drug Administration to treat cervical dystonia due to level A evidential support by the scientific community. Surgery known as GPi DBS (Globus Pallidus Pars Interna Deep Brain Stimulation) has come to be popular in treating phasic forms of dystonia, although cases involving posturing and tonic contractions have improved to a lesser extent with this surgery. A follow-up study has found that movement score improvements observed one year after the surgery was maintained after three years in 58% of the cases. It has also been proven effective in treating cervical and cranial-cervical dystonia.
Tics
Treatment of tics present in conditions such as Tourette’s syndrome begins with patient, relative, teacher and peer education about the presentation of the tics. Sometimes, pharmacological treatment is unnecessary and tics can be reduced by behavioral therapy such as habit-reversal therapy and/or counseling. Often this route of treatment is difficult because it depends most heavily on patient compliance. Once pharmacological treatment is deemed most appropriate, lowest effective doses should be given first with gradual increases. The most effective drugs belong to the neuroleptic variety such as monoamine-depleting drugs and dopamine receptor-blocking drugs. Of the monoamine-depleting drugs, tetrabenazine is most powerful against tics and results in fewest side effects. A non-neuroleptic drug found to be safe and effective in treating tics is topiramate. Botulinum toxin injection in affected muscles can successfully treat tics; involuntary movements and vocalizations can be reduced, as well as life-threatening tics that have the potential of causing compressive myelopathyMyelopathy
Myelopathy refers to pathology of the spinal cord. When due to trauma, it is known as spinal cord injury. When inflammatory, it is known as myelitis. Disease that is vascular in nature is known as vascular myelopathy....
or radiculopathy
Radiculopathy
Radiculopathy is not a specific condition, but rather a description of a problem in which one or more nerves are affected and do not work properly . The emphasis is on the nerve root...
. Surgical treatment for disabling Tourette’s syndrome has been proven effective in cases presenting with self-injury. Deep Brain Stimulation surgery targeting the globus pallidus, thalamus and other areas of the brain may be effective in treating involuntary and possibly life-threatening tics.
History
In the 16th century, Andreas Vesalius and Francesco Piccolomini were the first to distinguish between white matter, the cortex, and the subcortical nuclei in the brain. About a century later, Thomas WillisThomas Willis
Thomas Willis was an English doctor who played an important part in the history of anatomy, neurology and psychiatry. He was a founding member of the Royal Society.-Life:...
noticed that the corpus striatum was typically discolored, shrinkened, and abnormally softened in the cadavers of people who had died from paralysis. The view that the corpus striatum played such a large role in motor functions was the most prominent one until the 19th century when electrophysiologic stimulation studies began to be performed. For example, Gustav Fritsch
Gustav Fritsch
Gustav Theodor Fritsch was a German anatomist, anthropologist, traveller and physiologist from Cottbus, best known for his work with neuropsychiatrist Eduard Hitzig on the electric localization of the motor areas of the brain...
and Eduard Hitzig
Eduard Hitzig
Eduard Hitzig was a German neurologist and neuropsychiatrist born in Berlin.He studied medicine at the Universities of Berlin and Würzburg, and had as instructors, famous men such as Emil Du Bois-Reymond , Rudolf Virchow , Moritz Heinrich Romberg and Karl Friedrich Otto Westphal...
performed them on dog cerebral cortices in 1870, while David Ferrier
David Ferrier
Sir David Ferrier, FRS was a pioneering Scottish neurologist and psychologist.-Life:Ferrier was born in Woodside, Aberdeen and educated at Aberdeen Grammar School before studying for an MA at Aberdeen University...
performed them, along with ablation studies, on cerebral cortices of dogs, rabbits, cats, and primates in 1876. During the same year, John Hughlings Jackson
John Hughlings Jackson
John Hughlings Jackson, FRS , was an English neurologist.- Biography :He was born at Providence Green, Green Hammerton, near Harrogate, Yorkshire, the youngest son of Samuel Jackson, a yeoman who owned and farmed his land, and the former Sarah Hughlings, the daughter of a Welsh revenue collector...
posited that the motor cortex was more relevant to motor function than the corpus striatum after carrying out clinical-pathologic experiments in humans. Soon it would be discovered that the theory about the corpus striatum would not be completely incorrect.
By the late 19th century, a few hyperkinesias such as Huntington’s chorea, post-hemiplegic choreoathetosis, Tourette’s syndrome, and some forms of both tremor and dystonia were described in a clinical orientation. However, the common pathology was still a mystery. British neurologist William Richard Gowers
William Richard Gowers
Sir William Richard Gowers was a British neurologist.The Gowers' tract is named after him....
called these disorders “general and functional diseases of the nervous system” in his 1888 publication entitled A Manual of Diseases of the Nervous System. It was not until the late 1980s and 1990s that sufficient animal models and human clinical trials were utilized to discover the specific involvement of the basal ganglia in the hyperkinesia pathology. In 1998, Wichmann and Delong made the conclusion that hyperkinesia is associated with decreased output from the basal ganglia, and in contrast, hypokinesia is associated with increased output from the basal ganglia. This generalization, however, still leaves a need for more complex models to distinguish the more nuanced pathologies of the numerous diverse hyperkinesias which are still being studied today.
In the 2nd century, Galen
Galen
Aelius Galenus or Claudius Galenus , better known as Galen of Pergamon , was a prominent Roman physician, surgeon and philosopher...
was the first to define tremor as “involuntary alternating up-and-down motion of the limbs.” Further classification of hyperkinetic movements came in the 17th and 18th centuries by Franciscus Sylvius
Franciscus Sylvius
Franciscus Sylvius , born Franz de le Boë, was a Dutch physician and scientist who was an early champion of Descartes', Van Helmont's and William Harvey's work and theories...
and Gerard van Swieten
Gerard van Swieten
Gerard van Swieten was a Dutch-Austrian physician.Van Swieten was born in Leiden. He was a pupil of Hermann Boerhaave and became in 1745 the personal physician of the Austrian Empress Maria Theresa. In this position he implemented a transformation of the Austrian health service and medical...
. Parkinson’s disease was one of the first disorders to be named as a result of the recent classification of its featured hyperkinetic tremor. The subsequent naming of other disorders involving abnormal motions soon followed.
Research directions
Studies have been done with electromyographyElectromyography
Electromyography is a technique for evaluating and recording the electrical activity produced by skeletal muscles. EMG is performed using an instrument called an electromyograph, to produce a record called an electromyogram. An electromyograph detects the electrical potential generated by muscle...
to trace skeletal muscle activity in some hyperkinetic disorders. The electromyogram (EMG) of dystonia sometimes shows rapid rhythmic bursts, but these patterns can almost always be produced intentionally. In the myoclonus EMG, there are typically brief, and sometimes rhythmic, bursts or pauses in the recording pattern. When the bursts last for 50 milliseconds or less they are indicative of cortical myoclonus, but when they last up to 200 milliseconds, they are indicative of spinal or brainstem myoclonus. Such bursts can occur in multiple muscles simultaneously quite quickly, but high time resolution must be used in the EMG trace to clearly record them. The bursts recorded for tremor tend to be longer in duration than those of myoclonus, although some types can last for durations within the range for those of myoclonus. Future studies would have to examine the EMGs for tics, athetosis, stereotypies and chorea as there are minimal recordings done for those movements. However, it may be predicted that the EMG for chorea would include bursts varying in duration, timing, and amplitude, while that for tics and stereotypies would take on patterns of voluntary movements.
In general, research for treatment of hyperkinesia has most recently been focusing on ameliorating symptoms rather than attempting to correct the pathogenesis of the disease. Therefore, now and in the future it may be beneficial to inform the learning of the disease's pathology through carefully controlled, long-term, observation-based studies. As therapies are supported by proven effectiveness that can be repeated in multiple studies, they are useful, but the clinician may also consider that the best treatments for patients can only be evaluated on a case-by-case basis. It is the interplay of these two facets of neurology and medicine that may bring about significant progress in this field.