Hemiballismus or hemiballism is a basal ganglia syndrome resulting from damage to the

subthalamic nucleus The subthalamic nucleus (STN) is a small lens-shaped nucleus in the brain where it is, from a functional point of view, part of the basal ganglia system. In terms of anatomy, it is the major part of the subthalamus. As suggested by its name, the ...

in the

basal ganglia The basal ganglia (BG), or basal nuclei, are a group of subcortical nuclei, of varied origin, in the brains of vertebrates. In humans, and some primates, there are some differences, mainly in the division of the globus pallidus into an extern ...

. Hemiballismus is a rare hyperkinetic movement disorder, that is characterized by violent involuntary limb movements, on one side of the body, and can cause significant disability. ''Ballismus'' affects both sides of the body and is much rarer. Symptoms can decrease during sleep. Hemiballismus differs from

chorea Chorea (or choreia, occasionally) is an abnormal involuntary movement disorder, one of a group of neurological disorders called dyskinesias. The term ''chorea'' is derived from the grc, χορεία ("dance"; see choreia), as the quick movement ...

in that the movements occur in the proximal limbs whereas in chorea the limb movements are in the distal limbs. Also in chorea the movements are more dance-like, flowing from one region to another.

Presentation

''Ballism'' was defined by Meyers in 1968Meyer, R. (1968) Ballismus. In: Vinken, P.J. and Bruyn, G.W. (Eds.), Handbook of Clinical Neurology, Vol. 6, North-Holland Publishing Co., Amsterdam, pp. 476-490. as "Repetitive, but constantly varying, large amplitude involuntary movements of the proximal parts of the limbs. This activity is almost ceaseless and movements are often complex and combined". Hemiballismus is usually characterized by involuntary flinging motions of the extremities. The movements are often violent and have wide amplitudes of motion. They are continuous and random and can involve

proximal Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...

distal Standard anatomical terms of location are used to unambiguously describe the anatomy of animals, including humans. The terms, typically derived from Latin or Greek roots, describe something in its standard anatomical position. This position pro ...

muscles on one side of the body. Some cases even include the facial muscles. It is common for arms and legs to move together. The more a patient is active, the more the movements increase. With relaxation comes a decrease in movements. Physicians can measure the severity of the disorder by having the patient perform a series of basic, predetermined tasks and counting the hemiballistic movements during a set time session. The physicians then rate the patient on a severity scale. This scale gives scientists and clinicians a way to compare patients and determine the range of the disorder. The name ''hemiballismus'' literally means "half ballistic", referring to the violent, flailing movements observed on one side of the body.

Causes

In examining the causes of hemiballismus, it is important to remember that this disorder is extremely rare. While hemiballismus can result from the following list, just because a patient has one of these disorders does not mean they will also experience hemiballismus.

Stroke

Hemisballismus as a result of

stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop functionin ...

occurs in only about 0.45 cases per hundred thousand

patients. Even at such a small rate,

is by far the most common cause of hemiballismus. A stroke causes tissue to die due to a lack of oxygen resulting from an impaired blood supply. In the

, this can result in the death of tissue that helps to control movement. As a result, the brain is left with damaged tissue that sends damaged signals to the skeletal muscles in the body. The result is occasionally a patient with hemiballismus.

Traumatic brain injury

Hemiballismus can also occur as a result of a

traumatic brain injury A traumatic brain injury (TBI), also known as an intracranial injury, is an injury to the brain caused by an external force. TBI can be classified based on severity (ranging from mild traumatic brain injury TBI/concussionto severe traumatic b ...

. There are cases in which survivors of assault or other forms of violence have developed hemiballismus. Through these acts of violence, the survivor's brain has been damaged and the hemiballistic movements have developed.

Amyotrophic lateral sclerosis

This disease causes neuronal loss and

gliosis Gliosis is a nonspecific reactive change of glial cells in response to damage to the central nervous system (CNS). In most cases, gliosis involves the proliferation or hypertrophy of several different types of glial cells, including astrocytes, ...

, which can include the

and other areas of the brain. Essentially any disorder that causes some form of neuronal loss or

in the

has the potential to cause hemiballismus.

Nonketotic hyperglycemia

Patients with nonketotic

hyperglycemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1 mmol/L (200 mg/dL), but symptoms may not start to become noticeable until even ...

can develop hemiballismus as a complication to the disease through the development of a

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

. This is the second most common reported cause of hemiballismus. It can be found primarily in the elderly and many of the reported cases have come from East Asian origin, which suggests that there may be some genetic disposition to development of hemiballismus as a result of hyperglycemia. Hemiballistic movements appear when

blood glucose level Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the blo ...

s get too high and then subside once glucose levels return to normal. This time scale for this is usually several hours. In patients with this type of hemiballismus, imaging reveals abnormalities in the

putamen The putamen (; from Latin, meaning "nutshell") is a round structure located at the base of the forebrain (telencephalon). The putamen and caudate nucleus together form the dorsal striatum. It is also one of the structures that compose the basal n ...

contralateral to the movements as well as the

globus pallidus The globus pallidus (GP), also known as paleostriatum or dorsal pallidum, is a subcortical structure of the brain. It consists of two adjacent segments, one external, known in rodents simply as the globus pallidus, and one internal, known in rod ...

and

caudate nucleus The caudate nucleus is one of the structures that make up the corpus striatum, which is a component of the basal ganglia in the human brain. While the caudate nucleus has long been associated with motor processes due to its role in Parkinson's di ...

. While the hyperglycemia itself is not the cause of the hemiballistic movements, it has been suggested that petechial hemorrhage or a decreased production of GABA and

acetylcholine Acetylcholine (ACh) is an organic chemical that functions in the brain and body of many types of animals (including humans) as a neurotransmitter. Its name is derived from its chemical structure: it is an ester of acetic acid and choline. Part ...

could result secondary to the hyperglycemia. One of these issues could be responsible for the hemiballistic movements.

Neoplasms

neoplasm A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

is an abnormal growth of cells. Cases have shown that if this occurs somewhere in the

, hemiballismus can result.

Vascular malformations

Vascular malformations can cause abnormal blood flow to areas of the brain. If too little blood is delivered to the

, a

can occur.

Tuberculomas

This is another form of

tumor A neoplasm () is a type of abnormal and excessive growth of tissue. The process that occurs to form or produce a neoplasm is called neoplasia. The growth of a neoplasm is uncoordinated with that of the normal surrounding tissue, and persists ...

that can result in the brain as a result of a

tuberculous meningitis Tuberculous meningitis, also known as TB meningitis or tubercular meningitis, is a specific type of bacterial meningitis caused by the ''Mycobacterium tuberculosis'' infection of the meninges—the system of membranes which envelop the central nerv ...

infection. This type of

can also damage parts of the

, sometimes resulting in hemiballismus.

Demyelinating plaques

Demyelinating plaques attack the

myelin Myelin is a lipid-rich material that surrounds nerve cell axons (the nervous system's "wires") to insulate them and increase the rate at which electrical impulses (called action potentials) are passed along the axon. The myelinated axon can be ...

sheaths on

neurons A neuron, neurone, or nerve cell is an electrically excitable cell that communicates with other cells via specialized connections called synapses. The neuron is the main component of nervous tissue in all animals except sponges and placozoa. N ...

. This decreases the conduction velocity of the

, making the signals received by the

garbled and incomplete. This disorganized signal can also cause the chaotic movements characterized by hemiballismus.

Complications from HIV infection

Patients with

HIV The human immunodeficiency viruses (HIV) are two species of ''Lentivirus'' (a subgroup of retrovirus) that infect humans. Over time, they cause acquired immunodeficiency syndrome (AIDS), a condition in which progressive failure of the immune ...

often have complications that arise along with

AIDS Human immunodeficiency virus infection and acquired immunodeficiency syndrome (HIV/AIDS) is a spectrum of conditions caused by infection with the human immunodeficiency virus (HIV), a retrovirus. Following initial infection an individual m ...

Hypoglycemia Hypoglycemia, also called low blood sugar, is a fall in blood sugar to levels below normal, typically below 70 mg/dL (3.9 mmol/L). Whipple's triad is used to properly identify hypoglycemic episodes. It is defined as blood glucose belo ...

due to

pentamidine Pentamidine is an antimicrobial medication used to treat African trypanosomiasis, leishmaniasis, ''Balamuthia'' infections, babesiosis, and to prevent and treat pneumocystis pneumonia (PCP) in people with poor immune function. In African trypano ...

use in patients with

has been known to cause hemiballismus. In some patients, hemiballismus has been the only visible symptom to alert the physician that the patients may have

. It is typically a result of a secondary infection that occurs due to the compromised

immune system The immune system is a network of biological processes that protects an organism from diseases. It detects and responds to a wide variety of pathogens, from viruses to parasitic worms, as well as cancer cells and objects such as wood splinte ...

and the most common infection causing hemiballismus is cerebral

toxoplasmosis Toxoplasmosis is a parasitic disease caused by ''Toxoplasma gondii'', an apicomplexan. Infections with toxoplasmosis are associated with a variety of neuropsychiatric and behavioral conditions. Occasionally, people may have a few weeks or months ...

. Most of the

lesions A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classifi ...

that result from this infection are found in the

. As long as the diagnosis is not missed, this type of hemiballismus can be treated just as well as in patients without

Anatomy

Basal ganglia

The

are a collection of nuclei that connects to several other areas of the brain. Due to the diverse nuclei that they contain, the basal ganglia are involved in numerous functions, including motor control. It is within this structure that hemiballismus primarily occurs in the brain.

Subthalamic nucleus

This structure within the basal ganglia innervates other structures, including a very important connection to the

internal globus pallidus The internal globus pallidus (GPi or medial globus pallidus; in rodents its homologue is known as the entopeduncular nucleus) and the external globus pallidus (GPe) make up the globus pallidus. The GPi is one of the output nuclei of the basal gang ...

. The

essentially provides the excitement needed to drive the

. Injury to this area or its

efferent Efferent may refer to: Anatomical structures Meaning 'conveying away from a center': *Efferent arterioles, conveying blood away from the Bowman's capsule in the kidney *Efferent nerve fiber, carries nerve impulses away from the central nervous sy ...

or afferent connections can induce this disorder contralateral to the side of the lesion. The structure itself is a regulator of motor function and is also involved in associative and

limbic The limbic system, also known as the paleomammalian cortex, is a set of brain structures located on both sides of the thalamus, immediately beneath the medial temporal lobe of the cerebrum primarily in the forebrain.Schacter, Daniel L. 2012. ''Ps ...

functions. It was traditionally thought that the disorder was only caused by injury to the

, but later studies have shown that damage to other basal ganglia regions can also be responsible for causing this disorder. Hemiballismus caused by

in the subthalamic nucleus is more severe than other forms of the disorder.

Globus pallidus

From recent studies, it is now thought that hemiballismus can be associated with a decreased output of the globus pallidus. This is because studies have shown that firing rates decrease from 70/s to 40/s. In addition to a decreased firing rate, degenerative neurological disorders that cause patients to exhibit hemiballistic movements show a marked decrease in the globus pallidus mass as well. Increases in activity in this area causes there to be an inhibition of the motor

thalamus The thalamus (from Greek θάλαμος, "chamber") is a large mass of gray matter located in the dorsal part of the diencephalon (a division of the forebrain). Nerve fibers project out of the thalamus to the cerebral cortex in all directions, ...

. This causes cortical activation and thus a movement inhibition. In the case of hemiballismus, the opposite occurs, leading to the characteristic large, irregular movements.

Putamen

The

is also part of the basal ganglia and can be involved in hemiballismus due to the fact that it projects to the

premotor cortex The premotor cortex is an area of the motor cortex lying within the frontal lobe of the brain just anterior to the primary motor cortex. It occupies part of Brodmann's area 6. It has been studied mainly in primates, including monkeys and humans. ...

through the globus pallidus. As a result, damage to this area can also cause hemiballistic movements to be seen as it is also part of the chain in movement.

Caudate nucleus

The

is the portion of the basal ganglia that helps control voluntary movement. Damage to this area can also result in hemiballismus as it is directly related to voluntary movement.

Cortical structures

While the majority of damage that causes hemiballismus occurs within the basal ganglia, there are still cases that have been documented on which damage to cortical structures has caused hemiballistic movements.

Diagnosis

Diagnosis of hemiballismus is a clinical one, made with observation during clinical examination. Hemiballismus is a clinical sign with a number of different causes. Therefore, a diagnosis underlying this clinical sign should be sought. The observer should note sudden, flinging movements of a limb(s) and occasionally the face. This is commonly unilateral ("Hemiballismus"). The movements must be distinguished from other hyperkinetic movement disorders such as tremor (generally more rhythmic, and smaller amplitude) and chorea, akathisia and athetosis (all are often of lower amplitude and less violent).

Treatments

When treating hemiballismus, it is first important to treat whatever may be causing the manifestation of this disorder. This could be

, infections, or neoplastic

. Some patients may not even need treatment because the disorder is not severe and can be self-limited.

Dopamine blockers

When pharmacological treatment is necessary, the most standard type of drug to use is an antidopaminergic drug. Blocking

dopamine Dopamine (DA, a contraction of 3,4-dihydroxyphenethylamine) is a neuromodulatory molecule that plays several important roles in cells. It is an organic compound, organic chemical of the catecholamine and phenethylamine families. Dopamine const ...

is effective in about ninety percent of patients.

Perphenazine Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. Originally marketed in the United States as Trilafon, it has been in clinical use for decades. Perphenazine is roughly ten times as poten ...

pimozide Pimozide (sold under the brand name Orap) is an antipsychotic drug of the diphenylbutylpiperidine class. It was discovered at Janssen Pharmaceutica in 1963. It has a high potency compared to chlorpromazine (ratio 50-70:1). On a weight basis i ...

haloperidol Haloperidol, sold under the brand name Haldol among others, is a typical antipsychotic medication. Haloperidol is used in the treatment of schizophrenia, tics in Tourette syndrome, mania in bipolar disorder, delirium, agitation, acute psychosi ...

, and

chlorpromazine Chlorpromazine (CPZ), marketed under the brand names Thorazine and Largactil among others, is an antipsychotic medication. It is primarily used to treat psychotic disorders such as schizophrenia. Other uses include the treatment of bipolar dis ...

are standard choices for treatment. Scientists are still unsure as to why this form of treatment works, as

has not been directly linked to hemiballismus.

Anticonvulsants

An anticonvulsant called

topiramate Topiramate, sold under the brand name Topamax among others, is a carbonic anhydrase inhibitor medication used to treat epilepsy and prevent migraines. It has also been used in alcohol dependence. For epilepsy this includes treatment for gener ...

has helped patients in three cases and may be a viable treatment for the future.

ITB therapy

Intrathecal

baclofen Baclofen, sold under the brand name Lioresal among others, is a medication used to treat muscle spasticity such as from a spinal cord injury or multiple sclerosis. It may also be used for hiccups and muscle spasms near the end of life. It is ta ...

(ITB) therapy is used to treat a variety of movement disorders such as

cerebral palsy Cerebral palsy (CP) is a group of movement disorders that appear in early childhood. Signs and symptoms vary among people and over time, but include poor coordination, stiff muscles, weak muscles, and tremors. There may be problems with sensa ...

and

multiple sclerosis Multiple (cerebral) sclerosis (MS), also known as encephalomyelitis disseminata or disseminated sclerosis, is the most common demyelinating disease, in which the insulating covers of nerve cells in the brain and spinal cord are damaged. This d ...

. It can also be a possibility to help treat hemiballismus. In one case, before ITB the patient had an average of 10–12 ballism episodes of the right lower limb per hour. During episodes, the right hip would flex up to about 90 degrees, with a fully extended knee. After an ITB pump was implanted and the correct dosage was found, the frequency of ballistic right leg movements decreased to about three per day, and the right hip flexed to only 30 degrees. The patient was also able to better isolate individual distal joint movements in the right lower limb. The patient currently receives 202.4 microg/day of ITB and continues to benefit almost 6 years after the ITB pump was implanted.

Botulinum injections

New uses for

botulinum toxin Botulinum toxin, or botulinum neurotoxin (BoNT), is a neurotoxic protein produced by the bacterium ''Clostridium botulinum'' and related species. It prevents the release of the neurotransmitter acetylcholine from axon endings at the neuromusc ...

have included treatment of hemiballismus. However, this is still in the early stages of testing. This treatment deals with the muscular manifestations of hemiballismus as opposed to the neurological causes.

Tetrabenazine

Tetrabenazine Tetrabenazine is a drug for the symptomatic treatment of hyperkinetic movement disorders. It is sold under the brand names Nitoman and Xenazine among others. On August 15, 2008, the U.S. Food and Drug Administration approved the use of tetrabenaz ...

has been used to treat other movement disorders, but is now being used to treat hemiballismus. Patients using this medication have had a dramatic response. However, lowering the dosage leads to a return of symptoms. This drug works by depleting dopamine.

Antipsychotics

In one case, a patient had not been responding to haloperidol, thus the physician tried

olanzapine Olanzapine (sold under the trade name Zyprexa among others) is an atypical antipsychotic primarily used to treat schizophrenia and bipolar disorder. For schizophrenia, it can be used for both new-onset disease and long-term maintenance. It is ta ...

. The patient made a significant recovery. More research is being performed on the use of these types of drugs in treating hemiballismus.

Functional neurosurgery

Surgery as a treatment should only be used on patients with severe hemiballismus that has not responded to treatment. Lesioning of the globus pallidus or

deep brain stimulation Deep brain stimulation (DBS) is a neurosurgical procedure involving the placement of a medical device called a neurostimulator, which sends electrical impulses, through implanted electrodes, to specific targets in the brain (the brain nucleu ...

of the globus pallidus are procedures that can be used on humans. Usually, lesioning is favored over deep brain stimulation because of the maintenance required to continue stimulating the brain correctly and effectively.

Prognosis

In the past, the prognosis for patients with this disease had been very poor; with many patients experiencing severe disability or death. Now, patients are responding remarkably well to current treatments and the majority of patients go into spontaneous remission. For those that do not go into remission, the symptoms of hemiballismus can generally be very well controlled with medication. Due to the rarity of this disorder, scientists know very little about the details of hemiballismus. * There appears to be a discrepancy between this disorder in humans and animals that has yet to be explained. * Hemiballismus can also be induced by damage to other areas of the

besides the

. Research is being done in these areas in order to give scientists and clinicians a better model for this disease that will ultimately lead to better diagnosis and treatment of this disorder. * Research is also being done on why certain treatments seem to help hemiballistic patients when they should seemingly do more harm. An example of this is why lesioning the

seems to reduce hemiballistic movements. * The mechanism behind the effect of

on patients' symptoms remains unknown.

History

The work of J.R. Whittier, F.A. Mettler, and M.B. Carpenter in the mid-1900s helped scientists and clinicians form a more complete picture of hemiballismus. In their experiments, several

were made in the

structures in monkeys and then they monitored the results. They noticed that the majority of the time, the monkeys did not have any unusual movements. However, when at least twenty percent of the

was damaged, abnormal movements were seen in the limbs opposite to the side of the brain that was damaged. This observation caused scientists to believe that hemiballismus outside the

did not occur. It was not until much later that this classical model began to expand to include other areas of the

and even some cortical structures. They also noticed that unlike human patients, the unusual movements in the monkeys were mainly in the lower extremities. In about half of the monkeys, the hemiballismus continued until the monkey died. Other scientists have also worked on this perplexing disorder and have found that the symptoms can be induced by injecting

kainic acid Kainic acid, or kainate, is an acid that naturally occurs in some seaweed. Kainic acid is a potent neuroexcitatory amino acid agonist that acts by activating receptors for glutamate, the principal excitatory neurotransmitter in the central nervo ...

ibotenic acid Ibotenic acid or (''S'')-2-amino-2-(3-hydroxyisoxazol-5-yl)acetic acid, also referred to as ibotenate, is a chemical compound and psychoactive drug which occurs naturally in ''Amanita muscaria'' and related species of mushrooms typically found i ...

into the

. I. Hamada and M.R. DeLong found that by using these chemicals, they could destroy only four percent of the

and still see hemiballistic movements. However, the abnormal movements would usually disappear within four to five hours even though it did not appear as though the damaged tissue had healed. This suggests that the subthalamic nucleus is plastic enough to adapt to small amounts of damage in order to resume normal function.

References

External links

{{Nervous and musculoskeletal system symptoms and signs Extrapyramidal and movement disorders Symptoms and signs: Nervous system Articles containing video clips Rare diseases de:Hemiballismus