Hemiballismus
Encyclopedia
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. The symptoms can also decrease while the patient is asleep, unlike some movement disorders.
The name 'hemiballismus' literally means 'half ballistic', referring to the violent, flailing movements observed on one side of the body.
The basal ganglia
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 inside of the globus pallidus
. The subthalamic nucleus
essentially provides the excitement needed to drive the globus pallidus
. Injury to this area or its efferent
or afferent
connections can induce this disorder. The structure itself is a regulator of motor function and is also involved in associative and limbic functions. It was traditionally thought that the disorder was only caused by injury to the subthalamic nucleus
, but new studies are showing that damage to other areas of the brain can also be responsible for causing this disorder. Hemiballismus caused by lesions 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
. 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 putamen
is also part of the basal ganglia
and can be involved in hemiballismus due to the fact that it projects to the premotor cortex
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 caudate nucleus
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.
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 subthalamic nucleus
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 subthalamic nucleus
did not occur. It was not until much later that this classical model began to expand to include other areas of the basal ganglia
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
or ibotenic acid
into the subthalamic nucleus
. I. Hamada and M.R. DeLong found that by using these chemicals, they could destroy only four percent of the subthalamic nucleus
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.
Stroke
Hemisballismus as a result of stroke
occurs in only about 0.45 cases per hundred thousand stroke
victims. Even at such a small rate, stroke
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 basal ganglia
, 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
. There are cases in which victims of assault or other forms of violence have developed hemiballismus. Through these acts of violence, the victim’s brain has been damaged and the hemiballistic movements have developed.
Amyotrophic Lateral Sclerosis
This disease causes neuronal loss and gliosis
, which can include the subthalamic nucleus
and other areas of the brain. Essentially any disorder that causes some form of neuronal loss or gliosis
in the basal ganglia
has the potential to cause hemiballismus.
Nonketotic Hyperglycemia
Patients with nonketotic hyperglycemia
can develop hemiballismus as a complication to the disease through the development of a subthalamic nucleus
lesion
. 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 levels 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
contralateral to the movements as well as the globus pallidus
and caudate nucleus
. 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
could result secondary to the hyperglycemia. One of these issues could be responsible for the hemiballistic movements.
Neoplasms
A neoplasm is an abnormal growth of cells. Cases have shown that if this occurs somewhere in the basal ganglia
, 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 basal ganglia
, a stroke
can occur.
Tuberculomas
This is another form of tumor
that can result in the brain as a result of a tuberculous meningitis
infection. This type of tumor
can also damage parts of the basal ganglia
, sometimes resulting in hemiballismus.
Demyelinating plaques
Demyelinating plaques attack the myelin
sheaths on neurons. This decreases the conduction velocity of the neurons, making the signals received by the basal ganglia
garbled and incomplete. This disorganized signal can also cause the chaotic movements characterized by hemiballismus.
Complications from HIV infection
Patients with HIV
often have complications that arise along with AIDS
. Hypoglycemia
due to pentamidine
use in patients with AIDS
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 AIDS
. It is typically a result of a secondary infection that occurs due to the compromised immune system
and the most common infection causing hemiballismus is cerebral toxoplasmosis
. Most of the lesions that result from this infection are found in the basal ganglia
. As long as the diagnosis is not missed, this type of hemiballismus can be treated just as well as in patients without HIV
.
, infections, or neoplastic lesions. 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
is effective in about ninety percent of patients. Perphenazine
, pimozide
, haloperidol
, and chlorpromazine
are standard choices for treatment. Scientists are still unsure as to why this form of treatment works, as dopamine
has not been directly linked to hemiballismus.
Anticonvulsants
An anticonvulsant called topiramate
has helped patients in three cases and may be a viable treatment for the future.
ITB Therapy
Intrathecal baclofen (ITB) therapy is used to treat a variety of movement disorders such as cerebral palsy
and multiple sclerosis
. 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
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
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
. 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
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.
•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 basal ganglia
besides the subthalamic nucleus
. Why is this? 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 globus pallidus
seems to reduce hemiballistic movements.
•Why does blocking dopamine
help reduce patients’ symptoms?
. While a classical model for this disorder was developed in the 1950s, new discoveries are causing that model to shift. New treatments are also emerging, allowing for better control of symptoms as well as affecting those who did not respond to standard treatment. The prognosis for patients with this disorder is very good, as research in the area is continuing to reveal new insights into the pathophysiology. However, there are still many unanswered questions about this unusual movement disorder and scientists and clinicians are still learning new information as they probe deeper into the brain.
Parkinson's disease
Parkinson's disease is a degenerative disorder of the central nervous system...
. 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. The symptoms can also decrease while the patient is asleep, unlike some movement disorders.
General Definition
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 and/or distal 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.
Anatomy
Basal gangliaThe basal ganglia
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...
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
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...
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
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...
innervates other structures, including a very important connection to the inside of the globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
. 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...
essentially provides the excitement needed to drive the globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
. Injury to this area or its efferent
Efferent
Efferent is an anatomical term with the following meanings:*Conveying away from a center, for example the efferent arterioles conveying blood away from the Bowman's capsule in the kidney. Opposite to afferent....
or afferent
Afferent
Afferent is an anatomical term with the following meanings:*Conveying towards a center, for example the afferent arterioles conveying blood towards the Bowman's capsule in the Kidney. Opposite to Efferent.*Something that so conducts, see Afferent nerve fiber...
connections can induce this disorder. The structure itself is a regulator of motor function and is also involved in associative and limbic functions. It was traditionally thought that the disorder was only caused by injury 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...
, but new studies are showing that damage to other areas of the brain can also be responsible for causing this disorder. Hemiballismus caused by lesions in 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...
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
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
. 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
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
mass as well. Increases in activity in this area causes there to be an inhibition of the motor 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...
. 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 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...
is also part of the basal ganglia
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...
and can be involved in hemiballismus due to the fact that it projects to the premotor cortex
Premotor cortex
The premotor cortex is an area of motor cortex lying within the frontal lobe of the brain. It extends 3 mm anterior to the primary motor cortex, near the Sylvian fissure, before narrowing to approximately 1 mm near the medial longitudinal fissure, which serves as the posterior border for...
through the globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
. 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 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:...
is the portion of the basal ganglia
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...
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
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...
, there are still cases that have been documented on which damage to cortical structures has caused hemiballistic movements.
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 lesions were made in 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...
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 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...
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 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...
did not occur. It was not until much later that this classical model began to expand to include other areas of the basal ganglia
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...
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
Kainic acid is a natural marine acid present in some seaweed. It is a specific agonist for the kainate receptor used as an ionotropic glutamate receptor which mimics the effect of glutamate...
or ibotenic acid
Ibotenic acid
Ibotenic acid is a chemical compound that is naturally occurring in the mushrooms Amanita muscaria and Amanita pantherina, among others...
into 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...
. I. Hamada and M.R. DeLong found that by using these chemicals, they could destroy only four percent of 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 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.
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 suffers from one of these disorders does not mean they will also suffer from hemiballismus.Stroke
Hemisballismus as a result of stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
occurs in only about 0.45 cases per hundred thousand stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
victims. Even at such a small rate, stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
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 basal ganglia
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...
, 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
Traumatic brain injury
Traumatic brain injury , also known as intracranial injury, occurs when an external force traumatically injures the brain. TBI can be classified based on severity, mechanism , or other features...
. There are cases in which victims of assault or other forms of violence have developed hemiballismus. Through these acts of violence, the victim’s brain has been damaged and the hemiballistic movements have developed.
Amyotrophic Lateral Sclerosis
This disease causes neuronal loss and gliosis
Gliosis
Gliosis is a proliferation of astrocytes in damaged areas of the central nervous system . This proliferation usually leads to the formation of a glial scar....
, which can include 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 other areas of the brain. Essentially any disorder that causes some form of neuronal loss or gliosis
Gliosis
Gliosis is a proliferation of astrocytes in damaged areas of the central nervous system . This proliferation usually leads to the formation of a glial scar....
in the basal ganglia
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...
has the potential to cause hemiballismus.
Nonketotic Hyperglycemia
Patients with nonketotic hyperglycemia
Hyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
can develop hemiballismus as a complication to the disease through the development of a 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...
lesion
Lesion
A lesion is any abnormality in the tissue of an organism , usually caused by disease or trauma. Lesion is derived from the Latin word laesio which means injury.- Types :...
. 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 levels 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
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...
contralateral to the movements as well as the globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
and 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:...
. 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
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 acetylcholine
Acetylcholine
The chemical compound acetylcholine is a neurotransmitter in both the peripheral nervous system and central nervous system in many organisms including humans...
could result secondary to the hyperglycemia. One of these issues could be responsible for the hemiballistic movements.
Neoplasms
A neoplasm is an abnormal growth of cells. Cases have shown that if this occurs somewhere in the basal ganglia
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...
, 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 basal ganglia
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...
, a stroke
Stroke
A stroke, previously known medically as a cerebrovascular accident , is the rapidly developing loss of brain function due to disturbance in the blood supply to the brain. This can be due to ischemia caused by blockage , or a hemorrhage...
can occur.
Tuberculomas
This is another form of tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
that can result in the brain as a result of a tuberculous meningitis
Tuberculous meningitis
Tuberculous meningitis is also known as TB meningitis or tubercular meningitis.Tuberculous meningitis is Mycobacterium tuberculosis infection of the meninges—the system of membranes which envelops the central nervous system. It is the most common form of CNS tuberculosis.-Clinical features:Fever...
infection. This type of tumor
Tumor
A tumor or tumour is commonly used as a synonym for a neoplasm that appears enlarged in size. Tumor is not synonymous with cancer...
can also damage parts of the basal ganglia
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...
, sometimes resulting in hemiballismus.
Demyelinating plaques
Demyelinating plaques attack the myelin
Myelin
Myelin is a dielectric material that forms a layer, the myelin sheath, usually around only the axon of a neuron. It is essential for the proper functioning of the nervous system. Myelin is an outgrowth of a type of glial cell. The production of the myelin sheath is called myelination...
sheaths on neurons. This decreases the conduction velocity of the neurons, making the signals received by the basal ganglia
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...
garbled and incomplete. This disorganized signal can also cause the chaotic movements characterized by hemiballismus.
Complications from HIV infection
Patients with HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
often have complications that arise along with AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. Hypoglycemia
Hypoglycemia
Hypoglycemia or hypoglycæmia is the medical term for a state produced by a lower than normal level of blood glucose. The term literally means "under-sweet blood"...
due to pentamidine
Pentamidine
Pentamidine is an antimicrobial medication given for prevention and treatment of Pneumocystis pneumonia caused by Pneumocystis jirovecii , a severe interstitial type of pneumonia often seen in patients with HIV infection...
use in patients with AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
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 AIDS
AIDS
Acquired immune deficiency syndrome or acquired immunodeficiency syndrome is a disease of the human immune system caused by the human immunodeficiency virus...
. It is typically a result of a secondary infection that occurs due to the compromised immune system
Immune system
An immune system is a system of biological structures and processes within an organism that protects against disease by identifying and killing pathogens and tumor cells. It detects a wide variety of agents, from viruses to parasitic worms, and needs to distinguish them from the organism's own...
and the most common infection causing hemiballismus is cerebral toxoplasmosis
Toxoplasmosis
Toxoplasmosis is a parasitic disease caused by the protozoan Toxoplasma gondii. The parasite infects most genera of warm-blooded animals, including humans, but the primary host is the felid family. Animals are infected by eating infected meat, by ingestion of feces of a cat that has itself...
. Most of the lesions that result from this infection are found in the basal ganglia
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...
. As long as the diagnosis is not missed, this type of hemiballismus can be treated just as well as in patients without HIV
HIV
Human immunodeficiency virus is a lentivirus that causes acquired immunodeficiency syndrome , a condition in humans in which progressive failure of the immune system allows life-threatening opportunistic infections and cancers to thrive...
.
Treatments
When treating hemiballismus, it is first important to treat whatever may be causing the manifestation of this disorder. This could be hyperglycemiaHyperglycemia
Hyperglycemia or Hyperglycæmia, or high blood sugar, is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a glucose level higher than 13.5mmol/l , but symptoms may not start to become noticeable until even higher values such as 15-20 mmol/l...
, infections, or neoplastic lesions. 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
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
is effective in about ninety percent of patients. Perphenazine
Perphenazine
Perphenazine is a typical antipsychotic drug. Chemically, it is classified as a piperazinyl phenothiazine. It has been in clinical use for decades....
, 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 chlorpromazine
Chlorpromazine
Chlorpromazine is a typical antipsychotic...
are standard choices for treatment. Scientists are still unsure as to why this form of treatment works, as dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
has not been directly linked to hemiballismus.
Anticonvulsants
An anticonvulsant called 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...
has helped patients in three cases and may be a viable treatment for the future.
ITB Therapy
Intrathecal baclofen (ITB) therapy is used to treat a variety of movement disorders such as 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....
and multiple sclerosis
Multiple sclerosis
Multiple sclerosis is an inflammatory disease in which the fatty myelin sheaths around the axons of the brain and spinal cord are damaged, leading to demyelination and scarring as well as a broad spectrum of signs and symptoms...
. 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
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...
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
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...
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
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
.
Antipsychotics
In one case, a patient had not been responding to haloperidol
Haloperidol
Haloperidol is a typical antipsychotic. It is in the butyrophenone class of antipsychotic medications and has pharmacological effects similar to the phenothiazines....
, thus the physician tried olanzapine
Olanzapine
Olanzapine is an atypical antipsychotic, approved by the FDA for the treatment of schizophrenia and bipolar disorder...
. 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
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
or 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...
of the globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
are procedures that can be used on humans. Usually, lesioning is favored over 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...
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 suffering from 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.Further Questions
Due to the rarity of this disorder, scientists know very little about the details of hemiballismus. There are still many unanswered questions such as:•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 basal ganglia
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...
besides 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...
. Why is this? 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 globus pallidus
Globus pallidus
The globus pallidus also known as paleostriatum, is a sub-cortical structure of the brain. Topographically, it is part of the telencephalon, but retains close functional ties with the subthalamus - both of which are part of the extrapyramidal motor system...
seems to reduce hemiballistic movements.
•Why does blocking dopamine
Dopamine
Dopamine is a catecholamine neurotransmitter present in a wide variety of animals, including both vertebrates and invertebrates. In the brain, this substituted phenethylamine functions as a neurotransmitter, activating the five known types of dopamine receptors—D1, D2, D3, D4, and D5—and their...
help reduce patients’ symptoms?
Conclusion
Hemiballismus is a rare movement disorder that is caused primarily by damage to various areas in 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...
. While a classical model for this disorder was developed in the 1950s, new discoveries are causing that model to shift. New treatments are also emerging, allowing for better control of symptoms as well as affecting those who did not respond to standard treatment. The prognosis for patients with this disorder is very good, as research in the area is continuing to reveal new insights into the pathophysiology. However, there are still many unanswered questions about this unusual movement disorder and scientists and clinicians are still learning new information as they probe deeper into the brain.
External links
- MR, CT Imaging Diabetic Hyperglycemic Hemiballismus/Hemichorea