1. Causes

2. Mechanism

3. Diagnosis

4. Management

5. Research directions

6. History

7. References

8. External links

A variety of causes have been discovered to date, including damage or degradation of the cerebellum due to neurodegenerative diseases, trauma, tumor, stroke, or toxicity. There is currently no established pharmacological treatment; however, some success has been seen using treatments designed for essential tremors.^[1][3]

Causes

Intention tremors are common among individuals with multiple sclerosis (MS). One common symptom of multiple sclerosis is ataxia, a lack of coordinated muscle movement caused by cerebellar lesions characteristic of multiple sclerosis. The disease often destroys physical and cognitive function of individuals.

Intention tremors can be a first sign of multiple sclerosis, since loss or deterioration of motor function and sensitivity are often one of the first symptoms of cerebellar lesions.^[1][4]

Intention tremors have a variety of other recorded causes as well. These include a variety of neurological disorders, such as stroke, alcoholism, alcohol withdrawal, peripheral neuropathy, Wilson's disease, Creutzfeldt–Jakob disease, Guillain–Barré syndrome and fragile X syndrome, as well as brain tumors, low blood sugar, hyperthyroidism, hypoparathyroidism, insulinoma, normal aging, and traumatic brain injury.^[1][5][6][7] Holmes tremor, a rubral or midbrain tremor, is another form of tremor that includes intention tremors, among other symptoms. This disease affects the proximal muscles of the head, shoulders, and neck. Tremors of this disease occur at frequencies of 2–4 Hz or more.^[8]

Intention tremor is also known to be associated with infections, West Nile virus, rubella, H. influenza, rabies, and varicella.^[1][9] A variety of poisons have been shown to cause intention tremor, including mercury, methyl bromide, and phosphine.^[1][10][11] In addition, vitamin deficiencies have been linked to intention tremor, especially deficiency in vitamin E.^[12] Pharmacological agents such as anti-arrhythmic drugs, anti-epileptic agents, benzodiazepine, cyclosporine, lithium, neuroleptics, and stimulants have been known to cause intention tremor.^[3] Some ordinary activities including ingesting too much caffeine, cigarettes, and alcohol, along with stress, anxiety, fear, anger and fatigue

have also been shown to cause intention tremor by negatively affecting the cerebellum, brainstem, or thalamus, as discussed in mechanisms.^[5]

Mechanism

Intention tremors that are caused by normal, everyday activities, such as stress, anxiety, fear, anger, caffeine, and fatigue do not seem to result from damage to any part of the brain. These tremors instead seem to be a temporary worsening of a small tremor that is present in every human being. These tremors generally go away with time.^[5]

More persistent intention tremors are often caused by damage to certain regions of the brain. The most common cause of intention tremors is damage and/or degeneration in the cerebellum. The cerebellum is a part of the brain responsible for motor coordination, posture and balance. It is responsible for fine motor movements. When the cerebellum is damaged, a person may have difficulty executing a fine motor movement, such as attempting to touch one's nose with one's finger. One common way for the cerebellum to become damaged is through the development of cerebellar lesions.^[13] The most common site for cerebellar lesions that lead to intention tremors has been reported to be the superior cerebellar peduncle, through which all fibers carrying information to the midbrain pass, and the dentate nucleus, which is also responsible for linking the cerebellum to the rest of the brain.^[3] Alcohol abuse is one typical cause of this damage to the cerebellum. The alcohol abuse causes degeneration of the anterior vermis of the cerebellum. This leads to an inability to process fine motor movements in the individual and the development of intention tremors. In Multiple Sclerosis, damage occurs due to demyelination and neuron death, which again produces cerebellar lesions and an inability for those neurons to transmit signals.^[13] Because of this tight association with damage to the cerebellum, intention tremors are often referred to as cerebellar tremors.^[1]

Intention tremors can also be caused as a result of damage to the brainstem or thalamus. Both of these structures are involved in the transmission of information between the cerebellum and the cerebral cortex, as well as between the cerebellum and the spinal cord, and then on to the motor neurons. When these become damaged, the relay system between the cerebellum and the muscle which it is trying to act upon is compromised, resulting in the development of a tremor.^[13]

Diagnosis

A working diagnosis is made from a neurological examination and evaluation. Parts of a complete examination include a physical examination, MRI, patient history, and electrophysiological and accelerometric studies. A diagnosis of solely intention tremor can only be made if the tremor is of low frequency (below 5 Hz) and without the presence of any resting tremors.^[1] Electrophysiological studies can be useful in determining frequency of the tremor, and accelerometric studies quantify tremor amplitude. MRI is used to locate damage to and degradation of the cerebellum that may be causing the intention tremor. Focal lesions such as neoplasms, tumors, hemorrhages, demyelination, or other damage may be causing dysfunction of the cerebellum and correspondingly the intention tremor.^[14]

Physical tests are an easy way to determine the severity of the intention tremor and impairment of physical activity. Common tests that are used to assess intention tremor are the finger-to-nose and heel-to-shin tests. In a finger-to-nose test, a physician has the individual touch their nose with their finger while monitoring for irregularity in timing and control of the movement. An individual with intention tremors will have coarse side-to-side movements that increase in severity as the finger approaches the nose. Similarly, the heel-to-shin test evaluates intention tremors of the lower extremities. In such a test, the individual, in a supine position, places one heel on top of the opposite knee and is then instructed to slide the heel down the shin to the ankle while being monitored for coarse and irregular side-to-side movement as the heel approaches the ankle.

Important historical elements to the diagnosis of intention tremor are:

1. age at onset
2. mode of onset (sudden or gradual)
3. anatomical affected sites
4. rate of progression
5. exacerbating and remitting factors
6. alcohol abuse
7. family history of tremor^&91;15&93;
8. current medications^&91;12&93;

Secondary symptoms commonly observed are dysarthria (a speech disorder characterized by poor articulation and slurred speech), nystagmus (rapid involuntary eye movement, especially rolling of the eyes), gait problems (abnormality in walking), and postural tremor or titubation (to-and-fro movements of the neck and trunk). A postural tremor may also accompany intention tremors.^[1][12]

Management

It is very difficult to treat an intention tremor.^[16] The tremor may disappear for a while after a treatment has been administered and then return. This situation is addressed with a different treatment. First, individuals will be asked if they use any of the drugs known to cause tremors. If so, they are asked to stop taking the medication and then evaluated after some time to determine if the medication was related to the onset of the tremor. If the tremor persists, treatment that follows may include drug therapy, lifestyle changes, and more invasive forms of treatment, such as surgery and thalamic deep brain stimulation.^[14]

Intention tremors are known to be very difficult to treat with pharmacotherapy and drugs. Although there is no established pharmacological treatment for an intention tremor, several drugs have been found to have positive effects on intention tremors and are used as treatment by many health professionals. Isoniazid, buspirone hydrochloride, glutethimide, carbamazepine, clonazepam, topiramate, zofran, propranolol and primidone have all seen moderate results in treating intention tremor and can be prescribed treatments. Isoniazid inhibits γ-aminobutyric acid-aminotransferase, which the first step in enzymatic breakdown of GABA, thus increasing GABA, the major inhibitory neurotransmitter in the central nervous system. This causes a reduction in cerebellar ataxias. Another neurotransmitter targeted by drugs that has been found to alleviate intention tremors is serotonin. The agonist buspirone hydrochloride, which decreases serotonin's function in the central nervous system, has been viewed as an effective treatment of intention tremors.^[1]

A more radical treatment that is used in individuals who do not respond to drug therapy, physical therapy, or any other treatment listed above, with moderate to severe intention tremors, is surgical intervention. Deep brain stimulation and surgical lesioning of the thalamic nuclei has been found to be an effective long-term treatment with intention tremors.

Deep brain stimulation treats intention tremors but does not help related diseases or disorders such as dyssynergia and dysmetria.^[17] Deep brain stimulation involves the implantation of a device called a neurostimulator, sometimes called a 'brain pacemaker'. It sends electrical impulses to specific parts of the brain, changing brain activity in a controlled manner. In the case of an intention tremor, the thalamic nuclei is the region targeted for treatment. This form of treatment causes reversible changes and does not cause any permanent lesions. Since it is reversible, deep brain stimulation is considered fairly safe: Reduction in tremor amplitude is almost guaranteed and sometimes resolved. Some individuals with multiple sclerosis have seen sustained benefits in MS progress.^[18]

Research directions

Research has focused on finding a pharmacological treatment that is specific for intention tremor. Limited success has been seen in treating intention tremor with drugs effective at treating essential tremor.^[12] Clinical trials of levetiracetam, typically used to treat epilepsy, and pramipexole, used to treat resting tremor, were completed in 2009-2010 to establish their effectiveness in treating kinetic tremor.^[20][21] A clinical trial for riluzole, typically used to treat amyotrophic lateral sclerosis, was completed at the Sapienza University of Rome to evaluate its effectiveness of treating cerebellar ataxia and kinetic tremor.^[22]

History

In 1868, French neurologist Jean-Martin Charcot first characterized the distinction between multiple sclerosis (MS), with its resulting intention tremor, and the resting tremor characteristic of Parkinson's disease. Intention tremor became known as part of Charcot's triad{{citation needed|date=April 2018}} (not to be confused with the Charcot triad of acute cholangitis) which, along with nystagmus and scanning speech, act as strong indications of MS.^[23]

References

External links

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