Continuing Education Activity

An intention, rubral, cerebellar, or course tremor is defined as a rhythmic, oscillatory, and high amplitude tremor during a directed and purposeful motor movement, worsening before reaching the target. Intention tremors can be present with deficits in corticocerebellar tracts due to physiological or pathological disease. This activity reviews the definition, etiology, evaluation, and role of the interprofessional team in the treatment of intention tremors, and associated disorders.

Objectives:

• Identify the etiology of intention tremor medical conditions and emergencies.
• Outline the evaluation of intention tremor.
• Review the management options available for intention tremor.

Introduction

An intention, rubral, cerebellar, or course tremor is defined as a rhythmic, oscillatory, and high amplitude tremor during a directed and purposeful motor movement, worsening before reaching the target.[1][2][3] It is due to cerebellar dysfunction. It can affect precision in coordinated movements of speech muscles and limbs. The cerebellum, along with its sensory-motor white matter tracts, is responsible for motor coordination, posture and balance. The feedback mechanisms between the cerebellum, the cortex, and the brainstem become impaired, leading to kinetic errors, more prominent in fine motor skill tasks.[4] 

Intention tremor was first described by Jean-Martin Charcot in 1868, who noticed that multiple sclerosis (MS) patients could be differentiated from Parkinson disease (PD) patients by the type of tremor they present. MS is the most common cause of intention tremor. MS patients had intention tremors along with nystagmus and scanning speech, bearing his name as the Charcot's triad.[5]

Etiology

There are various causes of intention tremors:

• Physiological/psychiatric (e.g., anxiety, fear, anger, and fatigue)
• Iatrogenic (e.g., anti-epileptics such as phenytoin, and carbamazepine)
• Vascular (e.g., cerebellar infarct)
• Trauma (e.g., diffuse axonal injury)
• Neuroinflammatory or autoimmune (e.g., multiple sclerosis)
• Metabolic (e.g., hepatocerebral degeneration)
• Toxic (e.g., barbiturate overdose, alcohol dependence, mercury poisoning)
• Hereditary (e.g., Wilson disease)

Epidemiology

The epidemiology of intention tremor is challenging to ascertain, as it can be present in various disease at a different rate. Intention tremors can be present 9 % in head, 50% in the arms, and 27% in the legs.[4][6][7] Up to 38.5% of the patients with essential tremor can also have intention tremor and is correlated with a longer duration of the essential tremor and a younger age for the onset of the tremor. Prevalence can be as high as 44% of those patients with essential tremor.[8] Intention tremor is very rarely (4%) present in PD.[9]

Pathophysiology

In intention tremor, the central nervous system cerebellar feedback and error control centers are impaired. The relay system between the cerebellum and efferent muscle can be compromised, resulting in the action tremor. It is associated with damage to the superior cerebellar peduncle, dentate nucleus, and surrounding cerebellar tracts in the brainstem and the thalamus.[1] Thalamic nuclei involvement and feedback had also been implicated and are used as a neurophysiological basis for treatment management.[10]

A toxic disorder that is useful to examine the neuropathology of cerebellar degeneration is an alcohol abuse disorder. In a true alcoholic patient, cerebellar degeneration disorders involve Purkinje cells, including the molecular cell layer, with a distinct distribution, predominant in the anterior vermis.[11][12]

History and Physical

Clinical Symptoms

Patients with intention tremors usually complain of difficulties with activities of daily living, including drinking from a cup, grabbing utensils to eat, problems with coordination eye to an object, and problems with ambulation. Associated cerebellar signs can include nystagmus, dysmetria, dysdiadochokinesia, hypotonia, proprioception deficits, and gait ataxia.[1][3]

Physical Exam

• Finger-to-nose and heel-to-shin tests can be useful to evaluate for end-point intention tremors, especially when the patient is asked to do the maneuver quickly.
• Fine finger movements can be used as well to assess coordination and speed in tasks such as finger or foot tapping, buttoning/unbuttoning shirt, grabbing an object such as a cup or pencil.  The tremor will increase when the extremity is approaching the target.
• Another characteristic of intention tremors is that the oscillating amplitude can be decreased when the eyes are closed.
• Rapid alternating movement maneuvers can be used to identify dysdiadochokinesia.
• Proprioception of the great toes can be impaired as well. Gait testing may reveal wide-based ataxia, with difficulties with tandem gait and a positive Romberg. The patient may have slow saccadic movements and nystagmus.
• Depending on the etiology, patients may have increased reflexes and extensor Babinski reflexes.[3]

Evaluation

Magnetic resonance imaging (MRI) is the gold standard study to evaluate the brain and cerebellum. Many of the etiologies will be identified by this study. 

Specific etiologies should be evaluated as follows:

Physiological/psychiatric: a good history and physical, complete metabolic panel (CMP), psychiatric history, nonpharmacological management, stressful situations (anxiety, fear, anger, and fatigue).

Iatrogenic: a thorough review of home medications and establish a timeline to determine whether starting or discontinuing any particular medication could have triggered the tremor.

Vascular: a comprehensive stroke workup including a good history and physical, screening of vascular risk factors, A1C, lipid panel, blood pressure measurements, brain and vessel imaging (head computed tomographic (CT) scan, head CT angiography, CT perfusion, brain MRI), 2D Echocardiogram with bubble study, Holter monitoring.

Trauma: a CMP, complete blood count (CBC), coagulation studies, head CT scan, CT angiography, brain MRI, MR venous, electromyography, or nerve conduction.

Neuroinflammatory, autoimmune or paraneoplastic: CMP, CBC, erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), antinuclear antibodies, extractable nuclear antigen panel, Sjogren and lupus anticoagulant studies, antineutrophil cytoplasmic antibodies, angiotensin-converting enzyme test, head CT, brain and spine MRI, chest/abdomen/pelvis CT scan, and lumbar puncture with laboratory studies including cells with differential, glucose, protein, IgG index, myelin basic protein, oligoclonal bands, aquaporin four antibodies, myelin oligodendrocyte glycoprotein antibodies, paraneoplastic panel, flow cytometry/cytology.

Metabolic: CBC, CMP, vitamin deficiency workup, ammonia level, liver ultrasound, abdomen/pelvis CT scan with contrast, advanced metabolic testing. 

Toxic: urine toxicology, ethanol level, heavy metal testing.

Hereditary: CBC, CMP, ESR, CRP, copper/ceruloplasmin, slit eye lamp examination, head CT scan, brain MRI, genetic testing.

Treatment / Management

Treatment usually consists of treating the underlying disorder.

Noninvasive techniques: Include gait rehabilitation, visually guided techniques, tendon vibration, weighting extremities, positioning techniques, and manual techniques, all of which can be useful for the recovery of functional activities.[13]

Pharmacological treatment: There is no specific recommended treatment for intention tremor. Isoniazid is the most commonly used for patients with MS with results in about half of the patients, but others like botulinum toxin A, levetiracetam, 4-amino-pyridine, cannabis had been used.[13]

Invasive techniques: Thalamic deep brain stimulation can alleviate the tremor in MS, providing better functional performance.[14] Stereotactic radiosurgery thalamotomy at the nucleus ventralis intermedius with a median maximum dose of 140 Gy also provides good functional outcomes in patients with MS.[13][15] Radiofrequency thalamotomy had been successfully used in the past but has been replaced with the newer techniques of radiosurgery and deep brain stimulation as they had fewer adverse effects.

Differential Diagnosis

The differential diagnosis for intention tremor is physiological (essential tremor). Up to 38.5% of the patients with essential tremor can also have intention tremor.

The different etiologies have to be differentiated as they have divergent management. Iatrogenic (medication use) causes being the most common; however, serum laboratories, brain imaging, and cerebrospinal fluid studies may be used to distinguish between metabolic, neuroinfectious, neuroinflammatory, and paraneoplastic etiologies.[2]

Prognosis

The prognosis is dependent on the etiology of the intention tremor, but with rehabilitation, non-pharmacological, and pharmacological interventions, it should improve gradually. Permanent damage to cerebellar structures and tracts may cause irreversible dysmetria and intention tremors.

Complications

If the underlying cause is not addressed, intention tremors can lead to impairments in functional activities of daily living, which can be very frustrating for patients. On the bright side, there are no known life-threatening complications from intention tremors.

Consultations

Healthcare providers from the following department should be on-board while managing the patient with intention tremors:

• Neurology
• Movement disorder neurology
• Physical and occupational therapy
• Social services

Deterrence and Patient Education

Patients should be advised that if clinical symptoms are acute, they should seek care at the emergency room to rule out life-threatening diagnoses such as ischemic stroke and malignancy. If symptoms are gradual or intermittent, they should visit their primary care physician for a referral to a neurologist for evaluation and management.

Pearls and Other Issues

Here are some important points to take into consideration:

• Intention tremor is defined as a rhythmic, oscillatory, and high amplitude tremor during a directed and purposeful motor movement, worsening before reaching the endpoint.
• Incidence of intention tremor is challenging to ascertain, but the most common cause is essential tremor and physiological tremor (caused by stress, fear, anger).
• Feedback and feedforward centers are impaired, leading to deficits in fine motor movement, coordination, precision, and poor communication between tracts affecting the somatosensory, motor, and cerebellar function.
• It is associated with damage to the superior cerebellar peduncle, dentate nucleus, and surrounding cerebellar tracts in the brainstem and the thalamus.
• Intention tremors may be accompanied by other cerebellar dysfunction symptoms, including difficulties with activities of daily living (drinking from a cup, grabbing utensils, ambulating independently, eye-object coordination), nystagmus, slow saccades, dysmetria, dysdiadochokinesia, hypotonia, proprioception deficits, hyperreflexia, and ataxic gait.
• Treatment usually consists of treating the underlying cause of the tremor. Physical and gait rehabilitation can be useful for the recovery of functional activities.

Enhancing Healthcare Team Outcomes

At this time, there is no evidence-based study that guides the creation of an interdisciplinary team for intention tremor. However, a neurologist, movement disorder specialist, physical and occupational therapist, social worker, and geneticist should be consulted to provide the best care and quality of life for a patient and to inform medical decisions regarding long-term care.[2][4] [Level 5]