Management strategies in tremors: A bird's eye view
Correspondence Address: Source of Support: None, Conflict of Interest: None DOI: 10.4103/neuroindia.NI_749_17
Source of Support: None, Conflict of Interest: None
Tremor is an intrinsic part of movements made by normal individuals which is of an extremely small amplitude not visible to the naked eye. A neurosurgeon experiences normal physiological tremors after weight-lifting exercises and during the performance of surgery under a high magnification utilizing the operating microscope. The mechanics of joints determine the presence of oscillations; a complete ball-and-socket joint (such as the hip joint) is less likely to have oscillatory movements in comparison to a half-socket joint (such as the shoulder joint). In addition to the oscillatory movements, stiffness of the muscles around the joint also contribute to the tremulousness around the joints. Physiological tremor occurs at a frequency range of 8-12 Hz, and is more often noted at the distal joints than at the proximal joints. It can be enhanced by stress, anger, anxiety, excessive fatigue and sympathomimetic drugs. Interestingly, the physiological tremor increases in amplitude and reduces in frequency when the person is subjected to stress, as evidenced by an increased peripheral load. The phenomenon of tremor is dependent on the central oscillatory mechanisms in central neurological disorders.
Tremor is accentuated by certain positions and is discussed using terms, such as tremor at rest, during action, and those associated with posture or contraction.
Resting tremors occur in a body part at rest, completely supported against gravity and are not voluntarily activated, at a frequency of 3 to 6 Hz. Its amplitude is increased on activation and it disappears or diminishes on voluntary activity. When the arm is left in the position in which tremor was originally present, the tremor can recur after sometime. It is generated by central loop mechanisms. Its examples include the Parkinson's disease, multi-system atrophy, progressive supranuclear palsy, drug induced tremor, psychogenic tremor or rubral tremor.
Action tremor is a tremor generated by voluntary action and occurs at a frequency of 3 to 10 Hz. The action may be related to posture, contraction or voluntary movement. Its examples include the cerebellar, rubral or psychogenic tremor.
Postural tremor is noted while maintaining a position against gravity and occurs at a frequency of 5 to 9 Hz. Its examples include physiologic and psychogenic tremors, alcohol or drug induced tremors, essential tremors or those due to metabolic disturbances.
Isometric tremor is due to contraction of a group of muscles against resistance.
Kinetic tremor occurs during any voluntary movement which may or may not have a purpose. Tremors which occur on movement with a purpose are termed as intention tremors; and, tremors which occur on purposeless movements are called simple kinetic tremors.
Clinical assessment of tremor
Tremor, a rhythmic involuntary oscillatory movement of a body part, is a motor manifestation of various neurological disorders including idiopathic Parkinson's disease and atypical Parkinson's diseases. It is the most common of all involuntary movements and can affect the hands, arms, legs, eyes, face, head, vocal cords, and trunk. Tremor is easily detectable and is an early sign in several conditions, making it an important symptom to be understood. Tremors are studied using surface electromyography recordings and the movements are recorded using the accelerometer., This permits the study of the amplitude and frequency of tremor. The physiological tremors in a normal individual occur at a frequency of 6-12 Hz. The pathological tremors can be measured as low (<4Hz), medium (4-7Hz), or high (>7Hz) frequency tremors.
The tremor is described using its certain essential aspects. These include the topography of the tremor (involvement of the hands, arms, legs, eyes, face, head, vocal cords, and trunk); its activation by rest, posture or intention; its classification into simple or task specific tremor; and, the frequency of the tremor (low, medium or high). Several rating scales have been used to decide the clinical spectrum of the tremor and motor disability. The most commonly used scales are the unified Parkinson's disease rating scale (UPDRS), the essential tremor rating scale (ETRS), and the clinical rating scale of tremor.
Based on their specific clinical features, tremors are grouped into syndromes that can be separated on the basis of clinical observations. Movement Disorder Society ad hoc scientific committee issued a consensus statement, classifying tremors as per the clinical assessment of the patients.
The categories include physiologic tremor; enhanced physiologic tremor syndrome; essential tremor group (including classic tremor, indeterminate tremor, primary orthostatic tremor and task or position specifi c tremor [writing and isolated voice tremor]); dystonic tremor syndromes (including dystonic tremor, tremor associated with dystonia, and dystonia gene associated tremor); Parkinsonian tremor syndromes; cerebellar tremor syndromes; Holmes' tremor; palatal tremor syndrome; drug induced and toxic tremor syndromes; and, tremor syndromes in peripheral neuropathy [Videos 1-3].
Various illnesses affect different body parts and areas of the brain leading to different tremor manifestations. Apart from neurological disorders, tremor can be a manifestation of the underlying systemic illnesses, intoxications, drugs, poisoning and deficiencies. These can be listed as:
Neurodegenerative, hereditary and idiopathic: Essential tremor, tremor of Parkinson's disease (PD) and parkinsonian disorders, task specific tremors; tremors due to inflammatory lesions, infections, trauma and tumors: Multiple sclerosis; tremors in peripheral neuropathy: Guillain Barre syndrome; tremors associated with metabolic syndromes and poisoning: Hyperthyroidism, liverdysfunction, mercury poisoning, nicotine poisoning, B12 deficiency; and, drug induced tremor: Sympathomimetics, or steroids.
Routine blood tests include serum electrolytes, liver and renal function tests, thyroid function tests, serum calcium and parathormone levels, and specific investigations such as serum ceruloplasmin.
The treatment for various types of tremors is as follows:
In postural tremors, beta blockers, primidone, acetazolamide, clonazepam, botulinium toxin, brain gabapentin, deep brain stimulation and thalamotomy have been tried. In resting tremors, levodopa-carbidopa combination, anticholinergics and anti Parkinsonism More Details agents have been given. In severe cases, deep brain stimulation, pallidotomy or thalamotomy have been administered. In action tremors, wrist weights and isoniazid are recommended.
The guidelines for the diagnosis of essential tremor (ET) have been given., This type of tremor causes bilateral action tremors of hands and forearms in the absence of tremor at rest. There are no neurological signs present except for cogwheel rigidity. These patients may, however, have the presence of an isolated head tremor with normal posture. They are usually of a long duration of greater than 3 years, and often have a family history of tremors. In the presence of unilateral or focal tremors, rest or leg tremors, rapid or sudden onset tremors, an abnormal head posture or in the presence of drug treatment, a pathological tremor rather than an essential tremor should be considered.
Propranolol and primidone are the cornerstones of maintenance medical therapy for essential tremor. These medications provide a good benefit, reducing tremor amplitude in approximately 50-70% of patients.,, Other medications such as clozapine, gabapentin, mirtazipine, alprazolam, and clonazepam have also been tried.
Rationale of surgical management
Stereotactic lesioning of ventral intermediate (VIM) nucleus of the thalamus produces excellent results. Jankovic et al., retrospectively analyzed the outcomes of 60 patients (62 patient sides) with medically intractable tremor, who underwent stereotactic thalamotomy. Forty two of of these 60 patients had Parkinson's disease, 6 had essential tremor, 6 had cerebellar tremor, and 6 had post-traumatic tremor. The patients were followed up for 13 years, and reportedly, 86% of the patients with Parkinson's disease, 83% of the patients with essential tremor, 67% of the patients with cerebellar tremor, and 50% of the patients with post-traumatic tremor had cessation of, or moderate-to-marked improvement in their contralateral tremor, with a concomitant improvement in function. The VIM thalamotomy can be performed using radiofrequency lesion generator, using gamma knife radiosurgery, and by administering focused ultrasound. The popularity of the less invasive methodology of radiosurgical thalamotomy and magnetic resonance guided focused ultrasound (MRgFUS) is growing and is showing encouraging results. Niranjan et al., reported an effective relief for medically refractory, disabling, bilateral tremor without increased risk of neurological complications by staging the thalamotomy procedure. This procedure was used as an alternative treatment in patients not eligible for deep brain stimulation. MRgFUS VIM thalamotomy administered in order to relieve medication-resistant tremor, has been reported to be safe and effective in patients with ET, PD, and ET-PD, with less adverse events reported compared to the other approaches.
Stereotactic thalamotomy is less expensive than deep brain stimulation, does not require any hardware placement, and has been demonstrated to provide long-term efficacy. Its potential adverse effects include intracerebral hemorrhage, motor weakness, dystonia, speech disturbance, and memory loss.
Unilateral thalamic deep brain stimulation (DBS) is a safe and effective treatment of ET and the tremor of PD, reporting an average of 83% reduction in the contralateral arm tremor. Benabid et al., reported the effects of chronic VIM stimulation to be reversible, adaptable, and well tolerated even by patients undergoing bilateral surgery. Interestingly, a high incidence of physiological tolerance to anti-tremor effects of thalamic DBS is noted unlike the benefits in other symptoms of Parkinson's disease and can be as high as 9% even in the presence of an optimal location of the DBS lead placement. Both lesioning and stimulation thalamic surgery produce adverse effects with their effect on speech increasing three folds, that are worse with left-sided or bilateral procedures. This effect was higher after a thalamotomy compared to a DBS. Attempts have been made to perform a unilateral thalamotomy and a contralateral DBS [Figure 1] and [Figure 2].
During the past two decades, significant advances have been achieved in tremor research and its management. Though the pathophysiology still remains poorly understood, the clinical assessment and its description is well classified. Advances in the field of medications and surgery have allowed better treatment, with less invasive options for tremors becoming popular amongst the clinicians. This progress has become possible due to the progress in imaging that has led to a better precision of the techniques.
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Conflicts of interest
There are no conflicts of interest.
[Figure 1], [Figure 2]