ORIGIN
When motor units become entrained, e.g., due to stress & anxiety, drugs, or cold (as in shivering), physiological tremor (PT) develops into exaggerated or enhanced physiologic tremor (EPT). EPT has the same peripheral and central components as PT, but there is greater participation of the stretch reflex and of the 8–12 Hz central oscillator. PT is the result of numerous factors including the heart beat (cardioballistic thrust), low pass filtering properties of striated muscle, motor neurone firing, and synchronisation by spindle feedback.
CAUSES OF EPT
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Drug Induced |
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Antiarrhythmics |
Amiodarone, mexilitine, procaidamide |
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Antidepressant |
Amitriptyline, Lithium, SSRIs |
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Anti-epileptics |
Valproic acid, Lamotrigine |
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Bronchodilators |
Salbutamol |
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Chemotherapy |
Tamoxifen, cytarabine, ifosfamide |
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GI drugs |
Metoclopramide, cimetidine |
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Hormones |
Thyroxine, calcitonin, medroxyprogesterone |
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Immunosuppressants |
Tacrolimus, cyclosporine, interferon-alpha |
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Methylxanthines |
Theophylline, caffeine |
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Neuroleptics* |
Haloperidol, quetiapine, thioridazine, cinnarizine |
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Toxins |
Mercury, lead, manganese, alcohol, toluene, cocaine |
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Metabolic Disease associated |
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Thyroid |
Hyperthyroidism |
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Parathyroid |
Hyperparathyroidism |
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Cation Deficiency |
Hyponatraemia, hypocalcaemia, hypomagnesemia |
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Liver |
Hepatic Encephalopathy |
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Kidney |
Renal Failure |
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Vitamin |
Vitamin B12 deficiency |
CLINICAL FEATURES
Enhanced physiologic tremor is typically a high-frequency (8–12Hz), low-amplitude, mostly postural, bilateral tremor. In general, EPT does not affect activities of daily living, except in severe cases, and is potentially reversible if the cause is eliminated. Drugs and toxins, such as caffeine, commonly induce this form of tremor. Also, tremor intensifies with anxiety, stress, and after strenuous exercise. Drug-induced tremors can present with the whole range of clinical features of tremors (e.g. rest and action tremors) depending on the drug. Rest tremor can occur in isolation or as part of drug-induced Parkinsonism secondary to the use of antipsychotics, and can be clinically indistinguishable from PD tremor. The parkinsonian side effects of neuroleptics and other dopamine-blocking agents often persist for 6 months or longer after the offending agent is eliminated.
With respect to lithium in particular, it can frequently cause postural and kinetic hand tremor, which is unrelated to the dose and is reversible. However, a more generalized tremor can also be caused by its intoxication (also accompanied by confusion and other neurological signs). In addition, lithium may result in an irreversible intention tremor caused by cerebellar toxicity due to prolonged use, although intention tremor is not typical for enhanced physiologic tremor. Patients with PD, ET, and other hyperkinetic movement disorders (e.g., chorea, dyskinesia) often note that their involuntary movements are more intense from time to time, which is likely due to EPT.
(vv)EPT.mp4(tt)
From: Shanker VL. Case Studies in Tremor. Neurol Clin. 2016 Aug;34(3):651-65.
EXAMINATION
Very subtle tremor (e.g. EPT) can be visually demonstrated by placing a piece of paper over the outstretched hands and watching the ripple from the paper. Tremor may become most obvious when hands are outstretched such as holding a laser pointer. Spiral drawings are not tremulous, and there is no hand tremor while pouring water.
AGE OF ONSET
Increasing prevalence with age. However, 8% of healthy patients have enhanced physiologic tremor of central origin, with a frequency of 9–12 Hz (young patients) or 5–7 Hz (elderly)1.
DIAGNOSIS
In enhanced physiologic tremor, following weight loading, the tremor frequency peak decreases by more than 1 Hz, or there is a second tremor frequency peak at a lower frequency. When EPT becomes clinically symptomatic with posture or movement without provoking factors, it becomes phenomenologically similar to ET and may be difficult to separate from ET early in its course.
DIFFERENTIAL DIAGNOSIS
- Major differential is ET, but typically, the duration of EPT is less than the 3 years required by the definition of ET.
- Rhythmic cortical myoclonus.
DIAGNOSTIC TESTS
Limb weights reduce both the amplitude and frequency of EPT, but reduce the amplitude without altering the frequency in ET. This test is specific but insensitive2.
TREATMENT
Usually a single dose of a beta-blocking agent (e.g. propranolol 30–100 mg) just before a stressful situation can help to suppress this transient tremor. In contrast to ET, other beta-blockers have a similar effect because they probably work on the peripheral mechanisms of this tremor. In other cases of EPT, such as drug related, options are limited. If is not possible to stop or change the medication, propranolol may be tried in action tremors providing it does not have negative interactions with the causative drug. It has been shown to be effective in a small open series of valproate-induced tremors. If valproate cannot be stopped, a marked attenuation of the tremor has been reported with the addition of acetazolamide. The treatment attempts for tardive tremor have been with amantadine, trihexyphenidyl, clozapine or tetrabenazine. Vim DBS might be also effective in these tremors.