Essential tremor is chronic progressive neurological disease ( or perhaps family of diseases ) whose primary clinical feature is kinetic tremor of upper limbs , voice , head , face , chin , legs or a combination of these symptoms
A new term ET- Plus was coined in 2018 and classifies ET into two groups individuals with primary feature of ET – kinetic tremor individuals with additional neurological signs such as mild impaired memory , impaired tandem gait , subtle dystonic posturing , rest tremor or other neurological signs of unknown significance The two may co-exist within the same individual and having one seems to increase the risk of developing another.
ET is the most common tremor disorder worldwide ET is more prevalent than Parkinson’s disease or Alzheimer’s disease Metanalysis has shown - overall prevalence of 0.4 % to 0.9 % for all ages - 4.6 % to 6.3 % in populations above 65 ET prevalence increases with age ( as with most movement disorders ) Two peaks have been reported - young onset ( < 25 ) often with a + ve family history and alcohol responsiveness - late onset ( > 65 ) Children and young people can also be affected by ET No racial or gender differences
What happens -Pathogenesis remains unknown A link between ET and cerebellum is backed by evidence Several hypothesis have been made for e.g - loss or dysfunction of Purkinje fibers in the cerebellum - Lewy bodies within the locus coeruleus - presence of Torpedos which are ovoid enlargement of the proximal part of Purkinje axons and PC heterotopias ie misplacement of the PC stroma in the molecular layer of cerebellum Disturbed GABA- ergic mechanisms reduced GABAergic output GABAergic dysfunction in the cerebellar dentate nucleus & brainstem caused by neurodegeneration in these regions
It is known that transmission of ET is autosomal dominant with variable penetrance 1st degree relatives of ET patients are 4-5 times more likely to develop ET About 20 % to 90 % off patients will have a + ve family history of ED & this is more likely in young-onset cases No single gene has been identified yet Environmental factors have also been blamed as exposure to certain toxins.
Terminology can be confusing for us non-specialists-a quick recap Rest tremor happens when voluntary muscle activity is absent Action tremor -occurs during action for e.g when performing a specific task for e.g reaching for an object or bringing the object towards you. Action tremors are divided into postural , kinetic & intention tremors -> Postural tremor happens when a person voluntarily maintains a position against gravity for e. holding arms out-stretched in front -> Kinetic tremor happens with voluntary movement for e.g pouring , writing -> Intention tremor occurs when goal directed movement for e.g during finger-nose-movement and worsens as the body part in above case the finger approaches the target Amplitude -amount or range of movement caused by the tremor of a body part usually measured in cms or inches Frequency– tremor is a rhythmical movement and complete one cycle in similar fashion as the clock pendulum and frequency is the number of cycles it completes in 1 second. Measures in Hertz ( Hz ) ET usually has a frequency of 4 to 10 Hz
Presentation-Kinetic tremor involving hands and /or arms ( absent on rest ) Upper limbs typically b/l but asymmetric in nature dominant side affected more than non-dominant side Insidious onset and affects hands and arms in early stages Symptoms are generally progressive and can be potentially disabling Postural and / or kinetic tremor typically in the frequency range of 6 to 12 Hz In the beginning it may be intermittent during periods of stress or fatigue The frequency of the tremor decreases over time but the amplitude increases leading to functional disability The location of the tremor is 95 % in upper limbs ,34 % head , lower limb 20 % , voice 12 % , face 5 % and trunk 5 % Some patients may develop enhanced physiological tremor due to anxiety or other adrenergic mechanism which aggregates the underlying tremor.
The following questions may help in evaluation of ET When did this start Which parts of body are affected Was the onset insidious or sudden When does the tremor happen Any functional limitations Progression over time Any specific factors which make the tremor worse for e.g stress , caffeine or alcohol intake Do other family members suffer with tremor What affect does alcohol has on tremor – within a few minutes of ingestion and the following morning Any h/o head injury Full list of medications – beware medications which induce tremor include valproic acid , SSRIs , steroids , lithium , cyclosporine , beta adrenergic agonists , ephedrine , theophylline , tricyclic anti depressants and anti-psychotics.
Examination- Undertake a full neurological examination with particular attention to - specific features of tremor like amplitude , frequency , pattern and distribution ED can be elicited during two conditions (1 ) arms suspended against gravity in a fixed posture (2 ) goal directed activity ED becomes prominent when arms are held out-stretched It increases at the end of the goal directed movements such as drinking from a glass or finger-to-nose test It can be noticed during activities as eating , drinking , shaving and applying make up To elicit above you may ask the patient to draw an Archimedes spiral , draw a line , writing , pouring water into glass , drinking from a cup Enquire for other soft neurological symptoms which may suggest ET Plus
ED can also affect the head , the voice and uncommonly the face , legs and trunks. It is often mentioned in papers that if prominent tremors are seen in legs , Parkinson’s disease should be ruled out Head tremor ( more common in women and a late manifestation ) can be a yes-yes or no-no phenomena -it resolves in supine position
In about 50 % of patients symptoms improve with alcohol consumption H Boecker et al report that the alcohol-induced suppression of ET is mediated via a reduction of cerebellar synaptic over-activity resulting in increased afferent input to the inferior olivary nuclei Alcohol responsiveness is not pathognomic of ET
Four inclusion criteria’s-Isolated tremor syndrome of b/l upper limb action tremor Atleast 3 yr duration With or without tremor in other segments ( head , voice , lower limbs ) Absence of other neurological signs as dystonia , ataxia , parkinsonism
Isolated focal tremor (e.g voice , head ) Orthoststatic tremor with a frequency > 12 Hz Task or position specific tremors Sudden onset and stepwise deterioration
MRI may be considered if additional neurological signs are present to exclude other secondary causes DAT ( Dopamine transporter ) imaging has been proposed as a useful took to differentiate between tremor predominant PD from ET Uric acid has been studied as a biomarker for ET.
Distinguishing between ET/PD can be challenging Beware that it has been observed that 1/3rd of the patients who were diagnosed as ET were misdiagnosed with PD being the most common true diagnosis Various tremor types can be seen in both conditions Symptoms can be overlapping and some patients may actually meet the criteria for both diseases.
Symptoms may overlap and co-exist making the distinction between the two conditions difficult. In addition differences would be noted in nuerophysiological evaluation ( for e.g accelerometry and surface electromyography ) Archimedes spiral analysis is a useful aid Neuroimaging can be helpful in diagnostic evaluation.
Treatment is symptomatic Three broad categories of treatment are pharmacological , surgical & other therapies Further research is needed to manage this condition effectively When pharmacological treatment is considered propranolol & primidone are considered 1st line ( according to FDA & European Medicines Agency ) We would focus on these two medications – other treatment modalities are for the specialists and a cursory knowledge is enough in primary care There is no definitive cure for ET
Propranolol -First line and only beta blocker which is FDA approved Controlled trials inform - average effective dose is 185.2 mg/D - daily dose range is 60-800 mg/day - insufficient evidence that dose above 320 mg gives any additional benefit Prudent to start with a low dose and titrate gradually About 50 % of patients would respond Though to potentially reduce upper limb action tremor but has poor effect Small studies have shown that long-acting preparations are as effective as short acting formulations Evidence for use of propranolol comes from small RCTs mostly of a crossover design that only reported on result in the short term Use of other beta blockers is not recommended if patient is unable to take propranolol
Primidone -an anticonvulsant reduces high frequency repetitive firing of neurons and alteration of transmembrane Na and Ca channel ion movements -possible anti-tremor mechanism considered as an alternative when beta blockers cannot be used a more complex drug with potential for significant side effects as drowsiness , fatigue , nausea , depression , cognitive and behavioural adverse effects can be as effective as propranolol may improve hand tremor in the short term up to 10 weeks ( BMJ Cl Evidence 2015 ) typical starting dose is 50 mg best given before bed ( drowsiness potential )
Other therapies-You may hear a trial by specialists based on local guidance about the use of other medications as Topiramate Gabapentin / Pregabalin Benzodiazepines ( alprazolam & clonazepam ) Zonisamide Anti-psychotics Nimodipine Botox.
Surgical-Surgical options include Deep brain stimulation ( DBS ) Focused ultrasound Gamma knife
PATIENT INFORMATION LINKS
National Tremor Foundation– downloadable leaflet on ET https://tremor.org.uk/essential-tremor
National Institute of Neurological Disorders and Stroke – a comprehensive review https://www.ninds.nih.gov/Disorders/Patient-Caregiver-Education/Fact-Sheets/Tremor-Fact-Sheet
International Essential Tremor Foundation – the dedicated website for ET patients with a useful resource section Living with ET https://essentialtremor.org/
National Organization for Rare Disorders – Essential Tremor a good explainer for ET patients https://rarediseases.org/rare-diseases/essential-tremor/
Tremor Action Network online support group https://tremoraction.org/
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