Essential Tremor Flashcards
Tremor - Definition
Tremor Activation Behaviours
- Tremor is an involuntary, rhythmic, oscillatory movement of a body
part
Resting
Resting remor –> PD
* present in absence of voluntary muscle contraction
Action
* present during voluntary muscular contraction
Action tremor: intentioally doing movement
- Postural
- present while voluntarily maintaining a posture against gravity
- Kinetic
- present during movement
- Isometric
- result of muscular contraction against a rigid stationary object
- Task specific
- occurs only when performing a specific task
Essential tremor = action tremor for most part
Knietic = action tremor
Postural when you change positions = essential tremor
Classification of
Tremor
- Physiologic Tremor (8-12 Hz)
- Normal, fine tremor in hands while maintaining posture or executing an action
- Can be exacerbated by stress, anxiety, hypoglycemia, hypothermia, medications
physiologic tremor emerges under some stressful conditions. And when stressors’ removed, the tremor resolves - Rest Tremor (3-6 Hz)
- In idiopathic PD, MSA
- Cerebellar tremor (4-6 Hz)
- Common causes: stroke, MS, TBI
- Evidence during slow movements
- Psychogenic tremor
- Orthostatic tremor (13-18 Hz)
- Rapid lower limb tremor when moving from supine or seated to standing
- Tremor ceases upon walking
- Essential tremor (4-12 Hz
Essential Tremor (ET)
ET is a kinetic tremor with or without postural tremor
Simple ET defined as an
1. isolated tremor syndrome of bilateral upper limb action tremor
2. of at least three years duration
3. with or without tremor in other locations (e.g., head, voice, lower limbs)
4. an absence of other neurological signs such as dystonia, ataxia or
parkinsonism
ET Plus defined as:
* tremor with the characteristics of ET
* additional neurological signs such as impaired tandem gait, questionable dystonic
posturing, rest tremor, memory impairment or other mild neurologic signs of
unknown significance that do not suffice to make an additional syndrome
classification or diagnosis.
3 yrs: patients can appear as if they might have Parkinson disease. We’re checking to see if there’s progression
Presentation - Contrast
Feature PD ET
Usual duration of symptoms before medical
contact
6–12 mo
Usually several years or more
Family history
Generally negative (5%–15% with an affected first-degree relative)
Often positive (>60%), autosomal dominant
Response to small amount of alcohol:
Little or none
Often improves
Position of maximal activation:
Rest
Maintenance of posture or with movement
Frequency 3–6 Hz 6–12 Hz
Morphology:
Pill-rolling
Flexion-extension
Onset:
Unilateral Bilateral
Body parts affected:
Upper limb, lower limb, chin, lips, ortongue
Upper limb, head, voice
Handwriting Micrographic, atremulous Normal size, tremulous
Associated signs (eg, bradykinesia,
hypomimia)
Present Absent
Is the tremor present when walking? Yes No
Pathophysiology
- The inferior olivary nucleus and cerebellum are involved in
generation and propagation of abnormal oscillatory activity - In patients diagnosed with tremor, studies showed:
- Cerebellar neuronal damage
- ↓ CSF concentrations of GABA, glycine, serine, ↑ glutamate
- Abnormalities in GABA-A receptors
- Increased levels of norepinephrine in the locus ceruleus, dentate nucleus,
and cerebellar cortex - Suggested that ET may actually be a number of unique disorders
- Differences from one patient to another
- Changes involved in NT, receptors, cellular damage
area of cerebellum targeted for surgery
differences in various neurotransmitters, definitely cerebellar damage is found. It means patients can still do other activities, but obviously the cerebellum is important for movement.
Genetics
Autosomal dominant
* 60% of those with disease have 1st degree relative with ET
* 80% of early onset ET more frequently associated with positive FHx
- several single-nucleotide polymorphisms are associated with essential
tremor - Replicated with the gene that encodes LINGO1
- protein that inhibits cell differentiation during development, axonal
regeneration, synaptic plasticity - Genetic testing
- Not standard
- To date only 1 strong genetic association
Epidemiology
- Most common MDO
- 8x more common than PD
- Associated with age
- Worldwide affects 1% of the population
- 5% in people ≥60y
- 20% in people ≥95y
- Bimodal distribution for onset
- 15-20 years
- Can onset at birth
- Child-onset ET has a predominance in males
- 50-70 years
- Approximately 25-30% seek medical attention
- Approximately 8% receive medication for treatment
tremor is not diagnosed as, as quickly or as broadly as other movement disorders like Parkinson’s disease. But it is thought to be fairly common. So a lot of patients will self treat or they don’t need medication at all.
PD impairs fxn
Diagnosis and Assessment
- No biomarkers
- Physical exam
Assessment of tremor
* Physiologic – e.g. EMG
* Clinical – (handwriting, spiral drawing)
* Functional (maze tests, water cup hold)
* Impact – functional measures, QoL
* Onset – usually insidious
Exam/investigations to rule out:
* Drug withdrawal
* Hypothermia
* Hypoglycemia
* Pheochromocytoma
* Thyrotoxicosis
* Wilson’s disease
History
* Family history
* Medical history
Medication history
* Antiarrhythmics (amiodarone)
* Anticonvulsants (valproic acid)
* Antidepressants (SSRI, TCAs)
* Antihypertensives (methyldopa, reserpine)
* Antipsychotics
* Beta-agonists
* Cyclosporine
* Lithium
* Metoclopramide
* Methylxanthines (theophylline, caffeine)
* Thyroid preparations
* Substance use (amphetamines, cocaine)
* Response to alcohol
* Ephedrine
* Nicotine
Thyroid supplementation happens a lot in geriatrics as people age, their doses not adjusted. So they started on 150 μg when they’re younger and now after 20-25 years, it’s simply 2 high dose as their body changes.
Alcohol actually treats tremor
Patients with essential tremor can self treat and develop dependency and some misuse of alcohol.
Assessment
A – ET sentence
B – PD sentence (note
micrographia vs
tremulousness
Archimedes spiral
So we have patients eat, demonstrate how they might eat food that’s really hard to eat, like peas is one example or soup.
How much water spills when drinking or lifting
Drawing spiral and writing is very difficult\
There’s various ways all of these things can be scored so that if you were investigated at a movement disorder clinic, we would have scores for you. So we could compare how your rating improves or how your spiral improves from time-to-time
Clinical Presentation
Anatomic distribution
* Hands (85-95%)
* Head (can occur later in disease; 35-45%)
* Voice (15-20%)
* Legs (10-15%)
- Usually 4-12 Hz
Resolves with alcohol (in about 50-70% of patients)
* Peak effect 45-90 minute after ingestion
* May result in rebound after 3h
Progressive disease
* Spread/involve other parts of the body
* Greater amplitude in hands
* May worsen by 2-5%/year
Impact
- ADL (activities of daily living)
- E.g. brushing teeth, toileting, feeding
- Gait
- Speech
- Occupation: occupation doesn’t just mean your job, it just means how do you occupy your time, what do you do?
- Stigma: People automatically assume oldest person is just really nervous
- Psychiatric co-morbidities (up to 65%)
- Depression, social phobia, anxiety
- Approximately 10% of patients with ET report disability
- Questions to consider:
- If you have ET as a pharmacist, would you tell your employer?
- If you had to hire a pharmacist, would you hire someone with ET?
Goals of Therapy
- Currently there is no cure for ET
- General Goals
- Minimize disability
- Improve socialization
- Improve quality of life
- Patient specific goals
- E.g. put on necklace by self, eat soup
prevent any complications, especially psychiatric complications.
Treatment – Non-Pharmacologic
- Safety interventions
- E.g. Do not use pointed scissors
- Behavioural
- Place napkin between cup and saucer to avoid
rattling - Write with least disabled hand (?!)
- Avoid ordering foods that are difficult
- Devices
- Wrist weights (hands)
- Weighted utensils
- Plate guards
- Modified mouse/keyboard
not even a third of people seek medical attention because sometimes they tried to treat themselves.
So sometimes this is a helpful thing when patients give like little, little card saying, Hey, I have a disorder, I’m going to have a tremor. This is how it is. It’s a movement disorder, but I’m not intoxicated.
pharm tx level a
- No disease-modifying treatment
- Currently only symptomatic treatment
- Evidence of benefit
- Approximately 55% (range 50-70%) reduction in amplitude
- 30-50% of patients may not respond
- Level A Medications
- Primidone
- Propranolol
So these are the most effective drugs. We have RCTs and we know they’re effective
Pharmacologic Treatment – Level A
* Propranolol
- Dosing
- Start 10 mg BID
- Usual dosing range from 120-240 mg/day
- Up to 15% of responders may develop tolerance
- SE: bradycardia, bronchospasm (not great for asthma), dizziness, erectile dysfunction
- PRN – if episodic treatment needed
- e.g. going out for dinner
- There are some patients who choose to use it PRN. They’ll use an immediate release product in a certain period of time before they do an event like a presentation
- Scheduled – if condition is disabling
- IR or SR use may be appropriate
- Beta-blockers`
- Non-lipid soluble beta blockers (e.g. metoprolol) are not effective
- Medication must penetrate the CNS
start low because patients can often feel really, really fatigued. They get bradycardic. So we want to usually be at a much higher dose to control tremor if they’re gonna be taking it on a scheduled basis.
Crosses BBB = more AE but needed for central disorder
Again, something that is not lipid soluble is not going to work. It won’t get into the CNS
