Trem

rs
By Dr. Amir M. Hanafi PGY4
Nouf
Supervised by Dr. Youssef
Objectives
To know what is a tremor
To know the importance of identification of tremors in
1ary care
To know classification of tremors
To know whats the approach in a patient with tremors
To know the commonest tremors in 1ary care
To know when to refer a patient
To know the available treatment modalities in primary
care
What is a tremor?
Tremor is defined as:
involuntary
rhythmic
oscillatory movement of a body part
with a relatively constant frequency
and variable amplitude.
It is caused by alternating contractions of antagonistic
muscles
Importance of tremor identification
Tremor is the most common of all movement disorders.
The most common movement disorder encountered in
clinical practice.
no diagnostic standard to distinguish among common
types of tremor, which can make the evaluation
challenging.
establishing the underlying cause is important because
prognosis and specific treatment plans vary
considerably.
 The most common tremor in patients presenting to
primary care physicians is enhanced physiologic
tremor, followed by essential tremor and
parkinsonian tremor.
Classification of tremors
Action Occurs with voluntary contraction of muscle
Includes postural, isometric, and kinetic tremors
Postural Occurs when the body part is voluntarily maintained against gravity

Includes essential, physiologic, cerebellar, dystonic, and drug-induced tremors

Kinetic Occurs with any form of voluntary movement

Includes classic essential, cerebellar, dystonic, and drug-induced tremors

Intention Subtype of kinetic tremor amplified as the target is reached

Presence of this type of tremor implies that there is a disturbance of the

cerebellum or its pathways
Rest Occurs in a body part that is relaxed and completely supported against gravity

Most commonly caused by parkinsonism, but may also occur in severe essential
tremor
An essential tremor most commonly affects the ..?
A) Head
B) Voice
C) Tongue
D) Legs
E) Hands
A 65-year-old man presents to your office complaining of a right-hand
tremor. The patient reports the tremor is worse with sustained positions and
stressful situations. Surprisingly, a shot of scotch makes the tremor better.
He also reports a positive family history for tremors. There are no signs of
bradykinesia or rigidity. The most likely diagnosis is

A) Parkinsons
disease
B) Essential tremor
C) Huntingtons
disease
D) Caffeine
A 54-year-old previously healthy accountant sees you because of a
tremor which is most noticeable in his hands when he is holding something
or writing. He has noticed that it seems better after having a beer or two.
On examination, you note a very definite tremor when he unbuttons his shirt.
His gait is normal and there is no resting tremor. He has a previous history
of intolerance to -blockers. Of the following, which medication would be
the best choice for this patient?
A) Levodopa/carbidopa (Sinemet)
B) Amantadine (Symmetrel)
C) Primidone (Mysoline)
D) Lithium carbonate
Essential tremors (contd)
Essential tremor is an action
tremor, usually postural, but
kinetic and even sporadic
rest tremors have also been
described.
It is most obvious in the
wrists and hands when
patients hold their arms in
front of themselves
can also affect the head,
lower extremities, and voice.
PARKINSONISM
Parkinsonism is a clinical syndrome characterized by tremor,
bradykinesia, rigidity, and postural instability.
Many patients will also have micrographia, shuffling gait,
masked facies, and an abnormal heel-to-toe test.
Causes of parkinsonism include brainstem infarction, multiple
system atrophy, and medications that block or deplete
dopamine, such as methyldopa, metoclopramide, haloperidol,
and risperidone.
Idiopathic Parkinson disease is a chronic neurodegenerative
disorder; its prevalence increases with age. It is the most
common cause of parkinsonism.
PARKINSONISM
More than 70 percent of
patients with Parkinson
disease have tremor as
the presenting feature.
The classic parkinsonian
tremor begins as a low-
frequency, pill-rolling
motion of the fingers,
progressing to forearm
pronation/supination and
elbow flexion/extension.
PARKINSONISM
It is typically asymmetric,
occurs at rest, and
becomes less prominent
with voluntary
movement.
Although rest tremor is
one of the diagnostic
criteria for Parkinson
disease, most patients
exhibit a combination of
action and rest tremors.
ENHANCED PHYSIOLOGIC
TREMOR
A physiologic tremor is present in all persons.
It is a low-amplitude, high-frequency tremor at rest and
during action that is not reported as symptomatic.
This tremor can be enhanced by anxiety, stress, and
certain medications and metabolic conditions.
Patients with a tremor that comes and goes with
anxiety, medication use, caffeine intake, or fatigue do
not need further testing.
DRUG- AND METABOLIC-
INDUCED TREMORS
Patients with new-onset tremor should have a comprehensive
medication review.
Medications particularly prone to inducing or exacerbating tremor
are those that stimulate the sympathetic nervous system (e.g.,
amphetamines, terbutaline, pseudoephedrine) and psychoactive
medications (e.g., tricyclic antidepressants, haloperidol, fluoxetine).
When medication review reveals a likely culprit, a trial off of this
medication should be attempted.
Initial workup of tremor may include blood testing for hepatic
encephalopathy, hypocalcemia, hypoglycemia, hyponatremia,
hypomagnesemia, hyperthyroidism, hyperparathyroidism, and
vitamin B12deficiency.
Tremor causing medications
Amiodarone
Amphetamines
Atorvastatin (Lipitor)
Beta-adrenergic agonists (e.g., albuterol)
Caffeine
Carbamazepine (Tegretol)
Corticosteroids
Cyclosporine (Sandimmune)
Epinephrine
Fluoxetine (Prozac)
Haloperidol
Hypoglycemic agents
Lithium
Metoclopramide (Reglan)
Methylphenidate (Ritalin)
Pseudoephedrine
Terbutaline
Theophylline
Thyroid hormones
Tricyclic antidepressants
Valproic acid (Depakene)
Verapamil
CEREBELLAR TREMOR
The classic cerebellar tremor
presents as a disabling, low-
frequency, slow intention or
postural tremor, and is typically
caused by multiple sclerosis with
cerebellar plaques, stroke, or
brainstem tumors.
Other neurologic signs include
dysmetria (overshoot on finger-to-
nose testing), dyssynergia
(abnormal heel-to-shin testing
and/or atraxia), and hypotonia.
 PSYCHOGENIC TREMOR
Features consistent with
psychogenic tremor are abrupt
onset, spontaneous remission,
changing tremor characteristics,
and extinction with distraction.
Often, there is an associated
stressful life event.
Based on clinical experience, the
prevalence of psychogenic tremor is
thought to be high, but there are no
precise estimates.
PSYCHOGENIC TREMOR -
CHARECTERISTICS
Abrupt onset
Absence of other neurologic signs
Changing tremor characteristics
Clinical inconsistencies
Employed in allied health professions
Litigation or compensation pending
Multiple somatizations
Multiple undiagnosed conditions
No evidence of disease by laboratory or radiologic investigations
Presence of psychiatric disease
Presence of secondary gain
Reported functional disturbances in the past
Responsive to placebo
Spontaneous remission
Static course
Tremor increases with
attention, and lessens with distractibility
Unclassified tremor (complex tremors)
Unresponsive to antitremor medications
DYSTONIC TREMOR
Dystonic tremor is a rare tremor
found in 0.03 percent of the
population.
It typically occurs in patients
younger than 50 years.
The tremor is usually irregular
and jerky, and certain hand or arm
positions will extinguish the tremor.
Other signs of dystonia (e.g.,
abnormal flexion of the wrists) are
usually present.
WILSON DISEASE
Wilson disease is a rare,
autosomal recessive
disorder that manifests in
persons five to 40 years of
age, sometimes with a
wing-beating tremor.
Serum ceruloplasmin
level and 24-hour urinary
copper excretion should be
considered in young
patients presenting with
tremor to exclude this
potentially life-threatening
disease.
Diagnostic approach
Already present, enhanced
by stress and caffeine,

Abrupt onset, changing

character, stops by
distractions,
 Refer
ral

Refer
ral

Refer Refer
ral ral
Role of Imaging
Currently, the diagnosis of tremor remains primarily
clinical.
In difficult cases, single-photon emission computed
tomography (SPECT) to visualize the integrity of the
dopaminergic pathways in the brain may be useful to
diagnose Parkinson disease.
Plain CT and MRI are good choices to rule out secondary
causes of tremor (e.g., multiple sclerosis, stroke) when
the diagnosis of tremor is not obvious from history and
physical examination.
MOR
Essential tremors and Parkinsons

D ETAI
disease

E
Essential tremors
The most common pathologic tremor is essential
tremor.
In one-half of cases, it is transmitted in an autosomal
dominant fashion
affects 0.4 to 6 percent of the population.
most patients do not seek help for it until 70 years of
age because of its progressive nature.
up to 25 percent of those afflicted retire early or modify
their career path.
Essential tremors
ET is a type of postural and action tremor; these are
elicited during examination under two circumstances:
with the arms suspended against gravity in a fixed posture
during the course of goal-directed activity.
ET is referred to as familial tremor when there is a
family history.
The term "benign essential tremor" was used in the past
to distinguish ET from Parkinson disease.
However, the use of "benign" as a modifier for ET is best
omitted, since the tremor can be severe and disabling.
Essential tremors (contd)
It is generally bilateral and
interferes with ADLs.
Persons with essential tremor
typically have no other
neurologic findings; so, it is a
diagnosis of exclusion.
If the tremor responds to a
therapeutic trial of alcohol
consumption (two drinks per
day), the diagnosis of
essential tremor is assured.
Essential tremors (contd)
Essential tremor is an action
tremor, usually postural, but
kinetic and even sporadic
rest tremors have also been
described.
It is most obvious in the
wrists and hands when
patients hold their arms in
front of themselves
can also affect the head,
lower extremities, and voice.
Diagnosis
Dx contd
Dx contd
Non Pharmacological treatment
Find ways toreduce stressandrelax.
Avoid alcohol consumption. While small amounts of
alcohol seem to relieve essential tremor in some
patients, it may interact withmedicationsused to treat
ET and also have negative effects on the body, such as
alcohol dependency disorder orliverdamage. Most
experts do not recommend its use.
Consider taking a small dose of medication, such as
abeta-blocker, before a social outing; this may help to
reduce the tremors.
Non Pharmacological treatment
2
Avoid certain drugs that can aggravate tremor
likethyroidorasthma medicationsbefore attending a
social event. Be sure you check with your doctor first.
Avoid foods that containcaffeinelike sodas, coffee, tea,
andchocolate.
Place a napkin between cup and saucer to avoid rattling
when lifting to drink.
Avoid awkward or uncomfortable positions.
Use auto dial on a cell phone.
Non Pharmacological treatment
3
Add a littleweightto your hand
by wearing a heavy bracelet or
watch or holding something in
your hand. This may reduce
some tremors and restore more
control to your hands.
Drink beverages from half-filled
cups or glasses, and use a straw.
Get enough rest
andsleep.Fatigueoften makes a
tremor worse.
Approach to medical treatment
Whom to treat?
Need for intermittent versus continuous therapy
Utility of combined therapy
withprimidoneandpropranolol
Duration of benefit with pharmacologic treatment
Medical treatment failure
Approach to treatment (contd)
In most cases, ET can be managed by primary care
clinicians, beginning with exclusion of secondary causes
and followed by initiation of therapy withpropranololor
primidoneif the tremor is causing disability.
The decision to refer to a neurologist depends upon the
clinician's confidence in the diagnosis, comfort level
with use of the drugs recommended for tremor
suppression, and the patient's response to treatment.
Who?
Drug treatment should be offered to patients with ET
who have intermittent or persistent disability caused
by tremor.
Individuals with mild ET and little or no tremor-related
disability usually do not require treatment, although
some patients are bothered by the cosmetic effect of
even the least amount of shaking.
Patients may not complain of being bothered or
embarrassed by the tremor, they should be asked
about it directly.
Intermittent therapy
Some patients with ET develop exacerbations of tremor
triggered by stressful social occasions or public
performances.
Intermittent drug treatment of ET in anticipation of
these situations can be useful in such cases.
For patients with mild ET who have situational
exacerbations of tremor that cause concern, we suggest
treatment as needed withpropranolol.
Intermittent therapy 2
An alternative option is alcohol in small amounts (eg,
one or two alcoholic drinks).
Some experts report thatprimidonealso can be
effective when used intermittently for ET exacerbated
by situational stress or anxiety, but its slow onset of
action limits the utility of primidone in this setting.
Continuous therapy
Patients with persistent functional or psychological
disability (including embarrassment or anxiety) from
ET generally need continuous drug therapy.
In such cases, we recommend monotherapy
withpropranololorprimidoneas initial therapy.
Propranolol and primidone each may reduce tremor
amplitude by approximately 50 percent.
Continuous therapy 2
However, neither drug is effective for all patients
with ET.
In addition, acute adverse reactions with primidone
and chronic side effects of propranolol appear to be
important limitations to the use of these drugs.
For ET that is resistant to monotherapy with
eitherpropranololorprimidone, the two can be used
together. Moreover, switching from one to the other
is also a reasonable strategy if either agent is poorly
tolerated.
Duration of benefit
The symptomatic benefit of drugs used to treat ET
declines over time, probably due to disease progression
or the development of drug tolerance.
Propranololandprimidoneremain effective for limb
tremor reduction in the majority of patients for at least
one year, although increased doses of both drugs may
be needed by 12 months of therapy.
Treatment failure
Options for ET that fails continuous treatment with the
two primary drugs
includegabapentin,topiramate,nimodipine, and
combinations of agents that do not have additive
adverse effects.
Other beta blockers, anticonvulsants, and miscellaneous
drugs may also have a role in the treatment of ET.
Treatment failure 2
For patients who fail pharmacologic treatment with
these agents, options include:
surgery with deep brain stimulation or thalamotomy to treat
persistently disabling limb tremor, and
botulinum toxin injections to treat persistently disabling
head or vocal cord tremor
Gimme
propranolol, 60 to 320mg/day.
Long-
actingpropranolol(propranolol LA)
is also.
A single starting dose of 10 or 20
mg is suggested in anticipation,
and may be effective within an
hour.

The
Side effects :including
lightheadedness, fatigue,
impotence, and bradycardia.
relatively contraindicated in the
presence of heart block, asthma,
or type 1 diabetes mellitus.
may be used in patients with

Butter,
stable heart failure due to left
ventricular systolic dysfunction,
unless there are clear
contraindications, such as unstable
heart failure
Other BBs?
Atenolol, Sotalol, Nadolol probably reduce Ets
Metorolol uncertain
Pinolol does not reduce Ets
None of them is superior to Propranolol.
patients who do not respond to adequate doses of one
beta blocker for ET are unlikely to respond to another.
Primidone!
Anticonvulsant, Barbiturate.
up to 750mg/day,is effective
Side effects fromprimidonewere typically more severe
at treatment initiation
they included sedation, drowsiness, fatigue, depression,
nausea, vomiting, ataxia, malaise, dizziness,
unsteadiness, confusion, vertigo, and an acute toxic
reaction.
The mechanism of action ofprimidonein ET is unknown.
Other anticonvulsants?
Gabapentin reduces ET, start at 300mg TID up titrate to
400mg TID, may start with 100mg TID in elderly.
Topiramate reduces ET, high rate of adverse effects (tgt dose:
400mg/d)
Zonisamidetreatment reduced tremor severity in two small
open label studies at doses of up to 300mg/day.
Phenobarbitaltreatment for ET has shown conflicting outcomes
in a limited number of trials.
Levetiracetam, although not well studied for ET, appears to have
no significant benefit in most reports.
Pregabalintreatment showed no benefit for.
Other classes?
BenzodiazepinesBenzodiazepines are widely used because of the
usually mistaken belief that tremor is due to anxiety. Not preferable dt
abuse and withdrawal s/o.
Alprazolamis probably effective, though high-quality data are lacking.
Clonazepamis possibly effective.
Nimodipinecalcium channel blocker, is possibly effective at a dose of
30 mg four times daily.
Botulinum toxinBotulinum toxin type A (BoNT-A) injections have
modest benefit and are associated with dose-dependent hand weakness.
BoNT-A may reduce head tremor and voice tremor associated with ET,
but data are limited, and BoNT-A for voice tremor is associated with side
effects including breathiness, hoarseness, and swallowing difficulty.
Surgical ttt of ET
DBS:
effective for reduction of contralateral limb tremor in ET.
limited and conflicting evidence regarding DBS for treatment of voice
tremor and head tremor.
Adverse effects are related to equipment malfunction or lead displacement.
Thalamotomy:
Limited data suggest that unilateral thalamotomy is effective for treating
contralateral limb tremor
Gamma knife thalamotomy for ET is an unproven treatment, Transcranial
MRI-guided focused ultrasound thalamotomy is a novel method.
Limited data suggest that both deep brain stimulation (DBS) and
thalamotomy effectively suppress tremor in ET, but DBS appears to
have fewer adverse events than thalamotomy
Parkinsons disease
Parkinson disease is a progressive neurodegenerative
disorder that is pathologically defined by degeneration
of the dopaminergic neurons in the substantia nigra and
development of Lewy bodies in the residual
dopaminergic neurons.
Pathologic changes may be detected up to 20 years
before the onset of motor symptoms, and are
accompanied by a clinical prodrome of nonspecific
symptoms such as hyposmia, constipation, and fatigue.
The disease affects approximately 1% of older than 60
yrs, and up to 4% of those older than 80 yrs.
Diagnosis
cardinal features:
Bradykinesia
Rigidity
tremor
postural instability, coupled with gradual symptom
progression
a sustained response to therapy with levodopa.
Conditions commonly misdiagnosed as Parkinson
disease include nonparkinsonian tremors such as
essential tremor, and diseases with parkinsonian
features.
Characteristics of Conditions Commonly
Misdiagnosed as Parkinson Disease
CONDITION
Essential tremor
Vascular parkinsonism
Drug-induced parkinsonism
Dementia with Lewy bodies
Atypical parkinsonism (includes progressive
supranuclear palsy and multisystem atrophy)
CLINICAL FEATURES
Symmetric postural tremor; worsens with
movement; affects distal extremities, head, and
voice; family history common; improves with
alcohol, beta blockers
Clinical features similar to Parkinson disease; may
have focal neurologic findings; stepwise
progression with poor response to
carbidopa/levodopa; presence of basal ganglia
and/or thalamic infarcts on computed tomography
or magnetic resonance imaging
Clinical features similar to Parkinson disease; drug
history and drug withdrawal evaluation can confirm
diagnosis; antiemetics and psychotropic drugs most
common causative agents
Onset of motor symptoms accompanied by
dementia and visual hallucinations; patients
have marked fluctuations in attention and cognition;
poor response to carbidopa/levodopa
Clinical features similar to Parkinson disease, but
with other signs early in the disease process:
prominent gait and speech impairment,
prominent postural instability, and axial rigidity
greater than extremity rigidity; absence of resting
tremor and prominent autonomic dysfunction; poor
response to carbidopa/levodopa
Recommendations for Imaging in the Diagnosis of
Parkinson Disease
NATIONAL INSTITUTE SCOTTISH
FOR HEALTH AND INTERCOLLEGIATE
AMERICAN ACADEMY CLINICAL GUIDELINES
IMAGING MODALITY OF NEUROLOGY9 EXCELLENCE11 NETWORK4
Fludeoxyglucose Evidence insufficient to Use only in research Not recommended
positron emission make recommendation settings
tomography (PET)
Magnetic resonance Possibly useful to Not recommended for Not recommended for
imaging (MRI) distinguish Parkinson diagnosis of Parkinson routine diagnosis of
disease from disease idiopathic Parkinson
multisystem atrophy disease
Consider for diagnosis
of parkinsonian
syndromes
Single-photon emission Possibly useful to Distinguish Parkinson Distinguish Parkinson
computed tomography distinguish Parkinson disease from essential disease from
(SPECT) disease from essential tremor nondegenerative
tremor parkinsonism or other
tremor disorders

Ultrasonography (US) Evidence insufficient to No recommendation Not recommended

make recommendation
Prognosis
Patients with Parkinson disease experience
progressive decline in motor and cognitive
function and increased mortality.
Risk factors for more rapid decline in motor
function include:
older age at diagnosis
prominent bradykinesia and rigidity at
diagnosis.
Prognosis (contd)
Prominent tremor at diagnosis may predict a
slower rate of disease progression.
The incidence of dementia increases with:
patient age
duration of Parkinson disease, with 60 percent
of patients who have the disease developing
dementia within 12 years of diagnosis.
 Drug treatment
CatecholO- Entacapone
DRUG/DRUG CLASS EXAMPLES ADVANTAGES DISADVANTAGES
methyltransferas (Comtan), Used to treat motor Dopaminergic
Carbidopa/levodo Immediate- and
pa (Sinemet) sustained-release Most effective, Motor complications:
e inhibitors tolcapone (Tasmar) complications; no adverse effects,
carbidopa/levodopa improves disability, dyskinesias, titration, decreased discoloration of
prolongs capacity to dystonia, confusion, off time,* mild urine, tolcapone
perform psychosis, sedation improvement in associated with
instrumental
activities of daily explosive diarrhea
activities of daily
living living and quality- and fatal liver
Nonergot:
of-life scores toxicity
Dopamine
pramipexole Injectable Apomorphine
agonists Can be used as All:
(Mirapex), ropinirole dopamine (Apokyn) Reduces off time in Requires initiation
monotherapy in dopaminergic
(Requip)
early disease or adverse effects agonist late disease in hospital, regular
Ergot: bromocriptine added to (nausea,
(Parlodel), pergolide
subcutaneous
levodopa for vomiting,
treatment of orthostatic injections
motor hypotension), N-methyl-D- Amantadine
complications neuropsychiatri
aspartate Treatment of Cognitive adverse
Less risk of c adverse
developing effects(hallucina receptor inhibitor dyskinesias in late effects, livedo
motor tions, psychosis, disease reticularis, edema,
complications in impulse control development of
early disease disorder), tolerance, potential
excessive
daytime for withdrawal
sleepiness Anticholinergics Benztropine,
Ergot:
trihexyphenidyl Useful for the Use limited by
pulmonary
fibrosis, cardiac treatment of tremor anticholinergic
valve fibrosis, in patients younger adverse effects
erythromelalgia than 60 years
Monoamine Selegiline (Eldepryl),
without cognitive
oxidase-B rasagiline (Azilect) Can be used as Amphetamine and impairment
inhibitors monotherapy in methamphetamine
early disease or to metabolites may
treat motor cause adverse
complications in late effects, risk of
disease serotonin syndrome
Coenzyme Q10 appears to be most promising in the treatment of:
A) Parkinsons disease
B) Diabetes mellitus
C) CHF
D) Hyperthyroidism
Surgical treatment
Most patients will develop disabling symptoms despite optimal
medical therapy, and are candidates for deep brain stimulation, which
targets either the subthalamic nucleus or the globus pallidus interna.
Factors that predict a good response to surgery for advanced
Parkinson disease include good response to levodopa, few
comorbidities, absence of cognitive impairment, and absence of (or
well-controlled) depression.
Risks of surgery include intracranial hemorrhage; stroke; infection;
lead migration, misplacement, or fracture; and death.
Deep brain stimulation does not slow disease progression, and
patients eventually develop treatment-resistant symptoms such as
gait freezing.
Take home messages
Tremors are the most common movement disorder
presenting to primary care.
Diagnosis is purely clinical and imaging has limited role
in diagnosis.
Tremors can affect functioning and in Parkinsons
disease is associated with increased mortality.
Essential tremors can be disabling and require
treatment in patient with disability.
Parkinsons disease is a disabling progressive
neurodegenerative condition requiring specialist follow
up.
References
Differentiation and Diagnosis of Tremor
http://www.aafp.org/afp/2011/0315/p697.html
Parkinson Disease: An Update http://www.aafp.org/afp/2013/0215/p267.html
Tremors by Anwar Ahmed and Patrick Sweeney - July 2014
http://www.clevelandclinicmeded.com/medicalpubs/diseasemanagement/neurol
ogy/tremors/
Overview of tremor
https://www.uptodate.com/contents/overview-of-tremor?source=machineLea
rning&search=neuropathic%20tremors&selectedTitle=1~1&sectionRank=1&anc
hor=H15#H15
Essential tremor: Clinical features and diagnosis
https://www.uptodate.com/contents/essential-tremor-clinical-features-and-diag
nosis?source=see_link
Surgical treatment of essential tremor
https://www.uptodate.com/contents/surgical-treatment-of-essential-tremor?sou
rce=see_link
Living With Essential Tremor
http://www.webmd.com/brain/living-with-essential-tremor