Diagnosis and Treatment REVIEW ARTICLE


of Essential Tremor C O N T I N U UM A U D I O
I NT E R V I E W A V A I L AB L E
ONLINE
By Aparna Wagle Shukla, MD

VIDEO CONTENT
A V AI L A B L E O N L I N E

ABSTRACT
PURPOSE OF REVIEW: Essential tremor is a chronic, progressive syndrome that
primarily presents with an action tremor involving the arms and hands. This
article reviews the history and physical examination features pertinent for
diagnosis, differential diagnoses, and treatments and approaches for
optimal control of symptoms.

RECENT FINDINGS: Essential tremor is a syndrome with symptoms extending

beyond tremor to involve disturbances in gait, speech, cognition, and
mood. Although the new guidelines on the definition and biaxial CITE AS:
CONTINUUM (MINNEAP MINN)
classification scheme have provided clarity, some tremor experts have 2022;28(5, MOVEMENT DISORDERS):
critiqued the recently coined term essential tremor plus. For treatment, 1333–1349.
new orthotic devices and peripheral stimulation devices are now available
in addition to pharmacologic and surgical options. Address correspondence to
Dr Aparna Wagle Shukla, Norman
Fixel Institute for Neurological
Disorders, 3009 Williston Rd,
SUMMARY: Essential tremor has a rich clinical phenomenology with many Gainesville, FL 32608, aparna.
subtleties and nuances. A detailed history with open-ended questions and shukla@neurology.ufl.edu.
focused questions encompassing medical history, social history, and
RELATIONSHIP DISCLOSURE:
family history is key for establishing the diagnosis. The presence of Dr Wagle Shukla has received
bilateral action tremor for 3 years and absence of isolated head and personal compensation in the
range of $500 to $4999 for
voice tremor and absence of task- and position-dependent tremor are serving as a consultant for Jazz
necessary for diagnosis. Dystonic tremor, Parkinson disease tremor, Pharmaceuticals, Inc, as a
physiologic tremor, and drug-induced tremor are common differential reviewer with the National
Institutes of Health, and as the
diagnoses. Differentiating these tremor disorders from essential tremor Vice President of the board of
based on phenomenology and physical examination alone could be directors for the Tremor
challenging; thus, clinicians should seek additional clues from a Research Group and in the
range of $5000 to $9999 for
detailed history. Treatment could begin with noninvasive and serving on a scientific
nonpharmacologic therapies, especially in mild cases. As the severity advisory board for Acadia
Pharmaceuticals Inc. The
increases, they can advance stepwise to include pharmacotherapies institution of Dr Wagle Shukla
and surgical interventions. With the growing recognition that essential has received research support
tremor is not a monosymptomatic disorder, management should involve from the National Institutes
of Health.
a multidisciplinary team. Furthermore, treatment selection should be
based on shared decision making between patients and providers that UNLABELED USE OF
gives due consideration to severity of symptoms, level of functional PRODUCTS/INVESTIGATIONAL
USE DISCLOSURE:
disability, impact on social interactions, patient preferences, and Dr Wagle Shukla reports no
patient expectations. disclosure.

© 2022 American Academy

of Neurology.

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DIAGNOSIS AND TREATMENT OF ESSENTIAL TREMOR

INTRODUCTION

T
remor is an involuntary, rhythmic, oscillatory movement of a body
part.1 Essential tremor is a chronic, progressive syndrome that
primarily presents with an action tremor involving the arms and
hands. Essential tremor is among the most prevalent movement
disorders with a pooled prevalence estimate of about 1% across all
ages in population studies.2 The prevalence increases to 5% in people who
are older than 60 years and to 20% in people who are older than 95 years.3 Diagnosis
of essential tremor is clinical; however, the process is not straightforward because
the syndrome is highly nuanced. Many debates and discussions surround the
terminology, nosology, and phenomenology. The term essential implies a disorder
lacking a known proximate cause (ie, idiopathic) or, similar to essential
hypertension and essential thrombocythemia, a disorder that is unitary and
intrinsic to an individual.4 However, the pitfall of the continued use of the
term became increasingly apparent as the etiology and pathophysiologic
understanding of the disorder advanced. Despite serious concerns, a task force

CASE 5-1 A 72-year-old man presented for a neurologic consultation with a

bilateral hand tremor first noticed in high school. However, the tremor
was intially mild, intermittent, and did not affect day-to-day functioning.
He had several family members with similar tremors, including his
mother, grandmother, maternal uncle, and a cousin. He worked as an
accountant, and the tremor did not become bothersome until he reached
his fifties when it began to interfere with writing, typing, and using the
computer mouse and keyboard. At home, he had trouble using garage and
gardening tools and pouring himself coffee. He avoided going to
restaurants with friends because he had difficulty eating spaghetti with a
fork and soup with a spoon. He observed that a glass of wine helped his
tremor. He had been treated with propranolol 160 mg/d, which helped
him some. He later started receiving primidone as an additional
medication for further control of tremors. He tolerated both drugs
without dizziness, nausea, and gait imbalance. However, as the
symptoms continued despite adequate doses of medications, he decided
to seek early retirement.
The arm tremor was moderately severe on examination, involving the
metacarpophalangeal and wrist joints when he was asked to stretch his
arms forward. The tremor was also noted when asked to write, draw
spirals, and perform the finger-nose-finger maneuver. The tremor was
absent when his arm was resting. He decided to consider deep brain
stimulation surgery for control of his symptoms.

COMMENT This case illustrates the age of onset and familial nature of essential tremor,
gradual worsening of symptoms over decades, kinetic tremor interfering
with day-to-day fine motor activities, long-term social and professional
consequences, and consideration of surgical treatments when
pharmacologic agents do not alleviate symptoms.

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commissioned by the International Parkinson and Movement Disorder Society KEY POINTS
decided to retain the term because clinicians and researchers widely used it
● The involuntary
and patients and their families requested its continued use. The task force movements of essential
proposed a new biaxial scheme for classifying the tremor syndrome. The first tremor are both rhythmic
axis emphasizes detailed consensual clinical phenotyping based on the age of and oscillatory.
onset, sex, body distribution, and temporal evolution of symptoms, and the
● Tremor syndrome
second axis focuses on etiologic considerations.1 Alongside the recent
classification is biaxial, first
developments in clinical definitions and classifications, many treatments have based on clinical
emerged that can effectively control the symptoms. The purpose of this article is to phenotyping and second
discuss and recognize the clinical subtleties when approaching a patient with based on underlying
essential tremor for an accurate diagnosis and selection of appropriate treatments. etiologies.

● Essential tremor is among

MEDICAL HISTORY the most prevalent
A thorough history is an invaluable tool for the establishment of the diagnosis. The movement disorders.
first part of the interview should include open-ended questions to obtain pertinent
● Isolated tremor syndrome
clinical information. The characteristic history of essential tremor is the presence of of bilateral upper limb
a hand tremor that frequently interferes with activities of daily living such as eating, action tremor present for at
drinking, pouring, handling utensils, dressing, and using keys or other household least 3 years is a
tools. Some patients report using a smartphone, computer keyboard, and mouse as requirement for the
diagnosis of essential
quite problematic. The second part of the interview should include focused tremor.
questions with the following items for further improvement of diagnostic certainty.

SEX, AGE AT ONSET, AND TEMPORAL EVOLUTION

The prevalence estimates for men and women are about the same,5,6 and
symptoms present insidiously for most individuals. The age of onset in
multiple clinical studies has revealed a bimodal distribution pattern with peaks
occurring around the third and seventh decades of life. However,
community-based studies have found a steady age-associated increase in the
prevalence.7-9 Overall, an estimated 2% worsening of symptoms has been
reported to occur on a year-to-year basis.10 Some investigators have found
phenotypic differences between early-onset and late-onset essential tremor.11
Early-onset essential tremor is frequently associated with a positive family
history and a presence of a mild, stable tremor that progresses over many years
whereas late-onset essential tremor is observed to progress at a faster pace.12

DURATION OF SYMPTOMS, BODY DISTRIBUTION, AND ACTIVATION

CONDITIONS
The new definition for essential tremor requires the presence of an isolated
tremor of the arms and hands for at least 3 years that may or may not be
accompanied by a tremor in the head, voice, or lower limbs. Tremor less than
3 years is an indeterminate syndrome. A 3-year guardrail is meant to reduce the
odds of diagnosing concurrent neurologic signs (eg, dystonia, parkinsonism, or
ataxia).1 If other neurologic signs begin to codominate, regardless of whether
they occur early in the course or later after 3 years, symptoms should be labeled
as a combined tremor syndrome. Essential tremor is primarily an action tremor
syndrome affecting the arms that interferes with day-to-day motor tasks
(postural and kinetic components) (CASE 5-1). Sometimes essential tremor
worsens with precision goal-directed tasks (intention component), thus lending
difficulties in performing fine motor tasks such as working with a screwdriver,
inserting keys in a lock, applying makeup, or wearing jewelry. Essential tremor

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DIAGNOSIS AND TREATMENT OF ESSENTIAL TREMOR

in 20% of patients manifests during the resting state (resting component),

especially in long-standing cases; however, the tremor usually affects only the arms.
Essential tremor is not a task- and position-specific tremor. Head and voice tremors
usually evolve in 30% to 40% of patients after the onset of arm tremor.1 Isolated
focal tremor affecting the head or voice is inconsistent with the diagnosis. Head
tremor occurs when sitting, standing, and walking but tends to disappear when
lying down. Voice tremor is seen to manifest and affect daily conversations.13
Indeed, arm tremor is functionally disabling, but pronounced head and voice
tremors can lead to social embarrassment in day-to-day functioning.

DIET AND SOCIAL HISTORY

Dietary history including consumption of alcohol14 or environmental history that
contributes to essential tremor pathogenesis could provide clues for etiologic
origins. Some interest has been shown in assessing the relationship between high
amounts of meat in the diet and linkage with essential tremor because harmane,
which has tremorgenic properties, is abundantly present in meat.15 Eating meat
cooked at high temperatures for a long time is a particular risk,16 but a high
adherence to the Mediterranean composite diet, known for its high antioxidant
content, has been suggested to lower the odds of essential tremor.17 Besides
toxicity effects related to chronic consumption of alcohol,18 essential tremor has
been found to exacerbate with caffeine and improve with alcoholic drinks in the
acute clinical setting.19,20

FAMILY HISTORY
Ascertainment of family history is critical because essential tremor has shown
high rates (30% to 70%) of heritability.14,21 The family history is often consistent
with a Mendelian pattern of inheritance.14 The vast majority (more than 80%) of
patients with early-onset essential tremor report at least one affected first-degree
family member.9 Although several studies including genome-wide association
studies, linkage analysis, and whole-exome sequencing have attempted to advance
the genetic understanding, only a few reliable and replicable findings are available
so far. One such example is the single nucleotide polymorphism identified in the
region of LINGO1.22 Whether a single rare high-penetrant variant or many common
low-penetrant variants contribute to familial aggregation remains unclear.23

NEUROLOGIC EXAMINATION
The patient should be relaxed and seated comfortably. Bilateral arm tremor
elicited during postural and kinetic motor tasks is a hallmark finding. The
postural component is examined by having the patient outstretch both arms
extended directly forward, parallel to the ground, with the wrists straight and the
fingers extended and slightly abducted. The rhythmic oscillatory movements
comparable to a pendulum swinging from a fixed point (the shoulder joint in this
case) are usually distal, involving the metacarpophalangeal and wrist joints. The
oscillatory movements are flexion-extension rather than pronation-supination.
Another task for examining the postural component is an assumption of a
wing-beating position. The patient extends the arm outward and flexes the elbow
parallel to the ground to position the wrist under the chin. In this position, the
oscillatory movement increases in amplitude and tends to involve the proximal
wrist or elbow joints (these joints become the distal pendulum). In the
wing-beating posture, tremors in both arms sometimes oscillate out of phase,

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which could be leveraged for functional benefits. For example, a patient holding KEY POINT
a cup with both hands can counterbalance the dropping movement of one hand
● Patients with early-onset
with the other (VIDEO 5-1). The kinetic component is examined by asking patients to essential tremor commonly
perform standard tasks such as pouring water from a cup, writing a sentence, or report at least one affected
drawing spirals on a paper following standardized instructions. In the spiral- first-degree family member.
drawing task, tremor waveforms are drawn perpendicular to the pen movement,
and they characteristically align along an axis. A spiral drawn using the right hand
reveals an axis pointing toward the upper right quadrant, whereas a spiral drawn
with the left-hand points toward the upper left quadrant. This alignment is not
usually seen in other tremor disorders such as dystonic tremor and Parkinson
disease tremor. The intentional component can be elicited by patients touching their
nose precisely with their fingers and touching the examiners’ fingers, going back
and forth. This elicits a worsening of tremor amplitude because the task requires
a high level of visuomotor coordination. Another task is the dot approximation
task which requires the patient to point a pen close to a marking made on the paper.
The intentional component of head tremor can be evident when the patient
attempts to reach a spoon or cup during meals. For the resting component, it is
imperative that the patient is examined in a proper resting position. Patients should
be sitting on a chair with the arms fully relaxed and resting on the armrest or the
arms supported on their lap. If possible, patients could also be examined in a
lying-down position to achieve a proper resting condition.

GAIT AND COGNITION

It is increasingly recognized that essential tremor is not a monosymptomatic
disorder but is frequently associated with gait and cognitive changes.24,25 These
nonmotor abnormalities arguably justify the label “essential tremor is a tremor
syndrome,” as proposed by the Movement Disorders Society.1 Some have
advocated that essential tremor should be regarded as a disease or a family of
diseases. The disease entity encompasses a good amount of knowledge on
etiology, clinical presentation, course, and prognosis. As the knowledge of genes,
environmental factors, pathophysiology, and the natural disease course have
considerably advanced, it is reasonable to consider essential tremor as a disease.
Gait changes, which can be revealed during a simple bedside tandem walking
task, are frequently seen in essential tremor.26-28 Most studies have found that
about 30% to 50% of patients with essential tremor have two or more missteps
during walking.27-29 Gait impairment, albeit mild in most patients, can become
moderately severe and bothersome in some patients. These abnormalities, which
increase the susceptibility to falls, are more commonly associated with the head
tremor than the arm tremor.27 Neurologic examination should encompass
cognitive assessment to capture deficits in attention, concentration, working
memory, executive function, language, and global cognitive function; these have
been reported to be present in essential tremor.30

ESTABLISHMENT OF DIAGNOSIS
According to a recent consensus statement released by the Movement Disorder
Society, essential tremor is defined as an isolated tremor syndrome of bilateral
upper limb action tremor of at least a 3-year duration, with or without a tremor in
other locations (eg, head, voice, or lower limbs), and absence of other neurologic
signs, such as dystonia, ataxia, or parkinsonism.1 The consensus panel also
introduced a new term, essential tremor plus, defined as a tremor with the

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DIAGNOSIS AND TREATMENT OF ESSENTIAL TREMOR

characteristics of essential tremor with additional soft neurologic signs of

uncertain clinical significance, such as impaired tandem gait, questionable
dystonic posturing, memory impairment, or other mild neurologic signs of
unknown clinical significance. Essential tremor with a resting component is also
included within the spectrum of essential tremor plus.1 Many groups of
investigators have raised concerns over the term because the descriptors are
relatively subjective and it is not known whether essential tremor plus is
biologically distinct from essential tremor.31 Until further research sheds insights
into this newly coined entity, it is prudent that the clinician continues to document
the co-occurring neurologic features noted during the neurologic examination.

DIFFERENTIAL DIAGNOSIS
The overdiagnosis of essential tremor is common because many tremor disorders
can have overlapping phenomenology (FIGURE 5-1). Indeed, studies show that
30% to 50% of “essential tremor” cases have diagnoses other than essential
tremor, with many of these patients having dystonia or Parkinson disease.32

TREMOR IN DYSTONIA
The 2013 criteria laid out by the Movement Disorders Society propose that
dystonic tremor is a tremor in a body part affected by dystonia, and tremor
associated with dystonia is a label to be considered when dystonia and tremor are
found to affect different body parts.33 Although this criterion is debatable, in
clinical experience, patients with focal and/or segmental dystonia frequently
exhibit tremors affecting the head, arm, or voice.34 The prototypical history

FIGURE 5-1
Differential diagnoses of essential tremor with key characteristics for individual tremor disorders.

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consists of a 45- to 50-year-old woman presenting to the clinic with a long history
of isolated head tremor. Unlike essential tremor, the head tremor noticeable when
patients are seated comfortably upright in the chair may not resolve when they
assume a supine position. The patient may additionally report accompanying
symptoms of pulling, tightness, and spasms (described as “knots”) in the neck and
shoulder muscle groups. Restriction in head movements will result in pain, fatigue,
and difficulties with reading a book, watching television, driving a car, or working
for long strenuous hours on a computer. Patients sometimes have bioccipital
headaches. The head and neck symptoms could improve partially in response
to alcohol consumption, further complicating the distinction from essential
tremor. Symptoms could also be mitigated when the head is held in certain
positions (CASE 5-2). Sometimes the patient may endorse a “sensory trick,”
resulting in a “magical” disappearance of abnormal movements or posture.
A careful neurologic examination will provide further clues for diagnosis.
Besides the twisting movement and posture and apparent neck muscle
hypertrophy related to dystonia, the coarse and jerky or fine and rhythmic
character of the head tremor that is generally slow is elicitable during the

A 48-year-old woman presented with a chief complaint of head tremor, CASE 5-2
occipital headaches, head pulling, and neck muscle tightness for 3 years.
She had spasms and knots in her shoulder muscles. It was easier for her to
look to the right than the left. Her head tremor worsened when she
looked to the left. She worked as a schoolteacher, and her symptoms
worsened toward the end of the day. She found herself holding her chin
when talking to coworkers and children in the school. She could watch
television or read a book only if she had a pillow to support her head. She
denied symptoms in her eyes, jaws, and arms.
On examination, her head appeared to be preferentially turned to the
right and tilted toward her right shoulder. She had a mild to moderate
head tremor that worsened when asked to close her eyes and turn her
head to the extreme left. The head tremor was jerky and irregular and
persisted even when she laid down on her back on the examining bed. An
arm tremor was not observable. Her left sternocleidomastoid muscle was
slightly hypertrophic.
She was treated with IM onabotulinumtoxinA injections administered
every 12 weeks. OnabotulinumtoxinA was targeted mainly to the left
sternocleidomastoid, right splenius capitis, and right longissimus capitis
muscles, which helped control her headaches, neck pain, spasms, and
tremor. However, she reported the benefits lasted for only 9 of 12 weeks.

This case illustrates the characteristic history and examination features of a COMMENT
patient with cervical dystonia presenting with dystonic head tremor. The
age of onset; female sex; abnormal posturing; irregular, jerky tremor;
presence of sensory trick; hypertrophy of muscles; presence of null point;
and persistence of tremor during recumbent positioning all support a
diagnosis of dystonic tremor.

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DIAGNOSIS AND TREATMENT OF ESSENTIAL TREMOR

maintenance of posture or kinetic tasks (VIDEO 5-2). The examiner may observe
the head tremor as directional with a “null point,” which is a point during
performance of voluntary head movements that leads to the complete
disappearance of tremor. For example, in a patient with right torticollis (head
turned to the right) with head tremor, if the patient is instructed to turn to the
extreme left (against the will of dystonia), the tremor may worsen, but a
nullification may occur when the head turns in the same direction as dystonia
(following the will of dystonia). Sometimes, patients may not exhibit rhythmic
or oscillatory qualities during a clinical examination.1 Thus, whether the
“tremor” in the strictest sense of the word is a tremor is debatable. FIGURE 5-2
represents a simple illustration of rhythmicity, oscillations, sinusoidal waves, or
sawtooth waves that can be assessed with kinematic analysis.35
Arm tremors may occur with or without dystonic posture and movements.
Dystonic arm tremor is jerky, is usually a little proximal, and frequently manifests
in a resting position. However, if the arm tremor is fine and rhythmic, it may be
difficult to distinguish from essential tremor. In these circumstances, features
evident in the history could provide clues. Arm tremor in dystonia usually
manifests several years after the onset of head tremor. Head tremor reveals clear
underlying cervical dystonia, unlike a head tremor of essential tremor. Besides fine
motor difficulties involving distal hand fingers, patients may report trouble
holding a glass or cup or throwing a softball (proximal muscles). Tremor is mild in
many cases and is remarkably asymmetric or unilateral. The posturing of the arm
is appreciable during the physical examination as splaying and spooning of fingers,
thumb hyperextension, and/or shoulder elevation.36 The spiral drawing typically
does not reveal an axis.37 If dystonia involves other body parts, that can provide

FIGURE 5-2
Conceptual understanding of tremor. The horizontal arrows indicate the time interval
between two successive peaks of periodic waves. Rhythmic tremor that is regularly recurrent
has a constant interval. Irregular tremors with changing time intervals will clinically appear as
jerky. Oscillation indicates rotation around a central plane. Vertical arrows of different
lengths mean that the tremor is nonoscillatory. Such tremors clinically appear as directional.
If the periodic waves lose their sinusoidal characteristics and assume sawtooth waves, such
tremors will also clinically appear jerky.

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further clues. When the dystonic tremor affects the voice, patients report voice KEY POINTS
breaks or strangulated speech, which is not the case for essential tremor.
● Essential tremor is a
Distinguishing dystonic tremor from essential tremor is not always that syndrome with symptoms in
straightforward because these clues are not necessarily seen in all patients. many patients extending
Sometimes, the history can be confusing; for example, one family member reports beyond tremor to involve
classic essential tremor, but another member has clear history and examination disturbances in gait, speech,
mood, and cognition.
features consistent with a diagnosis of dystonia. Sometimes, patients with essential
tremor begin to exhibit dystonic characteristics with the progression of time. These ● Essential tremor with a
quandaries have resulted in considerable debates that will likely be resolved as resting component or
high-resolution imaging and physiology-based markers for reliable differentiation accompanied by soft signs
of the two tremor disorders become available in clinical practice.38,39 of dystonic posturing or
parkinsonism is labeled as
essential tremor plus;
PARKINSON DISEASE TREMOR currently, no evidence has
Although postural and kinetic components are the main elements of essential been found that essential
tremor, the presence of a resting tremor seen in a small proportion of patients tremor plus is biologically
distinct from essential
with advanced essential tremor can potentially lead to an erroneous diagnosis of tremor.
Parkinson disease. The arms and hands should be fully supported by the patient’s
lap or the armrests of the examination chair to elicit a true resting component ● Dystonic head tremor
(VIDEO 5-3).40 The resting component of essential tremor could be differentiated commonly affects women in
their fifth decade and
from tremor in Parkinson disease by noting observations during coactivation
includes headaches, neck
motor tasks such as walking or counting backward. These tasks do not increase pain, posturing, and isolated
amplitude in essential tremor, but a worsening of tremor in Parkinson disease head tremor.
will be seen.41 The resting tremor component in essential tremor is seen to mainly
involve the arms, but the resting tremor of Parkinson disease can affect both ● Isolated head tremor,
voice tremor, and task- or
arms and legs. Although a certain degree of asymmetry is commonly seen, position-specific tremor
essential tremor is a symmetric disease. However, tremor in Parkinson disease is should not be diagnosed as
remarkably unilateral or asymmetric.41 With the patient’s arms stretched in a essential tremor.
postural position, the arm tremor in Parkinson disease reveals a reemergent
● Unlike essential tremor,
quality (a tremor that occurs after a finite latency period from the time the dystonic head tremor often
patient assumes a horizontal posture of the arm to the onset of the wrist and/or persists when the patient is
finger tremor), which is not seen in essential tremor. Other clues supporting a examined while lying down.
diagnosis of Parkinson disease tremor include a history of rapid eye movement
● The tremor in dystonia
(REM) sleep behavior disorder or anosmia, pronounced bradykinesia, rigidity,
may be neither rhythmic nor
and gait and speech disturbances. Jaw tremor in Parkinson disease is seen when oscillatory.
the patient’s mouth is closed, whereas essential tremor appears during speaking.
These clinical features may not always be evident; thus, additional testing such as ● Arm tremor in dystonia is
dopamine transporter imaging for demonstration of presynaptic nigrostriatal frequently unilateral and
asymmetric.
dopaminergic innervation in Parkinson disease is used.42 In recent times,
measuring phosphorylated α-synuclein in CSF or peripheral tissue, such as a skin ● Unlike essential tremor,
biopsy, has been described in patients with Parkinson disease and might be dystonic arm tremor may not
useful in distinguishing patients with Parkinson disease tremor from those with reveal a clear axis during the
spiral-drawing task.
essential tremor.43 However, the accuracy, sensitivity, specificity, and the
optimal tissue analysis technique will require more studies before a broader ● Based on physical
implementation in clinical practice. examination alone, dystonic
tremor may not be
PHYSIOLOGIC AND DRUG-INDUCED TREMOR distinguishable from
essential tremor; history
In theory, when exposed to certain physiologic conditions, all healthy people are must be given consideration.
vulnerable to developing a tremor. Enhanced physiologic tremor occurs when
physiologic conditions such as hypoglycemia, hypothermia, hyperthyroidism, or
anxiety are heightened.44 Tremor is usually bilateral, affects the arm

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DIAGNOSIS AND TREATMENT OF ESSENTIAL TREMOR

symmetrically, and may affect the voice but tends to skip the head. Usually, no
intentional component is present during the finger-nose-finger maneuver.
Sometimes exposure to drugs leads to tremors as a side effect. Drug-induced
tremor is fast (high frequency), fine (low amplitude), and rhythmic in
most patients. Although psychotropic drugs, such as selective serotonin
reuptake inhibitors (SSRIs), tricyclic antidepressants, neuroleptics, and lithium
(CASE 5-3), are commonly implicated as a cause of drug-induced tremor; many
nonpsychotropic drugs such as β-agonists, immunosuppressants, and hormonal
therapies can also cause or exacerbate tremor.44 Most tremor-inducing drugs
cause postural tremor, but tremors induced by psychotropics and neuroleptics
can have resting and intentional components.45,46 Physiologic tremor is usually
fast (high frequency), fine (low amplitude), and rhythmic in most patients, but
sometimes, in patients receiving medications such as valproic acid, the tremor
can exhibit a coarse character (VIDEO 5-4). A simple bedside assessment may not
reliably distinguish enhanced physiologic tremor from essential tremor.47
Clinical electrophysiology testing may provide additional helpful information.
During EMG recordings, enhanced physiologic tremor generally exhibits a higher
frequency and lower amplitude. Given a predominant peripheral (mechanical)
origin, the response pattern to inertial loading, which applies weights to the wrist,
may reveal distinct findings. With inertial loading, the mechanical component
may sometimes separate from the central component, leading to a display of two
frequency peaks, which is not the case for essential tremor.48

CASE 5-3 A 55-year-old man presented for evaluation of a 1-year history of bilateral
symmetric hand tremor alongside progressive slowness of movements,
decreased facial expression, and a slight shuffling gait. Further
questioning revealed that the tremor appeared when he would sit on a
sofa with his arms resting as well as when his arms were engaged in
eating, drinking, dressing, and writing. His medical history revealed
treatments for long-standing bipolar disorder. He had been prescribed
lithium for the past year with doses titrated to 1800 mg/d.
On examination, he had a hypomimic facial expression, bradykinesia,
rigidity, a parkinsonian gait, and a bilateral fine distal hand tremor. He
underwent a trial with carbidopa/levodopa; doses were escalated to a
total daily dose of 1000 mg/d of levodopa with no improvement of
symptoms. He underwent dopamine transporter imaging, which was
unremarkable.

COMMENT This case exemplifies the importance of obtaining medication history,

which can provide important clues for a diagnosis of drug-induced tremor.
The patient had been receiving lithium for treatment of bipolar disorder; his
lithium levels were found to be 1.5 mEq/L instead of the recommended
therapeutic range of 0.6 mEq/L to 1.2 mEq/L. The history of symmetric
bilateral hand tremors was temporally related to the initiation of lithium
therapy. The case illustrates that lithium-induced tremors can be
potentially confused with essential tremor in clinical practice.

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TREMORS SECONDARY TO A STRUCTURAL AND GENETIC ETIOLOGIES KEY POINTS
Holmes tremor occurs in the setting of stroke, head trauma, and demyelination
● Unlike essential tremor,
involving brain regions in tremorgenic circuitry connecting the cerebellum, red resting tremor in Parkinson
nucleus, and thalamus. The Holmes tremor is usually slow and unilateral, disease increases in
affects the proximal arm, and reveals a kinetic > postural > resting component amplitude with walking and
(VIDEO 5-5).49 Another example of secondary tremor is fragile X-associated mental calculation and is
generally asymmetric.
tremor/ataxia syndrome. This syndrome is an X-linked recessive disorder
presenting with bilateral arm tremor in older men. The postural and kinetic ● Unlike essential tremor,
components are pronounced, but sometimes, notable resting and intentional arm tremor in Parkinson
components are present.50 As the name of the syndrome implies, these may have disease reveals a
features of progressive ataxia and sometimes parkinsonism and cognitive reemergent quality (a tremor
that occurs after a finite
impairment. Wilson Disease is an autosomal recessive disease that leads to latency period from the time
abnormal copper metabolism resulting in excessive deposition of copper in the patient assumes a
various tissues, including the brain. A tremor well appreciated during the horizontal posture of the
wing-beating position is a prototypical tremor, but a wide-ranging arm to the onset of the wrist
and/or finger tremor).
phenomenology can be seen. These tremors can be distinguished from essential
tremor based on other elements in the history and examination features such as ● In contrast to essential
cognitive changes, ataxia, and parkinsonism.51 tremor, the jaw tremor of
Parkinson disease is more
often noted when the
NEUROPATHIC AND FUNCTIONAL TREMOR
patient’s mouth is closed
Patients with acquired and familial neuropathies may also exhibit mild to and relaxed rather than
moderate action tremor of the arms. In these patients, important clues can be while the patient is
obtained from the history because the tremor often begins after the onset of speaking.
neuropathy. Although the severity of neuropathy correlates with the occurrence
● Head tremor is not a
of tremor, it does not necessarily correlate with the severity of the tremor.52 feature of enhanced
Functional tremor, a tremor without known organic etiology, should be on the physiologic tremor or
list of differential diagnoses. Functional tremor often has an abrupt-onset tremor drug-induced action tremor.
that fluctuates remarkably in amplitude and frequency and is distractible,
● Holmes tremor has
suggestible, and entrainable. Sometimes, a patient has a history of spontaneous resting, postural, and kinetic
remission. Examination features that are highly supportive of an underlying components.
functional basis include entrainment, distractibility, and suggestibility.
● Fragile X-associated
tremor/ataxia syndrome has
MANAGEMENT
a prominent intentional
Essential tremor is a syndrome with symptoms extending beyond tremor in component.
many patients to involve disturbances in gait, speech, mood, and cognition. A
multidisciplinary team involving neurology, neurosurgery, occupational ● Wilson disease has
therapy, physical therapy, neuropsychology, and psychiatry is warranted for a prominent wing-beating
postural tremor.
comprehensive assessment and high-quality holistic care (FIGURE 5-3).
Many options are available for treating the motor symptoms, and treatment ● Functional tremor is
selections mainly depend on the severity of symptoms, level of functional abrupt in onset and
disability, impact on social interactions, patient preferences, and patient distractible, suggestible,
and entrainable.
expectations.53-57 It is critical to treat the individual patient and not the disease.
A stepladder approach for treating essential tremor symptoms is proposed ● Management of
(FIGURE 5-4), and shared decision making between the patients and their essential tremor requires a
clinical providers at each step is encouraged. When the symptoms are mild, multidisciplinary team, and
nonpharmacologic therapies could be the first consideration. Occupational treatment selection requires
shared decision making
therapists can help develop a practical, individualized approach. An occupational between patients and
therapy evaluation will focus on modification of the functional task and encourages providers.
the use of compensatory strategies such as proper body mechanics and core
stability for hand control. Several adaptive devices, such as weighted spoons, forks,

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DIAGNOSIS AND TREATMENT OF ESSENTIAL TREMOR

FIGURE 5-3
Multidisciplinary team for management of essential tremor, which should be centered on the
patient and not the disease.

FIGURE 5-4
Stepwise approach for management of arm symptoms in essential tremor. Treatments assigned to
step 2 or 3 can be combined with treatments in step 1. Surgical treatments, even though powerful,
are considered only when the tremor is refractory to pharmacologic therapies.
DBS = deep brain stimulation; MRI = magnetic resonance imaging.

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utensils, or rocker knives; weighted pencils and pens; and modified computer KEY POINTS
mouses and keyboards, are available for a more efficient task performance. In
● Adaptive tools, orthotic
recent times, many wearable orthotic devices have become available. Although devices, limb cooling,
some devices follow the principles of increasing weights around the wrist to and peripheral stimulation
stabilize the arm mechanically, some use tuned mass damper technology to devices are useful
dampen vibrations and a gyroscope to reduce the angular momentum. Peripheral nonpharmacologic therapies
for essential tremor.
limb cooling with icepacks around the forearm is another technique that
modulates the feedback from the peripheral muscles to the brain that can ● If the tremor severity
temporarily control the tremor.58 In 2022, a peripheral wearable device that does not reduce despite
stimulates the median and radial nerve at the wrist to modulate the peripheral multiple medication trials,
feedback59 was cleared by the US Food and Drug Administration (FDA) to treat surgical intervention may
be warranted.
essential tremor symptoms.60 Thus, it is increasingly recognized that
nonpharmacologic therapies can potentially improve patients’ quality of life
without presenting many risks.
When the symptoms interfere significantly with activities of daily living,
pharmacologic therapies are initiated.61 Beta-blockers are FDA-approved
first-line agents for the treatment of essential tremor. Short- and long-acting
propranolol reduces tremor by 50% to 70% in 50% of patients at daily doses
varying from 60 mg/d to 200 mg/d.55 Dizziness, fatigue, erectile dysfunction,
and sedation are common side effects. Propranolol, a nonselective beta-blocker,
is contraindicated for patients with bronchial asthma. However, cardioselective
atenolol and metoprolol, which do not affect the bronchial muscles, could be
used in these circumstances.62,63 Primidone is an alternative first-line therapy
and is effective at a total daily dose of 250 mg/d. Besides direct benefits related
to actions against sodium channels in the neuronal membrane, the efficacy
of primidone is related to the metabolites such as phenobarbital and
phenylethylmalonamide.53 Confusion, ataxia, and nausea are side effects more
commonly seen in older patients using high doses. These side effects could be
minimized with the initiation of therapy at low doses and slow titration.64 In one
study, pretreatment with phenobarbital initiated 3 days before primidone was
found to mitigate the psychotropic side effects.65 Combined therapy with
propranolol and primidone has been observed to yield better clinical outcomes.
Although the medications improve arm tremor, efficacy in controlling the
head tremor is limited. When the arm and/or head tremor persists or the
medications cannot be tolerated, the next step in the treatment ladder is to use
topiramate,66 gabapentin,67 benzodiazepines,68 and botulinum toxin type A
injections.69,70 The medications investigated in clinical trials have shown these
agents to be relatively less efficacious compared with the first-line agents or have
revealed insufficient evidence for controlling symptoms.71 Thus, prescribing
these drugs is more justified in the presence of comorbidities. For example,
benzodiazepines could be chosen if psychiatric comorbidities are present.
Surgical intervention is recommended for symptoms that are refractory to all
available medications yet are functionally disabling and socially embarrassing.
Multiple surgical modalities are available, each with risks and benefits that need
due consideration. Deep brain stimulation is the most frequently used surgical
procedure; it electrically modulates the behavior of the tremor circuitry. Deep
brain stimulation has gained widespread acceptance and popularity because of its
efficacy in controlling arm and head tremors, and, more importantly, unlike
thalamotomy, which involves creating a lesion, the surgery is nondestructive and
reversible in nature. It can be used to treat bilateral tremor symptoms without the

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DIAGNOSIS AND TREATMENT OF ESSENTIAL TREMOR

high risk of severe complications, such as dysarthria, dysphagia, and ataxia reported
in studies with bilateral thalamotomy procedures.72 The main disadvantages are
high expenses and potential risks related to infection, seizure, stroke, and hardware
complications. The implantation of a battery in the chest with replacement at
appropriate time intervals requires general anesthesia, although rechargeable
batteries are becoming commonly available. In 2016, the FDA approved transcranial
MRI-guided focused ultrasound (MRgFUS) treatment, which is noninvasive or
minimally invasive and involves creating permanent lesions with ultrasound
energy.73 Although direct comparison has not been performed, MRgFUS has
efficacy similar to deep brain stimulation. The MRgFUS procedure does not require
drilling of a burr hole and implantation of hardware. It is essential to discuss that
complete hair removal is needed, and the patients will need to lie in an MRI scanner
for 3 to 4 hours during the MRgFUS procedure.74 No data are available on long-term
follow-up or whether unilateral MRgFUS can effectively control axial symptoms
such as head tremor. Nevertheless, because the procedure is noninvasive and has
immediate benefits, more and more centers are offering this procedure. Another
noninvasive procedure is stereotactic radiosurgery, which does not require a burr
hole or hair removal; however, the procedure is used less often because the clinical
benefits are delayed and unpredictable.72

CONCLUSION
Essential tremor is among the most prevalent movement disorders. A thorough
history and detailed neurologic examination are required to identify the patterns
and nuances for an accurate diagnosis. Treatments for tremor control involve the
use of adaptive and orthotic devices, pharmacotherapies, and surgical
interventions in medication-refractory cases. Because essential tremor is not a
monosymptomatic disorder, ideal management involves a multidisciplinary
team of a neurologist; neuropsychologist; occupational, speech, and physical
therapists; and in some cases a neurosurgeon.

VIDEO LEGENDS
VIDEO 5-1
Clinical characteristics of essential tremor. The
first segment shows a 65-year-old woman with mild
bilateral slightly asymmetric postural tremor
affecting the arms, most significantly in amplitude at
the wrist joint, rather than more proximal or distal
joints. Generally, the tremor involves wrist
flexion-extension rather than rotation-supination.
The kinetic component is observed during a dot
approximation task. The next segment shows a
60-year-old man with a similar asymmetric postural
arm tremor. The final segment reveals the out-of-
phase character seen in some patients (seesaw
effect seen when arms are held in the wing-beating
position). When a bimanual task is performed (not
shown in the video), the movement direction of one
side could potentially cancel the out-of-phase
direction of the other side; this can be leveraged by
the patients during a functional task.
© 2022 American Academy of Neurology.
VIDEO 5-2
Head tremor in patients with cervical dystonia. The
video shows a 68-year-old woman with cervical
dystonia and slow head-bobbing, a 78-year-old
woman with right arm dystonic tremor, and a
71-year-old man with cervical dystonia and a jerky
head tremor that remains persistent when he is lying
supine with his head at rest.
© 2022 American Academy of Neurology.
VIDEO 5-3
Resting tremor assessment in Parkinson disease.
The video shows a 78-year-old man diagnosed with
Parkinson disease exhibiting a resting tremor in his
left hand when his arm is resting on the armrest. A
resting tremor is seen in both legs, more in his left
than in his right. Resting tremor in his hand is also
elicited with his arm resting in his lap (both positions
are commonly used during the neurologic
examination). Tremor in Parkinson disease involves
the distal joints (fingers and wrist), is characterized
by wrist pronation-supination, and has a slight
pill-rolling quality.
© 2022 American Academy of Neurology.

1346 OCTOBER 2022

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VIDEO 5-4
Bilateral physiologic arm tremor. The video reveals
a spectrum of physiologic tremors. The first patient
is a 75-year-old woman presenting with a tremor
that manifested within a few months of using
valproic acid for a mood disorder. The tremor was
coarse with resting, postural, and kinetic
components. The second patient is a 50-year-old
woman with generalized anxiety disorder; she had
fine rhythmic distal tremors involving her hands.
© 2022 American Academy of Neurology.
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