Differential diagnosis of common tremor syndromes
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Postgrad Med J 2005;81:756–762. doi: 10.1136/pgmj.2005.032979
Tremor is one of the most common involuntary movement
disorders seen in clinical practice. In addition to the
detailed history, the differential diagnosis is mainly clinical
based on the distinction at rest, postural and intention,
activation condition, frequency, and topographical
distribution. The causes of tremor are heterogeneous and it
can present alone (for example, essential tremor) or as a
part of a neurological syndrome (for example, multiple
sclerosis). Essential tremor and the tremor of Parkinson’s
disease are the most common tremors encountered in
clinical practice. This article focuses on a practical
approach to these different forms of tremor and how to
distinguish them clinically. Evidence supporting various
strategies used in the differentiation is then presented,
followed by a review of formal guidelines or
recommendations when they exist.
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Dr R Bhidayasiri,
Department of Neurology,
Research Institute, UCLA
Medical Center, 710
Westwood Plaza, Los
Angeles, CA 90095, USA;
Submitted 24 January 2005
Accepted 16 April 2005
remor is one of the most common involun-
practice. It is defined as an involuntary,
approximately rhythmic, and roughly sinusoidal
movement of one or more body parts. It is
differentiated from other involuntary movement
disorders, such as chorea, athetosis, ballism, tics,
and myoclonus, by its repetitive, stereotyped
movements of a regular amplitude and fre-
quency. Tremor may be confused with rhythmic
myoclonus (incorrectly termed cortical tremor),
which is typically characterised by brief muscle
twitches, confined to one limb or to adjacent
body regions, associated with spike-wave com-
plexes on the electroencephalogram (EEG) or
spinal lesions. Clonus, unlike tremor, represents
a rhythmic movement, which is increased by
muscle stretching. Asterixis can be distinguished
from tremor on the basis of electromyographic
(EMG) findings of prolonged absence of EMG
activity during ‘‘flapping’’ or abduction of the
upper extremities. Stereotypies may have rhyth-
mic components, but nevertheless are domi-
nanted by complex movements. Lastly, epilepsia
partialis continua (EPC) can produce regular
jerks of the arm or hand, which can be difficult
to distinguish from tremor. EPC is associated
with EEG changes (which may need to be
identified with back-averaging techniques), and
MRI changes in contralateral sensorimotor cor-
tremor is to characterise the tremor. Various
types of tremor can be distinguished clinically,
based on the activation condition, frequency, and
topographical distribution. Different classifica-
tions of tremor have been proposed although the
most useful and widely accepted classification
divides tremor according to the behaviour it
occurs, that is rest and action tremor, which is
further subdivided into postural and kinetic
tremor (table 1).
prevalent of these types of tremor, occurs during
sustained extension of the arm and during
voluntary movements, such as writing or typing.
Resting tremor is suspected, if it occurs with the
patient sitting with his arms firmly supported
without any voluntary activities, if it increases
with mental stress (counting backwards), and if
it is suppressed by voluntary movements. The
most common cause of resting tremor is idio-
pathic Parkinson’s disease (PD). The most
common cause of postural and kinetic tremor is
essential tremor (ET). Physiological tremor is an
action tremor and is present in every healthy
person under certain conditions. Tremor can
present alone or as part of a neurological
syndrome, for example multiple sclerosis, dysto-
nia, and neuropathy. This article discusses
different types of tremor with an emphasis on
salient features and how to distinguish them
clinically. Evidence supporting various available
strategies is then presented, followed by a review
of established guidelines.
ESSENTIAL TREMOR: THE MOST
COMMON FORM OF ACTION TREMOR
Action tremor refers to any tremor that is
produced by voluntary contraction of muscles,
including postural, isometric, and kinetic tremor.
The last includes intention tremor. As there are
no validated serological, radiological, and patho-
logical markers in ET, the diagnosis is primarily
based on clinical findings (box 1).
observe the patient sitting at rest to note whether
there is evidence of a resting tremor of the head,
hands, or legs. Then, ask the patient to stretch
out the arms and hands completely and look for
a postural tremor, followed by checking finger-
nose-finger movements looking for a kinetic
tremor. Typically, essential tremor is an action
tremor, either postural or kinetic in character,
mainly affecting the hands. It is usually bilateral
with a frequency of 4 Hz to 12 Hz and largely
The upper limbs are affected in
EMG, electromyography; EEG,
electroencephalography; EPC, epilepsia partialis
continua; PD, Parkinson’s disease; ET, essential tremor;
PET, positron emission tomography; DAT, dopamine
transporter; DBS, deep brain stimulation; VIM, ventral
and the amplitude may increase.
The prevalence ranges from
common type of tremor.
Many studies have shown that ET
However, some experts suspected that the
Although the condition
cases are considered familial with an autosomal dominant
pattern of inheritance.
regions have been linked to familial ET, one on chromosome
and another on chromosome 2p22–25.
specific gene mutations have been identified to date. The
penetrance is thought to be high, suggesting that 89% of
patients at risk have signs of ET by the age of 65.
of onset is typically 60–70 years, but not uncommonly before
60 years, and both sexes are equally affected. The tremor
commonly involves the head, jaw, neck, facial muscles,
tongue, and upper extremities but not the lip, which suggests
the tremor of PD in those cases.
Clinically, the differentiation between ET and tremor of PD
can be difficult (table 2). However, important features that
support the tremor to be parkinsonian in origin include
asymmetric onset and it being at rest although 40% of tremor
in PD can be of mixed type of postural and resting tremors.
Tremor that occurs during walking usually suggests an
underlying diagnosis of PD. In addition, patients with ET
typically lack prominent extrapyramidal signs, including
bradykinesia, manifesting as progressive decrement in
amplitude and speed with ‘‘re-setting’’, postural instability
or rigidity. Fifty per cent of ET patients are alcohol responsive
but only temporarily.
Sometimes, it can be difficult to
pronounced postural tremor. In these circumstances, other
factors such as the presence of hypomimia and generalised
bradykinesia may need to be taken into account. A ‘‘no-no’’
or ‘‘yes-yes’’ head tremor is characteristic of ET and occurs
only rarely in PD. Handwriting is usually small and illegible
in PD but large and tremulous in ET (fig 1). If a noticeable
tremor is noted with speaking, ET is probable in most cases
with a possibility of isolated voice tremor in a minority. Most
patients with ET do not have abnormal neurological findings
except the tremor although signs of mild cerebellar dysfunc-
tion can be seen, supported by a recent study using positron
emission tomography (PET) showing increased cerebellar
When the presentation is atypical, functional
radiotracer 18-fluorodopa (FDOPA-PET) may permit the
diagnosis of PD in early stage, recording and quantifying
the deficiency of dopamine synthesis and storage within pre-
synaptic striatal nerve terminals. In addition, dopamine
transporter (DAT) single photon emission computed tomo-
graphy (SPECT), such as
distinguish between ET and PD in an early stage of the
disease with the results being within normal limits in ET.
drug history is mandatory as many drugs are capable of
producing postural and kinetic tremors (box 2). These drugs
include b-adrenergic agonists, valproic acid, thyroxin, tricyc-
lic antidepressants, selective serotonin reuptake inhibitors
(SSRIs), and lithium. These drugs may cause increased
physiological tremor that may be difficult to distinguish it
from ET. Therefore, clinicians must maintain a high level of
suspicion when a tremor develops after the start of a drug
treatment. The possibility of Wilson’s disease should always
be considered in any patient with an action tremor who is
younger than 40 years of age. A low serum ceruloplasmin is
useful screening test although not diagnostic and the level of
less than 200 mg/l has 95% sensitivity for this condition. A
slit-lamp examination for Kayser-Fleischer ring should also
be considered. However, patients with Wilson’s disease
usually present with dysarthria, dystonia, and parkinsonism
and very rarely present with isolated action tremor.
ET is believed to be of a central nervous system origin, but
central aetiology was partly supported by the beneficial effect
of thalamotomy, thalamic deep brain stimulation (DBS), and
drugs that act centrally. Numerous experimental physiologi-
cal and functional imaging studies have also implicated
dysfunction in brain stem structures, including the inferior
olive, locus coeruleus, red nucleus, thalamus, but cerebellum
seems to be a prime candidate for the site of dysfunction in
oscillator of a CNS ‘‘pacemaker’’ in a currently unknown
exact location that can be increased or suppressed by reflex
Classification of tremor
Tremor that occurs in a body part that
is not voluntarily activated and is
completed supported against gravity.
Any tremor that is produced by
voluntary contraction of muscle,
including postural, isometric, and
kinetic tremor. The last includes
Tremor that is present while
voluntarily maintaining a position
Tremor that occurs during any
voluntary movement. It may include
visually or non-visually guided
movements. Tremor during target
directed movement is called intention
muscle contraction against a rigid
Task specific tremor
Kinetic tremor that may appear or
become exacerbated during specific
Box 1 Clinical criteria for essential tremor
Definite essential tremor
Postural tremor of moderate amplitude is present in at
least one arm
Tremor of moderate amplitude is present in at least one
using a spoon to drink water drinking water, finger-to-
nose manoeuvre, and drawing a spiral.
Tremor must interfere with at least one activity of daily
Medications, hypothyroidism, alcohol, and other
Probable essential tremor
Medications, hyperthyroidism, alcohol, and other
neurological conditions are not the cause of tremor.
Common tremor syndromes
unsatisfactory. Probably, ET is not as benign as it is often
referred as benign essential or familial tremor. About 15%–
25% of patients with ET retire prematurely and 60% of
patients choose not to apply for a job or promotion because of
the uncontrollable shaking of their hands.
The two most
propranolol) and primidone. Because these drugs can result
in multiple side effects, especially during the titration phase,
they are not recommended for mild cases that do not cause
dysfunction or social embarrassment. Tremor of different
body parts and various tremor subtypes may also have
different pharmacological responsiveness. In general, the
start of specific pharmacological treatments is typically based
on patient age, coexistent conditions, prior exposure to drug
therapy, concurrent drug therapies, contraindications, physi-
cian and patient bias, as well as benefits and potential
adverse effects of certain agents. Drug dose is initially low,
gradually titrated upward as tolerated, and adjusted as
appropriate to identify the most efficacious dose with a
minimum of adverse effects (regulation of dose). If the drug
is of no benefit at a dose that causes adverse effects, dose
levels are gradually tapered down and treatment is eventually
stopped. If a drug is reported to be beneficial, it may be
continued at the regulated doses and the next drug may be
added to the drug regimen. If the response to a drug is
adequate and the dose well tolerated, the physician may keep
the patient at the same dose or decide to increase the dose
level (and continue to monitor tolerance). Propranolol, a
non-selective antagonist, is more effective than selective b
activity, with the dose of at least 120 mg/day resulting in a
response study of propranolol, 240–320 mg/day was found to
be the optimal dose range.
Furthermore, long acting
effective as conventional propranolol and has better com-
Propranolol is generally well tolerated. However,
arterioventricular block, and diabetes mellitus, have limited
its use in some patients. The mechanism of propranolol in ET
is not exactly known although central and peripheral
mechanisms have been proposed.
of patients obtain symptomatic relief from propranolol, but
dramatic improvement occurs in a much smaller percentage.
Similarly, primidone, an anticonvulsant in doses of up to
750 mg/day, has been shown to be effective than placebo in
reducing tremor. Although initial tolerability has limited the
use of primidone, we find that slow titration, beginning as
low as 12.5 mg/day, may lessen side effects (mainly drowsi-
ness) and increase tolerability. The mechanism of action of
primidone’s antitremor effect is also unknown. Phenobarbital
is one of primidone’s active metabolites but it has little, if
At rest, increases with walking.
Decreases with posture holding or
Hands and legs
Hands, head, voice
Stable or slowly progressive
Less common (1%)
Other neurological signs
Bradykinesia, rigidity, loss of
Substances that improve tremor
Alcohol, propranolol, primidone
Patients usually have other
parkinsonian features, requiring
subthalamic nucleus or internal globus
pallidus deep brain stimulation (DBS)
Thalamic VIM DBS or thalamotomy
Comparison of handwriting
in patients with PD (top) and ET
(bottom). Note that the handwriting in
PD is small and illegible in contrast with
ET, which is large and tremulous.
effects include nausea, vertigo, drowsiness, and unsteadiness.
Koller et al
showed in a placebo controlled study that
amplitude of hand tremor in both untreated and propranolol
treated patients. There was no correlation between therapeu-
tic response and serum concentrations. Neither drug was
conclusively shown to be superior to the other but more
patients had a preference for primidone than for propranolol
in one study.
In addition to the first line treatments, many other drugs
Topiramate has been shown to be effective as well as
gabapentin and alprazolam.
intrinsic hand muscles can be considered in medically
Lastly, DBS in the ventral intermedius
Therapy) is effective, with over 90% of patients having a
satisfactory result. Because this rate of improvement cannot
generally be achieved with current pharmacological therapy
and several long term studies have also shown the long term
efficacy, the Food and Drug Administration (FDA) has
approved this device for medically intractable cases and it
has now replaced thalamotomy.
PARKINSONIAN TREMOR: THE MOST COMMON
The tremor in PD typically occurs at rest and becomes less
prominent with voluntary movement. It typically occurs
initially in the distal upper extremity, and over time, moves
proximally and then to the other upper extremity, again in a
distal to proximal pattern. Seventy per cent of patients with
PD present with tremor and it usually has a better prognosis,
compared with PD patients with early postural instability and
akinesia. Action or postural tremor does occur in PD, either
alone or in combination, making the diagnosis difficult in
some cases, especially in the early stage.
In fact, pure rest
of rest and postural kinetic tremors. Isolated postural and
kinetic tremor rarely occurs in PD. As a result of the
variability of the clinical expression of tremors in PD, the
definition is based on the general diagnosis of PD rather than
on specific features of tremors. Only the rest tremor
component is by itself, a positive diagnostic criterion for PD
but other tremors are often seen. When the diagnosis is
unclear, levodopa trial may be considered to record the
remarkable improvement in patients with PD. In contrast
with akinesia and rigidity, the response of parkinsonian
tremor to dopaminergic treatment can be so variable and it is
the overall improvement that counts and supports the
A variety of agents have been used for tremor
gics, budipine, and as second line treatments, clozapine,
propranolol, and clonazepam.
However, double blind,
tremor in early PD are few with different methodologies
and the results are variable.
trihexylphenidyl, have been shown to be effective but rarely
used now because of its side effects, especially in the elderly
Therefore, anticholinergics are not generally
patients over 65 years of age. Both dopaminergic and
anticholinergics are probably equally effective in parkinso-
nian tremor, but dopaminergic substances additionally
improve other parkinsonian signs. Dopamine agonists, such
as pramipexole and ropinirole, are probably the most effective
antitremor drugs among all dopaminergic treatments and
should be considered in all newly diagnosed tremor
predominant PD patients who have no cognitive impair-
Improvement of tremor has also been reported with
other dopamine agonists, including pergolide and bromo-
Dopamine agonists are also useful in advanced
As for akinesia and rigidity, after longer
necessary for adequate control of resting tremor in many
Some patients have a predominant postural tremor in
addition to their rest tremor. This form is uncommon and has
been considered to be a combination of an ET with PD
although the relation between postural tremor that is
phenomenologically similar to ET and PD has not been well
defined. Further studies are needed to define the relation
between ET and other tremors, including PD and other task
WHAT IS THE PHYSIOLOGICAL TREMOR?
Physiological tremor is seen in all normal people when
muscles are activated. The tremor is typically postural and is
thought to arise from the resonant oscillation of a limb as a
result of mechanical factors affecting it. Because the
physiological tremor has 8–12 Hz, and a rhythm in the
electroencephalogram has a similar frequency (7–13 Hz), a
common central hypothesis was raised.
interfere with activities of daily living. The frequency of
physiological tremor is ,6 Hz before age 9 years, increasing
to 12 Hz by the mid-teen years, and decreasing slightly above
60 years. The frequency usually decreases when large inertia
loads are applied to the limb, as shown with accelerometry
The amplitude is typically so low as
Increased physiological tremor is defined by the easy visibility
of high frequency, postural tremor with no evidence of an
underlying neurological disease.
Furthermore, the cause is
logic tremor, for example stress and anxiety before public
performance. Indeed, some professional performers have
learned to avoid this response by taking a b blocker before the
event. Fatigue because of lack of sleep and consuming a large
amount of caffeine can be precipitating factors although one
study did not find physiological tremor to be significantly
increased by caffeine.
Relaxation sessions have been shown
Monoamine oxidase inhibitors
In general, no drugs are
be useful in some people, for example ophthalmic surgeons,
when fine coordinative movements are required.
thyrotoxicosis, pheochromocytoma, hypoglycaemia, withdra-
wal from opioids or sedatives.
Tremor is a common side effect of many drugs (box 2 lists
commonly used drugs that can cause tremor). Various drugs
and toxins can cause all types of tremor known clinically
although increased physiological tremor is most commonly
seen. Tremor is the dose limiting side effect of the b
adrenergic agonists, salbutamol and terbutaline, used to treat
month of starting valproic acid treatment and is more evident
when a dose is .750 mg/day although it can also occur when
the dose is within therapeutic range. It is the most common
tremorogenic drug among anticonvulsants, affecting up to
25% of patients.
Intention tremor may occur in patients on
lithium levels and manifests almost 100% in patients with
Tardive tremor, a rare disorder, represents a
to a dopamine receptor blocking agent (DRBA) within six
months of the onset of symptoms and persisting for at least
one month after stopping the offending drug.
It is usually
movements, such as eating and writing. Tremor can also
occur as a toxic reaction to marijuana, and 3,4-methylene-
dioxymethamphetamine or ecstasy.
The tremor is typically of low frequency below 5 Hz. It is
characteristically kinetic in nature and has an added
volitional component and particularly affects the head and
the upper half of the body. Postural tremor may be present,
but rest tremor is usually absent. When kinetic tremor occurs
or worsens as the target is reached, it is referred to as
terminal tremor. In rare occasions, cerebellar tremor also has
a rest component in which case it would be described as
Holmes’ tremor. In cerebellar tremor, the oscillations are of
variable amplitude and are perpendicular to the direction of
movement. It is usually best elicited during the finger-nose-
finger or heel-shin-heel tests. Furthermore, cerebellar tremor
is often associated with dysmetria, dyssynergia, and hypoto-
nia. Titubation is another tremor that is probably a result of
abonormality of the cerebellum or its afferent/efferent path-
ways and is a slow frequency oscillation depending on
postural innervation. Its rhythmicity is, at times, the only
sign distinguishing it from ataxia of the trunk. Multiple
sclerosis is a common cause of cerebellar tremor. Other
causes include Friedreich’s ataxia, spinocerebellar degenera-
tion, and cerebellar infarction. Although no clear correlations
between cerebellar lesions and tremor have been established,
lesions in the superior cerebellar peduncle and dentate
nucleus are the most common reported sites resulting in
Unfortunately, there is no established pharmacological
treatment are often less than satisfactory. However, as
multiple neurotransmitters as well as feedback pathways,
including brain stem, thalamus and cortical neurons, seem to
be involved, several drugs have been tried, but with variable
success, including odansetron (5-HT
refractory cases, chronic DBS of the VIM (or less commonly
provide an alternative.
Although few studies used highly
periods were generally one year or less, the data suggested
that chronic DBS of the VIM produced improved tremor
control in multiple sclerosis.
However, complete cessation of
cases in which tremor control decreased over time, and
frequent reprogramming became necessary.
The criteria suggestive of psychogenic tremor are sudden
onset but rarely a remitting course (box 3). The onset is
mostly associated with a stressful life event. According to a
modified Fahn’s criteria for psychogenic dystonia, the
diagnosis of psychogenic tremor is accepted with the
followings; (1) the major causes of symptomatic tremors
(such as medications, thyroid dysfunction, and hormonal or
metabolic dysfunction) have been excluded, (2) essential and
parkinsonian tremors are excluded on the basis of clinical
criteria, (3) no evidence for any other neurological disorders
is present, and (4) the patients had a period without tremor
of at least two weeks during the observation period.
resting and postural or intention tremors and most often
involves both arms, followed by the head and then the legs.
The tremor may be continuous or intermittent with fluctuat-
ing frequency and amplitude, but lacks the physiological
pattern. As mentioned, the onset is usually abrupt (73%)
with maximal disability (46%) at the onset that had static
course in 46% and fluctuating course in 17%.
tremor, the diagnosis can be obvious in patients with
usually stops during the examination as they are exhausting
for patients. Differential diagnosis in this setting is limited,
but includes orthostatic tremor, essential stance tremors, or
the rare stance tremor of PD.
The examination, especially the two clinical signs, are very
useful in this situation; the entrainment of tremor frequency
Box 3 Clinical features suggestive of
Unclassified tremor (complex tremors)
Changing tremor characteristics
Unresponsive to antitremor drugs
Tremor increases with attention, and lessens with
Responsive to placebo
Absence of other neurological signs
Multiple underdiagnosed conditions
Spontaneous remissions or cures of symptoms
No evidence of disease by laboratory or radiological
Employed in allied health professionals
Litigation or compensation pending
Presence of secondary gain
Presence of psychiatric disease
Reported functional disturbances in the past
Entrainment entails requiring the
part (finger or foot) at a different frequency than the
suspicious tremor. A psychogenic tremor automatically
changes to the frequency that is being enforced on the
uninvolved hand or foot, because it is difficult to maintain
two different volitional movement frequencies simulta-
neously in two different body parts. During passive move-
ment of the involved limb, an increased tone can be palpated
by the examiner. Once the increased tone disappears, the
tremor also disappears (coactivation sign). Cogwheeling in
the setting of PD and ET differs from the present coactivation
sign as the first is present over the whole range of movement
of a particular joint. In contrast, coactivation in psychogenic
tremor resembles voluntary coactivation with overlying
rhythmic trembling. In addition, coactivation can produce
bizarre positioning of the hands when they are out-
stretched. The absence of finger tremor is also suggestive of
psychogenic in origin. While physiological and pathological
tremors show a decrease of tremor amplitude when postural
with and without loading is compared, psychogenic tremor
tends to show an increase of their tremor amplitudes during
procedures before the final diagnosis is established. A review
of medical history in these patients usually shows multiple
functional somatic or psychosomatic illnesses. Once the
diagnosis is made, most patients continue to have a
fluctuating or constant course, followed by improving and
progressive periods suggesting the prognosis is far from
benign. The therapeutic success is also variable, but the
treatment approach should include various combinations of
psychotherapy as well as drugs, such as mild anxiolytics and
antidepressants. While pharmacological treatment in organic
tremor may reduce amplitude, but does not change the
tremor frequency, the effect of treatment in psychogenic
tremor usually varies from total suppression of tremor,
especially when associated with the suggestion of a ‘‘cure’’
to no benefit.
Interestingly, most of successfully treated
OTHER TYPES OF TREMOR
forms of tremor that are less common and some of them have
only been reported in a few case studies. Of these, dystonic
tremor is worth mentioning as many patients with dystonia
have tremor and it is sometimes difficult to distinguish
dystonic tremors from static tremors associated with dysto-
nia, which occur unspecifically in regions unaffected by
dystonia. Dystonic tremor is mainly a postural and kinetic
tremor in an extremity or body part affected by dystonia and
is not usually seen during complete rest.
It is now considered
range of frequencies (mainly less than 7 Hz), and remains
localised. A typical example is tremulous spasmodic torticol-
lis. The tremor tends to be localised, asymmetric, and
irregular in amplitude and periodicity. Many patients with
dystonic tremor use their own tricks (geste antagoniste or
sensory tricks) to reduce the tremor amplitude. These
together with the absence of attempts at suppressing the
tremor by voluntary muscle contractions are a fairly reliable
diagnostic sign. Head tremor is common in patients with
cervical dystonia and treatment with botulinum toxin often
results in significant improvement of tremor as well as
Orthostatic tremor is a rare disorder of middle aged or
elderly people that is characterised by unsteadiness on
standing, secondary to 16 Hz tremor in the lower extremities.
Characteristically, the tremors remit on walking, but
disappear when sitting or lying down.
Patients prefer to
ripple of muscle activity is visible. Confirmation of the
diagnosis can be obtained by EMG showing a 16 Hz pattern
in the leg muscles with the patient standing. In terms of
treatment, the drug most commonly used is clonazepam,
followed by levodopa and then drugs used for ET. Overall,
the treatment response seems to be unsatisfactory, but
some success has been reported with gabapentin (300–
2400 mg/day) in a small placebo controlled, double blind,
Holmes’ tremor is a term, proposed by the Ad Hoc
previously used midbrain tremor, rubral tremor, thalamic
tremor, myorhythmia, and Benedikt’s syndrome.
It is a
frequency (,4.5 Hz) during postural in nature, worsening
during movement and goal directed tasks. Like cerebellar
tremor, Holmes’ tremor is almost always attributable to
lesions, reported in upper brain stem, thalamus, or cerebel-
lum, interrupting pathways in the midbrain tegmentum
(rubro-olivocerebellorubral loop, rubrospinal fibres, nigros-
triatal fibres), and the serotonergic brain stem telencephalic
Palatal tremor, previously termed palatal myoclonus,
cerebellar lesions or essential without any identified brain
lesions. In symptomatic palatal tremor, inferior olivary
pseudohypertrophy is seen and considered as a hallmark
for the condition.
essential cases, patients usually have characteristic ear clicks
(rhythmic movements of the tensor veli palatini muscle),
which do not present in a symptomatic variety. Botulinum
toxin injection into each tensor veli palatini has been
reported to be of some benefits.
Tremors, mostly postural
peripheral neuropathy, particularly demyelinating neuropa-
thies (especially dysgammaglobulinaemic neuropathies). The
term ‘‘cortical tremor’’ is a misnomer as it is not a tremor but
a specific form of rhythmic myoclonus.
tremor) can be difficult because the driving muscle contrac-
tions can be so brisk resulting in longer pauses between
Tremor is a common problem seen in clinical practice.
Among all types of tremor, essential tremor is the most
common cause. In most cases of tremor, there is no
diagnostic laboratory test to confirm or exclude a particular
type of tremor and the diagnosis heavily relies on physician’s
own observation and thorough clinical examination as well
as clinical history. In persons younger than 40 years of age,
the possibility of Wilson’s disease should be excluded, as it is
a treatable and reversible condition if recognised promptly.
Differentiation between essential tremor and tremor of PD is
particularly important as the management and prognosis in
these two conditions are vastly different. Almost all drugs
used to treat tremor should be titrated slowly as side effects
and tolerability are the main issues of compliance. The
treatment should be evidence based. We recommend that the
first line treatments, if available, should be firstly attempted,
followed by second line treatments that are supported by
prospective clinical trials before finally choosing drugs from
Funding: Roongroj Bhidayasiri is supported by Lilian Schorr Postdoctoral
Fellowship of Parkinson’s Disease Foundation (PDF).
Conflicts of interest: none.
Common tremor syndromes
1 Deuschl G, Bain P, Brin M. Consensus statement of the Movement Disorder
Society on Tremor. Ad Hoc Scientific Committee. Mov Disord 1998;13(suppl
3 Grimes DA. Tremor—easily seen but difficult to describe and treat.
Can J Neurol Sci 2003;30(suppl 1):S59–63.
4 Louis, ed. Clinical practice. Essential tremor. N Engl J Med
5 Elble RJ. Essential tremor frequency decreases with time. Neurology
6 Brin MF, Koller W. Epidemiology and genetics of essential tremor. Mov Disord
7 Bharucha NE, Bharucha EP, Bharucha AE, et al. Prevalence of Parkinson’s
disease in the Parsi community of Bombay, India. Arch Neurol
8 Haerer AF, Anderson DW, Schoenberg BS. Prevalence of essential tremor.
Results from the Copiah County study. Arch Neurol 1982;39:750–1.
9 Louis ED, Ford B, Frucht S, et al. Risk of tremor and impairment from tremor in
relatives of patients with essential tremor: a community-based family study.
Ann Neurol 2001;49:761–9.
10 Bain PG, Findley LJ, Thompson PD, et al. A study of hereditary essential
tremor. Brain 1994;117:805–24.
11 Schrag A, Munchau A, Bhatia KP, et al. Essential tremor: an overdiagnosed
condition? J Neurol 2000;247:955–9.
12 Louis ED, Ford B, Barnes LF. Clinical subtypes of essential tremor. Arch Neurol
13 Louis ED, Barnes LF, Ford B, et al. Ethnic differences in essential tremor. Arch
14 Jankovic J. Essential tremor: a heterogenous disorder. Mov Disord
15 Gulcher JR, Jonsson P, Kong A, et al. Mapping of a familial essential tremor
gene, FET1, to chromosome 3q13. Nat Genet 1997;17:84–7.
16 Higgins JJ, Pho LT, Nee LE. A gene (ETM) for essential tremor maps to
chromosome 2p22–p25. Mov Disord 1997;12:859–64.
17 Rautakorpi I, Takala J, Marttila RJ, et al. Essential tremor in a Finnish
population. Acta Neurol Scand 1982;66:58–67.
18 Chouinard S, Louis ED, Fahn S. Agreement among movement disorder
specialists on the clinical diagnosis of essential tremor. Mov Disord
19 Wills AJ, Jenkins IH, Thompson PD, et al. A positron emission tomography
study of cerebral activation associated with essential and writing tremor. Arch
20 Asenbaum S, Pirker W, Angelberger P, et al. [123I]beta-CIT and SPECT in
essential tremor and Parkinson’s disease. J Neural Transm
21 Benamer TS, Patterson J, Grosset DG, et al. Accurate differentiation of
parkinsonism and essential tremor using visual assessment of [123I]-FP-CIT
SPECT imaging: the [123I]-FP-CIT study group. Mov Disord 2000;15:503–10.
22 Roberts EA, Schilsky ML. A practice guideline on Wilson disease. Hepatology
23 Deuschl G, Elble RJ. The pathophysiology of essential tremor. Neurology
24 Deuschl G, Wenzelburger R, Loffler K, et al. Essential tremor and cerebellar
dysfunction clinical and kinematic analysis of intention tremor. Brain
25 Wilms H, Sievers J, Deuschl G. Animal models of tremor. Mov Disord
26 Larsen TA, Calne DB. Essential tremor. Clin Neuropharmacol
27 Dietrichson P, Espen E. Effects of timolol and atenolol on benign essential
tremor: placebo-controlled studies based on quantitative tremor recording.
J Neurol Neurosurg Psychiatry 1981;44:677–83.
28 Koller WC. Dose-response relationship of propranolol in the treatment of
essential tremor. Arch Neurol 1986;43:42–3.
29 Cleeves L, Findley LJ. Propranolol and propranolol-LA in essential tremor: a
double blind comparative study. J Neurol Neurosurg Psychiatry
30 Young RR. Essential-familial tremor and other action tremors. Semin Neurol
31 Jefferson D, Jenner P, Marsden CD. beta-Adrenoreceptor antagonists in
essential tremor. J Neurol Neurosurg Psychiatry 1979;42:904–9.
32 Koller WC, Royse VL. Efficacy of primidone in essential tremor. Neurology
33 Gorman WP, Cooper R, Pocock P, et al. A comparison of primidone,
propranolol, and placebo in essential tremor, using quantitative analysis.
J Neurol Neurosurg Psychiatry 1986;49:64–8.
34 Connor GS. A double-blind placebo-controlled trial of topiramate treatment
for essential tremor. Neurology 2002;59:132–4.
35 Ondo W, Hunter C, Vuong KD, et al. Gabapentin for essential tremor: a
multiple-dose, double-blind, placebo-controlled trial. Mov Disord
36 Brin MF, Lyons KE, Doucette J, et al. A randomized, double masked,
controlled trial of botulinum toxin type A in essential hand tremor. Neurology
37 Koller W, Pahwa R, Busenbark K, et al. High-frequency unilateral thalamic
stimulation in the treatment of essential and parkinsonian tremor. Ann Neurol
38 Limousin P, Speelman JD, Gielen F, et al. Multicentre European study of
thalamic stimulation in parkinsonian and essential tremor. J Neurol Neurosurg
39 Koller WC, Hubble JP. Levodopa therapy in Parkinson’s disease. Neurology
40 Wasielewski PG, Burns JM, Koller WC. Pharmacologic treatment of tremor.
Mov Disord 1998;13(suppl 3):90–100.
41 Koller WC. Pharmacologic treatment of parkinsonian tremor. Arch Neurol
42 Hughes AJ, Lees AJ, Stern GM. Apomorphine in the diagnosis and treatment
of parkinsonian tremor. Clin Neuropharmacol 1990;13:312–17.
43 Katzenschlager R, Sampaio C, Costa J, et al. Anticholinergics for symptomatic
management of Parkinson’s disease. Cochrane Library. Issue 2. Oxford:
Update Software, 2003.
44 Navan P, Findley LJ, Jeffs JA, et al. Double-blind, single-dose, cross-over
study of the effects of pramipexole, pergolide, and placebo on rest tremor and
UPDRS part III in Parkinson’s disease. Mov Disord 2003;18:176–80.
45 Pogarell O, Gasser T, van Hilten JJ, et al. Pramipexole in patients with
Parkinson’s disease and marked drug resistant tremor: a randomised, double
blind, placebo controlled multicentre study. J Neurol Neurosurg Psychiatry
46 Schrag A, Keens J, Warner J. Ropinirole for the treatment of tremor in early
Parkinson’s disease. Eur J Neurol 2002;9:253–7.
47 Korczyn AD, Brunt ER, Larsen JP, et al. A 3-year randomized trial of ropinirole
and bromocriptine in early Parkinson’s disease. The 053 Study Group.
48 van Laar T, Lledo A, Quail D, et al. An analysis of the improvement in activities
of daily living (ADL) and motor score associated with pergolide monotherapy
in the treatment of Parkinson’s disease. Eur J Neurol 1999;6:133.
49 Pizzuti GP, Byford GH, Cifaldi S, et al. Finger tremor and the central nervous
system. J Biomed Eng 1992;14:356–9.
50 Deuschl G, Raethjen J, Lindemann M, et al. The pathophysiology of tremor.
Muscle Nerve 2001;24:716–35.
51 Koller W, Cone S, Herbster G. Caffeine and tremor. Neurology
52 Comby B, Chevalier G, Bouchoucha M. A new method for the measurement of
tremor at rest. Arch Int Physiol Biochim Biophys 1992;100:73–8.
53 Karas BJ, Wilder BJ, Hammond EJ, et al. Valproate tremors. Neurology
54 Vestergaard P. Clinically important side effects of long-term lithium treatment:
a review. Acta Psychiatr Scand Suppl 1983;305:1–36.
55 Stacy M, Jankovic J. Tardive tremor. Mov Disord 1992;7:53–7.
56 Demirkiran M, Jankovic J, Dean JM. Ecstasy intoxication: an overlap between
serotonin syndrome and neuroleptic malignant syndrome. Clin
57 Finsterer J, Muellbacher W, Mamoli B. Yes/yes head tremor without
appendicular tremor after bilateral cerebellar infarction. J Neurol Sci
58 Thach WT, Goodkin HP, Keating JG. The cerebellum and the adaptive
coordination of movement. Annu Rev Neurosci 1992;15:403–42.
59 Sandyk R. Successful treatment of cerebellar tremor with clonazepam. Clin
60 Trelles L, Trelles JO, Castro C, et al. Successful treatment of two cases of
intention tremor with clonazepam. Ann Neurol 1984;16:621.
61 Wishart HA, Roberts DW, Roth RM, et al. Chronic deep brain stimulation for
the treatment of tremor in multiple sclerosis: review and case reports. J Neurol
Neurosurg Psychiatry 2003;74:1392–7.
62 Nandi D, Aziz TZ. Deep brain stimulation in the management of neuropathic
pain and multiple sclerosis tremor. J Clin Neurophysiol 2004;21:31–9.
63 Deuschl G, Koster B, Lucking CH, et al. Diagnostic and pathophysiological
aspects of psychogenic tremors. Mov Disord 1998;13:294–302.
64 Kim YJ, Pakiam AS, Lang AE. Historical and clinical features of psychogenic
tremor: a review of 70 cases. Can J Neurol Sci 1999;26:190–5.
65 Koller W, Lang A, Vetere-Overfield B, et al. Psychogenic tremors. Neurology
66 Uddin MK, Rodnitzky RL. Tremor in children. Semin Pediatr Neurol
67 Onofrj M, Thomas A, Paci C, et al. Gabapentin in orthostatic tremor: results of
a double-blind crossover with placebo in four patients. Neurology
68 Samie MR, Selhorst JB, Koller WC. Post-traumatic midbrain tremors.
69 Deuschl G, Toro C, Valls-Sole J, et al. Symptomatic and essential palatal
tremor. 1. Clinical, physiological and MRI analysis. Brain 1994;117:775–88.
70 Deuschl G, Toro C, Hallett M. Symptomatic and essential palatal tremor. 2.
Differences of palatal movements. Mov Disord 1994;9:676–8.
71 Cho JW, Chu K, Jeon BS. Case of essential palatal tremor: atypical features
and remarkable benefit from botulinum toxin injection. Mov Disord
72 Bhidayasiri R, Waters MF, Giza CC. Neurological differential
diagnosis: a prioritized approach. Oxford: Blackwell, 2005.
73 Manyam BV. Uncommon forms of tremor. In: Watts RL, Koller WC, eds.
Movement disorders: neurologic principles and practice. 2nd ed. New York: