Essential tremor: Clinical features and diagnosis

Official reprint from UpToDate® www.uptodate.com

©2023 UpToDate®

Essential tremor: Clinical features and diagnosis

Author: Tsao-Wei Liang, MD
Section Editor: Howard I Hurtig, MD
Deputy Editor: April F Eichler, MD, MPH

Contributor Disclosures

All topics are updated as new evidence becomes available and our peer review process is complete.

Literature review current through: Sep 2023. | This topic last updated: Jun 06, 2022.

INTRODUCTION

Essential tremor (ET) is the most common cause of action tremor in adults. It classically involves the
hands and is brought out by arm movement and sustained antigravity postures, affecting common daily
activities such as writing, drinking from a glass, and handling eating utensils. ET is slowly progressive
and can involve the head, voice, and rarely the legs, in addition to the upper limbs.

ET often runs in families and can be 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 (PD).
However, the use of "benign" as a modifier for ET is best omitted, since the tremor can be severe and
disabling.

This topic will cover the epidemiology, pathogenesis, clinical features, and diagnostic evaluation of ET.
The treatment and prognosis of ET are discussed separately. (See "Essential tremor: Treatment and
prognosis" and "Surgical treatment of essential tremor".)

EPIDEMIOLOGY

ET is the most common cause of action tremor, with an estimated prevalence worldwide of 1 percent
overall and approximately 5 percent in adults over the age of 60 years [1-3]. The incidence of ET
increases with age, although childhood and early adulthood presentations do occur, especially when ET
is familial [4].

The prevalence of ET is similar in males and females, although some studies report a slight male
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Essential tremor: Clinical features and diagnosis

predominance [3].

PATHOGENESIS AND GENETICS

The pathogenesis of ET is largely unexplained, and phenotypic and genetic heterogeneity suggest that
ET may represent a syndrome of related disorders rather than a single disease [5,6].

There appears to be a strong genetic component. A family history of tremor is present in 30 to 70

percent of patients with ET. The proportion is as high as 80 percent among those with onset at or before
the age of 40 years [7,8]. Evidence from family and linkage studies suggests an autosomal dominant
inheritance pattern with reduced penetrance [7,9-13].

First-degree relatives of patients with ET have an increased risk of developing the disorder, particularly
when the proband develops ET at an early age [14]. The lack of 100 percent concordance among
monozygotic twins suggests that environmental factors are also involved in the pathogenesis [15].

A number of risk variants have been identified in genome-wide association studies [16]. Putative risk
genes requiring further validation include leucine-rich repeat and immunoglobulin domain-containing
protein 1 (LINGO1), solute carrier family 1 member 2 (SLC1A2), serine/threonine kinase 32B (STK32B),
PPARG coactivator 1 alpha (PPARGC1A), and catenin alpha 3 (CTNNA3) [17-21]. An apparently pathogenic
rare variant in the fused in sarcoma (FUS) gene, distinct from those that cause a form of familial
amyotrophic lateral sclerosis, was reported in one large family with hereditary ET [22]. Repeat guanine-
guanine-cytosine (GGC) expansion in the notch 2 N-terminal like C (NOTCH2NLC) gene has been
associated with ET in a small subset of Chinese families with ET [23]. (See "Familial amyotrophic lateral
sclerosis", section on 'ALS6 (FUS gene)'.)

The neuropathologic basis of ET remains poorly defined and controversial, but the cerebellum and
brainstem (locus ceruleus) have been most commonly implicated [24,25]. A systematic review of 51
neuroimaging studies in patients with ET noted that most studies identified functional and structural
brain abnormalities in various parts of the cerebellum, but these reports lacked consistent findings that
would support a conclusive topography of neurodegeneration. In addition, it was unclear whether the
neuroimaging abnormalities contributed to the clinical symptoms of ET [24,26-33].

CLINICAL FEATURES

Tremor characteristics — ET is an action tremor that classically affects the hands and arms, is typically

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Essential tremor: Clinical features and diagnosis

bilateral, and is often slightly asymmetric. It can also affect the head, voice, and less commonly the face
or trunk.

Tremor is activated by voluntary movement or when the arms are held in a fixed posture against gravity.
ET becomes immediately apparent in the arms when they are held outstretched and is often amplified
by goal-directed movements such as drinking from a glass or finger-to-nose testing. Tremor is absent
when the affected body part is fully relaxed and supported against gravity. At times, action tremor may
overflow into a limb or other body part when not completely relaxed, giving the appearance of a rest
tremor.

Tremor frequency is typically moderate to high (6 to 12 Hz), although there is considerable variability
[34,35]. The type of tremor in ET may vary from a low-amplitude, high-frequency postural tremor of the
hands to a much larger-amplitude tremor that is activated by particular postures and actions.

Tremor of the head in patients with ET may be vertical ("yes-yes") or horizontal ("no-no") and is usually
associated with tremor of the hand or voice [36]. According to diagnostic criteria, isolated head or voice
tremor is exclusionary for ET [37]. Isolated head tremor often suggests the possibility of cervical
dystonia with dystonic head tremor, and isolated tremor of the voice is usually due to spasmodic
dysphonia. (See 'Dystonic head tremor' below and 'Spasmodic dysphonia' below.)

Lower limb tremor is highly unusual in ET and often suggests Parkinson disease (PD). (See 'Parkinson
disease' below.)

Exacerbating and relieving factors — Patients with ET can develop enhanced physiologic tremor due
to anxiety, excitement, or other adrenergic stimulation, thereby worsening the underlying tremor. In
contrast to physiologic tremor, ET is not usually exacerbated by caffeine. ET is typically relieved by small
amounts of alcohol.

"Soft" neurologic signs — By definition, tremor should be the only neurologic manifestation of ET.
However, in some cases, difficulty with tandem gait, mild cognitive impairment, and slight overflow of
the tremor into a resting posture may be present. Proposed, though controversial, terminology used to
describe ET with such soft neurologic signs is so-called "ET plus" [37,38]. (See 'Clinical criteria' below.)

Preliminary studies suggest that very mild cognitive deficits with reduced performance on tests of
memory and frontal executive function may be more common in patients with ET than age-matched
controls [39-42], and that ET may be associated with an increased risk of dementia [43,44].

Natural history — ET tends to worsen gradually over time. Symptoms of ET are often present for years
to decades before patients seek medical attention.
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Essential tremor: Clinical features and diagnosis

The course is generally slowly progressive, but may be exacerbated by anxiety, medical stressors, or
new medications. There may sometimes appear to be a stepwise worsening of tremor, perhaps due to
other contributing factors such as anxiety, medical illness, or the addition of new medications. Spread to
previously uninvolved body parts may also occur. Disability from the tremor is often significant, as it
very typically affects writing, signing of checks and other documents, using tools or eating utensils, and
holding drinks. (See "Essential tremor: Treatment and prognosis", section on 'Prognosis'.)

DIFFERENTIAL DIAGNOSIS

Although ET may be the most common isolated action tremor syndrome ( table 1), there is a broad
differential diagnosis for kinetic and postural tremors. The main considerations in the differential
diagnosis of ET are enhanced physiologic tremor, parkinsonian tremor, and dystonic tremor (
algorithm 1).

Enhanced physiologic tremor — Enhanced physiologic tremor is a common cause of action tremor
and can mimic mild ET.

Healthy individuals have a symmetrical, very low-amplitude, high-frequency (8 to 12 Hz) physiologic

action tremor in the upper limbs. Physiologic tremor is usually not visible under ordinary circumstances,
although some people have a natural proclivity to demonstrate mild, nondisabling physiologic
tremulousness.

Many factors can enhance physiologic tremor to the point of detection, most often by increasing
sympathetic activity. Common factors that lead to enhanced physiologic tremor are stress, anxiety,
excitement, muscle fatigue, fever, hypoglycemia, alcohol or opioid withdrawal, and a variety of
medications, drugs, and substances ( table 2). (See "Overview of tremor", section on 'Physiologic
tremor'.)

Resolution of enhanced physiologic tremor with removal of the precipitating factor distinguishes it from
ET. The duration of tremor is also useful, as patients typically report a much shorter duration of
enhanced physiologic tremor than of ET.

Parkinson disease — Differentiating between a parkinsonian tremor and ET is the most common
scenario facing clinicians and is a primary concern of patients presenting with tremor.

In its classic form, tremor due to Parkinson disease (PD) is a rest tremor and at onset typically begins
unilaterally, which distinguishes it from ET ( table 3). The absence of rest tremor is generally
reassuring that tremor is due to ET and not PD, especially combined with an otherwise normal
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Essential tremor: Clinical features and diagnosis

neurologic examination (ie, no bradykinesia or rigidity).

However, some overlap exists. Patients with PD can have a rapid postural or action tremor
indistinguishable from ET [45]. In fact, it is not unusual for patients with PD to present with a postural
tremor shortly before they display other signs of PD. The presence of subtle bradykinesia, rigidity, or
micrographia in early cases of parkinsonian postural tremor supports the diagnosis of PD, although
these signs may not appear until later. In addition, a tremor of the same frequency and amplitude as the
rest tremor may emerge after a latency during posture holding (the so-called re-emergent tremor). By
contrast, ET is apparent immediately with a posture-holding maneuver.

Conversely, patients with severe ET may have a rest component to their tremor in the arms or hands.
Older adult patients with ET may have subtle bradykinesia or limb cogwheel rigidity, which needs to be
followed as it may signify the emergence of PD.

Involvement of certain body parts can also be helpful in distinguishing PD and ET. While a tremor of the
head and neck is more likely to be a symptom of ET, tremor of the jaw or lips is more commonly due to
PD. A rest tremor involving the foot or legs almost always suggests a parkinsonian tremor.

Evaluation for classic motor signs of PD (bradykinesia, rigidity, gait, and nonmotor features such as
rapid eye movement [REM] sleep behavior disorder and hyposmia) will further distinguish PD from ET.
Additional characteristics of tremor in patients with PD are reviewed separately. A handwriting and
drawing sample are helpful in distinguishing ET from PD. (See "Clinical manifestations of Parkinson
disease", section on 'Tremor'.)

Dystonic head tremor — When head tremor occurs in relative isolation, without action tremor in the
upper limbs or signs of cerebellar dysfunction, the possibility of dystonic head tremor due to cervical
dystonia (spasmodic torticollis) should be considered.

Cervical dystonia is the most common isolated focal dystonia and typically leads to head rotation
(torticollis), tilt (laterocollis), flexion, or extension. Tremor of the head is common in cervical dystonia, in
which it may be due either to a coincidence of ET and cervical dystonia or to a manifestation of dystonic
muscle spasm. Cervical dystonia may also present primarily as an isolated head tremor, with minimal
pain, stiffness, or deviation of the head.

Head tremor due to cervical dystonia tends to be more irregular and jerky than ET-related head tremor
and increases with various changes in head position, most often when rotating the head away from the
side of torticollis. ET-related head tremor usually subsides with the head supported on a pillow, while in
cervical dystonia head tremor often persists in the reclining position. (See "Etiology, clinical features,
and diagnostic evaluation of dystonia", section on 'Cervical dystonia'.)
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Essential tremor: Clinical features and diagnosis

To help distinguish head tremor in ET from dystonic head tremor, patients should be examined in the
supine position with the head fully supported and relaxed. Essential head tremor tends to resolve in the
supine position, whereas dystonic head tremor generally persists [46]. In addition, other signs of
dystonic tremor include emergence with specific positions (eg, head turn, neck flexion-extension) or
tasks (eg, writing). Posture of the head and shoulders in repose and passive range of motion of the neck
in the horizontal and vertical planes should also be examined for evidence of an underlying dystonia.

Spasmodic dysphonia — Voice tremor may be a manifestation of ET but rarely occurs in isolation; when
it does, it is important to differentiate it from spasmodic dysphonia, a focal dystonia. Essential voice
tremor is best identified by asking the patient to hold a steady note such as "ahhhh" or "eeeee." With
essential tremor, the voice sounds unstrained and quavering; with spasmodic dysphonia, the vocal
tremor is accompanied by hoarseness, straining, a strangulated quality, or voice breaks. (See "Etiology,
clinical features, and diagnostic evaluation of dystonia", section on 'Laryngeal dystonia'.)

Other action tremors — Cerebellar outflow tremor should be considered when the tremor oscillations
increase steadily before arriving at the target rather than at the termination of goal-directed activity. For
example, ET-related tremor is often mild or even absent during the course of finger-nose testing but will
first appear or increase within a few seconds after reaching the target. However, a distinction between
the two is often difficult. The presence of ataxia, dysmetria, proximal distribution of the tremor, or wide-
based and ataxic gait usually suggests a cerebellar disorder as a cause of tremor rather than ET.
However, mild cerebellar signs are present in some severe forms of ET [47]. (See "Overview of tremor",
section on 'Cerebellar tremor'.)

Other less common causes of action tremor that may occasionally overlap in some ways with ET,
including task-specific tremor such as writing tremor and orthostatic tremor, a form of postural tremor,
are reviewed separately. (See "Overview of tremor", section on 'Action tremors'.)

EVALUATION

ET is a clinical diagnosis, and the goal of the evaluation is to identify characteristic features of ET and to
recognize any atypical features that may suggest an alternative cause of tremor.

History and neurologic examination — The history should include information on age of onset of
tremor, degree of progression over time, involved body parts, activities that are most affected by the
tremor, relieving factors such as alcohol, and family history of ET in grandparents, parents, or siblings.
In addition, details about embarrassment, level of social disability, and specific ways in which the tremor
affects patient function are important to elicit and document.

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Essential tremor: Clinical features and diagnosis

Exacerbating factors such as exercise, fatigue, or stress should be elicited. Interestingly, caffeine usually
does not aggravate ET, although it does aggravate physiologic tremor. A complete list of medications
should be reviewed to exclude the possibility that a medication is exacerbating a physiologic tremor.
(See 'Enhanced physiologic tremor' above.)

A detailed neurologic examination aims to identify specific features of the tremor, including its
frequency (estimated by visual inspection), amplitude, body distribution, and activating conditions (ie,
whether the tremor appears at rest, with antigravity posture, or voluntary goal-directed activity), and to
identify other neurologic findings if present, in particular signs of parkinsonism (eg, rigidity,
bradykinesia, postural instability) [48]. In patients with relatively isolated head tremor, the head should
be examined in the supine position, fully supported. (See 'Dystonic head tremor' above.)

Laboratories — Routine laboratory tests should be performed to exclude common treatable causes of
enhanced physiologic tremor, including electrolytes (particularly serum calcium) and a thyroid function
test. Diagnostic studies to exclude Wilson disease should be considered in anyone under age 40 who
has unexplained tremor or other involuntary movements. (See "Wilson disease: Clinical manifestations,
diagnosis, and natural history".)

Indications for brain imaging — Structural brain imaging (magnetic resonance imaging [MRI] or
computed tomography [CT]) is not required in patients with typical clinical features of ET. Neuroimaging
should be pursued when there are focal neurologic examination findings or sudden onset of symptoms
that suggest a possible structural cause for tremor, such as stroke, demyelinating disease, or mass
lesion.

DIAGNOSIS

The diagnosis of ET is purely based on clinical features [49]. Dopamine transporter imaging is useful in
selected patients but is not necessary to diagnose ET in the majority of patients.

Clinical criteria — Diagnostic criteria from the International Parkinson and Movement Disorder Society
(IPMDS) task force define ET by the following four features [37]:

● Isolated tremor consisting of bilateral upper limb action (kinetic and postural) tremor, without
other motor abnormalities

● At least three years in duration

● With or without tremor in other locations (eg, head, voice, or lower limbs)
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Essential tremor: Clinical features and diagnosis
● Absence of other neurologic signs, such as dystonia, ataxia, or parkinsonism

The IPMDS consensus statement also defines the diagnostic category of ET plus, which should be used
to label patients with "soft" neurologic signs that are of uncertain significance and relationship to the
tremor, such as questionable dystonic posturing, rest component of tremor, and memory impairment
[37]. (See '"Soft" neurologic signs' above.)

Previous criteria for ET recognized family history of ET and beneficial response to alcohol as secondary
criteria [50]; while these are common in patients with ET, the IPMDS felt that they were not consistent
enough to include in the definition [37].

Role of dopamine transporter imaging — Striatal dopamine transporter imaging using ioflupane I-
123 single-photon emission computed tomography (SPECT; DaTscan) is normal in patients with ET and
can reliably distinguish ET from disorders associated with nigrostriatal degeneration, namely Parkinson
disease (PD) and other parkinsonian syndromes (ie, dementia with Lewy bodies, multiple system
atrophy, progressive supranuclear palsy, and corticobasal degeneration). (See "Diagnosis and
differential diagnosis of Parkinson disease", section on 'DaTscan'.)

While DaTscan is not necessary or indicated to diagnose ET in most patients, DaTscan may be helpful for
the following scenarios:

● Patients for whom the diagnosis of ET versus PD is unclear after serial clinical evaluations

● Patients with longstanding ET who later develop equivocal signs of PD and fail to respond to
levodopa

● Patients with ET who are possible candidates for deep brain stimulation but have emerging signs
of parkinsonism

SOCIETY GUIDELINE LINKS

Links to society and government-sponsored guidelines from selected countries and regions around the
world are provided separately. (See "Society guideline links: Essential tremor".)

PATIENT PERSPECTIVE TOPICS

Patient perspectives are provided for selected disorders to help clinicians better understand the patient

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Essential tremor: Clinical features and diagnosis

experience and patient concerns. These narratives may offer insights into patient values and
preferences not included in other UpToDate topics. (See "Patient perspective: Essential tremor with
onset in childhood" and "Patient perspective: An artist with essential tremor".)

SUMMARY AND RECOMMENDATIONS

● Epidemiology – Essential tremor (ET) is the most common nonphysiologic cause of action tremor (
table 1), with an estimated prevalence worldwide of 1 percent overall and approximately 5
percent in adults over the age of 60 years. (See 'Epidemiology' above.)

● Pathogenesis – Although the pathogenesis of ET is largely unexplained, there is a strong genetic

component. A family history is present in 30 to 70 percent of patients with the disorder. (See
'Pathogenesis and genetics' above.)

● Clinical features – ET is an action tremor that classically affects the hands and arms, is virtually
always bilateral, and is often slightly asymmetric. It can also affect the head, voice, and less
commonly the face or trunk. The tremor affects common daily activities such as writing, drinking
from a glass, and handling eating utensils. (See 'Tremor characteristics' above.)

ET is often aggravated by anxiety or other adrenergic stimulation and may be relieved by small
amounts of alcohol. (See 'Exacerbating and relieving factors' above.)

● Differential diagnosis – The main considerations in the differential diagnosis of ET are enhanced
physiologic tremor, Parkinson disease (PD) and other parkinsonian syndromes ( table 3), and
dystonic head tremor. Spasmodic dysphonia should also be considered in patients with isolated
vocal tremor. (See 'Differential diagnosis' above.)

● Evaluation – ET is a clinical diagnosis. Aside from tremor, the neurologic examination should be
normal. A detailed neurologic examination aims to identify abnormalities, in particular
parkinsonism (eg, rigidity, bradykinesia, postural instability) or ataxia, that suggest an alternative
diagnosis ( algorithm 1). (See 'History and neurologic examination' above.)

Routine laboratory tests should be performed to exclude common treatable causes of enhanced
physiologic tremor, including electrolytes (particularly serum calcium) and a thyroid function test.
Structural brain imaging is not required in patients with typical clinical features of ET. (See
'Laboratories' above and 'Indications for brain imaging' above.)

● Diagnosis – Diagnostic criteria define ET as an isolated tremor syndrome consisting of bilateral

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Essential tremor: Clinical features and diagnosis

upper limb action tremor; at least three years in duration; with or without head, voice, or lower
limb tremor; and absent other neurologic signs such as dystonia, ataxia, or parkinsonism. (See
'Clinical criteria' above.)

● Role of dopamine transporter imaging – Striatal dopamine transporter imaging using ioflupane
I-123 single-photon emission computed tomography (SPECT; DaTscan) is not routinely indicated in
patients with typical features of ET but can be useful in selected patients, such as those with subtle
parkinsonism in whom the diagnosis of ET versus PD remains unclear after serial clinical
evaluations. (See 'Role of dopamine transporter imaging' above.)

ACKNOWLEDGMENTS

The UpToDate editorial staff acknowledges Ludy Shih, MD, and Daniel Tarsy, MD, who contributed to
earlier versions of this topic review.

REFERENCES

1. Dogu O, Sevim S, Camdeviren H, et al. Prevalence of essential tremor: door-to-door neurologic

exams in Mersin Province, Turkey. Neurology 2003; 61:1804.

2. Benito-León J, Bermejo-Pareja F, Morales JM, et al. Prevalence of essential tremor in three elderly
populations of central Spain. Mov Disord 2003; 18:389.

3. Louis ED, Ferreira JJ. How common is the most common adult movement disorder? Update on the
worldwide prevalence of essential tremor. Mov Disord 2010; 25:534.

4. Jankovic J, Madisetty J, Vuong KD. Essential tremor among children. Pediatrics 2004; 114:1203.

5. Louis ED. 'Essential tremor' or 'the essential tremors': is this one disease or a family of diseases?
Neuroepidemiology 2014; 42:81.

6. Hopfner F, Haubenberger D, Galpern WR, et al. Knowledge gaps and research recommendations
for essential tremor. Parkinsonism Relat Disord 2016; 33:27.

7. Clark LN, Louis ED. Challenges in essential tremor genetics. Rev Neurol (Paris) 2015; 171:466.

8. Louis ED, Dogu O. Does age of onset in essential tremor have a bimodal distribution? Data from a
tertiary referral setting and a population-based study. Neuroepidemiology 2007; 29:208.

9. Gulcher JR, Jónsson P, Kong A, et al. Mapping of a familial essential tremor gene, FET1, to
chromosome 3q13. Nat Genet 1997; 17:84.

10. Higgins JJ, Pho LT, Nee LE. A gene (ETM) for essential tremor maps to chromosome 2p22-p25. Mov

- Page 10 of 13 -
Essential tremor: Clinical features and diagnosis

Disord 1997; 12:859.

11. Shatunov A, Sambuughin N, Jankovic J, et al. Genomewide scans in North American families reveal
genetic linkage of essential tremor to a region on chromosome 6p23. Brain 2006; 129:2318.

12. Kovach MJ, Ruiz J, Kimonis K, et al. Genetic heterogeneity in autosomal dominant essential tremor.
Genet Med 2001; 3:197.

13. Bain PG, Findley LJ, Thompson PD, et al. A study of hereditary essential tremor. Brain 1994; 117 ( Pt
4):805.

14. 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.

15. Tanner CM, Goldman SM, Lyons KE, et al. Essential tremor in twins: an assessment of genetic vs
environmental determinants of etiology. Neurology 2001; 57:1389.

16. Jasinska-Myga B, Wider C. Genetics of essential tremor. Parkinsonism Relat Disord 2012; 18 Suppl
1:S138.

17. Stefansson H, Steinberg S, Petursson H, et al. Variant in the sequence of the LINGO1 gene confers
risk of essential tremor. Nat Genet 2009; 41:277.

18. Thier S, Lorenz D, Nothnagel M, et al. LINGO1 polymorphisms are associated with essential tremor
in Europeans. Mov Disord 2010; 25:717.

19. Jiménez-Jiménez FJ, García-Martín E, Lorenzo-Betancor O, et al. LINGO1 and risk for essential
tremor: results of a meta-analysis of rs9652490 and rs11856808. J Neurol Sci 2012; 317:52.

20. Thier S, Lorenz D, Nothnagel M, et al. Polymorphisms in the glial glutamate transporter SLC1A2 are
associated with essential tremor. Neurology 2012; 79:243.

21. Müller SH, Girard SL, Hopfner F, et al. Genome-wide association study in essential tremor identifies
three new loci. Brain 2016; 139:3163.

22. Merner ND, Girard SL, Catoire H, et al. Exome sequencing identifies FUS mutations as a cause of
essential tremor. Am J Hum Genet 2012; 91:313.

23. Sun QY, Xu Q, Tian Y, et al. Expansion of GGC repeat in the human-specific NOTCH2NLC gene is
associated with essential tremor. Brain 2020; 143:222.

24. Louis ED, Faust PL, Vonsattel JP, et al. Neuropathological changes in essential tremor: 33 cases
compared with 21 controls. Brain 2007; 130:3297.

25. Louis ED, Babij R, Lee M, et al. Quantification of cerebellar hemispheric purkinje cell linear density:
32 ET cases versus 16 controls. Mov Disord 2013; 28:1854.

26. Louis ED. Essential tremor: evolving clinicopathological concepts in an era of intensive post-

- Page 11 of 13 -
Essential tremor: Clinical features and diagnosis

mortem enquiry. Lancet Neurol 2010; 9:613.

27. Louis ED. Understanding essential tremor: progress on the biological front. Curr Neurol Neurosci
Rep 2014; 14:450.

28. Jellinger KA. Is there cerebellar pathology in essential tremor? Mov Disord 2014; 29:435.

29. Rajput AH, Robinson CA, Rajput ML, Rajput A. Cerebellar Purkinje cell loss is not pathognomonic of
essential tremor. Parkinsonism Relat Disord 2011; 17:16.

30. Symanski C, Shill HA, Dugger B, et al. Essential tremor is not associated with cerebellar Purkinje cell
loss. Mov Disord 2014; 29:496.

31. Rajput AH, Adler CH, Shill HA, Rajput A. Essential tremor is not a neurodegenerative disease.
Neurodegener Dis Manag 2012; 2:259.

32. Shill HA, Adler CH, Sabbagh MN, et al. Pathologic findings in prospectively ascertained essential
tremor subjects. Neurology 2008; 70:1452.

33. Cerasa A, Quattrone A. Linking Essential Tremor to the Cerebellum-Neuroimaging Evidence.

Cerebellum 2016; 15:263.

34. Jankovic J. Essential tremor: a heterogenous disorder. Mov Disord 2002; 17:638.

35. Louis ED. Essential tremors: a family of neurodegenerative disorders? Arch Neurol 2009; 66:1202.

36. Louis ED, Dogu O. Isolated head tremor: part of the clinical spectrum of essential tremor? Data
from population-based and clinic-based case samples. Mov Disord 2009; 24:2281.

37. Bhatia KP, Bain P, Bajaj N, et al. Consensus Statement on the classification of tremors. from the task
force on tremor of the International Parkinson and Movement Disorder Society. Mov Disord 2018;
33:75.

38. Louis ED, Bares M, Benito-Leon J, et al. Essential tremor-plus: a controversial new concept. Lancet
Neurol 2020; 19:266.

39. Lombardi WJ, Woolston DJ, Roberts JW, Gross RE. Cognitive deficits in patients with essential
tremor. Neurology 2001; 57:785.

40. Gasparini M, Bonifati V, Fabrizio E, et al. Frontal lobe dysfunction in essential tremor: a preliminary
study. J Neurol 2001; 248:399.

41. Benito-León J, Louis ED, Bermejo-Pareja F, Neurological Disorders in Central Spain (NEDICES) Study
Group. Population-based case-control study of cognitive function in essential tremor. Neurology
2006; 66:69.

42. Benito-León J, Louis ED, Sánchez-Ferro Á, Bermejo-Pareja F. Rate of cognitive decline during the
premotor phase of essential tremor: a prospective study. Neurology 2013; 81:60.

- Page 12 of 13 -
Essential tremor: Clinical features and diagnosis

43. Benito-León J, Louis ED, Bermejo-Pareja F, Neurological Disorders in Central Spain Study Group.
Elderly-onset essential tremor is associated with dementia. Neurology 2006; 66:1500.

44. Thawani SP, Schupf N, Louis ED. Essential tremor is associated with dementia: prospective
population-based study in New York. Neurology 2009; 73:621.

45. Pahwa R, Koller WC. Is there a relationship between Parkinson's disease and essential tremor? Clin
Neuropharmacol 1993; 16:30.

46. Agnew A, Frucht SJ, Louis ED. Supine head tremor: a clinical comparison of essential tremor and
spasmodic torticollis patients. J Neurol Neurosurg Psychiatry 2012; 83:179.

47. Stolze H, Petersen G, Raethjen J, et al. The gait disorder of advanced essential tremor. Brain 2001;
124:2278.

48. Thenganatt MA, Louis ED. Distinguishing essential tremor from Parkinson's disease: bedside tests
and laboratory evaluations. Expert Rev Neurother 2012; 12:687.

49. Haubenberger D, Hallett M. Essential Tremor. N Engl J Med 2018; 378:1802.

50. Bain P, Brin M, Deuschl G, et al. Criteria for the diagnosis of essential tremor. Neurology 2000;
54:S7.

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