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Year : 2017  |  Volume : 20  |  Issue : 2  |  Page : 138-141

Clinical and imaging study of isolated and mixed rest and action tremor-essential tremor versus Parkinson's disease

1 Department of Neurology, Ospedale San Martino, Neurology Service, San Martino Hospital, Belluno, Italy
2 Neurology Service, Santorso Hospital, Santorso, Italy
3 Department of Internal, Neurology Service, San Martino Hospital, Belluno, Italy
4 Department of Neurology, University of Trieste, Trieste, Italy

Date of Web Publication8-May-2017

Correspondence Address:
Michele Pistacchi
Garziere Street 73, 36014 Santorso
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/aian.AIAN_497_16

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Background: Some patients present an unusual association of both action tremor (AT) and rest tremor (RT) making the differential diagnosis between essential tremor (ET) and Parkinson's disease (PD) difficult. Aim: To investigate this particular clinical picture trying to focus on possible peculiar clinical inferences. Patients and Methods: Twenty-three patients with atypical tremor syndrome were selected for the study. They underwent neurological examination, neuroimaging study, and brain DaTSCAN single-photon emission computed tomography. Results: Twenty-three patients were evaluated; 17 presented mixed-tremor syndrome, while six patients showed only isolated AT or RT. DaTSCAN was pathological in 19 patients and normal in 3 patients. The emerging statistical data highlighted a positive correlation between disease duration and DaTSCAN abnormalities; Fisher's exact test showed a marked difference in evolution toward a dysfunction of dopaminergic pathways in patients with both AT and RT phenotype. Conclusion: The possible correlation between PD and ET has often been discussed without any clear findings. Are these patients suffering from ET prone to develop PD? Or are they the expression of a specific clinical phenotype? Our clinical survey has not led to absolute considerations; however, it seeks to highlight the clinical markers that might arouse the suspicion of extrapyramidal disease in patients with atypical tremor syndrome.

Keywords: Action tremor, essential tremor, Parkinson's disease, resting tremor

How to cite this article:
Marsala SZ, Pistacchi M, Gioulis M, Ferracci F, Capus L. Clinical and imaging study of isolated and mixed rest and action tremor-essential tremor versus Parkinson's disease. Ann Indian Acad Neurol 2017;20:138-41

How to cite this URL:
Marsala SZ, Pistacchi M, Gioulis M, Ferracci F, Capus L. Clinical and imaging study of isolated and mixed rest and action tremor-essential tremor versus Parkinson's disease. Ann Indian Acad Neurol [serial online] 2017 [cited 2021 Sep 23];20:138-41. Available from:

   Introduction Top

Tremor is the main symptom of Parkinson's disease (PD) and essential tremor (ET), and usually, it shows distinct semeiological characteristics within these two conditions.

Nevertheless, some patients could present a peculiar clinical picture typified by both action tremor (AT) and rest tremor (RT) or isolated RT without other extrapyramidal features. In these conditions, the differential diagnosis between ET and PD may be difficult. RT is likely to occur in 20% of ET patients,[1] particularly in the elderly, while postural tremor may sometimes be a presenting symptom of PD.[2] Several clinical series about the greater risk of developing PD of ET patients have been recorded in literature. This topic has been debated for a long time: some authors maintain that there is a link between these two diseases,[3],[4],[5],[6],[7],[8],[9],[10] whereas others deny it.[11] Moreover, the possible presence of a monosymptomatic Parkinsonian syndrome exclusively characterized by RT should be considered.[12],[13]

Therefore, we selected a group of patients with isolated tremor symptomatology – typical of neither PD nor ET – who underwent DaTSCAN single-photon emission computed tomography (SPECT) imaging to identify the clinical parameters suggestive for nigrostriatal dysfunction.

   Patients and Methods Top

Twenty-three patients (13 males, 10 females) with at least a 6-month history of atypical tremor were selected from our clinical consecutive series of 392 patients followed by the Movement Disorder Outpatient Clinic of the Neurological Departments of Trieste and Belluno. We ruled out other possible causes of tremor and pseudodementia dosing thyroid hormone levels, Vitamin B12 and folate, and testing liver and kidney functions. Other exclusion criteria included the presence of neuropsychiatric disorders (depression, anxiety disorder, dementia, restless leg syndrome, sleep disorders, etc.); the chronic use of neurological or psychiatric medications (excluding medication for tremor) that could cause tremor (anti-asthma drugs such as theophylline and salbutamol, stimulants such as amphetamines, heart medicines such as amiodarone, procainamide, thyroid medication such as levothyroxine, cancer medicines such as thalidomide and cytarabine, anti-epileptic drugs such as valproic acid) or could affect cognitive functions (e.g., antiepileptic agents, antidepressants, etc.); the presence of disorders of prostate, diabetes mellitus, any kind of cancer; declining to participate; and other reasons of intellectual disability.

ET was categorized based on the criteria set in [Table 1], and PD was diagnosed in accordance with the UK Brain Bank criteria.
Table 1: Demographic, clinical, and instrumental data

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Those patients whose clinical phenotype consisted of an association by both AT and RT, or isolated postural tremor or monosymptomatic RT without any other extrapyramidal signs, were evaluated by a movement disorder specialist. They had a mean 5-year period of follow-up. Complete neurological and general examinations were assessed. We evaluated tremor according to the Consensus Statement of the Movement Disorder Society on Tremor.[4] All patients underwent brain DaTSCAN SPECT and neuropsychological tests so as to ensure comparability in terms of cognitive functions (short-term memory, attention, and working memory). Tests consisted of mini-mental state examination, Rey auditory-verbal learning test (Rey-Rey-I and D), Digit Span, Symbol Digit Modalities Test, Raven Progressive Matrices (Raven), activities of daily living (ADL) and instrumental ADL. Neuropsychological tests, brain TC, or magnetic resonance imaging to exclude cognitive impairment and other symptomatic causes of tremor were performed. All patients were treated with L-Dopa, b-blockers, or primidone. We also evaluated the possible benefit after a small amount of alcohol.

The study protocol was conducted in accordance with the ethical principles stated in the “Declaration of Helsinki.” The study was approved by the local ethics board.

Statistical analysis

SPSS 21.0 was used for statistical analysis SPSS 21.0 (SPSS, Chicago, IL, USA). The definitive statistics from the study were summarized by the arithmetic mean, mean ± standard deviation, etc. Numbers and percentages were used in the representation of categorical variables. Kruskal–Wallis test was used for representation of numerical data regarding the comparison of control and patient groups, under the assumption that the data were not distributed normally. The comparisons for categorical variables were represented and analyzed by cross-tabulation (Chi-square test). Fisher's exact test was used to compare the frequency of DaTSCAN SPECT abnormality imaging between the PD and ET groups.

A statistical significance limit of P< 0.05 was used. As for correlations, we carried out Pearson's correlation analysis.

   Results Top

Twenty-three patients were evaluated, 13 males and 10 females [Table 2]. Seventeen patients presented a tremor syndrome constituted by the association of rest with AT, while 6 showed either isolated AT or RT. Within the overall sample, the mean age was 76.27 ± 8.84 years, the onset of tremor symptoms was at 57.36 ± 16.22 years, and the mean duration of tremor was 19.27 ± 16.67 years. Both groups shared similar sociodemographic features (age, gender, education level, and employment).
Table 2: Comparison of the rate of DaTSCAN abnormalities in both groups

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The DaTSCAN was abnormal in 20 patients and normal in three patients.

Group of patients with associated rest and action tremor

In group of patients with both AT and RT, family history was frequent (12/17 patients) and tremor was mainly asymmetric [Table 2]. Their action component had been evident since the clinical onset. This cohort showed longer disease duration. The long follow-up highlighted mild late extrapyramidal features, such as the reduction of pendular movements, micrography, and slight muscle rigidity.

Group with isolated tremor symptomatology

In this group, patients had exclusively AT or RT. DaTSCAN showed pathologic findings only in those individuals whose resting tremor was clearly identified.

The emerging statistical data are (1) positive correlation between disease duration and DaTSCAN abnormalities: longer disease was correlated with the onset of possible Parkinsonian syndrome; (2) Fisher's exact test showed a marked difference in the evolution toward a dysfunction of dopaminergic pathways in patients with phenotype RT + AT, compared with patients in whom the initial phase RT or AT dominated singularly [Table 1].

   Discussion Top

Tremor is the most common movement disorder and it is one of the main clinical manifestations of PD and ET, though with different semeiological aspects. However, the presence of clinical cases characterized by the simultaneous presence of RT and AT, or monosymptomatic RT, may support the hypothesis that ET can predispose patients to PD; otherwise, a novel exclusively tremor disease phenotype could be suspected. ET and PD are different diseases; however, they might share some common features regarding the role of the thalamus in the oscillator circuit. The literature confirms a possible clinical epidemiological correlation between ET and PD.[3],[4],[5] Currently there is no evidence of a precise-related neuropathology in ET, even though the presence of the Lewy bodies reported in ET strengthened a possible link between these two conditions.[14] Indeed, the nonmotor signs in ET suggest the involvement of other circuits in the oscillatory cerebellar-thalamic-cortical one.

Our clinical study mainly included patients with a complex tremor syndrome, having characteristics of both AT and RT. In addition, we distinguished a minority group with rather isolated unspecific tremor, AT or RT. The presence of impaired putaminal uptake in these individuals can be the link between the functional impairment and the anatomical basis. Are these patients suffering from ET prone to develop PD? Or are they the expression of a specific clinical phenotype? The neurological literature has often debated whether there is a connection between PD and ET; however, the analyses of various systematic works – including neuropathological data – have provided no clear evidence for this topic. Specifically, a neuropathological correlation between the two diseases still has not been established. These patients could suffer from a clinical phenotype characterized only by mild evolution tremor symptomatology, mainly with asymmetrical AT. Dopaminergic treatment brought only partial or no benefits. Undoubtedly, our sample was limited and further studies are needed to clarify this point. Nevertheless, there is a possibility that these patients might represent a rare clinical phenotype, often underestimated and with mainly exclusively tremor features, based on the association of AT and RT.

   Conclusion Top

In clinical practice, atypical tremor syndromes are rare but not so uncommon. This implies a careful analysis of the patient, since certain conditions of action tremor, may be secondary to a dysfunction of the basal ganglia, although not configuring a classic picture of Parkinson's Disease.


We would like to acknowledge the support of Santorso Hospital (Santorso, Italy) and San Martino Hospital (Belluno, Italy).

Financial support and sponsorship


Conflicts of interest

There are no conflicts of interest.

   References Top

Cohen O, Pullman S, Jurewicz E, Watner D, Louis ED. Rest tremor in patients with essential tremor: Prevalence, clinical correlates, and electrophysiologic characteristics. Arch Neurol 2003;60:405-10.  Back to cited text no. 1
Jankovic J, Schwartz KS, Ondo W. Re-emergent tremor of Parkinson's disease. J Neurol Neurosurg Psychiatry 1999;67:646-50.  Back to cited text no. 2
Jankovic J, Beach J, Schwartz K, Contant C. Tremor and longevity in relatives of patients with Parkinson's disease, essential tremor, and control subjects. Neurology 1995;45:645-8.  Back to cited text no. 3
Giménez-Roldán S, Mateo D. Cinnarizine-induced Parkinsonism. Susceptibility related to aging and essential tremor. Clin Neuropharmacol 1991;14:156-64.  Back to cited text no. 4
Jankovic J, Contant G, Perlmutter J. Essential tremor and PD [Letter]. Neurology 1993;43:1447-8.  Back to cited text no. 5
Lee MS, Kim YD, Im JH, Kim HJ, Rinne JO, Bhatia KP. 123I-IPT brain SPECT study in essential tremor and Parkinson's disease. Neurology 1999;52:1422-6.  Back to cited text no. 6
Grosset DG, Lees AJ. Long duration asymmetric postural tremor in the development of Parkinson's disease. J Neurol Neurosurg Psychiatry 2005;76:9.  Back to cited text no. 7
Shahed J, Jankovic J. Exploring the relationship between essential tremor and Parkinson's disease. Parkinsonism Relat Disord 2007;13:67-76.  Back to cited text no. 8
Louis ED, Levy G, Côte LJ, Mejia H, Fahn S, Marder K. Clinical correlates of action tremor in Parkinson disease. Arch Neurol 2001;58:1630-4.  Back to cited text no. 9
Chandran V, Pal PK. Essential tremor: Beyond the motor features. Parkinsonism Relat Disord 2012;18:407-13.  Back to cited text no. 10
Adler CH, Shill HA, Beach TG. Essential tremor and Parkinson's disease: Lack of a link. Mov Disord 2011;26:372-7.  Back to cited text no. 11
Brooks DJ, Playford ED, Ibanez V, Sawle GV, Thompson PD, Findley LJ, et al. Isolated tremor and disruption of the nigrostriatal dopaminergic system: An 18F-dopa PET study. Neurology 1992;42:1554-60.  Back to cited text no. 12
Deuschl G, Bain P, Brin M. Consensus statement of the movement disorder society on tremor. Ad Hoc Scientific Committee. Mov Disord 1998;13 Suppl 3:2-23.  Back to cited text no. 13
Louis ED, Honig LS, Vonsattel JP, Maraganore DM, Borden S, Moskowitz CB. Essential tremor associated with focal nonnigral Lewy bodies: A clinicopathologic study. Arch Neurol 2005;62:1004-7.  Back to cited text no. 14


  [Table 1], [Table 2]


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