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Clinical Correlates of Action Tremor in Parkinson Disease
Elan D. Louis, MD, MS;
Gilberto Levy, MD;
Lucien J. Côte, MD;
Helen Mejia, MA;
Stanley Fahn, MD;
Karen Marder, MD, MPH
Arch Neurol. 2001;58:1630-1634.
ABSTRACT
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Background Action tremor is often noted in patients with Parkinson disease (PD),
yet the clinical correlates of this type of tremor have been the focus of
few studies. It is not clear whether this action tremor is a manifestation
of the underlying basal ganglia disease.
Objective To determine whether the severity of action tremor in PD is associated
with age, age at disease onset, disease duration, levodopa dose, severity
of rest tremor, or other motor (ie, bradykinesia, rigidity) and nonmotor manifestations
of PD.
Methods Patients with PD (N = 197) were ascertained as part of a familial aggregation
study. All patients underwent a neurological examination. Rest tremor was
rated with the Unified Parkinson Disease Rating Scale; and action tremor,
with the Washington Heights–Inwood Genetic Study of Essential Tremor
Rating Scale.
Results Action tremor was present in 184 (93.4%) of 197 patients. Four patients
(2%) met criteria for definite essential tremor. The action tremor score was
not associated with age, age at onset, or disease duration. The action tremor
score was associated with the rest tremor score (r
= 0.37; P<.001), and more strongly with the ipsilateral
than contralateral rest tremor score. The association between the action tremor
score and the rest tremor score was diminished but still significant (r = 0.21, P<.02) even when
we excluded these 63 patients with re-emergent tremor. Neither the action
nor the rest tremor score was associated with the bradykinesia or rigidity
scores, Hoehn and Yahr scale score, or modified Mini-Mental State Examination
score.
Conclusions Action tremor was associated with rest tremor in PD, suggesting that,
at least in part, action tremor is a manifestation of the underlying basal
ganglia disease. Neither tremor was associated with other motor and nonmotor
manifestations of PD. This in turn suggests that tremor in PD may represent
an underlying pathophysiological process different from these other manifestations.
INTRODUCTION
ACTION TREMOR often has been observed in Parkinson disease (PD).1, 2 The prevalence may be as high as 92%.1 While some consider this tremor to be of minor importance,
in clinical practice, a moderate action tremor is regarded to be more disabling
than a severe rest tremor.3
The basis for the action tremor in PD is not clear. In some patients,
the tremor has been reported to be more pronounced on the side of the body
that is more affected by PD.2 Also, a significant
reduction in action tremor amplitude has been reported with single-dose challenges
of dopaminergic and anticholinergic agents,4
suggesting that, like rest tremor, action tremor may be a manifestation of
the underlying basal ganglia disease. However, based on tremor recordings,
others have suggested that the action tremor in PD may represent an exaggeration
of normal physiological tremor.2, 3
Although action tremor has been reported and its prevalence estimated,1, 2, 5, 6, 7
the clinical correlates of this tremor have received little attention, and
a study focused on these could provide some insight into the basis for action
tremor in PD. As part of a familial aggregation study, we examined several
hundred patients with PD using standardized tremor rating scales. While action
tremor was highly prevalent in this group, most did not meet diagnostic criteria
for essential tremor (ET).8, 9
We distinguished, based on clinical observation, between postural tremor that
began after a latency period (ie, "re-emergent tremor")9
and that which did not. The purpose of this study was to determine whether
the severity of action tremor in PD correlated with age, age at onset, disease
duration, dose of medication, severity of rest tremor, or severity of other
motor and nonmotor manifestations of PD (eg, bradykinesia, rigidity, modified
Mini-Mental State Examination score10).
PATIENTS AND METHODS
PATIENTS
Patients with PD were enrolled in a study of the genetic epidemiology
of the disease. They were ascertained from neurology clinics or neurologists'
offices at the Neurological Institute of New York, Columbia-Presbyterian Medical
Center (New York, NY). Diagnoses were based on a standardized neurological
evaluation.11 Idiopathic PD, defined by clinical
and research criteria,12, 13, 14
did not include PD plus syndromes.
STUDY PROCEDURE
As part of the current evaluation, a neurologist examined each patient
and administered and rated the motor portion of the Unified Parkinson Disease
Rating Scale (UPDRS)15 and assigned a Hoehn
and Yahr scale score.16 In addition, all patients
were interviewed by a trained tester who collected demographic data, information
on names and dosages of medications, age at onset of motor signs of PD, age
at diagnosis of PD, and disease duration. The trained tester administered
a modified Mini-Mental State Examination (range, 0-57 [high]).10
The tester also administered and videotaped a detailed examination designed
to elicit action tremor, in which the following 6 items were assessed: sustained
arm extension (first with arms held in front of body and then in a wing-beat
position), pouring water between 2 cups, drinking water from a cup, using
a spoon to drink water, finger-to-nose movements, and drawing Archimedes spirals.8, 17 Each of these 6 items was performed
both with the dominant and the nondominant arm (12 items total). A manually
operated video camera recorder (Sony CCD-TR700; Sony Corp, Park Ridge, NJ)
was used to videotape the examination.
The videotaped examination was reviewed by a neurologist (K.M.) who
rated the 12 action tremor items using the Washington Heights–Inwood
Genetic Study of Essential Tremor (WHIGET) Rating Scale.8
Ratings were 0 (no visible tremor), 1 (low-amplitude or intermittent tremor),
2 (tremor of moderate amplitude, clearly oscillatory, and usually present),
and 3 (large-amplitude tremor). This is a reliable and validated tremor rating
scale.8, 17
As part of the videotaped examination, patients were asked to raise
their arms from a position where they had been resting in their laps, to horizontal
outstretched positions (first with arms held in front of body and then in
a wing-beat position), and to maintain their arms in each of these positions
for 10 seconds. Time, in seconds, minutes, and hours, was automatically displayed
in the margin of the video recording. The shortest latency period, in seconds,
between the newly achieved horizontal position and the onset of a clinically
observable postural tremor was noted. The neurologist (K.M.) had been specifically
instructed to observe this latency period.
DEFINITIONS
Action tremor consists of both kinetic and postural tremor. Kinetic tremor was defined as a tremor present during hand movement
(eg, finger-to-nose maneuver or writing). Postural tremor was defined as a tremor present during sustained arm extension. Rest tremor was defined as a tremor present while the arms
are resting in the lap or at the side. Re-emergent
tremor was defined as a postural tremor occurring after any latency period
(>0 seconds).9
SCORES
The kinetic tremor score (range, 0-30) was the sum of the ratings of
kinetic tremor on the WHIGET Tremor Rating Scale. Ten items (5 per arm) were
rated from 0-3. The postural tremor score (range, 0-6) was the sum of the
ratings of postural tremor on the WHIGET Tremor Rating Scale. Two items (1
per arm) were rated from 0-3. The action tremor score (range, 0-36) was the
sum of the kinetic and postural tremor scores. The rest tremor score (range,
0-8) was the sum of the ratings of rest tremor in the arms on the UPDRS. Two
items (1 per arm) were rated from 0 to 4. The bradykinesia score (range, 0-24)
was the sum of the ratings of bradykinesia in the arms on the UPDRS. Six items
(3 per arm) were rated from 0 to 4. The rigidity score (range, 0-8) was the
sum of the ratings of rigidity in the arms on the UPDRS. Two items (1 per
arm) were rated from 0 to 4.
STATISTICAL ANALYSES
To assess associations between categorical variables,  2
tests were used, and for continuous variables, Pearson correlation coefficients
were used. A t test was used to assess differences
between continuous variables. Multiple linear regression analyses were performed,
in which the dependent variable was the action tremor score, and the independent
variables were the rest tremor score, patient sex, and smoking.
RESULTS
There were 197 patients with PD (Table 1). Action tremor, defined as having a WHIGET rating of 1
or greater (mild tremor) on 1 of the 12 action tremor items, was present in
184 patients (93.4%), and 102 patients (51.8%) had an action tremor rated
2 or greater (moderate tremor) on at least 1 of the 12 action tremor items.
If patients had not had PD, then based on their action tremor, 4 (2.0%) would
have met either our previously published diagnostic criteria for definite
ET (postural tremor that received a rating of  2, and kinetic tremor that
received a rating of 2 on at least 4 items)8
or criteria for definite ET (visible and persistent bilateral postural tremor)
formulated by the Tremor Research Investigation Group.9
Mean tremor scores are presented in Table
2. The action tremor score was associated with age, age at onset
of motor signs of PD, years since onset of motor signs of PD, or years since
diagnosis of PD. Rest tremor score was associated with none of these variables.
Patients who were currently taking levodopa had similar mean action tremor
scores compared with those who were not taking levodopa (7.33 vs 8.13; t = 0.98, P = .33). The relationship
between dose (milligrams) of levodopa and the action tremor score (r = -0.13) did not reach statistical significance (P = .07). Action tremor was not associated with the dose of any of
the dopamine agonists (pergolide, bromocriptine, or pramipexole), amantadine,
selegiline, or anticholinergic agents (trihexyphenidyl, procyclidine, biperiden,
or benztropine). By contrast, there was a negative association between dose
of levodopa and severity of rest tremor (r = -0.24, P = .001) such that higher doses of levodopa were associated
with less severe rest tremor.
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Table 1. Characteristics of 197 Patients With Parkinson Disease*
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Table 2. Action and Rest Tremor Scores in 197 Patients With Parkinson
Disease*
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The action tremor was much more likely to be more severe on the side
of the body in which the rest tremor was predominant (2 =
21.1, P<.001). Moreover, the action tremor score
was correlated with the rest tremor score (r = 0.37, P<.001) (Table 3),
even when controlling for dose of levodopa (r = 0.34, P<.001). Because re-emergent tremor is considered to
be a form of rest tremor,9 we removed 63 patients
(32.0%) with re-emergent tremor. The association between the action tremor
score and the rest tremor score was diminished but still significant (r = 0.21, P<.02) even when
we excluded these 63 patients with re-emergent tremor.
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Table 3. Correlations Between Action Tremor Scores and Rest Tremor
Scores in 197 Patients With Parkinson Disease*
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The association between the postural tremor score and the rest tremor
score (r = 0.53, P<.001)
was greater than the association between the kinetic tremor score and the
rest tremor score (r = 0.30, P<.001); however, when we excluded the 63 patients with re-emergent
tremor, the associations were more similar (r = 0.27, P = .002 and r = 0.17, P = .04, respectively).
The action tremor score was not associated with the bradykinesia or
rigidity scores, Hoehn and Yahr scale score, or the modified Mini-Mental State
Examination score. Neither was the rest tremor score associated with any of
these items. By contrast, the rigidity and bradykinesia scores were associated
with each other (r = 0.60, P<.001)
as well as with the Hoehn and Yahr scale score (r
= 0.40 and 0.61, respectively; P<.001 for both
associations). There was an association between the bradykinesia score and
modified Mini-Mental State Examination score (r = -0.32, P<.001; ie, greater bradykinesia was associated with
more cognitive impairment). The association between the rigidity and modified
Mini-Mental State Examination scores did not reach significance (r = -0.14, P = .07).
Males had higher mean action tremor scores than did females (8.53 vs
6.60; t = 2.59, P = .01).
Disease duration did not differ by sex. Other factors (eg, smoking) may have
contributed to enhanced tremor among males. Data on smoking was collected
on some of these individuals participating in another study of risk factors
for PD. These data were available on 76 patients. Patients who reported ever
smoking had higher total tremor scores than those who did not (8.86 vs 6.13; t = 2.06, P = .04). When smoking
and sex were both included as independent variables in a multiple linear regression
analysis with the outcome variable being the total tremor score, only smoking
(P = .04) was associated with the total tremor score.
COMMENT
The presence of action tremor has been noted in cohorts of 30 to 80
patients with PD.1, 2, 5, 6, 7
However, the clinical correlates of this action tremor (ie, the nature and
extent of the relationships between this action tremor and other disease manifestations)
have received little attention. In addition, few studies have distinguished
between re-emergent tremor (a form of rest tremor) and tremor that does not
occur after a latency period. Examination of clinical correlates could provide
additional insight into the basis for the action tremor in PD. As part of
a familial aggregation study of PD, approximately 200 patients with PD were
examined, providing an opportunity to study associations between the severity
of action tremor and age, age at onset, disease duration, dosage of levodopa,
and severity of rest tremor and other motor and nonmotor features of PD using
a standardized assessment of action tremor.
The severity of action tremor was associated with the severity of rest
tremor, particularly ipsilateral rest tremor. This provides support for the
notion that the action tremor in PD is at least partly a manifestation of
the underlying basal ganglia disease. There may be other support for this
notion. In a study of PD kindreds, several of the relatives who had isolated
mild postural tremor demonstrated reduced fluoro-dopa uptake in the putamen.18
Although the association between the rest tremor and action tremor scores
was highly significant, the rest tremor score explained only 13.7% of the
variance in the action tremor score (r = 0.37, r2 = 0.137, P<.001),
and the bradykinesia and rigidity scores were not associated with the action
tremor score. The dose of levodopa only explained 1.7% of the variance in
the action tremor score (r = -0.13, r2 = 0.017). Even when combined, rest tremor score, dose
of levodopa, disease duration, sex, and age only explained 18.6% of the variance
in the action tremor score (r = 0.43, r2 = 0.186, P<.001). This suggests
that other factors contribute to the severity of the action tremor in PD,
and that the severity of the action tremor in PD is probably not exclusively
a manifestation of the underlying basal ganglia disease. As previously suggested,2, 3 a component of physiological or enhanced
physiological tremor could be contributing to the severity of the action tremor
in PD.
We reported that there were no relationships between the severity of
action tremor and other manifestations of PD. The severity of action tremor
was not associated with the severity of bradykinesia, rigidity, the Hoehn
and Yahr scale score, the Mini-Mental State Examination score or the disease
duration. This observation, that action tremor is associated with some manifestations
of PD (eg, rest tremor) but not with other manifestations (eg, bradykinesia
and rigidity) suggests that different mechanisms may underlie tremor (rest
and action) and bradykinesia or rigidity. Further support for this comes with
the observation that there was no association between the rest tremor score
and bradykinesia and rigidity scores. There is evidence in the literature
that the tremor in PD may represent a different underlying pathophysiological
process than the rigidity and bradykinesia. First, factor analysis of signs
in PD showed that rest tremor was relatively independent of the other cardinal
signs of PD.19 Second, we previously reported
that while bradykinesia and rigidity worsened at similar annual rates in PD,
rest tremor did not clearly worsen with time.20
Finally, there was no correlation between rest tremor and striatal 18F-dopa uptake in patients with PD.21
One previous study examined the association between action and rest
tremor in PD.6 An association was reported
between postural and rest tremor, but not between kinetic and rest tremor.
In a larger sample, we found that rest tremor was associated with both postural
and kinetic tremor. As in the previous study, the association between rest
tremor and postural tremor was particularly robust. However, when we excluded
individuals with a reemergent tremor, the associations (rest tremor-postural
tremor and rest tremor-kinetic tremor) were similar. This supports the previously
suggested view that re-emergent tremor in PD is a form of rest tremor.9 It also underscores the importance of distinguishing
between different types of postural tremor in PD. Clinicians who use the UPDRS
to rate action tremor should distinguish re-emergent tremors from tremor not
occcuring after a latency period. Those that occur after a latency are usually
an expression of the patient's rest tremor.
We realize that this study had limitations. Quantitative computerized
tremor analysis was not performed in our patients, and this would have provided
more precise quantification of tremor amplitudes. Despite this, significant
associations were detected between action tremor and postural tremor.
In summary, action tremor was associated with rest tremor in PD, suggesting
that, at least in part, action tremor is a manifestation of the underlying
basal ganglia disease. Neither tremor was associated with other motor and
nonmotor manifestations of PD, suggesting that tremor in PD may represent
a different underlying pathophysiological process than these other manifestations.
AUTHOR INFORMATION
Accepted for publication July 6, 2001.
This work was supported by grant R01 NS36630 from the National Institutes
of Health, Bethesda, Md, and grant RR00645 from the General Clinical Research
Center (New York, NY) and the Parkinson's Disease Foundation (New York).
We would like to thank Susan Bressman, MD, Blair Ford, MD, Steve Frucht,
MD, Paul Greene, MD, and Cheryl Waters, MD, for referring patients to this
study.
From the Gertrude H. Sergievsky Center (Drs Louis, Levy, Côte,
and Marder, and Ms Mejia) and the Department of Neurology (Drs Louis, Côte,
Marder, and Fahn), College of Physicians and Surgeons, Columbia University,
New York, NY.
Corresponding author and reprints: Elan D. Louis, MD, MS, Unit 198,
Neurological Institute, 710 W 168th St, New York, NY 10032 (e-mail:
EDL2{at}columbia.edu).
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