Beginning in March 2012 and ending in July 2012, ET and PD patients ≥18
years of age were enrolled prospectively and consecutively from the clinical practices of three movement disorder neurologists (Roy N. Alcalay, Oren A. Levy, Elan D. Louis) at the time of regularly scheduled outpatient visits. The initial diagnosis of ET was based on the presence of moderate or greater amplitude kinetic tremor in the arms or head in the absence of another known cause (e.g., medications, PD, dystonia); this diagnosis was reconfirmed in each case using published diagnostic criteria (Louis et al., 1997
). The PD diagnosis was based on the presence of two or more cardinal features of parkinsonism in the absence of other possible causes (e.g., medication, atypical parkinsonian syndromes). There were five refusals. Patients were not permitted to enroll if they had simultaneous diagnoses of ET and PD. Each enrollee signed a Columbia University Medical Center (CUMC) Institutional Review Board consent form.
Patients completed semi-structured demographic and clinical questionnaires designed for this study and then underwent a videotaped Unified Parkinson’s disease Rating Scale (UPDRS) assessment (Fahn and Elton, 1987
) and videotaped assessments of tremor, including postural tremor (straight-arm extension and winged arm extension) and the finger-nose-finger maneuver (10 repetitions per arm). The camera was positioned so that all joints of the upper limbs were visible. Each patient also drew an Archimedes spiral (an exercise that tests for kinetic tremor) with each hand. Patients with a history of deep brain stimulation surgery were asked to turn their stimulators off prior to the start of the videotaped assessments.
Videotaped examinations were reviewed by a senior neurologist specializing in movement disorders (Elan D. Louis) who rated the severity of kinetic tremor and postural tremor (overall and at individual joints) using the Washington Heights-Inwood Genetic Study of Essential Tremor (WHIGET) rating scale (possible scores
0, 0.5, 1, 1.5, 2, or 3) (Louis et al., 1997
). In each upper limb joint, postural tremor was rated in each possible direction. For example, at the wrist joint, tremor was rated separately in three directions (flexion-extension, adduction-abduction, and pronation-supination), while at the MCP joint, tremor was rated separately in two directions. For the overall presence or absence of tremor, we used both a liberal definition of “present” (any WHIGET score
0.5) and a conservative definition of “present” (any WHIGET score
1). The use of a liberal definition, in particular, allowed for greater precision in measurement. Re-emergent tremor (i.e., latently emerging postural tremor) was also assessed. As in previous studies, intention tremor [i.e., tremor that occurs with goal-directed movement (finger-nose-finger movement) and worsens when approaching the target] was rated as a 0 (absent), 0.5 (probable), 1 (definite), and patients with definite intention tremor in at least one arm or probable intention tremor in both arms were considered to have intention tremor (Louis et al., 2009
). The severity of rest tremor was rated with the UPDRS (ratings from 0 to 4) (Louis et al., 2009
). Hoehn and Yahr scores (Goetz et al., 2004
) were assigned to PD patients.
Pre-study sample size calculations indicated that 50 ET and 50 PD patients would be sufficient (i.e., >90% power) to achieve statistical significance for each of our main comparisons, assuming two sided tests with alpha
0.05. Statistical analyses were performed in SPSS (version 19; Chicago, IL, USA). We used chi-square tests (χ2
) to assess categorical data and non-parametric (Mann–Whitney) tests to analyze ordinal data.
To formally test whether the four clinical anecdotal impressions were correct, we calculated several indices. The first clinical impression involved the issue of proximal vs. distal postural tremor, which we assessed in several overlapping ways. First, to compare the prevalence of isolated proximal (shoulder
wrist) postural tremor and isolated distal [MCP
phalanges (including thumb)] postural tremor, we determined the number of patients in which proximal postural tremor was present in the absence of distal postural tremor, and vice versa. For completeness, both liberal (tremor score
0.5) and conservative (tremor score
1) thresholds of tremor presence were used. Second, to determine the relative severity of overall proximal vs. overall distal postural tremors, we calculated a “proximal – distal postural tremor” index (see footnote g in Table ). Third, we subtracted the highest WHIGET postural tremor score in the MCP joint from the highest WHIGET postural tremor score in the wrist (wrist – MCP postural tremor, see footnote h in Table ).
Clinical examination data for ET and PD patients.
The second clinical impression involved the issue of flexion-extension vs. pronation-supination tremor at the wrist during arm extension. To assess this, we used the highest WHIGET tremor scores, and calculated the difference between wrist flexion-extension postural tremor and wrist pronation-supination postural tremor (wrist flexion/extension tremor – wrist pronation/supination tremor).
The third clinical impression addressed thumb tremor. We examined the prevalence of postural thumb tremor in the absence of other postural tremor. For completeness, again, we used both liberal (tremor score
0.5) and conservative (tremor score
1) definitions of tremor presence.
Our fourth clinical impression was that intention tremor is present in ET but not PD. Other than the rating scale discussed above, no additional indices were used in establishing the presence of intention tremor.
As the study involved the testing of several a priori hypotheses (i.e., four clinical impressions), correction for multiple comparisons was not required for these comparisons.