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In Parkinson's disease, a postural/kinetic tremor may occur in association with the classical resting tremor. According to the consensus statement of the Movement Disorder Society on tremor,1 this association is classified as type I (classical parkinsonian tremor) if the difference between the frequencies of postural/kinetic tremor and resting tremor is less than 1.5 Hz; and as type II if this difference is more than 1.5 Hz. In type I tremor, resting tremor and postural tremor share common pharmacological properties, responding to levodopa.2,3 Type II tremor (that is, a predominant postural/kinetic tremor associated with a resting tremor of a lower frequency) is considered to be a combination of essential tremor and parkinsonian tremor, and is reported in between 3% and 24% of the patients diagnosed as having Parkinson’s disease.3 Though postural/kinetic tremor and resting tremor may show some overlap in their electrophysiological properties in Parkinson’s disease, the postural/kinetic component does not respond to levodopa.3 Nevertheless, clinical criteria may be insufficient to differentiate between Parkinson’s disease and essential tremor.
We report a case of a 70 year old patient affected by essential tremor and Parkinson's disease, in whom acute dopaminergic challenge tests allowed us to differentiate between the two components of severe bilateral arm tremor.
Acute dopaminergic challenge tests, which are well accepted as a diagnostic tool in Parkinson’s disease, may be helpful in various clinical settings—for example, postural/kinetic tremor of mixed origin—by identifying the parkinsonian component and predicting the responsiveness of the tremor to dopaminergic treatment.
A 70 year old right handed woman was referred to us because of disabling postural tremor and resting tremor of both hands. At age 61, the patient had developed a postural/kinetic right handed tremor. Two years later, she had also developed resting tremor in the same limb. The resting tremor and the postural/kinetic tremor worsened progressively, with significant impairment of her daily activities and social life. Two months before our first evaluation, she had started to notice a postural/kinetic tremor of her left upper arm.
On neurological evaluation, she had mild asymmetrical parkinsonism with a bilateral resting tremor, a postural/kinetic tremor of the upper limbs, and a moderate voice tremor. The UPDRS motor score (items 18–31) in the off-state was 27. The upper limb right sided resting tremor was constant, of moderate amplitude, and with a frequency of 5 Hz on surface EMG; the left sided resting tremor was intermittent and milder than on the right. A postural/kinetic tremor of both upper limbs was also present; this was marked and disabling on the right, mild and constant on the left (fig 1, panel A). The kinetic tremor was more pronounced than the postural component on the left.
The patient underwent acute dopaminergic challenge tests, including a test with a single dose of levodopa–carbidopa 200/50 mg, and on the next day, a sequential test with increasing doses (1.5 mg, 3 mg, 4.5 mg, 6 mg) of subcutaneous apomorphine. Clinical evaluation was performed before each single dose (off-state), and after one hour for levodopa and 30 minutes for apomorphine by the UPDRS scale (motor examination, items 18–31) and writing (writing a phrase and drawing a spiral) (fig 1, panels B and C).
The levodopa/carbidopa test mainly improved akinesia and rigidity, the right sided postural/kinetic tremor and resting tremor being improved by only 33%. The left sided resting tremor and postural/kinetic tremor did not change significantly. A progressive improvement in the tremor was observed with increasing doses of apomorphine, with total disappearance of the right sided resting tremor at a dose of 6 mg, and of the left sided resting tremor at 1.5 mg. The right postural component was reduced by 60% by 1.5 mg of apomorphine and disappeared at the 6 mg dose, while a mild kinetic tremor persisted unchanged. The left sided postural/kinetic tremor did not change.
A diagnosis of essential tremor and Parkinson's disease was made, and antiparkinsonian treatment with levodopa/benserazide 100/25 mg three times daily and pergolide 0.25 mg three times daily was started. On this treatment, the resting tremor improved on the right side and disappeared on the left. In contrast, the postural/kinetic tremor persisted unchanged on the left, though it clearly improved on the right, allowing the patient to perform most of her daily activities. A therapeutic trial with primidone (Mysoline) was started, and this resulted in substantial improvement in the left sided tremor and a further positive effect on the right sided residual postural/kinetic tremor (fig 1, panel D).
Our patient presented with a combination of essential tremor and Parkinson’s disease, with a differential response of the tremors to acute dopaminergic challenge tests. The opposite lateral predominance of the tremors (right for Parkinson’s disease and left for essential tremor) allowed us to differentiate the pharmacological response of the two tremors more easily: the resting tremor responded to apomorphine, disappearing at the highest dose on the right side and at lower doses on the left side, while the postural/kinetic tremor showed a different response on the two sides, nearly disappearing on the right (except for a mild kinetic tremor), while persisting almost unchanged in both its postural and kinetic components on the left. The dopaminergic tests clearly indicated the presence of a postural/kinetic tremor which did not respond to dopaminergic stimulation and which was diagnosed as essential tremor. In accordance with the results of the acute challenge tests, chronic treatment with dopamine agonists and levodopa significantly improved the parkinsonian tremor (both the resting and the postural component) on the right side, while the left sided postural/kinetic tremor responded selectively to primidone.
The different pharmacological response of essential tremor and parkinsonian tremor confirms that they are separate pathophysiological entities, often difficult to distinguish on a clinical basis.3 The mainstays of treatment for essential tremor include β adrenergic blocking drugs and primidone. The response of parkinsonian tremor to antiparkinsonian treatment is variable. Both the resting tremor and the postural tremor, which share similar electrophysiological properties (as in type I tremor) seem to respond to antiparkinsonian treatment (L-dopa or dopamine agonists)—providing an adequate dosage is given—but not to primidone or β blockers. When both types of tremor (essential tremor and parkinsonian tremor) coexist, combined treatment is necessary, in line with their different pathophysiology.
Dopaminergic acute challenge tests are a well accepted diagnostic tool for diagnosis and evaluation of dopaminergic responsiveness in Parkinson’s disease, including parkinsonian tremor.4,5 Our observations show that in particular clinical settings, such as when both essential tremor and parkinsonian tremor are suspected, acute dopaminergic challenge tests may differentiate these two entities and define the best treatment strategies.