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Tremor

Tremor

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Why don't the drugs help my tremor?
Rodger J. Elble, MD, PhD,
Department of Neurology, Southern Illinois
University School of Medicine, Springfield, Illinois

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I frequently speak at Parkinson support group meetings throughout central and southern Illinois, and I usually see someone in each audience with a prominent head tremor and no facial masking. During the question and answer period, this person usually asks in a tremulous voice "Why don't my Parkinson medications help my tremor?" The answer is usually simple; the diagnosis is essential tremor, not Parkinson disease. Essential tremor in older patients is commonly confused with Parkinson disease, so it is appropriate to review the differences between these two common conditions.

Clinical classification and diagnosis of tremor

Tremor is an involuntary oscillation of a body part that is classified as rest tremor, postural tremor, or kinetic tremor according to whether the tremor occurs at rest, during a voluntary posture, or during a movement. The definitions of these three classifications and related classifications are presented in Table 1.

Clinical classifications of tremor

Rest tremor occurs in a body part that is supported in such a way that muscle contraction is neither necessary nor intended. The patient is recumbent on a bed or seated on a couch, with the body part supported.Tremor is often enhanced by the performance of cognitive tasks or motor tasks with other body parts, and it is often suppressed, at least temporarily, by voluntary muscle contraction.

Postural tremor occurs in an attempt to hold a body part motionless against the force of gravity Extending the upper limbs horizontally; pointing at objects; sitting erectly without support for the upper body; protruding the tongue.

Kinetic tremor occurs during a voluntary movement Nose-finger-nose testing; heel-knee-shin testing; reaching; writing; drawing; pouring water into a cup; drinking from a cup; eating with utensils; speaking. Action tremor Occurs during any voluntary contraction of skeletal muscle and is therefore a postural tremor, kinetic tremor or both. As in postural tremor and kinetic tremor.

Intention tremor is a unique form of kinetic tremor that occurs during a visually guided movement toward a target destination. Little or no tremor is present during the initial posture or movement, but there is a crescendo and somewhat paroxysmal increase in tremor as the limb approaches its target Nose-finger-nose testing; heel-knee-shin testing; reaching; writing; drawing; pouring water into a cup; drinking from a cup; eating with utensils.

The classification schema above is often expanded to include subtypes of tremor with unique characteristics. Pill-rolling rest tremor is a rest tremor in which the fingers and wrist move in a manner reminiscent of a rhythmic voluntary manipulation of small objects or pills in the hand. Degeneration or pharmacologic blockade (as with antipsychotic neuroleptic medications such as haloperidol and chlorpromazine) of the nigrostriatal dopaminergic pathway produces this unique tremor. Idiopathic Parkinson disease is by far the most common etiology of pill-rolling rest tremor. A unique characteristic of Parkinson rest tremor is the tendency for this tremor to appear in the hands while the patient is walking.

Essential tremor is typically a mixture of postural and kinetic tremors although one form may predominate over the other. Rest tremor occurs rarely in elderly patients with advanced essential tremor, and physicians must always consider the possibility of coexistent Parkinson disease or some other cause of parkinsonism in patients with rest tremor. In most instances, the "rest tremor" in essential tremor is actually a postural tremor that is caused by incomplete muscle relaxation. Patients are often examined while seated in a chair that does not provide complete support for the head, neck, torso, and proximal limb muscles. Consequently, the muscles of these body parts are active against gravity, producing a tremor that is mistakenly classified as rest tremor. This common error can be avoided by examining patients in recumbent and seated positions with complete body support. Essential tremor does not cause a pill-rolling rest tremor.

Essential tremor develops insidiously and progresses gradually at a variable rate, as determined by factors that are as yet unknown. It is common for patients with essential tremor to have tremor for many years before seeking medical consultation. Approximately 50% of patients with essential tremor are unaware of their condition because it is mild or simply ignored as "nervousness". Essential tremor affects people of all ages, but its prevalence increases with age, affecting at least 5% of people age 65 and older. Therefore, essential tremor is about 4-5 times more common than Parkinson disease.

Many patients with essential tremor do not develop symptoms until late in life. The reason for this late onset is unclear. Essential tremor in older patients is often misdiagnosed as Parkinson disease or "old age." The common view is that 50% of patients inherit essential tremor through an autosomal dominant gene (familial essential tremor or familial tremor). In other words, a parent with familial tremor has a 50:50 chance of passing the condition on to each child. Thus, genetic factors play much more of a role in essential tremor than in Parkinson disease. Markers for two genes have been discovered on chromosomes 2 and 3, and additional genes are expected. However, essential tremor seems to occur sporadically in many patients, particularly those who are older, and the true prevalence of inherited versus sporadic essential tremor is uncertain.

Table 2: Guidelines for identifying essential tremor

Core criteria

Bilateral action tremor of the hands and forearms (but not rest tremor) Absence of other neurologic signs, except for cogwheel phenomenon (palpable tremor during manipulation of the patient's limbs)

May have isolated head tremor with no abnormal posture

Secondary criteria

  • Long duration ( 3 years)
  • Family history
  • Beneficial response to ethanol
  • Indications of Parkinson disease
  • Unilateral tremor or symptomatic leg tremor
  • Rest tremor
  • Facial masking, hypophonia, gaitdisturbance, rigidity, bradykinesia
  • Rapid or recent onset
    Distinguishing essential tremor from Parkinson disease is usually straightforward. Essential tremor is a bilateral postural or kinetic tremor (i.e., action tremor), whereas a key distinguishing feature of Parkinson disease is its pill-rolling rest tremor with coexistent bradykinesia and rigidity. General guidelines for identifying essential tremor are presented in Table 2. Essential tremor nearly always affects the hands (~95% of patients) but also affects the head (~34%), face (~5%), voice (~12%), trunk (~5%), and lower extremities (~20%). Thus, most patients have tremor in the upper limbs, frequently in isolation. In contrast to Parkinson disease, essential tremor in the lower limbs is uncommon and usually asymptomatic. Patients with essential tremor shake, but they are otherwise neurologically normal. That is, they do not have bradykinesia, rigidity or gait disturbance, as seen in Parkinson disease. Many Parkinson patients exhibit action tremor in the upper limbs, and this may be a source of diagnostic confusion when there is little or know coexistent rest tremor, facial masking, bradykinesia or rigidity.

    Isolated head tremor may occur in essential tremor but not in Parkinson disease. When considering the diagnosis of essential tremor in patients with isolated head tremor, clinicians must take great care to exclude patients with abnormal posturing (i.e., a head tilt or turn) and muscular co-contraction, which are signs of dystonia (spasmodic torticollis). Parkinson disease rarely, if ever, causes head or voice tremor, although the upper extremities may shake so violently in Parkinson disease that the head and torso shake secondarily.

    Parkinson disease and essential tremor are common movement disorders. Therefore, it is not uncommon for patients to have both conditions. In such patients, there is often a long history (many years) of mild-moderate postural and kinetic tremor in the hands, and a family history of tremor is also common. The recent occurrence of greatly increased tremor and a tendency for the hands to shake at rest or while walking are frequently the initial signs of Parkinson disease in these patients. Patients with essential tremor and Parkinson disease may have a particularly disabling tremor and relatively little bradykinesia or rigidity. Diagnosis in these patients can be difficult, and such patients should be evaluated, at least once, by a movement disorder specialist when the tremor is not readily classifiable or when the etiology of tremor is uncertain.

    A careful drug history is mandatory in all patients with tremor. Many drugs produce parkinsonian rest tremor (antipsychotic neuroleptics such as haloperidol; metoclopramide), action tremor (beta-adrenergic agonists and methylxanthines used for asthma, valproic acid, thyroxin, antidepres-sants, tocainamide, and lithium), and mixed rest and action tremors (lithium, amiodarone, valproic acid, and neuroleptics). Little is known about the mechanisms of these tremors. Thyrotoxicosis and hyperadrenergic states produced by systemic disease, psychiatric conditions, or drugs cause an enhanced physiologic tremor that may be difficult to distinguish from essential tremor. Any of these drugs or conditions can exacerbate Parkinson tremor and essential tremor.

    Treatment

    The cause of essential tremor is unknown. In contrast to Parkinson disease, autopsies of patients with essential tremor have revealed no neuronal death or chemical deficiencies. The cause(s) of essential tremor will remain a mystery until the underlying genetic defects are identified. Such research is in progress. The most effective medications are primidone (50-750 mg per day) and beta-adrenergic blockers such as propranolol (60-240 mg per day). Interestingly, essential tremor and Parkinson tremor both respond to ventrolateral thalamotomy and deep brain stimulation, but essential tremor does not respond to anti-Parkinson medications. Patients with both Parkinson disease and essential tremor often require a combination of anti-Parkinson drugs and primidone or propranolol.

    Additional reading

    Elble RJ. Diagnostic criteria for essential tremor and differential diagnosis. Neurology 2000;54(Suppl 4):S2-6.

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