Approach
Tremor must be differentiated from other involuntary movements (e.g., myoclonus, chorea, dystonia, clonus, and tics). Once tremor is identified, initial consideration should be given to whether the tremor is a rest or action tremor.
History
A thorough history should explore type, onset, exacerbating and relieving factors, body region affected, medicines, possible exposure to toxins, family history, and associated symptoms. It should also assess functional limitations (e.g., cup holding, hand writing, social embarrassment).
Key considerations include:
Rest versus action tremor: patients with rest tremor often notice their tremor when the affected limb is at rest. For example, patients often notice rest hand tremor when sitting in a chair watching TV or when lying down to sleep. Action tremors often interfere with performing activities of daily living, such as writing, using a cup or glass, pouring, applying make-up, buttoning, or doing anything that requires fine dexterity. It is also important to determine whether the tremor occurs with only one specific task.
Age at tremor onset: although Parkinson's disease (PD) can occur at any age, the median age range of onset for symptoms is 58 to 62 years. The prevalence and incidence of essential tremor increase with age, but it can appear in early adulthood in those who have a family history of the condition. Wilson's disease usually occurs in patients <40 years of age, so this must be considered in any atypical tremor, especially if the tremor develops in patients <40 years of age.
Nature of tremor onset: most tremors have a gradual onset and are noticed intermittently before occurring constantly. A functional (psychogenic) cause should be considered if a significant tremor starts abruptly.
Body region affected: PD typically affects the arms, legs, and chin, but rarely causes head tremor. Essential tremor involves the hands, head, and voice, but uncommonly involves the legs. Isolated head tremor may suggest a dystonic tremor.
Exacerbating and alleviating factors: most tremors worsen with stress, anxiety, cold, and fatigue. Alcohol intake may lead to suppression of essential tremor and dystonic tremor.[15]
Medicines: medicine lists should be carefully scrutinised. Any of the following medicines can cause tremor: neuroleptics, atypical antipsychotics, anti-nausea agents (metoclopramide, prochlorperazine, promethazine), calcium-channel blockers (flunarizine, cinnarizine), dopamine depletors (tetrabenazine), antidepressants (serotonin-reuptake inhibitors, tricyclics, monoamine oxidase inhibitors), mood stabilisers (lithium), antiepileptic drugs (valproic acid), cardiac drugs (amiodarone), immunosuppressants (ciclosporin, tacrolimus, corticosteroids), anti-asthma drugs (salbutamol, theophylline), and stimulants (amphetamines).
Social history: a history of alcohol misuse may alert the examiner to an alcohol withdrawal syndrome. Drug misuse, especially with amphetamines, is frequently associated with action tremors. Clinicians should also enquire about caffeine use.
Family history: approximately 50% of patients with essential tremor have a positive family history (autosomal-dominant pattern). In patients with fragile X tremor ataxia syndrome (FXTAS), there may be a history of premature ovarian failure in female family members, or intellectual disability in male family members.[13]
Review of symptoms: a careful review should be conducted with the emphasis on parkinsonian symptoms (micro-graphia, slowness of movement, drooling, dysphagia, shuffling gait, postural abnormalities, hypophonia, rapid eye movement sleep behaviour disorder, reduced sense of smell, constipation, urinary frequency); presence of cognitive impairment; presence of incoordination, falls, or visual symptoms; comorbidities such as multiple sclerosis, trauma, stroke or hypertension, and neuropathy; diaphoresis, tachycardia, palpitations, and weight loss; psychiatric history (e.g., anxiety or depression); and pulling sensations or muscle contractions that would suggest dystonia.
Observation
Initially, the tremor should be differentiated from other involuntary movements. For example:
Myoclonus presents with brief shock-like jerks or pauses in muscle activity and is usually irregular.
Chorea refers to irregular, non-stereotyped, random, flowing involuntary movements of limbs (often distal), face, or trunk.
Dystonia is sustained muscle contraction resulting in twisting or abnormal posturing of a body part. Dystonic tremor refers to tremor occurring in a body part affected by dystonia.
Clonus is an abnormal rapidly alternating muscular contraction and relaxation, often elicited by stretch in a spastic limb.
Tics are stereotyped, repetitive movements that can be simple or complex and usually preceded by a feeling of tension. Tics can be distinguished from other movements by suppressibility.
Epilepsia partialis continua is a form of partial status epilepticus with simple motor manifestations that are maintained for >1 hour, with clonic activity restricted to one body part and recurring at fairly regular intervals.
Fasciculations are small, local, involuntary muscle contraction (twitching) visible under the skin that arise from the spontaneous discharge of a bundle of skeletal muscle fibres.
Once the tremor is identified, characterising its type is of prime importance. The tremor should be observed and differentiated as a rest or action tremor. For hand tremor, the patient should be observed with hands resting on the lap, with hands held straight out in sustention, and with the arms bent at the elbows with hands in front of the face. A postural tremor may be present in only 1 position. The patient should also be asked to perform finger-to-nose or finger-to-finger movements. If a rest tremor is present and PD is suspected, it should be noted whether the distribution is unilateral or asymmetrical, and whether there is bradykinesia or rigidity. If functional (psychogenic) tremor is suspected, it is important to check for tremor distractibility or other non-organic signs such as give-way weakness. It may also be useful to observe the patient drinking from a glass or writing. The tremor should be classified as to body part (e.g., arms, legs, head), when it occurs, its frequency, and its amplitude (i.e., fine or coarse). If tremor involves the head, the physician should look for dystonic posturing of the head and neck.
Neurological examination
A detailed neurological examination should be performed on every patient with tremors. Mental status should be tested to investigate cognitive impairment and to assess speech. Cranial nerve testing is important to rule out findings that could be attributable to progressive supra-nuclear palsy (impairment of vertical more than horizontal voluntary eye movements), multiple sclerosis (afferent pupillary defect, inter-nuclear ophthalmoplegia), stroke (facial droop, visual field cut), or multiple system atrophy (nystagmus, dysmetric saccades).
Cerebellar function testing is important to identify ataxia, but also to investigate possible kinetic tremor. Sensory examination may rule out a neuropathy. Gait examination may reveal shuffling, decreased arm swing, or difficulty with tandem walking. Asymmetrical reflexes may suggest a central cause for the tremor.
Investigations
Laboratory investigations including basic metabolic panel (with liver function tests and serum calcium) may be helpful to rule out some metabolic causes of tremor. Thyroid function tests should be performed in all patients with action tremor. For patients with suspected dementia with Lewy bodies, thyroid-stimulating hormone and vitamin B12 levels will help exclude reversible causes of cognitive impairment. For patients with suspected Wilson's disease, 24-hour urinary copper and serum ceruloplasmin determinations will assist the diagnosis; slit-lamp examination of the eyes for Kayser-Fleischer rings will also be helpful.
In patients with suspected PD, a positive response to a dopaminergic agent highly suggests the diagnosis. In patients with suspected PD and atypical features (e.g., atypical course, dementia, significant imbalance in early disease, autonomic dysfunction, gaze abnormalities, or atypical abnormalities on neurological examination), a magnetic resonance imaging (MRI) cranial scan should be considered.[16] For other rest tremors, cranial MRI or computed tomography (CT) scans should be considered to rule out structural causes of parkinsonism. Positron emission tomography (PET) and single-photon emission computed tomography (SPECT) can detect abnormalities of the dopaminergic system that may help distinguish parkinsonism from essential tremor. These PET and SPECT tracers typically bind to the dopamine transporter or vesicular monoamine transporter to give an idea of dopamine terminal integrity. (123)I-Ioflupane dopamine transporter SPECT imaging (DaTscan) may be considered for differentiating parkinsonian tremor from essential tremor when it is difficult to distinguish the conditions clinically.
MRI and CT studies are also important in cases of intention tremor when a stroke, tumour, or multiple sclerosis is suspected.
Genetic testing is required for suspected FXTAS.
Use of this content is subject to our disclaimer