Neurologist Dr Mark Price’s update on distinguishing essential tremor from Parkinson’s, medical management and the surgical options
Neurologist Dr Mark Price's update on distinguishing essential tremor from Parkinson's, medical management and the surgical options
Tremor is the most common movement disorder and – as with so many conditions – our ageing population means GPs are likely to come across it more frequently.
The most common aetiology is essential tremor, with the population prevalence estimated to be between 0.4% and 3.9%.1
The biggest diagnostic challenge is distinguishing essential tremor from Parkinson's disease, so this is covered in detail later. But there are many other possible aetiologies including multiple sclerosis, Huntington's disease and Wilson's disease.
This article will cover key information on the classification and diagnosis of tremor, the medical management of essential tremor and Parkinson's, and a brief description of the surgical options.
Definition and classification
Tremor is defined as the involuntary, rhythmic oscillation of a body part.2 There are various ways of classifying tremor, but the most clinically useful is by the ‘state of activity' – whether it occurs at rest or with action – at a particular site.
Those classifications are:
• Rest tremor – when the body part is completely supported against gravity and not voluntarily activated.
• Action tremor – any tremor produced during voluntary contraction of muscles. This can be further divided into:
– postural tremor, which is seen while voluntarily maintaining a position against gravity, such as holding hands stretched out in front of the body
– kinetic tremor, which occurs during any voluntary movement, including at the beginning of the movement, during it or when the target is reached – this last type is termed intention tremor
– task-specific tremor, which is a specific type of kinetic tremor that typically occurs during certain tasks such as writing or speaking
– isometric tremor, which is a result of muscle contraction without movement, for example clenching a fist.
History and investigations
A thorough clinical history and examination is vital. History should include:
• age at onset of tremor
• pattern of onset – gradual or sudden
• body part first affected
• sequence of any spread
• rate of progression
• family history of tremor, Parkinson's disease or other neurological disorder.
Some aspects of a neurological examination – such as severity rating – would be most commonly done in secondary care. But GPs should note:
• location of tremor
• type or ‘state of activity' of tremor
• presence of bradykinesia, rigidity or postural changes, which are suggestive of Parkinson's
• presence of ataxia, cerebellar findings suggestive of MS
• presence of dystonia.
Examine the tremor in different positions. If an upper limb is affected, it should be examined resting on the arm of a chair or in the patient's lap to look for a rest tremor. Asking the patient to hold their arms stretched out will make postural tremor and the delayed – or ‘re-emergent' – tremor of Parkinson's more evident.
Kinetic tremors can be spotted by finger-to-nose testing. Asking the patient to write a sentence and draw a spiral can be very useful. A large, expansive spiral with jagged handwriting is typical of essential tremor, while a small, tight spiral with a decrease in the size of the letters towards the end of the sentence (micrographic) is more typical of Parkinson's.
Other findings include:
• optic disk changes – suggesting MS
• Kayser-Fleisher rings and hepatomegaly – suggesting Wilson's disease
• peripheral neuropathy or distal muscle atrophy – suggesting Charcot-Marie-Tooth disease.
A specialist will screen for suspected Wilson's disease by measuring 24-hour urine copper (high) and serum ceruloplasmin (low). An MRI scan will identify a focal lesion – especially useful if the tremor is on one side of the body.
Single-photon emission computed tomography (SPECT) is not currently available everywhere, but can distinguish between essential tremor and degenerative conditions such as Parkinson's or multiple system atrophy. Even if it is available, SPECT is often reserved for cases where the diagnosis remains doubtful after thorough clinical evaluation or even a therapeutic trial of dopaminergic medication.
Electromyography and nerve conduction studies are used to confirm the presence of peripheral neuropathy such as Charcot-Marie-Tooth disease.
Excluding physiological tremor
Physiological tremor is a normal finding – seen as a fine action tremor. It is not symptomatic, except sometimes during motor tasks requiring great precision such as watchmaking and microsurgery. But it can be exacerbated by anxiety, metabolic disorders, caffeine, drugs such as valproate, neuroleptic drugs and tricyclic antidepressants or alcohol withdrawal.3
Distinguishing Parkinson's disease from essential tremor
Typical presentations of Parkinson's and essential tremor have characteristic tremor features that often make them easy to distinguish. Parkinson's tremor is a low-frequency rest tremor typically defined as a pill-rolling tremor. The main features are outlined in the box (left), but key is that essential tremor is a single-symptom postural and kinetic tremor, while the hallmark presentation in Parkinson's is rest tremor, accompanied by bradykinesia.
But it's important to remember there can be overlap. Essential tremor may be a risk factor for subsequent Parkinson's, with one study identifying a four-fold increased risk.4
Medical management of tremor
Carefully explaining the problem and the reassurance of regular follow-up may be all that is needed in patients with both mild essential tremor and early Parkinson's disease. The NHS Clinical Knowledge Summary website has good-quality patient information material on both (www.cks.nhs.uk).
Propranolol (up to 40mg two or three times daily) is generally regarded as the first-line treatment, and both it and primidone (up to 250mg tds, but titrated up slowly) have been shown to be effective. The epilepsy treatment topiramate is also backed by similar quality evidence, but tends to be used third line.
Combining propranolol and primidone is more effective than using either drug alone and should be considered for patients on maximal doses of either drug. Alternatives to these are:
• busiprone 5mg tds
• clonazepam 0.5-3mg daily in divided doses – with the usual warnings of habituation.
There is some evidence that about half of patients with essential tremor respond to two to four units of alcohol a day, but the mechanism behind this is unknown.5 Typically two units of alcohol will suppress the tremor for around four hours, but there is often a rebound worsening of tremor the next morning.
The tremor associated with Parkinson's usually improves with dopaminergic and anticholinergic medications. Combining a dopaminergic and an anticholinergic is effective in tremor-predominant Parkinson's disease. But side-effects such as dry mouth, blurry vision and confusion can limit the use of anticholinergic therapy.
These drugs should be avoided in older patients, and if they have to be stopped or stepped down this needs to done gradually to avoid severe rebound effect on tremor.
Other types of tremor
Neuropathic tremors and the tremor associated with multiple sclerosis are difficult to treat effectively using medication. But there are treatment options for the following:
• Head tremor The treatment of choice for severe isolated head tremors is intramuscular botulinum toxin. Other cerebellar tremors are very difficult to treat medically.
• Task-specific tremor Propranolol, primidone, anticholinergics or botulinum toxin treatment are sometimes helpful.
• Primary orthostatic tremor Clonazepam gives partial response, but patients often get more benefit from carrying a portable stool with them so they can rest whenever they need to.5
Stereotactic neurosurgery can be effective in contralateral limb tremor in patients with Parkinson's disease, dystonic tremors, writing tremor, Holmes' tremor, post-traumatic tremor and tremor in MS. Patients with the more severe, intractable forms of essential tremor can also benefit.6
Lesions are created using a heated electrode guided into different parts of the thalamus depending on the type of tremor. A temporary lesion is made, followed by testing the still-conscious patient's speech, language and co-ordination before heating the probe again to create a permanent lesion. The goal is to target the lesion so precisely that the tremor permanently disappears without disrupting normal brain function.
Deep brain stimulation is an alternative surgical technique, suitable for treating Parkinsonian tremor and essential tremor. Implantable electrodes send high-frequency electrical signals to the thalamus and the patient uses a small magnet to activate a pulse generator implanted under the skin, temporarily disabling the tremor.
The advantage is that it is much safer than lesional surgery – particularly for bilateral procedures -but the post-operative costs are far higher.
Dr Mark Price is a consultant neurologist for the Betsi Cadwaladr University Health Board in WalesHand rigidity test for tremor Hand rigidity test for tremor features of essential tremor versus parkinson's