ManagementSection Topic

Tremor

remor is a common condition that can occur in isolation or be part of an evolving neurological Tcondition. It is amenable to treatment in most cases, but if first line therapies fail then often the management is complex and consideration for is considered. In this short review we outline a pragmatic approach to the patient with .

Definition and Classification ment approaches its target, it is termed an intention tremor. Tremor is defined as a rhythmic sinusoidal movement of a This latter tremor suggests damage in the and its body part, due to regular rhythmic muscle contractions. The efferent connections to the and is of a frequency most useful classification of is clinical and based on of 2-3Hz. Psychogenic tremors are generally rare and the circumstances in which they are seen (see Table 1). Static typically are of sudden onset with a variable but rarely Roger Barker is co-editor tremor occurs when a relaxed limb is fully supported at rest. in chief of ACNR, and is remitting clinical course and typically affect the trunk or Honorary Consultant in Postural tremor appears when a part of the body is main- limb with standing and/or using the limb respectively. at The tained in a fixed position and may also persist during move- Physiologic tremor has a frequency in the 7-11 Hz band Cambridge Centre for ment. Kinetic or action tremor occurs specifically during and is typically symptomatic in states of increased sympa- Brain Repair. He trained in neurology at active voluntary movement of a body part. If the amplitude thetic nervous activity whilst symptomatic postural tremors Cambridge and at the of such an action tremor increases as goal-directed move- occur in association with a wide range of neurologic National Hospital in London. His main area of research is into Table 1: Classification of tremor neurodegenerative and movement disorders, in particular Parkinson's and Type Definition Causes Huntington's disease. He is also the university lecturer in Neurology at ● STATIC or REST Present with hands Parkinson’s disease Cambridge where he or head held relaxed ● continues to develop his at rest (inc. -induced, postencephalitic) clinical research into these ● diseases along with his Other extrapyramidal diseases basic research into brain ● repair using neural transplants. POSTURAL When limb or body ● Physiological tremor is held in certain ● Exaggerated physiological position tremor, as in: Thyrotoxicosis anxiety states and stress (e.g. sympathomimetics, anti depressants, sodium valproate, lithium) heavy metal poisoning (i.e. David J Burn is the editor of our conference news mercury—the ‘hatter’s shakes’) section and Consultant ● Structural neurological disease, as in: and Reader in Neurology severe cerebellar at the Regional (‘red nucleus or midbrain tremor’)1 Neurosciences Centre, Newcastle upon Tyne. He Wilson’s disease qualified from Oxford Neurosyphilis University and Newcastle peripheral neuropathies upon Tyne Medical School in 1985. His MD was in the ● Essential (familial) tremor functional imaging of ● Task specific tremors (e.g. primary parkinsonism. He runs writing tremor)2 Movement Disorders clin- ics in Newcastle upon Tyne and Sunderland. Research KINETIC or ACTION When performing an ● Brain-stem or cerebellar interests include progres- (inc intention) action of some sort, disease, as in: sive supranuclear palsy such as picking up Multiple sclerosis and with Lewy bodies. He is also involved cup of tea Spinocerebellar degenerations in several drugs studies for Vascular disease Parkinson's Disease. Tumour

PSYCHOGENIC

1. Midbrain tremors results from damage in the region of the red nucleus, typically in the context of either MS, head trauma or a vascular insult. It is characterised by a combination of rest, postural and action tremor which is often severely disabling and very hard to treat, and this includes using stereotactic surgical thalamic lesions. 2. Dystonic tremors can be kinetic, postural or task specific and are irregular asynchronous and usually affect the arm and neck. Primary writing tremor is such an example.

ACNR • VOLUME 4 NUMBER 1 MARCH/APRIL 2004 13 Management Topic

disorders. These tremors can be distin- tremulous or “corrugated”. The cause of ET Table 2: Investigation of tremor guished neurophysiologically as they have a is unknown but a positive family history is different frequency, although there is signifi- obtained in over half of such patients and Routine haematology and biochemistry to exclude cant overlap in tremor frequency in several the pattern of inheritance in such families major metabolic problem including renal failure, liver common conditions associated with tremor indicates an autosomal dominant trait. No disease +/- (for example, and pathological or biochemical abnormality has Thyroid function tests Parkinson’s disease). been identified in essential tremor, but Immunoglobulins and electrophoretic strip recent functional imaging studies have Copper/Caeruloplasmin in young patients Clinical approach to the patient with pointed towards abnormal activation of the Consider genetic tests such as SCA screening tremor cerebellum, red nucleus and , and The most useful approach to a patient with in some patients alcohol relieves the tremor. tremor is a clinical one. In a small number of families, genetic loci, Consider imaging, EMG-NCS, and CSF but only History and examination: but not the causative gene(s), have been iso- if tremor is late onset or evolving with other neuro- ● When did it first appear? lated. logical Long standing implies essential tremor (ET) The typical clinical presentation is tremor ● Where is the exaggerated physiological in one or both hands on maintaining a pos- tremor? ture, as when holding a cup or glass, but is Table 3: Treatment of tremor* Hands: Unilateral versus bilateral with bilat- not present at rest. On movement, as in fin- eral tremor implying exaggerated physiolog- ger-nose testing, the tremor continues but Stop any drug that may be causing tremor ical or ET. Unilateral tremor is more sugges- does not get strikingly worse, as is the case Inc. Lithium, SSRIs, neuroleptics, sodium valproate, tive of either Parkinson’s disease or dystonic with cerebellar intention tremor. Tremor of beta agonists, thyroxine, aminophylline etc tremor the head (titubation) and jaw is present in Voice involvement implies dystonic or ET about 50 per cent of cases, and tremor of the Drugs which are worth trying: Head involvement with head titubation sug- legs occurs in about a third. Despite the Beta blockers gests either cerebellar/brainstem pathology, tremor, tests of co-ordination usually are dystonic head tremor or ET performed normally, is unaffected, Legs/body involvement especially when at and there are no other neurological abnor- Gabapentin rest with a feeling that standing still pro- malities. duces an intense sense of imbalance that Some other variants of the syndrome are passes off with walking is highly suggestive encountered occasionally. Thus isolated, Botulinum toxin injections for some dystonic of orthostatic tremor inherited, head tremor may occur, with tremors ● What, if anything, makes it better? either ‘yes-yes’ or ‘no-no’ movements, and Alcohol helping the tremor suggests ET tremulous ‘writer’s cramp’ (primary writing Deep brain stimulation/ of VIM ● What brings out the tremor? tremor) is recognised. This is classified by thalamic nucleus Certain actions or movements implying it is some as a dystonic tremor. Tremor of the either an action tremor, postural tremor, legs on standing, at around 5 to 8 Hz may Other drugs and manipulations which have been intention tremor or dystonic (e.g. with writ- occur in some patients with essential tremor tried in the treatment of tremor (ET unless otherwise ing) (see Table 1). and is thought to be different from primary indicated) with possible benefit in some cases: All tremors worsen with stress and anxiety, orthostatic tremor (see below). Phenobarbitone so this is non-discriminatory The treatment of this condition involves Carbonic anhydrase inhibitor (Methazolamide) ● Is there any family history of a tremor? beta-blockers which work in about 30-40% Clonidine Helpful for ET and other inherited condi- of cases (up to a dose of 240mg/day). Amantadine tions where tremor is a feature (beware of Primidone, in standard Clonidine (probably not effective in ET) the patient diagnosed as “tremor dominant dosages, also helps some patients but is very (probably not effective for intention Parkinson’s disease” where ET was actually sedating. These two classes of drug have a tremor) more likely). Are there any other neurologi- reasonably solid evidence base for efficacy in Clozapine/Olazepine/Quietapine cal symptoms – bradykinesia, ET. Other therapies, with little or no evi- Mirtazapine and so on suggestive of Parkinson’s disease dence to support their use, include clon- Vagal nerve stimulation or other neurodegenerative condition azepam, gabapentin and topiramate, (see ● Are there any medical problems and what Table 3). Stereotaxic thalamotomy may be * the treatment of the tremor in PD lies outside the drugs is the patient taking? required in the very small number of scope of this article but clearly revolves around the Especially important to look for thyrotoxi- patients whose tremor is so severe although use of L-dopa and dopamine agonists. It is controver- cosis or paraproteinaemic neuropathies. For more recently this has been superceded by sial whether anti-cholinergic agents and the newer example, consider cimetidine, valproate, the use of deep brain stimulation in the ven- dopaminergic agonists have more anti-PD tremor amiodarone, }eta-agonist inhalers. tral intermediate nucleus of the thalamus. effects than L-dopa based therapies. Investigation (see Table 2) Treatment (see Table 3) ORTHOSTATIC TREMOR This is a very rare condition in which there is Certain specific tremor conditions tremor of the legs and body especially when ESSENTIAL (FAMILIAL) TREMOR the patient stands still, which gives the An illness characterised by a 5-8Hz postural patient the feeling of being very unsteady tremor of the arms and head. ET can present when standing still. As soon as they start at any age, is slowly progressive and general- moving the condition improves. ly causes mild disability although severe The tremor can be seen in some patients cases may be functionally incapacitating although in others it is best diagnosed by lis- Correspondence to: (hence the potentially inappropriate use of tening over the thighs where the tremor can Roger Barker, E-Mail: the term “benign”, sometimes used to prefix be heard as the sound of distant helicopters. [email protected] or It responds well to . David Burn, E-Mail: this disorder). It can cause handwriting to be [email protected]

14 ACNR • VOLUME 4 NUMBER 1 MARCH/APRIL 2004