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Myoclonus Can Occur in Many Different Settings

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Myoclonus Can Occur in Many Different Settings Management Topic Section Myoclonus yoclonus can occur in many different settings and SEPs, which are giant in cortical myoclonus, and is Min a range of neurological disorders, as well as being therefore most consistently found in the rare group of seen physiologically when falling asleep in lectures for patients with progressive myoclonic epilepsy example! The essential feature of the condition, which More sophisticated neurophysiology can also be makes it instantly recognisable is the sudden, brief and undertaken such as jerk-locked EMG to EEG back aver- shock-like nature of the movement (and equates to EMG aging, but this is not routinely available in most hospitals. bursts of activity of about 10-50msec). There are differ- ent ways in which it is defined according to: what pro- Other tests to be considered vokes it; where it is; and what it is associated with neuro- ■ Genetic tests – looking for DRPLA and mitochondrial Roger Barker is co- logically as well as pathophysiologically. As with all move- disease editor in chief of ment disorders it can be associated with other involun- ■ Skin biopsy – looking for neuronal ceroid lipofusci- ACNR, and is Honorary Consultant in tary movements. nosis (NCL). Neurology at The In this short review I will briefly discuss the different ■ Axillary skin biopsy – looking for Lafora body disease Cambridge Centre for types of myoclonus and their salient features and present and Unverricht-Lundborg disease Brain Repair. He trained ■ in neurology at a pragmatic approach to the patient with this type of Muscle biopsy – looking for mitochondrial disease as Cambridge and at the movement disorder. well NCL, Lafora body disease National Hospital in ■ Enzyme assays in urine and blood – looking for sialdo- London. His main area Clinical evaluation of myoclonus sis, gangliosidosis and Gaucher’s disease of research is into neurodegenerative and The initial evaluation is undertaken to decide whether ■ Systemic investigation looking for a primary malignan- movement disorders, in the myoclonus is spontaneous, and this may require a rel- cy – CT chest/abdomen; whole body PET scan etc particular parkinson's atively prolonged period of observation. If not present ■ Brain biopsy – looking for vasculitis and possibly to and Huntington's disease. He is also the then it is worth trying to provoke it. In the first instance confirm the nature of a neurodegenerative disorder university lecturer in this involves getting the patient to move (such as putting Neurology at their hands out in front of them) which typically pro- Treatment of Myoclonus Cambridge where he continues to develop his vokes action myoclonus, and in some cases holding the In many cases treatment is not necessary, as there is either clinical research into hands out in front causes them to flap (asterixis) which a clear underlying aetiology that needs rectifying; the these diseases along reflects negative myoclonus (which equates to a brief loss myoclonus does not cause any major disabilities; or the with his basic research of EMG activity). Finally in order to see whether there is myoclonus is in the presence of advanced neurodegener- into brain repair using neural transplants. any stimulus sensitivity, one should flick the distal finger ative disease. joints and/or make a sudden loud noise (clap hands) to If drug therapy is required the most successful are: see if either of these manoeuvres provokes a reflex ● Clonazepam for all forms of myoclonus myoclonus. ● Sodium valproate for most forms of myoclonus This having been achieved the next question is to ● Piracetam for post-anoxic myoclonus decide the distribution of the myoclonus and this may ● Levetiracetam for post-anoxic myoclonus provide clues as to aetiology and pathophysiological ori- ● Tetrabenazine is said to be helpful for segmental gin. In particular is the myoclonus confined to one area myoclonus (i.e. focal such as a jerking limb for example); is it seg- ● Botulinum injections for some forms of focal mental (adjacent body parts- shoulder), multifocal (wide- myoclonus, especially hemifacial spasm ly distributed, unpredictable and not synchronised) or ● Other drugs that may have a role include primidone generalised (synchronised jerks affecting most of body). for cortical myoclonus and fluoxetine in postanoxic Finally one examines the patient to see whether there and action myoclonus. are other associated systemic or neurological abnormali- ties which are associated with the myoclonus. Some myoclonic syndromes Defining the pathophysiological basis is not necessary ESSENTIAL MYOCLONUS/MYOCLONIC DYSTONIA although focal myoclonus is normally of focal origin - so This is a heterogeneous condition, which consists of involves the cortex or spinal cord, whilst subcortical sites widespread myoclonus affecting all four limbs, trunk, of origin produce generalised or multifocal myoclonus. neck, and face, occurring at about 10 to 50/min, enhanced by action and sensory stimuli. Onset is usually Investigation of myoclonus History and examination is followed by a series of investi- Table 1. The classification of myoclonus gations that may help identify the cause, although the nature of the tests will to some extent be determined by the Clinical Clinical Neurophysiological Aetiology duration and type of myoclonus and whether it is associ- Presentation Distribution Origin ated with other neurological or systemic abnormalities. Full biochemical screen looking for major electrolyte, ● Spontaneous - typically ● Generalised ● Cortical ● Physiological renal or hepatic abnormalities and consider arterial seen normally or in patients (often associated with metabolic ● Multifocal with giant SEPs) ● Essential blood gases. encephalopathies or CJD Autoantibody screen in particular looking for coeliac ● Segmental ● Subcortical ● Symptomatic disease; paraneoplastic syndromes and anti-GAD for ● Action - which (brainstem and occurs during active ● Focal includes hyperekplexia; jerking stiff man syndrome. muscular contractions, brainstem reticular Imaging to exclude cerebrovascular, neoplastic or obvi- and is very disabling. myoclonus and ous neurodegenerative condition as well as focal lesion in palatal myoclonus) patients with focal myoclonus, especially in spinal and ● Reflex - which occurs ● Spinal (typically propriospinal myoclonus. to somesthetic, visual and associated with a EEG to see whether there is evidence that myoclonus is auditory stimuli. focal spinal cord lesion) part of an epileptic syndrome or whether the patient has ● Propriospinal epilepsia partialis continua as well as looking for CJD. 20 ACNR • VOLUME 3 NUMBER 5 NOVEMBER/DECEMBER 2003 Management Topic Table 2 Causes of myoclonus in childhood or adolescence, but disability is strikingly mild in most cases. There is no progression, intellect is normal, fits do not occur, and no other deficit appears. Generalised myoclonus Some patients report that alcohol helps their jerks. Essential myoclonus Whilst many cases are sporadic, in some cases there is Non-progressive condition in which myoclonus is only or most important neurological symptom a positive family history suggesting an autosomal domi- and sign. Progressive myoclonic encephalopathies (PME) nant condition with variable penetrance and expression. Conditions in which there is obvious myoclonus (with or without seizures) as part of a In some case the myoclonus may be associated with progressive encephalopathy. dystonia (myoclonic dystonia) – with the latter often ● With demonstrable metabolic cause (e.g. Lafora body disease, mitochondrial encephalomy- being the dominant clinical feature. It often shows a dra- opathy (esp.MERFF); Sialidosis; Neuronal ceroid lipofuscinosis) matic response to alcohol and is associated in some cases ● Hereditary myoclonus with no known metabolic cause (e.g. Familial myoclonic epilepsy with mutations in the ø-sarcoglycan gene, but is geneti- (Unverricht–Lundborg disease); rarely seen in HD and DRPLA) cally heterogenous with associations with the D2 receptor ● Other sporadic diseases (e.g. Subacute sclerosing panencephalitis (SSPE), Creutzfeldt–Jacob gene (chromosome 11q23) and a Canadian family linked disease, Alzheimer’s disease, Parkinsonian plus conditions- especially corticobasal degenera- tion; paraneoplastic; vasculitis; coeliac disease) to chromosome 18p11. ● Metabolic myoclonus (e.g. uraemia, hepatic failure, CO2 narcosis) Static myoclonic encephalopathies PROGRESSIVE MYOCLONIC ENCEPHALOPATHIES Condition in which there is obvious myoclonus after some acute and now static cerebral insult. (PME) E.g. Postanoxic action myoclonus (Lance–Adams syndrome). Most of the diseases causing a progressive myoclonic Myoclonic epilepsies encephalopathy are rare and a discussion of them lies Conditions in which epilepsy is the main problem, but myoclonus is present. outside the scope of this short review. Those that cause Focal myoclonus this: Conditions in which the myoclonus is restricted to one small discrete part of the body ■ with cognitive decline and epilepsy include Lafora ● Spinal myoclonus body disease; neuronal ceroid lipofuscinosis (in the ● Propriospinal myoclonus form of Kuf’s disease in adults); MERFF, sialidosis; ● Palatal myoclonus (see Case on ACNR website, www.acnr.co.uk) DRPLA ● Hemifacial spasm ● Cortical myoclonus ■ with minimal cognitive involvement and epilepsy ● Epilepsia partialis continua include Unverricht-Lundborg disease and the progres- sive myoclonic ataxias (e.g. coeliac disease and some of the SCAs) angioma, or after spinal cord trauma.
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