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Other movement disorders
MOVEMENT DISORDERS
Other movement disorders
Key points C
Ataxias are caused by dysfunction of the cerebellum or its connections and cause irregular disordered movement
C
The differential diagnosis of ataxia is large but the speed of onset helps in making a diagnosis
C
Hyperkinetic movement disorders are associated with excess involuntary movements that often interfere with normal movements. The type of hyperkinetic movement disorder is usually apparent after careful observation of the patient
C
In chorea, the involuntary movements are random in nature
C
In dystonia, the movements are patterned and sustained
C
In tremor, the movements are rhythmic
C
In myoclonus, the movements are very brief and irregular
C
In tics, the movements are suppressible and associated with an underlying urge sensation
Monty A Silverdale
Abstract This article examines movement disorders other than Parkinson’s disease, including ataxias and hyperkinetic movement disorders. Ataxias are caused by dysfunction of the cerebellum or its connections and cause irregular disordered movement. Hyperkinetic movement disorders involve involuntary movements that often interfere with normal movements. There are several different hyperkinetic movement disorders, which can usually be distinguished by clinical assessment: in chorea, the involuntary movements are random in nature; in dystonia, the movements are patterned; in tremor, the movements are rhythmic; in myoclonus, the movements are very brief, jerky and irregular; and in tics, the movements are suppressible and associated with an underlying urge sensation This article gives an approach to diagnosing patients with ataxic and hyperkinetic movement disorders, and discuss some of the more common and important associations. It also discusses treatment including using deep brain stimulation, which can be extremely effective in correctly selected patients.
Keywords Ataxia; chorea; dystonia; myoclonus; tardive dyskinesia; tics; Tourette’s syndrome; tremor
Speech: patients with ataxic disorders often have dysarthria. Cerebellar dysarthria can be difficult to distinguish from other forms of dysarthria. Getting the patient to say ‘Ta Ta Ta’ repetitively can help. In cerebellar dysarthria, speech can be irregular (analogous to ‘atrial fibrillation’ of speech).
Introduction Upper limbs: when testing for upper limb ataxia, the finger enose test is used. The examiner asks the patient to stretch out their arm in order to touch the examiner’s finger, then flex their arm to touch their own nose with their fingertip. The process is then repeated. The examiner is looking for poorly coordinated movements that can overshoot or undershoot the target, sometimes developing a tremor as the target is approached (intention tremor). It is important that the examiner gets the patient to straighten their arm fully as subtle ataxia may only develop as the arm extends to approach the target. A disorder of rapidly alternating movement (dysdiadochokinesia) is tested by asking the patient to alternately pronate and supinate the tapping hand.
Ataxic disorders are caused by dysfunction of the cerebellum or its connections and cause irregular disordered movement. Hyperkinetic movement disorders cause involuntary movements. Simply observing the patient allows most hyperkinetic movement disorders to be diagnosed. Much of this observation can be performed while taking the history. Table 1 illustrates some of the tricks used during examination to help reach a diagnosis of a hyperkinetic movement disorder.
Ataxia Definition The cerebellum fine-tunes and coordinates movement so patients with ataxia complain of clumsiness on attempted movement. They can also have poor balance when walking, and slurred speech.
Lower limbs: ataxia in the lower limbs is tested using the heel eshin test, in which the heel is passed up and down the shin.
Testing for ataxia Eye movements: pursuit eye movements (following a finger) are often very jerky in ataxic patients. Saccadic eye movements (looking from one target to another) often undershoot or overshoot the target. Nystagmus may be seen.
Gait: an ataxic gait is usually broad-based and unsteady. Patients usually struggle with tandem walking (where the heel of the front foot touches the toes of the back foot with each step).
Causes of ataxia There are many causes of ataxia (Table 2). It is helpful to divide cerebellar disorders into those presenting acutely (seconds, minutes or hours), those presenting subacutely (days or weeks) and those presenting over a chronic time course (months or years). Toxic causes such as alcohol are usually obvious from the
Monty A Silverdale PhD FRCP is a Consultant Neurologist and Movement Disorder Specialist at the Greater Manchester Neuroscience Centre, Manchester, UK. Competing interests: none declared.
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Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Silverdale MA, Other movement disorders, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.06.010
MOVEMENT DISORDERS
Examining a patient with a hyperkinetic movement disorder C
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Important causes of ataxia Immediate onset Cerebellar stroke Cerebellar bleed Onset over days Wernicke’s encephalopathy Multiple sclerosis relapse Viral cerebellitis (mainly in children) Onset over weeks or months Paraneoplastic CreutzfeldteJakob disease Autoimmune (e.g. anti-Glutamic Acid Decarboxylase (GAD) antibodies) Posterior fossa tumour (months or years depending on speed of tumour growth) Onset over years Alcoholic cerebellar degeneration (can also present more quickly) Friedreich’s ataxia (autosomal recessive) Spinocerebellar ataxia (autosomal dominant, many genes) Mitochondrial disease (can also present acutely or subacutely) Multiple system atrophy (progresses over months or 1e2 years) Idiopathic late-onset ataxia Ataxia with vitamin E deficiency Non-cerebellar causes Sensory ataxia (impaired proprioception, positive Romberg’s test) Bilateral vestibulopathy, (unsteady gait, positive Romberg’s test, impaired dynamic visual acuity test)
Observe the patient at rest with their hands resting on their lap. This can be done while taking the history Distract the patient by asking them to close their eyes and recount the months of the year backwards. Most movement disorders worsen with distraction Ask the patient to hold their arms outstretched. The involuntary movements of dystonia, chorea and essential tremor usually worsen on sustained posture Ask the patient to perform actions including writing and pouring water between cups. Most hyperkinetic movement disorders, including chorea, dystonia and essential tremor, become more obvious with action Ask the patient to try and suppress the movements for 10 seconds. Tic disorder can usually be partially or completely suppressed but will become much worse afterwards Test the patient for motor impersistence by asking them to stick their tongue out for a count of 10 seconds. Patients with chorea are not usually able to do this, and the tongue will keep popping in and out of the mouth Ask the patient to walk. Many movement disorders including chorea and dystonia worsen on walking Perform a full general and neurological examination looking for other clues to the diagnosis If a psychogenic tremor is suspected, check for entrainment by getting the patient to tap a rhythm with one hand and see whether the frequency of tremor in the other hand changes to the tapping frequency
Table 2
Table 1
syndrome and polycythaemia, Sydenham’s chorea (post-streptococcal) and chorea during pregnancy (chorea gravidarum). Medications, including levodopa, the oral contraceptive pill, anticholinergic drugs, anticonvulsants and antidepressants, can cause chorea.
history. Structural problems usually show on cranial magnetic resonance imaging. The age of onset often helps to reach a diagnosis in chronic cerebellar disorders. Many genetic conditions present at a younger age, whereas other conditions such as multiple system atrophy present at an older age. Cranial imaging can help in chronic cerebellar disorders: some conditions cause cerebellar atrophy (e.g. ataxia telangiectasia) whereas others usually do not (e.g. Friedreich’s ataxia). Cerebellar disorders are discussed in more detail elsewhere.1
Huntington’s disease: this is an autosomal dominant condition caused by an expanded trinucleotide repeat in the huntingtin gene on chromosome 4. It causes psychiatric problems (depression, personality change), cognitive problems and a movement disorder (usually chorea but sometimes dystonia or parkinsonism).
Chorea Other causes: these include benign hereditary chorea, senile chorea and various Huntington’s mimics.2
Definition Chorea denotes involuntary movements that are completely random in nature. In most cases, the whole body is affected. A patient with chorea can initially appear simply fidgety, and it is sometimes difficult to distinguish an anxious, restless person from someone with chorea. A fidgety patient is usually able to suppress the movements when concentrating on something such as writing, whereas chorea usually worsens on action, and writing can be difficult. Testing for motor impersistence often helps (Table 1).
Dystonia Definition In dystonia, sustained muscle contractions lead to twisting movements and abnormal postures. Whereas chorea causes random movements, dystonia causes patterned movements e meaning that the same movement is performed over and over again. For example, if the head turns to the left, it repeatedly turns to the left. Dystonia is focal when only one body part is affected, for example the neck (cervical dystonia), the eyes (blepharospasm) or the limbs. It can also be generalized, meaning that the whole body is affected.
Causes Medical causes: these include non-ketotic hyperglycaemia, hyperthyroidism, systemic lupus erythematosus, anticardiolipin
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Please cite this article in press as: Silverdale MA, Other movement disorders, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.06.010
MOVEMENT DISORDERS
Types Task-specific dystonia: this occurs only with certain activity, such as writing (writer’s cramp). In this case, the patient finds their fingers or arm adopt an unusual posture when they try to write, making writing difficult. This condition is particularly common in people who do a lot of writing. Other high-intensity activities can also be associated with task-specific dystonia, including playing a musical instrument (e.g. piano, violin) and certain sports (e.g. the ‘yips’ in golf).
Causes Medical causes: we all have a high-frequency physiological tremor that becomes more apparent with stress. Hyperthyroidism and drugs (including b-adrenoceptor agonists, lithium and sodium valproate) can cause or worsen tremor, and careful attention should be paid to the drug history. Essential tremor: this causes a postural and action tremor of slightly lower frequency than physiological tremor. Unlike a Parkinsonian re-emergent tremor, essential tremor occurs immediately on sustained posture. The tremor worsens on action (which is unusual for parkinsonian tremor). A typical patient with a parkinsonian tremor might complain that their tremor was worst when watching television, whereas patients with essential tremor typically complain about difficulty holding a cup of tea. Essential tremor is usually familial, although the causative gene is unknown. Although often termed ‘benign’, essential tremor can in severe cases be very disabling.
Primary torsion dystonia: it is usually genetic in nature. Patients are neurologically normal apart from the dystonia (and sometimes tremor). Some, although not all, of the genes involved have been characterized. When the condition starts in childhood, it usually presents as lower limb dystonia, which gradually progresses into generalized dystonia. Adults developing dystonia usually present with focal dystonia, in particular cervical dystonia and blepharospasm. Cerebral palsy: although classically caused by neonatal jaundice, any cause of cerebral palsy can be associated with dystonia.
Other causes: there are many other causes including dystonic tremor, Holmes’ tremor (rubral or midbrain tremor) and cerebellar tremor.4
Dopa-responsive dystonia: this form is an autosomal dominant condition often presenting with childhood dystonia that can mimic dystonic cerebral palsy. Patients respond dramatically to levodopa and can go from needing a wheelchair to having normal mobility. Although it is rare, it is important not to miss this, and all patients thought to have dystonic cerebral palsy should have a trial of levodopa (e.g. co-careldopa 125 mg three times daily for 2 weeks).
Myoclonus Definition Myoclonus refers to brief jerks of the muscles. It can affect the whole body at once (generalized myoclonus) or a small area such as the fingers (focal myoclonus). Myoclonus can be positive (in which the jerks are brief contractions of the muscle) or negative (whereby the jerks are caused by brief loss of sustained muscle contraction).
Wilson’s disease: this is caused by an autosomal recessive defect in copper metabolism. It can present with hepatic disease or neurological problems, including personality change, dystonia and tremor. Most patients have a ring of copper around the cornea that can be seen on slit-lamp examination (Kayser eFleischer ring) as well as a low serum ceruloplasmin concentration and high urinary copper excretion. Early diagnosis is important to commence treatment and prevent permanent disability.
Causes A large number of conditions can cause myoclonus, and the diagnosis is usually made by recognizing the features of these conditions other than myoclonus itself. Medical causes: several medical conditions can cause myoclonus. The metabolic flap of the outstretched arms seen in respiratory, hepatic and renal failure is a form of negative myoclonus (asterixis). Drugs including opioids can also cause myoclonus.
Other causes: rarer causes of dystonia include neuroacanthocytosis and neurodegeneration with brain iron accumulation.3
Neurological causes: myoclonus can originate at any level of the central nervous system, including the cortex, subcortical regions and spinal cord. Neurological conditions causing myoclonus include several epileptic disorders, Alzheimer’s disease, cortical Lewy body disease, CreutzfeldteJacob disease and post-hypoxic myoclonus.5
Tremor Definition Tremor is a rhythmic oscillation about a body part. It can affect any part of the body, most commonly the upper limbs. The nature of the tremor gives an important clue to the diagnosis, in particular whether it is a rest tremor or a postural and action tremor. Predominantly resting tremors are usually due to Parkinson’s disease. Parkinsonian tremor can sometimes occur with a sustained posture, but there is usually a delay between the arms being outstretched and the tremor developing (this tremor is termed a postural re-emergent tremor). An action tremor rarely occurs in Parkinson’s disease.
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Tics Definition A tic is a movement performed in response to an internal urge (in the same manner that an itching sensation causes a desire to scratch). Tics can usually be suppressed for a brief period if the patient is asked to do so, but worsen when patients stop trying to suppress them. Tics can affect any part of the body, although
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Please cite this article in press as: Silverdale MA, Other movement disorders, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.06.010
MOVEMENT DISORDERS
Some drugs used to treat hyperkinetic movement disorders Drug
Starting dose
Typical maintenance dose
Comments
Tetrabenazine
12.5 mg daily
25e75 mg/day e divided into three doses
Haloperidol
500 micrograms daily
1e15 mg/day e divided into two or three doses
Baclofen Trihexyphenidyl
5 mg daily 1 mg daily
20e60 mg/day e divided into three doses 3e9 mg/day e divided into three doses
Propranolol Primidone
80 mg daily using a long-acting preparation 50 mg daily
Clonidine
50 micrograms daily
80e160 mg/day e once daily using a longacting preparation 250e500 mg/day e once daily or divided into two doses 200e400 microgram/day e divided into two doses
Sodium valproatea
300 mg daily
Can help chorea, dystonia, tics and tardive dyskinesia. Adverse effects include parkinsonism and depression Can help chorea, dystonia and tics. Can cause sedation and parkinsonism. Prolonged use can cause tardive dyskinesia Mainly used for dystonia. Can cause sedation May improve dystonia. Can make chorea worse. Adverse effects including dry eyes, dry mouth, urinary retention, sedation and cognitive problems Useful treatment for essential tremor. Contraindicated in asthmatic patients Useful treatment for essential tremor. May cause sedation Useful treatment for tics (unlicensed indication in the UK) and Tourette’s syndrome. Adverse effects include sedation and hypotension Useful treatment for myoclonus. Adverse effects include tremor. Teratogenic
a
600e2000 mg/day e divided into two doses
Use for this indication is unlicensed in the UK and not described in the BNF.
Table 3
Deep brain stimulation
eye-blinking, eyebrow-raising and shoulder movements are common. These motor tics can be confused with other movement disorders unless the patient is asked about internal urge and an attempt is made to see whether they can suppress the movements. As well as these motor tics, vocal tics such as throatclearing are common. Swearing (coprolalia) can occur but is less common.
Deep brain stimulator lead Electrodes Subthalamic nucleus
Causes Tics are very common, affecting >10% of the population in childhood and adolescence. They usually improve after adolescence, but can occasionally worsen in adulthood. Tourette’s syndrome is a severe form of tic disorder, often accompanied by obsessiveecompulsive disorder and attention-deficit hyperactivity disorder. Tic disorder can also occur in other neurological conditions including Huntington’s disease.
Connective wires
Pacemaker
Tardive dyskinesia Prolonged treatment with dopamine receptor blocking drugs can lead to involuntary movements termed tardive dyskinesia. The most commonly implicated drugs are neuroleptics, including haloperidol and chlorpromazine. The dopamineblocking anti-nausea drugs prochlorperazine and metoclopramide can also cause tardive dyskinesia. The most common manifestations of tardive dyskinesia are repetitive orolingual movements that reduce when the patient speaks or eats. Virtually any movement disorder can be tardive in nature, including dystonia, tremor and an internal restlessness termed akathisia.
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Figure 1 Deep brain stimulation is effective treatment for some movement disorders, particularly Parkinson’s disease, essential tremor and dystonia. A wire is placed in a small area of the basal ganglia. The specific target varies between different conditions and includes the subthalamic nucleus, the globus pallidus, the thalamus and the zona incerta. The wire is attached to a pacemaker box in the chest wall that passes a high-frequency current into the basal ganglia target. The settings can be manipulated using a computer, often leading to dramatic improvements in correctly selected patients.
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Please cite this article in press as: Silverdale MA, Other movement disorders, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.06.010
MOVEMENT DISORDERS
disorders are often associated with adverse effects that can be worse than the movements themselves. Many patients with hyperkinetic movement disorders prefer to avoid drug treatment. Table 3 illustrates some of the drugs used to treat these disorders. In more severe cases, deep brain stimulation is used and can be extremely effective in the correctly chosen patient (Figure 1).A
Psychogenic movement disorders Many of the above-mentioned movement disorders can have psychogenic causes, which make up at least 5% of referrals to a movement disorder clinic. Distinguishing a psychogenic movement disorder from an organic movement disorder can be difficult. It is important to look for incongruity (the movement disorder is not typical for a known movement disorder) and inconsistency (the movement disorder changes over time). Unlike organic movement disorders, most psychogenic movement disorders improve with distraction. Entrainment is common in psychogenic tremor (see Table 1).
KEY REFERENCES 1 Teive HA, Ashizawa T. Primary and secondary ataxias. Curr Opin Neurol 2015; 28: 413e22. 2 Walker RH. Differential diagnosis of chorea. Curr Neurol Neurosci Rep 2011; 11: 385e95. 3 Phukan J, Albanese A, Gasser T, Warner T. Primary dystonia and dystonia-plus syndromes: clinical characteristics, diagnosis, and pathogenesis. Lancet Neurol 2011; 10: 1074e85. 4 Alty JE, Kempster PA. A practical guide to the differential diagnosis of tremor. Postgrad Med J 2011; 87: 623e9. 5 Kojovic M, Cordivari C, Bhatia K. Myoclonic disorders: a practical approach for diagnosis and treatment. Ther Adv Neurol Disord 2011; 4: 47e62.
Treatment of other movement disorders Some forms of ataxia can be treated by addressing the underlying cause, for example giving thiamine for Wernicke’s encephalopathy or immunotherapy for autoimmune ataxia. Other than this, drug treatment of ataxias is disappointing. If there is a secondary cause of a hyperkinetic movement disorder, treatment should initially focus on this. Botulinum toxin injections are very effective in the treatment of focal dystonia and also for some focal tics. The drugs used to treat hyperkinetic movement
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Please cite this article in press as: Silverdale MA, Other movement disorders, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.06.010
Other movement disorders
Key points C
Ataxias are caused by dysfunction of the cerebellum or its connections and cause irregular disordered movement
C
The differential diagnosis of ataxia is large but the speed of onset helps in making a diagnosis
C
Hyperkinetic movement disorders are associated with excess involuntary movements that often interfere with normal movements. The type of hyperkinetic movement disorder is usually apparent after careful observation of the patient
C
In chorea, the involuntary movements are random in nature
C
In dystonia, the movements are patterned and sustained
C
In tremor, the movements are rhythmic
C
In myoclonus, the movements are very brief and irregular
C
In tics, the movements are suppressible and associated with an underlying urge sensation
Monty A Silverdale
Abstract This article examines movement disorders other than Parkinson’s disease, including ataxias and hyperkinetic movement disorders. Ataxias are caused by dysfunction of the cerebellum or its connections and cause irregular disordered movement. Hyperkinetic movement disorders involve involuntary movements that often interfere with normal movements. There are several different hyperkinetic movement disorders, which can usually be distinguished by clinical assessment: in chorea, the involuntary movements are random in nature; in dystonia, the movements are patterned; in tremor, the movements are rhythmic; in myoclonus, the movements are very brief, jerky and irregular; and in tics, the movements are suppressible and associated with an underlying urge sensation This article gives an approach to diagnosing patients with ataxic and hyperkinetic movement disorders, and discuss some of the more common and important associations. It also discusses treatment including using deep brain stimulation, which can be extremely effective in correctly selected patients.
Keywords Ataxia; chorea; dystonia; myoclonus; tardive dyskinesia; tics; Tourette’s syndrome; tremor
Speech: patients with ataxic disorders often have dysarthria. Cerebellar dysarthria can be difficult to distinguish from other forms of dysarthria. Getting the patient to say ‘Ta Ta Ta’ repetitively can help. In cerebellar dysarthria, speech can be irregular (analogous to ‘atrial fibrillation’ of speech).
Introduction Upper limbs: when testing for upper limb ataxia, the finger enose test is used. The examiner asks the patient to stretch out their arm in order to touch the examiner’s finger, then flex their arm to touch their own nose with their fingertip. The process is then repeated. The examiner is looking for poorly coordinated movements that can overshoot or undershoot the target, sometimes developing a tremor as the target is approached (intention tremor). It is important that the examiner gets the patient to straighten their arm fully as subtle ataxia may only develop as the arm extends to approach the target. A disorder of rapidly alternating movement (dysdiadochokinesia) is tested by asking the patient to alternately pronate and supinate the tapping hand.
Ataxic disorders are caused by dysfunction of the cerebellum or its connections and cause irregular disordered movement. Hyperkinetic movement disorders cause involuntary movements. Simply observing the patient allows most hyperkinetic movement disorders to be diagnosed. Much of this observation can be performed while taking the history. Table 1 illustrates some of the tricks used during examination to help reach a diagnosis of a hyperkinetic movement disorder.
Ataxia Definition The cerebellum fine-tunes and coordinates movement so patients with ataxia complain of clumsiness on attempted movement. They can also have poor balance when walking, and slurred speech.
Lower limbs: ataxia in the lower limbs is tested using the heel eshin test, in which the heel is passed up and down the shin.
Testing for ataxia Eye movements: pursuit eye movements (following a finger) are often very jerky in ataxic patients. Saccadic eye movements (looking from one target to another) often undershoot or overshoot the target. Nystagmus may be seen.
Gait: an ataxic gait is usually broad-based and unsteady. Patients usually struggle with tandem walking (where the heel of the front foot touches the toes of the back foot with each step).
Causes of ataxia There are many causes of ataxia (Table 2). It is helpful to divide cerebellar disorders into those presenting acutely (seconds, minutes or hours), those presenting subacutely (days or weeks) and those presenting over a chronic time course (months or years). Toxic causes such as alcohol are usually obvious from the
Monty A Silverdale PhD FRCP is a Consultant Neurologist and Movement Disorder Specialist at the Greater Manchester Neuroscience Centre, Manchester, UK. Competing interests: none declared.
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Ó 2016 Published by Elsevier Ltd.
Please cite this article in press as: Silverdale MA, Other movement disorders, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.06.010
MOVEMENT DISORDERS
Examining a patient with a hyperkinetic movement disorder C
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Important causes of ataxia Immediate onset Cerebellar stroke Cerebellar bleed Onset over days Wernicke’s encephalopathy Multiple sclerosis relapse Viral cerebellitis (mainly in children) Onset over weeks or months Paraneoplastic CreutzfeldteJakob disease Autoimmune (e.g. anti-Glutamic Acid Decarboxylase (GAD) antibodies) Posterior fossa tumour (months or years depending on speed of tumour growth) Onset over years Alcoholic cerebellar degeneration (can also present more quickly) Friedreich’s ataxia (autosomal recessive) Spinocerebellar ataxia (autosomal dominant, many genes) Mitochondrial disease (can also present acutely or subacutely) Multiple system atrophy (progresses over months or 1e2 years) Idiopathic late-onset ataxia Ataxia with vitamin E deficiency Non-cerebellar causes Sensory ataxia (impaired proprioception, positive Romberg’s test) Bilateral vestibulopathy, (unsteady gait, positive Romberg’s test, impaired dynamic visual acuity test)
Observe the patient at rest with their hands resting on their lap. This can be done while taking the history Distract the patient by asking them to close their eyes and recount the months of the year backwards. Most movement disorders worsen with distraction Ask the patient to hold their arms outstretched. The involuntary movements of dystonia, chorea and essential tremor usually worsen on sustained posture Ask the patient to perform actions including writing and pouring water between cups. Most hyperkinetic movement disorders, including chorea, dystonia and essential tremor, become more obvious with action Ask the patient to try and suppress the movements for 10 seconds. Tic disorder can usually be partially or completely suppressed but will become much worse afterwards Test the patient for motor impersistence by asking them to stick their tongue out for a count of 10 seconds. Patients with chorea are not usually able to do this, and the tongue will keep popping in and out of the mouth Ask the patient to walk. Many movement disorders including chorea and dystonia worsen on walking Perform a full general and neurological examination looking for other clues to the diagnosis If a psychogenic tremor is suspected, check for entrainment by getting the patient to tap a rhythm with one hand and see whether the frequency of tremor in the other hand changes to the tapping frequency
Table 2
Table 1
syndrome and polycythaemia, Sydenham’s chorea (post-streptococcal) and chorea during pregnancy (chorea gravidarum). Medications, including levodopa, the oral contraceptive pill, anticholinergic drugs, anticonvulsants and antidepressants, can cause chorea.
history. Structural problems usually show on cranial magnetic resonance imaging. The age of onset often helps to reach a diagnosis in chronic cerebellar disorders. Many genetic conditions present at a younger age, whereas other conditions such as multiple system atrophy present at an older age. Cranial imaging can help in chronic cerebellar disorders: some conditions cause cerebellar atrophy (e.g. ataxia telangiectasia) whereas others usually do not (e.g. Friedreich’s ataxia). Cerebellar disorders are discussed in more detail elsewhere.1
Huntington’s disease: this is an autosomal dominant condition caused by an expanded trinucleotide repeat in the huntingtin gene on chromosome 4. It causes psychiatric problems (depression, personality change), cognitive problems and a movement disorder (usually chorea but sometimes dystonia or parkinsonism).
Chorea Other causes: these include benign hereditary chorea, senile chorea and various Huntington’s mimics.2
Definition Chorea denotes involuntary movements that are completely random in nature. In most cases, the whole body is affected. A patient with chorea can initially appear simply fidgety, and it is sometimes difficult to distinguish an anxious, restless person from someone with chorea. A fidgety patient is usually able to suppress the movements when concentrating on something such as writing, whereas chorea usually worsens on action, and writing can be difficult. Testing for motor impersistence often helps (Table 1).
Dystonia Definition In dystonia, sustained muscle contractions lead to twisting movements and abnormal postures. Whereas chorea causes random movements, dystonia causes patterned movements e meaning that the same movement is performed over and over again. For example, if the head turns to the left, it repeatedly turns to the left. Dystonia is focal when only one body part is affected, for example the neck (cervical dystonia), the eyes (blepharospasm) or the limbs. It can also be generalized, meaning that the whole body is affected.
Causes Medical causes: these include non-ketotic hyperglycaemia, hyperthyroidism, systemic lupus erythematosus, anticardiolipin
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Please cite this article in press as: Silverdale MA, Other movement disorders, Medicine (2016), http://dx.doi.org/10.1016/j.mpmed.2016.06.010
MOVEMENT DISORDERS
Types Task-specific dystonia: this occurs only with certain activity, such as writing (writer’s cramp). In this case, the patient finds their fingers or arm adopt an unusual posture when they try to write, making writing difficult. This condition is particularly common in people who do a lot of writing. Other high-intensity activities can also be associated with task-specific dystonia, including playing a musical instrument (e.g. piano, violin) and certain sports (e.g. the ‘yips’ in golf).
Causes Medical causes: we all have a high-frequency physiological tremor that becomes more apparent with stress. Hyperthyroidism and drugs (including b-adrenoceptor agonists, lithium and sodium valproate) can cause or worsen tremor, and careful attention should be paid to the drug history. Essential tremor: this causes a postural and action tremor of slightly lower frequency than physiological tremor. Unlike a Parkinsonian re-emergent tremor, essential tremor occurs immediately on sustained posture. The tremor worsens on action (which is unusual for parkinsonian tremor). A typical patient with a parkinsonian tremor might complain that their tremor was worst when watching television, whereas patients with essential tremor typically complain about difficulty holding a cup of tea. Essential tremor is usually familial, although the causative gene is unknown. Although often termed ‘benign’, essential tremor can in severe cases be very disabling.
Primary torsion dystonia: it is usually genetic in nature. Patients are neurologically normal apart from the dystonia (and sometimes tremor). Some, although not all, of the genes involved have been characterized. When the condition starts in childhood, it usually presents as lower limb dystonia, which gradually progresses into generalized dystonia. Adults developing dystonia usually present with focal dystonia, in particular cervical dystonia and blepharospasm. Cerebral palsy: although classically caused by neonatal jaundice, any cause of cerebral palsy can be associated with dystonia.
Other causes: there are many other causes including dystonic tremor, Holmes’ tremor (rubral or midbrain tremor) and cerebellar tremor.4
Dopa-responsive dystonia: this form is an autosomal dominant condition often presenting with childhood dystonia that can mimic dystonic cerebral palsy. Patients respond dramatically to levodopa and can go from needing a wheelchair to having normal mobility. Although it is rare, it is important not to miss this, and all patients thought to have dystonic cerebral palsy should have a trial of levodopa (e.g. co-careldopa 125 mg three times daily for 2 weeks).
Myoclonus Definition Myoclonus refers to brief jerks of the muscles. It can affect the whole body at once (generalized myoclonus) or a small area such as the fingers (focal myoclonus). Myoclonus can be positive (in which the jerks are brief contractions of the muscle) or negative (whereby the jerks are caused by brief loss of sustained muscle contraction).
Wilson’s disease: this is caused by an autosomal recessive defect in copper metabolism. It can present with hepatic disease or neurological problems, including personality change, dystonia and tremor. Most patients have a ring of copper around the cornea that can be seen on slit-lamp examination (Kayser eFleischer ring) as well as a low serum ceruloplasmin concentration and high urinary copper excretion. Early diagnosis is important to commence treatment and prevent permanent disability.
Causes A large number of conditions can cause myoclonus, and the diagnosis is usually made by recognizing the features of these conditions other than myoclonus itself. Medical causes: several medical conditions can cause myoclonus. The metabolic flap of the outstretched arms seen in respiratory, hepatic and renal failure is a form of negative myoclonus (asterixis). Drugs including opioids can also cause myoclonus.
Other causes: rarer causes of dystonia include neuroacanthocytosis and neurodegeneration with brain iron accumulation.3
Neurological causes: myoclonus can originate at any level of the central nervous system, including the cortex, subcortical regions and spinal cord. Neurological conditions causing myoclonus include several epileptic disorders, Alzheimer’s disease, cortical Lewy body disease, CreutzfeldteJacob disease and post-hypoxic myoclonus.5
Tremor Definition Tremor is a rhythmic oscillation about a body part. It can affect any part of the body, most commonly the upper limbs. The nature of the tremor gives an important clue to the diagnosis, in particular whether it is a rest tremor or a postural and action tremor. Predominantly resting tremors are usually due to Parkinson’s disease. Parkinsonian tremor can sometimes occur with a sustained posture, but there is usually a delay between the arms being outstretched and the tremor developing (this tremor is termed a postural re-emergent tremor). An action tremor rarely occurs in Parkinson’s disease.
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Tics Definition A tic is a movement performed in response to an internal urge (in the same manner that an itching sensation causes a desire to scratch). Tics can usually be suppressed for a brief period if the patient is asked to do so, but worsen when patients stop trying to suppress them. Tics can affect any part of the body, although
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MOVEMENT DISORDERS
Some drugs used to treat hyperkinetic movement disorders Drug
Starting dose
Typical maintenance dose
Comments
Tetrabenazine
12.5 mg daily
25e75 mg/day e divided into three doses
Haloperidol
500 micrograms daily
1e15 mg/day e divided into two or three doses
Baclofen Trihexyphenidyl
5 mg daily 1 mg daily
20e60 mg/day e divided into three doses 3e9 mg/day e divided into three doses
Propranolol Primidone
80 mg daily using a long-acting preparation 50 mg daily
Clonidine
50 micrograms daily
80e160 mg/day e once daily using a longacting preparation 250e500 mg/day e once daily or divided into two doses 200e400 microgram/day e divided into two doses
Sodium valproatea
300 mg daily
Can help chorea, dystonia, tics and tardive dyskinesia. Adverse effects include parkinsonism and depression Can help chorea, dystonia and tics. Can cause sedation and parkinsonism. Prolonged use can cause tardive dyskinesia Mainly used for dystonia. Can cause sedation May improve dystonia. Can make chorea worse. Adverse effects including dry eyes, dry mouth, urinary retention, sedation and cognitive problems Useful treatment for essential tremor. Contraindicated in asthmatic patients Useful treatment for essential tremor. May cause sedation Useful treatment for tics (unlicensed indication in the UK) and Tourette’s syndrome. Adverse effects include sedation and hypotension Useful treatment for myoclonus. Adverse effects include tremor. Teratogenic
a
600e2000 mg/day e divided into two doses
Use for this indication is unlicensed in the UK and not described in the BNF.
Table 3
Deep brain stimulation
eye-blinking, eyebrow-raising and shoulder movements are common. These motor tics can be confused with other movement disorders unless the patient is asked about internal urge and an attempt is made to see whether they can suppress the movements. As well as these motor tics, vocal tics such as throatclearing are common. Swearing (coprolalia) can occur but is less common.
Deep brain stimulator lead Electrodes Subthalamic nucleus
Causes Tics are very common, affecting >10% of the population in childhood and adolescence. They usually improve after adolescence, but can occasionally worsen in adulthood. Tourette’s syndrome is a severe form of tic disorder, often accompanied by obsessiveecompulsive disorder and attention-deficit hyperactivity disorder. Tic disorder can also occur in other neurological conditions including Huntington’s disease.
Connective wires
Pacemaker
Tardive dyskinesia Prolonged treatment with dopamine receptor blocking drugs can lead to involuntary movements termed tardive dyskinesia. The most commonly implicated drugs are neuroleptics, including haloperidol and chlorpromazine. The dopamineblocking anti-nausea drugs prochlorperazine and metoclopramide can also cause tardive dyskinesia. The most common manifestations of tardive dyskinesia are repetitive orolingual movements that reduce when the patient speaks or eats. Virtually any movement disorder can be tardive in nature, including dystonia, tremor and an internal restlessness termed akathisia.
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Figure 1 Deep brain stimulation is effective treatment for some movement disorders, particularly Parkinson’s disease, essential tremor and dystonia. A wire is placed in a small area of the basal ganglia. The specific target varies between different conditions and includes the subthalamic nucleus, the globus pallidus, the thalamus and the zona incerta. The wire is attached to a pacemaker box in the chest wall that passes a high-frequency current into the basal ganglia target. The settings can be manipulated using a computer, often leading to dramatic improvements in correctly selected patients.
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MOVEMENT DISORDERS
disorders are often associated with adverse effects that can be worse than the movements themselves. Many patients with hyperkinetic movement disorders prefer to avoid drug treatment. Table 3 illustrates some of the drugs used to treat these disorders. In more severe cases, deep brain stimulation is used and can be extremely effective in the correctly chosen patient (Figure 1).A
Psychogenic movement disorders Many of the above-mentioned movement disorders can have psychogenic causes, which make up at least 5% of referrals to a movement disorder clinic. Distinguishing a psychogenic movement disorder from an organic movement disorder can be difficult. It is important to look for incongruity (the movement disorder is not typical for a known movement disorder) and inconsistency (the movement disorder changes over time). Unlike organic movement disorders, most psychogenic movement disorders improve with distraction. Entrainment is common in psychogenic tremor (see Table 1).
KEY REFERENCES 1 Teive HA, Ashizawa T. Primary and secondary ataxias. Curr Opin Neurol 2015; 28: 413e22. 2 Walker RH. Differential diagnosis of chorea. Curr Neurol Neurosci Rep 2011; 11: 385e95. 3 Phukan J, Albanese A, Gasser T, Warner T. Primary dystonia and dystonia-plus syndromes: clinical characteristics, diagnosis, and pathogenesis. Lancet Neurol 2011; 10: 1074e85. 4 Alty JE, Kempster PA. A practical guide to the differential diagnosis of tremor. Postgrad Med J 2011; 87: 623e9. 5 Kojovic M, Cordivari C, Bhatia K. Myoclonic disorders: a practical approach for diagnosis and treatment. Ther Adv Neurol Disord 2011; 4: 47e62.
Treatment of other movement disorders Some forms of ataxia can be treated by addressing the underlying cause, for example giving thiamine for Wernicke’s encephalopathy or immunotherapy for autoimmune ataxia. Other than this, drug treatment of ataxias is disappointing. If there is a secondary cause of a hyperkinetic movement disorder, treatment should initially focus on this. Botulinum toxin injections are very effective in the treatment of focal dystonia and also for some focal tics. The drugs used to treat hyperkinetic movement
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