The Patient with Ataxia Saf FG Maggs

42 Acute Medicine 2014; 13(1): 42-47

Problem-Based Review

42 The Patient with Ataxia saf FG Maggs

Abstract In this article we look at the causes of ataxia, and how the patient presenting with ataxia should be managed. One of the difficulties in managing the patient with ataxia is that acute ataxia has many causes, but usually these can be teased out by means of a careful history and examination. Investigations can then be targeted at confirming or disproving the differential diagnosis. Some patients with ataxia need to be managed in hospital, but many can be investigated, and receive therapy, as an outpatient. Keywords Ataxia, Unsteadiness, Coordination, Cerebellum

Key points • In the patient presenting with acute ataxia consider cerebellar infarcts, acute intoxication, Miller-Fisher syndrome and Wernicke-Korsakoff syndrome: these diagnoses must not be missed and require urgent management • An MRI scan of the brain is the preferred imaging modality for the cerebellum • Many patients with acute ataxia will need to be admitted, especially if there is a need for ongoing monitoring, or a risk of falls that means the patient would be unsafe at home. However, if an MRI head is normal, and the patient is well, then further investigations could be carried out as an outpatient

What is ataxia? (e.g. anticonvulsants). In adults, the most frequent The word ataxia comes from Greek meaning a “lack causes are ischaemic or haemorrhagic strokes in of order”. Ataxia is the manifestation of dysfunction the cerebellum or brain stem, intoxication (such as of the parts of the nervous system that coordinate therapeutic drugs, alcohol, and drugs of abuse), and movement, and is characterised by clumsy and Wernicke-Korsakoff syndrome due to nutritional uncoordinated intentional movement of the limbs, deprivation (usually, but not always, in alcoholic trunk, and cranial muscles. people). Demyelinating lesions such as multiple Ataxia may result from pathology in the sclerosis can also have a rapid onset and, if they cerebellum (cerebellar ataxia), may be due to loss occur in the cerebellum or its connections, present of proprioception as a result of dysfunction of the with acute ataxia. The Miller-Fisher variant form of dorsal columns of the spinal cord (sensory ataxia), Guillain-Barre syndrome should to be considered in or may be due to vestibular dysfunction (vestibular patients presenting with acute ataxia. ataxia). The three types of ataxia have overlapping causes, and therefore can either coexist or occur in Case scenario isolation. A 66 year old retired teacher was referred to the medical take complaining of leg weakness, general malaise and lethargy. What are the causes of ataxia? He described feeling as if his legs could not hold him, and Inherited ataxias may be classified by their mode had to hold onto things to steady himself, but his legs were Fenella G Maggs of inheritance. For example, Wilson’s disease1 not painful, and he did not complain of any numbness or DPhil, MRCP is a recessive gene disorder which results in an sensory loss. Four weeks previously he had been able to play Consultant in Acute inability to properly excrete copper from the body: golf but was now mobile only with two sticks. He described Medicine, Royal United Hospital, Bath accumulation of copper in the nervous system can some weight loss. cause ataxia. Degenerative ataxia is a term used to His past medical history included hypertension, Correspondence: denote ataxia due to cerebellar atrophy of both hypercholesterolaemia and peripheral vascular disease, but F G Maggs genetic and unknown causation. he lived an active and independent life. He was taking Royal United Hospital, The list of acquired causes of ataxia is extensive simvastatin, bendroflumethiazide, felodipine, enalapril Combe Park, Bath. BA1 3NG (Box 1). Age at onset is an important determinant of and aspirin. He was a current smoker, smoking 15 – 20 Email: fgmaggs@doctors. cause. Ataxia of acute onset in a child is most likely to cigarettes per day for 53 years, and drank up to 40 units of net.uk result from acute cerebellitis or may be drug-induced alcohol per week.

The Patient with Ataxia

Box 1. Causes of acquired ataxia

Examples Notes Focal lesions Stroke, tumour, multiple sclerosis Cause the type of ataxia corresponding to the site of the lesion Exogenous substances Alcohol, lithium,2 antiepileptic drugs,3 Lithium level over 1.5mEq/L metronidazole,4 benzodiazepines,5 amiodarone,6 recreational drugs,7 Exposure to high levels of methylmercury solvent poisoning,8 methylmercury9 through consumption of fish with high mercury concentrations Radiation poisoning Acute radiation poisoning with an absorbed dose of more than 30 Grays10 Degenerative causes Alcohol, paraneoplasia, normal Paraneoplastic syndromes: ataxia may appear pressure hydrocephalus, high altitude months or years before the cancer is diagnosed. cerebral oedema, Coeliac disease,11 cerebellitis Cerebellitis usually seen in children Nutritional Vitamin B12 deficiency12 Cerebellar and sensory ataxia

Vitamin B1 deficiency 13 Often part of Wernicke-Korsakoff syndrome in alcoholic people and other patients who have severe nutritional deficiency

Severe vitamin E deficiency14 Occurs in fat malabsorption Infections Chicken pox15 Ataxia may appear in the healing stages of the infection and last for days or weeks. Normally, the ataxia resolves completely over time.

Cerebellar abscess Rapid onset of ataxia with headache; can be a complication of middle ear infections

HIV infection16 Progressive ataxia that becomes debilitating over several months; many cases of HIV dementia may exhibit ataxia at onset Prion protein disease can have a predominantly ataxic presentation17 Endocrine Hypothyroidism18 Reversible cerebellar ataxia, dementia, peripheral neuropathy, psychosis and coma. Most of the neurological complications improve completely Hyponatraemia19 after thyroid hormone replacement therapy. Peripheral neuropathy Isolated sensory ataxia

On examination he appeared well. He was afebrile, with between light-headedness and vertigo, which are blood pressure 130/65, pulse 72 bpm, respiratory rate 21/ often lumped together as a feeling of ‘dizziness’. A min, and oxygen saturations 98% on air. Cardiovascular, history of vertigo, tinnitus, and hearing problems respiratory and abdominal examinations were unremarkable. may indicate a peripheral vestibular problem, Neurological examination revealed proximal muscle wasting while the presence of speech disturbance and visual but no other abnormal neurology. His gait was ataxic but symptoms suggests cerebellar pathology. Explore there were no other cerebellar signs. symptoms that may indicate increased intracranial pressure (e.g. headache, nausea, vomiting) or What are the vital clues from the problems in structures contiguous to the cerebellum history? (e.g. weakness or sensory problems in the limbs or cranial nerve deficits). Presenting complaint The duration of symptoms may give clues as to Precise questions may need to be asked to be sure the underlying cause: strokes usually present with a what the patient is experiencing. Patients will be short history while a degenerative cause may have a likely to describe ataxia as unsteadiness, a lack of prolonged history. In slow-onset, chronic bilateral balance or giddiness. It is important to distinguish cases of vestibular dysfunction, dysequilibrium may

The Patient with Ataxia

be the sole presentation, while acute labyrinthitis differentiate cerebellar ataxia from other types of is usually unilateral and associated with prominent incoordination. vertigo, nausea and vomiting. Co-ordination Systemic enquiry / Past medical history • There is uncontrolled tremor of limbs during Evaluate risk factors for cerebrovascular disease such relatively slow but targeted movements as hypertension and hypercholesterolaemia. Ask • There may also be tremor of the head and about falls: many patients with ataxia may be able trunk (titubation)22 to investigated and managed as outpatients, but a • Inspect for limb dysmetria (lack of coordination history of falls may preclude this. Studies examining typified by the undershoot or overshoot falls in patients with ataxia show that 74-93% of of intended position) by testing finger- patients have fallen at least once in the past year and to-nose, and heel-to-shin, movements,22 up to 60% admit to fear of falling.20,21 Ask about dysdiadokokinesia, and heel-tapping symptoms of hypothyroidism. Determine whether • Check for overshooting with the wrist-tapping there has been any weight loss which may suggest an test, in which the patient is unable to maintain underlying malignancy. postures against an unexpected displacement Speech Drug history • Evaluate the speech for dysarthria and scanning Several prescription drugs can cause ataxia. Most speech. In scanning speech, the volume of the antiepileptic drugs have cerebellar ataxia as a possible patient’s voice varies from low to high22 adverse effect,3 high lithium levels can lead to ataxia,2 • There may also be slurring of speech and and, in high doses, benzodiazepines can cause short tremor of the voice term ataxia.3 Ask about cannabis ingestion and other Eye movements recreational drugs.7 • Examine eye movements for nystagmus, jerkiness on attempted smooth pursuit, and Social history slowed saccades. Oculomotor palsy can be Alcohol causes reversible cerebellar and vestibular associated with some disorders ataxia via a depressant effect on central nervous • Primary position nystagmus and lateralised past system function. A history of smoking may point pointing may suggest an acute vestibulopathy, towards lung cancer, which may cause ataxia via but distinction between vestibulopathy and a cerebellar metastases or paraneoplastic phenomena. small brain stem infarct can be difficult It is crucial to establish whether the patient drives, Gait particularly if they are being managed in an outpatient • Evaluate the gait by checking for broad-based or ambulatory setting. stance and staggering or lurching gait22 • Test heel-to-toe walking (tandem gait) Family history • Dysfunction of the vestibulocerebellum causes Is there any family history of ataxia? Although postural instability, in which the person tends most patients will know if spinocerebellar ataxia or to separate his feet upon standing, in order to Freidrich’s ataxia runs in their family, this may be the gain a wider base and to avoid titubation. The first presentation of an autosomal recessive disorder, instability is therefore worsened when standing and both Wilson’s disease and Freidrich’s ataxia may with the feet together, regardless of whether present as late as 30 years of age. the eyes are open or closed. Thus the patient is unable to carry out Romberg’s test, because the What examination should be individual feels unstable even with open eyes. performed? • Dysfunction of the spinocerebellum presents A full cardiovascular, respiratory and abdominal with a wide-based “drunken sailor” gait examination may suggest clues as to the cause of (truncal ataxia) the ataxia. Examination should include a careful assessment for signs of alcohol abuse and liver Sensory ataxia is characterised by limb cirrhosis, malignancy or hypothyroidism. incoordination associated with lack of proprioception. A thorough neurological examination should be Clinical signs include impaired vibration and performed. position sense. Patients present with an unsteady “stomping” gait with heavy heel strikes, as well as a Cerebellar ataxia produces a characteristic set postural instability that is usually worsened when the of signs.22 The presence of speech and oculomotor lack of proprioceptive input cannot be compensated signs related to cerebellar pathology can clearly for by visual input (a positive Romberg’s test). Eye

The Patient with Ataxia

movements and speech are not affected, unless Imaging sensory and cerebellar features co-exist. A chest X-ray should be performed to exclude a lung malignancy. MRI scanning of the brain is the With vestibular ataxia the discoordination in preferred imaging modality for the cerebellum:23 the limbs is in the nature of “past pointing” rather this will show infarcts, haemorrhages, tumours and than true dysmetria, and eye movement problems evidence of demyelination in patients with multiple are often confined to nystagmus in the primary sclerosis. Spinal imaging may be necessary if the position. A direction-changing nystagmus may history and examination suggest a spinal ataxia. indicate a brain stem infarct, rather than a vestibular lesion. Hearing loss and tinnitus are associated with Further tests lesions in the eighth cranial nerve or the vestibular Paraneoplastic antibodies may be helpful in some apparatus. Dysarthria is not a feature of vestibular cases, particularly if other investigations are normal. disease, but nausea and oscillopsia (objects in the If findings compatible with multiple sclerosis or visual field appear to oscillate) may be seen. cerebellitis are found, cerebrospinal fluid examination should be performed. Electrophysiological Gait problems examination of the neuromuscular system may Many types of gait problem can resemble ataxia. be helpful in patients with suspected Miller Fisher Examples include gait abnormalities from bilateral syndrome; CSF examination may reveal high protein frontal lobe lesions (frontal ataxia or Brun ataxia) and levels. GQ1b antibodies are also commonly elevated occasionally dystonic gait. Gait disorders from muscle in Miller-Fisher syndrome. disease, neuropathies, and spinal cord problems can usually be differentiated by clinical examination. Case Continued Thoracic CT demonstrated advanced pulmonary fibrosis and Case Continued a right lung tumour with hilar and right upper lobe nodules. Blood tests showed a normal full blood count and normal CT scanning staged the disease as a T3, N3, M1b. He biochemistry apart from a sodium of 127 mmol/L. Plasma proceeded to a CT guided biopsy, and immunohistochemisty viscosity was slightly raised at 1.87 mPa.s, but a CRP was revealed small cell lung cancer. “Paraneoplastic antibodies normal. Liver function tests, haematinics and TSH were all were detected, suggesting that the ataxia was due to a normal. Corrected calcium was 2.61mmol/L. paraneoplastic syndrome”. A chest X-ray showed increased lung markings of a granular appearance, while a MRI head scan showed age- How should the patient with ataxia be related changes only. An echocardiogram demonstrated managed following referral to the AMU? normal systolic function and no valvular lesions. Some important management considerations for While he was admitted and undergoing investigations he patients on the AMU are highlighted in Box 2. Many began to feel better, with the lethargy resolving. However, he patients with acute ataxia will need to be admitted, continued to be unsteady on his feet, with the physiotherapists especially if there is a need for ongoing monitoring, documenting occasional scissoring and a high-stepping gait. or a risk of falls that means the patient would be He was keen to go home, so was discharged four days after unsafe at home. However, if an MRI head is normal, admission with ongoing physiotherapy at home. He was and the patient is well, then further investigations investigated further with an outpatient CT chest, and can often be carried out as an outpatient or in an paraneoplastic antibodies. ambulatory care setting. Treatment depends on the cause, and wherever What investigations should be possible the underlying cause should be addressed, performed? e.g. by discontinuing a causative drug, replacing vitamin deficiencies or abstention from alcohol. Blood tests Spontaneous resolution may occur in cases caused by These should include thyroid function tests and viral infection or demyelination. Recovery tends to vitamin B12 levels. In young patients in whom be better in individuals with a single focal injury (such Wilson’s Disease is suspected send liver function tests as stroke or a benign tumour), compared to those and caeruloplasmin. Check a drug level in patients who have a neurological degenerative condition.24 In taking lithium, phenytoin or carbamazepine. It may patients with paraneoplastic ataxia, treatment of the be necessary to screen for drugs of abuse and measure underlying cancer may halt any further neurological alcohol levels if the history is unclear, but Wernicke- deterioration, but any neurological dysfunction Korsakoff syndrome is diagnosed primarily on a already present is likely to be irreversible. clinical basis and by a rapid response to vitamin B1 Although several drug treatments that have been and other nutritional replacement. used to attempt to control degenerative ataxias (e.g.

The Patient with Ataxia

Box 2. Important considerations for patients presenting 5-hydroxytryptophan) there is little or no evidence to the AMU to support their use25 and currently physiotherapy represents the mainstay of treatment. Physiotherapy is Cerebellar strokes often highly individualized and gait and coordination Ischaemic and haemorrhagic cerebellar strokes training are large components of therapy. A recent can result in increased intracranial pressure in the systematic review suggested that physical therapy posterior fossa which may be life-threatening and may is effective, but there is only moderate evidence to need urgent decompression. Patients may develop support this conclusion.26 Occupational therapy additional and sometimes life-threatening problems related to extension of the stroke. Recognition of these uses strategies to manage difficulties with everyday complications with judicious monitoring is important activities, by using adaptive devices such as sticks or and patients should be admitted to acute stroke units. walkers for walking, modified utensils for eating and Miller-Fisher syndrome communication aids for speaking. Speech therapy aims to improve speech and aid swallowing. Consider this variant form of Guillain-Barre syndrome if there is ataxia, oculomotor palsy, and areflexia, with Drivers who have ataxia need to be told that they or without additional weakness in the limbs, bulbar must inform the DVLA. The DVLA’s ‘Guide to the muscles, and trunk. Miller-Fisher syndrome can rapidly current medical standards of fitness to drive’ states evolve to affect the muscles of swallowing, as well that for those who suffer with ‘liability to sudden as respiratory and limb muscles. These patients need attacks of unprovoked or unprecipitated disabling monitoring of their respiratory function and may giddiness’ should ‘cease driving on diagnosis’.26 The require critical care support. Guillain-Barre syndrome website gov.uk states ‘You must tell DVLA if you is also associated with autonomic dysfunction such as arrhythmias, and warrants cardiac telemetry. have ataxia’. Driving is permitted when satisfactory control of symptoms is achieved. Wernicke-Korsakoff syndrome Patients who have ongoing ataxia may suffer from This is usually seen in patients with alcohol a loss of independence and may develop depression dependency and associated nutritional deficiency, and anxiety. There are several support groups for although other causes of nutritional deprivation may patients with ataxia or for patients with an underlying also be implicated. Patients have rapid onset of a confusional state with an amnesia (problem forming condition, such as cancer or multiple sclerosis. new memories, often associated with confabulation), nystagmus, oculomotor palsies, and ataxia. This needs Case Outcome to be recognised urgently and treated with high-dose He was referred to oncology, and underwent palliative parenteral vitamin B1 in addition to general nutritional chemotherapy with carboplatin and etoposide. After the support. first two cycles of chemotherapy his walking improved and Acute intoxication he described improved hand dexterity. However, by the Many cerebellotoxic drugs can cause acute ataxia, fourth cycle of chemotherapy his condition deteriorated with as can alcohol inebriation. Careful drug history and significant weight loss and tiredness, and he was managed serum drug levels (if appropriate) are diagnostic, symptomatically with support from the palliative care team. and management usually involves discontinuing the offending drug. Conflict of Interest The authors have no conflict of interest to declare.

The Patient with Ataxia

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