Medical Guidelines Diagnosis Investigations Adults Details of appropriate investigations for adults are found in Table 3. Primary care investigations to be done by the GP comprise those that are relatively inexpensive, common and widely available. Their purpose is to exclude medical and neurological conditions that may contribute to ataxia. Secondary care investigations are generally done by a neurologist, with referral and input from other specialists as appropriate. It is important to consider genetic tests for common inherited ataxias, particularly if there is a family history. In certain cases the potential diagnosis may be apparent following the first clinical consultation and therefore a ‘third line’ genetic test, for example, may be undertaken immediately. See also section Genetics for genetic tests. Table 3: Diagnostic investigations in adults Primary care U&Es Creatinine FBC ESR/CRP Liver enzymes γ-GT TFT Vitamin B12 Folate Random blood sugar CXR Secondary care (first line) α –FP Blood film Caerulopasmin/copper Coeliac screena Creatine kinase Genetic tests for FA, SCA1, 2, 3, 6, 7 (12, 17) Lactate Lipid-adjusted Vitamin E and lipoproteins electrophoresis Lumbar puncture (cells, protein, glucose*, cytology, oligoclonal bands*, Lactate, Ferritin) MRI brain and cervical spine Anti-Hu/Yo and other paraneoplastic antibodies† Anti-GAD Anti-VGCC† CT (chest, abdomen, pelvis) 14-3-3 and other proteins in CSF (prion diseases)† b Secondary care (second line) Cholestanol Coenzyme Q10 (ubiquinone)c Electroencephalography Long chain fatty acids Muscle biopsy Ophthalmology tests Peripheral nerve conduction studies Phytanic acid Remaining genetic tests Total body PET scan White cell enzymes *With blood† In patients with rapid progression All the diagnostic tests in Table 3 should be readily available in primary or secondary care.Tests marked a-c are only available in certain laboratories: If testing for gluten ataxia is not readily available clinicians can contact Professor Marios Hadjivassiliou who runs a specialised gluten ataxia clinic. Contact details: Sheffield Teaching Hospitals NHS Foundation Trust, Sheffield S10 2JF. Tel: 0114 271 2502.Also see section Treatable ataxias on gluten ataxia. Testing for 14-3-3 protein in the CSF can be carried out at the National Creutzfeldt-Jakob Disease Research & Surveillance Unit, Western General Hospital, Edinburgh. Contact details: Main office telephone: 0131 537 1980/2128/3103; website: www.cjd.ed.ac.uk. Coenzyme Q10 (CoQ10) levels to test for ataxia with CoQ10 deficiency. Testing of CoQ10 deficiency can be performed on skeletal muscle samples or on blood mononuclear cells23. Testing is available at the Neurometabolic Unit, National Hospital for Neurology and Neurosurgery, London. Contact Dr Iain Hargreaves or Prof Simon Heales: [email protected] or [email protected] Tel: 0203 44 83844. Children If a child presents with ataxic symptoms, an urgent referral to local paediatric services is necessary. Targeted investigations will then depend on the clinical assessment. This includes obtaining details such as family history, whether the ataxia is acute, intermittent or chronic, any precipitants and associated conditions. It is important to consider examination findings, especially those distinguishing central from sensory ataxia. See Table 4 for differential diagnoses of ataxia that guide the choice of appropriate diagnostic tests. The investigation of acquired ataxia in children is generally more urgent because of the necessity of excluding posterior fossa and brainstem tumours. It is also important to consider that there is a need for investigation in children as there is a risk that the cause will be genetic, and their parents may wish to have further children. Table 4: Differential diagnoses of ataxia to guide diagnostic investigations in children Acute Intermittent Chronic Inflammatory Intoxication Metabolic Vascular Trauma Raised intra-cranial pressure Epileptic Sensory Vertigo Psychogenic Episodic ataxias Glut1 deficiency Metabolic Epileptic Structural Psychogenic Hereditary ataxias Space occupying lesion Structural Leukodystrophies Lysosomal storage Metabolic Vitamin deficiencies Auto-immune Sensory Psychogenic Table 5 is not exhaustive but covers diagnostic investigations in children for most conditions. These investigations are generally carried out in tertiary care. Local paediatric services should only investigate in the light of clinical judgment and in consultation with the local tertiary paediatric neurology service. Urgent referral to tertiary paediatric neurology services is almost always necessary to complete investigations and for advice about management. In first line investigation neuroimaging is mandatory, to exclude a tumour and to look for a white matter disorder or structural condition. MR imaging of the brain (+/- spine) is the best way to view the posterior fossa24, but if urgent MR imaging is not available, a CT scan will help to exclude a tumour. If possible MR spectroscopy should be obtained as well. In acute ataxia MR angiography might be indicated. For further information on the availability of diagnostic tests see Adults section above and section Genetics. Table 5: Diagnostic investigations in children within tertiary care First line MRI brain (+/- spine) including 3DT1 MPRAGE, T2w in all planes, coronal FLAIR (except neonates) and DTI CT scan (if magnetic resonance imaging [MRI] is unavailable) MR spectroscopy (if possible) MR angiography (in acute ataxia) Second line (acute) Acute central ataxia without encephalopathy Blood: serology (viral, mycoplasma) Viral cultures (throat swab, urine, stool) EEG Acute central ataxia with encephalopathy Blood: serology (viral, mycoplasma); culture; toxicology including heavy metals; metabolic (liver function tests, ammonia, amino acids, blood gas, lactate, pyruvate, glucose, biotinidase); antithyroid antibodies. Urine: viral culture; toxicology; amino acids; organic acids. CSF: pressure; cell count, glucose, protein; viral and bacterial studies (culture including TB, serology, PCR); oligoclonal bands; lactate and pyruvate. Throat swab, and faeces (or rectal swab): viral and bacterial culture Mantoux test EEG Sensory ataxia Nerve conduction studies and electromyography Cerebrospinal fluid protein Blood: anti-GM1 and anti GQ1b antibodies; Viral cultures (throat swab, urine, stool) Viral and mycoplasma serology Stool culture or rectal swab (esp. C. jejuni) Opsoclonus myoclonus: Neuroblastoma (consult oncologist): Chest Xray Ultrasound scan of neck, abdomen and pelvis I123 metaiodobenzylguanidine (MIBG) scintigraphy scan Urine catecholamine metabolites–if negative do MR imaging of neck, chest and abdomen Second line (intermittent) All ataxias Blood: DNA for episodic ataxias, Glut 1 deficiency and metabolic disorders; lactate, amino-acids Urine: organic acids CSF: fasting glucose and lactate, both with simultaneous blood values EEG Second line (chronic) Depending on clinical features Suspected Friedreich’s ataxia: DNA for FXN gene EMG and nerve conduction studies (NCV) Echocardiography Fasting glucose Exclude vitamin E and vitamin B12 deficiencies (lipid corrected vitamin E level, vitamin B12 level, plasma homocysteine, urine methylmalonic acid) Suspected Ataxia-telangiectasia: Plasma α-fetoprotein level Immunoglobulin levels DNA for ATM gene Other conditions Blood: Full blood count with vacuolated lymphocytes (light and electron microscopy); lipid adjusted vitamin E, vitamin B12, biotinidase, white cell CoQ10, α-fetoprotein, immunoglobulins, copper, caeruloplasmin, phytanic acid, cholestanol, lipid electrophoresis, cholesterol, thyroid function, acyl-carnitines, white cell lysosomal enzymes, very long chain fatty acids, transferrin IEF, red cell purine nucleotide species, thyroid and antigliadin antibodies. Micro-array testing (or karyotype, FISH 22q and Angelman deletions); chromosomal radiation fragility; DNA (for specific tests and to store). Urine: organic acids, purine and pyrimidines. CSF: fasting glucose, lactate and amino-acids, with simultaneous blood values ECG Echocardiogram Electromyography and nerve conduction studies Tissue biopsies; muscle CoQ10 level This information is taken from Management of the ataxias - towards best clinical practice third edition, July 2016. This document aims to provide recommendations for healthcare professionals on the diagnosis and management of people with progressive ataxia. To view the full document, including references, click here.