Overview of the genetic and non-genetic causes of cerebellar ataxia, with clinical clues from history or examination, and suggestions for initial investigations
| Cause | Clinical clues | Suggestions for investigation |
|---|---|---|
| Genetic ataxias | ||
| Dominant | ||
| Autosomal dominant cerebellar ataxias | Family history, slowly progressive ataxia, some genotype-specific features (online supplementary table S1) | Mutation analysis of SCA genes |
| Dentato-rubro-pallidoluysian atrophy | Dementia, chorea, myoclonus, mainly in the Japanese | Mutation analysis of ATN1 gene |
| Alexander disease | (Pseudo)bulbar signs, spasticity, hyperreflexia | Mutation analysis of GFAP gene |
| Recessive | ||
| Autosomal recessive cerebellar ataxias | Family history, systemic features, often neuropathy (see also online supplementary table S2) | Mutation analysis of relevant recessive genes, lysosomal enzymes, α-fetoprotein, metabolic investigation |
| Other | ||
| ‘Mitochondrial’ disorders | Family history (diabetes mellitus, deafness), multisystem involvement | Mutation analysis of polymerase γ and mitochondrial DNA |
| Muscle biopsy | ||
| Fragile X-associated tremor/ataxia syndrome | Action tremor, behavioural changes, autonomic dysfunction; family history (learning disability) | Mutation analysis of FMR1 gene, typical MRI (figure 4) |
| Non-genetic ataxias | ||
| Degenerative | ||
| Multiple system atrophy | Autonomic failure, Parkinsonism | MRI (figure 8), nuclear imaging, autonomic testing, see also online supplementary table S1 |
| Idiopathic late onset cerebellar ataxia | Mostly pure, slowly progressive ataxia | No specific test, other causes excluded |
| Sporadic Creutzfeldt–Jakob disease | Rapid progression, myoclonus, cognitive disturbances | EEG, CSF 14-3-3 protein/tau, typical MRI (figure 9) |
| Inflammatory | ||
| Gluten ataxia | Gastro-intestinal symptoms | Antigliadin/-tissue transglutaminase/-endomysium antibodies |
| Hashimoto encephalopathy | Subacute, seizures, myoclonus | Anti-TPO antibodies |
| Paraneoplastic cerebellar degeneration | Rapid progression, history of malignancy | Neuronal antibodies, tumour screen |
| Anti-GAD ataxia | Subacute, type 1 diabetes mellitus | Anti-GAD antibodies |
| (Para)infectious | ||
| Miller Fisher syndrome | Subacute, ophthalmoplegia, areflexia | Anti-GQ1b antibodies, EMG |
| Epstein–Barr virus | Subacute, preceding infection | CSF, serologic testing |
| HIV | Known HIV status | CSF, search for opportunistic infections |
| Structural lesions | ||
| Stroke, tumour, multiple sclerosis, etc | Focal neurological signs | MRI, other investigations depend on imaging findings |
| Toxic | ||
| Alcohol | Medical history, peripheral neuropathy | Liver function |
| Drugs (eg, lithium, phenytoin) | Medical history | Screening drug level, stop offending drug |
| Metabolic | ||
| Acquired vitamin deficiencies | ||
| Vitamin E | Diarrhoea | Vitamin E level, coeliac screen, serum amylase |
| Vitamin B1 | Confusion, nystagmus, ophthalmoplegia | Vitamin B1, typical MRI |
| Hypothyroidism | Fatigue, weight gain, constipation | Thyroid stimulating hormone, free T4 |
| Hypoparathyroidism | Cataract, extrapyramidal symptoms | Parathyroid hormone, calcium, phosphate, typical CT scan (figure 2) |
| Other | ||
| Superficial siderosis | Sensorineural deafness | Typical MRI (figure 7), audiogram, xanthochromic CSF |
CSF, cerebrospinal fluid; EMG, electromyogram; GAD, glutamic acid decarboxylase; SCA, spinocerebellar ataxia; TPO, thyroperoxidase.