A 52-year-old man with newly diagnosed acute myeloid leukaemia (AML) is started on cytarabine as part of induction chemotherapy. On day 5 of treatment, he develops severe mucositis and diarrhoea. Which investigation would be most appropriate to assess for cytarabine-induced cerebellar syndrome, a dose-limiting toxicity?

Explanation

## Cytarabine Toxicity Profile **Key Point:** Cytarabine (arabinosyl cytosine) is a pyrimidine antimetabolite that causes dose-dependent neurotoxicity, with cerebellar syndrome being the most clinically significant neurological complication at high doses (>3 g/m²). ## Clinical Presentation of Cerebellar Syndrome Cerebellar toxicity from cytarabine manifests as: - Dysarthria, ataxia, and dysmetria - Nystagmus and vertigo - Gait disturbance - Onset typically 3–8 days after high-dose infusion - Risk increases with age >50 years, renal dysfunction, and hepatic impairment ## Why MRI Brain is the Investigation of Choice **High-Yield:** MRI brain with contrast is the gold standard for detecting cytarabine-induced cerebellar syndrome because it: 1. Visualizes cerebellar oedema, atrophy, or necrosis 2. Excludes other CNS pathology (infection, haemorrhage, metastases) 3. Provides prognostic information — reversible oedema vs. irreversible necrosis 4. Guides dose modification or cessation of cytarabine **Clinical Pearl:** Early MRI detection of cerebellar changes may allow dose reduction or discontinuation before irreversible damage occurs, making this the most clinically useful investigation. ## Comparison with Other Investigations | Investigation | Role | Limitation in Cytarabine Toxicity | |---|---|---| | **MRI brain** | Structural imaging of CNS | Gold standard; detects oedema and necrosis | | **Serum creatinine/electrolytes** | Renal and metabolic assessment | Identifies risk factors, not the toxicity itself | | **Lumbar puncture/CSF** | Infection/leukaemic involvement | Does not visualize structural brain changes | | **EEG** | Electrical brain activity | Non-specific; may show slowing but not diagnostic | **Mnemonic:** **SCAN** for cytarabine neurotoxicity = **S**tructural imaging (MRI), **C**erebellar signs, **A**void high doses, **N**eurological monitoring.