A 4-year-old boy is reviewed on the paediatric oncology ward. He is being treated with a continuous intravenous morphine infusion for severe oral mucositis following a recent cycle of chemotherapy.
Over the last 12 hours, the nursing staff report he has developed intermittent myoclonic jerks. On assessment, he is irritable and displays significant hyperalgesia to gentle palpation.
There is no fever, rash, or focal neurological deficit. A recent laboratory review confirms his renal function is normal.
What is the most likely diagnosis?
CORRECT ANSWER:
Opioid-induced neurotoxicity (OIN) is the most likely diagnosis. This child presents with classic features of OIN: myoclonus and hyperalgesia.
Morphine is metabolised in the liver to morphine-6-glucuronide (M6G), an active analgesic, and morphine-3-glucuronide (M3G). The accumulation of M3G, a neurotoxic metabolite, is primarily responsible for OIN, causing symptoms like myoclonus, allodynia, hyperalgesia, and delirium.
While impaired renal function is a major risk factor for accumulation, OIN can occur in patients with normal renal function, particularly with high morphine doses required for severe chemotherapy-induced mucositis. The cornerstone of management, as per best practice guidelines, is to reduce the opioid burden. This involves either reducing the morphine dose or, more commonly, rotating to a different opioid, such as oxycodone or fentanyl, which have different metabolic pathways and may be better tolerated.
WRONG ANSWER ANALYSIS:
Option A (Meningitis) is less likely as the presentation lacks typical features such as fever, headache, or neck stiffness, making the specific symptoms more attributable to a pharmacological cause.
Option C (Hypocalcaemia) is incorrect because while it can cause neuromuscular irritability and tetany, it does not typically cause hyperalgesia.
Option D (Brain metastasis) is unlikely as it would typically present with focal neurological deficits, seizures, or signs of raised intracranial pressure rather than this specific neuroexcitatory syndrome.
Option E (Electrolyte imbalance) is incorrect as it is a non-specific term, and no single common electrolyte disturbance characteristically presents with both myoclonus and hyperalgesia.