Osmotic demyelination syndrome: An under-recognised cause of delirium?

To the Editor

Osmotic demyelination syndrome (ODS), comprising central pontine and extrapontine myelinolysis, has been typically associated with rapid correction of hyponatraemia. It has also been described in many other settings with normal sodium levels (Martin, 2004) and, in particular, it can present as a delirium that fails to resolve. Missing the diagnosis represents a lost opportunity to limit progression and complications and to protect against future recurrence in settings of expected risk.

We recently encountered a 58-year-old male presenting with persistent delirium in the immediate aftermath of percutaneous neph–rolithotripsy. Magnetic resonance imaging (MRI) undertaken 5 weeks postoperatively showed a region of T2 hyperintensity involving the central pons, which was more clearly defined compared to a previous scan done 3 weeks postoperatively, and was suggestive of central pontine myelinolysis. Serum sodium levels had been stable throughout. Elevated serum glucose was noted intra-operatively (17 mmol/L), requiring the administration of subcutaneous insulin in theatre and insulin–dextrose infusions later that day. There was no history of heavy alcohol use.

Laboratory tests were negative for autoimmune, infectious and paraneoplastic encephalitis. Cerebrospinal fluid analysis 10 days postoperatively was remarkable for elevated glucose (7.5 mmol/L; reference: 2.8–4.4 mmol/L) and protein (0.71 g/L; reference: 0.15–0.45 g/L) and few lymphocytes (9 × 10⁶/L). Electroencephalography showed an encephalopathic pattern 5 weeks postoperatively, some improvement at 8 weeks, and no abnormality at 15 weeks. The delirium clinically resolved within 8 weeks with supportive measures. A diagnosis of probable ODS, secondary to the use of copious endoscopic irrigation fluid and the glucose fluctuations, was made. The general practitioner was advised of the need to alert surgeons to limit future endoscopic irrigation to a minimum and to monitor serum glucose peri- and intra-operatively.

ODS is most commonly associated with chronic alcoholism, rapid correction of hyponatraemia, and the first month post-liver transplantation. It has been reported with other mal–nutrition states, burns, prolonged diuretic use and following surgical procedures involving copious use of irrigation fluids (Kleinschmidt-Demasters et al., 2006; Martin, 2004). The clinical presentation is variable (Martin, 2004). Neurological symptoms can be absent in small lesions but include dysarthria/dysphagia, quadriplegia, oculomotor signs and/or, in severe cases, locked-in syndrome. Neuropsychiatric symptoms include apathy, disinhibition, emotional lability, delusions, and impairment of attention, memory retrieval and executive function (Kleinschmidt-Demasters et al., 2006). MRI changes, including T1 hypointensity in the acute phase and T2 hyperintensity subacutely, may only become apparent days or weeks after the insult (Takei et al., 2003). A retrospective study of 34 patients showed that, among the 32 who survived, 11 patients had no residual cognitive and/or neurologic deficits (Menger and Jörg, 1999). The authors associated survival with avoidance of secondary complications including aspiration pneumonia, urosepsis and venous thromboembolism. In addition to cautious management of electrolyte balance and nutrition status in affected patients or patients at risk, there is some evidence of a protective role for steroids and myoinositol in certain settings (Kleinschmidt-Demasters et al., 2006). Minocycline has also demonstrated protective benefit in experimental models of demyelination and further evidence is awaited (Gankam-Kengne et al., 2010).

ODS can arise in many clinical contexts and warrants a high index of suspicion for early detection and management in patients with persistent delirium.