Osmotic Demyelination Syndrome (ODS) is a condition that always sounded mythical to me and appeared to be only present in medical textbooks until I saw my first patient with it. Finally I understood why endocrinologists were always fussing about sodiums rising too fast.
A middle-aged male patient had come in with a fall and a longstanding history of alcohol excess. As his initial sodium was 100mmol/L, he was managed in the intensive care unit with careful followthrough of his sodium levels, though at some points, the sodium had risen rather rapidly, and further rise had been stalled by infusing dextrose. He was eventually transferred up to the general ward and was noted to be severely deconditioned requiring intensive physiotherapy. Although this was initially attributed to critical illness myopathy and sarcopenia from his alcohol abuse and poor dietary intake, we soon realised that his improvement was plateauing and his responses were rather slow. He also developed increased tone and rigidity. An MRI brain subsequently revealed changes in the pons suggestive of possible ODS.
The pathophysiology
In chronic (i.e. > 48hours) hyponatraemia, the body, and particularly the neurons in our central nervous system develop incredible adaptations to prevent water from flowing from the blood to the interstitium and into the neurons which have a higher tonicity (higher solute content). If the water did flow in, you can imagine the neurons might swell and even burst.
To prevent this from happening, the neurons extrude osmotically active intracellular solutes such as potassium and organic solutes such as glutamate and glutamine, allowing the cells to get rid of excess water that follows along with these osmolytes.
The problem occurs when we start correcting the hyponatraemia rapidly and the neurons are unable to reacquire these lost solutes at the same rate as the sodium correction. As a result, the extracellular space may develop a higher tonicity to the intracellular space resulting in water being drawn out of the neurons. This causes protein aggregation, DNA fragmentation and apoptosis of these cells leading to demyelination, osmotic injury, and possible breakdown of the blood brain barrier with vasogenic oedema.
Risk factors for ODS:
Severe hyponatraemia < 120
Chronicity of hyponatraemia (sodium low for > 48 hours)
Advanced liver disease
Chronic alcoholism
Malnutrition
Hypoalbuminaemia
Hypokalaemia
Clinical Features
•Typically develop 2-6 days after rapid correction of sodium
•Dysarthria, dysphagia, paraparesis/quadriparesis
•Behavioural disturbances
•Movement disorders – grasping or rooting reflexes
•Increased muscle tone
•Facial weakness
•Seizures, lethargy, confusion
•Disorientation, obtundation, coma
•If severe: locked in syndrome
Pontine involvement: speech abnormalities start early and persist, patients may become mute
Extrapontine involvement: psychiatric disturbances, catatonia, postural limb tremors, myoclonic jerks, choreosthetosis, dystonia – these may respond to dopaminergic treatment
Corticospinal signs: Hyperreflexia and bilateral Babinski signs
Corticobulbar signs: Brisk jaw jerk
Typical Radiological findings:
CT – may show low attenuation crossing the midline in the lower pons but is not ideal for imaging at the skull base, MRI is preferred
MRI – earliest changes are seen on diffusion weighted imaging (DWI) with restriction in the lower pons – eventually high T2 signal and then low T1 signal is seen (these can occur over 2 weeks) – classic trident-shaped appearance/piglet sign
For classic examples, see the radiopaedia.org link below.
How to prevent and manage ODS
The main key to preventing ODS is to slow the rise of sodium levels, especially in patients with hyponatraemia of >48 hours. Guidelines suggest keeping a target of not more than 8-10mmol/24hours and not more than 16-18mmol/L over 48 hours as a rolling target from any defined time point.
If the sodium level has already risen drastically. considerations include the option of relowering the sodium in those with a high risk of ODS. Studies in a small number of patients have shown that relowering can be done using dextrose 5% and desmopressin. Relowering sodium by 12-16mmol/L over 12-14 hours resulted in reversal of neurologic symptoms. However there was no placebo comparison and hence no clear evidence of improved outcomes as compared to watchful waiting (see references 2,3,4)
Intubation and sedation should be used as necessary for complications such as aspiration pneumonia and to maintain the airway. Structured rehabilitation with physiotherapy over 6 to 8 weeks has been shown to achieve significant neurological recovery. A study (n=36 pts) in ODS patients in a critical care unit showed that 69% survived, 56% of survivors had minimal residual neurologic sequelae and initial severity was not predictive of longterm prognosis. (See reference 5)
Experimental treatments have been tried. There are 3 case reports of the use of plasmapheresis started immediately upon diagnosis of ODS on MRI. Although there were no changes in MRI findings, 2 of 3 patients improved markedly with no neurological deficits. The third patient had impaired intermediate term memory and could only walk with assistance. In rats, the use of minocycline given along with hypertonic saline has been shown to reduce the severity of neurologic symptoms and histologic demyelination. (See references 6-10)
https://radiopaedia.org/articles/osmotic-demyelination-syndrome
Rafat et al. Clin J AM Soc Nephrol 2014 PMID 24262506
Perianayagam et al Clin J AM Soc Nephrol 2008 PMID 18235152
Macmillan and Cavalcanti Am J Med 2018 PMID 29061503
Louis et al. 2012 Crit Care Med PMID: 22036854
Suzuki et al. J Am Soc Nephrol. 2010 PMID 21030598
Gankam-Kengne F et al. J Am Soc Nephrol 2010 PMID 21051736
Bibl et al. Lancet 1999 PMID: 10209986
Grimaldi et al. J Neurol. 2005 PMID 15742105
Saner et al Transpl Int 2008. PMID 18069924
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