This document provides an overview of osmotic demyelination syndrome (ODS), also known as central pontine myelinolysis. It discusses the history, controversies in nomenclature, pathology, epidemiology, pathophysiology, clinical features, diagnosis, management including prevention, re-lowering sodium levels, supportive care and investigational therapies, prognosis, and key references. The document is intended as an educational resource for physicians on ODS.

1. Osmotic demyelination
syndrome
-Dr. Sachin AAdukia

2. History
 1959- Victor and Adams first described central pontine myelinolysis
 clinical findings- quadriparesis, pseudobulbar paralysis
 Pathology- myelin loss confined within the central pons
 was felt as a sequela of alcoholism or malnutrition
 1962- recognised that lesions can occur outside the pons:- extrapontine
myelinolysis (EPM).
 1976- Tomlinson – suggested link with rapid correction of sodium in
hyponatraemic patients was established
 1981: Kleinschmidt-DeMasters and Norenberg conclusively
demonstrated a link between ODS and rapid correction of hyponatremia

3. ‘‘…whenever a patient who is gravely ill with alcoholism
and malnutrition or a systemic medical disease develops
confusion, quadriplegia, pseudobulbar palsy, and pseudo
coma (‘locked-in syndrome’) over a period of several days,
one is justified in making a diagnosis of central pontine
myelinolysis’.

4. Controversy in nomenclature
 1962- extrapontine myelinolysis (EPM) may also occur hence
broader term- Osmotic demyelination syndrome.
 But as per Victor and Adams:
 location of principal lesion is given  neurological
consequences of the lesion can be deduced.
 term “demyelination” avoided so as to distinguish this condition
in which myelin loss occurs without obvious inflammatory
infiltrate from inflammatory nature of MS.

7. Pathology
 Predominantly - basis pontis, sparing the tegmentum
 may extend up to midbrain, very rarely down to medulla
 Pathologically, loss of myelin sheath with relative sparing of axons and
neurons in sharply demarcated lesion
 absence of an inflammatory infiltrate in these lesions
 Reason for localisation within this region:
 this is a region of maximal admixture of grey and white matter elements
 Similarly lesions of EPM are seen in similar regions of grey–white apposition.

8. Epidemiology
 Rare disease, frequency not known.
 Majority of pathologically diagnosed ODS cases are clinically asymptomatic
 Largest autopsy series :- prevalence of 0.25% to 0.5% in a general population,
majority were not diagnosed premortem
 Populations, such as alcoholics and liver transplant have higher rates of ODS
 Liver transplant pts- postmortem rate of ODS 10%.
 Peak incidence in adults aged 30 to 60 years
 Male preponderance, ? Higher alcoholism in this age group

9. Pathophysiology

11. Role of organic osmolytes
 Hyponatremia – causes loss of osmotically active, protective,
organic osmolytes within few hours to days of hyponatremia
 Glycine, taurine, myoinositol, glutamate, glutamine from astrocytes
 However, not as quickly replaced when brain volume begins
to shrink due to correction of hyponatremia
 As a result, brain volume falls below normal with rapid
correction of hyponatremia.

13. Factors which may increase risk of acute
hyponatremia encephalopathy
 Estrogen
 inhibits Na-K-ATPase pump
 Thus ODS is more common in women of childbearing age
 Arginine vasopressin
 decreased cerebral perfusion and decrease ATP availability for ion
exchange
 Hypoxia
 limits ATP availability
Ayus JC, Achinger SG, Arieff A. Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin and hypoxia. Am J Physiol
Renal Physiol 2008;295:F619 –24.

14. Disorders of solute
metabolism
Associated with alterations
in cellular volume control.

15. Duration of Hyponatremia to cause ODS
 Brain damage does not occur when hyponatremia < 1 day
duration is rapidly corrected
 If persists for > 2 to 3 days same treatment results in ODS
 However duration is often not known.
 Thus, assume that pt. has chronic hyponatremia unless the
history suggests acute water intoxication.
 marathon runners
 psychotic patients
 users of ecstasy

16. Clinical features
 Appear 2 to 6 days after rapid correction of sodium
 Include:
 Central pontine myelinolysis (CPM)
 Extra pontine myelinolysis (EPM)
 Movement disorders in EPM

17. Central pontine myelinolysis (CPM)
 Biphasic clinical course,
 initially encephalopathic or seizures from hyponatraemia,
 then recovering rapidly as normonatraemia is restored
 deteriorate several days later.- Manifested by s/o CPM
 dysarthria and dysphagia (secondary to corticobulbar fibre involvement),
 a flaccid quadriparesis (corticospinal tract) later becomes spastic
 hyperreflexia and bilateral Babinski signs
 if tegmentum of pons is involved pupillary, oculomotor abnormalities
 apparent change in conscious level -‘‘locked-in syndrome’’

19. Diagnosis
 Clinical suspicion
 any patient presenting with new-onset neurological symptoms with a
recent rapid increase in serum sodium.
 postliver transplant
 other risk factors listed
 Diagnosis clinico-radiological
 no role for tissue examination

20. Typical MRI lesions
 Trident shaped / spreading bushfire pattern in central pons
 Signal characteristics of affected region include:
 T1: mildly or moderately hypointense
 T2: hyperintense, sparing the periphery and corticospinal tracts
 FLAIR: hyperintense
 DWI: hyperintense
 ADC: signal low or signal loss
 T1 C+ (Gd): usually there is no enhancement
 Radiologic findings do not improve over time, despite complete or nearly complete
clinical recovery

26. Radiological differential diagnosis of CPM
 General imaging differential considerations include:
 demyelination - multiple sclerosis (MS)
 infarction from basilar perforators can be central
 pontine neoplasms - astrocytomas

27. Management
 Prevention
 Re-lowering Serum Sodium
 Supportive care
 Experimental therapies

28. Prevention
 Rate of sodium correction to avoid ODS
 < 10 to 12 mEq/L per 24 hours
 < 18 mEq/L in 48 hours
 Presence of other risk factors require slower rates- max 8 mEq/L per 24 hrs
 Some may have risk factors and have urgent symptoms of hyponatremia
necessitating immediate correction, such as seizures or obtundation
 Generally, most life-threatening manifestations of hyponatremia will abate
with a 5% rise in serum sodium
 Subsequent correction  no more than 8 to 12 mEq/L per 24 hours
Geoghegan P, Harrison AM, Thongprayoon C, et al. Sodium Correction Practice and Clinical Outcomes in Profound Hyponatremia. Mayo Clin Proc 2015;
90:1348

29. Re-lowering Serum Sodium
 Goals of therapy
 Rate of lowering sodium is 1 meq/L per hour
 Target a rate of correction of < 8 meq/L in any 24-hour period and < 16 meq/L in
any 48-hour period.
 D5%, 6 mL/kg lean body weight, infused over 2 hours.
 lowers Serum sodium by approximately 2 meq/L
 infusion should be repeated until the therapeutic goal
 dDAVP, 2 mcg intravenously or subcutaneously q6h
 can be increased to 4 mcg in those who do not respond
 dDAVP is continued, even after D5W infusions have ceased, to prevent serum
sodium from rising again d/t excretion of dilute urine
Rafat C, Schortgen F, Gaudry S, et al. Use of desmopressin acetate in severe hyponatremia in the intensive care unit. Clin J Am Soc Nephrol 2014; 9:229
Oya S, Tsutsumi K, Ueki K, Kirino T. Reinduction of hyponatremia to treat central pontine myelinolysis. Neurology 2001; 57:1931.

30. Supportive care
 Ventilator
 Physiotherapy and Neuro-rehab
 Anti-Parkinsonism drugs

31. Investigational therapies
 Minocycline
 minocycline crosses BBB  inhibits microglial activation  reducing
microglial production of inflammatory cytokines
 no available data in humans
 Dexamethasone- no available data in humans
 myoinositol  Exogenous myoinositol rapidly restores the brain myoinositol
content to normal levels
 no available data in humans
 Plasmpheresis
 ?? Spontaneous rapid clinical recovery
•Zhu S, Stavrovskaya IG, Drozda M, et al. Minocycline inhibits cytochrome c release and delays progression of ALS in mice. Nature 2002; 417:74.
•Sugimura Y, Murase T, Takefuji S, et al. Protective effect of dexamethasone on osmotic-induced demyelination in rats. Exp Neurol 2005; 192:178
•Saner FH, Koeppen S, et al. Treatment of central pontine myelinolysis with PLEX / IVIg in liver transplant patient. Transpl Int 2008; 21:390.

32. Prognosis
 25% develop severe, incapacitating neurological disease
requiring lifelong support
 Variable persistent paralysis
 severe ataxia
 Bulbar symptoms
 Less common- persistence of cognitive/ beahvioural symptoms
Menger H, Jorg J. Outcome of central pontine and extrapontine myelinolysis (n 44). J Neurol 1999;246:700 –5.

33. References
 Martin RJ. Central pontine and extrapontine myelinolysis: the osmotic
demyelination syndromes. Journal of Neurology, Neurosurgery & Psychiatry.
2004 Sep 1;75(suppl 3):iii22-8.
 King JD, Rosner MH. Osmotic demyelination syndrome. Am J Med Sci. 2010
Jun 1;339(6):561-7.
 Uptodate website- 2017

34. Thank You