ODS is a complex pathologic entity characterized by osmotic myelinolysis due to osmolality disorders, that determines an acute onset of neurologic symptoms.
ODS was formerly described as central pontine myelinolysis, since pons and brainstem are the most sensitive to osmotic stress. However, ODS refers to a more complex syndrome that can affect both pontine and extrapontine structures (50% of cases), or the isolated pons(30%). The occurrence of isolated extrapontine myelinolysis is the less common (20% of cases), which makes the diagnosis even more challenging, underscoring the importance of recognizing the ODS spectrum’s symptoms.
Pathogenesis
Several causes of osmolality disorders are recognized and could be associated with pathologic conditions such as hemodialysis, organs transplantation, AIDS, hypopituitarism, malignancies (especially hematologic), or physical and social conditions (i.e. malnutrition, alcoholism, uncontrolled diabetes).
It has been reported that pathogenesis involves glial cells, particularly astrocytes. During acute onset of hyponatremia, to maintain the correct isoosmolality of intracellular and extracellular fluids, water moves from the blood into brain cells, leading to cell swelling. In this scenario, astrocytes, whose function is to protect neurons, swell first.
Brain cells quickly adapt to hyponatremia by losing inorganic osmolytes (electrolytes) in order to re-establish normal cell volume; i.e. fluids movements through cellular walls are secondary to the movements of little osmolyte like Na+, that is the principal osmolytes released from cells. In more prolonged hyponatriemia, brain cells also expel organic osmolytes (that move slower than electrolytes).
When hyponatremy establish slowly there is sufficient time to re-establish the osmotic equilibrium with the blood, with a compensation of the extracellular hypotonia. Treatment of chronic hyponatremia, using a hypertonic saline solution, causes brain cell dehydration and the loss of vital electrolytes, in addition to organic osmolytes such as myo-inositol, taurine, glutamine, glutamate, creatine, phosphocreatine, and glycerophosphorylcholine. When the speed of correction of hyponatriemia exceed the capability to compensate the increasing plasma tonicity within cells, an osmotic stress occurs while preventing the reabsorption of organic osmolytes into the cell; the result of osmotic stress is the shrinkage of the cells, and this is of particular concern in oligodendrocytes, which appear to be the most susceptible cells to this kind of damage.
Astrocytes seem to have a further role in this events: the osmotic stress determines a deregulation of their protective function and an impairment of blood–brain barrier function, that may allow injurious substance released from endothelial cells (plasminogen activator, complement proteinase, cytokines, immunoglobulins, and neural proteases) access to myelin sheaths. This damages the oligodendrocytes, with resulting intramyelinic splitting, vacuolization, and rupture of myelin sheats.
These mechanisms explain why the damage particularly affects oligodendrocytes. Accordingly, the distribution of the changes that occur with osmotic demyelination syndrome parallels the distribution of oligodendroglial cells that embed large neurons in thalamus, putamen, lateral geniculate and particularly the central pons. In this location it has been hypothesized that either the grid arrangement of the descending and crossing tracts in the pons or perhaps its vulnerable vascularity is responsible for the peculiar focal nature of the lesion. An uncommon laminar necrosis of the cortex among extrapontine demyelination was observed, suggesting that the white matter just below the gray matter is particularly susceptible to osmotic distress.
ODS is characterized by the acute onset of neurologic symptoms like seizures, alterations in mental status and stiffness. The typical course of pathology is biphasic, with a rapid improvement of mental status and the regression of neurologic symptoms after the restoring of normonatriemia.
After a period of approximately one week, an abrupt worsening of neurological status occurs with onset of movement disorders, dysarthria, dysphagia, pseudobulbar palsy, where the variety and the severity of the symptoms are related to the affected areas. The latter symptoms of this syndrome are quadriparesis and pseudobubar palsy, reflecting damage to the corticospinal and corticobulbar tracts in the pons.