Central Pontine Myelinosis and Osmotic Demyelination Syndrome

Abstract

Background: Osmotic demyelination syndrome (ODS), which embraces central pontine myelinolysis (CPM) and extrapontine myelinosis (EPM), is often underdiagnosed in clinical practice, but can be fatal. In this article, we review the etiology, patho- physiology, clinical features, diagnosis, treatment, and prognosis of ODS.

Methods: Pertinent publications from the years 1959 to 2018 were retrieved by a selective search in PubMed.

Results: The most common cause of ODS is hyponatremia; particular groups of patients, e.g., liver transplant recipients, are also at risk of developing ODS. The pathophysiology of ODS consists of cerebral apoptosis and loss of myelin due to osmotic stress. Accordingly, brain areas that are rich in oligodendrocytes and myelin tend to be the most frequently affected. Patients with ODS often have a biphasic course, the first phase reflecting the underlying predisposing illness and the second phase reflecting ODS itself, with pontine dysfunction, impaired vigilance, and movement disorders, among other neurological abnormalities. The diagnostic modality of choice is magnetic resonance imaging (MRI) of the brain, which can also be used to detect oligosymptomatic ODS. The current mainstay of management is prevention; treatment strategies for manifest ODS are still experimental. The prognosis has improved as a result of MRI-based diagnosis, but ODS can still be fatal (33% to 55% of patients either die or remain permanently dependent on nursing care).

Conclusion: ODS is a secondary neurological illness resulting from a foregoing primary disease. Though rare overall, it occurs with greater frequency in certain groups of patients. Clinicians of all specialties should therefore be familiar with the risk constellations, clinical presentation, and prevention of ODS. The treatment of ODS is still experimental at present, as no evidence-based treatment is yet available.

Figure 1

Pathophysiology of hyponatremia: a) Initial situation b) Changes in acute hyponatremia. Depending on the osmotically activated sodium gradient, the volume of brain cells initially increases, leading to cerebral edema and subsequent hospitalization. c) Compensation mechanisms in prolonged hyponatremia: to regulate cell volume, so-called osmolytes—osmotically active, inorganic ions (approximately 30% potassium and 20% chloride) and organic substances (with myo-inositol as the most important representative)—are released from cells. Inorganic osmolytes are transported via volume-sensitive potassium and chloride channels () while organic compounds diffuse along the concentration gradients via so-called leakage pathways () (17). The cell volume then normalizes, and the osmotically activated gradient between intra- and extracellular space equalizes. d) Conditions in chronic hyponatremia e) Processes of correction for chronic hyponatremia. Cells are in a relatively hypertonic milieu and are exposed to osmotic stress, as on the one hand intracellular osmolytes are not replicated quickly enough, and on the other hand the reuptake of organic osmolytes via the bidirectional leakage pathways is much slower than their loss (18). Cells contract as a result of osmotic stress, and apoptosis is triggered.

Figure 2

Preventive measures to avoid osmotic demyelination syndrome