Water Channelopathies Beyond NMOSD: A Pathophysiological Discussion on Two Real World Clinical Cases

Background. Water channel functions have been clarified since the 1950`s, and their disorders are now well recognized as autoimmune, toxic or vascular. Neuromyelitis optica remains one of the most significant neurological water channelopathies, involving immune attack of a well-defined auto antibody to water channels not only on optic nerves and spinal cord but also in the brain. On the other hand, a more diffuse pattern of dysfunction triggered by toxicity and/or vascular insult targeting water channel structures evolves acutely as an encephalopathy syndrome, potentially but not always reversible.

Objectives. We present two cases of posterior reversible encephalopathy syndrome (PRES), its different pathophysiological mechanisms and possible correlations to NMOSD management.

Method. In the first case, a patient with hypertensive renal disease on hemodialysis was admitted to ER on hypertensive crisis and generalized convulsive epileptic status. In the second case, a woman with bilateral nephrectomy and renal transplantation, immunosuppression with tacrolimus and steroids, was also admitted to ER with generalized convulsive epileptic status.

Results. Both patients share comorbidities. They were admitted to ICU due to acute encephalopathy and had good outcomes after proper management. The first patient showed parieto-occipital cortical linear areas of hyperintense signal on T2W/FLAIR with patches of diffusion restriction, while the second exhibit a holohemispheric watershed pattern involving cortical and periventricular areas with hyperintense signal on T2W/FLAIR and no diffusion restriction.

Conclusion. We exemplify two hypotheses for PRES pathophysiology: the hemodynamic hypothesis, wherein rapid increase in blood pressure leads to hyperperfusion, breakdown of autoregulation, vascular leakage and vasogenic edema. The neurotoxicity hypothesis suggests endothelial dysfunction due to endogenous or exogenous toxins, also leading to vascular leakage and vasogenic edema. We finally discuss possible implication of PRES on NMOSD patients, some of them have undergone rituximab treatment, as well as a possible role of anti-aquaporin 4 antibody on its mechanism.