We believe that Dr. Siegel's concern about osmotic demyelination is unfounded. There is no actual evidence that "osmotic demyelination" has ever been caused by any rate of correction of hyponatremia (1). A recent prospective study showed no relationship (2). More important, in patients with hyponatremic encephalopathy, therapy with small increases in plasma sodium, as suggested by Dr. Siegel, leads to 100% mortality (2). With symptomatic hyponatremia, increased intracranial pressure secondary to cerebral edema is the critical factor, and its management determines patient outcome. Thus, such patients must be treated with hypertonic sodium chloride, which increases plasma sodium levels sufficiently to relieve brain edema (1). Such a maneuver was used in the six patients in our report who survived and were neurologically intact after 1 year of follow-up. More important, the patient who received no therapy died of brain stem herniation, without demyelination lesions.

Dr. Siegel also suggests that the present syndrome is both rare and a hypovolemic state (3). Both statements are incorrect. The syndrome is not rare—18% of distance runners develop hyponatremia—and the pathogenesis is related to overhydration (3). The challenge will be to consider the diagnosis of hyponatremic encephalopathy in the distance runner presenting with respiratory insufficiency and to initiate early therapy when indicated. Failure to do so may lead to death, as occurred in patient 7 in our report, in whom the diagnosis was not made (4).

Dr. Wijdicks believes we failed to prove that our patients had cerebral edema. Our patients had clinical evidence of hyponatremic encephalopathy (nausea, emesis, respiratory insufficiency, obtundation) and, more important, responded to therapy directed at dehydration of an edematous brain (hypertonic sodium chloride). His comments about neuroimaging are also irrelevant because each of six adult patients (mean age [±SD], 37 ± 7 years) had serial neuroimaging studies: initially, after therapy was completed, and after 1 year of follow-up. While a single neuroimaging study might be misleading in small children, these six adults had unequivocal evidence of cerebral edema, based on serial studies and response to therapy.

Dr. Wijdicks also asks how cerebral edema was diagnosed in the patient who did not have CT or MRI. The diagnosis was established at autopsy, which showed massive cerebral edema. Delay in diagnosis and effective management may well result in unnecessary deaths (4).