Subject(s)
DiGeorge Syndrome/complications , Hypernatremia/complications , Hypernatremia/diagnostic imaging , Myelinolysis, Central Pontine/complications , Myelinolysis, Central Pontine/diagnostic imaging , Child, Preschool , DiGeorge Syndrome/diagnosis , Diffusion Magnetic Resonance Imaging/methods , Female , Fluid Therapy/methods , Follow-Up Studies , Humans , Hypernatremia/blood , Hypernatremia/therapy , Rare Diseases , Risk Assessment , Treatment OutcomeABSTRACT
Adipsic (or essential) hypernatremia is a rare hypernatremia caused by a deficiency in thirst regulation and vasopressin release. In 2010, we reported a case in which autoantibodies targeting the sensory circumventricular organs (sCVOs) caused adipsic hypernatremia without hypothalamic structural lesions demonstrable by magnetic resonance imaging (MRI); sCVOs include the subfornical organ (SFO) and organum vasculosum of the lamina terminalis (OVLT), which are centers for the monitoring of body-fluid conditions and the control of water and salt intakes, and harbor neurons innervating hypothalamic nuclei for vasopressin release. We herein report three newly identified patients (3- to 8-year-old girls on the first visit) with similar symptoms. The common features of the patients were extensive hypernatremia without any sensation of thirst and defects in vasopressin response to serum hypertonicity. Despite these features, we could not detect any hypothalamic structural lesions by MRI. Immunohistochemical analyses using the sera of the three patients revealed that antibodies specifically reactive to the mouse SFO were present in the sera of all cases; in one case, the antibodies also reacted with the mouse OVLT. The immunoglobulin (Ig) fraction of serum obtained from one patient was intravenously injected into wild-type mice to determine whether the mice developed similar symptoms. Mice injected with a patient's Ig showed abnormalities in water/salt intake, vasopressin release, and diuresis, which resultantly developed hypernatremia. Prominent cell death and infiltration of reactive microglia was observed in the SFO of these mice. Thus, autoimmune destruction of the SFO may be the cause of the adipsic hypernatremia. This study provides a possible explanation for the pathogenesis of adipsic hypernatremia without demonstrable hypothalamus-pituitary lesions.
Subject(s)
Autoantibodies/blood , Hypernatremia/diagnostic imaging , Hypernatremia/immunology , Subfornical Organ/diagnostic imaging , Subfornical Organ/immunology , Adolescent , Animals , Brain/diagnostic imaging , Brain/immunology , Brain/pathology , Cell Death/physiology , Child , Disease Models, Animal , Female , Humans , Hypernatremia/pathology , Male , Mice, Inbred C57BL , Microglia/immunology , Microglia/pathology , Subfornical Organ/pathologySubject(s)
Hypernatremia/complications , Myelinolysis, Central Pontine/etiology , Diagnosis, Differential , Female , Humans , Hypernatremia/diagnostic imaging , Hypernatremia/physiopathology , Hypernatremia/therapy , Middle Aged , Myelinolysis, Central Pontine/diagnostic imaging , Myelinolysis, Central Pontine/physiopathology , Myelinolysis, Central Pontine/rehabilitationABSTRACT
We present two newborn infants with hypernatremic dehydration with central nervous system (CNS) involvement. Both patients showed similar imaging findings, demonstrating generalized brain parenchymal abnormality and multifocal areas of hemorrhage or hemorrhagic infarction. These findings are compatible with previously described CNS pathologic findings in hypernatremia.
