Chronic Hyponatremia and Brain Structure and Function Before and After Treatment

Rationale & ObjectiveHyponatremia is the most common electrolyte disorder and is associated with significant morbidity and mortality. This study investigated neurocognitive impairment, brain volume, and alterations in MRI-based measures of cerebral function in patients before and after treatment for hyponatremia.Study DesignProspective cohort study.Setting & ParticipantsPatients with presumed chronic hyponatremia without signs of hypo- or hypervolemia treated in the Emergency Department of a German tertiary care hospital.ExposureHyponatremia ([Na+] <125 mmol/L) before and after treatment leading to [Na+] >130 mmol/L.OutcomesStandardized neuropsychological testing (Mini-Mental-State examination [MMSE], DemTect, Trail-Making Test [TMT] A/B, Beck's Depression Inventory, Timed Up and Go) and resting-state MRI were performed prior to and following treatment of hyponatremia to assess volumes of total brain, white and gray matter, as well as neuronal activity and its synchronization.Analytical ApproachChanges in outcomes after treatment for hyponatremia assessed using bootstrapped confidence intervals and Cohen's d. Associations between parameters were assessed using correlation analyses.ResultsDuring a 3.7-year period, 26 patients were enrolled. Complete data were available for 21 patients. Mean [Na+] was 118.4 mmol/L before treatment and 135.5 mmol/L following treatment. Most measures of cognition improved significantly. Comparison of MRI studies showed a decrease in brain tissue volumes, neuronal activity, and synchronization across all gray matter after normalization of [Na+]. Volume effects were particularly prominent in the hippocampus. During hyponatremia, synchronization of neuronal activity was negatively correlated with [Na+] (r=-.836, [-.979, -.446]) and cognitive function (MMSE: r=-.523, [-.805, -.069]; DemTect: r=-.744, [-.951, -.385] and TMT-A: r=.692, [.255, .922]).LimitationsSmall sample size, insufficient quality of several MRI scans due to motion artifact.ConclusionsResolution of hyponatremia was associated with improved cognition and reductions in brain volumes and neuronal activity. Impaired cognition during hyponatremia is closely linked to increased neuronal activity rather than to tissue volumes. Furthermore, the hippocampus appears to be particularly susceptible to hyponatremia, exhibiting pronounced changes in tissue volume.