These results suggest that rabphilin-3A is a major autoantigen in LINH. Autoantibodies to rabphilin-3A may serve as a biomarker for the diagnosis of LINH and be useful for the differential diagnosis in patients with CDI.
Hyponatremia is the most common clinical electrolyte disorder. Once thought to be asymptomatic in response to adaptation by the brain, recent evidence suggests that chronic hyponatremia may be linked to attention deficits, gait disturbances, risk of falls, and cognitive impairments. Such neurologic defects are associated with a reduction in quality of life and may be a significant cause of mortality. However, because underlying diseases such as adrenal insufficiency, heart failure, liver cirrhosis, and cancer may also affect brain function, the contribution of hyponatremia alone to neurologic manifestations and the underlying mechanisms remain unclear. Using a syndrome of inappropriate secretion of antidiuretic hormone rat model, we show here that sustained reduction of serum sodium ion concentration induced gait disturbances; facilitated the extinction of a contextual fear memory; caused cognitive impairment in a novel object recognition test; and impaired long-term potentiation at hippocampal CA3-CA1 synapses. In vivo microdialysis revealed an elevated extracellular glutamate concentration in the hippocampus of chronically hyponatremic rats. A sustained low extracellular sodium ion concentration also decreased glutamate uptake by primary astrocyte cultures, suggesting an underlying mechanism of impaired long-term potentiation. Furthermore, gait and memory performances of corrected hyponatremic rats were equivalent to those of control rats. Thus, these results suggest chronic hyponatremia in humans may cause gait disturbance and cognitive impairment, but these abnormalities are reversible and careful correction of this condition may improve quality of life and reduce mortality.
Context: Most patients with defective synthesis and/or secretion of thyroglobulin (Tg) present relatively high serum free T 3 (FT 3 ) concentrations with disproportionately low free T 4 (FT 4 ) resulting in a high FT 3 /FT 4 ratio. The mechanism of this change in FT 3 /FT 4 ratio remains unknown.Objective: We hypothesize that increased type 2 iodothyronine deiodinase (D2) activity in the thyroid gland may explain the higher FT 3 /FT 4 ratio that is frequently observed in patients with abnormal Tg synthesis.
Background Mild hyponatremia (serum sodium 130–135 mEq/L) is a common electrolyte disorder in the elderly. However, its association with both sarcopenia and cognitive function remains to be clarified. Therefore, here we investigated the association of mild hyponatremia with skeletal muscle mass, physical function, and cognitive function in the elderly. Methods We enrolled 75 participants with mild hyponatremia and 2907 with normonatremia (serum sodium, 136–145 mEq/L) aged ≥70 years who visited the Memory Disorder Outpatient Center of Japan’s National Center for Geriatrics and Gerontology. Skeletal muscle mass index (SMI), grip strength (GS), walking speed (WS), one-leg standing (OLS) test times, and neuropsychological test scores were determined. Results One-way analysis of covariance showed that elderly participants with mild hyponatremia had lower SMI (7.1 ± 0.2, 7.2 ± 0.2 kg/m2, p = 0.04), weaker GS (19.1 ± 1.9 vs 21.4 ± 1.8 kg, p = 0.01), slower WS (0.9 ± 0.1 vs 1.1 ± 0.1 m/s, p = 0.001), and higher GDS- 15 score (6.4 ± 0.9 vs 5.2 ± 0.9, p = 0.002) than those with normonatremia. Multiple logistic regression analysis indicated that mild hyponatremia was independently associated with sarcopenia (odds ratio [OR]: 2.2, p = 0.02), slower WS (OR: 5.3, p = 0.04) and shorter OLS time (OR: 2.5, p = 0.02) as well as with severe depressive mood (OR: 2.6 p = 0.006) but not with SMI (OR: 1.6, p = 0.2) or GS (OR: 1.9, p = 0.09). Conclusions Our results suggest that elderly people with even mild hyponatremia had physical function impairment and depressive mood.
Overly rapid correction of chronic hyponatremia can cause osmotic demyelination syndrome (ODS). Minocycline protects ODS associated with overly rapid correction of chronic hyponatremia with hypertonic saline infusion in rats. In clinical practice, inadvertent rapid correction frequently occurs due to water diuresis, when vasopressin action suddenly ceases. In addition, vasopressin receptor antagonists have been applied to treat hyponatremia. Here the susceptibility to and pathology of ODS were evaluated using rat models developed to represent rapid correction of chronic hyponatremia in the clinical setting. The protective effect of minocycline against ODS was assessed. Chronic hyponatremia was rapidly corrected by 1 (T1) or 10 mg/kg (T10) of tolvaptan, removal of desmopressin infusion pumps (RP), or administration of hypertonic saline. The severity of neurological impairment in the T1 group was significantly milder than in other groups and brain hemorrhage was found only in the T10 and desmopressin infusion removal groups. Minocycline inhibited demyelination in the T1 group. Further, immunohistochemistry showed loss of aquaporin-4 (AQP4) in astrocytes before demyelination developed. Interestingly, serum AQP4 levels were associated with neurological impairments. Thus, minocycline can prevent ODS caused by overly rapid correction of hyponatremia due to water diuresis associated with vasopressin action suppression. Increased serum AQP4 levels may be a predictive marker for ODS.
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