Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0036572 (seizures)
 80,221 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Patients with hyponatremia are exposed to major neurological complications. On the one hand hyponatremia itself produces brain edema, increased intracranial pressure which potentially leads to subsequent neuropathological sequelae or death. On the other hand excessive correction could be followed by development of brain demyelinating lesions (central pontine or extrapontine myelinolysis) with major disability or fatal outcome. Understanding of brain adaptative mechanisms to changes in osmolality largely contributes to explain these neurological events. When serum sodium decreases, the brain prevents swelling by extruding electrolytes and organic osmolytes, a process almost fully achieved after 48 h. Conversely, during subsequent increase in serum sodium, reestablishment of intracerebral osmolytes occurs but their reuptake is more delayed (+/- 5 days). In both circumstances, these mechanisms can be overwhelmed, leading to brain damage. Acute hyponatremia (< 48 h) is generally hospital-acquired, mainly in the postoperative state and/or after excessive fluid administration. After abrupt fall in serum sodium, seizure, respiratory arrest and coma may develop and these manifestations are sometimes explosive in nature. Recognition of even minor symptoms is crucial and implies prompt correction. There is generally no risk of brain myelinolysis in acute hyponatremia. Some factors are suspected to aggravate the prognosis of hyponatremic encephalopathy, including female gender (menstruant women), hypoxia and young age. Chronic hyponatremia (> 48 h) usually develops outside the hospital and is generally better tolerated. The risks of brain myelinolysis can be largely reduced by limiting the correction level to < or = 15 mEq/1/24 h. However, if necessary, the initial rate of correction can be rapid provided that the final correction remains < 15 mEq/1/24 h. However, when other recognized risk factors for myelinolysis (hypokalemia, liver disease, poor nutritional state, burns) are present, correction should not exceed 10 mEq/1/24 h. Demyelinization is also observed in hypernatremia but it follows greater (50%) increase in serum sodium than from hyponatremic baseline. For symptomatic hyponatremia, rapid correction is usually obtained by hypertonic saline (3%) infusion. Another option consists in administration of intravenous or oral urea. Urea allows a rapid reduction of brain edema and intracranial pressure which is followed by subsequent correction of hyponatremia. Experimental data also suggest that treatment of hyponatremia with urea is associated with a lower incidence of myelinolysis. In hyponatremic patients without symptoms, there is no need for rapid correction and the treatment should be more conservative. Close monitoring of the serum sodium is indicated initially and if necessary, correction must be stopped and diuresis interrupted with dDAVP. Given recent experimental data, in patients overly corrected (delta SNa > 15 mEq/1/24 h), the risk of myelinolysis could be greatly reduced by rapidly decreasing the serum sodium through hypotonic fluids administration and dDAVP.
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PMID:Therapeutic recommendations for management of severe hyponatremia: current concepts on pathogenesis and prevention of neurologic complications. 887 50

Hyponatremia is often associated with arginine vasopressin (AVP) dysregulation that is regulated by the hypothalamo-neurohypophyseal tract in response to changes in plasma osmolality, commonly in patients with the syndrome of inappropriate antidiuretic hormone secretion (SIADH). Potentially lethal complications of hyponatremia most frequently involve the central nervous system and include anorexia, fatigue, lethargy, delirium, seizures, hypothermia and coma, and require prompt treatment. Chronic hyponatremia also complicates patient care and is associated with increased morbidity and mortality, particularly among patients with congestive heart failure. Conventional treatments for hyponatremia (e.g. fluid restriction, diuretic treatment, and sodium replacement) may not be effective in all patients and can lead to significant adverse events. Preclinical and clinical trial results have shown that AVP receptor antagonism is a promising approach to the treatment of hyponatremia that directly addresses the effects of increased AVP and consequent decreased aquaresis, the electrolyte-sparing excretion of free water. Agents that antagonize V(2) receptors promote aquaresis and can lead to increased serum sodium. Dual-receptor antagonism, in which both V(2) and V(1A) receptors are blocked, may provide additional benefits in patients with hyponatremia.
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PMID:Hyponatremia, arginine vasopressin dysregulation, and vasopressin receptor antagonism. 1717 May 24