Hyponatremia is a well-known disorder commonly faced by clinicians managing neurologically ill patients. Neurological disorders are often associated with hyponatremia during their acute presentation and can be associated with specific neurologic etiologies and symptoms. Patients may present with hyponatremia with traumatic brain injury, develop hyponatremia subacutely following aneurysmal subarachnoid hemorrhage, or may manifest with seizures due to hyponatremia itself. Clinicians caring for the neurologically ill patient should be well versed in identifying these early signs, symptoms, and etiologies of hyponatremia. Early diagnosis and treatment can potentially avoid neurologic and systemic complications in these patients and improve outcomes. This review focuses on the causes and findings of hyponatremia in the neurologically ill patient and discusses the pathophysiology, diagnoses, and treatment strategies for commonly encountered etiologies.
YeeAHBurnsJDWijdicksEF. Cerebral salt wasting: pathophysiology, diagnosis, and treatment. Neurosurg Clin N Am. 2010;21(2):339–352.
2.
HumanTCookAMAngerB, et al.Treatment of hyponatremia in patients with acute neurological injury. Neurocrit Care. 2017;27(2):242–248.
3.
DiringerMNZazuliaAR. Hyponatremia in neurologic patients: consequences and approaches to treatment. Neurologist. 2006;12(3):117–126.
4.
ArieffAILlachFMassrySG. Neurological manifestations and morbidity of hyponatremia: correlation with brain water and electrolytes. Medicine. 1976;55(2):121–129.
5.
MoritzMLAyusJC. The pathophysiology and treatment of hyponatraemic encephalopathy: an update. Nephrol Dial Transplant. 2003;18(12):2486–2491.
6.
BourqueCW. Central mechanisms of osmosensation and systemic osmoregulation. Nat Rev Neurosci. 2008;9(7):519–531.
7.
SternsRH. Disorders of plasma sodium—causes, consequences, and correction. N Engl J Med. 2015;372(1):55–65.
8.
AndersonRJChungHMKlugeRSchrierRW. Hyponatremia: a prospective analysis of its epidemiology and the pathogenetic role of vasopressin. Ann Intern Med. 1985;102(2):164–168.
9.
BichetDG. Physiopathology of hereditary polyuric states: a molecular view of renal function. Swiss Med Wkly. 2012;142:w13613.
10.
Pasantes-MoralesHFrancoROrdazBOchoaLD. Mechanisms counteracting swelling in brain cells during hyponatremia. Arch Med Res. 2002;33(3):237–244.
11.
VerbalisJG. Brain volume regulation in response to changes in osmolality. Neuroscience. 2010;168(4):862–870.
12.
Pasantes-MoralesHCruz-RangelS. Brain volume regulation: osmolytes and aquaporin perspectives. Neuroscience. 2010;168(4):871–884.
13.
VerbalisJGGoldsmithSRGreenbergA, et al.Diagnosis, evaluation, and treatment of hyponatremia: expert panel recommendations. Am J Med. 2013;126(10 suppl 1):S1–42.
14.
LiottaEMRomanovaALLizzaBD, et al.Osmotic shifts, cerebral edema, and neurologic deterioration in severe hepatic encephalopathy. Crit Care Med. 2018;46(2):280–289.
15.
PetersJPWeltLGSimsEAOrloffJNeedhamJ. A salt-wasting syndrome associated with cerebral disease. Trans Assoc Am Physicians. 1950;63:57–64.
16.
WijdicksEFRopperAHHunnicuttEJRichardsonGSNathansonJA. A trial natriuretic factor and salt wasting after aneurysmal subarachnoid hemorrhage. Stroke. 1991;22(12):1519–1524.
17.
SudohTMinaminoNKangawaKMatsuoH. C-type natriuretic peptide (CNP): a new member of natriuretic peptide family identified in porcine brain. Biochem Biophys Res Commun. 1990;168(2):863–870.
18.
DillinghamMAAndersonRJ. Inhibition of vasopressin action by atrial natriuretic factor. Science. 1986;231(4745):1572–1573.
19.
KikumotoKKuboAHayashiY, et al.Increased plasma concentration of adrenomedullin in patients with subarachnoid hemorrhage. Anesth Analg. 1998;87(4):859–863.
20.
KuboYOgasawaraKKakinoSKashimuraHYoshidaKOgawaA. Cerebrospinal fluid adrenomedullin concentration correlates with hyponatremia and delayed ischemic neurological deficits after subarachnoid hemorrhage. Cerebrovasc Dis. 2008;25(1-2):164–169.
21.
WijdicksEFVermeulenMten HaafJAHijdraABakkerWHvan GijnJ. Volume depletion and natriuresis in patients with a ruptured intracranial aneurysm. Ann Neurol. 1985;18(2):211–216.
22.
KatayamaYHaraokaJHirabayashiH, et al.A randomized controlled trial of hydrocortisone against hyponatremia in patients with aneurysmal subarachnoid hemorrhage. Stroke. 2007;38(8):2373–2375.
23.
EllisonDHBerlT. Clinical practice. The syndrome of inappropriate antidiuresis. N Engl J Med. 2007;356(20):2064–2072.
24.
RobertsonGL. Regulation of arginine vasopressin in the syndrome of inappropriate antidiuresis. Am J Med. 2006;119(7 suppl 1):S36–S42.
25.
FenskeWKChrist-CrainMHorningA, et al.A copeptin-based classification of the osmoregulatory defects in the syndrome of inappropriate antidiuresis. J Am Soc Nephrol. 2014;25(10):2376–2383.
26.
JohnsonBEChuteJPRushinJ, et al.A prospective study of patients with lung cancer and hyponatremia of malignancy. Am J Respir Crit Care Med. 1997;156(5):1669–1678.
27.
LiamisGMilionisHElisafM. A review of drug-induced hyponatremia. Am J Kidney Dis. 2008;52(1):144–153.
28.
GowrishankarMLinSHMallieJPOhMSHalperinML. Acute hyponatremia in the perioperative period: insights into its pathophysiology and recommendations for management. Clin Nephrol. 1998;50(6):352–360.
29.
HumphriesJESiragyH. Significant hyponatremia following DDAVP administration in a healthy adult. Am J Hematol. 1993;44(1):12–15.
30.
VerbalisJGGreenbergABurstV, et al.Diagnosing and treating the syndrome of inappropriate antidiuretic hormone secretion. Am J Med. 2016;129(5):537.e539-537.e523.
31.
MiellJDhanjalPJamookeeahC. Evidence for the use of demeclocycline in the treatment of hyponatraemia secondary to SIADH: a systematic review. Int J Clin Pract. 2015;69(12):1396–1417.
32.
LehrichRWGreenbergA. Hyponatremia and the use of vasopressin receptor antagonists in critically ill patients. J Intensive Care Med. 2012;27(4):207–218.
33.
UdelsonJESmithWBHendrixGH, et al.Acute hemodynamic effects of conivaptan, a dual V(1A) and V(2) vasopressin receptor antagonist, in patients with advanced heart failure. Circulation. 2001;104(20):2417–2423.
34.
GaltonCDeemSYanezND, et al.Open-label randomized trial of the safety and efficacy of a single dose conivaptan to raise serum sodium in patients with traumatic brain injury. Neurocrit Care. 2011;14(3):354–360.
35.
NaidechAMPaparelloJLieblingSM, et al.Use of conivaptan (Vaprisol) for hyponatremic neuro-ICU patients. Neurocrit Care. 2010;13(1):57–61.
36.
KonstamMAGheorghiadeMBurnettJCJr, et al.Effects of oral tolvaptan in patients hospitalized for worsening heart failure: the EVEREST Outcome Trial. JAMA. 2007;297(12):1319–1331.
37.
RobertsonGL. Vaptans for the treatment of hyponatremia. Nat Rev Endocrinol. 2011;7(3):151–161.
38.
UchinoAYuzurihaTMurakamiM, et al.Magnetic resonance imaging of sequelae of central pontine myelinolysis in chronic alcohol abusers. Neuroradiology. 2003;45(12):877–880.
39.
SternsRHThomasDJHerndonRM. Brain dehydration and neurologic deterioration after rapid correction of hyponatremia. Kidney Int. 1989;35(1):69–75.
40.
SternsRHRiggsJESchochetSSJr. Osmotic demyelination syndrome following correction of hyponatremia. N Engl J Med. 1986;314(24):1535–1542.
41.
YunBCKimWRBensonJT, et al.Impact of pretransplant hyponatremia on outcome following liver transplantation. Hepatology. 2009;49(5):1610–1615.
42.
MartinRJ. Central pontine and extrapontine myelinolysis: the osmotic demyelination syndromes. J Neurol Neurosurg Psychiatry. 2004;75(suppl 3):iii22–iii28.
43.
BrunnerJERedmondJMHaggarAMKrugerDFEliasSB. Central pontine myelinolysis and pontine lesions after rapid correction of hyponatremia: a prospective magnetic resonance imaging study. Ann Neurol. 1990;27(1):61–66.
44.
AllemanAM. Osmotic demyelination syndrome: central pontine myelinolysis and extrapontine myelinolysis. Semin Ultrasound CT MR. 2014;35(2):153–159.
45.
SoupartAPenninckxRStenuitAPerierODecauxG. Reinduction of hyponatremia improves survival in rats with myelinolysis-related neurologic symptoms. J Neuropathol Exp Neurol. 1996;55(5):594–601.
46.
PerianayagamASternsRHSilverSM, et al.DDAVP is effective in preventing and reversing inadvertent overcorrection of hyponatremia. Clin J Am Soc Nephrol. 2008;3(2):331–336.
47.
SugimuraYMuraseTTakefujiS, et al.Protective effect of dexamethasone on osmotic-induced demyelination in rats. Exp Neurol. 2005;192(1):178–183.
48.
MengerHJorgJ. Outcome of central pontine and extrapontine myelinolysis (n = 44). J Neurol. 1999;246(8):700–705.
49.
LouisGMegarbaneBLavoueS, et al.Long-term outcome of patients hospitalized in intensive care units with central or extrapontine myelinolysis. Crit Care Med. 2012;40(3):970–972.
50.
ChangCHLiaoJJChuangCHLeeCT. Recurrent hyponatremia after traumatic brain injury. Am J Med Sci. 2008;335(5):390–393.
51.
SternsRH. Severe symptomatic hyponatremia: treatment and outcome. A study of 64 cases. Ann Intern Med. 1987;107(5):656–664.
52.
MeltonJEPatlakCSPettigrewKDCserrHF. Volume regulatory loss of Na, Cl, and K from rat brain during acute hyponatremia. Am J Physiol. 1987;252(4 pt 2):F661–669.
53.
Gankam KengneFDecauxG. Hyponatremia and the brain. Kidney Int Rep. 2018;3(1):24–35.
54.
SchrierRWGrossPGheorghiadeM, et al.Tolvaptan, a selective oral vasopressin V2-receptor antagonist, for hyponatremia. N Engl J Med. 2006;355(20):2099–2112.
55.
SpasovskiGVanholderRAllolioB, et al.Clinical practice guideline on diagnosis and treatment of hyponatraemia. Nephrol Dial Transplant. 2014;29(suppl 2):i1–i39.
56.
ArieffAIAyusJC. Pathogenesis of hyponatremic encephalopathy. Current concepts. Chest. 1993;103(2):607–610.
57.
CluitmansFHMeindersAE. Management of severe hyponatremia: rapid or slow correction?Am J Med. 1990;88(2):161–166.
58.
RenneboogBMuschWVandemergelXMantoMUDecauxG. Mild chronic hyponatremia is associated with falls, unsteadiness, and attention deficits. Am J Med. 2006;119(1):71.e71-78.
59.
ArieffAIAyusJCFraserCL. Hyponatraemia and death or permanent brain damage in healthy children. BMJ. 1992;304(6836):1218–1222.
60.
CourchesneEChisumHJTownsendJ, et al.Normal brain development and aging: quantitative analysis at in vivo MR imaging in healthy volunteers. Radiology. 2000;216(3):672–682.
61.
AyusJCWheelerJMArieffAI. Postoperative hyponatremic encephalopathy in menstruant women. Ann Intern Med. 1992;117(11):891–897.
62.
AyusJCArieffAI. Pulmonary complications of hyponatremic encephalopathy. Noncardiogenic pulmonary edema and hypercapnic respiratory failure. Chest. 1995;107(2):517–521.
63.
SmithWSMatthayMA. Evidence for a hydrostatic mechanism in human neurogenic pulmonary edema. Chest. 1997;111(5):1326–1333.
64.
AyusJCAchingerSGArieffA. Brain cell volume regulation in hyponatremia: role of sex, age, vasopressin, and hypoxia. Am J Physiol Renal Physiol. 2008;295(3):F619–624.
65.
QureshiAISuarezJIBhardwajA, et al.Use of hypertonic (3%) saline/acetate infusion in the treatment of cerebral edema: effect on intracranial pressure and lateral displacement of the brain. Crit Care Med. 1998;26(3):440–446.
66.
QureshiAISuarezJI. Use of hypertonic saline solutions in treatment of cerebral edema and intracranial hypertension. Crit Care Med. 2000;28(9):3301–3313.
67.
BentsenGBreivikHLundarTStubhaugA. Hypertonic saline (7.2%) in 6% hydroxyethyl starch reduces intracranial pressure and improves hemodynamics in a placebo-controlled study involving stable patients with subarachnoid hemorrhage. Crit Care Med. 2006;34(12):2912–2917.
SmithSJ. EEG in the diagnosis, classification, and management of patients with epilepsy. J Neurol Neurosurg Psychiatry. 2005;76(suppl 2):ii2–ii7.
70.
NigroNWinzelerBSuter-WidmerI, et al.Symptoms and characteristics of individuals with profound hyponatremia: a prospective multicenter observational study. J Am Geriatr Soc. 2015;63(3):470–475.
71.
SpasovskiGVanholderRAllolioB, et al.Clinical practice guideline on diagnosis and treatment of hyponatraemia. Eur J Endocrinol. 2014;170(3):G1–47.
72.
SarnaikAPMeertKHackbarthRFleischmannL. Management of hyponatremic seizures in children with hypertonic saline: a safe and effective strategy. Crit Care Med. 1991;19(6):758–762.
73.
Castilla-GuerraLdel Carmen Fernandez-MorenoMLopez-ChozasJMFernandez-BolanosR. Electrolytes disturbances and seizures. Epilepsia. 2006;47(12):1990–1998.
