Mechanism, spectrum, consequences and management of hyponatremia in tuberculous meningitis

Abstract

Hyponatremia is the commonest electrolyte abnormality in hospitalized patients and is associated with poor outcome. Hyponatremia is categorized on the basis of serum sodium into severe (< 120 mEq/L), moderate (120-129 mEq/L) and mild (130-134mEq/L) groups. Serum sodium has an important role in maintaining serum osmolality, which is maintained by the action of antidiuretic hormone (ADH) secreted from the posterior pituitary, and natriuretic peptides such as atrial natriuretic peptide and brain natriuretic peptide. These peptides act on kidney tubules via the renin angiotensin aldosterone system. Hyponatremia <120mEq/L or a rapid decline in serum sodium can result in neurological manifestations, ranging from confusion to coma and seizure. Cerebral salt wasting (CSW) and syndrome of inappropriate secretion of ADH (SIADH) are important causes of hyponatremia in tuberculosis meningitis (TBM). CSW is more common than SIADH. The differentiation between CSW and SIADH is important because treatment of one may be detrimental for the other; evidence of hypovolemia in CSW and euvolemia or hypervolemia in SIADH is used for differentiation. In addition, evidence of dehydration, polyuria, negative fluid balance as assessed by intake output chart, weight loss, laboratory evidence and sometimes central venous pressure are helpful in the diagnosis of these disorders. Volume contraction in CSW may be more protracted than hyponatremia and may contribute to border zone infarctions in TBM. Hyponatremia should be promptly and carefully treated by saline and oral salt, while 3% saline should be used in severe hyponatremia with coma and seizure. In refractory patients with hyponatremia, fludrocortisone helps in early normalization of serum sodium without affecting polyuria or functional outcome. In SIADH, V2 receptor antagonist conivaptan or tolvaptan may be used if the patient is not responding to fluid restriction. Fluid restriction in SIADH has not been found to be beneficial in TBM and should be avoided.

Keywords: SIDH; Tuberculous meningitis; cerebral salt wasting; hyponatremia; natriuretic peptide; stroke.

Figure 1.. Duration of polyuria and onset of stroke in tuberculous meningitis patients with cerebral salt wasting (CSW).

The vertical grey bars denote the onset (lower limit) and subsidence (upper limit) of polyuria in each patient. The red traingles denote the day of stroke after admission. A total of 10 out of 16 patients developed stroke during CSW (high urinary output). (Reproduced from Misra UK, Kalita J, Kumar M, et al.: Hypovolemia due to cerebral salt wasting may contribute to stroke in tuberculous meningitis. QJM. 2018; 111(7): 455–60. with permission).

Figure 2.. Cranial T2 FLAIR MRI axial sections in a 45- year-old male, stage III tuberculous meningitis (TBM) with type 2 diabetes mellitus and hypertension, and a 15-year-old male, stage III TBM patient.

( A and B) Infarcts are shown in the ( A) ischemic and ( B) peri ventricular region bilaterally (internal border zone) of the 45- year-old male. Cerebral salt wasting (CSW) was diagnosed on Day 40. The patient developed infarctions on Day 68 of admission. Hyponatremia was corrected after 12 days and urinary output normalized after 3 months. ( C) 15-year-old male showing asymptomatic infarct in right peri-ventricular white matter (internal border zone) with CSW diagnosed at admission (Day 1). (Reproduced from Misra UK, Kalita J, Kumar M, et al.: Hypovolemia due to cerebral salt wasting may contribute to stroke in tuberculous meningitis. QJM. 2018; 111(7): 455–60; with permission) .

Figure 3.. Schematic diagram shows management of hyponatremia.

art= arterial.