Cerebral salt wasting following tuberculous meningoencephalitis in an infant.

In patients with central nervous system disease, life-threatening hyponatremia can result from either the syndrome of inappropriate secretion of antidiuretic hormone or cerebral salt wasting. Clinical manifestations of the two conditions may be similar, but their pathogeneses and management protocols are different. Cerebral salt wasting syndrome is a disorder in which excessive natriuresis and hyponatremia occurs in patients with intracranial diseases. We report a 6-month-old girl with CSWS associated with tuberculous meningoencephalitis. She was diagnosed as having CSWS on the basis of hypovolemia, polyuria, natriuresis, and the relatively high level of fractional excretion of uric acid. Aggressive replacement of urine salt and water losses using 0.9% or 3% sodium chloride was done. Fludrocortisone was started at 0.1 mg twice daily on the seventh day of admission and was continued for 17 days.

Introduction

Hyponatremia is a common electrolyte abnormality seen in hospitalized patients. It is particularly observed in neurological disorders because of the major role of central nervous system (CNS) in the regulation of sodium and water homeostasis.[1] The main differential diagnoses in such a situation includes: Cerebral salt wasting syndrome (CSWS) and the syndrome of inappropriate secretion of antidiuretic hormone (SIADH).[23] Differentiation of CSWS from SIADH is crucial, as their management is completely different. The use of fludrocortisone in the treatment of CSWS has been reported in isolated pediatric cases.[3-5] We report an infant with tuberculous meningoencephalitis who developed CSWS and was managed with fludrocortisone.

Case Report

A 6-month-old girl presented with low grade continuous fever, weight loss (one month), and right focal seizure. She was exclusively breast fed. Her father was receiving treatment for pulmonary tuberculosis. On admission, she was in Glasgow coma scale (GCS) of 5 (Eyes 1, Motor 2, Verbal 2). Her blood pressure was 90/60 mm Hg. Her weight was 4.9 kg and length was 57 cm (both below 5th percentile for age and sex). Mild pallor was present. She demonstrated no cranial nerve palsy. There was hypertonia in all four limbs, brisk deep tendon reflexes, and absent abdominal reflex. There were no meningeal signs or involuntary movements. Systemic examination was normal. Investigations revealed: Hemoglobin 9.8 gm/dL, total leucocyte count 12300/cumm (neutrophils 60%, lymphocyte 40%), platelet count 2.1 lakh/cumm. Cerebrospinal fluid examination showed 360 cells (neutrophils 60%, lymphocytes 40%), protein 160 mg and sugar 38 mg/dL. Liver function, renal function tests, serum electrolytes, and serum calcium were normal. Urine output on the day of admission was 2.2 mL/kg/hour. Mantoux test was positive i.e. 24 mm. Magnetic resonance imaging of the brain was s/o tuberculous meningoencephalitis [Figure 1]. Intravenous fluids, intravenous mannitol, dexamethasone, and antituberculous therapy were started. There was no improvement in her sensorium. On the fifth day of admission, she developed hyponatremia, polyuria (8.6 mL/kg/hour), and hypotension [Table 1]. A diagnosis of CSWS was made on the basis of above investigations. Mannitol was discontinued. Fluid correction was given (volume-to-volume) with normal saline. Despite volume-to-volume correction with normal saline, the serum sodium dropped to 108 mEq/L on the seventh day. Urine output was 17 mL/kg/hour and urinary sodium 190 mEq/L. Hence, sodium correction with 3% saline and fludrocortisone (0.1 mg/day) were started on the seventh day. Fludrocortisone was gradually increased to 0.6 mg/day with monitoring of serum potassium and blood pressure. Over the next 7 days, there was a gradual increase in the serum sodium with improvement in the sensorium ([GCS 10, E4M3V3]). Although serum sodium had normalized, fludrocortisone was continued because of polyuria. The urine output gradually decreased to <2 mL/kg/hour on the 24th hospital day and fludrocortisone was stopped. The serial values of serum sodium, urine output, and urine sodium are shown in Table 1. Her sensorium had improved and GCS score was 13 at the time of discharge.

Figure 1

T2 weighted coronal image showing hyperintensity along cortical gyri in parafalci region and bilateral temporal lobes s/o meningoencephalitis. Also seen is a hypotense focus in subcortical parafalcine location s/o focal hemorrhage

Table 1

Serial values of investigations done in the patient

Discussion

The concept of CSWS was first described by Peters et al. in 1950.[6] Initially, the loss of CNS control on renal sodium regulation was considered the cause of hyponatremia and the entity was termed CSWS.[6] However, with the subsequent description of SIADH by Schwartz et al., CSWS became viewed as either an extremely rare disorder or a misnomer for what was truly SIADH.[7] Only recently, CSWS has been thought as a distinct entity with some authors considering it to be more common than SIADH.[89] The pathophysiology and treatment of these two conditions is different.[2-4] In SIADH, there is renal conservation of water and dilutional hyponatremia. In CSWS, there is renal salt and water loss, resulting in hyponatremia and decreased intravascular volume. Hence, SIADH is treated by fluid restriction and CSWS by sodium and water replacement.[2-4] CSWS has been described with tuberculous meningitis, encephalitis, brain tumors, and following neurosurgical interventions.[3-5] The failure of renin-aldosterone system, vasopressin secretion due to volume depletion and excessive secretion of humoral factors, such as atrial natriuretic peptide (ANP), brain natriuretic peptide (BNP), and ouabain-like factors are responsible for renal salt wasting in cerebral disease.[2451011] The failure of renin-aldosterone levels to rise accounts for the lack of renal potassium wasting.[11]

The critical point for distinguishing CSWS from SIADH is the presence of hypovolemia and a negative salt balance.[341011] Table 2 shows the comparison of SIADH and CSWS.[21011] Patients with CSWS have symptoms and laboratory findings suggestive of intravascular volume depletion.[1011] The fractional excretion of uric acid can be used to distinguish CSWS from SIADH.[211] In both the syndromes, hyponatremia co-exists with hypouricemia and elevated fractional excretion of uric acid. When hyponatremia is corrected, hypouricemia and elevated fractional excretion of uric acid are corrected in SIADH, but persists in CSWS. Definitive diagnosis of CSWS is made by documenting elevated levels of the natriuretic peptides.[3] These could not be done in our patient due to financial constraints. Replacement of urine salt and water losses using 0.9% or 3% sodium chloride is the cornerstone of treatment of CSWS.[2-410] The use of hypertonic saline solution should be restricted to situations with very low serum sodium (<120 mEq/L).[10] Rapid correction of hyponatremia should be avoided, as it can cause pontine or extrapontine myelinolysis. Once euvolemia is achieved, the goal of therapy is to maintain a positive salt balance and to prevent volume depletion by matching the urinary output with volume repletion. Fludrocortisone can be used in doses of 0.1 to 1 mg/day to treat the CSWS.[2-410] It exerts its effects by stimulating reabsorption of sodium and water in the distal tubule, lead-ing to expansion of the intravascular volume. It is however difficult to put an exact time frame on when fludrocortisone should be commenced. However, it has been suggested that this could be considered after several days when the diagnosis is clear and management by replacement of salt and fluids is not readily achieved or is causing practical difficulties.[4] The common adverse effects as-sociated with fludrocortisone include hypokalemia and hypertension.[24] The length of therapy depends on the clinical course of the hyponatremia and the underlying pathol-ogy associated with CSW. Once the underlying pathology is corrected, CSWS is usually a transient condition that resolves within three to four weeks.[23] Hence, long-term therapy is usually not needed.

Table 2

Comparison of biochemical markers of SIADH and CSWS