Hyponatremia in a patient with meningitis and Crohn disease: Cerebral salt wasting or SIADH?

Sir,

Electrolyte disorders, especially hyponatremia, are common problems in patients with CNS disease. Although hyponatremia due to CNS disease is often attributed to SIADH, CSW and SIADH have similar laboratory findings and they overlap in their association with intracranial diseases.[12] In SIADH, there is a relatively volume-expanded state with hyponatremia, decreased serum osmolality, and inappropriately high ADH.[3] On the other hand, CSW is characterized by natriuresis with concomitant diuresis, decreased intravascular volume, and extracellular fluid depletion.[23] Thus, SIADH and CSW treatment require different approaches. SIADH treatment requires fluid restriction, whereas CSW treatment consists of fluid replacement with saline and mineralocorticoid.[45] Improper therapy can worsen the underlying condition and it is important that clinicians distinguish properly between CSW and SIADH.[67]

A 16 year-old male was admitted to the hospital with nausea and vomiting. One week before admission, his oral intake had become poor and he had been vomiting 5–6 times a day for two weeks. Three to four days before the hospital admission, his stools were bloody. He was treated as Crohn disease patient for three months with sulfasalazin, ferrous sulphate, folic acid, and omega 3.

Physical examination revealed that the patient was dehydrated and lethargic. His temperature was 38.2°C, the pulse rate was 100 beats per minute, and the blood pressure 90/60 mm Hg. His weight was 31 kg (< 3 P) and his height was 153 cm (< 3 P). His eyes were sunken and there was tenting of the skin. Bowel movements were positive and increased bowel sounds were heard by auscultation. He had nuchal rigidity and positive Kernig and Brudzinski signs. The other results of the physical examination were normal.

Laboratory tests performed after admission showed: the complete blood count WBC 6600/mm3, hemoglobin 9.7 g/dL, platelets 119000/mm3. A peripheric blood smear showed 87% neutrophils, 17% leukocytes, hypochromia, and anisocytosis. The serum contained 127 mmol/L sodium, 3.95 mmol/L potassium, 96.6 mmol/L chloride, 5 mg/dL urea, 0.4 mg/dL creatinine, and 0.7 mg/dL uric acid.

Monteux test was negative and a computed tomographic (CT) scan of the head was normal. Cerebrospinal fluid examination revealed a lymphocytic picture (130 cells/mm3) with 65 mg/dL (0–45 normal) protein and 20 mg/dL glucose levels. Simultaneously performed laboratory tests revealed that levels of serum glucose and chloride were 90 mg/dL and 108 mmol/L respectively.

Based on these findings indicating meningitis, intravenous ceftriaksone was started and 20 mL/kg normal saline was given in one hour for volume depletion. This was followed by hypertonic NaCl (3% NaCl) with an IV fluid dose of 2500 mL/m2/day. On day two, hemiplegia developed in the right side of the body and a CT scan of the head was repeated and found to be normal. Biochemical tests were repeated and severe hyponatremia was detected (Na: 118 mmol/L) despite saline resuscitation. Hypovolemia persisted without any source of GIS fluid loss; a normal serum urea level (4.8 mg/dL) and increased urine output (4.5 L/day) were also noted. Serum osmolality was 225 mOsm/kg and urine Na 294 mmol/L. However, SIADH was ruled out because of the increased fractional Na (3.1%) and uric acid (3.2%) excretion seen with the observed polyuria.

The patient had the clinical and laboratory findings of CSW and was managed with IV fluids: hypertonic sodium solutions and IV corticosteroids (prednisolone 2 mg/kg/day). Serum sodium levels increased gradually to the level of 136 mmol/L [Figure 1]. On day 10, the patient became confused, developed respiratory distress, and died on day 11.

Figure 1

Serum sodium level and urine output in the course of the disease

Electrolyte disorders are common problems in patients with central nervous system insult such as trauma, infection, or hemorrhage. The management of electrolyte and fluid balance in these patients can be difficult. The serum sodium levels, rapid alterations of sodium levels, and the duration of hyponatremia are factors that worsen the underlying CNS conditions.

How common CSW is uncertain. Previous studies show that it is as common as SIADH whereas some studies say that it is overstated.[8] CSW is regarded as a rare entity[5] in childhood and its prevalence is insufficient, there being mostly isolated case reports and the report of one small series in literature.

Central nervous system infections, including tuberculosis meningitis, bacterial meningitis, and viral meningoencephalitis can cause cerebral salt wasting. However, there are a few case reports in literature that describe the association of CSW with infection.[9] The mechanism by which cerebral disease leads to renal salt wasting is not well known. Decisions regarding treatment can be taken by investigating the levels of natriuretic peptides (ADH, ANP, BNP, renin-aldosterone axis elements). AVP and BNP were shown to be elevated eight days after cerebral injury when compared to the controls.[4] However, this may not be an universal finding in all patients.[5] Controversy exists around the cause of hyponatremia in tuberculosis meningitis as some studies report the cause to be inappropriate secretion of ADH whereas others cite increased ANP levels as the cause.[1011]

Due to the distinction between CSW and SIADH, CWS responds to sodium and water replacement, whereas SIADH is treated by fluid restriction. Our case had symptomatic hyponatremia with polyuria and natriuresis. Urinary Na and fractional excretion of Na were also high. This salt-losing condition ruled out SIADH wherein urine output is usually high. This feature plays an important role in the diagnosis, as discussed in previous reports.[8] In our patient, a high urine output (> 4–5 litres per day) lasted for five days. A diagnosis of CSW was made on the basis of the following findings: 1. marked natriuresis with negative sodium and water balance, 2. the patient's hyponatremic and relatively salt-depleted state despite infusions of hypertonic saline solutions, and 3. persistent high fractional uric acid excretion rates throughout the course of the disease.

There is no evidence in literature that Crohn disease and/or salazopryrine cause salt wasting.

The key feature of CSW is the hyponatremia which is the initial marker that leads to the diagnosis. The next most important event is treating and protecting the patient from its negative effects by matching the Na and water input to their output. Mineralocorticoid therapy was found to be effective in most patients. Doses of 0.1–0.4 mg/day fludrocortisone with saline and water replacement increased Na concentrations to normal serum levels.[49] We could not obtain fludrocortisone and other steroids which have higher mineralocorticiod activity than prednisolone, therefore, 2 mg/kg/day prednisolone doses were used. Sodium levels increased to 136 mmol/L with this additional therapy.

In conclusion, one reason for hyponatremia in patients with meningitis can be cerebral salt wasting and management must take this situation into consideration.[12] Glucocorticosteroids can be used as alternatives for the mineralocorticoid, fludrocortisone, when it can not be obtained.