Case Report

A 26 year old man was admitted through the A&E department to a local district general hospital with four days of episodic confusion. There was no significant past medical or family history. Recreational drug use was denied and a urine screen was negative. A diagnosis of toxic encephalopathy was made. On day 2 he became pyrexial and agitated, and was sedated with haloperidol. Otherwise his examination was unremarkable, and his Glasgow coma scale (GCS) was 15, with no focal neurology. Routine blood tests, chest x ray, and computed tomography (CT) of the head were normal. CSF examination revealed a lymphocytic picture (130 cells/cm) with a protein of 1.9 g/l and a glucose of 2.3 mmol/l. A diagnosis of probable viral meningoencephalitis was made and he was started on intravenous acyclovir, together with benzylpenicillin, clarythromycin, and metronidazole.

On day 4 he remained pyrexial and confused, and he developed respiratory distress with clinical and radiographic consolidation in the right mid/lower zones. He became hypoxic and required intubation.

He was transferred to a tertiary intensive care unit. Repeat routine blood tests, blood cultures, atypical serology, urine, and protected catheter specimens were unremarkable. During day 5 he was rapidly weaned off sedation and extubated. His GCS was 15, with no focal neurology. Over the course of 12 hours his gas exchange again deteriorated owing to collapse of his left lung. Following reintubation, bronchoscopy revealed viscid sputum obstructing the left main bronchus. Sedation was again weaned (on day 6) and he developed some complex partial seizures. A repeat CT revealed no intracranial pathology, and repeat lumbar puncture showed a lymphocytosis of 5 cells/cm. On day 8 an EEG revealed anterior delta rhythm activity, consistent with an encephalopathy. Polymerase chain reaction tests for herpex simplex and varicella were negative.

On day 9 his GCS deteriorated to 8 and he needed increased ventilatory support. An acute hyponatraemia was noted (plasma sodium 132 mmol/l, falling to 123 mmol/l over 12 hours). It was also noted that the central venous pressure fell, urine output increased (6 litres in 24 hours), and he lost 1.5 kg in weight. Biochemistry supported the diagnosis of cerebral salt wasting syndrome, with a high urine sodium loss (148 mmol/l), normal serum osmolality (280 mmol/l), a urine osmolality of 432 mmol/l, and normal urea. In the picture of SIADH one would instead see a relatively normal central venous pressure and a low volume of “inappropriately” concentrated urine (urine sodium > 20 mmol/l and urine osmolality greater than plasma osmolality). Biochemically, SIADH would be characterised by a lower serum osmolality (< 260 mmol) and a low or low normal plasma urea, indicating serum dilution with excess water (table 1⇓).

Intravenous 0.9% saline was begun (initially at a rate of 3.5 ml/kg/h), and a single dose of 100 mg of hydrocortisone was given (table 1⇑). Over the next 36 hours the serum sodium normalised and the high renal sodium loss ceased. During treatment the urine osmolality fell from 432 mmol/kg to 256 mmol/kg, which represents a state of “hyperhydration” as a result of the large volume fluid replacement. He was extubated two days later and went on to make a full recovery.

Discussion

Cerebral salt wasting syndrome was first described by Peters et al,¹ seven years before the identification of SIADH. Despite outward similarities, the pathophysiology, biochemistry, and treatment of these two conditions is very different (table 2⇓). In SIADH there is renal conservation of water and dilutional hyponatraemia. Cerebral salt wasting syndrome is defined as a natriuresis with sodium and water loss and a decrease in intravascular volume.² As a result, SIADH is treated by fluid restriction and cerebral salt wasting responds to sodium and water replacement.

Cerebral salt wasting syndrome has been reported in neurosurgical cases³ and in a case of tuberculous meningitis.⁴ However, there are no reports of this condition in other infective neurological processes. Its mechanism has been linked with natriuretic peptides similar to atrial natriuretic factor. Both brain natriuretic peptide and C-type natriuretic peptide have been implicated, and indeed brain natriuretic peptide has been shown to be increased in early subarachnoid haemorrhage.⁵

This case shows the difference between cerebral salt wasting syndrome and SIADH, and the importance of correct diagnosis and correct treatment. In cerebral salt wasting syndrome, saline infusion under central venous pressure guidance will correct the metabolic deficit, and in our case the mineralocorticoid effect of intravenous hydrocortisone helped to reduce the renal sodium loss. The mineralocorticoid fludrocortisone acetate acts directly on the renal tubule to reduce sodium excretion, and Hasan et al have shown that it significantly reduces the negative sodium balance in similar cases.⁶