Cerebral Salt Wasting Syndrome in Amyotrophic Lateral Sclerosis: A Rare Occurrence

Hyponatremia is a common electrolyte abnormality in central nervous system (CNS) diseases, most often linked to Syndrome of Inappropriate Antidiuretic Hormone Secretion (SIADH) and less frequently to cerebral salt wasting syndrome (CSWS). Although both share similar biochemical features, they differ in volume status and management, which makes their distinction clinically crucial.[1] CSWS is typically reported with intracranial pathologies but is rarely associated with amyotrophic lateral sclerosis (ALS), a progressive and fatal motor neuron disease. We report a rare case of CSWS occurring in a patient with ALS, which was successfully managed in our intensive care unit (ICU).

A 60-year-old male with a 4-year history of sporadic ALS and quadriparesis was admitted to our ICU with altered sensorium (Glasgow Coma Scale [GCS]: 13) and mild respiratory difficulty. He had been receiving oral riluzole 50 mg twice daily since the time of diagnosis. On admission, his blood pressure and heart rate were 120–125/70–74 mm Hg and 102–105 beats per minute, respectively. In the room air, oxygen saturation was 91 to 92%. The patient was administered supplemental oxygen via face mask at 5 L/min. On clinical examination, the patient appeared dehydrated, and assessment of volume status using point-of-care ultrasound revealed hypovolemia. There was no recent history of gastrointestinal infection or diuretic use. Arterial blood gas analysis on room air revealed hypoxemia (PaO₂: 74 mm Hg), hypercarbia (PaCO₂: 69 mm Hg), profound hyponatremia (serum sodium: 119 mmol/L), and hypokalemia (serum potassium: 2.1 mmol/L), which were subsequently confirmed by laboratory testing. Bilevel positive airway pressure (BiPAP) ventilation was initiated. Laboratory investigations demonstrated low serum osmolality (225.34 mOsm/kg), elevated urine osmolality (448.91 mOsm/kg), increased urine output (2,550 mL/day), and high urinary sodium (99 mmol/L), with a normal thyroid profile ([Table 1]). Clinical examination and laboratory findings were consistent with CSWS.

Table 1 Comparison of biochemical parameters on admission (baseline) and day 4

Parameters (units)	On admission (baseline)	On day 4
Serum sodium (mmol/L)	119	133
Serum osmolality (mOsm/kg)	225.34	277.12
Urine osmolality (mOsm/kg)	448.91	157.8
Urinary sodium (mmol/L)	99	10

Initial management involved correction of hyponatremia with boluses of 3% hypertonic saline (HTS, 100 mL every 45 minutes) and treatment of hypovolemia with 0.9% normal saline, aiming for a serum sodium rise of no more than 12 mmol/L per day. Boluses of 3% HTS (four boluses) were discontinued after 3 hours once the serum sodium reached 125 mmol/L, after which a continuous infusion was initiated at 15 mL/h until the level increased to 130 mmol/L. Serum sodium was monitored by arterial blood gas (ABG) at 45-minute intervals for 3 hours, followed by 4-hourly measurements over the next 24 hours. Simultaneously, hypokalemia was corrected with a potassium chloride infusion administered over 24 hours. The patient's sensorium improved following correction of the dyselectrolytemia. On day 3 of admission, the serum sodium level again decreased from 134 to 125 mmol/L, following which oral fludrocortisone 100 μg once daily and oral salt supplementation (5 g every 6 hours) were started. By day 4, serum sodium had increased to 133 mmol/L, accompanied by a rise in serum osmolality to 277.12 mOsm/kg, a decrease in urine sodium to 10 mmol/L, urine osmolality of 157.8 mOsm/kg, and stabilization of urine output at 1,200 to 1,400 mL/day ([Table 1]). Thereafter, the serum sodium level remained consistently above 130 mmol/L.

In ALS, hyponatremia is most commonly attributed to SIADH.[2] [3] [4] In contrast, reports of CSWS in ALS are scarce. The proposed mechanisms for CSWS include hypothalamic or autonomic dysfunction affecting sodium homeostasis, elevated brain natriuretic peptide levels secondary to intracranial hypertension during carbon dioxide narcosis, stress-induced natriuresis, and diuretic overuse.[5] [6] In our case, carbon dioxide narcosis could possibly be one of the contributing factors.

Riluzole, the U.S. Food and Drug Administration (FDA)-approved oral agent for ALS, acts mainly by inhibiting voltage-gated sodium channels, thereby reducing glutamate release and subsequent glutamatergic neurotoxicity. Its use has been shown to modestly prolong survival in patients with ALS. A previous report suggested a possible association between riluzole and hyponatremia secondary to SIADH, although the evidence remains inconclusive.[7] In our case, the clinical profile and laboratory findings were consistent with CSWS, and the patient responded well to intravenous fluids, oral salt supplementation, and fludrocortisone. However, further evidence is needed to substantiate these observations.

Conflict of Interest

None declared.

• References

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• 2 Inoue Y, Murakami T, Nakamura T. et al. Syndrome of inappropriate antidiuretic hormone secretion associated with amyotrophic lateral sclerosis in a patient developing carbon dioxide narcosis. Intern Med 2017; 56 (07) 797-803
• 3 Ceriz Sr T, Diegues A, Alves SR, Simões P, Blanco MP. Amyotrophic lateral sclerosis-related respiratory failure and association with inappropriate secretion syndrome of the antidiuretic hormone. Cureus 2023; 15 (02) e34851
• 4 Martín FJM, Fernández MG, González MC, Escudero JCM. Urea treatment of syndrome of inappropriate antidiuretic hormone secretion secondary to amyotrophic lateral sclerosis. Eur J Case Rep Intern Med 2020; 7 (04) 001444
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Publication History

Article published online:
11 December 2025