Chronic hyponatremia – Why care? A case report

Hyponatremia (<136 mmol/L) is the most common electrolyte disturbance []. It presents with a broad range of clinical expressions and very different treatment indications and strategies. The acute severe hyponatremia ([Na⁺] <125 mmol/L for less than 48 h) with serious complications as brain edema, seizures and death has well-defined treatment strategies and needs acute medical intervention. The mild to moderate chronic hyponatremia ([Na⁺] 125–136 mmol/L for more than 48 h) has a much less well-defined treatment strategy. It is often perceived as asymptomatic and treatment resistant. Chronic hyponatremia does however pose a grave problem for many patients treated with various antiepileptic drugs (AEDs) and may have serious consequences as illustrated in this case report.

The patient, a 46-year old woman, was diagnosed in 1985 (at age of 14) with idiopathic focal epilepsy, as no pathology was found by cerebral MRI. The diagnosis was supported by electroencephalographic findings in form of bi-temporal paroxystic activity. The patient was treated with various AEDs until 2012 with limited effect due to an unsatisfactory seizure control and several severe side-effects.

In November 2012, the patient was started on monotherapy with eslicarbazepine acetate (Zebinix, Eisai, Stockholm, Sweden) (1200 mg daily) and obtained almost complete seizure control with only one side-effect in the form of asymptomatic hyponatremia (Fig. 1). At the end of September 2013 the patient was prescribed the antidepressant citalopram (Cipramil, Lundbeck, Valby, Denmark) (10 mg daily). Three weeks later, in October 2013, she was admitted to the ER due to a tonic-clonic seizure. Upon arrival the seizure had stopped and apart from appearing post-ictal the patients was generally well and could not relate any current health wise complaints or illness leading up to the seizure. The physical examination was normal without any neurological sign. The blood test taken on arrival at the ER (Table 1) showed severe hyponatremia (118 mmol/L), a slightly decreased creatinine and potassium and a normal blood glucose. There were no seizure-provoking factors other than hyponatremia, which was corrected with intravenous isotonic saline before discharge. At the following consultation with her neurologist the treatment with citalopram was withdrawn and the possibility of changing AED was discussed, but the patient wished to continue treatment with eslicarbazepine acetate. Instead she was started on salt tablets (1.25 g daily) but for unknown reasons the patient stopped taking the supplement shortly after at her own will and the hyponatremia remained.

In October 2017 the patient was again admitted to the ER with two consecutive tonic-clonic seizures only hours apart. At the time of admission the patient was post-ictal but the physical as well as the neurological examinations were normal. The blood tests taken upon admission (Table 1) showed severe hyponatremia (119 mmol/L), a slightly decreased creatinine and a normal blood glucose. When asked about recent changes in medication, lifestyle or other provoking factors the patient told that she had been on a juice-diet consisting of only fruit- and vegetable-juice for the past two days, without consulting her physician. No other provoking factors were found. After correction of sodium the patient was discharged.

At the following consultation the patient was still not interested in changing medication but was started on an intensive correction of the chronic hyponatremia consisting of a salt supplement of 3 g daily. The increased salt intake resulted in an increase in sodium level to 136 mmol/L. The dosage was further increased to 9 g daily, resulting in a sodium level of 139 mmol/L. On this dosage the patient only experienced a slightly increased thirst, but no other side-effects were observed. The blood pressure (137/96 mmHg) was acceptable.

Since November 2012, the patient has only been hospitalized due to seizures related to hyponatremia otherwise she was seizure-free.

Chronic hyponatremia affects up to 46% of patients treated with AEDs []. Especially patients treated with carbamazepine, oxcarbazepine but also eslicarbazepine acetat are at high risk of developing chronic hyponatremia, and although it is often perceived as asymptomatic, accumulating data suggest that chronic hyponatremia is far from benign. Hence, studies have shown that even mild asymptomatic hyponatremia is associated with attention deficits, gait-instability, increased risk of falls, fractures and osteoporosis [].

The hyponatremia in association with AED treatment is believed to be caused by a form of nephrogenic Syndrome of Inappropriate ADH secretion (SIADH) where water retention causes hyponatremia. In this case report, chronic hyponatremia resulted in an increased susceptibility to acute severe hyponatremia and subsequent episodes with seizures. In October 2013, at the time of the first seizure, the patient was recently started on citalopram treatment, an antidepressant which is known to have an SIADH effect causing hyponatremia. It is therefore possible that citalopram had an additive or synergetic effect on the hyponatremia leading to the acute drop in sodium level (118 mmol/L) causing the seizure. In October 2017, at the time of the second seizure, the patient was on a completely liquid juice-diet possibly resulting in an acute drop in serum sodium (119 mmol/L), due to either an increased intake of fluids or decreased intake of salt. A juice diet will approximately contain 2–40 mg of salt pr. 100 g juice, as oppose to the average daily intake for women which is 7–8 g pr. day, and will predispose to hyponatremia [].

There is no doubt that chronic hyponatremia can have severe consequences for the patients affected. This case illustrates that it can lead to both life-threatening complications and may also affect quality of life. Health care professionals should therefore be aware of common risk factors reinforcing the disorder such as initiating other drugs with SIADH effect, diuretics affecting the salt-water balance or lifestyle changes leading to unusual intake of salt and/or water. Therefore, we recommend careful counselling on these matters of patients at risk as well as monitoring the sodium level in relation to regular consultations at least on yearly basis.

This case illustrates that chronic hyponatremia may have profound and life-threatening consequences for the patients’ daily lives. Regardless of the treatment choice it is important to remember that even mild chronic hyponatremia is far from benign, poses a risk to the patient and should not be left unattended.

This research did not receive any specific grant from funding agencies in the public, commercial, or not-for-profit sector.

SSD has received research grants from Eisai Co, Ltd. A-SS has since the initiation of the work been employed by Novo Nordisk A/S.

Sarah Seberg Diemar has received research grants from Eisai Co, Ltd.

Anne-Sophie Sejling has since the initiation of the work been employed by Novo Nordisk A/S.

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