Ticks and Tick-borne Diseases 5 (2014) 284–286

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Ticks and Tick-borne Diseases

journal homepage: www.elsevier.com/locate/ttbdis

Original article

Evaluation of hyponatraemia in patients with tick-borne encephalitis

– A preliminary study
Piotr Czupryna, Anna Moniuszko ∗ , Adam Garkowski, Sławomir Pancewicz,
Katarzyna Guziejko, Joanna Zajkowska
Department of Infectious Diseases and Neuroinfections, Medical University in Białystok, Żurawia Street 14, Białystok 15-540, Poland

a r t i c l e i n f o a b s t r a c t

Article history: Hyponatraemia is one of the most frequently observed, but sometimes overlooked, electrolyte disorder.
Received 21 April 2013 Patients with meningitis are predisposed to develop hypovolaemic hyponatraemia. However, hypona-
Received in revised form traemia in meningitis may also be caused by the syndrome of inappropriate secretion of antidiuretic
19 November 2013
hormone (SIADH). Proper differentiation of these pathomechanisms is crucial in patient’s treatment as
Accepted 30 November 2013
dehydration requires fluid supplementation, while SIADH is treated with fluid restriction. The aim of
Available online 10 February 2014
the present study was the evaluation of frequency, potential causes, and risk factors of hyponatraemia
in patients with tick-borne encephalitis (TBE). A total of 61 patients (22 women, 39 men) aged 18–80
Keywords:
Hyponatraemia
years, with a history of TBE was included in the study. Hyponatraemia was diagnosed when sodium
SIADH concentration was below 135 mmol/l. Hyponatraemia was considered mild when sodium concentration
Tick-borne encephalitis was 130–134 mmol/l, moderate when 125–129 mmol/l, and severe when <125 mmol/l. Among the 61
patients, hyponatraemia was observed in 41% (25 patients). In 20 patients (33%), hyponatraemia was
mild, in 3 (5%) it was moderate, and in 2 (3%) severe. Two patients with severe hyponatraemia and one
with moderate hyponatraemia fulfilled the SIADH criteria. In the non-SIADH patients, sodium concen-
tration normalized within 1–2 (1.1 ± 0.2) days while in the SIADH group, the disturbances lasted for 4–8
(6 ± 2) days. Sodium concentration correlated with patients age (R Spearmann – 0.27, p < 0.05). There
were no significant differences as far as gender or clinical form of the disease are concerned. Hypona-
traemia, usually mild, is a common disorder in the course of TBE, although it is not significantly more
frequent than in other hospitalized patients. Dehydration seems to be the main cause of hyponatraemia
in the course of TBE. SIADH is a less common cause of hyponatraemia in the course of TBE, although it
should be taken into consideration as the treatment differs significantly. Patients >60 years of age with
TBE are more susceptible to hyponatraemia than younger patients.
© 2014 Elsevier GmbH. All rights reserved.

Introduction volume status into hypo-, eu-, and hypervolaemic hyponatraemia

Hyponatraemia is one of the most frequently observed,
but sometimes overlooked, electrolyte disorder in hospitalized
patients. It is reported that mild hyponatraemia occurs in 15–30% of
hospitalized patients and moderate/severe hyponatraemia in 1–7%
(Upadhyay et al., 2006; Ellison and Berl, 2007; Anderson et al., 1985;
Thompson and Hoorn, 2012).
Hyponatraemia represents an excess of water relative to total
body sodium, arising as a result of impaired water excretion by
the kidneys or the depletion of sodium in excess of water. Hypo-
tonic (dilutional) hyponatraemia is classified by the extracellular
∗ Corresponding author. Tel.: +48 85 7409514; fax: +48 85 7409515.
E-mail address: annamoniuszko@op.pl (A. Moniuszko).
(Thompson and Hoorn, 2012).
Hyponatraemia is associated with many diseases, e.g. con-
gestive heart failure, hepatic cirrhosis, nephrotic syndrome,
hypothyroidism, Addison’s disease (Thompson et al., 2012). It
was proven that it is associated with negative outcomes in many
chronic diseases (Sherlock et al., 2009; Boscoe et al., 2006). It
is also a known complication of acute meningitis (Karandanis
and Shulman, 1976; von Vigier et al., 2001). Patients with
meningoencephalitis are predisposed to develop hypovolaemic
hyponatraemia due to dehydration (because of fever, vomits, poor
oral intake). Also anti-oedematous treatment (hyperosmolar fluids
like mannitol) may contribute to a decrease in serum sodium
concentration. However, hyponatraemia in meningoencephalitis
may also be caused by the syndrome of inappropriate secretion
of antidiuretic hormone (SIADH). Proper differentiation of these
pathomechanisms is crucial in patient’s treatment as dehydration

http://dx.doi.org/10.1016/j.ttbdis.2013.11.005
1877-959X/© 2014 Elsevier GmbH. All rights reserved.
 P. Czupryna et al. / Ticks and Tick-borne Diseases 5 (2014) 284–286 285

requires fluid supplementation while SIADH is treated by fluid

restriction. The aim of the study was the evaluation of frequency,
potential causes, and risk factors of hyponatraemia in patients
diagnosed with tick-borne encephalitis (TBE).

Materials and methods

A total of 61 patients (22 women, 39 men) aged 18–80 (mean age

45.7 ± 16.9 years) with a history of TBE treated in the Department
of Infectious Diseases and Neuroinfections (Białystok, Poland) in
the year 2012 were included in the study. None of the patients had
been vaccinated against TBE, and all of them had a history of tick
bites. Diagnosis was made on the basis of clinical manifestation, Fig. 1. Severity of hyponatraemia in different age groups.
cerebrospinal fluid (CSF) examination, and the presence of serum-
specific intrathecal antibodies in the CSF.
Results
Thirty-seven patients (61%) reported a prodromal phase of the
disease. The mean pleocytosis in the CSF was 129.43 ± 178.63 cells
Among 61 patients, hyponatraemia was observed in 41% (25
and mean protein concentration 61.43 ± 21.2 mg/dl. All patients
patients). In 20 patients (33%), hyponatraemia was mild, in 3 (5%)
had IgM antibodies against TBE virus, and 50 patients had IgG
it was moderate, and in 2 (3%) severe (Table 1). Two patients with
antibodies. The mean time of hospitalization was 19.5 ± 15.9 days.
severe hyponatraemia and one with moderate hyponatraemia ful-
Twenty-four patients were diagnosed with meningitis, 34 with
filled SIADH criteria. The patients with mild hyponatraemia in
meningoencephalitis, and 3 with meningoencephalomyelitis. TBE
the majority of cases quickly regained electrolyte concentration
antibody titre was measured with Enzygnost Anti-TBE/FSME Virus
after fluid supplementation. Patients with SIADH were treated with
(IgG, IgM) Siemens test.
water restriction and concentrated natrium.
Patients voluntarily agreed to participate in the study and gave
Comparison of groups with normonatraemia, mild hypona-
their written informed consent. In all patients, electrolytes (sodium,
traemia, and moderate/severe hyponatraemia showed statistically
potassium, chloride), creatinine, urea and uric acid concentrations
significant differences as far as age is concerned. The mean age
in blood, serum and urine osmolality, and urine sodium were
of patients with normonatraemia was 42.2 ± 16.3 years, with
measured. Hyponatraemia was diagnosed when sodium concen-
mild hyponatraemia 46.2 ± 14.6 years, and with moderate/severe
tration was below 135 mmol/l. Hyponatraemia was considered
hyponatraemia 69.4 ± 12.6 years (p < 0.05) (Fig. 1). Patients with
mild when sodium concentration was 130–134 mmol/l, moder-
SIADH (2 males and one female) were significantly older than the
ate when concentration was 125–129 mmol/l, and severe with
rest of the analyzed group (78.3 ± 2.1 years, p < 0.05), and all were
<125 mmol/l.
diagnosed with the encephalomenigitis form of TBE.
SIADH was defined according to the following 10 criteria (Ellison
In 16 patients (26%), hyponatraemia was diagnosed on admis-
and Berl, 2007):
sion, the rest developed hyponatraemia during hospitalization. In
the non-SIADH patients, sodium concentration normalized within
• decreased effective serum osmolality (<275 mOsm/kg of water); 1–2 (1.1 ± 0.2) days while in the SIADH group, the disturbances
• urinary osmolality >100 mOsm/kg of water during hypotonicity; lasted for 4–8 (6 ± 2) days.
• clinical euvolaemia; Sodium concentration correlated with patient age (R Spearmann
• no clinical signs of volume depletion of extracellular fluid; – 0.27, p < 0.05). There were no significant differences as far as gen-
• no orthostasis, tachycardia, decreased skin turgor, or dry mucous der or the clinical form of the disease are concerned (Table 2). Also
membranes; there was no correlation with dosage and duration of mannitol
• no clinical signs of excessive volume of extracellular fluid; treatment.
• no oedema or ascites;
• urinary sodium >40 mmol/l with normal dietary salt intake; Discussion
• normal thyroid and adrenal function;
• no recent use of diuretic agents. Hyponatraemia is a common disorder in meningitis (either bac-
terial or aseptic). Karandanis et al. observed hyponatraemia in
All patients were treated with 20% mannitol, which was consid- 73% of patients with tuberculous meningitis, in 32% with bacte-
ered in the interpretation of results. The initial dose and duration rial meningitis, and in 19% with aseptic meningitis (Sherlock et al.,
of treatment depended on the clinical status of patients. 2009). Our study was focused on the prevalence of hyponatraemia
Statistical analysis was performed using Statistica 10. Groups in TBE patients.
were compared by Kruskal–Wallis and Mann–Whitney tests. A p TBE is a viral disease, transmitted by Ixodes ricinus ticks, with
value <0.05 was considered statistically significant. Correlations an increasing incidence in Europe. In Poland, which is an endemic
were measured by Spearmann’s rank test. region of tick-borne diseases, the highest incidence of TBE is

Table 1
Comparison of patients with normonatraemia and with mild-, moderate- and severe hyponatraemia.

Sodium concentration Age Males Females Mean sodium 20% mannitol

n % n % concentration in Mean initial dosage Mean duration
serum (mmol/l) (ml/day) (days)

Normal (n = 36) 42.2 ± 16.3 22 61 14 39 137.7 ± 1.9 364.5 ± 48.6 9.3 ± 2.3
Mild hyponatraemia (n = 20) 46.2 ± 14.6 13 65 7 35 133 ± 1.2 388.2 ± 92.8 8.8 ± 2.8
Moderate hyponatraemia (n = 3) 62.7 ± 12.2 3 100 0 0 127 ± 1.7 300 ± 100 7.7 ± 4
Severe hyponatraemia (n = 2) 79.5 ± 0.5 1 50 1 50 122.5 ± 2.1 300 10
286 P. Czupryna et al. / Ticks and Tick-borne Diseases 5 (2014) 284–286
Table 2
Comparison of patients with different clinical forms of tick-borne encephalitis.
Clinical form n Mean sodium concentration in
serum (mmol/l)
Meningitis 24 135.1 ± 3.8
Meningoencephalitis 34 134.7 ± 4.4
Meningoencephalomyelitis 3 137.3 ± 2.5
reported in the Podlaskie and Warmińsko-Mazurskie region. TBE
occurs in a few clinical forms: meningitis, meningoencephalitis,
meningoencephaloradiculitis, and meningoencephalomyelitis.
In our study, 41% of patients diagnosed with TBE had hypona-
traemia. Usually it is mild and normalizes within 1–2 days, however
we observed that patients >45 years had a tendency to develop
moderate hyponatraemia and required a more intensive treatment.
In the majority of cases, hyponatraemia was caused by dehy-
dration, and natrium concentration normalized after short period
of time. Our study showed that the only risk factor of hypona-
traemia development in the course of TBE was patient age. This
is in accordance with the majority of studies, which proved that
elderly patients were more susceptible to electrolyte disturbances
(Upadhyay et al., 2006; Hawkins, 2003). No correlations with
patient gender or the clinical form of TBE were observed.
One of the most important aspects in the approach to patients
with hyponatraemia is a proper identification of the causative fac-
tor as the treatment depends on pathophysiological mechanisms
of the disorder. Many authors consider SIADH as the main cause of
hyponatraemia in meningitis (Kaplan and Feigin, 1980; Feigin and
Kaplan, 1977; Cotton et al., 1991). Therefore, they recommend fluid
restriction as a standard treatment. However, in studies conducted
on children with meningitis, SIADH was responsible for only 7–9%
cases of hyponatraemia (Kanakriyeh et al., 1987; Chemtob et al.,
1985). A study performed by Singhi et al. (1995) proved that fluid
restriction as a standard treatment in meningitis does not improve
the outcome of the disease. In a review by Møller et al. (2001), the
authors state that in many studies, SIADH might be overdiagnosed.
In our study, only 3 patients (5%) fulfilled SIADH criteria and
benefited from fluid restriction. In the remaining group of patients,
hyponatraemia was present in the first 1–2 days after admission
and was caused by dehydration due to fever, vomits, and poor oral
fluid intake. The sodium concentration in this group normalized
without intervention or after fluid supplementation. One of the fac-
tors that might influence the electrolyte balance of patients with
meningitis is treatment with hyperosmolar anti-oedematous flu-
ids such as mannitol. It was proven that mannitol in high doses
may cause transient hyponatraemia and hyperkaliaemia (Cottrell
et al., 1977). Also in a dehydrated patient, osmotic diuresis caused
by mannitol may have worsened the symptoms. In our study, we
did not find any correlation between hyponatraemia and mannitol
dosage or treatment duration. However, the osmotic effect of man-
nitol treatment is very short and therefore it is hard to assess the
full impact of this therapy on temporal electrolyte balance. Further
studies on this subject are required.
Conclusions
Hyponatraemia, usually mild, is a common disorder in the
course of TBE, although in our study it is not significantly more fre-
quent than in other hospitalized patients. However, further studies
are needed. Dehydration seems to be the main cause of hypona-
traemia in the course of TBE.
p Mean age p
0.83 41.0 ± 16.2 0.21
48.9 ± 17.0
47.7 ± 18.8
SIADH is a less common cause of hyponatraemia in the course
of TBE, although it should be taken into consideration as the treat-
ment differs significantly from treatment of hyponatraemia due to
dehydration.
Patients >60 years old with TBE are more susceptible than
younger patients to develop hyponatraemia because of poor
homoeostasis.
Conflict of interest
The authors declare that they have no conflict of interest.
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