50 J Gandhara Med Dent Sci

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ORIGINAL ARTICLE

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HYPONATREMIA IN PATIENTS WITH TUBERCULOUS MENINGITIS: A CLINICAL OVERVIEW
Husnain Ahmed1, Muhammad Ishfaq2, Alvina Ahmed3, Filza Ajmal4, Iman Aly5, Afsheen Mehmood6

ABSTRACT
OBJECTIVES
This study aims to determine the frequency of hyponatraemia in patients
suffering from tuberculous meningitis in a tertiary care hospital.
METHODOLOGY
A cross-sectional study was conducted from January to June 2024 at the
Department of Medicine, Hayatabad Medical Complex, Peshawar. We
conducted this study on 219 patients. Presenting with tuberculous meningitis,
having an age between 18 to 60 years of either gender. Patients with bipolar
affective disorder, posttraumatic stress, lung carcinoma, hypothyroidism, or
hyperthyroidism and pregnant women were excluded. The frequency of
hyponatraemia was determined.
RESULTS
This study was conducted on 219 patients presenting with tuberculous
meningitis. The mean age of the study patients was 42.41 ± 11.38 years. The
frequency of hyponatremia in our study was 75 (34.2%). Stratification of
hyponatremia with age, gender, diabetes, hypertension and duration of
disease was not significant with a p-value> 0.05.
CONCLUSION
Hyponatremia is a fairly common occurrence in Tuberculous me ningitis
patients, and its early detection and management are crucial to patient
management.
KEYWORDS: Hyponatremia, Tuberculous meningitis, Tertiary Care
hospital, Central Nervous System

How to cite this article

Ahmed H, Ishfaq M, Ahmed A, Ajmal
F, Aly I, Mehmood A. Hyponatremia
in Patients with Tuberculous
Meningitis: A Clinical Overview. J
Gandhara Med Dent Sci.2025;12(3):

Date of Su bmission: 20-05-2025
Date Revised 28-05-2025
Date Acceptance: 02-06-2025

1Postgraduate Trainee, Department of
Medicine, Hayatabad Medical
Complex, Peshawar

3Postgraduate Trainee, Department of
Medicine, Hayatabad Medical
Complex, Peshawar

4Postgraduate Trainee, Department of
Medicine, Hayatabad Medical
Complex, Peshawar

5Postgraduate Trainee, Department of
Medicine, Hayatabad Medical
Complex, Peshawar

6Associate Professor, Khyber Girls
Medical College, Peshawar

Correspondence

2Muhammad Ishfaq, Associate
Professor, Department of Medicine,
Hayatabad Medical Complex,
Peshawar

+92-333-9005472
dashfaq@gmail.com

INTRODUCTION

Tuberculosis is a leading cause of infection-related
mortality worldwide. The most typical type of CNS
tuberculosis is tuberculous meningitis (TBM). The most
frequent electrolyte abnormality seen in TBM patients
who have been admitted is hyponatraemia.1 There is a
significant link between sodium problems and
morbidity and mortality. Before any treatment
intervention, the differential diagnosis of
hyponatraemia must be considered because of its high
prevalence and associated neurological limitations.1
The main mechanism for hyponatraemia in CNS
infection is SIADH (syndrome of inappropriate
antidiuretic hormone secretion); however, there are
other potential causes as well. Cerebral salt wasting
syndrome (CSWS) is considered an alternative
mechanism.2 Due to the enhancement of renal water
retention by antidiuretic hormone, SIADH lead to
volume expansion. Following renal salt depletion,
CSWS is characterized by a reduction in effective

arterial blood volume.3 It is still uncertain what the
exact mechanism is that causes cerebral salt-wasting
syndrome. It has been linked to natriuretic peptides,
such as brain natriuretic peptides and C-type natriuretic
peptides. The pathophysiology of SIADH is associated
with injury to hypothalamus cells that result in ADH
leakage into the bloodstream.4 The osmoreceptors in the
hypothalamus are reset as part of another pathway. A
clinician should be able to distinguish between SIADH
and CSWS because both have the same incidence of
hyponatremia. Moreover, it is significant because these
two disorders have similar environmental influences.5

In cases of tuberculous meningitis (TBM), a study
observed that among patients with hyponatremia, 50%
were attributed to cerebral salt wasting (CSW), and
8.82% were related to the syndrome of inappropriate
antidiuretic hormone secretion (SIADH).6 Additionally,
another study reported that 40 % of patients with TBM
had hyponatremia.7 Severe hyponatremia may lead to
complications like lethargy, seizure, and coma due to
brain edema.8 There is a notable scarcity of literature

50-53. https://doi.org/10.37762/jgmds.
12-3.693

51J Gandhara Med Dent Sci

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available on the rate of hyponatremia in tuberculosis
meningitis (TBM) cases in Pakistan. Hence, this study
aims to determine the frequency of hyponatremia
among TBM patients in our local healthcare setting. By
analyzing the data collected, this study aimed to fill the
existing knowledge gap. The results of this study will
not only contribute to the existing body of research but
will also be instrumental in facilitating the timely
diagnosis of hyponatremia in TBM patients. Early
detection and appropriate management of hyponatremia
can play a crucial role in preventing adverse outcomes
and improving the overall prognosis of TBM patients.
In a recent large cohort study, moderate to profound
hyponatremia was associated with significantly high
mortality and hence required more intense medical
care.9 Consequently, this research holds significant
potential for enhancing clinical practice and patient care
in our region.

METHODOLOGY

This cross-sectional study was conducted at the
Department of Medicine, Hayatabad Medical Complex
Peshawar. The study spanned six months, from January
to June 2024. It was a cross-sectional study. The sample
size was calculated using the WHO calculator, with a
40% frequency of hyponatraemia in patients with
tuberculous meningitis, a 6.5% margin of error, and a
95% confidence level. The sample consisted of 219
patients, who were selected using the non-probability
consecutive sampling technique. The study included
patients with tuberculous meningitis of both genders,
aged 18 to 70. World Health Organization (WHO)
criteria for the diagnosis of tuberculous meningitis
(TBM) is made if any two or more of the following
clinical characteristics are observed within one week: a
fever of 99°F or higher persisting for more than one
week; a headache with a visual analogue scale (V AS)
score of 6 or higher for at least three hours a day for
over a week, where 0 represents no pain and 10
indicates the most severe pain; or vomiting for at least
three times daily for up to three successive days. In
addition to these symptoms, any of the following
laboratory results are considered indicative of TBM: a
positive acid-fast bacilli (AFB) smear on cerebrospinal
fluid (CSF), a positive AFB culture on CSF, elevated
protein levels in the CSF (greater than 100 mg/dl), or
low glucose levels in the CSF (less than 60% of the
plasma level), measured simultaneously with the CSF
assessment. A blood test diagnosed hyponatraemia
when the serum sodium level was less than 130 mEq/L.
Patients with bipolar affective disorders, posttraumatic
stress, lung carcinoma, hypothyroidism or
hyperthyroidism, and pregnant women were excluded.
These patients may be using certain drugs that can

affect their sodium levels. Pregnancy causes
physiological changes in fluid balance and sodium
regulation, which can influence sodium levels. Upon
receiving approval, data collection commenced
following authorization by the hospital ethics
committee. All patients meeting the inclusion criteria
were enrolled, and informed consent was obtained from
all participants. Demographic information, medical
history, and physical examination findings were
documented for each patient. Data was recorded using a
predetermined proforma and analyzed with SPSS v.23
software. Numerical variables, such as age and disease
duration, were presented as mean ± standard deviation.
In contrast, categorical variables, including gender,
hyponatremia, diabetes, hypertension, and residence
area, were presented as frequencies and percentages.
Hyponatremia was categorized according to age,
gender, presence of diabetes, hypertension status, and
residential areas to determine potential effect modifiers.
A post-stratification chi-square test was applied.

RESULTS
This study included 219 patients who presented with
tuberculous meningitis. The study population‘s mean
age was 42.41 ± 11.38 years, and the mean duration of
the disease was 3.95 ± 1.98 days. The age distribution
of the patients in our study was as follows: 18 to 30
years (40 patients, 18.3%), 31 to 40 years (44 patients,
20.1%), 41 to 50 years (73 patients, 33.3%), and 51 to
60 years (62 patients, 28.3%). Regarding gender
distribution, the study included 119 male patients
(54.3%) and 100 female patients (45.7%). The
frequency of hyponatraemia in our study was 75
(34.2%) (Table 1). The frequency of diabetes in our
study was 29 (13.2%). The frequency of hypertension
in our study was 19 (8.7%). According to the residence
area, there were 126 (57.5%) patients from rural areas,
and 93 (42.5%) patients were from urban areas.
Hyponatremia in tuberculous meningitis patients
showed no significant association with age, gender,
diabetes, hypertension, or disease duration (p > 0.05).
Although more frequent in males, non-diabetics, and
those with shorter disease duration, these differences
were not statistically significant. Figure 1;

Figure 1: Frequency of Hyponatremia

Hyponatremia in Patients with Tuberculous Meningitis

52 J Gandhara Med Dent Sci

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Table 2: Stratification of Hyponatremia with Age Distribution,
Gender, Diabetes, Hypertension and Duration of Disease

DISCUSSION

Tuberculosis (TB) remains a significant global health
concern, ranking among the top infectious diseases in
terms of morbidity and mortality. According to the
World Health Organisation’s Global TB Report,
approximately 10.8 million people were affected by
tuberculosis (TB) in 2023. Within the category of
extrapulmonary TB, central nervous system (CNS)
tuberculosis is identified as the second most prevalent
form of the disease.9,10 TBM is the most common
presentation of CNS tuberculosis.11 Hyponatraemia is
the most common electrolyte irregularity observed in
admitted patients with TBM. Significant morbidity and
mortality are associated with sodium disorders.7
Considering the high prevalence and potential for
neurological complications, it is crucial to evaluate the
differential diagnosis of hyponatremia before
commencing any therapeutic interventions.
Hyponatremia can arise from multiple mechanisms,
such as the syndrome of inappropriate antidiuretic
hormone secretion (SIADH) and cerebral salt wasting
(CSW). This condition has the potential to cause
significant neurological impairments. In our study, the
frequency of hyponatraemia in TBM patients was
34.2%, indicating that it’s a relatively common
electrolyte abnormality in TBM patients. This is
consistent with the reported prevalence of 30-50% of
TBM patients, emphasizing its clinical significance. A

Age
Distribution

Gender Diab
etes

Hyper
tension

Durati
on of
Disease

Hypon
atremia

18
to
30
ye
ars

31
to
40

M
ale

Fem
ale

Yes

1-5

Yes 12

43 32 12 63

8 67

55 20
No 28

76 68 17

127

133 38
Total 40 44 73 62 119 100 29 190

200

161

58
P-
Value

0.38 0.52 0.38 0.45 0.96

ye
ars

41
to
50
ye
ars

51
to
60
ye
ars

No Yes No
days days

106

hospital-based prospective study involving 76 patients
with tuberculous meningitis (TBM) found that 34
patients (44.7%) had hyponatraemia. Further analysis
revealed that hyponatraemia was attributed to cerebral
salt wasting in 17 cases, the syndrome of inappropriate
secretion of antidiuretic hormone in 3 cases, and other
miscellaneous causes in 14 cases.6 The prevalence of
hyponatraemia was higher in the 41-50 years age group
(38.4%); however, the association between the age
group and hyponatraemia was not significant,
indicating that age alone is not a factor in causing
hyponatraemia in TBM. The high frequency in middle-
aged groups could be due to disease severity. A

retrospective analysis by Xaiolin and colleagues found
that hyponatraemia is more common in older people
with TBM.12 Hyponatremia exhibited a marginally
higher prevalence in males compared to females;
however, this difference was not statistically
significant. The male predominance could be due to a
potential difference in disease severity among genders.
Similarly, patients with diabetes and hypertension have
a higher prevalence of hyponatraemia, which could be
attributed to renal involvement or vascular
complications in these diseases. Diabetes can lead to
hyponatraemia by the dilutional effect of glycosuria.
Thus, results can be misleading.13 Wasay et al. found
that patients with hypertension are more likely to
experience cerebral infarction and, therefore, can lead
to altered sodium homeostasis in TBM patients.14
Similarly, hyponatremia has been reported in cirrhotic
patients, and its correlation with severity of hepatic
encephalopathy has been documented.15,16 Frequency of
hyponatraemia was also more common in those patients
who presented earlier. The study highlights the
importance of early sodium monitoring in TBM
patients. Electrolyte management is essential in such
patients as hyponatraemia develops in 30% of cases.17,18
The two most common causes of hyponatraemia are
SIADH and CSWS, so for appropriate management,
differentiated theses are essential. CSWS is a
significant issue affecting children.

LIMITATIONS

While the study provides valuable information, some
limitations need to be addressed. Firstly, there is a lack
of differentiation between the Syndrome of
Inappropriate Antidiuretic Hormone Secretion (SIADH)
and Cerebral Salt-Wasting Syndrome (CSWS). Further
research, including detailed investigations such as urine
osmolality and urine sodium measurements, would be
essential to distinguish between these two conditions.
This differentiation is crucial as it impacts the
management and treatment strategies for patients.
Secondly, it is crucial to stratify hyponatremia
assessment based on the severity of tuberculosis
meningitis (TBM). Analyzing the severity of TBM in
conjunction with hyponatremia levels would provide
deeper insights into the correlation between the two
conditions. This stratification could help identify
patterns and outcomes associated with varying degrees
of TBM severity. By addressing these limitations,
future studies can enhance the understanding and
management of hyponatremia in TBM patients, leading
to improved patient care and outcomes.

CONCLUSIONS

Because hyponatraemia is so common in TBM patients

Hyponatremia in Patients with Tuberculous Meningitis

53J Gandhara Med Dent Sci

July - September 2025

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(34.2%) and can lead to serious problems, all TBM
cases, no matter what their age, gender, or other health
issues, should have their blood sodium levels checked
as part of the standard diagnostic and therapeutic
protocols. To stop neurological decline and enhance
patient outcomes, it is important to find and fix
hyponatraemia as soon as possible. Also, doctors
should learn how to spot and treat the numerous causes
of hyponatraemia, such as SIADH and cerebral salt
wasting, so that they can give the right medication.

CONFLICT OF INTEREST: None

FUNDING SOURCES: None

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Hyponatremia in Patients with Tuberculous Meningitis

Husnain Ahmed - Concept & Design; Data Acquisition; Data
Data Analysis/Interpretation: Drafting Manuscript; Critical
Revision; Supervision; Final Approval
Muhammad Ishfaq- Concept & Design; Data Acquisition;
Data Analysis/Interpretation; Drafting Manuscript; Critical
Revision; Supervision; Final Approval
Alvina Ahmed – Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript; Critical
Revision; Supervision; Final Approval
Filza Ajmal - Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript; Critical Revision

Iman Aly - Concept & Design; Data Acquisition; Data
Analysis/Interpretation; Drafting Manuscript; Final Approval
Afsheen Mehmood - Concept & Design; Data Acquisition;
Data Analysis/Interpretation; Drafting Manuscript; Critical
Revision; Supervision; Final Approval

Final Approval

AUTHORS CONTRIBUTION

The authors accept responsibility for all aspects of the work
and will ensure that any concerns regarding the accuracy or
integrity of any part are properly investigated and resolved.