Central nervous system tuberculosis (CNS-TB) is a rare but deadly clinical manifestation of Mycobacterium tuberculosis (MTB) infection of the brain and spinal cord [1]. It is caused by the haematogenous spread of MTB from the main infection sites across the blood–brain barrier, resulting in granulomatous inflammation at the base of the meninges [2] and cerebral pathology [3, 4]. CNS Tuberculosis is one of the most difficult diseases to diagnose clinically with significant morbidity and fatality rates. It is the deadliest type of TB, affecting 1% of all TB patients. Given the 10 million new TB patients diagnosed each year, approximately 100,000 new cases of CNS TB occurred in 2019 [5]. CNS-TB frequently manifests as meningitis-like neurological problems, including fever, headache, and stiff neck [6, 7]. Unfortunately, CNS-TB can cause incapacitating neurological consequences (5%–24%) and has high mortality rates (10%–20%) [8]. TB meningitis, tuberculoma, tuberculous abscess, and TB arachnoiditis are some of the symptoms of CNS TB [9]. An underlying HIV infection can make treatment more challenging and frequently increases the risk of contracting or reactivating TB [10]. HIV significantly increases the risk of TB coinfection, including CNS TB; early diagnosis and treatment of CNS TB are essential in minimizing morbidity and mortality. However, recognizing CNS TB in HIV+ populations is especially challenging due to the increased risk of CNS opportunistic infections and malignancies that may mimic CNS TB [11]. Typically, clinical, laboratory and radiographic evidence must be assessed to detect CNS-TB [12]. Radiological imaging using computed tomographic scans and magnetic resonance imaging of the brain and spine can detect abnormalities like meningeal enhancement, tuberculomas, hydrocephalus, and infarctions. Laboratory analysis of cerebrospinal fluid (CSF) or biopsy of brain tissue can confirm the presence of MTB infection. A comprehensive medical history and physical examination can assess the symptoms and risk factors associated with CNS-TB [13]. Although effective, the diagnostic procedure is time-consuming and arduous, requiring at least six weeks to culture the isolates and obtain results [14].

Aims & Objectives:

To assess the socio-demographic profile, clinical characteristics, risk factors, radiological and laboratory findings, complications, and prognosis of patients with CNS TB.

This hospital-based cross-sectional study was conducted in the Department of Neurology, in a tertiary care Indian hospital, for two years. A total of 50 patients diagnosed with CNS tuberculosis or tuberculous meningitis during the study period were included for analysis.

Inclusion criteria

•        Patients of ≥ 18 years of age of both genders

•        Patients diagnosed with CNS tuberculosis

•        Patients who gave written informed consent for the study

Exclusion criteria

•        Patients aged less than 18 years

•        Patients who are unwilling to participate in the study

Diagnosis of CNS TB was made based on clinical features like fever > 2 weeks, headache, vomiting, convulsions, signs of meningeal irritation with or without neurological deficit, and positive CSF studies (staining or culture) or clinical features and supportive criteria (3 or more criteria) such as:

1. CSF examination suggestive of TBM (proteins > 60 mg%, sugar <40 mg%, cells > 50 cu/mm, lymphocytosis > 60%)
2. CSF PCR positive for TB and CSF ADA >10u/L
3. CT/MRI findings (one or more) showing meningeal enhancement, infarcts, basal exudates, obstructive hydrocephalus, tuberculomas
4. Evidence of additional culture-positive or histopathologically proven and radiologically proven extrapulmonary TB or miliary TB
5. Response to treatment

The demographic profile, risk factors, clinical, laboratory, and radiographic data were collected in a pre -  designed proforma. All patients underwent thorough investigation with routine tests as well as specific tests for TB, including ESR, Mantoux test, sputum and aspirate from lymph node for Ziehl-Neelsen stain, CSF analysis for microscopy and biochemistry, and CT/ MRI scan (Plain and contrast) of the brain. All patients received anti-tuberculous therapy as per Revised National Tuberculosis Control Programme (RNTCP) guidelines.

STATISTICAL ANALYSIS:

Statistical analysis was performed using SPSS version 22.0 (SPSS, Chicago, IL, USA). Continuous variables were expressed as mean ± standard deviation (SD), and categorical variables as count (percentages). For analysis of variance, the chi-square test and the student's t-test were used; P < 0.05 was regarded as statistically significant.

The majority of patients (40%) were more than 50 years old, with a male preponderance (66%). Most patients (68%) resided in rural areas and belonged to the lower socio-economic class (42%). 38 % of the patients had education up to secondary school, and 52% were underweight for their age. (Table 1)

Table 1: Socio-demographic characteristics of study patients

The common risk factors for CNS tuberculosis were diabetes mellitus (64%), smoking (60%), alcoholism (52%), immunocompromised state (30%), malnutrition (26%) and HIV (20%).

(Table 2)

Table 2: Risk factors associated with the CNS tuberculosis

Common symptoms were fever (100%), weight loss (82%), headache (72%) and vomiting (64%). The most common signs were neck stiffness (84%) followed by Kernig’s sign (78%) and Brudzinski’s sign (74%). A detailed description of clinical presentation is shown in Table 3.

Table 3: Clinical presentation of CNS tuberculosis patients

CSF staining was positive in 12% of patients; The mean CSF protein was 157 mg%. 64% of patients had CSF lymphocytosis (count >90%) and CSF PCR was positive in 74%. CSF ADA levels were high (> 10 U/L) in 52% of patients. (Table 4)

Table 4: CSF findings in cases of CNS tuberculosis

62% of patients had meningeal enhancement followed by infract (14%) and 10% of patients had tuberculomas on radiological findings of CNS tuberculosis cases. (Graph 1)

Graph 1: Radiological findings of CNS tuberculosis patients

Central nervous system (CNS) tuberculosis (TB) is a devastating infection with high rates of morbidity and mortality worldwide, manifesting as meningitis, intracranial tuberculoma, spinal arachnoiditis, and rarely tuberculous encephalopathy. Sociodemographic factors, such as being young, male sex, from a low-resource setting, and non-white ethnicity, including other inequities, should be part of the core target for interventions, especially in developing countries [15]. In our study, the prevalence of CNS tuberculosis increased with age and was more common in males, similar to findings obtained by B.A. Ayele et al. [16]. The majority of CNS TB patients resided in rural areas, belonged to the lower socio-economic class, and had lower education status in the present study, in agreement with Rock et al. [17]. The common risk factors for the development of TBM were extremes of age, alcoholism, smoking, diabetes, malignancy, recent corticosteroid use, and HIV infection, reported in this research, with results comparable to those of Machuca I et al. [18] and Asare-Baah et al. [19]. These comorbidities weaken the immune system, making it more challenging to manage TB infection clinically. We found that the common symptoms were fever, headache, and vomiting, whereas the most common signs were neck stiffness, followed by Kernig’s sign and Brudzinski’s sign, concordant with Wang et al. [20] and Huang M et al. [21]. Diagnosis based solely on clinical grounds is impossible, necessitating the importance of CSF studies and neuroimaging; CSF studies are the principal diagnostic tool in TBM. In the present study, CSF showed pleocytosis with lymphocytes, elevated protein, and low sugar between 20-40 mg%, with results correlating with other studies done by A.N. Flores et al. [22]. Usually, a high level of CSF protein indicates disruption of the blood-brain barrier and subarachnoid blockage of the CNS circulation in the central nervous system involvement of tuberculosis, especially in tuberculous meningitis [23]. The incidence of hemiparesis, paraparesis, and cranial nerve palsies in the current study was consistent with the study done by Bayındır C et al. [24]. Mantoux positivity may also help if the suspicion is strong. The key to diagnosis lies in CSF analysis and radiological investigations. In our study, CSF staining was positive in 12% of patients, following Kumar et al. [25]. The current study found that the most common radiological finding was meningeal enhancement among CNS TB patients, collaborative with the findings of Dian et al. [26].

We conclude that CNS-TB is associated with higher mortality rates than non-CNS-TB. Smoking, malnutrition, HIV, and diabetes are common risk factors associated with CNS-TB. Early diagnosis, prompt initiation of appropriate treatment, and comprehensive management of comorbidities are crucial to improving outcomes and reducing mortality rates among patients with CNS-TB. Rapid and early diagnosis by positive CSF PCR and CT/MRI findings should replace CSF Acid Fast Bacilli (AFB) staining and culture for the diagnosis of CNS TB.

We conclude that CNS-TB is associated with higher mortality rates than non-CNS-TB. Smoking, malnutrition, HIV, and diabetes are common risk factors associated with CNS-TB. Early diagnosis, prompt initiation of appropriate treatment, and comprehensive management of comorbidities are crucial to improving outcomes and reducing mortality rates among patients with CNS-TB. Rapid and early diagnosis by positive CSF PCR and CT/MRI findings should replace CSF Acid Fast Bacilli (AFB) staining and culture for the diagnosis of CNS TB.

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