Proliferative Arachnoiditis and Vasculitis in Central Nervous System Tuberculosis: A Retrospective Analysis of Clinical Features and Outcomes from a Tertiary Centre in India

Technical Summary: Proliferative Arachnoiditis and Vasculitis in Central Nervous System Tuberculosis

Problem Statement
Central nervous system tuberculosis (CNS TB), particularly tuberculous meningitis (TBM), is a severe manifestation of tuberculosis associated with high morbidity and mortality. While TBM accounts for a small fraction of total TB cases, its sequelae are devastating, often leading to long-term disability. The disease pathophysiology involves hematogenous dissemination and the rupture of subependymal tubercles, resulting in dense basal exudates and intense meningeal inflammation. This inflammatory cascade precipitates severe complications, including obstructive hydrocephalus, tuberculous vasculitic infarcts, optochiasmatic arachnoiditis (OCA), and spinal arachnoiditis (SA). These complications can present at diagnosis or develop paradoxically during anti-tubercular treatment (ATT) due to an exaggerated immune response. Despite the availability of potent anti-tubercular agents and adjunctive corticosteroids, the prognosis for patients with these specific complications remains poor, and evidence regarding optimal management strategies for OCA, SA, and vasculitis is limited.

Methodology
This study is a retrospective cohort analysis conducted at a tertiary care center in New Delhi, India, between October 2020 and September 2023. The study screened 318 patients admitted with suspected CNS TB. Inclusion criteria required patients aged 14 years or older with a diagnosis of CNS TB (classified as definite, probable, or possible based on consensus criteria) who presented with specific complications: proliferative arachnoiditis (OCA or SA) or TB-associated CNS vasculitis. Patients with incomplete data or those lacking a minimum three-month follow-up (excluding those who expired) were excluded.

Data collection encompassed clinical presentations, demographics, comorbidities, biochemical parameters, CSF studies, and neuroimaging findings. Baseline assessments included TBM Medical Research Council (MRC) staging, visual status, limb power, and consciousness levels. The study evaluated the use of standard ATT regimens (first-line, augmented, or MDR) and adjunctive therapies, including pulse methylprednisolone, intrathecal hyaluronidase, thalidomide, and aspirin. Outcomes were measured via mortality rates, the modified Rankin Scale (mRS) at discharge and follow-up, and subjective visual improvement on a Likert scale. Statistical analysis involved chi-square tests, Student's t-tests, and survival analysis using Cox proportional hazards models.

Key Results
Among the 318 screened patients, 87 were identified with complicated CNS TB, with complete follow-up data available for 69 patients. The cohort had a mean age of 28 years, with 48.3% being male. The distribution of complications included vasculitis in 76% (66 patients), spinal arachnoiditis in 47% (41 patients), and optochiasmatic arachnoiditis in 30% (26 patients).

• Mortality and Functional Outcomes: The overall mortality rate among the 69 patients with follow-up was 49% (34 deaths). Among survivors, 88.6% showed improvement with treatment, achieving a median mRS of 2 (range 1–3).
• Optochiasmatic Arachnoiditis (OCA): Visual follow-up was available for 15 of the 26 OCA patients. Only 26.7% achieved complete visual improvement, while 60% showed partial improvement. Statistical analysis revealed no significant association between visual improvement and the use of pulse methylprednisolone (p=0.48), intrathecal hyaluronidase (p=0.43), or thalidomide (p=0.24).
• Spinal Arachnoiditis (SA): Of the 41 patients with SA, 19 were alive at follow-up with a median mRS of 1. Notably, 23.5% of patients with imaging-proven SA were asymptomatic at diagnosis and remained alive with good functional outcomes (median mRS 1.5). In contrast, patients with symptomatic SA had a mortality rate of 44.1%. No significant difference in mRS improvement was observed based on the use of pulse steroids, hyaluronidase, or thalidomide.
• Vasculitis: Among 66 patients with vasculitic infarcts, 30 (45.5%) received aspirin. The use of aspirin was not associated with improved mRS scores (p=0.374) or reduced mortality (p=0.685). Survival analysis confirmed no significant difference in survival between those treated with aspirin and those who were not (HR=1.37, p=0.454).
• Predictors of Mortality: Univariable analysis identified age, hemoglobin, and CRP levels as significant predictors of mortality. However, in a multivariable Cox proportional hazards model, only age at diagnosis remained an independent predictor of mortality (HR 1.04, 95% CI 1.01–1.08, p=0.012).

Significance and Claims
The authors conclude that TB arachnoiditis and CNS vasculitis represent severe complications of CNS TB with high morbidity and mortality, and that current management strategies remain challenging. The study highlights that despite the use of various adjunctive therapies—including high-dose steroids, intrathecal hyaluronidase, thalidomide, and aspirin—therapeutic responses have been suboptimal in this cohort. Specifically, the lack of statistically significant benefit from aspirin in vasculitis and the limited efficacy of other agents in OCA and SA underscore the need for further investigation.

The paper modestly claims that these findings emphasize the necessity for larger, prospective trials to establish standardized treatment protocols and to search for alternative agents to improve long-term neurological and functional outcomes. The study does not propose new experimental interventions but rather calls for rigorous evaluation of existing and novel adjunctive therapies to address the high burden of disease in this population.