Tuberculous Meningitis Presenting with Bilateral Optic Neuritis: A Case Report and Review of Literature Open Access

Mycobacterium tuberculosis (TB) is the causative agent for TB, which by itself is a major cause of morbidity and mortality. According to the World Health Organization (WHO) 2022 reports, the estimated incidence of TB in 2021 alone was around 10.6 million people worldwide, with a higher disease burden in sub-Saharan Africa, Southeast Asia, and parts of Eastern Europe [1]. Additionally, according to the latest WHO report, the estimated mortality of TB is around 1.6 million people in 2021 [1]. TB is well known to present in various forms but most commonly presents as pulmonary TB [2]. However, a substantial number of TB patients initially present with extrapulmonary manifestations, with nearly 5–15% of them initially presenting with central nervous system TB (CNS-TB) symptoms [3].

Patients affected with CNS-TB can usually present with TB meningitis (TBM), space-occupying tuberculomas, arachnoiditis, and less commonly abscess and encephalitis [2]. Another subtype of CNS-TB that has not been widely described in literature is the neuro-ophthalmic features of TB. Interestingly, there are myriad neuro-ophthalmic manifestations that were found in nearly 82% of patients affected with TBM, with vision loss being the most common neuro-ophthalmic feature [2, 4]. Vision loss in CNS-TB has been attributed to various causes such as tuberculous optic neuropathy, posterior visual pathway involvement, paradoxical reaction to anti-TB therapy (ATT), or toxic optic neuropathy [4]. While unilateral optic neuritis is a well-known consequence of CNS-TB, bilateral involvement of the optic nerves is not an established manifestation. Herein, we present a case of TBM in a young male patient who presented with bilateral optic neuritis as the initial symptom. We aim to highlight the importance of considering TBM as a differential diagnosis in patients presenting with bilateral optic neuritis, particularly in regions with a high burden of TB. Furthermore, we discuss the epidemiology of TBM and its association with optic neuritis and review of existing literature on similar cases. The CARE Checklist has been completed by the authors for this case report, attached as online supplementary material (for all online suppl. material, see https://doi.org/10.1159/000536086).

A 36-year-old Indian male patient presented to the emergency department with a complaint of vision loss for 20-day duration. He gave a history of left-eye blurry vision and irritation for the same duration. Initially, the patient visited a private outpatient clinic, where he was prescribed topical management. However, his symptoms gradually worsened, and for the last 2 days prior to presentation, he had a complete left eye vision loss along with right eye blurry vison. Additionally, he developed a left-sided headache. He denied having dysarthria, facial weakness, limb weakness, or loss of sensation. He denied having fever, cough, joint pain, weight loss, recent upper respiratory tract infection, or history of trauma. The patient had no significant past medical or surgical history. He was not on any medications, and he did not have a significant family history of similar illnesses. He smokes two to three cigarettes and drinks one glass of alcohol during weekends only. He worked in construction.

On physical examination, the patient had right visual impairment (6/36) and complete vision loss in the left eye. He also had an associated left rapid afferent papillary defect. Color vision was intact on the right side. Extraocular muscle movements were intact in both eyes. However, fundus examination revealed blurring of the optic disc margin along with disc swelling. Meningeal signs were absent, and the rest of the neurological and systemic exams were unremarkable.

The patient underwent urgent head computed tomography (CT) scan which showed no evidence of acute intracranial abnormalities. Lumbar puncture (LP) was performed, and it showed an opening pressure of 34 cm H₂O, white blood cell count of 58 with 90% lymphocytes, glucose of 4 mmol/L, and normal protein. Viral polymerase chain reaction (PCR), bacterial and fungal cultures, as well as acid fast bacilli (AFB) smear and TB PCR from cerebrospinal fluid (CSF), were all done and yielded negative results. CSF aquaporin-4 antibody was sent to Mayo Clinic laboratories in the USA for assessment of neuromyelitis, and the results were also negative. Basic laboratory investigations, vitamin levels, autoimmune screening, and viral screening were all grossly unremarkable (Table 1). Magnetic resonance imaging (MRI) of the head, spine, and orbit with contrast was done and was significant for bilateral optic neuritis with no other abnormalities identified (Fig. 1). Visual Evoked Potential was done and showed evidence of bilateral optic neuropathy involving the left optic nerve more than the right.

The patient was diagnosed with optic neuritis of unknown etiology (possible etiology could be autoimmune, infectious, or nutritional). Multidisciplinary decision was made by both neurology and infectious diseases teams to initiate treatment with intravenous (IV) methylprednisolone at 1,000 mg for 5 days, IV acyclovir at 710 mg every 8 h (10 mg/kg), and vitamin B-12 at 1,000 μg oral daily for borderline low B12 level. Acyclovir was later stopped after 7 days, as the results had then showed negative herpes virus PCR. The patient was then discharged home with outpatient follow-up in both ophthalmology and neurology clinics.

One week after discharge, the patient developed sudden onset left arm twitching that lasted for few seconds followed by loss of consciousness and generalized tonic-clonic seizure that was spontaneously aborted minutes later, according to his roommate who witnessed the event. The patient did not have associated nausea, vomiting, limb weakness, tongue bite, or loss of sphincter control. Physical examination did not reveal any neurological abnormalities. Electroencephalogram was done and was found to be normal. Then the patient was discharged home again as a case of first epileptic seizure with an outpatient neurology follow-up.

Ten days later, the patient presented again to the emergency department with right-sided weakness and aphasia for 4-hour duration. The symptoms were not associated with loss of consciousness. He was agitated and was found to have right-sided motor weakness with a 0/5 power. Stroke protocol was activated, and the patient underwent a CT head perfusion study and angiogram under sedation. CT scan did not show acute vascular abnormalities. Following the CT scan, the patient’s weakness improved, but he spiked fever and was still drowsy. The patient was admitted to the medical ward with a differential diagnosis of either seizure with Todd’s paralysis or meningoencephalitis. He underwent LP and was started on both IV ceftriaxone 2 mg twice daily and IV acyclovir 710 mg (10 mg/kg) to cover for a suspected CNS infection and was also started on oral levetiracetam 500 mg twice daily for seizure. The LP showed elevated white blood cells with lymphocytic predominance (Table 1). However, a repeated MRI head showed findings that were suggestive of leptomeningitis with intra-axial tuberculomas (Fig. 2). The infectious diseases team was consulted, and their main working diagnosis at that point based on the imaging findings was CNS-TB. Ceftriaxone and acyclovir were stopped, and the patient was started on oral prednisolone 40 mg daily (which was then tapered over 4 weeks) along with an oral Rifafour combined anti-TB regimen (4 tablets of rifampicin, isoniazid, pyrazinamide, and ethambutol 150/75/400/275 mg along with additional oral pyrazinamide 500 mg and oral pyridoxine 50 mg daily). Ophthalmological reassessment was done and was negative for choroidal tubercles. Then, the patient underwent a repeated LP with the aim of increasing the yield of TB workup but it was also negative. The patient was finally discharged home with follow-up in the infectious diseases TB clinic.

During his follow-up visits, the patient reported strict compliance to ATT and tolerated the therapy without any significant side effects. He also showed a significant improvement in his previously reported symptoms, including visual impairment and motor weakness. After 3 months from discharge, he underwent a follow-up MRI of the brain which showed significant regression of the leptomeningeal inflammatory process with complete resolution of the tuberculomas. The patient completed a total of 1 year of ATT and, lastly, underwent a final follow-up MRI which showed complete clearance of the initial TB radiological findings (Fig. 3).

The presented case highlights the diagnostic challenge that could be faced by rare presentations of TBM. Delayed diagnosis and treatment of TBM results in significant morbidity and mortality, including visual impairment and visual loss in some cases [2]. However, bilateral optic neuritis as the sole presenting manifestation of TBM is rare, with scarce evidence in the literature, thus it remains an area for further research.

TB infections, particularly CNS-TB, have been reported to cause several neuro-ophthalmic manifestations including vision impairment and cranial nerve palsies [2]. Such neuro-ophthalmic complications have been described in around 82% of TBM cases, with vision impairment being the most common, with nearly 72% of TBM cases being affected [2]. The pathogenesis behind tuberculous optic neuropathy is attributed to either direct optic nerve infiltration from the nearby choroid plexus or hematogenous extension from the primary pulmonary source [2]. Additionally, vascular compromise due to vasculitis or thrombosis associated with TB infection may contribute to optic nerve ischemia and subsequent neuritis. However, another explanation for tuberculous optic neuropathy could possibly be related to hypersensitivity reaction secondary to ATT [2, 5].

In this case, the patient presented multiple times to the hospital and underwent extensive investigations and workup for causes of optic neuritis. Taking into consideration the rareness of the condition, a high index of suspicion of CNS-TB was required to recognize the diagnosis. A multidisciplinary approach involving a neurologist, an ophthalmologist, and an infectious disease specialist input is usually essential in managing such cases with tentative presentations. CSF analysis, including examination for AFB, molecular tests, and cytokine profiles, remains an essential step in CNS-TB diagnosis. The conclusive diagnosis of the condition relies on the detection of AFB in CSF [6]. However, the sensitivity of smear microscopy in identifying these bacilli is modest, varying from 10% to 60% [7]. Similarly, the sensitivity of CSF culture is also limited, with a rate as low as 25% [7]. Additionally, the extended duration of 2–6 weeks needed for culture incubation further contributes to diagnostic delays and subsequent treatment initiation, as noted by Erdem et al. [7]. In addition to these diagnostic methods, neuroimaging techniques such as MRI can be valuable in providing significant insights, including the identification of meningeal enhancement or tuberculomas [6]. Hence, the British Infection Society guidelines recommend initiating ATT in patients exhibiting risk factors and features of TBM despite the absence of a positive CSF microbiologic TB workup [6].

Regarding the treatment of TBM, WHO guidelines recommend extended treatment regimen which comprises ATT for 9–12 months. However, a similar regimen to pulmonary TB with a duration of 6 months can be used in adults with TBM. The addition of corticosteroids to the regimen is essential in all TBM cases to reduce mortality and morbidity [8].

To the best of our knowledge, there have been few reported cases of TBM presenting with bilateral optic neuritis. Gupta et al. [9] described a similar case in which a 37-year-old diabetic male presented with bilateral optic neuritis and was subsequently diagnosed with TBM. The diagnosis was based on a constellation of imaging, Mantoux test, and exclusion of alternative causes; CSF smear was negative [9]. In another case report, a 22-year-old female presented with bilateral optic neuritis as the initial manifestation of TBM, confirmed with TB PCR from CSF [10]. On the other hand, a similar case was reported in a 71-year-old elderly male with multiple comorbidities in Malaysia in 2021 [11]. In the case reported by Hitam et al. [11], TBM diagnosis was presumed based on meningeal enhancement on CT, and a positive Mantoux test, CSF culture, and PCR were negative. It is notable in the previous cases, along with the present case, that the rare occurrence of bilateral optic neuritis was an initial complaint of an underlying TBM.

Several similarities can be observed among the aforementioned cases. First, all mentioned cases were reported in TB-endemic areas. Second, most cases involved young individuals. However, the reported case by Hitam et al. [11] signifies the importance of considering TBM as a possible diagnosis in even older age groups [9‒11]. Additionally, the initial symptoms in all cases were predominantly related to vision impairment which overshadows the classical features of TBM such as headache and neck stiffness. Such ambiguity in the presentation highlights the diagnostic challenge associated with recognizing TBM in the presence of prominent optic nerve involvement. Furthermore, due to the variable sensitivity of the CSF smear, the clinical providers in all the mentioned cases had to rely on the constellation of the clinical evaluation, blood and CSF investigation, and clinical imaging to reach the diagnosis [9‒11]. Lastly, most cases demonstrated a favorable response to ATT and corticosteroids, with varying degrees of visual recovery, except in the case reported by Narayanan et al. [10], in which the patient suffered from a persistent visual impairment [9‒11].

Finally, such similarities emphasize the importance of considering TBM in the differential diagnosis of patients presenting with bilateral optic neuritis, especially in the absence of an alternative clear etiology. Healthcare providers should ascertain a high index of suspicion for TB, particularly in regions with a high disease burden, and ensure a multidisciplinary approach. The goal of such efforts should be directed to start ATT as soon as possible to decrease the likelihood of developing debilitating neuro-ophthalmic complications including permanent visual impairment.

Our presented case, along with the previous reports, highlights the diagnostic challenges, potential complications, and management strategies associated with TBM presenting with bilateral optic neuritis. Clinical providers should consider CNS-TB in the differential diagnosis of patients presenting with bilateral optic neuritis, especially in regions with a high incidence of TB. Further research and collaboration are necessary to enhance our understanding of this rare association and optimize the management of such cases.

This case report was approved by the Hamad Medical Corporation’s Medical Research Center (protocol number: MRC-04-23-433). Written informed consent was obtained from the patient for publication of this case report and any accompanying images.

The authors have no conflicts of interest to disclose.

Qatar National Library funded the open access publication fees for this case report.

Khaled W. Sadek and Mohamed A. Atta: medical management of the case, literature review, writing the initial draft of the manuscript, and revising and approving the final draft. Najwa Y. Sultan: literature review, writing the initial draft of the manuscript, and revising and approving the final draft. Anas A. Ashour: conceptualization and supervision, medical management, literature review, and revising the manuscript critically.

All data generated or analyzed during this study are included in this article and its online supplementary material. Further inquiries can be directed to the corresponding author.