Optochiasmatic involvement in tuberculous meningitis: A case series with a review of literature

INTRODUCTION

Optochiasmatic involvement in tuberculosis (TB) can manifest as either optochiasmatic arachnoiditis (OCA) of the leptomeninges around the chiasma or tuberculoma, both of which are vision-debilitating forms of TB meningitis (TBM). It accounts for about 18% of cases of TBM and can result in significant vision loss and/or cranial nerve damage.^[1] Optochiasmatic involvement refers to the inflammation of the pia-arachnoid mater of the optic nerve and chiasma in the chiasmatic and suprasellar cisterns. It is typically severe exudative meningitis, characterized by large amounts of inflammatory exudate in the optic chiasm and suprasellar cisterns. Visual loss in these cases can be due to the direct mechanical compressive effect on the anterior optic pathway – optic nerve and chiasma – or, ischemia or both. Involvement of the vasa vasorum supplying these nerves as vasculitis can also result in visual deficits.^[2] Early diagnosis and prompt initiation of treatment are critical in preventing vision loss.

CASE SERIES

We report six cases of tuberculous meningitis with optochiasmatic involvement managed at a tertiary care institution in south India. All patients underwent contrast-enhanced magnetic resonance imaging (CE-MRI) as per institutional protocol. Cerebrospinal fluid (CSF) analysis and visual assessment were done on admission. Ophthalmology evaluation included extraocular movement assessment for cranial nerve palsies and swinging flashlight test for pupillary light reflex. The corrected visual acuity was assessed along with a fundus examination. The clinical presentations, neuroimaging findings, CSF analysis, and follow-up of these cases are summarized in Table 1.

All six patients were females and the median age involved was 15 years (range: 3–36 years). Three of the six patients (50%) were previously diagnosed with TBM and were already on antituberculous treatment (ATT) at the time of onset of visual symptoms. The mean time interval between the initiation of ATT and the development of visual symptoms was 5.67 months (±2.05 months). One patient had co-infections with retroviral and hepatitis-B infections.

The severity of TBM using the Medical Research Council staging system^[3] is as below - stage I (patient fully conscious with no deficits) – 3 patients; stage II (minor neurological deficits with little to no impairment in sensorium) – 2 patients and; stage III (severe sensorium impairment ± convulsions/deficits) - one. Three of six patients presented with seizures including the one with immunocompromised status. The severity of vision impairment was categorized using the World Health Organization definition.^[4] At presentation, 4/6 patients (66.67%) had visual impairment or blindness (one mild, two moderate, and three complete vision loss). One of the six patients had right third nerve palsy and another had bilateral sixth nerve palsy.

The patients exhibited ring-enhancing lesions (RELs), primarily conglomerate or coalescent, in the suprasellar cistern, with or without accompanying leptomeningeal enhancement in the chiasmal area [Figures 1-6]. Other findings included RELs in various supra- or infratentorial regions, vasculitic infarcts, and hydrocephalus.

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Figure 1:

A 20-year-old female with optochiasmatic tuberculomas. (a) Sagittal T1-weighted post-contrast image shows few ring-enhancing lesions in the chiasmatic cistern. (b) Mild reduction in size of the lesions on 3-year follow-up.

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Figure 2:

An 11-year-old female with optochiasmatic tuberculomas. (a) Sagittal T1-weighted post-contrast image shows multiple conglomerate ring-enhancing lesions in hypothalamus, inferior third ventricle, suprasellar and interpeduncular cisterns. (b) Fluid-attenuated inversion recovery (FLAIR) axial image showing edema along the bilateral optic tracts and mid-brain. A tuberculoma with partial FLAIR suppression is seen in the interpeduncular cistern. (c and d) Reduction in size and number of lesions and edema on 1-year 3-month follow-up.

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Figure 3:

A 20-year-old female with tuberculosis meningitis with optochiasmatic involvement. (a) Axial T1-weighted post-contrast image shows coalescent ring-enhancing lesion in the left anterolateral recess of suprasellar cistern. (b) Heavily T2-weighted SPACE axial sequence shows the lesion compressing the optic chiasma on the left side (arrow). (c) Reduction in size on 1 year 4 months follow-up and (d) Small residual lesion on imaging after 8 years.

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Figure 4:

A 36-year-old female with tuberculosis meningitis and vasculitis. (a) Sagittal T1-weighted post-contrast image shows leptomeningeal thickening with conglomerate ring-enhancing lesions in anterior commissure, optic chiasm, and infundibulum. Few nodular enhancing lesions are noted in midbrain tectum at the level of inferior colliculus, pons, and posterior surface of cervical cord. (b and c) Axial T1-weighted post-contrast image shows thick exudates along optic chiasma and multiple ring-enhancing lesions in anterior interhemispheric fissure, bilateral cerebral hemispheres, and right thalamus. (d) Diffusion-weighted image shows acute infarct in the left basal ganglia. (e) Time-of-flight angiography shows luminal narrowing in bilateral middle cerebral, anterior cerebral, and posterior cerebral arteries (left more than right).

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Figure 5:

A 6-year-old female child with tuberculosis meningitis. (a) Axial T1-weighted post-contrast image shows thick basal exudates in bilateral Sylvian cisterns (right > left), suprasellar and interpeduncular cisterns. (b) Sagittal T1-weighted post-contrast image shows conglomerate ring-enhancing lesions (RELs) in supra-optic recess and hypothalamic regions. Few RELs are noted in the frontal lobe.

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Figure 6:

A 12-year-old female child with optochiasmatic arachnoiditis. (a) Axial unenhanced computed tomography showing hydrocephalus. (b) Axial T1-weighted post-contrast image shows leptomeningeal enhancement in basal cisterns and chiasmatic region. (c) Sagittal T1-weighted post-contrast image shows ring-enhancing lesions in bilateral cerebellar hemispheres. (d) Axial T1-weighted post-contrast image shows enhancement along cisternal portion of bilateral seventh and eighth nerve complex. The same patient had tuberculosis left hip joint. (e) Coronal T2-fat suppressed image of pelvis shows marrow edema in the left femoral neck with mild joint effusion. (f) X-ray pelvis on 1-year follow-up showing progression of the disease with sclerosis of subchondral region and neck of femur.

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All patients received ATT and steroids (dexamethasone or prednisolone for 4 weeks, tapered thereafter). Symptomatic treatment, such as antiepileptics for those with seizures, was also administered. Four out of six patients (66.67%) had associated hydrocephalus and underwent ventriculoperitoneal shunting. One patient had previously undergone surgical excision of a cerebellar tuberculoma. Three of the six patients underwent follow-up imaging, which showed a significant reduction in the size and number of the tuberculomas and a reduction in edema.

DISCUSSION

OCA was first described as a clinical entity in 1929 and was known as the “Syndrome de Balado.”^[1] The first reports were in patients with Meningovascular syphilis followed by the first documented case of tuberculous OCA reported by Yuhl and Rand in 1951.^[5] Other reported etiologies of OCA include rheumatoid pachymeningitis, sarcoidosis, and Epstein–Barr viral infection.^[6]

The optochiasmatic region predominantly consists of a suprasellar cistern and its contents. The suprasellar cistern is the subarachnoid space around the optic chiasm above the sella turcica and consists of the chiasmatic cistern, the interpeduncular cistern, and the cistern of lamina terminalis. It is a vital CSF space that contains the circle of Willis, optic nerves, chiasm, hypothalamus, and pituitary stalk.^[7]

Tuberculous meningitis has a strong predilection for basal parts of the brain. Exudates of tuberculous meningitis present in the basal cisterns (interpeduncular, suprasellar chiasmatic, and Sylvian cisterns) result in OCA and/or tuberculomas.^[8] It may result from the infectious process itself but is more usually seen as a paradoxical reaction to ATT.^[9,10] There is a thickening of the arachnoid mater at the base of the brain with thick exudates surrounding the optic chiasm and the adjacent cranial nerve roots. Apart from the basal exudates, the edema, vasculitis, infarction, and expansion of tuberculomas may also compress and occlude the blood supply to the optic nerve and the optic chiasma leading to severe vision loss.^[2,11] However, other potential causes of visual impairment in patients with tuberculosis should also be ruled out which include primary optic neuritis, toxic optic neuropathy (often associated with ATT drug ethambutol), chiasmal compression secondary to hydrocephalus and increased intracranial pressure, and chiasmal prolapse.^[12]

This clinical entity more frequently affects young adults. Previous studies have identified that female sex, younger age, and raised CSF protein content as predictors for developing OCA.^[1,6] In our study, all six patients were females, and the median age involved was 15 years (range 3–36).

Frequently, optochiasmatic tuberculoma and OCA develop paradoxically while a patient is being treated with anti-TB drugs.^[13,14] Visual loss during the treatment of TBM may be related to either drug-related toxicity or arachnoiditis or tuberculoma involving the anterior optic pathway.^[15,16] The mean time interval between the initiation of ATT and the development of visual symptoms was 5.67 months (±2.05 months) in our case series.

These findings are similar to that of a large series by Aaron et al.,^[6] who analyzed 163 patients with TBM admitted over 6 years and found 23 (14%) developing optic chiasmal atrophy. Of these 23 patients, 18 (78%) developed OCA while on ATT, and 5 (22%) were newly diagnosed with TBM. Among those already receiving treatment, 12 (52%) were on ATT alone, while 6 (26%) had received a combination of steroids and ATT at varying doses and duration. The average time from TBM diagnosis to the onset of visual symptoms was 6.4 months. They identified female sex, age under 27 years, and protein content in the CSF >260% mg as significant risk factors for developing this complication. At 6-month follow-up, among those treated with steroids and ATT, 17% showed improvement, and no further deterioration in visual acuity was noted in 52% of patients. In another series by Sinha et al.,^[17] the meantime for developing paradoxical optochiasmatic tuberculomas was even shorter, with the onset occurring 41 days after initiating anti-TB therapy in 8 patients studied. Of the eight patients, paradoxical optochiasmatic tuberculoma led to vision deterioration in all, with 6 experiencing severe vision loss (visual acuity of 6/60). All patients received an extended course of dexamethasone for 6 weeks in addition to ATT. On follow-up, two patients died at 2 and 7 months and follow-up imaging in the remaining patients showed resolution of the optochiasmatic tuberculoma. At 9 months followup, three patients had complete vision recovery, while three others had partial improvement.

Visual impairment is the most devastating complication because vision loss persists, unlike the other cranial nerve involvement, which might improve or recover completely with time. The prognosis is poor if there is a delay in the diagnosis and/or treatment. Treatment in itself is challenging and involves anti-TB drugs and a prolonged course of steroids (often >8 weeks). In the central nervous system, TB with visual impairment, ethambutol is often replaced with ofloxacin, levofloxacin, or streptomycin as a first-line drug to prevent further visual deterioration.^[9] Corticosteroids are the primary treatment for paradoxical reactions, though other immunomodulators such as thalidomide and infliximab are being investigated as potential alternatives.^[1,12] In cases with non-response or failure of medical management, surgical exploration of the optochiasmatic region and decompression/release of the optic chiasma/tracts from the surrounding leptomeningeal fibrosis has been described to be beneficial as it relieves the mechanical factor or at least arrest the optic atrophy.^[7,13]

CONCLUSION

The development of visual impairment in a patient receiving ATT should raise concerns for optochiasmatic involvement apart from drug toxicity. The prompt management requires a CE MRI of the brain and swift initiation of steroid treatment that significantly improves the prognosis, as evidenced by the reduction in lesion size and neurological function in most of our cases. However, challenges remain, especially in regions with a high burden of TB, where diagnosis may be delayed due to the non-specific nature of the symptoms. Timely intervention can reduce the long-term impact on vision and avoid potentially treatable vision loss and/or neurological deficits.