The Neuro-Ophthalmology of Tuberculosis

Abstract

Tuberculosis (TB) is a global health concern and central nervous system (CNS) TB leads to high mortality and morbidity. CNS TB can manifest as tubercular meningitis, tuberculoma, myelitis, and arachnoiditis. Neuro-ophthalmological involvement by TB can lead to permanent blindness, ocular nerve palsies and gaze restriction. Visual impairment is a dreaded complication of tubercular meningitis (TBM), which can result from visual pathway involvement at different levels with varying pathogenesis. Efferent pathway involvement includes cranial nerve palsies and disorders of gaze. The purpose of this review is to outline the various neuro-ophthalmological manifestations of TB along with a description of their unique pathogenesis and management. Optochiasmatic arachnoiditis and tuberculomas are the most common causes of vision loss followed by chronic papilloedema. Abducens nerve palsy is the most commonly seen ocular nerve palsy in TBM. Gaze palsies with deficits in saccades and pursuits can occur due to brainstem tuberculomas. Corticosteroids are the cornerstone in the management of paradoxical reactions, but other immunomodulators such as thalidomide and infliximab are being explored. Toxic optic neuropathy caused by ethambutol necessitates careful monitoring and immediate drug discontinuation. Cerebrospinal fluid diversion through ventriculo-peritoneal shunting may be required in patients with hydrocephalus in stage I and II of TBM to prevent visual impairment. Early diagnosis and prompt management are crucial to prevent permanent disability. Prevention strategies, public health initiatives, regular follow-up and timely intervention are essential in reducing the burden of CNS TB and its neuro-ophthalmological complications.

Keywords: Tubercular meningitis; optochiasmatic arachnoiditis; toxic optic neuropathy; tuberculoma; vision loss.

Figure 1.

A 28-year-female presented with a 1 month history of fever, headache and three episodes of seizures followed by new onset binocular diplopia on left gaze, painless, bilateral diminution of vision, dysphagia for 5–7 days and drowsiness for 1 day. She was started on with anti-tubercular treatment (rifampicin, isoniazid, pyrazinamide and streptomycin) with intravenous corticosteroids and referred to our centre. Her drowsiness and headache improved. Examination revealed signs of meningeal irritation, a best corrected visual acuity of 6/60 in each eye, a sluggish light reflex on the left, temporal optic disc pallor bilaterally, bilateral lateral rectus palsies (left >> right) (a), and bilateral IX, X, and left XII cranial nerve palsies. On the basis of the history, chronic meningitis was suspected with multiple cranial nerve palsies. Imaging was expected to show involvement of the optic nerves/chiasm with involvement of other cranial nerves. However, gadolinium-enhanced magnetic resonance imaging of her brain showed only minimal hydrocephalus with minimal leptomeningeal enhancement but no exudates and no optochiasmatic arachnoiditis/tuberculoma (b: T2 axial image, c: T1-weighted contrast axial image). What is the cause of visual impairment? The imaging does not explain the severity of the vision loss. Hence, slit lamp examination of the fundus was performed which revealed multiple retinal tubercles (black arrow heads) with a tubercle just over the left macula (d, blue arrow), and swelling of the right macula (e, red arrow), explaining the cause of the visual impairment.

Figure 2.

A 15-year-female presented with a 15-day history of holocranial headache followed by fever, severe neck pain, neck stiffness and altered sensorium. Examination revealed signs of meningeal irritation, bilateral lateral rectus restriction, bilateral sluggishly reacting pupils, with a normal fundoscopic examination. Cerebrospinal fluid (CSF) analysis showed an opening pressure of 12 cmCSF, 139 cells/mm³ (10% neutrophils, 89% lymphocytes), a protein level of 73 mg%, a glucose level of 37 mg%, negative India ink stain and cryptococcal antigen, and a positive Genxpert Ultra test for Mycobacterium tuberculosis that was rifampicin sensitive. She was started on antitubercular treatment (rifampicin, isoniazid, pyrazinamide and streptomycin) with intravenous corticosteroids. When she regained consciousness she reported only light perception in each eye. Gadolinium-enhanced magnetic resonance imaging of her brain did not show any optochiasmatic arachnoiditis or tuberculomas in the optic pathway. There was no enhancement of the orbital optic nerve (a), but there was minimal enhancement over the left pre-chiasmal optic nerve (b, yellow arrows on a T1-weighted contrast-enhanced image and c, T1-weighted contrast-enhanced coronal image). A diagnosis of tubercular optic neuritis was made and she was given intravenous methylprednisolone followed by oral corticosteroids. After 1 month all the associated symptoms improved significantly except there was no improvement in vision and both optic discs started showing temporal pallor (d, right and e, left). After 3 months’ follow up her vision remained at perception of light bilaterally.

Figure 3.

A 60-year-old diabetic male presented with a 2-month history of progressive, bilateral, painless diminution of vision associated with loss of colour perception as well as colour desaturation. He had been started on antitubercular treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol) for pulmonary tuberculosis 6 months previously. He was taking ethambutol at a dose of 1375 mg/day (21.1 mg/kg/day). On examination he could only count fingers at 1 m with each eye and had sluggish pupillary reactions. Fundal examination revealed bilateral optic atrophy (a, right and b, left). Perimetry showed severe diffuse loss of visual fields (c, right and d, left). Magnetic resonance imaging of his brain showed hyperintense signal in both optic nerves (e, T2-weighted axial image and f, T2-weighted coronal image) with minimal contrast enhancement in the optic chiasm (red arrow g, T1-weighted coronal contrast-enhanced image). A diagnosis of ethambutol-induced optic neuropathy was made and the drug was immediately discontinued. His vision showed no improvement but did not deteriorate further.

Figure 4.

A 19-year-female was diagnosed with tubercular meningitis and started on antitubercular treatment (ATT) (rifampicin, isoniazid, pyrazinamide and streptomycin) with initial improvement in fever, headache and vomiting. After 2 months of ATT she presented with bilateral, painless, diminution of vision. Fundoscopic examination revealed bilateral optic disc pallor (a, left and b, right). In view of the length of treatment with initial improvement the possibility of optochiasmatic arachnoiditis was considered. Gadolinium-enhanced magnetic resonance imaging of her brain revealed extensive exudates lining the base of the brainstem (c, T1-weighted contrast-enhanced sagittal image), and entrapping the optochiasmatic region, peri-mesencephalic cisterns and bilateral middle cerebral arteries (d, T1-weighted contrast-enhanced axial image), confirming the clinical suspicion.

Figure 5.

A 30-year-female was diagnosed as definite tubercular meningitis on the basis of the clinical picture, radiological appearance, cerebrospinal fluid analysis and being positive GenXpert Ultra positive for Mycobacterium tuberculosis. She was given antitubercular treatment (ATT) (rifampicin, isoniazid, pyrazinamide and streptomycin) along with dexamethasone. When corticosteroids were stopped after slow tapering at the third month of ATT, she developed sustained gaze towards the left side with an inability to look to the right side. Clinically, the lesion localised to either the left frontal eye field or the right paramedian pontine reticular formation. Gadolinium-enhanced magnetic resonance imaging (MRI) of her brain was repeated, which revealed a large tuberculoma over the right pons at the floor of fourth ventricle (yellow arrow in a, T1-weighted contrast-enhanced axial image and b, T1-weighted contrast-enhanced sagittal image) with multiple tuberculomas in both cerebral and cerebellar hemispheres. She was restarted on dexamethasone followed by the addition of thalidomide (as a steroid sparing agent), following which her symptoms improved completely over the next 10 days. A repeat MRI performed 3 months later revealed marked reduction in the number and size of the tuberculomas (c, T1-weighted contrast-enhanced axial image and d, T1-weighted contrast-enhanced sagittal image).

Figure 6.

A 23-year-female had been diagnosed with tubercular meningitis 7 months previously. She had a poor compliance with medication and presented with a 2 week history of recurrence of fever, continuous headache, and vomiting followed by altered sensorium for 1 day. On examination she was emaciated and stuporous with wincing to painful stimuli but no motor response. She had persistent downgaze (a) with intermittent downbeating nystagmus. Her pupils were not reactive to light and fundoscopic examination revealed bilateral optic disc pallor. Her knee and ankle jerks were absent. Anatomical localisation to the cervico-medullary junction (CVJ) was made in view of the downbeat nystagmus. Gadolinium-enhanced magnetic resonance imaging of her brain and whole spine revealed obstructive hydrocephalus, and extensive exudates around the base of brainstem as well as around the CVJ with myelitis (b, T2-weighted sagittal image of the CVJ and cervical spine; c, T1-weighted contrast-enhanced sagittal image of CVJ and cervical spine; d, T1-weighted contrast-enhanced axial image of the brain; and E, T1-weighted contrast-enhanced sagittal image of the brain). In addition, there was extensive spinal arachnoiditis until the cauda equina and distal nerve roots (f, T1-weighted contrast-enhanced sagittal image of the lower thoracic and lumbosacral spine). Cerebrospinal fluid analysis revealed 450 cells/mm³ (95% lymphocytes), a protein level of 622 mg%, and a glucose level of 14 mg%. The GenXpert Ultra test for Mycobacterium tuberculosis came positive (rifampicin sensitive). The cytology, cryptococcal antigen and India ink tests were negative. She was started on antitubercular treatment (rifampicin, isoniazid, pyrazinamide and streptomycin) along with intravenous dexamethasone and she underwent ventriculoperitoneal shunting. She became conscious and oriented immediately after the shunt procedure and continued to improve further.

Figure 7.

A 24-year-female developed fever and headache, followed by bilateral diminution of vision over a duration of 4 months. She was diagnosed with tubercular meningitis and started on antitubercular treatment (rifampicin, isoniazid, pyrazinamide, and ethambutol) at a private hospital. She deteriorated and presented to our emergency services. Examination revealed meningeal signs, a visual acuity of 6/18 in her right eye and 6/36 in her left eye, with bilateral optic disc pallor (d, left eye and E, right eye) and bilateral VI cranial nerve palsies (left > right). Gadolinium-enhanced magnetic resonance (MR) imaging showed diffuse leptomeningitis with extensive optochiasmatic arachnoiditis (a, T1-weighted contrast-enhanced axial image) and hydrocephalus (b, T1-weighted contrast-enhanced axial image). MR angiography revealed severe attenuation of the left supraclinoid internal carotid artery and the M1 segment of the left middle cerebral artery with attenuation of left-sided collaterals (c). Ethambutol was substituted with streptomycin and she was started on corticosteroids and thalidomide due to the extensive exudates. (f) and (g) show T1-weighted contrast-enhanced axial brain MR images after 1 and 2 months of thalidomide, respectively with marked reduction in the exudates.