Journal of the Neurological Sciences 352 (2015) 120–121
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Tuberculous optic neuritis: A case report Keywords: Visual loss Optic neuritis Tuberculous meningitis
Dear Sir, A 37 years old diabetic male presented with a history of painless progressive visual loss in his right eye for 5 days followed by visual loss in the left eye for 2 day duration. He also had moderate grade fever on and off for the past 7 days. He denied any history of headache, loss of weight or appetite or any other systemic symptoms. On presentation he was not able to perceive light in the right eye and had a visual acuity of 20/200 in the left eye. This progressed over 3 days to no perception of light in the left eye. There was a relative afferent pupillary defect (RAPD) on the right side. Examination of the fundus was normal. The rest of the general physical, systemic and neurological examination was normal.
Laboratory evaluation revealed a normal hemogram, erythrocyte sedimentation rate (2 mm/h), renal and liver function tests and serum electrolytes. Blood and urine cultures were negative and chest X-ray was normal. Serum angiotensin converting enzyme (ACE) levels, anti-nucleic acid (ANA), anti-neutrophilic cytoplasmic antibodies (ANCA), Venereal Disease Research Laboratory (VDRL) test, human immunodeficiency virus (HIV), hepatitis B surface antigen and anti-hepatitis C virus antibodies were negative. Gadolinium enhanced magnetic resonance imaging (MRI) of optic nerves and brain revealed bulky and grossly thickened optic nerves on both sides with intense enhancement (Fig. 1A, B), basal exudates in the ambient cisterns (Fig. 1C) and an acute infarct in left thalamus (Fig. 1D). There was no evidence of optochiasmatic arachnoiditis. Cerebrospinal fluid (CSF) was clear and revealed low glucose {CSF glucose = 14 mg/dl, plasma glucose = 175 mg/dl; CSF: plasma glucose ratio (0.08)} with lymphocytic pleocytosis (500 cells, 98% lymphocytes) and raised protein (91 mg/dl). CSF adenosine deaminase (ADA) was 30 IU/l (normal value b 10 IU/l) and tubercular polymerase chain reaction (TB-PCR) was negative. Gram stain, India ink, bacterial and fungal culture, cryptococcal antigen test, VDRL and malignant cytology were negative. Contrast enhanced CT scan (CECT) of chest and abdomen was normal. The Mantoux test was strongly positive (25 mm).
Fig. 1. A. TIW fat suppressed post-contrast axial MRI image of orbit showing bilateral thick, bulky, intensely enhancing optic nerves (arrow). B. TIW fat suppressed post-contrast coronal MRI image of orbit showing bilateral thick, bulky, intensely enhancing optic nerves (arrow). C. TIW post-contrast axial MRI image of brain showing basal exudates (arrow). D. Diffusion weighted axial MRI image of brain showing acute infarct in left thalamus (arrow). E. Follow-up TIW post-contrast axial MRI image of brain showing complete resolution of basal exudates.
http://dx.doi.org/10.1016/j.jns.2015.03.028 0022-510X/© 2015 Elsevier B.V. All rights reserved.
Letter to the Editor
The differential diagnosis of infective granulomatous pathology like tuberculosis, non-infective inflammatory granulomatous disease like sarcoidosis and infiltrating lymphoma was considered. A final diagnosis of probable tuberculous meningitis presenting as bilateral tuberculous optic neuritis was made. Diagnosis of TBM was based on the consensus diagnostic criteria published in 2010 [2]. A. Positive clinical entry criteria—fever and lethargy. B. Total diagnostic score of 12 (linical: symptom duration more than 5 days, cranial nerve palsy; CSF: clear CSF with 500 cells, lymphocytic predominance, CSF to plasma glucose ratio less than 50%; maging: basal meningeal enhancement with thalamic infarct). C. Exclusion of alternative causes. He was started on 4 drug anti-tuberculous treatment (Isoniazid 300 mg, Rifampicin 600 mg, Pyrazinamide 1200 mg and Streptomycin 1000 mg) with 1 g intravenous methylprednisolone for 3 days followed by tapering dose of dexamethasone for 8 weeks. He improved symptomatically, fever subsided and vision started improving. At 2 year follow-up, his visual acuity is finger counting at 3 ft in the left eye and perception of light in the right eye. He is functionally independent in activities of daily living. Fundus shows bilateral optic atrophy. Repeat CEMRI brain revealed complete resolution of basal exudates with bilateral atrophy of optic nerves (Fig. 1E). Mycobacterium tuberculosis causes highly devastating CNS disease with a high mortality and morbidity. CNS involvement occurs in approximately 1% of all cases of tuberculosis [1]. The sixth cranial nerve is most commonly affected [3]. Vision loss due to optic nerve involvement may occasionally be a dominant presenting illness. A number of pathological processes either singly or in combination may contribute to vision loss in tuberculous meningitis [4]. 1. Optic atrophy secondary to chronic papilledema as a result of obstructive hydrocephalus. 2. Ischemic and pressure related damage to optic nerves resulting from constricting optochiasmatic arachnoiditis. 3. Mass lesions (tuberculomas/tuberculous abscess) exerting direct pressure on the optic nerve/chiasm. 4. Toxic neuritis due to antituberculous drugs (ethambutol/isoniazid). 5. Infarction of the chiasm due to tuberculous endarteritis. 6. Damage to the occipital lobes secondary to untreated hydrocephalus or ischemia resulting from arteritis of posterior cerebral arteries causing cortical blindness. 7. Tuberculous optic neuritis (border zone inflammatory perineuritis). In a retrospective series of 62 eyes of 49 patients, papillitis was found to be the most common manifestation of tuberculous optic neuropathy (51.6%), followed by neuroretinitis (14.5%), orbital apex syndrome (12.9%) and optic nerve tubercle (11.3%). Only 5 cases of retrobulbar optic neuritis (8.1%) were seen [5]. Optic nerve or brain imaging was performed only in 19 patients out of 49 (38.8%). The intraocular fluid was negative for acid fast bacilli or Mycobacterium tuberculosis nucleic acid amplification (NAA) assay in all. Sensitivity of both acid-fast bacilli (AFB) detection and culture isolation of Mycobacterium tuberculosis from cerebrospinal fluid (CSF) is low (10–20%) [6,7]. CSF commercial NAA assays for the diagnosis of TBM also have a low sensitivity (56%), though the specificity is high (98%) [8]. Due to an already compromised optic nerve status in patients with tuberculous optic neuropathy, close monitoring is required to look
121
for any deterioration in color vision, visual acuity, and/or visual field when the patient is on ethambutol and/or isoniazid (both cause drug induced optic nerve toxicity). In addition, pyridoxine is routinely combined with isoniazid to protect against peripheral neuropathy. The benefit of corticosteroids in tuberculosis is thought to be organ specific as they help in reducing inflammation and the damage caused thereof. In a recent systematic review and meta-analysis, steroids were found to be effective in reducing mortality for all forms of tuberculosis [9]. This patient had a partial recovery of vision in his left eye, implicating the savage nature of the disease and the need for a prompt diagnosis and management. To conclude, optic neuritis can be the presenting manifestation of tuberculous meningitis. Diagnosis of TBM in practice relies predominantly on clinical evidence, which combines supportive laboratory and radiological findings. The time to starting treatment is the single most important determinant of outcome. Clinical suspicion in appropriate settings and timely recognition can prevent irreversible damage by this dreaded but treatable condition.
Conflict of interest No conflict of interest.
Acknowledgments Nil.
References [1] Cherian A, Thomas SV. Central nervous system tuberculosis. Afr Health Sci 2011;11: 116–27. [2] Marais S, Thwaites G, Schoeman JF, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis 2010;10:803–12. [3] Berger JR. Tuberculous meningitis. Curr Opin Neurol 1994;7:191–200. [4] Udani PM, Bhat US, Dastur DK. Tuberculosis of central nervous system. Indian Pediatr 1973;10:647–56. [5] Davis EJ, Rathinam SR, Okada AA, et al. J Ophthalmic Inflamm Infect 2012;2:183–9. [6] van Well GT, Paes BF, Terwee CB, Springer P, Roord JJ, Donald PR, et al. Twenty years of pediatric tuberculous meningitis: a retrospective cohort study in the Western Cape of South Africa. Pediatrics 2009;123:e1–8. [7] Thwaites G, Chau TT, Mai NT, Drobniewski F, McAdam K, Farrar J. Tuberculous meningitis. J Neurol Neurosurg Psychiatry 2000;68:289–99. [8] Pai M, Flores LL, Pai N, Hubbard A, Riley LW, Colford Jr JM. Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis 2003;3:633–43. [9] Critchley JA, Young F, Orton L, Garner P. Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2013;13:223–37.
Anu Gupta Manoj Kumar Goyal Manish Modi Vivek Lal⁎ E-mail addresses: [email protected] (A. Gupta), [email protected] (M.K. Goyal), [email protected] (M. Modi), [email protected] (V. Lal). ⁎Corresponding author. Tel.: +91 9872155572. 24 February 2015
Contents lists available at ScienceDirect
Journal of the Neurological Sciences journal homepage: www.elsevier.com/locate/jns
Letter to the Editor Tuberculous optic neuritis: A case report Keywords: Visual loss Optic neuritis Tuberculous meningitis
Dear Sir, A 37 years old diabetic male presented with a history of painless progressive visual loss in his right eye for 5 days followed by visual loss in the left eye for 2 day duration. He also had moderate grade fever on and off for the past 7 days. He denied any history of headache, loss of weight or appetite or any other systemic symptoms. On presentation he was not able to perceive light in the right eye and had a visual acuity of 20/200 in the left eye. This progressed over 3 days to no perception of light in the left eye. There was a relative afferent pupillary defect (RAPD) on the right side. Examination of the fundus was normal. The rest of the general physical, systemic and neurological examination was normal.
Laboratory evaluation revealed a normal hemogram, erythrocyte sedimentation rate (2 mm/h), renal and liver function tests and serum electrolytes. Blood and urine cultures were negative and chest X-ray was normal. Serum angiotensin converting enzyme (ACE) levels, anti-nucleic acid (ANA), anti-neutrophilic cytoplasmic antibodies (ANCA), Venereal Disease Research Laboratory (VDRL) test, human immunodeficiency virus (HIV), hepatitis B surface antigen and anti-hepatitis C virus antibodies were negative. Gadolinium enhanced magnetic resonance imaging (MRI) of optic nerves and brain revealed bulky and grossly thickened optic nerves on both sides with intense enhancement (Fig. 1A, B), basal exudates in the ambient cisterns (Fig. 1C) and an acute infarct in left thalamus (Fig. 1D). There was no evidence of optochiasmatic arachnoiditis. Cerebrospinal fluid (CSF) was clear and revealed low glucose {CSF glucose = 14 mg/dl, plasma glucose = 175 mg/dl; CSF: plasma glucose ratio (0.08)} with lymphocytic pleocytosis (500 cells, 98% lymphocytes) and raised protein (91 mg/dl). CSF adenosine deaminase (ADA) was 30 IU/l (normal value b 10 IU/l) and tubercular polymerase chain reaction (TB-PCR) was negative. Gram stain, India ink, bacterial and fungal culture, cryptococcal antigen test, VDRL and malignant cytology were negative. Contrast enhanced CT scan (CECT) of chest and abdomen was normal. The Mantoux test was strongly positive (25 mm).
Fig. 1. A. TIW fat suppressed post-contrast axial MRI image of orbit showing bilateral thick, bulky, intensely enhancing optic nerves (arrow). B. TIW fat suppressed post-contrast coronal MRI image of orbit showing bilateral thick, bulky, intensely enhancing optic nerves (arrow). C. TIW post-contrast axial MRI image of brain showing basal exudates (arrow). D. Diffusion weighted axial MRI image of brain showing acute infarct in left thalamus (arrow). E. Follow-up TIW post-contrast axial MRI image of brain showing complete resolution of basal exudates.
http://dx.doi.org/10.1016/j.jns.2015.03.028 0022-510X/© 2015 Elsevier B.V. All rights reserved.
Letter to the Editor
The differential diagnosis of infective granulomatous pathology like tuberculosis, non-infective inflammatory granulomatous disease like sarcoidosis and infiltrating lymphoma was considered. A final diagnosis of probable tuberculous meningitis presenting as bilateral tuberculous optic neuritis was made. Diagnosis of TBM was based on the consensus diagnostic criteria published in 2010 [2]. A. Positive clinical entry criteria—fever and lethargy. B. Total diagnostic score of 12 (linical: symptom duration more than 5 days, cranial nerve palsy; CSF: clear CSF with 500 cells, lymphocytic predominance, CSF to plasma glucose ratio less than 50%; maging: basal meningeal enhancement with thalamic infarct). C. Exclusion of alternative causes. He was started on 4 drug anti-tuberculous treatment (Isoniazid 300 mg, Rifampicin 600 mg, Pyrazinamide 1200 mg and Streptomycin 1000 mg) with 1 g intravenous methylprednisolone for 3 days followed by tapering dose of dexamethasone for 8 weeks. He improved symptomatically, fever subsided and vision started improving. At 2 year follow-up, his visual acuity is finger counting at 3 ft in the left eye and perception of light in the right eye. He is functionally independent in activities of daily living. Fundus shows bilateral optic atrophy. Repeat CEMRI brain revealed complete resolution of basal exudates with bilateral atrophy of optic nerves (Fig. 1E). Mycobacterium tuberculosis causes highly devastating CNS disease with a high mortality and morbidity. CNS involvement occurs in approximately 1% of all cases of tuberculosis [1]. The sixth cranial nerve is most commonly affected [3]. Vision loss due to optic nerve involvement may occasionally be a dominant presenting illness. A number of pathological processes either singly or in combination may contribute to vision loss in tuberculous meningitis [4]. 1. Optic atrophy secondary to chronic papilledema as a result of obstructive hydrocephalus. 2. Ischemic and pressure related damage to optic nerves resulting from constricting optochiasmatic arachnoiditis. 3. Mass lesions (tuberculomas/tuberculous abscess) exerting direct pressure on the optic nerve/chiasm. 4. Toxic neuritis due to antituberculous drugs (ethambutol/isoniazid). 5. Infarction of the chiasm due to tuberculous endarteritis. 6. Damage to the occipital lobes secondary to untreated hydrocephalus or ischemia resulting from arteritis of posterior cerebral arteries causing cortical blindness. 7. Tuberculous optic neuritis (border zone inflammatory perineuritis). In a retrospective series of 62 eyes of 49 patients, papillitis was found to be the most common manifestation of tuberculous optic neuropathy (51.6%), followed by neuroretinitis (14.5%), orbital apex syndrome (12.9%) and optic nerve tubercle (11.3%). Only 5 cases of retrobulbar optic neuritis (8.1%) were seen [5]. Optic nerve or brain imaging was performed only in 19 patients out of 49 (38.8%). The intraocular fluid was negative for acid fast bacilli or Mycobacterium tuberculosis nucleic acid amplification (NAA) assay in all. Sensitivity of both acid-fast bacilli (AFB) detection and culture isolation of Mycobacterium tuberculosis from cerebrospinal fluid (CSF) is low (10–20%) [6,7]. CSF commercial NAA assays for the diagnosis of TBM also have a low sensitivity (56%), though the specificity is high (98%) [8]. Due to an already compromised optic nerve status in patients with tuberculous optic neuropathy, close monitoring is required to look
121
for any deterioration in color vision, visual acuity, and/or visual field when the patient is on ethambutol and/or isoniazid (both cause drug induced optic nerve toxicity). In addition, pyridoxine is routinely combined with isoniazid to protect against peripheral neuropathy. The benefit of corticosteroids in tuberculosis is thought to be organ specific as they help in reducing inflammation and the damage caused thereof. In a recent systematic review and meta-analysis, steroids were found to be effective in reducing mortality for all forms of tuberculosis [9]. This patient had a partial recovery of vision in his left eye, implicating the savage nature of the disease and the need for a prompt diagnosis and management. To conclude, optic neuritis can be the presenting manifestation of tuberculous meningitis. Diagnosis of TBM in practice relies predominantly on clinical evidence, which combines supportive laboratory and radiological findings. The time to starting treatment is the single most important determinant of outcome. Clinical suspicion in appropriate settings and timely recognition can prevent irreversible damage by this dreaded but treatable condition.
Conflict of interest No conflict of interest.
Acknowledgments Nil.
References [1] Cherian A, Thomas SV. Central nervous system tuberculosis. Afr Health Sci 2011;11: 116–27. [2] Marais S, Thwaites G, Schoeman JF, et al. Tuberculous meningitis: a uniform case definition for use in clinical research. Lancet Infect Dis 2010;10:803–12. [3] Berger JR. Tuberculous meningitis. Curr Opin Neurol 1994;7:191–200. [4] Udani PM, Bhat US, Dastur DK. Tuberculosis of central nervous system. Indian Pediatr 1973;10:647–56. [5] Davis EJ, Rathinam SR, Okada AA, et al. J Ophthalmic Inflamm Infect 2012;2:183–9. [6] van Well GT, Paes BF, Terwee CB, Springer P, Roord JJ, Donald PR, et al. Twenty years of pediatric tuberculous meningitis: a retrospective cohort study in the Western Cape of South Africa. Pediatrics 2009;123:e1–8. [7] Thwaites G, Chau TT, Mai NT, Drobniewski F, McAdam K, Farrar J. Tuberculous meningitis. J Neurol Neurosurg Psychiatry 2000;68:289–99. [8] Pai M, Flores LL, Pai N, Hubbard A, Riley LW, Colford Jr JM. Diagnostic accuracy of nucleic acid amplification tests for tuberculous meningitis: a systematic review and meta-analysis. Lancet Infect Dis 2003;3:633–43. [9] Critchley JA, Young F, Orton L, Garner P. Corticosteroids for prevention of mortality in people with tuberculosis: a systematic review and meta-analysis. Lancet Infect Dis 2013;13:223–37.
Anu Gupta Manoj Kumar Goyal Manish Modi Vivek Lal⁎ E-mail addresses: [email protected] (A. Gupta), [email protected] (M.K. Goyal), [email protected] (M. Modi), [email protected] (V. Lal). ⁎Corresponding author. Tel.: +91 9872155572. 24 February 2015
