Clinical/Scientific Notes
Alexander E. Merkler, MD George Parlitsis, MD Sarju Patel, MD Cristiano Oliveira, MD Ehud Lavi, MD Audrey Schuetz, MD Alison May, MD Dara Bier, MD Sara Simpson, MD Szilard Kiss, MD Marc Dinkin, MD
INFECTION OF THE OPTIC APPARATUS AND HYPOTHALAMUS BY MYCOBACTERIUM HAEMOPHILUM
Mycobacterium haemophilum is a nontuberculous mycobacterium that primarily manifests as cutaneous ulcerations in immunocompromised adults and cervical lymphadenitis in immunocompetent children.1 We present a case of M haemophilum infection of the optic chiasm, tract, and hypothalamus in a patient with AIDS. Case report. A 44-year-old man with AIDS, treated syphilis, and cytomegalovirus retinitis in his right eye (OD) presented with decreased vision in his left eye (OS) and headache. On examination, visual acuity was 20/40 OD and counting fingers OS. There was a left relative afferent pupillary defect. Funduscopy demonstrated nonactive chorioretinal scarring from his prior episode of chorioretinitis and a new, focal area of chorioretinitis with satellite lesions OS. Optical coherence tomography indicated extension of the lesion from the outer retinal layer inward, suggesting spread from the choroid. Humphrey visual field testing revealed severe field loss OS and a temporal hemianopsia OD. Laboratory evaluation revealed a CD4 count of 4 and viral load of 49,927 copies. Rapid plasma reagin was reactive, with fluorescent treponemal antibody absorption test (1:8). Angiotensin-converting enzyme (ACE) was elevated at 83 U/L (reference 9–67). Bacterial and fungal cultures, toxoplasma antibodies, and cryptococcal antigen were negative. Quantiferon TB gold testing was twice indeterminate. Brain MRI revealed a 9 3 16 3 12–mm enhancing, T2 hyperintense mass centered in and expanding the optic chiasm with T2 hyperintensity extending into the left optic tract (figure). CSF analysis revealed 9 leukocytes, protein 40 mg/dL, glucose 47 mg/dL, and a negative Gram stain, culture, KOH prep, cryptococcal antigen, acid-fast bacillus culture, Mycobacterium tuberculosis amplification, viral studies, cytology, flow cytometry, and Venereal Disease Research Laboratory. CSF ACE was normal at 1.4. Vitreous biopsy revealed negative Gram stain, culture, and KOH prep. Body PET-CT revealed no abnormal fluorodeoxyglucose uptake. A biopsy of the optic chiasm revealed a T-cell lymphocytic infiltrate in a perivascular distribution with
massive demyelination and axonal preservation (figure). Spirochete stains were negative. The pathologic interpretation was demyelinating optic chiasmitis and 5 days of IV immunoglobulin was administered, followed by 3 days of IV methylprednisolone, which resulted in rapid improvement in visual acuity to 20/60 OD and 20/400 OS. Ten days later, vision worsened OS and repeat MRI revealed an increase in the right aspect of the chiasmal mass and new extension along the right optic tract. Steroids were restarted with visual improvement. Acid-fast stain of the biopsied chiasm revealed innumerable bacilli, which DNA PCR revealed to be M haemophilum (figure). Antibiotics and oral steroids were initiated and 2 weeks later, visual acuity improved to 20/25 OD. Seven months later, in the setting of noncompliance with antibiotics, chiasmal enhancement had improved, but the left optic nerve newly enhanced and acuity decreased to light perception OS. One month later, there was extension into the hypothalamus (figure) and a new focal area of chorioretinitis OD. Discussion. We report a case of M haemophilum infection of the optic apparatus and hypothalamus and concurrent chorioretinal lesion. The perivascular T-cell infiltrate with demyelination and axonal sparing represent a unique pathologic presentation for mycobacterial disease in the CNS, and may be a reflection of the severely immunocompromised state of our patient. CNS involvement is rare in cases of nontuberculous mycobacterium, manifesting mostly as a meningoencephalitis in patients with Mycobacterium avium complex.2 The one prior report of M haemophilum affecting the CNS was in a 40-year-old man with AIDS who presented with right hemiparesis, ataxia, and vertigo found to have a spindle cell pseudotumor containing both M haemophilum and Mycobacterium simiae.3 Lesions of the optic chiasm are not atypical in patients with AIDS and the differential diagnosis should include other infectious agents such as M tuberculosis, syphilis, or cryptococcus and neoplasms such as lymphoma.4–7 Although vitreous biopsy did not confirm intraocular M haemophilum, the appearance of this chorioretinal lesion concurrent with the haemophilum chiasmitis, as well as the subsequent response of the lesion to the targeted treatment, suggests that it was also a site of infection. The route of entry of the Neurology 83
August 12, 2014
659
Figure
MRI of the optic pathway and biopsy of the inferior chiasm
chiasmitis, specifically from M haemophilum, should be considered in the differential diagnosis of enhancing, expansive chiasmopathies in immunocompromised patients, since early identification may lead to directed treatment and sparing of vision loss. From Weill Cornell Medical College (A.E.M., G.P., S.P., C.O., E.L., A.S., A.M., D.B., S.K., M.D.), New York Presbyterian, New York; and the University of British Columbia (S.S.), Vancouver, Canada. Author contributions: Dr. Merkler contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Parlitis contributed to data collection, manuscript preparation, and manuscript revision. Dr. Patel contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Oliveira contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Lavi contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Schuetz contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. May contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Bier contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Simpson contributed to data collection and data interpretation. Dr. Kiss contributed to data collection and data interpretation. Dr. Dinkin contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Acknowledgment: The authors thank Dr. Marshall Glesby, who cared for the patient. Study funding: No targeted funding reported. Disclosure: The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. Received December 19, 2013. Accepted in final form April 14, 2014.
Correspondence to Dr. Dinkin: [email protected]
© 2014 American Academy of Neurology 1.
Lindeboom JA, Bruijnesteijn van Coppenraet LES, van Soolingen D, Prins JM, Kuijper EJ. Clinical manifestations,
(A) Axial postcontrast MRI reveals a 9 3 16 3 12–mm enhancing T2 hyperintense mass centered in and expanding the optic chiasm. (B) Axial T1 postcontrast MRI 8 months later showed spread into the hypothalamus. The progression was subsequently linked to patient noncompliance with the antibiotic regimen. Immunochemistry with CD3, a T-cell marker (C), highlights numerous T lymphocytes (shown in blue), which are found in perivascular areas and infiltrate into the chiasmal tissue. Luxol fast blue stain (D), which normally shows intense blue throughout the chiasmal tissue, demonstrates a remarkable myelin loss, especially at the center of the specimen. (E) Relative preservation of axons by neurofilament immunohistochemistry. (F) Acid-fast organisms (shown in red by acid-fast bacillus stain).
organism was likely cutaneous with subsequent hematogenous spread to both the eye and CNS. Hematogenous spread to the eye is supported by ocular tomography evidence of spread from the highly vascular choroid to the retina and eventual bilateral ocular involvement. We present a case of M haemophilum infection affecting the anterior visual pathways and CNS. Although a rare entity, atypical mycobacterium
660
Neurology 83
August 12, 2014
2.
diagnosis, and treatment of Mycobacterium haemophilum infections. Clin Microbiol Rev 2011;24:701–717. Katoch VM. Infections due to non-tuberculous mycobacte-
3.
ria (NTM). Indian J Med Res 2004;120:290–304. Phowthongkum P, Puengchitprapai A, Udomsantisook N, Tumwasorn S, Suankratay C. Spindle cell pseudotumor of the brain associated with Mycobacterium haemophilum and
4.
Mycobacterium simiae mixed infection in a patient with AIDS: the first case report. Int J Infect Dis 2008;12:421–424. Cohen DB, Glasgow BJ. Bilateral optic nerve cryptococcosis in sudden blindness in patients with acquired immune defi-
5.
ciency syndrome. Ophthalmology 1993;100:1689–1694. Garg RK, Paliwal V, Malhotra HS. Tuberculous optochiasmatic arachnoiditis: a devastating form of tuberculous men-
6.
ingitis. Expert Rev Anti Infect Ther 2011;9:719–729. Lee AG, Tang RA, Roberts D, Schiffman JS, Osborne A. Primary central nervous system lymphoma involving the
7.
optic chiasm in AIDS. J Neuroophthalmol 2001:95–98. Hausman L. Syphilitic arachnoiditis of the optic chiasm. Arch Neurpsych 1937;37:929–958.
Infection of the optic apparatus and hypothalamus by Mycobacterium haemophilum Alexander E. Merkler, George Parlitsis, Sarju Patel, et al. Neurology 2014;83;659-660 Published Online before print July 9, 2014 DOI 10.1212/WNL.0000000000000702 This information is current as of July 9, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/83/7/659.full.html
References
This article cites 6 articles, 1 of which you can access for free at: http://www.neurology.org/content/83/7/659.full.html##ref-list-1
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
Alexander E. Merkler, MD George Parlitsis, MD Sarju Patel, MD Cristiano Oliveira, MD Ehud Lavi, MD Audrey Schuetz, MD Alison May, MD Dara Bier, MD Sara Simpson, MD Szilard Kiss, MD Marc Dinkin, MD
INFECTION OF THE OPTIC APPARATUS AND HYPOTHALAMUS BY MYCOBACTERIUM HAEMOPHILUM
Mycobacterium haemophilum is a nontuberculous mycobacterium that primarily manifests as cutaneous ulcerations in immunocompromised adults and cervical lymphadenitis in immunocompetent children.1 We present a case of M haemophilum infection of the optic chiasm, tract, and hypothalamus in a patient with AIDS. Case report. A 44-year-old man with AIDS, treated syphilis, and cytomegalovirus retinitis in his right eye (OD) presented with decreased vision in his left eye (OS) and headache. On examination, visual acuity was 20/40 OD and counting fingers OS. There was a left relative afferent pupillary defect. Funduscopy demonstrated nonactive chorioretinal scarring from his prior episode of chorioretinitis and a new, focal area of chorioretinitis with satellite lesions OS. Optical coherence tomography indicated extension of the lesion from the outer retinal layer inward, suggesting spread from the choroid. Humphrey visual field testing revealed severe field loss OS and a temporal hemianopsia OD. Laboratory evaluation revealed a CD4 count of 4 and viral load of 49,927 copies. Rapid plasma reagin was reactive, with fluorescent treponemal antibody absorption test (1:8). Angiotensin-converting enzyme (ACE) was elevated at 83 U/L (reference 9–67). Bacterial and fungal cultures, toxoplasma antibodies, and cryptococcal antigen were negative. Quantiferon TB gold testing was twice indeterminate. Brain MRI revealed a 9 3 16 3 12–mm enhancing, T2 hyperintense mass centered in and expanding the optic chiasm with T2 hyperintensity extending into the left optic tract (figure). CSF analysis revealed 9 leukocytes, protein 40 mg/dL, glucose 47 mg/dL, and a negative Gram stain, culture, KOH prep, cryptococcal antigen, acid-fast bacillus culture, Mycobacterium tuberculosis amplification, viral studies, cytology, flow cytometry, and Venereal Disease Research Laboratory. CSF ACE was normal at 1.4. Vitreous biopsy revealed negative Gram stain, culture, and KOH prep. Body PET-CT revealed no abnormal fluorodeoxyglucose uptake. A biopsy of the optic chiasm revealed a T-cell lymphocytic infiltrate in a perivascular distribution with
massive demyelination and axonal preservation (figure). Spirochete stains were negative. The pathologic interpretation was demyelinating optic chiasmitis and 5 days of IV immunoglobulin was administered, followed by 3 days of IV methylprednisolone, which resulted in rapid improvement in visual acuity to 20/60 OD and 20/400 OS. Ten days later, vision worsened OS and repeat MRI revealed an increase in the right aspect of the chiasmal mass and new extension along the right optic tract. Steroids were restarted with visual improvement. Acid-fast stain of the biopsied chiasm revealed innumerable bacilli, which DNA PCR revealed to be M haemophilum (figure). Antibiotics and oral steroids were initiated and 2 weeks later, visual acuity improved to 20/25 OD. Seven months later, in the setting of noncompliance with antibiotics, chiasmal enhancement had improved, but the left optic nerve newly enhanced and acuity decreased to light perception OS. One month later, there was extension into the hypothalamus (figure) and a new focal area of chorioretinitis OD. Discussion. We report a case of M haemophilum infection of the optic apparatus and hypothalamus and concurrent chorioretinal lesion. The perivascular T-cell infiltrate with demyelination and axonal sparing represent a unique pathologic presentation for mycobacterial disease in the CNS, and may be a reflection of the severely immunocompromised state of our patient. CNS involvement is rare in cases of nontuberculous mycobacterium, manifesting mostly as a meningoencephalitis in patients with Mycobacterium avium complex.2 The one prior report of M haemophilum affecting the CNS was in a 40-year-old man with AIDS who presented with right hemiparesis, ataxia, and vertigo found to have a spindle cell pseudotumor containing both M haemophilum and Mycobacterium simiae.3 Lesions of the optic chiasm are not atypical in patients with AIDS and the differential diagnosis should include other infectious agents such as M tuberculosis, syphilis, or cryptococcus and neoplasms such as lymphoma.4–7 Although vitreous biopsy did not confirm intraocular M haemophilum, the appearance of this chorioretinal lesion concurrent with the haemophilum chiasmitis, as well as the subsequent response of the lesion to the targeted treatment, suggests that it was also a site of infection. The route of entry of the Neurology 83
August 12, 2014
659
Figure
MRI of the optic pathway and biopsy of the inferior chiasm
chiasmitis, specifically from M haemophilum, should be considered in the differential diagnosis of enhancing, expansive chiasmopathies in immunocompromised patients, since early identification may lead to directed treatment and sparing of vision loss. From Weill Cornell Medical College (A.E.M., G.P., S.P., C.O., E.L., A.S., A.M., D.B., S.K., M.D.), New York Presbyterian, New York; and the University of British Columbia (S.S.), Vancouver, Canada. Author contributions: Dr. Merkler contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Parlitis contributed to data collection, manuscript preparation, and manuscript revision. Dr. Patel contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Oliveira contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Lavi contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Schuetz contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. May contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Bier contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Dr. Simpson contributed to data collection and data interpretation. Dr. Kiss contributed to data collection and data interpretation. Dr. Dinkin contributed to data collection, data interpretation, manuscript preparation, and manuscript revision. Acknowledgment: The authors thank Dr. Marshall Glesby, who cared for the patient. Study funding: No targeted funding reported. Disclosure: The authors report no disclosures relevant to the manuscript. Go to Neurology.org for full disclosures. Received December 19, 2013. Accepted in final form April 14, 2014.
Correspondence to Dr. Dinkin: [email protected]
© 2014 American Academy of Neurology 1.
Lindeboom JA, Bruijnesteijn van Coppenraet LES, van Soolingen D, Prins JM, Kuijper EJ. Clinical manifestations,
(A) Axial postcontrast MRI reveals a 9 3 16 3 12–mm enhancing T2 hyperintense mass centered in and expanding the optic chiasm. (B) Axial T1 postcontrast MRI 8 months later showed spread into the hypothalamus. The progression was subsequently linked to patient noncompliance with the antibiotic regimen. Immunochemistry with CD3, a T-cell marker (C), highlights numerous T lymphocytes (shown in blue), which are found in perivascular areas and infiltrate into the chiasmal tissue. Luxol fast blue stain (D), which normally shows intense blue throughout the chiasmal tissue, demonstrates a remarkable myelin loss, especially at the center of the specimen. (E) Relative preservation of axons by neurofilament immunohistochemistry. (F) Acid-fast organisms (shown in red by acid-fast bacillus stain).
organism was likely cutaneous with subsequent hematogenous spread to both the eye and CNS. Hematogenous spread to the eye is supported by ocular tomography evidence of spread from the highly vascular choroid to the retina and eventual bilateral ocular involvement. We present a case of M haemophilum infection affecting the anterior visual pathways and CNS. Although a rare entity, atypical mycobacterium
660
Neurology 83
August 12, 2014
2.
diagnosis, and treatment of Mycobacterium haemophilum infections. Clin Microbiol Rev 2011;24:701–717. Katoch VM. Infections due to non-tuberculous mycobacte-
3.
ria (NTM). Indian J Med Res 2004;120:290–304. Phowthongkum P, Puengchitprapai A, Udomsantisook N, Tumwasorn S, Suankratay C. Spindle cell pseudotumor of the brain associated with Mycobacterium haemophilum and
4.
Mycobacterium simiae mixed infection in a patient with AIDS: the first case report. Int J Infect Dis 2008;12:421–424. Cohen DB, Glasgow BJ. Bilateral optic nerve cryptococcosis in sudden blindness in patients with acquired immune defi-
5.
ciency syndrome. Ophthalmology 1993;100:1689–1694. Garg RK, Paliwal V, Malhotra HS. Tuberculous optochiasmatic arachnoiditis: a devastating form of tuberculous men-
6.
ingitis. Expert Rev Anti Infect Ther 2011;9:719–729. Lee AG, Tang RA, Roberts D, Schiffman JS, Osborne A. Primary central nervous system lymphoma involving the
7.
optic chiasm in AIDS. J Neuroophthalmol 2001:95–98. Hausman L. Syphilitic arachnoiditis of the optic chiasm. Arch Neurpsych 1937;37:929–958.
Infection of the optic apparatus and hypothalamus by Mycobacterium haemophilum Alexander E. Merkler, George Parlitsis, Sarju Patel, et al. Neurology 2014;83;659-660 Published Online before print July 9, 2014 DOI 10.1212/WNL.0000000000000702 This information is current as of July 9, 2014 Updated Information & Services
including high resolution figures, can be found at: http://www.neurology.org/content/83/7/659.full.html
References
This article cites 6 articles, 1 of which you can access for free at: http://www.neurology.org/content/83/7/659.full.html##ref-list-1
Permissions & Licensing
Information about reproducing this article in parts (figures,tables) or in its entirety can be found online at: http://www.neurology.org/misc/about.xhtml#permissions
Reprints
Information about ordering reprints can be found online: http://www.neurology.org/misc/addir.xhtml#reprintsus
Neurology ® is the official journal of the American Academy of Neurology. Published continuously since 1951, it is now a weekly with 48 issues per year. Copyright © 2014 American Academy of Neurology. All rights reserved. Print ISSN: 0028-3878. Online ISSN: 1526-632X.
