Case Report
HIV-Associated Neurocysticercosis
Journal of the International Association of Providers of AIDS Care 1–3 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2325957414555232 jiapac.sagepub.com
Kuljeet Singh Anand, MD, DM (Neurology)1, Ankur Wadhwa, MD1, Jyoti Garg, MD, DNB, DM (Neurology)1, and Rakesh Kumar Mahajan, MD (Microbiology)1
Abstract Few cases of HIV and neurocysticercosis co-infection have been reported till date. The symptomatic manifestation of cysticercosis may be further reduced by interactions between the 2 disease processes. In patients with HIV, the diagnosis of neurocysticercosis is challenging and management must be individualized depending on the stage and the coexistent opportunistic conditions. We present 2 such cases. First was a 35-year-old driver seropositive for HIV-1 presented with complex partial seizures and a CD4 count of 530 cells/mm3. The second case was a 40-year-old businessman with a CD4 count of 350 cells/mm3. Both of them had multiple parenchymal lesions, with 1 being a large cystic lesion. Relatively high CD4 count and a positive enzyme-linked immunosorbent assay increased the likelihood for diagnosis and treatment. Both of our patients received cysticidal therapy, and none of them deteriorated with treatment. Keywords neurocysticercosis, HIV
Introduction Neurocysticercosis (NCC) is considered to be the most common parasitic infestation of the central nervous system and the single most common cause of epilepsy in the developing countries.1 Human cysticercosis results from the ingestion of food, water, and vegetables contaminated with Taenia solium eggs or even by autoinfection in case of persons with intestinal taeniasis. Relatively few cases of HIV and NCC co-infection have been reported, even in areas where there is high prevalence of both diseases individually, and the influence of HIV infection on the natural history of cysticercosis is yet to be defined.2 Moreover as exemplified by various studies, the symptomatic manifestation of cysticercosis may be further reduced by interactions between the 2 disease processes.2 Symptomatic NCC largely depends on the host inflammatory response, and decreased cell-mediated immunity characteristic of advanced HIV infection makes cysticercosis more likely to remain asymptomatic.3 Neurocysticercosis, therefore, may be more likely to present when the CD4 count is relatively spared. Above all, an accurate diagnosis and management of the coinfection remains challenging. Here, we present 2 cases of NCC with coincident HIV infection.
enzyme-linked immunosorbent assay (ELISA). His initial CD4 count was 115 cells/mm3, which rose to 530 cells/mm3 after 1 year of regular antiretroviral therapy (ART). He was referred to neurology for recurrent, complex partial seizures with secondary generalization for 3 months prior to presentation. General physical, systemic, and neurological examinations were normal. Routine hematological and biochemical analyses including chest X-ray, electrocardiogram (ECG), and ocular B scan were normal. X-ray of thighs showed multiple soft tissue calcifications. Serum venereal disease research laboratory (VDRL), cryptococcal antigen, and toxoplasma immunoglobulin (Ig) G were negative. Enzyme-linked immunosorbent assay for IgM antibodies against T solium was reactive. Contrast computerized tomography of head showed 2 enhancing rounded lesions with eccentric nodules and small nodular calcified lesions in bilateral cerebral hemispheres (Figure 1). Magnetic resonance imaging (MRI; T1, fluid-attenuated inversion recovery [FLAIR], T2 weighted, and postcontrast T1) of brain also demonstrated 2 thin rim-enhancing lesions in bilateral cerebral hemispheres. The lesions were hypointense to isointense on T1 and hyperintense on T2 weighted with suppression on FLAIR images. The MRI
1
Department of Neurology and Microbiology, Dr. R. M. L. Hospital, New Delhi, India
Case 1 A 35-year-old man, driver by occupation, presented to our institute with a 2-month history of watery diarrhea 1 year back. Workup for chronic diarrhea revealed positive HIV serology by
Corresponding Author: Ankur Wadhwa, Block B-1B, House No. 1, 2nd Floor, JanakPuri, New Delhi 110058, India. Email: [email protected]
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 23, 2015
2
Journal of the International Association of Providers of AIDS Care
Figure 2. MRI brain showing ring lesion with eccentric nodule and adjacent large cystic lesion in right parieto occipital region. Figure 1. Contrast computerized tomography of head showing two enhancing rounded lesions with eccentric nodules.
findings were suggestive of NCC in varying stages. He was treated with cysticidal drug (albendazole 15 mg/kg/d for 28 days) along with steroids per the American academy of neurology guidelines.4
Case 2 A 40-year-old businessman who was detected to be HIV positive 1 year ago presented to us with multiple episodes of complex partial seizures and sudden loss of vision in left hemifield of both eyes for 20 days’ duration. He was on regular ART and his CD4 count was 350 cells/mm3. General physical and systemic examinations were normal. Neurological examination revealed blurring of optic disc margin bilaterally with left homonymous hemianopia. There were no motor, sensory, or reflex deficits. Planter responses were flexor. Routine hematological, biochemical tests, chest skiagram, ECG, and ocular B scan were normal. Ultrasound of abdomen was unremarkable. Serum VDRL, echinococcus IgG, and toxoplasma IgG were nonreactive. Enzyme-linked immunosorbent assay for IgM antibodies against T solium was reactive. The MRI of brain demonstrated 3 ring lesions with eccentric nodule within them in right parietal, right frontal, and left parafalcine posterior frontal lobe lesions with mild peripheral enhancement. In addition, there was large cystic lesion in right parietooccipital lobe with effacement of adjacent sulcal spaces (Figure 2). There was no midline shift. Magnetic resonance spectroscopy revealed haphazard curves with small unknown peaks with normal
N-acetylaspartate (NAA) peaks and small choline–creatine peaks representing benign lesions. The MRI was suggestive of vesicular to colloidal stages of cysticerci with 1 giant cysticercal cyst. Cerebrospinal fluid (CSF) analysis showed clear fluid, no cells, 98 mg% sugar, and 109 mg% protein. India ink staining for cryptococci was negative. The CSF-adenosine deaminase was 0.4 U/L (normal < 5). He was managed with albendazole 15 mg/kg/d for 28 days with steroids per the American academy of neurology guidelines.4 At last follow-up, he was on levetiracetam without seizure recurrence.
Discussion Due to the increased frequency of HIV infection, cysticercosis has become one of the most frequent opportunistic infections and the most common cause of focal brain lesions in patients infected with HIV-1.5 There may be varied presentations of NCC in HIV-like multiple parenchymal lesions (enhancing or nonenhancing cysts), single parenchymal lesions, atypical forms (giant brain cyst and spinal epidural lesion), or a mixture of these. However, due to paucity of data, the exact prevalence of these lesions and their relationship with CD4 counts cannot be discerned. Both of our cases had multiple parenchymal lesions with 1 being a large cystic lesion in right parietooccipital lobe. Briefly, the life cycle of T solium comprises 2 natural hosts, humans as the definite and swine as the intermediate host. Human harbors the adult tapeworm; eggs produced by the worm are disseminated to the environment through feces. The pig ingests some of these eggs, which develop into cysticerci in internal organs like muscle and brain. When human consumes
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 23, 2015
Anand et al
3
contaminated pork containing cysticerci, they develop into an adult worm in the small intestine. Taenia solium is a hermaphrodite and the gravid proglottides, containing the eggs, reach the environment by passive discharge in the feces. After being liberated from the proglottides, the eggs can be ingested by swine and humans. Once in the digestive tract, the eggs lose their coat and liberate oncospheres. The oncospheres cross the intestinal wall and local venules, enter systemic circulation, and are carried to different organs of the host. Here the oncospheres lose their hooklets, acquire a vesicular shape, and evolve into cysticerci. However, human may also become an intermediate host and develop the larval stage of the disease. Diagnosis of cysticercosis in HIV-infected patients is complicated as there is a greater incidence of mass lesions due to other causes like tuberculosis, toxoplasmosis, and so on.6 Although ELISA is most widely available for serodiagnosis of cysticercosis, the gold standard in serodiagnosis is the enzyme electroimmune transfer blot (EITB). The EITB assay is more likely to be positive in serum than in CSF samples. This test is currently commercially available and is also included as a criterion for diagnosis of NCC.7 However, the initially reported high sensitivity and specificity of the EITB assay may be misleading. The sensitivity may be reduced in particular groups of patients and in individuals from areas where cysticercosis has high seroprevalence.8 In our patients, a relatively high CD4 count indicated the capacity for sufficient inflammation in the case of cysticercal infection, possibly accounting for the patients’ symptoms and a positive ELISA increased the likelihood for diagnosis, thus warranting treatment with cysticidal drugs. In comparison to NCC in non-HIV patients, the presence of co-infection may alter the efficacy of treatment with antihelminthics and make the management more challenging.4 Hence, it is proposed that in addition to empirical treatment trial with antitoxoplasma agents, a rational approach might include early use of the serum EITB/ELISA and starting cysticidal therapy (if result is positive) before resorting to brain biopsy. Moreover, the CD4 count may be an important determinant in deciding the start of cysticidal therapy or to entertain other diagnoses.9 Both of our patients had high CD4 counts and none of them deteriorated with treatment.
Hence, management must be individualized depending on the stage of HIV infection and the coexistent opportunistic conditions. Also there is still a paucity of data especially from developing countries where both these infections are prevalent and much more about the coexistence of these diseases still needs to be learned. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Prasad KN, Prasad A, Verma A, Singh AK. Human cysticercosis and Indian scenario: a review. J Biosci. 2008;33:(4)571–582. 2. Serpa JA, Moran A, Goodman JC, Giordano TP, White C Jr. Neurocysticercosis in the HIV era: a case report and review of the literature. Am J Trop Med Hyg. 2007;77(1):113–117. 3. White AC Jr, Robinson P, Kuhn R. Taenia solium cysticercosis: hostparasite interactions and the immune response. Chem Immunol. 1997;66:209–230. 4. Baird RA, Wiebe S, Zunt JR, Halperin JJ, Gronseth G, Roos KL. Evidence based guideline: treatment of Parenchymal neurocysticercosis: report of the guideline development subcommittee of the American academy of neurology. Neurology. 2013;80(15):1424–1429. 5. Foyaca-Sibat H, Ibanez-Valdes LdeF. Intraventricular neurocysticercosis in HIV patients. Internet J Neurol. 2003;2(1):23–31. 6. White AC Jr, Dakik H, Diaz P. Asymptomatic neurocysticercosis in a patient with AIDS and cryptococcal meningitis. Am J Med. 1995;99(1):101–102. 7. Del Brutto OH, Rajshekhar V, White AC Jr, et al. Proposed diagnostic criteria for neurocysticercosis. Neurology. 2001;57(2):177–183. 8. Kojic EM, White AC Jr. A positive enzyme-linked immunoelectrotransfer blot assay result for a patient without evidence of cysticercosis. Clin Infect Dis. 2003;36(1):e7–e9. 9. Prasad S, MacGregor RR, Tebas P, Rodriguez LB, Bustos JA, White AC Jr. Management of potential neurocysticercosis in patients with HIV infection. Clin Inf Dis. 2006;42(4):e30–e34.
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 23, 2015
HIV-Associated Neurocysticercosis
Journal of the International Association of Providers of AIDS Care 1–3 ª The Author(s) 2014 Reprints and permission: sagepub.com/journalsPermissions.nav DOI: 10.1177/2325957414555232 jiapac.sagepub.com
Kuljeet Singh Anand, MD, DM (Neurology)1, Ankur Wadhwa, MD1, Jyoti Garg, MD, DNB, DM (Neurology)1, and Rakesh Kumar Mahajan, MD (Microbiology)1
Abstract Few cases of HIV and neurocysticercosis co-infection have been reported till date. The symptomatic manifestation of cysticercosis may be further reduced by interactions between the 2 disease processes. In patients with HIV, the diagnosis of neurocysticercosis is challenging and management must be individualized depending on the stage and the coexistent opportunistic conditions. We present 2 such cases. First was a 35-year-old driver seropositive for HIV-1 presented with complex partial seizures and a CD4 count of 530 cells/mm3. The second case was a 40-year-old businessman with a CD4 count of 350 cells/mm3. Both of them had multiple parenchymal lesions, with 1 being a large cystic lesion. Relatively high CD4 count and a positive enzyme-linked immunosorbent assay increased the likelihood for diagnosis and treatment. Both of our patients received cysticidal therapy, and none of them deteriorated with treatment. Keywords neurocysticercosis, HIV
Introduction Neurocysticercosis (NCC) is considered to be the most common parasitic infestation of the central nervous system and the single most common cause of epilepsy in the developing countries.1 Human cysticercosis results from the ingestion of food, water, and vegetables contaminated with Taenia solium eggs or even by autoinfection in case of persons with intestinal taeniasis. Relatively few cases of HIV and NCC co-infection have been reported, even in areas where there is high prevalence of both diseases individually, and the influence of HIV infection on the natural history of cysticercosis is yet to be defined.2 Moreover as exemplified by various studies, the symptomatic manifestation of cysticercosis may be further reduced by interactions between the 2 disease processes.2 Symptomatic NCC largely depends on the host inflammatory response, and decreased cell-mediated immunity characteristic of advanced HIV infection makes cysticercosis more likely to remain asymptomatic.3 Neurocysticercosis, therefore, may be more likely to present when the CD4 count is relatively spared. Above all, an accurate diagnosis and management of the coinfection remains challenging. Here, we present 2 cases of NCC with coincident HIV infection.
enzyme-linked immunosorbent assay (ELISA). His initial CD4 count was 115 cells/mm3, which rose to 530 cells/mm3 after 1 year of regular antiretroviral therapy (ART). He was referred to neurology for recurrent, complex partial seizures with secondary generalization for 3 months prior to presentation. General physical, systemic, and neurological examinations were normal. Routine hematological and biochemical analyses including chest X-ray, electrocardiogram (ECG), and ocular B scan were normal. X-ray of thighs showed multiple soft tissue calcifications. Serum venereal disease research laboratory (VDRL), cryptococcal antigen, and toxoplasma immunoglobulin (Ig) G were negative. Enzyme-linked immunosorbent assay for IgM antibodies against T solium was reactive. Contrast computerized tomography of head showed 2 enhancing rounded lesions with eccentric nodules and small nodular calcified lesions in bilateral cerebral hemispheres (Figure 1). Magnetic resonance imaging (MRI; T1, fluid-attenuated inversion recovery [FLAIR], T2 weighted, and postcontrast T1) of brain also demonstrated 2 thin rim-enhancing lesions in bilateral cerebral hemispheres. The lesions were hypointense to isointense on T1 and hyperintense on T2 weighted with suppression on FLAIR images. The MRI
1
Department of Neurology and Microbiology, Dr. R. M. L. Hospital, New Delhi, India
Case 1 A 35-year-old man, driver by occupation, presented to our institute with a 2-month history of watery diarrhea 1 year back. Workup for chronic diarrhea revealed positive HIV serology by
Corresponding Author: Ankur Wadhwa, Block B-1B, House No. 1, 2nd Floor, JanakPuri, New Delhi 110058, India. Email: [email protected]
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 23, 2015
2
Journal of the International Association of Providers of AIDS Care
Figure 2. MRI brain showing ring lesion with eccentric nodule and adjacent large cystic lesion in right parieto occipital region. Figure 1. Contrast computerized tomography of head showing two enhancing rounded lesions with eccentric nodules.
findings were suggestive of NCC in varying stages. He was treated with cysticidal drug (albendazole 15 mg/kg/d for 28 days) along with steroids per the American academy of neurology guidelines.4
Case 2 A 40-year-old businessman who was detected to be HIV positive 1 year ago presented to us with multiple episodes of complex partial seizures and sudden loss of vision in left hemifield of both eyes for 20 days’ duration. He was on regular ART and his CD4 count was 350 cells/mm3. General physical and systemic examinations were normal. Neurological examination revealed blurring of optic disc margin bilaterally with left homonymous hemianopia. There were no motor, sensory, or reflex deficits. Planter responses were flexor. Routine hematological, biochemical tests, chest skiagram, ECG, and ocular B scan were normal. Ultrasound of abdomen was unremarkable. Serum VDRL, echinococcus IgG, and toxoplasma IgG were nonreactive. Enzyme-linked immunosorbent assay for IgM antibodies against T solium was reactive. The MRI of brain demonstrated 3 ring lesions with eccentric nodule within them in right parietal, right frontal, and left parafalcine posterior frontal lobe lesions with mild peripheral enhancement. In addition, there was large cystic lesion in right parietooccipital lobe with effacement of adjacent sulcal spaces (Figure 2). There was no midline shift. Magnetic resonance spectroscopy revealed haphazard curves with small unknown peaks with normal
N-acetylaspartate (NAA) peaks and small choline–creatine peaks representing benign lesions. The MRI was suggestive of vesicular to colloidal stages of cysticerci with 1 giant cysticercal cyst. Cerebrospinal fluid (CSF) analysis showed clear fluid, no cells, 98 mg% sugar, and 109 mg% protein. India ink staining for cryptococci was negative. The CSF-adenosine deaminase was 0.4 U/L (normal < 5). He was managed with albendazole 15 mg/kg/d for 28 days with steroids per the American academy of neurology guidelines.4 At last follow-up, he was on levetiracetam without seizure recurrence.
Discussion Due to the increased frequency of HIV infection, cysticercosis has become one of the most frequent opportunistic infections and the most common cause of focal brain lesions in patients infected with HIV-1.5 There may be varied presentations of NCC in HIV-like multiple parenchymal lesions (enhancing or nonenhancing cysts), single parenchymal lesions, atypical forms (giant brain cyst and spinal epidural lesion), or a mixture of these. However, due to paucity of data, the exact prevalence of these lesions and their relationship with CD4 counts cannot be discerned. Both of our cases had multiple parenchymal lesions with 1 being a large cystic lesion in right parietooccipital lobe. Briefly, the life cycle of T solium comprises 2 natural hosts, humans as the definite and swine as the intermediate host. Human harbors the adult tapeworm; eggs produced by the worm are disseminated to the environment through feces. The pig ingests some of these eggs, which develop into cysticerci in internal organs like muscle and brain. When human consumes
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 23, 2015
Anand et al
3
contaminated pork containing cysticerci, they develop into an adult worm in the small intestine. Taenia solium is a hermaphrodite and the gravid proglottides, containing the eggs, reach the environment by passive discharge in the feces. After being liberated from the proglottides, the eggs can be ingested by swine and humans. Once in the digestive tract, the eggs lose their coat and liberate oncospheres. The oncospheres cross the intestinal wall and local venules, enter systemic circulation, and are carried to different organs of the host. Here the oncospheres lose their hooklets, acquire a vesicular shape, and evolve into cysticerci. However, human may also become an intermediate host and develop the larval stage of the disease. Diagnosis of cysticercosis in HIV-infected patients is complicated as there is a greater incidence of mass lesions due to other causes like tuberculosis, toxoplasmosis, and so on.6 Although ELISA is most widely available for serodiagnosis of cysticercosis, the gold standard in serodiagnosis is the enzyme electroimmune transfer blot (EITB). The EITB assay is more likely to be positive in serum than in CSF samples. This test is currently commercially available and is also included as a criterion for diagnosis of NCC.7 However, the initially reported high sensitivity and specificity of the EITB assay may be misleading. The sensitivity may be reduced in particular groups of patients and in individuals from areas where cysticercosis has high seroprevalence.8 In our patients, a relatively high CD4 count indicated the capacity for sufficient inflammation in the case of cysticercal infection, possibly accounting for the patients’ symptoms and a positive ELISA increased the likelihood for diagnosis, thus warranting treatment with cysticidal drugs. In comparison to NCC in non-HIV patients, the presence of co-infection may alter the efficacy of treatment with antihelminthics and make the management more challenging.4 Hence, it is proposed that in addition to empirical treatment trial with antitoxoplasma agents, a rational approach might include early use of the serum EITB/ELISA and starting cysticidal therapy (if result is positive) before resorting to brain biopsy. Moreover, the CD4 count may be an important determinant in deciding the start of cysticidal therapy or to entertain other diagnoses.9 Both of our patients had high CD4 counts and none of them deteriorated with treatment.
Hence, management must be individualized depending on the stage of HIV infection and the coexistent opportunistic conditions. Also there is still a paucity of data especially from developing countries where both these infections are prevalent and much more about the coexistence of these diseases still needs to be learned. Declaration of Conflicting Interests The author(s) declared no potential conflicts of interest with respect to the research, authorship, and/or publication of this article.
Funding The author(s) received no financial support for the research, authorship, and/or publication of this article.
References 1. Prasad KN, Prasad A, Verma A, Singh AK. Human cysticercosis and Indian scenario: a review. J Biosci. 2008;33:(4)571–582. 2. Serpa JA, Moran A, Goodman JC, Giordano TP, White C Jr. Neurocysticercosis in the HIV era: a case report and review of the literature. Am J Trop Med Hyg. 2007;77(1):113–117. 3. White AC Jr, Robinson P, Kuhn R. Taenia solium cysticercosis: hostparasite interactions and the immune response. Chem Immunol. 1997;66:209–230. 4. Baird RA, Wiebe S, Zunt JR, Halperin JJ, Gronseth G, Roos KL. Evidence based guideline: treatment of Parenchymal neurocysticercosis: report of the guideline development subcommittee of the American academy of neurology. Neurology. 2013;80(15):1424–1429. 5. Foyaca-Sibat H, Ibanez-Valdes LdeF. Intraventricular neurocysticercosis in HIV patients. Internet J Neurol. 2003;2(1):23–31. 6. White AC Jr, Dakik H, Diaz P. Asymptomatic neurocysticercosis in a patient with AIDS and cryptococcal meningitis. Am J Med. 1995;99(1):101–102. 7. Del Brutto OH, Rajshekhar V, White AC Jr, et al. Proposed diagnostic criteria for neurocysticercosis. Neurology. 2001;57(2):177–183. 8. Kojic EM, White AC Jr. A positive enzyme-linked immunoelectrotransfer blot assay result for a patient without evidence of cysticercosis. Clin Infect Dis. 2003;36(1):e7–e9. 9. Prasad S, MacGregor RR, Tebas P, Rodriguez LB, Bustos JA, White AC Jr. Management of potential neurocysticercosis in patients with HIV infection. Clin Inf Dis. 2006;42(4):e30–e34.
Downloaded from jia.sagepub.com at HOWARD UNIV UNDERGRAD LIBRARY on February 23, 2015
