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January 31, 2017; 88 (5) Article

New-onset seizure in HIV-infected adult Zambians

A search for causes and consequences

Omar K. Siddiqi, Melissa A. Elafros, Christopher M. Bositis, Igor J. Koralnik, William H. Theodore, Jason F. Okulicz, Lisa Kalungwana, Michael J. Potchen, Izukanji Sikazwe, Gretchen L. Birbeck
First published December 21, 2016, DOI: https://doi.org/10.1212/WNL.0000000000003538
Omar K. Siddiqi
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
MD, MPH
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Melissa A. Elafros
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
MD, PhD
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Christopher M. Bositis
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
MD
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Igor J. Koralnik
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
MD
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William H. Theodore
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
MD
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Jason F. Okulicz
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
MD
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Lisa Kalungwana
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
MS
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Michael J. Potchen
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
MD
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Izukanji Sikazwe
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
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Gretchen L. Birbeck
From the Global Neurology Program, Department of Neurology (O.K.S., I.J.K.), and Center for Virology and Vaccines Research, Department of Internal Medicine (O.K.S., I.J.K.), Beth Israel Deaconess Medical Center, Boston, MA; Department of Internal Medicine (O.K.S.), University of Zambia School of Medicine (UNZA-SOM), Lusaka; College of Human Medicine (M.A.E.), Michigan State University (MSU), East Lansing; Greater Lawrence Family Health Center (C.M.B.); Clinical Epilepsy Division (W.H.T.), United States National Institutes of Health, Bethesda, MD; HIV Evaluation Unit (J.F.O.), Infectious Disease Service, San Antonio Military Medical Center, TX; Department of Psychiatry (L.K.), University of Zambia (UNZA), Lusaka; Neuroradiology Division, Department of Imaging Sciences (M.J.P.), and Strong Epilepsy Center, Department of Neurology (G.L.B.), University of Rochester, NY; Department of Radiology (M.J.P.), Lusaka Apex Medical University; Centre for Infectious Disease Research in Zambia (CIDRZ) (I.S.), Lusaka; and Epilepsy Care Team (G.L.B.), Chikankata Hospital, Mazabuka, Zambia.
MD, MPH, DTMH
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Citation
New-onset seizure in HIV-infected adult Zambians
A search for causes and consequences
Omar K. Siddiqi, Melissa A. Elafros, Christopher M. Bositis, Igor J. Koralnik, William H. Theodore, Jason F. Okulicz, Lisa Kalungwana, Michael J. Potchen, Izukanji Sikazwe, Gretchen L. Birbeck
Neurology Jan 2017, 88 (5) 477-482; DOI: 10.1212/WNL.0000000000003538

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Abstract

Objective: To identify the etiology of new-onset seizure in HIV-infected Zambian adults and identify risk factors for seizure recurrence.

Methods: A prospective cohort study enrolling HIV-infected adults with new-onset seizure within 2 weeks of index seizure obtained clinical, laboratory, and neuroimaging data to determine seizure etiology. Participants were followed to identify risk factors for seizure recurrence. Risk factors for mortality were examined as mortality rates were unexpectedly high.

Results: Eighty-one patients with CSF for analysis were enrolled and followed for a median of 306 days (interquartile range 61–636). Most (91%) were at WHO stage III/IV and 66 (81%) had a pre-seizure Karnofsky score ≥50. Prolonged or multiple seizures occurred in 46 (57%), including 12 (15%) with status epilepticus. Seizure etiologies included CNS opportunistic infections (OI) in 21 (26%), hyponatremia in 23 (28%), and other infections in 8 (10%). OIs included Cryptococcus (17%), JC virus (7%) and 5% each for tuberculosis, cytomegalovirus, and varicella-zoster virus. No etiology could be identified in 16 (20%). Thirty (37%) patients died during follow-up and 20 (25%) had recurrent seizures with survival being the only identifiable risk factor.

Conclusions: HIV-infected adults with new-onset seizure in Zambia often have advanced HIV disease with OI being the most frequent seizure etiology. Seizure recurrence is common but no risk factors for recurrence other than survival were identified. These findings suggest an urgent need for immune reconstitution in this population. Initiating treatment for seizure prophylaxis where only enzyme-inducing antiepileptic medications are available could threaten antiretroviral efficacy.

GLOSSARY

AED=
antiepileptic drug;
AIDC=
Adult Infectious Disease Center for Excellence;
cART=
combined antiretroviral therapy;
CHASE=
Cohort of HIV-Associated Seizure and Epilepsy;
CrAg=
cryptococcal antigen;
EBV=
Epstein-Barr virus;
IQR=
interquartile range;
IRIS=
immune reconstitution inflammatory syndrome;
OI=
opportunistic infections;
RPR=
rapid plasma reagin;
TPHA=
Treponema pallidum hemagglutination assay;
UTH=
University Teaching Hospital

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received March 26, 2016.
  • Accepted in final form October 26, 2016.
  • © 2016 American Academy of Neurology
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