in patients presenting with their first seizure , identifiable structural brain abnormalities are a risk factor for recurrent seizure and imaging helps guide clinicians in determining whether or not to recommend the initiation of chronic treatment with antiepileptic drugs ( aeds ) after an initial seizure . the epidemiologic data that informs this decision - making process was obtained in studies of hiv negative individuals . whether structural brain lesions in people with hiv , a significant proportion of which may represent transient , infectious phenomena , are predictive of recurrent seizures and indicate the need for chronic therapy is unknown . in resource - limited settings , where enzyme - inducing aeds may be the only available medications , initiating long - term epilepsy treatment carries the additional concern of adverse aed - antiretroviral ( arv ) interactions and warrants especially careful consideration . in the us , neuroimaging is indicated in hiv+ patients with new onset seizure for diagnostic purposes and to assure that lumbar puncture is not contraindicated . in sub - saharan african ( ssa ) countries , hiv remains the number one cause of disease and disability , despite the availability of arvs . although neuroimaging was not routinely available in most african settings in 2004 , there is some evidence that , at least in tertiary care centers , access to imaging technology is improving . there are few studies of hiv - related neuroimaging findings in africa , and viral clade differences may make extrapolations from the united states and european studies inappropriate . in african children with hiv , brain atrophy with dilatation of the lateral ventricles , calcification of the basal ganglia , and periventricular white matter involvement are the most common neuroimaging findings . we report the neuroimaging findings in a cohort study of hiv - associated seizures and epilepsy ( chase study ) which was conducted in zambia . acute clinical and demographic risk factors for imaging abnormalities and the prognostic value of imaging for seizure recurrence and death are also described . hiv+ adults who presented to the university teaching hospital in lusaka , zambia with new onset seizure between august 1 , 2011 and june 19 , 2013 were enrolled in chase . additional inclusion criteria included age 18 years and no prior history of seizures except for childhood febrile seizures . written consent from the patient or their proxy was required . at enrollment , clinical and demographic characteristics were obtained as well as an electroencephalograph and , for patients who consented to lumbar puncture , cerebrospinal fluid ( csf ) analysis which included extensive studies using pcr technology to identify opportunistic infections ( ois ) . after discharge , neuropsychiatric assessments with instruments previously used in zambia to detect hiv - associated neurocognitive disorders ( hand ) and psychiatric morbidity were conducted by a neuropsychologist ( lk ) including the shona symptom questionnaire ( ssq ) , the international hiv dementia scale ( ihds ) and the zambian mini - mental state exam ( zmmse).12 - 14 chase participants were followed prospectively with explicit assessments made during their hiv clinic visits to identify recurrent seizures . death outcomes were obtained through clinic and hospital records and contact with family members through december 21 , 2013 . when family members were interviewed after the death of a participant , specific questions were asked regarding recurrent seizures including seizures around the time of death . a head computed tomography ( ct ) with contrast was performed as part of the study for chase participants in whom no seizure etiology was established based upon other diagnostic assessments , including csf analyses . ct imaging was acquired on a siemens ct2007ys ct scanner and magnetic resonance ( mr ) imaging on a siemen s magnetom essenza 1.5 t mri scanner siemens , munich , germany ) . ct protocols included : 1.5 mm contiguous axial imaging from the foramen magnum through the vertex for 3d reconstruction with 4 mm oblique axial imaging pre- and post - contrast . mri protocols included sagittal t1 , axial t2 , flair , diffusion weighted imaging with apparent diffusion coefficients , and t1 pre and post contrast , as well as coronal t2 images . several participants had neuroimaging studies , including 2 mris , obtained as part of their routine clinical care . in these patients , there were no predetermined criteria for contrast administration and not all of them received contrast , possibly due to medical contraindications or cost incurred directly by the patient . both ct and mri findings were interpreted and coded using an early version of neurointerp which codes dichotomous or ordinal values for specific anatomical findings . these included the presence of cortical abnormalities , the presence of white matter abnormalities , the extent of white matter involvement , deep structural abnormalities , and posterior fossa abnormalities . other radiographic findings captured included the presence of : abnormal masses or mass effect , abnormal fluid collections , intracranial bleeds , and calcifications . the extent of ventricular size ( decreased , normal or increased ) , and brain volume ( on a scale of 1 - 5 with 3 being normal ) were determined as well as contrast enhancement , if contrast was administered . the study radiologist ( mjp ) interpreted both the clinical and research images . he was provided with age and gender and was aware of the patients hiv status and presenting symptoms , but was blinded to other clinical findings and outcome . we used chi - square , t - test analysis or the kruskal - wallis test where population variances were non - homogenous to i ) identify clinical and demographic risk factors for imaging findings , and ii ) determine if imaging findings were predictive of death or recurrent seizure . a p - value < 0.05 was considered statistically significant . prior to study initiation , the michigan state university biomedical institutional review board ( msu birb ) and the university of zambia , school of medicine biomedical research ethics committee ( unza brec ) provided ethical approval of the study . written consent for participation was obtained from the participant or their proxy , if the participant was incapacitated . a total of 43 chase participants were imaged : 41 with ct and 2 using mri . the mean age of participants was 37 years ; 24 were male . approximately 80% had advanced hiv infection ( who stage iii or iv ; mean cd4 count 186 cells / mm ) and 44% had an oi identified . the neuropsychiatric symptom burden was high , with over half of participants endorsing symptoms of anxiety and depression severe enough to warrant further clinical evaluation based upon who recommendations using the ssq . over half also scored below normal values on the ihds and on the less specific zmmse suggesting a substantial burden of cognitive impairment in this cohort ( table 1 ) . imaging abnormalities were identified in 70% of participants , with white matter abnormalities being the most common finding ( 56% ) , primarily from vasogenic edema . deep gray ( 19% ) , posterior fossa ( 21% ) , and cortical abnormalities ( 28% ) were also common . brain volumes were increased in 17% of subjects usually associated with cns infections , while other participants showed evidence of generalized atrophy . isolated enlarged ventricles , indicative of subcortical atrophy , were seen in 16% ( table 2 ) . given the prevalence of imaging abnormalities in this cohort , our analyses had ~90% power to detect an effect size difference of 22% or more in the primary outcomes of interest ( death and recurrent seizure ) . during follow - up , patients with entirely normal brain images had a lower burden of depression and anxiety symptoms based upon the ssq ( 3.0 vs. 5.3 , p=0.04 ) and patients with subcortical atrophy had a lower mean ihds score ( 5.2 vs. 9.3 , p=0.002 ) . although edema was associated with ois ( 36 vs. 6% , or 8.79 ( 95%ci : 1.03 - 236 , p=0.04 ) , none of the imaging findings , including cortical lesions , were predictive of seizure recurrence or death ( table 3 ) . in this cohort of hiv - positive patients with their first seizure , most had advanced hiv disease and status epilepticus was common . the imaging findings were diverse and included evidence of acute ois as well chronic atrophic changes . structural brain lesions , evident primarily using ct , were not predictive of recurrent seizure or death in this cohort . this patient population was evaluated at zambia s only tertiary care referral center and as such they may not be representative of all adults with hiv in zambia . attempts to recruit from a community - based hiv clinic for more than 6 months failed to identify anyone with hiv presenting in the outpatient settings within 2 weeks of a new onset seizure . mri imaging may have identified lesions not evident on ct . however , ct is more readily available and less expensive in most african tertiary care centers and therefore this data may be particularly useful in such resource limited settings . imaging was preferentially obtained on chase patients who had no evident etiology for their seizure after a thorough work up including extensive csf studies . recurrent seizures in participants who died may not have been adequately identified , but there was also no association between imaging abnormalities and death . participants with any abnormality on their brain image had a higher burden of psychiatric symptoms . this is particularly interesting since psychiatric morbidity , as measured by the ssq , has previously been shown to predict early mortality in rural zambians with hiv , even after controlling for hiv stage and socioeconomic status . subcortical atrophy was associated with clinical evidence of cognitive impairment based upon lower ihds scores . previous research in south africa using mri technology identified brain atrophy in several brain regions ( white matter , thalamus , gray matter , subcortical regions ) in hiv+ vs. hiv  individuals . using ct technology , we found that subcortical atrophy was specifically associated with the evidence of lower mean scores on the ihds but not zmmse . neuropsychiatric morbidity , including cognitive impairment , depression and anxiety , are likely underdiagnosed and undertreated in most resource limited settings . the association between psychiatric symptoms and structural brain lesions provides further support for the need to institute basic neuropsychiatric screening in hiv clinics . epilepsy is a common non - communicable disease in ssa , where most people with hiv reside and the inevitable co - occurrence of two common conditions is further compounded by the high risk of provoked seizure in people with hiv due to ois , metabolic derangements , arvs which reduce the seizure threshold , and other challenges . further studies are needed to determine neurologic vulnerabilities and outcomes in people with hiv , particularly in rural and pediatric populations . as hiv continues to evolve from a fatal to a chronic condition and neuroimaging becomes increasingly available , clinicians and researchers need additional epidemiologic and natural history data relevant to this population to direct care and set research priorities .