HIV Encephalitis Research Articles

Longitudinal Study of Cognitive Function in People with HIV and Toxoplasmic Encephalitis or Latent toxoplasma Infection.

Neurocognitive impairment (NCI) may occur during and persist even after recovery from HIV-related CNS co-infections such as toxoplasmic encephalitis (TE). The long-term cognitive effects of TE and latent toxoplomasmic infections (LTI) among persons with HIV (PWH) are unknown. We measured longitudinal effects on NC functioning in PWH with TE compared to LTI or no toxoplasmal infection. PWH (n = 345) followed in two longitudinal cohort studies underwent comprehensive neurocognitive assessments and an anti-Toxoplamic IgG assay. Participants were classified into one of three groups: TE+ (n = 39), LTI+ (n = 34), LTI- (n = 272). The primary outcome was change in neurocognitive function between baseline and 7-year visit. The mean age was 48 ± 11 years, mean educational level 13 ± 3 years, and 13% were female. TE+ patients were less likely to have undetectable viral loads (≤50 copies/mL) and had lower absolute CD4 counts. The TE+ group had the highest prevalence of NCI globally and in domains of verbal, executive function, learning, recall, working memory, processing speed and motor at baseline and at 7-year follow-up. Changes in longitudinal NC function over 7 years were small and did not differ significantly among all groups, except that speed of information processing improved more in TE+ compared with LTI- participants. PWH with a history of TE had cognitive impairment over a broad range of severity at both baseline and last follow-up. Changes in cognition from baseline to last examination in all groups were minimal and did not differ significantly among the groups with the exception of speed of information processing.

Human immunodeficiency virus infected patient with decreased of consciousness, what do we think?

Central nervous system (CNS) disorders are estimated to occur in approximately 10-20% of people living with human immunodeficiency virus (HIV). Neurological manifestations in HIV-infected patients can be caused directly by HIV or by opportunistic infections. Here we present a case report of a 47-year-old male initially diagnosed with decreased of consciousness in HIV-infected patients on ARV. Differential diagnosis of HIV-infected patients with decreased consciousness must be made. We can consider causes of opportunistic infections such as toxoplasma encephalitis, HIV encephalitis, or both.

Assessment of the relationship between the dopaminergic pathway and severe acute respiratory syndrome coronavirus 2 infection, with related neuropathological features, and potential therapeutic approaches in COVID-19 infection.

Dopamine is a known catecholamine neurotransmitter involved in several physiological processes, including motor control, motivation, reward, cognition, and immune function. Dopamine receptors are widely distributed throughout the nervous system and in immune cells. Several viruses, including human immunodeficiency virus and Japanese encephalitis virus, can use dopaminergic receptors to replicate in the nervous system and are involved in viral neuropathogenesis. In addition, studies suggest that dopaminergic receptors may play a role in the progression and pathogenesis of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infection. When SARS-CoV-2 binds to angiotensin-converting enzyme 2 receptors on the surface of neuronal cells, the spike protein of the virus can bind to dopaminergic receptors on neighbouring cells to accelerate its life cycle and exacerbate neurological symptoms. In addition, recent research has shown that dopamine is an important regulator of the immune-neuroendocrine system. Most immune cells express dopamine receptors and other dopamine-related proteins, indicating the importance of dopaminergic immune regulation. The increase in dopamine concentration during SARS-CoV2 infection may reduce immunity (innate and adaptive) that promotes viral spread, which could lead to neuronal damage. In addition, dopaminergic signalling in the nervous system may be affected by SARS-CoV-2 infection. COVID -19 can cause various neurological symptoms as it interacts with the immune system. One possible treatment strategy for COVID -19 patients could be the use of dopamine antagonists. To fully understand how to protect the neurological system and immune cells from the virus, we need to study the pathophysiology of the dopamine system in SARS-CoV-2 infection.

Negative HIV encephalitis and meningoencephalitis management algorithm Decision-making

Meningoencephalitis is a serious, relatively frequent infection, with a worldwide incidence of 3.5 to 7.4 per 100,000 inhabitants per year and a high mortality rate (10 to 12%). The objective of our work was to determine the etiologies of encephalitis and meningoencephalitis using the most modern microbiological diagnostics and to propose a management algorithm diagnosis. Materials and methods: This is a prospective descriptive study of 141 patients aged over 28 days with symptoms suggestive of HIV-negative encephalitis and meningoencephalitis during the period from April 1, 2012 to August 31, 2015. Several types of analyzes of the various samples (LCS, serum, nasopharyngeal samples) were carried out, including 2671 by PCR, 404 direct examinations and bacterial culture, 219 viral cultures and 380 serologies. The number of pathogens screened for the patients included in this study varied from 1 to 31 pathogens. Results: In Batna, a wide range of pathogens cause acute encephalitis. Of the 141 patients, 111 (78.7%) had at least one etiological diagnosis (63 certain, 80 probable and 32 possible). Diagnosis was confirmed for 58 (41.2%) patients, probable for 41 (29.1%), and possible for 12 (8.5%). The overall incidence of encephalitis in our region is 2.15 / 100,000 inhabitants with an average age of 30.8 years (standard deviation = 21.5 years). The most frequently identified etiological pathogen was KB 30 (21.3%), followed by EBV 20 (14.2%), HSV 14 (9.9%), CMV 11 (7.8%), Coronavirus 18 (12.5), and Adenovirus 6 (4.3%).The search for patients with a confirmed and/or probable monomicrobial agent, numbering 53 (37.6%), was essential to come out with a decision-making algorithm regarding the diagnostic approach. Coinfections were identified for 48 patients (34%), of whom 12 (8.5%) had more than 2 pathogens found. 21.3% of cases remained of undetermined cause. Evolution was unfavorable for 67 or 47.2%. There were 43 cases of death (30.5%), with 20 cases of after-effects. Conclusion: This study made it possible to highlight for the first time the etiologies of encephalitis and meningoencephalitis with their clinical and para-clinical particularities, in the region of eastern Algeria (Batna), which allowed the development of a decision-making algorithm for the diagnostic approach allowing rapid and appropriate care for our patients.

Comprehensive analyses identify potential biomarkers for encephalitis in HIV infection

Human immunodeficiency virus encephalitis (HIVE) is a severe neurological complication after HIV infection. Evidence shows that genetic factors play an important role in HIVE. The aim of the present study was to identify new potential therapeutic targets for HIVE. Differentially expressed gene (DEG), functional annotation and pathway, and protein–protein interaction analyses were performed to identify the hub genes associated with HIVE. Gene co-expression analysis was carried out to confirm the association between the hub genes and HIVE. Finally, the role of the hub genes in HIVE therapy was evaluated by conducting drug–gene interaction analysis. A total of 20 overlapping DEGs closely related to HIVE were identified. Functional annotation and pathway enrichment analysis indicated that the markedly enriched DEG terms included ion transport, type II interferon signaling, and synaptic signaling. Moreover, protein–protein interaction analysis revealed that 10 key HIVE-related genes were hub genes, including SCN8A, CDK5R2, GRM5, SCN2B, IFI44L, STAT1, SLC17A7, ISG15, FGF12, and FGF13. Furthermore, six hub genes were co-expressed with HIVE-associated host genes in human brain tissue. Finally, three hub genes (STAT1, ISG15, and SCN2B) interacted with several inflammation-associated drugs. These findings suggested that SCN8A, CDK5R2, GRM5, SCN2B, IFI44L, STAT1, SLC17A7, ISG15, FGF12, and FGF13 may be new targets for diagnosis and therapy of HIVE.

Simian immunodeficiency virus-infected rhesus macaques with AIDS co-develop cardiovascular pathology and encephalitis.

Despite effective antiretroviral therapy, HIV co-morbidities remain where central nervous system (CNS) neurocognitive disorders and cardiovascular disease (CVD)-pathology that are linked with myeloid activation are most prevalent. Comorbidities such as neurocogntive dysfunction and cardiovascular disease (CVD) remain prevalent among people living with HIV. We sought to investigate if cardiac pathology (inflammation, fibrosis, cardiomyocyte damage) and CNS pathology (encephalitis) develop together during simian immunodeficiency virus (SIV) infection and if their co-development is linked with monocyte/macrophage activation. We used a cohort of SIV-infected rhesus macaques with rapid AIDS and demonstrated that SIV encephalitis (SIVE) and CVD pathology occur together more frequently than SIVE or CVD pathology alone. Their co-development correlated more strongly with activated myeloid cells, increased numbers of CD14+CD16+ monocytes, plasma CD163 and interleukin-18 (IL-18) than did SIVE or CVD pathology alone, or no pathology. Animals with both SIVE and CVD pathology had greater numbers of cardiac macrophages and increased collagen and monocyte/macrophage accumulation, which were better correlates of CVD-pathology than SIV-RNA. Animals with SIVE alone had higher levels of activated macrophage biomarkers and cardiac macrophage accumulation than SIVnoE animals. These observations were confirmed in HIV infected individuals with HIV encephalitis (HIVE) that had greater numbers of cardiac macrophages and fibrosis than HIV-infected controls without HIVE. These results underscore the notion that CNS and CVD pathologies frequently occur together in HIV and SIV infection, and demonstrate an unmet need for adjunctive therapies targeting macrophages.

HIV-1 subtype B Tat enhances NOTCH3 signaling in astrocytes to mediate oxidative stress, inflammatory response, and neuronal apoptosis.

NOTCH receptors are relevant to multiple neurodegenerative diseases. However, the roles and mechanisms of NOTCH receptors in HIV-associated neurocognitive disorder (HAND) remain largely unclear. Transactivator of transcription (Tat) induces oxidative stress and inflammatory response in astrocytes, thereby leading to neuronal apoptosis in the central nervous system. We determined that NOTCH3 expression was upregulated during subtype B or C Tat expression in HEB astroglial cells. Moreover, bioinformatics analysis of the Gene Expression Omnibus (GEO) dataset revealed that NOTCH3 mRNA expression in the frontal cortex tissues of HIV encephalitis patients was higher than that of HIV control patients. Of note, subtype B Tat, rather than subtype C Tat, interacted with the extracellular domain of the NOTCH3 receptor, thus activating NOTCH3 signaling. Downregulation of NOTCH3 attenuated subtype B Tat-induced oxidative stress and reactive oxygen species generation. In addition, we demonstrated that NOTCH3 signaling facilitated subtype B Tat-activated NF-κB signaling pathway, thereby mediating pro-inflammatory cytokines IL-6 and TNF-α production. Furthermore, downregulation of NOTCH3 in HEB astroglial cells protected SH-SY5Y neuronal cells from astrocyte-mediated subtype B Tat neurotoxicity. Taken together, our study clarifies the potential role of NOTCH3 in subtype B Tat-induced oxidative stress and inflammatory response in astrocytes, which could be a novel therapeutic target for the relief of HAND.

Gene Co-Expression Network Modular Analysis Reveals Altered Immune Mechanisms in HIV-HAND.

Although the introduction of HAART has completely changed the natural course of HIV infection, the number of chronic forms of HIV-associated neurocognitive disorder (HAND) has risen. It is estimated that up to half of subjects undergoing HAART therapy exhibit mild cognitive impairments. In the current study, we apply the gene co-expression network modular analysis, a well-established system biology approach, to the gene expression profiles of cases from the National NeuroAIDS Tissue Consortium (NNTC). We observed a negative enrichment for genes associated with the control of immune responses and putatively regulated by the transcription factors IRF8 and SPI1 and by both type I and II interferons. Our study provides evidence of altered immune responses, which are likely associated with the occurrence of HAND in the absence of HIV encephalitis (HIVE).

Clinicoepidemiological profile and outcome among children with acute encephalitis syndrome from Central India

Background: Acute encephalitis syndrome (AES) is defined as the acute onset of fever and a change in mental status and/or new onset of seizures (excluding simple febrile seizures) in a person of any age at any time of the year. Aims and Objectives: The objectives of the study were as follows: (a) To study clinicoepidemiological profile and outcome among children with AES admitted at M.Y.H. Hospital and MGM Medical College, Indore, M.P., and (b) to study prognostic factors associated with bad outcomes. Materials and Methods: This prospective observational study was conducted over 12 months (July 2019–August 2020) at the pediatric department of our hospital. Inclusion criteria: Inpatient children aged 6 months–14 years meeting the case definitions of acute encephalitis syndrome. Exclusion criteria: Simple febrile seizures. Results: Out of 50 AES cases, majority were between 1 and 5 years of age (40%). There were more males 31 (62%) than 19 (38%) females. Most of the cases were reported during the monsoon period 29 (58%) followed by post-monsoon 13 (26%) and pre-monsoon 8 (16%). Out of 50 cases, all had fever and altered sensorium, 37 (74%) had convulsions, 14 (28%) had vomiting, and 9 (18%) had headache. Out of 50 cases, 42 (84%) had viral etiology including 7 (14%) of dengue encephalitis and 1 (2%) of case of human immunodeficiency virus encephalitis. Only 5 (10%) cases had bacterial etiology. Those who needed inotropes and mechanical ventilation showed significant mortality. Conclusion: The peak of AES cases occurred during the monsoon period. A higher proportion of such cases had viral etiology on cerebrospinal fluid analysis. Use of inotropes and mechanical ventilation was identified to be associated with significant mortality.

Biotypes of HIV-associated neurocognitive disorders based on viral and immune pathogenesis.

HIV-associated neurocognitive disorders (HAND) continues to be prevalent in people living with HIV despite antiretroviral therapy. However, understanding disease mechanisms and identifying therapeutic avenues has been challenging. One of the challenges is that HAND is a heterogeneous disease and that patients identified with similar impairments phenotypically may have very different underlying disease processes. As the NeuroAIDS field is re-evaluating the approaches used to identify patients with HIV-associated neurological impairments, we propose the subtyping of patients into biotypes based on viral and immune pathogenesis. Here we review the evidence supporting subtyping patients with HIV-associated neurological complications into four biotypes: macrophage-mediated HIV encephalitis, CNS viral escape, T-cell-mediated HIV encephalitis, and HIV protein-associated encephalopathy. Subtyping patients into subgroups based on biotypes has emerged as a useful approach for studying heterogeneous diseases. Understanding biotypes of HIV-associated neurocognitive impairments may therefore enable better understanding of disease mechanisms, allow for the development of prognostic and diagnostic markers, and could ultimately guide therapeutic decisions.

P.057 When you hear hoofbeats, think horses AND zebras

Background: HIV-associated CD8 encephalitis (CDE) is a severe inflammatory disorder characterized by infiltration of the brain by CD8+ T-lymphocytes in HIV positive patients, often when the virus is well-controlled by anti-retroviral therapy (ART). Hallmark clinical features include headache, confusion and progressive cognitive decline. Most patients who receive prompt corticosteroid therapy evolve favorably, though if left untreated, CDE can lead to coma and even death. The therapeutic impact of altering the ART regimen while giving corticosteroids remains unclear. Methods: Patient chart, functional measures, and laboratory findings were reviewed for the length of the patient’s two hospitalisations for CDE in 2019 and 2021. Results: Here we present a case of an HIV positive 43-year-old male who presented with headache, confusion and memory issues both in 2019 and 2021. Imaging and lumbar puncture guided the diagnosis of CDE in 2019, while careful patient history on the patient’s second hospitalisation confirmed the diagnosis of HIV encephalitis due to medication non-compliance in 2021. Conclusions: This case adds to the current state of knowledge regarding the clinical presentation of CD8 encephalitis, while highlighting both similarities and differences with other CNS pathology seen in the context of HIV.

Patterns of Cerebrospinal Fluid Alzheimer's Dementia Biomarkers in People Living with HIV: Cross-Sectional Study on Associated Factors According to Viral Control, Neurological Confounders and Neurocognition.

People living with HIV (PLWH) age with an excess burden of comorbidities that may increase the incidence of age-related complications. There is controversy surrounding the hypothesis that HIV can accelerate neurodegeneration and Alzheimer’s dementia (AD). We performed a retrospective study to analyze the distribution of cerebrospinal fluid (CSF) AD biomarkers (beta amyloid 1–42 fragment, tau, and phosphorylated tau) in adult PLWH (on cART with undetectable viremia, n = 136, with detectable viremia, n = 121, and with central nervous system CNS disorders regardless of viremia, n = 72) who underwent a lumbar puncture between 2008 to 2018; HIV-negative controls with AD were included (n = 84). Five subjects (1.5%) presented CSF biomarkers that were compatible with AD: one was diagnosed with AD, whereas the others showed HIV encephalitis, multiple sclerosis, cryptococcal meningitis, and neurotoxoplasmosis. Regardless of confounders, 79.6% of study participants presented normal CSF AD biomarkers. Isolated abnormalities in CSF beta amyloid 1–42 (7.9%) and tau (10.9%) were associated with age, biomarkers of intrathecal injury, and inflammation, although no HIV-specific feature was associated with abnormal CSF patterns. CSF levels of AD biomarkers very poorly overlapped between HIV-positive clinical categories and AD controls. Despite the correlations with neurocognitive performance, the inter-relationship between amyloid and tau proteins in PLWH seem to differ from that observed in AD subjects; the main driver of the isolated increase in tau seems represented by non-specific CNS inflammation, whereas the mechanisms underlying isolated amyloid consumption remain unclear.

Clinical characteristics and outcomes after new-onset seizure among Zambian children with HIV during the antiretroviral therapy era.

ObjectiveThis study describes clinical profiles including human immunodeficiency virus (HIV) disease history and seizure etiology among children living with HIV presenting with new‐onset seizure during the era of antiretroviral therapy (ART) in Zambia. 30‐day mortality and cause of death are also reported.MethodsChildren living with HIV (CLWHIV) with new‐onset seizures were prospectively evaluated at one large urban teaching hospital and two non‐urban healthcare facilities. Interviews with family members, review of medical records, and where needed, verbal autopsies were undertaken. Two clinicians who were not responsible for the patients' care independently reviewed all records and assigned seizure etiology and cause of death with adjudication as needed.ResultsFrom April 2016 to June 2019, 73 children (49 urban, 24 rural) were identified. Median age was 6 years (IQR 2.2‐10.0) and 39 (53%) were male children. Seizures were focal in 36 (49%) and were often severe, with 37% presenting with multiple recurrent seizures in the 24 hours before admission or in status epilepticus. Although 36 (49%) were on ART at enrollment, only 7 of 36 (19%) were virally suppressed. Seizure etiologies were infectious in over half (54%), with HIV encephalitis, bacterial meningitis, and tuberculous meningitis being the most common. Metabolic causes (19%) included renal failure and hypoglycemia. Structural lesions identified on imaging accounted for 10% of etiologies and included stroke and non‐accidental trauma. No etiology could be identified in 12 (16%) children, most of whom died before the completion of clinical investigations. Twenty‐two (30%) children died within 30 days of the index seizure.SignificanceDespite widespread ART roll out in Zambia, new‐onset seizure in CLWHIV occurs in the setting of advanced, active HIV disease. Seizure severity/burden is high as is early mortality. Enhanced programs to assure early ART initiation, improve adherence, and address ART failure are needed to reduce the burden of neurological injury and premature death in CLWHIV.

Vascular inflammation in the central nervous system.

Vascular inflammation in the central nervous system.

Effect of antiretroviral treatment on blood-brain barrier integrity in HIV-1 infection

BackgroundBlood-brain barrier (BBB) injury is prevalent in patients with HIV-associated dementia (HAD) and is a frequent feature of HIV encephalitis. Signs of BBB damage are also sometimes found in neuroasymptomatic HIV-infected individuals without antiretroviral therapy (ART). The aim of this study was to investigate the integrity of the BBB before and after initiation of ART in both neuroasymptomatic HIV infection and in patients with HAD.MethodsWe determined BBB integrity by measuring cerebrospinal fluid (CSF)/plasma albumin ratios in archived CSF samples prior to and after initiation of ART in longitudinally-followed neuroasymptomatic HIV-1-infected individuals and patients with HAD. We also analyzed HIV RNA in blood and CSF, IgG Index, CSF WBC counts, and CSF concentrations of β2-micoglobulin, neopterin, and neurofilament light chain protein (NfL).ResultsWe included 159 HIV-infected participants; 82 neuroasymptomatic individuals and 77 with HAD. All neuroasymptomatic individuals (82/82), and 10/77 individuals with HAD, were longitudinally followed with a median (interquartile range, IQR) follow-up of 758 (230–1752) days for the neuroasymptomatic individuals, and a median (IQR) follow-up of 241 (50–994) days for the individuals with HAD. Twelve percent (10/82) of the neuroasymptomatic individuals and 80% (8/10) of the longitudinally-followed individuals with HAD had elevated albumin ratios at baseline. At the last follow-up, 9% (7/82) of the neuroasymptomatic individuals and 20% (2/10) of the individuals with HAD had elevated albumin ratios. ART significantly decreased albumin ratios in both neuroasymptomatic individuals and in patients with HAD.ConclusionThese findings indicate that ART improves and possibly normalizes BBB integrity in both neuroasymptomatic HIV-infected individuals and in patients with HAD.

Suspected Central Nervous System Infections in HIV-Infected Adults.

Objectives: To study the differential diagnosis of HIV-infected patients with suspected central nervous system (CNS) infections and the association of CD4 counts with the final diagnosis.Methods: We analyzed HIV-infected patients from a prospective cohort study on the diagnostic accuracy of clinical and laboratory characteristics in adults with suspected CNS infections in an academic hospital in Amsterdam, the Netherlands, who underwent cerebrospinal fluid (CSF) examination.Results: Thirty-four (9.4%) out of 363 patients with suspected CNS infections were HIV-positive of whom 18 (53%) were diagnosed to have CNS infection, with median CD4 counts of 255 cells/μl. The spectrum of CNS infections consisted of progressive multifocal leukoencephalopathy in three patients (17%); cryptococcal meningoencephalitis, toxoplasma encephalitis, angiostrongylus eosinophilic meningitis, and HIV encephalitis each in two (11%); and cytomegalovirus encephalitis, neurosyphilis, tuberculous meningoencephalitis, histoplasma encephalitis, and varicella-zoster virus meningitis each in one (6%). Clinical characteristics and blood parameters did not differ between HIV-infected patients with CNS infections and other diagnoses. The best predictor for CNS infections was the CSF leukocyte count (AUC = 0.77, 95 CI% 0.61–0.94). The diagnosis of CNS infection was not associated with the CD4 count (median 205 vs. 370, p = 0.21). Two patients (11%) with CNS infections died and two (11%) had neurological sequelae.Conclusions: Half of the patients with suspected CNS infections are diagnosed with a CNS infection, and this was not related to CD4 counts. The best predictor for CNS infections was the CSF leukocyte count.

In vitro evaluation of new 4-thiazolidinones on invasion and growth of Toxoplasma gondii

Treatments for toxoplasmosis such as pyrimethamine have shown numerous side effects. It has been reported that the likelihood of relapse associated with pyrimethamine-based therapy in patients with HIV and toxoplasmic encephalitis (TE) can have significant implications, even for patients who often develop new lesions in areas of the brain previously free of infection. This led us to research for new agents against Toxoplasma gondii. Recent findings have shown the potent biological activity of 4-thiazolidinones. We proposed to design and synthesize a new series of 2-hydrazono-4-thiazolidinones derivatives to evaluate the in vitro growth inhibition effect on T. gondii. The growth rates of T. gondii tachyzoites in Human Foreskin Fibroblast (HFF) cell culture were identified by two in vitro methodologies. The first one was by fluorescence in which green fluorescent RH parasites and cherry-red fluorescent ME49 parasites were used. The second one was a colorimetric methodology using β-Gal parasites of the RH strain constitutively expressing the enzyme beta-galactosidase. The 4-thiazolidinone derivatives 1B, 2B and 3B showed growth inhibition at the same level of Pyrimethamine. These compounds showed IC50 values of 1B (0.468–0.952 μM), 2B (0.204–0.349 μM) and 3B (0.661–1.015 μM) against T. gondii. As a measure of cytotoxicity the compounds showed a TD50 values of: 1B (60 μM), 2B (206 μM) and 3B (125 μM). The in vitro assays and molecular modeling results suggest that these compounds could act as possible inhibitors of the Calcium-Dependent Protein Kinase 1 of T. gondii. Further, our results support the fact that of combining appropriate detection technologies, combinatorial chemistry and computational biology is a good strategy for efficient drug discovery. These compounds merit in vivo analysis for anti-parasitic drug detection.

HIV-Associated CD8 Encephalitis: A UK Case Series and Review of Histopathologically Confirmed Cases.

HIV-associated CD8-encephalitis (HIV-CD8E) is a severe inflammatory disorder dominated by infiltration of the brain by CD8+ T-lymphocytes. It occurs in people with HIV, typically when the virus is apparently well-controlled by antiretroviral treatment (ART). HIV-CD8E presents with symptoms and signs related to marked cerebral inflammation and swelling, and can lead to coma and death unless treated promptly with corticosteroids. Risk events such as intercurrent infection, antiretroviral therapy interruption, immune reconstitution inflammatory syndrome (IRIS) after starting ART, and concomitant associations such as cerebrospinal fluid (CSF) HIV viral escape have been identified, but the pathogenesis of the disorder is not known. We present the largest case series of HIV-CD8E to date (n = 23), representing histopathologically confirmed cases in the UK. We also summarize the global literature representing all previously published cases with histopathological confirmation (n = 30). A new variant of HIV-CD8E is described, occurring on a background of HIV encephalitis (HIVE).Together these series, totalling 53 patients, provide new insights. CSF HIV viral escape was a frequent finding in HIV-CD8E occurring in 68% of those with CSF available and tested; ART interruption and IRIS were important, both occurring in 27%. Black ethnicity appeared to be a key risk factor; all but two UK cases were African, as were the majority of the previously published cases in which ethnicity was stated. We discuss potential pathogenic mechanisms, but there is no unifying explanation over all the HIV-CD8E scenarios.

Neurosyphilis and the Jarisch-Herxheimer reaction: A therapy concern with HIV disease.

Jarisch-Herxheimer reaction (JHR) should be anticipated in treating neurosyphilis with coexistent human immunodeficiency virus (HIV) encephalitis. In that context we have devised a staging classification for JHR. In addition, an illustrative case is provided to emphasize the need to consider the diagnosis of neurosyphilis in HIV patients, and if delineated, to be prepared for a severe JHR.

Acute Viral Encephalitis Neuroimaging Spectrum

Acute viral encephalitis involves inflammation of the brain caused by multiple different viruses, with CT of the head and MR imaging of the brain involved in the initial diagnostic work-up. Although viral encephalitis may have nonspecific findings on neuroimaging, some imaging patterns have been identified in viral subtypes on MR imaging. The most common cause of encephalitis is herpes simplex virus, with the typical imaging features demonstrating unilateral medial temporal lobe signal abnormalities. Bilateral temporal lobe, cerebellum, and brain stem signal abnormalities are seen in herpes simplex virus 2, with associated edema, necrosis, and hemorrhage. Signal abnormalities are commonly seen in the bilateral basal ganglia, thalami, and mesial temporal lobes in West Nile virus encephalitis. HIV encephalitis is associated with symmetric signal abnormality in the periventricular and deep white matter, which can be differentiated from progressive multifocal leukoencephalopathy by asymmetric U-fiber involvement. The purpose of this article is to present imaging findings associated with typical and atypical cases of viral encephalitis to guide diagnosis, promote early intervention, and improve clinical outcomes.Learning Objective: Identify unique radiologic findings associated with different types of viral encephalitis to guide diagnosis and improve clinical outcomes.