Apolipoprotein E ε4 genotype status is not associated with neuroimaging outcomes in a large cohort of HIV+ individuals

Previous neuroimaging studies suggest a negative relationship between the apolipoprotein (ApoE) ε4 allele and brain integrity in human immunodeficiency virus (HIV)-infected (HIV+) individuals, although the presence of this relationship across adulthood remains unclear. The purpose of this study is to clarify the discrepancies using a large, diverse group of HIV+ individuals and multiple imaging modalities sensitive to HIV. The association of ApoE ε4 with structural neuroimaging and magnetic resonance spectroscopy (MRS) was examined in 237 HIV+ individuals in the CNS HIV Anti-Retroviral Therapy Effects Research (CHARTER) study. Cortical and subcortical gray matter, abnormal and total white matter, ventricles, sulcal cerebrospinal fluid (CSF), and cerebellar gray matter, white matter, and CSF volumes, and MRS concentrations of myo-inositol, creatine, N-acetyl-aspartate, and choline in the frontal white matter (FWM), frontal gray matter (FGM), and basal ganglia were examined. Secondary analyses explored this relationship separately in individuals ≥50 years old (n?=?173) and <50 years old (n?=?63). No significant differences were observed between ApoE ε4+ (ApoE ε3/ε4 and ApoE ε4/ε4) individuals (n?=?69) and ApoE ε4? (ApoE ε2/ε3 and ApoE ε3/ε3) individuals (n?=?167). When individuals were further divided by age, no significant genotype group differences were identified in individuals <50 or ≥50 years of age on any neuroimaging outcome. The ApoE ε4 allele did not affect brain integrity in this large, diverse sample of HIV+ individuals. The effects of ApoE ε4 may not be apparent until more advanced ages and may be more prominent when present along with other risk factors for neuronal damage.     

International neurocognitive normative study: neurocognitive comparison data in diverse resource-limited settings: AIDS Clinical Trials Group A5271

Infrastructure for conducting neurological research in resource-limited settings (RLS) is limited. The lack of neurological and neuropsychological (NP) assessment and normative data needed for clinical interpretation impedes research and clinical care. Here, we report on ACTG 5271, which provided neurological training of clinical site personnel and collected neurocognitive normative comparison data in diverse settings. At ten sites in seven RLS countries, we provided training for NP assessments. We collected normative comparison data on HIV? participants from Brazil (n?=?240), India (n?=?480), Malawi (n?=?481), Peru (n?=?239), South Africa (480), Thailand (n?=?240), and Zimbabwe (n?=?240). Participants had a negative HIV test within 30 days before standardized NP exams were administered at baseline and 770 at 6 months. Participants were enrolled in eight strata, gender (female and male), education (<10 and ≥10 years), and age (<35 and ≥35 years). Of 2400 enrolled, 770 completed the 6-month follow-up. As expected, significant between-country differences were evident in all the neurocognitive test scores (p?<?0.0001). There was variation between the age, gender, and education strata on the neurocognitive tests. Age and education were important variables for all tests; older participants had poorer performance, and those with higher education had better performance. Women had better performance on verbal learning/memory and speed of processing tests, while men performed better on motor tests. This study provides the necessary neurocognitive normative data needed to build infrastructure for future neurological and neurocognitive studies in diverse RLS. These normative data are a much-needed resource for both clinicians and researchers.     

Neurocognitive impairment with hepatitis C and HIV co-infection in Southern Brazil

Although cognitive impairment has been well documented in human immunodeficiency virus (HIV) and hepatitis C virus (HCV) mono-infections, research on neurocognitive effects is limited in the context of HIV/HCV co-infection. The aims of this study were to explore the interplay between HIV and HCV infections in the expression of neurocognitive impairment (NCI), and to examine the differences in test performance between HIV/HCV co-infected and HIV or HCV mono-infected patients. A total of 128 participants from Southern Brazil underwent a comprehensive neuropsychological (NP) battery comprising 18 tests. Participants were grouped according to their serological status: HCV mono-infected (n?=?20), HIV mono-infected (n?=?48), HIV/HCV co-infected (n?=?12), and HIV?/HCV-uninfected controls (n?=?48). The frequencies of HIV subtypes B and C between the HIV mono-infected and HIV/HCV co-infected groups were comparable. There was greater prevalence of neuropsychological impairment among all three infection groups compared with the uninfected control group, but no statistically significant differences among mono- and co-infected groups were found. HCV infection was associated with cognitive deficits, independently of liver dysfunction. HCV infection did not show an additive effect on neurocognitive function among HIV+. NCI was independent of HCV RNA on peripheral blood, CSF, and hepatic injury. While we did not find additive global effect, in the present study, there was some evidence of additive HIV/HCV co-infection effects in speed of information processing, executive function, and verbal fluency domains when comparing the co-infected group with the other three groups. NP impairment was not dependent on HCV subtypes.     

Preliminary study of a novel cognitive assessment device for the evaluation of HIV-associated neurocognitive impairment

Given the high prevalence of HIV-associated neurocognitive disorders (HAND), we examined the performance of a novel computerized cognitive assessment device (NCAD) for the evaluation of neurocognitive impairment in the setting of HIV. In addition to a standard 8-test neuropsychological battery, each participant underwent testing with the NCAD, which requires approximately 20 min and has been shown to accurately measure neurocognition in elderly individuals. The NCAD yields seven subtest scores in addition to an overall predictive score that is calculated based on subtest results. Thirty-nine HIV-infected participants were included in this study; the majority of which (71.8 %) had undetectable plasma HIV RNA levels and a history of significant immunocompromise (median nadir CD4+ count 34 cells/μl). The mean composite neuropsychological score (NPT-8) was 46.07, and mean global deficit score (GDS) was 0.59. NCAD total subtest accuracy correlated significantly with NPT-8 (Pearson correlation r?=?0.59, p?<?0.0001) as well as GDS (Spearman’s rho?=??0.36, p?=?0.02). NCAD predictive score also correlated significantly with NPT-8 (Spearman’s rho?=??0.5601, p?=?0.0016) and GDS (Spearman’s rho?=?0.45, p?=?0.0144). When using the most recent nosology of HAND criteria for neurocognitive impairment, the area under the curve (AUC) for NCAD total subtest accuracy was 0.7562 (p?=?0.012), while the AUC for the HIV dementia scale was 0.508 (p?=?0.930). While not as comprehensive as a full neuropsychological battery, the NCAD shows promise as a rapid screening tool for HIV-infected individuals, and additional research of this device is indicated.     

Effects of HIV and childhood trauma on brain morphometry and neurocognitive function

A wide spectrum of neurocognitive deficits characterises HIV infection in adults. HIV infection is additionally associated with morphological brain abnormalities affecting neural substrates that subserve neurocognitive function. Early life stress (ELS) also has a direct influence on brain morphology. However, the combined impact of ELS and HIV on brain structure and neurocognitive function has not been examined in an all-female sample with advanced HIV disease. The present study examined the effects of HIV and childhood trauma on brain morphometry and neurocognitive function. Structural data were acquired using a 3T Magnetom MRI scanner, and a battery of neurocognitive tests was administered to 124 women: HIV-positive with ELS (n?=?32), HIV-positive without ELS (n?=?30), HIV-negative with ELS (n?=?31) and HIV-negative without ELS (n?=?31). Results revealed significant group volumetric differences for right anterior cingulate cortex (ACC), bilateral hippocampi, corpus callosum, left and right caudate and left and right putamen. Mean regional volumes were lowest in HIV-positive women with ELS compared to all other groups. Although causality cannot be inferred, findings also suggest that alterations in the left frontal lobe, right ACC, left hippocampus, corpus callosum, left and right amygdala and left caudate may be associated with poorer neurocognitive performance in the domains of processing speed, attention/working memory, abstraction/executive functions, motor skills, learning and language/fluency with these effects more pronounced in women living with both HIV and childhood trauma. This study highlights the potential contributory role of childhood trauma to brain alterations and neurocognitive decline in HIV-infected individuals.     

Long-term efavirenz use is associated with worse neurocognitive functioning in HIV-infected patients

Neurocognitive (NC) complications continue to afflict a substantial proportion of HIV-infected people taking effective antiretroviral therapy (ART). One contributing mechanism for this is antiretroviral neurotoxicity. Efavirenz (EFV) is associated with short-term central nervous system (CNS) toxicity, but less is known about its long-term effects. Our objective was to compare NC functioning with long-term use of EFV to that of a comparator, lopinavir-ritonavir (LPV/r), in a cohort of well-characterized adults. Four hundred forty-five patients were selected from the CNS HIV Antiretroviral Therapy Effects Research (CHARTER) cohort based on their use of either EFV (n?=?272, mean duration 17.9 months) or LPV/r (n?=?173, mean duration 16.4 months) and the lack of severe NC comorbidities. All patients had undergone standardized comprehensive NC testing. Univariable and multivariable analyses to predict NC outcomes were performed. Compared with LPV/r users, EFV users were more likely to be taking their first ART regimen (p?<?0.001), were less likely to have AIDS (p?<?0.001) or hepatitis C virus (HCV) coinfection (p?<?0.05), had higher CD4+ T cell nadirs (p?<?0.001), had lower peak (p?<?0.001) and current (p?<?0.001) plasma HIV RNA levels, and were less likely to have detectable HIV RNA in cerebrospinal fluid (CSF) (p?<?0.001). Overall, EFV users had worse speed of information processing (p?=?0.04), verbal fluency (p?=?0.03), and working memory (p?=?0.03). An interaction with HCV serostatus was present: Overall among HCV seronegatives (n?=?329), EFV users performed poorly, whereas among HCV seropositives (n?=?116), LPV/r users had overall worse performance. In the subgroup with undetectable plasma HIV RNA (n?=?269), EFV users had worse speed of information processing (p?=?0.02) and executive functioning (p?=?0.03). Substantial differences exist between EFV and LPV/r users in this observational cohort, possibly because of channeling by clinicians who may have prescribed LPV/r to more severely ill patients or as second-line therapy. Despite these differences, EFV users had worse functioning in several cognitive abilities. A potentially important interaction was identified that could indicate that the NC consequences of specific antiretroviral drugs may differ based on HCV coinfection. The complexity of these data is substantial, and findings would best be confirmed in a randomized clinical trial.     

Suicide risk and prevalence of major depressive disorder (MDD) among individuals infected with HIV-1 subtype C versus B in Southern Brazil

Major depressive disorder (MDD) is among the most prevalent neuropsychiatric disorders associated with HIV infection; however, its risks and neurobiologic correlates in diverse cultures are poorly understood. This study aimed to examine the frequency of MDD among HIV+ participants in southern Brazil. We hypothesized that the frequency and severity of MDD would be higher among individuals with HIV+ compared with HIV? and higher in HIV subtype B compared with C. Individuals with HIV (n?=?39) as well as seronegative controls (n?=?22) were enrolled in a cross-sectional, prospective, observational study. Current and lifetime history of MDD was diagnosed by MINI-Plus; symptom severity was assessed by Beck Depression Inventory-II (BDI-II). Current and past episodes of MDD were significantly more frequent in the HIV+ versus HIV? group: current MDD, 15 (38.5 %) vs. 0 (0 %), p?=?0.0004; past MDD, 24 (61.5 %) vs. 3 (13.6 %), p?=?0.0004. The median BDI-II score in the HIV+ group was significantly higher than that in the HIV? (13 (8–27.5) vs. 2.5 (1–5.5); p?<?0.0001). Current suicide risk, defined as during the last month, was found in 18 % of participants in the HIV-positive and none in the HIV-negative group. Neither current MDD frequency (8 (57.1 %) vs. 6 (40 %), p?=?0.47) nor BDI-II score differed across subtypes B and C. HIV+ group may be more likely to experience current MDD than HIV?. This was the first study to compare the frequency and severity of MDD in HIV subtypes B and C; we found no difference between HIV subtypes B and C.     

Neurofilament light chain in blood is negatively associated with neuropsychological performance in HIV-infected adults and declines with initiation of antiretroviral therapy

HIV-associated neurocognitive disorder (HAND) persists in the combination antiretroviral therapy (cART) era and is associated with diminished quality of life. The disorder remains challenging to diagnose given the requirement for comprehensive neuropsychological testing. Blood biomarkers are needed to facilitate the diagnosis of HAND and to gauge neurological response to antiretroviral therapy. We performed a study of plasma neurofilament light chain (NFL) that included 37 HIV-infected and 54 HIV-negative adults. In the univariate mixed-effect model involving HIV-infected participants, there was a statistically significant linear relationship between composite neuropsychological score (NPT-11) and plasma NFL (slope?=???9.9, standard error?=?3.0 with 95% confidence interval ??3.2 to ??16.6 and p?=?0.008 when testing slope?=?0). Similarly, in the multivariate mixed-effect model, higher plasma NFL was significantly associated with worse NPT-11 (slope?=???11.5, standard error?=?3.3 with 95% confidence interval ??3.7 to ??19.0 and p?=?0.01 when testing slope?=?0). The association between NPT-11 and NFL appeared to be driven by the group of individuals off cART. In a subset of participants who had visits before and after 24 weeks on cART (n?=?11), plasma NFL declined over time (median?=?22.7 versus 13.4 pg/ml, p?=?0.02). In contrast, plasma NFL tended to increase over time among HIV-negative participants (median 10.3 versus 12.6 pg/ml, p?=?0.065, n?=?54). Plasma NFL therefore shows promise as a marker of neuropsychological performance during HIV. Larger studies are needed to determine if NFL could serve as a diagnostic tool for HAND during suppressive cART.     

Post-traumatic stress is associated with verbal learning,memory, and psychomotor speed in HIV-infected and HIV-uninfected women

The prevalence of post-traumatic stress disorder (PTSD) is higher among HIV-infected (HIV+) women compared with HIV-uninfected (HIV?) women, and deficits in episodic memory are a common feature of both PTSD and HIV infection. We investigated the association between a probable PTSD diagnosis using the PTSD Checklist-Civilian (PCL-C) version and verbal learning and memory using the Hopkins Verbal Learning Test in 1004 HIV+ and 496 at-risk HIV? women. HIV infection was not associated with a probable PTSD diagnosis (17 % HIV+, 16 % HIV?; p?=?0.49) but was associated with lower verbal learning (p?<?0.01) and memory scores (p?<?0.01). Irrespective of HIV status, a probable PTSD diagnosis was associated with poorer performance in verbal learning (p?<?0.01) and memory (p?<?0.01) and psychomotor speed (p?<?0.001). The particular pattern of cognitive correlates of probable PTSD varied depending on exposure to sexual abuse and/or violence, with exposure to either being associated with a greater number of cognitive domains and a worse cognitive profile. A statistical interaction between HIV serostatus and PTSD was observed on the fine motor skills domain (p?=?0.03). Among women with probable PTSD, HIV? women performed worse than HIV+ women on fine motor skills (p?=?0.01), but among women without probable PTSD, there was no significant difference in performance between the groups (p?=?0.59). These findings underscore the importance of considering mental health factors as correlates to cognitive deficits in women with HIV.     

Blood brain barrier impairment is associated with cerebrospinal fluid markers of neuronal damage in HIV-positive patients

Blood brain barrier impairment occurs early in the course of infection by HIV and it may persist in a subset of patients despite effective antiretroviral treatment. We tested the hypothesis that HIV-positive patients with dysfunctional blood brain barrier may have altered biomarkers of neuronal damage. In adult HIV-positive highly active antiretroviral treatment (HAART)-treated patients (without central nervous system infections and undergoing lumbar punctures for clinical reasons) cerebrospinal fluid albumin to serum ratios (CSAR), total tau, phosphorylated tau, 1–42 beta amyloid, and neopterin were measured. In 101 adult patients, cerebrospinal fluid-to-serum albumin ratios were 4.8 (3.7–6.1) with 12 patients (11.9 %) presenting age-defined impaired blood brain barrier. A significant correlation was observed between CSAR and total tau (p?=?0.005), phosphorylated tau (p?=?0.008), and 1–42 beta amyloid (p?=?0.040). Patients with impaired blood brain barrier showed significantly higher total tau (201.6 vs. 87.3 pg/mL, p?=?0.010), phosphorylated tau (35.3 vs. 32.1 ng/mL, p?=?0.035), and 1–42 beta amyloid (1134 vs. 830 pg/mL, p?=?0.045). Despite effective antiretroviral treatment, blood brain barrier impairment persists in some HIV-positive patients: it is associated with markers of neuronal damage and it was not associated with CSF neopterin concentrations.     

Reproducible and persistent weakness in adult rats after surgical resection of motor cortex: evaluation with limb placement test

Object

The purpose of this study was to develop a new rat model for surgical brain injury with motor weakness and to find an adequate behavior test for the application of the model.

Methods

Thirty rats were divided into three groups: craniectomy (n?=?10), durotomy (n?=?10), and corticectomy (n?=?10) groups. The coordinates of the three points from the bregma (coordinate A?=?+4,+1, B?=??2,+1, and C?=?+4,+6). We evaluated right limb motor performance by the modified limb placement test and the cylinder test.

Conclusion

Persistent motor weakness was observed for 2 months in the corticectomy group by the limb placement test, whereas the cylinder test could not detect the weakness. We established a reproducible and persistent rat brain injury model and found that the modified limb placement test is sensitive enough to evaluate residual subtle weakness in this model.

     

Vocal emotion processing deficits in HIV-infected individuals

We aimed to explore the brain imaging correlates of vocal emotion processing in a group of HIV+ individuals and to compare the vocal emotion processing of HIV+ individuals with a group of healthy adults. We conducted multiple linear regressions to determine the cerebral correlates of a newly designed vocal emotion processing test in a sub-group of HIV+ individuals who completed the cerebral magnetic resonance scan (n = 36). Separately, we test whether the association between our test scores and each cerebral measure persisted regardless of the presence of neurocognitive impairment. We also calculated differences in average test scores between the total HIV+ group (n = 100) and a healthy adult group (n = 46). We found a positive association between the test scores and several brain area volumes: right frontal, temporal and parietal lobes, bilateral thalamus, and left hippocampus. We found a negative association between inflammatory markers in frontal white matter and the test scores. After controlling by neurocognitive impairment, several brain area volumes remained positively associated to the prosody test scores. Moreover, the whole HIV+ sample had significantly poorer test scores than healthy adults, but only in the subset of HIV+ individuals with neurocognitive impairment. For the first time, our results suggest that cerebral dysfunctions in particular brain areas involved in the processing of emotional auditory stimuli may occur in HIV+ individuals. These results highlight the need for broad characterization of the neuropsychological consequence of HIV brain damages.     

Relationship between brain large artery characteristics and their downstream arterioles

We aimed to test the hypothesis that brain large artery diameters relate to distal downstream arteriolar diameters. In a sample of 110 autopsied individuals (69% men, 76% HIV+, mean age 51), we used multilevel models to relate large artery lumen and lumen-to-wall ratio to left frontal lobe arteriolar lumen and lumen-to-wall ratio adjusting for demographics and vascular risk factors. Comparing the large artery characteristics of the whole brain did not disclose significant associations with frontal lobe arteriolar characteristics. However, restricting the comparison to large arteries upstream of the studied arterioles demonstrated an independent association between left-sided frontal lobe arteriolar luminal diameter with large artery luminal diameters (B?=?1.82?±?0.77, P?=?0.01) and with large artery lumen-to-wall ratio (B?=?0.58?±?0.29, P?=?0.05). In stratified models, the point estimates in the HIV+ subsample were larger than in the HIV? subsample. These finding suggest coupling between higher proximal blood flow represented by large artery diameter and lower distal resistance represented by arteriolar dilatation. The relationship between arteriolar dilatation and brain parenchyma homeostasis should be further studied.     

Social networks and symptomatic and functional outcomes in schizophrenia: a systematic review and meta-analysis

Purpose

To conduct a systematic review and meta-analysis to examine the strength of associations between social network size and clinical and functional outcomes in schizophrenia.

Method

Studies were identified from a systematic search of electronic databases (EMBASE, Medline, PsycINFO, and Web of Science) from January 1970 to June 2016. Eligible studies included peer-reviewed English language articles that examined associations between a quantitative measure of network size and symptomatic and/or functional outcome in schizophrenia-spectrum diagnoses.

Results

Our search yielded 16 studies with 1,929 participants. Meta-analyses using random effects models to calculate pooled effect sizes (Hedge’s g) found that smaller social network size was moderately associated with more severe overall psychiatric symptoms (N?=?5, n?=?467, g?=???0.53, 95% confidence interval (CI)?=???0.875, ??0.184, p?=?0.003) and negative symptoms (N?=?8, n?=?577, g?=???0.75, 95% CI?=???0.997, ??0.512, p?=?0.000). Statistical heterogeneity was observed I²?=?63.04%; I²?=?35.75%,) which could not be explained by low-quality network measures or sample heterogeneity in sensitivity analyses. There was no effect for positive symptoms (N?=?7, n?=?405, g?=???0.19, 95% CI?=?0.494, 0.110, p?=?0.213) or social functioning (N?=?3, n?=?209, g?=?0.36, 95% CI?=???0.078, 0.801, p?=?0.107). Narrative synthesis suggested that larger network size was associated with improved global functioning, but findings for affective symptoms and quality of life were mixed.

Conclusion

Psychosocial interventions which support individuals to build and maintain social networks may improve outcomes in schizophrenia. The review findings are cross-sectional and thus causal direction cannot be inferred. Further research is required to examine temporal associations between network characteristics and outcomes in schizophrenia and to test theoretical models relating to explanatory or mediating mechanisms.

     

Association between the growth rate of subependymal giant cell astrocytoma and age in patients with tuberous sclerosis complex

Purpose

The most common neurological complications associated with tuberous sclerosis complex (TSC) include intractable seizures that begin in infancy and subependymal giant cell astrocytoma (SEGA) complicated by hydrocephalus with increasing age. Information on SEGA growth of TSC patients is limited. This study aimed to examine the TSC-SEGA growth rates by periodic neuroimaging.

Methods

This study evaluated the TSC-SEGA growth rates by serial neuroimaging. Fifty-eight patients with TSC underwent systematic evaluation, including a review of medical history and serial brain neuroimaging.

Results

While magnetic resonance imaging was more sensitive in detecting cortical tubers than computed tomography (73.1 vs. 0 %, p?<?0.001), its efficacy in identifying intracranial lesions was comparable to that of computed tomography (96.2 vs. 100 %, p?=?0.658). Significant tumor growth was observed in children (p?=?0.012) and adults (p?=?0.028) during follow-up periods, respectively (median for children 23.5 months, interquartile range 18–40 months and median for adults 23 months, interquartile range 12–34 months). Further, the SEGA growth rate in children was significantly higher than that in adults (75.6 vs. 16.5 %, p?=?0.03).

Conclusions

The results of the study show that SEGA has a significantly higher growth rate in children using serial follow-up brain imaging, suggesting the importance of performing follow-up neuroimaging at yearly intervals in childhood to identify and prevent potential comorbidities.

     

Monogenic disorders that mimic the phenotype of Rett syndrome

Rett syndrome (RTT) is caused by mutations in methyl-CpG-binding protein 2 (MECP2), but defects in a handful of other genes (e.g., CDKL5, FOXG1, MEF2C) can lead to presentations that resemble, but do not completely mirror, classical RTT. In this study, we attempted to identify other monogenic disorders that share features with RTT. We performed a retrospective chart review on n?=?319 patients who had undergone clinical whole exome sequencing (WES) for further etiological evaluation of neurodevelopmental diagnoses that remained unexplained despite extensive prior workup. From this group, we characterized those who (1) possessed features that were compatible with RTT based on clinical judgment, (2) subsequently underwent MECP2 sequencing and/or MECP2 deletion/duplication analysis with negative results, and (3) ultimately arrived at a diagnosis other than RTT with WES. n?=?7 patients had clinical features overlapping RTT with negative MECP2 analysis but positive WES providing a diagnosis. These seven patients collectively possessed pathogenic variants in six different genes: two in KCNB1 and one each in FOXG1, IQSEC2, MEIS2, TCF4, and WDR45. n?=?2 (both with KCNB1 variants) fulfilled criteria for atypical RTT. RTT-associated features included the following: loss of hand or language skills (n?=?3; IQSEC2, KCNB1 x 2); disrupted sleep (n?=?4; KNCB1, MEIS2, TCF4, WDR45); stereotyped hand movements (n?=?5; FOXG1, KNCB1 x 2, MEIS2, TCF4); bruxism (n?=?3; KCNB1 x 2; TCF4); and hypotonia (n?=?7). Clinically based diagnoses can be misleading, evident by the increasing number of genetic conditions associated with features of RTT with negative MECP2 mutations.     

Amygdala Volume Differences in Autism Spectrum Disorder Are Related to Anxiety

Recent studies suggest that longstanding findings of abnormal amygdala morphology in ASD may be related to symptoms of anxiety. To test this hypothesis, fifty-three children with ASD (mean age?=?11.9) underwent structural MRI and were divided into subgroups to compare those with at least one anxiety disorder diagnosis (n?=?29) to those without (n?=?24) and to a typically developing control group (TDC; n?=?37). Groups were matched on age and intellectual level. The ASD and anxiety group showed decreased right amygdala volume (controlled for total brain volume) relative to ASD without anxiety (p?=?.04) and TDCs (p?=?.068). Results suggest that youth with ASD and co-occurring anxiety have a distinct neurodevelopmental trajectory.     

Evaluating the accuracy of self-report for the diagnosis of HIV-associated neurocognitive disorder (HAND): defining “symptomatic” versus “asymptomatic” HAND

The criteria for differentiating symptomatic from asymptomatic HIV-associated neurocognitive disorder require evaluation of (1) cognitive impairment, (2) daily functioning declines, and (3) whether the functional declines are attributable to cognitive versus physical problems. Many providers rely only on self-report to evaluate these latter criteria. However, the accuracy of patient-provided information may be limited. This study evaluated the validity of self-assessment for HIV-associated neurocognitive disorder (HAND) diagnoses by comparing objective findings with self-report of criteria 2 and 3 above. Self-reports were used to stratify 277 cognitively impaired HIV+ individuals into functionally dependent (n?=?159) and independent (n?=?118) groups, followed by group comparisons of objective functional problems. The dependent group was then divided into those who self-attributed their functional dependence to only cognitive (n?=?80) versus only physical (n?=?79) causes, for further comparisons on objective findings. The functionally dependent group was significantly worse than the independent group on all objective disability characteristics except severity of cognitive impairment, while those who attributed their dependence to physical (versus cognitive) factors were similar on all objective physical, cognitive, and functioning variables. Of note, 28 % of physical attributors showed no physical abnormalities on neuromedical examinations. Results suggest that patient report is consistently associated with objective measures of functional loss; in contrast, patient identification of physical versus cognitive causes is poorly associated with objective criteria. These findings caution against relying solely on patient self-report to determine whether functional disability in cognitively impaired HIV+ individuals can be attributed to strictly physical causes.     

Infant brain tumours: a tale of two cities

Introduction

Infantile brain tumours (age?<?1 year) are increasingly being diagnosed due to advances in prenatal and perinatal diagnostic imaging. We present here our retrospective study of 64 infant brain tumours that brings to the fore the epidemiology, clinical presentation, pathology and outcome of this unique subset of paediatric brain tumours presenting to two tertiary referral centres in Kolkata in India and Lille in France between the years 1999 and 2014.

Methods

Data was retrospectively collected from Kolkata (n?=?30) and Lille (n?=?34) for patients presenting with infant brain tumours and analysed for factors such as age at presentation, clinical features, gender, location of tumour, pathology, management and outcome. Follow-up was available for all patients.

Results

Mean age at presentation was 6.8 months at Kolkata and 6.3 months at Lille. More than two-thirds of tumours in both the groups were supratentorial and presented with signs of raised intracranial pressure. There was also a similar proportion of tumours presenting as congenital tumours. At Kolkata, germ cell tumours (n?=?7) were the most common while low-grade gliomas (n?=?11) formed the largest group at Lille. Kolkata had a higher incidence of high-grade gliomas (n?=?5) and PNETs (n?=?4) while ATRT (n?=?3) and choroid plexus carcinoma (n?=?4) were more common at Lille. Surgery was the mainstay of treatment at both centres.

Conclusion

Brain tumours in infants presenting to tertiary centres in Europe and India are challenging to manage and usually have dismal prognosis. These tumours differ markedly in the pathology and, therefore, overall outcome. Surgery forms mainstay of treatment. Radiotherapy is best avoided in this age group.