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Objective To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+). Design 24-week randomized o

Human immunodeficiency virus (HIV) is a rapidly evolving virus, allowing its genetic sequence to act as a fingerprint for epidemiological processes among, as well as within, individual infected hosts. Though primarily infecting the CD4+ T-cell population, HIV can also be found in monocytes, an immune cell population that differs in several aspects from the canonical T-cell viral target. Using single genome viral sequencing and statistical phylogenetic inference, we investigated the viral RNA diversity and relative contribution of each of these immune cell types to the viral population within the peripheral blood. Results provide evidence of an increased prevalence of circulating monocytes harboring virus in individuals with high viral load in the absence of suppressive antiretroviral therapy. Bayesian phyloanatomic analysis of three of these individuals demonstrated a measurable role for these cells, but not the circulating T-cell population, as a source of cell-free virus in the plasma, supporting the hypothesis that these cells can act as an additional conduit of virus spread., (© The Author(s) 2020. Published by Oxford University Press.)

HIV-associated neurocognitive disorder (HAND) remains a challenge despite antiretroviral therapy (ART), and has been linked to monocyte/macrophage (M/M) migration to the brain. Due to the potential impact of T cell effector mechanisms in eliminating activated/HIV-infected M/M, T cell activation may play a role in the development of HAND. We sought to investigate the relationship between cognition and both CD8 + T cell activation (HLA-DR + /CD38 + ) and HIV-specific CD8 + T cell responses at the time of HIV diagnosis and 12 months postinitiation of ART. CD8 + T cell activation was increased in HAND compared to cognitive normal (NL) individuals and correlated directly with plasma viral load and inversely with the cognitive status. In addition, Gag-specific cytolytic activity (CD107a/b + ) was decreased in HAND compared with NL individuals and correlated with their neurological testing, suggesting a potential role of cytotoxic CD8 + T cells in the mechanism of HAND development.

Background: Children with vertically acquired HIV exhibit persistent cognitive impairments, yet the corresponding neuroimaging signature of vertical infection remains unclear., Methods: Fifty healthy control children and 51 vertically infected children were included in the study. The HIV-infected group consisted of survivors who had not received antiretroviral therapy at birth. The HIV-infected group averaged 11.4 (2.5) years of age, with a median CD4 count of 683 cells/mm(3). Most (71%) of the HIV-infected children were on antiretroviral therapy for a median of 34 months (range: 33-42) with HIV RNA <40 copies/mL in 89% of the sample. The HIV-uninfected group averaged 10.6 (2.6) years of age. Magnetic resonance imaging was acquired to determine volumes of the caudate, putamen, thalamus, pallidum, hippocampus, nucleus accumbens, total white matter, total gray matter and cortical gray matter. Correlational analyses examined the degree of shared variance between brain volumes and both cognitive performances and laboratory markers of disease activity (T cells and plasma viral load)., Results: HIV-infected children exhibited larger volumes of the caudate, nucleus accumbens, total gray matter and cortical gray matter when compared with the controls. Volumetric differences were predominately evident in children under 12 years of age. HIV-infected children performed worse than controls on most neuropsychologic tests, though neither cognitive performances nor laboratory markers corresponded to brain volumes in the HIV-infected children., Conclusions: Outcomes of the present study suggest abnormal brain maturation among HIV-infected pediatric survivors. Longitudinal studies of brain integrity and related resilience factors are needed to determine the impact of neuroimaging abnormalities on psychosocial function in pediatric HIV.

Background: Magnetic resonance imaging (MRI) is used for neuroradiologic evaluation of patients with idiopathic growth hormone deficiency (IGHD)., Objectives: To compare pituitary height and morphology at MRI between patients with IGHD and controls., Materials and Methods: This retrospective study was conducted in pediatric patients, 3 years-15 years old, who had had brain MRI with non-contrast-enhanced midsagittal T1-weighted images. These images were measured for pituitary height and morphology of the pituitary gland including shape, stalk and posterior pituitary bright spot was evaluated., Results: One hundred and nineteen patients were included, with 49 and 70 patients assigned to the study and control groups, respectively. Mean pituitary height was significantly less in the IGHD group than in the control group (3.81 mm±1.38 vs. 4.92 mm±1.13, retrospectively; P<0.001). Subgroup analysis revealed a significant difference in the pituitary height between groups in the prepubertal (8-10 years) and pubertal (11-13 years) periods (P=0.039 and P=0.006, respectively) and a trend toward significance in the postpubertal period (P=0.053). There was a significant difference in pituitary shape between IGHD and controls when combining grades III, IV and V (P=0.007). Other abnormal MRI findings of the pituitary stalk and posterior bright spot were significantly more often observed in the IGHD group (P<0.05)., Conclusion: Pituitary height was significantly smaller in patients with IGHD than in controls during prepuberty and puberty. Abnormal concave superior contour, hypoplastic stalk and absent/ectopic posterior bright spot were observed significantly more often among patients with IGHD.

Purpose: Flame-shaped pseudo-occlusion of the extracranial internal carotid artery (ICA) is a flow-related phenomenon that creates computed tomographic angiography (CTA) and digital subtraction angiography (DSA) findings that mimic tandem intracranial-extracranial ICA occlusion or dissection. We aim to determine the diagnostic performance of mid-cervical flame-shaped extracranial ICA sign on CTA in hyperacute ischemic stroke patients., Methods: We retrospectively included consecutive anterior circulation ischemic stroke patients presenting within 6 h of symptom onset who underwent 4D brain CTA and arterial-phase neck CTA using a 320-detector CT scanner during August 2012 to July 2015. Two blinded readers independently reviewed arterial-phase neck CTA and characterized the extracranial ICA configurations into mid-cervical flame-shaped, proximal blunt/beak-shaped, and tubular-shaped groups. 4D whole brain CTA was used as a reference standard for intracranial ICA occlusion detection. Diagnostic performance of the mid-cervical flame-shaped extracranial ICA sign and interobserver reliability were calculated., Results: Of the 81 cases, 11 had isolated intracranial ICA occlusion, and 6 had true extracranial ICA occlusion. Mid-cervical flame-shaped extracranial ICA sign was found in 45.5% (5/11) of isolated intracranial ICA occlusions but none in the true extracranial ICA occlusion group. The sensitivity, specificity, PPV, NPV, and accuracy of the mid-cervical flame-shaped extracranial ICA sign for the detection of isolated intracranial ICA occlusion were 45.5, 100, 100, 92.1, and 92.6%, respectively. Interobserver reliability was 0.90., Conclusion: The mid-cervical flame-shaped extracranial ICA sign may suggest the presence of isolated intracranial ICA occlusion and allow reliable exclusion of tandem extracranial-intracranial ICA occlusion in hyperacute ischemic stroke setting.

Background: Central nervous system (CNS) infiltration by CD8 T cells is associated with neuroinflammation in many neurodegenerative diseases, including HIV-associated dementia. However, the role of CD8 T cells in the CNS during acute HIV infection (AHI) is unknown., Methods: We analyzed the phenotype, gene expression, T cell receptor (TCR) repertoire, and HIV specificity of CD8 T cells in cerebrospinal fluid (CSF) of a unique cohort captured during the earliest stages of AHI (n = 26), chronic (n = 23), and uninfected (n = 8)., Results: CSF CD8 T cells were elevated in AHI compared with uninfected controls. The frequency of activated CSF CD8 T cells positively correlated to CSF HIV RNA and to markers of CNS inflammation. In contrast, activated CSF CD8 T cells during chronic HIV infection were associated with markers of neurological injury and microglial activation. CSF CD8 T cells in AHI exhibited increased functional gene expression profiles associated with CD8 T cells effector function, proliferation, and TCR signaling, a unique restricted TCR Vbeta repertoire and contained HIV-specific CD8 T cells directed to unique HIV epitopes compared with the periphery., Conclusions: These results suggest that CSF CD8 T cells in AHI expanding in the CNS are functional and directed against HIV antigens. These cells could thus play a beneficial role protective of injury seen in chronic HIV infection if combination antiretroviral therapy is initiated early.

Introduction: Frontoethmoidal encephalomeningocele (FEEM) is a congenital disorder characterized by herniation of brain and meninges through an anterior skull defect. The main pathological changes are found internally at the foramen cecum and externally at the frontonaso-orbital region. The aim of this study was to determine the incidence of developmental anomalies found in FEEM using multidetector computed tomography images of the facial bone., Methods: A total of 78 patients who underwent multidetector computed tomography scan of the facial bone during the January 1, 2003 to June 31, 2012 study period were retrospectively reviewed. Demographic data, size of internal defect, and intracranial anomalies were recorded., Results: Associated brain and ophthalmic anomalies were identified in 53 patients (67.9%), and all of those had brain anomalies. The most common brain anomalies were absent/undetermined septum pellucidum (75.5%), ventricular dilatation (71.7%), abnormal frontal horn (67.9%), and dysgenesis of the corpus callosum (58.5%). Eight patients (10.3%) had ophthalmic anomalies. Patients with brain and ophthalmic anomalies tended to have a higher incidence of large-size internal defects., Conclusion: The authors found a high prevalence of developmental anomalies in FEEM patients. Absent/undetermined septum pellucidum was the most commonly found anomaly in this study. Brain and ophthalmic anomalies tended to have a higher incidence of large-size internal bone defects. Consistent with the authors' acknowledged limitation, further studies using dedicated brain MRI and magnetic resonance angiography to evaluate parenchymal abnormalities and vascular anomalies may be beneficial for surgical planning, prognosis, and the identification of clinical correlations.

Epstein-Barr virus-associated undifferentiated (lymphoepithelial) carcinoma is a malignancy that most commonly arises in the nasopharynx but can also occur in other locations including the lacrimal sac. Generally, this tumor strongly expresses cytokeratin, making the diagnosis straightforward. In the absence of confirmatory immunohistochemistry, the diagnosis can be problematic, particularly for tumors arising in unusual locations. Only 3 cases arising in the lacrimal sac in association with Epstein-Barr virus have been reported in the English literature, and all showed typical pathologic findings. The authors report a fourth case, unique in that it showed negative immunostaining for all cytokeratins tested. The clue to the nature of the tumor came from identification of Epstein-Barr virus by in-situ hybridization and demonstration of tonofilaments by electron microscopy. This case demonstrates that a multimodal approach may be needed in the diagnosis of Epstein-Barr virus-associated carcinoma, especially when occurring in uncommon locations.

Objective: To determine the incidence, timing, and severity of neurologic findings in acute HIV infection (pre-antibody seroconversion), as well as persistence with combination antiretroviral therapy (cART)., Methods: Participants identified with acute HIV were enrolled, underwent structured neurologic evaluations, immediately initiated cART, and were followed with neurologic evaluations at 4 and 12 weeks. Concurrent brain MRIs and both viral and inflammatory markers in plasma and CSF were obtained., Results: Median estimated HIV infection duration was 19 days (range 3-56) at study entry for the 139 participants evaluated. Seventy-three participants (53%) experienced one or more neurologic findings in the 12 weeks after diagnosis, with one developing a fulminant neurologic manifestation (Guillain-Barré syndrome). A total of 245 neurologic findings were noted, reflecting cognitive symptoms (33%), motor findings (34%), and neuropathy (11%). Nearly half of the neurologic findings (n = 121, 49%) occurred at diagnosis, prior to cART initiation, and most of these (n = 110, 90%) remitted concurrent with 1 month on treatment. Only 9% of neurologic findings (n = 22) persisted at 24 weeks on cART. Nearly all neurologic findings (n = 236, 96%) were categorized as mild in severity. No structural neuroimaging abnormalities were observed. Participants with neurologic findings had a higher mean plasma log10 HIV RNA at diagnosis compared to those without neurologic findings (5.9 vs 5.4; p = 0.006)., Conclusions: Acute HIV infection is commonly associated with mild neurologic findings that largely remit while on treatment, and may be mediated by direct viral factors. Severe neurologic manifestations are infrequent in treated acute HIV., (© 2016 American Academy of Neurology.)

Craniofacial arteriovenous malformation (AVM), although very rare, has been a very difficult problem to treat especially when it is large and involves important structures. Surgical resection often results in unacceptable complications but still not curative. At our institution, treatment by combined intralesional neodymium-doped yttrium aluminium garnet laser and intratumoral ligation has been successful in venous malformation. This minimally invasive technique was then applied to more challenging AVM on the head and neck. Disease control was studied using clinical parameters and magnetic resonance imaging.Four patients with moderate-to-severe (Schobinger 2-4) craniofacial AVM were treated by this technique from 2001 to 2011. Patient age ranged from 2 to 51 years (mean: 25 years). After 2 to 4 treatments and follow-up period of 1456 days, 3 (75%) were cured. One of them was infant with huge mass and secondary pulmonary hypertension. Clinical cure was achieved after 3 treatments without residual cardiovascular compromise. The other patient (25%) had cheek mass with intraorbital involvement. The authors did not treat periorbital lesion so as to avoid triggering intraorbital spreading. The rest of the cheek lesion was clinically and radiologically cured.Laser energy setting, ablative technique, and skin cooling are the main factors determining the success. Individualized laser settings and properly set endpoints can increase treatment effectiveness in shorter period. In conclusion, this minimally invasive technique was successful in curing AVM without complication. With more clinical study and development of soft tissue monitoring tools, it is possible that intralesional laser could become the treatment of choice for all cutaneous AVM.

Objective: Combination antiretroviral therapy (cART) can suppress plasma HIV RNA to undetectable levels; yet reports indicate persistent HIV-associated neurocognitive disorders (HAND) among treated individuals. We sought to investigate imaging correlates of incomplete cognitive recovery among individuals with chronic HIV., Methods: We used single voxel proton magnetic resonance spectroscopy in 4 regions of the brain to measure changes in neuronal and glia biomarkers in cART-naive subjects before (n = 59, 27 with HAND) and after 12 months of cART., Results: At baseline, we observed elevated total choline (CHO) in the basal ganglia (BG, P = 0.002) and in the posterior cingulate gyrus (PCG, P = 0.022) associated with HIV infection. Myo-inositol (MI) was elevated in the frontal white matter (FWM, P = 0.040). N-acetylaspartate was elevated in the BG (P = 0.047). Using a mixed model approach among all HIV-infected individuals, at 6 months, we observed decreased n- acetylaspartate in FWM (P = 0.031), decreased creatine in PCG (P = 0.026) and increased MI in frontal gray matter (FGM, P = 0.023). At 12 months, we observed an increase in BG MI (P = 0.038) and in FGM (P = 0.021). Compared to those with normal cognition, HAND cases had higher FGM MI (P = 0.014) at baseline. At 12 months, individuals that remained cognitively impaired compared with those without HAND exhibited elevated CHO in the PCG (P = 0.018) and decreased glutamate in both FWM (P = 0.027) and BG (P = 0.013)., Conclusions: cART started during chronic HIV is associated with reduced neuronal-glia and inflammatory markers. Alterations in CHO are noted among individuals who remain impaired after 12 months of cART.

Background: It is unknown whether neuronal injury begins during acute human immunodeficiency virus (HIV) infection, and whether immediate initiation of combination antiretroviral therapy (cART) prevents neuronal injury., Methods: Cerebrospinal fluid (CSF) neurofilament light chain (NFL), a measure of axonal injury, was assessed before and after cART initiation in individuals starting treatment during acute or chronic HIV infection. Nonparametric statistics examined relationships between NFL and disease progression, neuroinflammation, and cognitive performance., Results: Before treatment, subjects with acute infection had lower CSF NFL levels, with elevations for their age in 1 of 32 subjects with acute infection (3.1%) and 10 of 32 with chronic infection (31%) (P = .006). This persisted after cART initiation, with 1 of 25 acute (4%) and 4 of 9 chronic subjects (44%) showing elevated NFL levels (P = .01). In acute infection, pre-cART NFL levels were inversely correlated with proton magnetic resonance spectroscopic findings of N-acetylaspartate/creatine in frontal gray matter (r = -0.40; P = .03), frontal white matter (r = -0.46; P = .01), and parietal gray matter (r = -0.47; P = .01); correlations persisted after treatment in the frontal white matter (r = -0.51; P = .02) and parietal gray matter (r = -0.46; P = .04)., Conclusions: CSF NFL levels are not elevated in untreated acute HIV infection or after 6 months of immediately initiated cART but are abnormal in chronic HIV infection before and after treatment. In acute HIV infection, CSF NFL levels are inversely associated with neuroimaging markers of neuronal health., (© The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.)

Objective: To compare central nervous system (CNS) outcomes in participants treated during acute HIV infection with standard combination antiretroviral therapy (cART) vs. cART plus integrase inhibitor and CCR5 antagonist (cART+)., Design: 24-week randomized open-label prospective evaluation., Method: Participants were evaluated then randomized to initiate cART (efavirenz, tenofovir, and either emtricitabine or lamivudine) vs. cART+ (cART plus raltegravir and maraviroc) during acute HIV and re-evaluated at 4, 12 and 24 weeks. We examined plasma and CSF cytokines, HIV RNA levels, neurological and neuropsychological findings, and brain MRS across groups and compared to healthy controls., Results: At baseline, 62 participants were in Fiebig stages I-V. Randomized groups were similar for mean age (27 vs. 25, p = 0.137), gender (each 94% male), plasma log10 HIV RNA (5.4 vs. 5.6, p = 0.382), CSF log10 HIV RNA (2.35 vs. 3.31, p = 0.561), and estimated duration of HIV (18 vs. 17 days, p = 0.546). Randomized arms did not differ at 24 weeks by any CNS outcome. Combining arms, all measures concurrent with antiretroviral treatment improved, for example, neuropsychological testing (mean NPZ-4 of -0.408 vs. 0.245, p<0.001) and inflammatory markers by MRS (e.g. mean frontal white matter (FWM) choline of 2.92 vs. 2.84, p = 0.045) at baseline and week 24, respectively. Plasma neopterin (p<0.001) and interferon gamma-induced protein 10 (IP-10) (p = 0.007) remained elevated in participants compared to controls but no statistically significant differences were seen in CSF cytokines compared to controls, despite individual variability among the HIV-infected group., Conclusions: A 24-week course of cART+ improved CNS related outcomes, but was not associated with measurable differences compared to standard cART.

Background: Perinatal use of combination antiretroviral therapy dramatically reduces vertical (mother-to-child) transmission of HIV but has led to a growing population of children with perinatal HIV-exposure but uninfected (HEU). HIV can cause neurological injury among children born with infection, but the neuroanatomical and developmental effects in HEU children are poorly understood., Methods: We used structural magnetic resonance imaging with diffusion tensor imaging to compare brain anatomy between 30 HEU and 33 age-matched HIV-unexposed and uninfected (HUU) children from Thailand. Maps of brain volume and microstructural anatomy were compared across groups; associations were tested between neuroimaging measures and concurrent neuropsychological test performance., Results: Mean (standard deviation) age of children was 10.3 (2.8) years, and 58% were male. All were enrolled in school and lived with family members. Intelligence quotient (IQ) did not differ between groups. Caretaker education levels did not differ, but income was higher for HUU (P < 0.001). We did not detect group differences in brain volume or diffusion tensor imaging metrics, after controlling for sociodemographic factors. The mean (95% confidence interval) fractional anisotropy in the corpus callosum was 0.375 (0.368-0.381) in HEU compared with 0.370 (0.364-0.375) in HUU. Higher fractional anisotropy and lower mean diffusivity were each associated with higher IQ scores in analyses with both groups combined., Conclusions: No differences in neuroanatomical or brain integrity measures were detectable in HEU children compared with age-matched and sex-matched controls (HUU children). Expected associations between brain integrity measures and IQ scores were identified suggesting sufficient power to detect subtle associations that were present.

Purpose: This study aimed to observe the prevalence and associated factors of neurovascular contact hemifacial spasm (HFS)., Design: This was a cross-sectional analytical study., Methods: Medical records of patients with HFS in a neuro-ophthalmology clinic in Thailand between June 2008 and June 2012 were reviewed. A positive magnetic resonance imaging finding was defined as an adjacent variant vessel that directly compressed or placed pressure on the affected facial nerve. Prevalence and associated factors were analyzed., Results: A total of 60 participants were enrolled, composed of 12 male patients and 48 female patients with a median age of 54 years [interquartile range (IQR), 44.0-64.75] and a disease duration ranging from 4 months to 16 years (median, 2 years; IQR, 1.0-6.0). The prevalence of neurovascular contact HFS was 41.7%. Neurovascular contact HFS was more prevalent among women, with an overall ratio of 3.33. In age group analysis, the prevalence was higher among older patients. In univariate analysis, right-sided symptoms and diabetes mellitus were statistically significant in their association with neurovascular contact HFS (P = 0.040 and P = 0.029, respectively). Right-sided symptoms were significant in a multiple logistic regression analysis (P = 0.038), with an odds ratio of 3.30 [95% confidence interval (CI), 1.07-10.15]. Diabetes mellitus was not statistically significant (P = 0.051), with an odds ratio of 9.99 (95% CI 0.99-96.34)., Conclusions: The prevalence of neurovascular contact in patients with HFS was 41.7%. Right-sided symptoms were significantly associated with this condition.

This study aimed to determine the effects of human immunodeficiency virus (HIV) on brain structure in HIV-infected individuals with and without HIV-associated neurocognitive disorders (HAND). Twenty-nine HIV-uninfected controls, 37 HIV+, treatment-naïve, individuals with HAND (HIV+HAND+; 16 asymptomatic neurocognitive impairment (ANI), 12 mild neurocognitive disorder (MND), and 9 HIV-associated dementia HAD), and 37 HIV+, treatment-naïve, individuals with normal cognitive function (HIV+HAND-) underwent magnetic resonance imaging (MRI) and neuropsychological assessment. The HIV-infected participants had a mean (SD) age of 35 (7) years, mean (interquartile range (IQR)) CD4 count of 221 (83-324), and mean (IQR) log10 plasma viral load of 4.81 (4.39-5.48). Six regions of interest were selected for analyses including total and subcortical gray matter, total white matter, caudate, corpus callosum, and thalamus. The HIV+/HAND+ group exhibited significantly smaller brain volumes compared to the HIV-uninfected group in subcortical gray and total gray matter; however, there were no statistically significant differences in brain volumes between the HIV+HAND+ and HIV+HAND- groups or between HIV+/HAND- and controls. CD4 count at time of combination antiretroviral therapy (cART) initiation was associated with total and subcortical gray matter volumes but not with cognitive measures. Plasma viral load correlated with neuropsychological performance but not brain volumes. The lack of significant differences in brain volumes between HIV+HAND+ and HIV+HAND- suggests that brain atrophy is not a sensitive measure of HAND in subjects without advanced immunosuppression. Alternatively, current HAND diagnostic criteria may not sufficiently distinguish patients based on MRI measures of brain volumes.

Objective: Extratemporal lobe epilepsy is difficult to localize. We aimed to define the best parameter(s) of SPECT for confirmation of seizure origin among the region of maximum cerebral perfusion in ictal phase (MP), maximum change of cerebral perfusion from interictal to ictal phase (MC), and maximum extent of hyperperfusion in ictal phase (ME) of (99m)Tc ECD brain perfusion SPECT as well as combined SPECT parameters, and combined SPECT and MRI for seizure localization in extratemporal lobe epilepsy., Materials and Methods: Twenty intractable extratemporal lobe epilepsy patients who had (99m)Tc-ECD brain SPECT were reviewed. Sensitivity, specificity, positive predictive value, negative predictive value and accuracy of single SPECT parameter, combined SPECT parameters, and combined SPECT and MRI parameters for localization of seizure origin were calculated using pathology and surgical outcomes (Engel class I and II) as gold standards., Results: Combined SPECT parameters provided more specificity, PPV and accuracy than single SPECT parameters. The best combined SPECT parameters was MP+MC with 80.6 % accuracy, 92.4 % specificity and 43.8 % PPV. Combination of SPECT parameter with MRI (ME+MRI) was the most sensitive (41.7 %), specific (97.5 %), accurate (88.2 %) parameter and had highest PPV (76.9 %) and NPV (89.3 %) for seizure localization. It improved specificity and PPV when compared to MRI alone., Conclusion: Combined SPECT parameters improved the specificity and accuracy in seizure localization. The most specific and accurate SPECT combination is MP+MC. The combined SPECT parameter with MRI further improved sensitivity, specificity, accuracy, PPV and NPV. The authors recommend using SPECT combination, MP+MC, when MRI is negative and ME+MRI when there is MRI lesion.

Objective: To examine associations between regional brain volumes and HIV DNA in peripheral CD14 cells (monocytes) among HIV-infected individuals naive to combination antiretroviral therapy (cART)., Design: A prospective study of HIV-infected Thai individuals who met Thai national criteria for cART initiation. Enrolment was stratified by HIV DNA in a blinded fashion., Methods: CD14 cells were isolated from peripheral mononuclear cells to high purity (median 91.4% monocytes by flow cytometry), and HIV DNA was quantified by multiplex real-time PCR. Baseline regional brain volumes obtained by T1-weighted 1.5-Tesla MRI were compared between HIV DNA groups using analysis of covariance (ANCOVA)., Results: We studied 60 individuals with mean (SD) age of 34.7 (7.0) years, CD4 T-lymphocyte count of 232 (137) cells/μl and log10 plasma HIV RNA of 4.8 (0.73). Median (interquartile range, IQR) HIV DNA copy number per 10 CD14 cells was 54 (102). Using our previously determined optimal cut-point of 45 copies/10 cells for this cohort, a threshold value above which CD14 HIV DNA identified HIV-associated neurocognitive disorders (HANDs), we found that CD14 HIV DNA  ≥ 45 copies/10 cells was associated with reduced volumes of the nucleus accumbens (P=0.021), brainstem (P=0.033) and total gray matter (P=0.045) independently of age, CD4 cell count and intracranial volume., Conclusion: HIV DNA burden in CD14 monocytes is directly linked to brain volumetric loss. Our findings implicate peripheral viral reservoirs in HIV-associated brain atrophy and support their involvement in the neuropathogenesis of HAND, underscoring the need for therapies that target these cells.

Pituitary metastasis is an uncommon first presentation of systemic malignancy. The most common presenting symptom of pituitary metastasis is diabetes insipidus reflecting involvement of the stalk and/or posterior pituitary. We herein present a unique case of the coexistence of both a functioning pituitary adenoma (prolactinoma) and pituitary metastasis of advanced colorectal cancer with pituitary apoplexy as the first manifestation of underlying malignancy. The present case emphasizes the need to consider pituitary metastasis as a differential diagnosis in patients presenting with pituitary lesions and be aware that tumor-to-tumor metastasis can occur unexpectedly in those with pituitary metastases.

Objective: Outcome predictors from the pure cohorts of patients with temporal lobe epilepsy (TLE) with hippocampal sclerosis (HS) are limited The aim of the present study was to assess seizure outcomes and predictive factors in groups of well-defined patients with TLE-HS., Material and Method: One hundred forty eight patients with drug resistant TLE who had magnetic resonance imaging (MRI) that demonstrated unilateral HS underwent temporal lobectomy between 2004 and 2008 by a single neurosurgeon. All patients had completed at least two years of follow-up. Seizure outcome was categorized into seizure-free and not seizure-free., Results: Ninety-five patients (64.2%) were seizure-free after surgery at two years of follow-up. At four years follow-up, 47 patients (77.1%) were seizure-free for at least two years. There was no operative mortality or significant morbidity. No clinical variables are predictive of surgical outcomes at two and four years offollow-up., Conclusion: Temporal lobectomy for drug-resistant TLE with HS is safe and effective. The authors did not identify predictive factors of surgical outcomes in TLE-HS.

Background: Understanding the earliest central nervous system (CNS) events during human immunodeficiency virus (HIV) infection is crucial to knowledge of neuropathogenesis, but these have not previously been described in humans., Methods: Twenty individuals who had acute HIV infection (Fiebig stages I-IV), with average 15 days after exposure, underwent clinical neurological, cerebrospinal fluid (CSF), magnetic resonance imaging, and magnetic resonance spectroscopy (MRS) characterization., Results: HIV RNA was detected in the CSF from 15 of 18 subjects as early as 8 days after estimated HIV transmission. Undetectable CSF levels of HIV (in 3 of 18) was noted during Fiebig stages I, II, and III, with plasma HIV RNA levels of 285651, 2321, and 81978 copies/mL, respectively. On average, the CSF HIV RNA level was 2.42 log(10) copies/mL lower than that in plasma. There were no cases in which the CSF HIV RNA level exceeded that in plasma. Headache was common during the acute retroviral syndrome (in 11 of 20 subjects), but no other neurological signs or symptoms were seen. Intrathecal immune activation was identified in some subjects with elevated CSF neopterin, monocyte chemotactic protein/CCL2, and interferon γ-induced protein 10/CXCL-10 levels. Brain inflammation was suggested by MRS., Conclusions: CSF HIV RNA was detectable in humans as early as 8 days after exposure. CNS inflammation was apparent by CSF analysis and MRS in some individuals during acute HIV infection.

Objective: Single voxel proton magnetic resonance spectroscopy (MRS) can be used to monitor changes in brain inflammation and neuronal integrity associated with HIV infection and its treatments. We used MRS to measure brain changes during the first weeks following HIV infection and in response to antiretroviral therapy (ART)., Methods: Brain metabolite levels of N-acetyl aspartate (NAA), choline (tCHO), creatine (CR), myoinositol (MI), and glutamate and glutamine (GLX) were measured in acute HIV subjects (n = 31) and compared to chronic HIV+individuals (n = 26) and HIV negative control subjects (n = 10) from Bangkok, Thailand. Metabolites were measured in frontal gray matter (FGM), frontal white matter (FWM), occipital gray matter (OGM), and basal ganglia (BG). Repeat measures were obtained in 17 acute subjects 1, 3 and 6 months following initiation of ART., Results: After adjustment for age we identified elevated BG tCHO/CR in acute HIV cases at baseline (median 14 days after HIV infection) compared to control (p = 0.0014), as well as chronic subjects (p = 0.0023). A similar tCHO/CR elevation was noted in OGM; no other metabolite abnormalities were seen between acute and control subjects. Mixed longitudinal models revealed resolution of BG tCHO/CR elevation after ART (p = 0.022) with tCHO/CR similar to control subjects at 6 months., Interpretation: We detected cellular inflammation in the absence of measurable neuronal injury within the first month of HIV infection, and normalization of this inflammation following acutely administered ART. Our findings suggest that early ART may be neuroprotective in HIV infection by mitigating processes leading to CNS injury.

Motor neglect is an impairment in the ability to initiate movement not attributable to muscle weakness. The neural network of this syndrome is not precisely defined. We present the diffusion tensor imaging (DTI)-base tractography findings in an acute stroke patient presenting with isolated motor neglect following infarction in the posterior limb of the internal capsule within the anterior choroidal artery territory. A left-handed 17-year-old woman presented with an acute onset of motor neglect of her left arm. Motor tasks performed with the affected limb were awkward; however, the tasks could be accomplished with effort. Magnetic resonance imaging (MRI) including DTI of the brain were performed. DTI-based tractography extracted the fiber tracts originating from regions of interest placed on the ischemic lesion. MRI revealed an acute ischemic infarction at the posterior part of the posterior limb of the right internal capsule within the territory of the anterior choroidal artery. DTI-based tractography showed fiber tracts projecting from the lesion to the posterior part of the supplementary motor area and some fiber tracts projecting to posterior aspects of the thalamus. DTI-based tractography may be a useful tool for visualizing white matter pathways in vivo following an acute infarction. Our case study supports the notion that fiber tracts connecting the posterior part of the posterior limb of the internal capsule, supplementary motor area, and posterior aspect of the thalamus are key areas of a neural network involved in motor neglect syndrome.

Patients of 50 years or older account for a small but significant portion of the patient population that receives surgical treatment for epilepsy. There have been few studies reporting surgical outcomes from temporal lobectomy in older patients. We examined seizure outcome and surgical complications after anterior temporal lobectomy for temporal lobe epilepsy with pathological evidence of unilateral hippocampal sclerosis. Two patient groups were compared in this study: patients 50 years or older (mean age 55.5 years old, n=16) and patients less than 50 years old (mean age 32.9 years old, n=184). After a minimum of one year follow up, younger patients (79.4%, n=146) were significantly more likely to be seizure-free (p=0.041) compared to older patients (56.3%, n=9). There was no significant difference (p=0.404) between the two age groups in the percentage of patients withdrawn from medication following surgery. Surgical complications were significantly higher in the older age group compared to the younger age group (p=0.009), although there was no permanent morbidity. Thus, while surgical treatment of temporal lobe epilepsy with unilateral hippocampal sclerosis is still beneficial in older patients who are refractory to medical therapy, surgical treatment should be considered at as early an age as possible, to maximize the chance for a better outcome with fewer complications., (Copyright © 2010 British Epilepsy Association. Published by Elsevier Ltd. All rights reserved.)

Epithelioid sarcoma is a rare soft-tissue tumor that usually occurs in young adults, with a median age of 26 years. This malignancy has been divided into distal and proximal types. The latter is found in proximal body sites including the head and neck region. We present a rare case of parotid proximal-type epithelioid sarcoma in a 1-year-old male child; this is the 4th reported case in the literature and the youngest in a pediatric patient to date. The tumor showed prominent rhabdoid features by light microscopy. Immunohistochemical studies revealed positive staining to cytokeratin (AE1/AE3), epithelial membrane antigen, vimentin, and BAF47. Thus, while the tumor resembled a malignant rhabdoid tumor, the positive staining for BAF47 supported instead a diagnosis of epithelioid sarcoma, according to our current understanding of these 2 tumor types. Also, the clinical course was not the typical aggressive behavior of a rhabdoid tumor. The patient underwent radical parotidectomy without adjuvant therapy and remained disease-free at follow-up, 14 months after surgery.

Objective: Establish criteria for the diameters of normal extraocular muscles using computerized tomography in a Thai population., Material and Method: Diameters of extraocular muscles (medial, lateral, superior complex, and inferior rectus) were calculated for 200 patients on coronal direction of screening paranasal sinuses. The effects of age and sex were also analyzed., Result: Normal ranges for the diameters (mean +/- 2 SDs) of extraocular muscles were 3.7 +/- 0.9 mm for medial rectus, 3.6 +/- 1.2 mm for lateral rectus, 4.0 +/- 1.4 mm for inferior rectus and 3.8 +/- 1.4 mm for the superior group. The mean diameter of the extraocular muscles in male patients was not significantly larger than in female patients (p > 0.05). There was also no statistically significant correlation between age, diameter of each extramuscular muscle and the sum of all four muscles., Conclusion: The present result may help radiologists and ophthalmologists to accurately assess enlargement of the extraocular muscles, particularly in Oriental populations.

Background: Body composition changes complicate antiretroviral therapy. Improvements in lipoatrophy after a switch in nucleoside reverse-transcriptase inhibitors (NRTIs) have been demonstrated. We investigated 60 patients switching from failed NRTIs to ritonavir-boosted indinavir and efavirenz., Methods: Body composition (assessed by dual-energy x-ray absorptiometry scan and by single-slice computed tomography of the abdomen through the level of the fourth lumbar vertebra [L4] and the mid-right thigh) and fasted metabolics were measured at the baseline time-point at switch and at weeks 48 and 96 thereafter. Mitochondrial DNA and RNA were extracted from right-thigh subcutaneous fat and peripheral-blood mononuclear cells (PBMCs) at weeks 0 and 48. The primary end point was the change in mean limb fat over 48 weeks., Results: At week 96, we observed increases in mean (standard deviation [SD]) limb fat (+620 [974] g; P=.003), L4 subcutaneous adipose tissue (+20 [35] cm(2); P<.001), mid-thigh subcutaneous adipose tissue (+5 [10] cm(2); P<.001), and L4 visceral adipose tissue (+11 [34] cm(2); P=.01), but we also observed reduced lean limb mass (-831 [1,100] g; P=.3). Mean (SD) mtDNA content in subcutaneous fat and in PBMCs increased (+109 [274] and +45 [100] copies/cell, respectively). Improved virological control or immune recovery did not explain the results. Triglyceride, total cholesterol, estimated low-density lipoprotein cholesterol, ratio of total cholesterol to high-density lipoprotein cholesterol, and blood glucose levels deteriorated (i.e., had increased by 206%, 67%, 58%, 19%, and 6%, respectively, at week 96)., Conclusions: This regimen was associated with statistically significant but clinically modest increases in peripheral fat, visceral fat, and mitochondrial nucleic acid content. A predominantly adverse metabolic profile developed.

A 19-year old female with intractable gelastic seizures was found to have 0.7 x 1.8 x 1.8 cm elliptical mass on the floor of the third ventricle. The signal intensity on the Magnetic Resonance Imaging (MRI) was consistent with the Hypothalamic Hamartoma (HH). Ictal EEG demonstrated rhythmic 7 Hz waves over Fp2, F4, and C4 with spreading to the right temporal region and then bilaterally. Ictal Single Photon Emission Computerized Tomography (SPECT) showed hyperperfusion at hypothalamic and medial frontopolar regions. The patient underwent surgical resection using Trans Callosal Subchoroidal Approach (TCSA) to the third ventricle. Pathological finding confirmed the diagnosis of hypothalamic hamartoma. Following the operation, she has been seizure free up to 12 months. Thereafter, provoked seizures seldom occurred and there has been improvement in her memory, emotional control and independence. This appears to be the first report of this surgical approach for HH, which is less likely to disturb memory function compared to previously described interfoniceal approach.

The authors report the first invasive electroencephalography (EEG) monitoring in Thailand in a patient who had intractable left temporal lobe epilepsy. The seizure origin and functioning cortices were identified The corresponding epileptogenic zone was resected without functional deficit. The patient has become seizure free 1 year since surgery. Subdural EEG monitoring with cortical stimulation have been developed at this tertiary epilepsy center The technique provides essential evidence for the surgical decision so that the best post operative outcome can be achieved.

Screening sinus computed tomography (SCCT) of 133 patients performed from March 2003 to February 2004, were retrospectively reviewed, concerning anatomic variation at ostiomeatal unit (OMU) and nasal septal deviation. Six patterns of inflammatory sinus disease were designated: maxillary infundibulum, nasofrontal duct, OMU, sphenoethmoidal recess, polyposis and sporadic. The most common anatomic variation was concha bullosa (14.3%), followed by Haller cell (9.4%), large Agger nasi cell (7.9%) and paradoxical middle turbinate (5.3%). Nasal septal deviation was presented in 75 patients (56.4%). Inflammatory sinus disease was presented in 181 lateral nasal walls (68%) and maxillary infundibular pattern was the most common (33.1%). There was significant correlation between large Agger nasi cell and nasofrontal duct pattern (p < 0.05). The remaining anatomic variations and nasal septal deviation had no significant correlation to the inflammatory sinus disease. Overall, the anatomic variation which can compromise the mucociliary drainage was frequently observed, however, only the large Agger nasi cell had significant correlation to the inflammatory sinus disease.

Leiomyosarcomas of the central nervous system are extremely rare; however they are becoming more prevalent in immunocompromised patients. The authors present MRI (Magnetic Resonance Imaging) of six cases of pathological proved leiomyosarcomas of the central nervous system in patients infected with human immunodeficiency virus. MR images of 4 cases of intraspinal leiomyosarcoma showed lobulated masses expanding multilevel of neural foramina with extradural and intradural extension, giving dumbbell appearance which mimic neurofibroma. Two cases of intracranial leiomyosarcoma revealed a mass at the left cavernous sinus involving prepontine cistern in one case and two lesions in the other case showing masses with dural based appearance at the region of the planum sphenoidale and the posterior aspect of the falx cerebri which mimiced a meningioma. The leiomyosarcoma should be included in the differential diagnosis of extra-axial CNS lesions in HIV-infected patients.

Superficial siderosis of the central nervous system (SSCN) is a very rare disorder. The clinical syndrome of SSNC consists of sensorineural hearing loss, cerebellar ataxia and myelopathy. The clinical syndrome together with the typical appearance on magnetic resonance imaging (MRI) of hyposignal intensity along the leptomeninges in T2 sequence permit the diagnosis of SSCN. A 58 year-old man who has a history of chronic progressive hearing loss and gait instability for 5 years is presented. The neurological examination revealed bilateral sensorineural hearing loss, cerebellar ataxia and mild spasticity of the lower extremities. MRI showed classical superficial siderosis in the form of hyposignal intensity along the leptomeninges in T2 sequence. The prominent sites of hemosiderin deposition in this case were cerebellar vermis, trigeminal nerves, vestibulocochlear nerves, around the brain stem and spinal cord surface. Cerebrospinal fluid findings confirmed chronic subarachnoid hemorrhage but bleeding site could not be demonstrated. There is no specific treatment available for idiopathic SSCN.

Mutations in the fibroblast growth factor receptor genes (FGFR) have been known to be associated with many craniosynostosis syndromes with overlapping phenotypes. We studied a 15-year-old Thai boy with an unspecified craniosynostosis syndrome characterized by multiple suture craniosynostoses, a persistent anterior fontanel, corneal scleralization, choanal stenosis, atresia of the auditory meatus, broad thumbs and great toes, severe scoliosis, acanthosis nigricans, hydrocephalus, and mental retardation. Radiography revealed bony ankyloses of vertebral bodies of T9-12, humero-radio-ulnar joints, intercarpal joints, distal interphalangeal joints of fifth fingers, fibulo-tibial joints, intertarsal joints, and distal interphalangeal joints of the first toes. The patient was a heterozygous for a 870G --> T change resulting in a W290C amino acid substitution in the extracellular domain of the fibroblast growth factor receptor 2 gene (FGFR2). This mutation has previously been reported in a patient with severe Pfeiffer syndrome type 2 that is distinct from the craniosynostosis in our patient. These findings emphasize locus, allelic, and phenotypic heterogeneity of craniofacial-skeletal-dermatological syndrome due to FGFR2 mutations., (Copyright 2002 Wiley-Liss, Inc.)

Spontaneous internal carotid dissection typically occurs in young or middle-aged patients. It is associated with a high rate of recovery and low mortality. Anticoagulant and antiplatelet drugs fail to demonstrate a significant improvement when compared with placebo. A 38 year-old woman with spontaneous dissection of the internal carotid artery diagnosed by MRI is reported. She had an excellent recovery without treatment and no recurrent attack occurred after one year of follow-up. The clinical manifestations, diagnostic tests and treatment of spontaneous internal carotid disection are briefly reviewed in this communication.

A unique concurrent occurrence of spinal epidural osteochondroma and angiolipoma was found in the first thoracic level of a 21-year-old man. The combined lesions produced longstanding motor and sensory disturbances because of compression of the corresponding segment of the spinal cord, and abrupt paraparesis presumably due to spontaneous hemorrhage from the angiomatous component of the angiolipoma. The neurological deficits were satisfactorily improved after surgical removal of the hematoma as well as of both lesions which were regarded as mesenchymal hamartomas.