Reversible large-scale network disruption correlates with neurocognitive improvement in HIV-associated minor neurocognitive disorder with combined anti-retroviral therapy intensification: a prospective longitudinal resting-state functional magnetic resonance imaging study.

OBJECTIVE: HIV-associated neurocognitive disorder (HAND) affects multiple cognitive domains and currently, the neuropsychological testing is the gold standard to identify these deficits. The aim of this longitudinal 12-month pilot study is to determine the effect of intensified combination antiretroviral therapy (cART) on rs-fMRI in virally suppressed (both in CSF and blood) patients with active HAND (those who have progressive neurocognitive impairment) and correlated with neurocognitive function tests. METHODS: In this pilot study, we have evaluated sixteen patients with active HAND with viral suppression in both blood and CSF to study the effect of cART on functional connectivity. Participants underwent rs-fMRI at the baseline (time point-1 (TP-1) and 12-month visits (time point-2 (TP-2)). Connectivity in the five major networks was measured at TP-1 and TP-2 using the seed-based approach. All the participants underwent a five-domain neuropsychological battery at TP-1 and TP-2. Neurocognitive scores (NC) as well as blood and CSF markers were correlated with functional connectivity (FC). RESULTS: There was a significant increase in the FC between the two time points within the executive, salience, default mode, dorsal attention, and visual networks at voxel level threshold of p < 0.001 and cluster level threshold of p < 0.05 and corrected for false detection rate (FDR). The neurocognitive scores were positively correlated with all the networks at similar cluster and voxel level thresholds. CONCLUSIONS: These results indicate that rs-fMRI can be potentially used as one of the biomarkers for treatment efficacy in HAND.

Multiparametric imaging in the evaluation of intracerebral abscesses.

Cerebral abscesses are uncommon space occupying lesions; they are associated with high morbidity and mortality, though are potentially treatable. Patients often present with non-specific symptoms and may have few clinical signs. Routine clinical imaging may not give a definite diagnosis, as the findings can be indistinguishable from those of other intracranial mass lesions. We review the role of advanced MR techniques to characterise brain abscesses and discuss the role of imaging in monitoring their response to the treatment.

Atypical presentations and course of JC virus infection.

There is increasing evidence that the spectrum of human polyomavirus 2 (JCV) CNS disease includes novel syndromes other than progressive multifocal leukoencephalopathy (PML), the appreciation of which is increasingly important in the context of MS therapies and immunodeficiency states. Our objective is to describe unusual presentations of JCV infection to heighten clinician awareness. We describe three case reports of various PML presentations. Firstly a 56-year-old HIV positive male with decades of viral suppression and normal immune function presented with 1 month of non-specific headache that spontaneously resolved despite an MRI showing a new area of PML and CSF being JC DNA + . He had had two similar episodes in 2013 and 2014 with MRI scans consistent with PML, CSF, JCV, and PCR positivity once and brain biopsy-positive twice. Another 61-year-old male presented with subacute binocular vision loss and was found to have newly diagnosed HIV and JCV DNA detected in CSF. MRI brain only demonstrated symmetrical chiasmo-hypothalamic enhancement. There has been some improvement with combination antiretroviral therapy and corticosteroids for immune reconstitution inflammatory syndrome (IRIS). Thirdly, a 65-year-old male presented with subacute progressive confusion and behavioural disturbance, one year post-bilateral lung transplantation. MRI brain demonstrated no evidence of PML but CSF on three occasions demonstrated a progressively increasing JCV DNA load. Despite reduction in his immunosuppression, the patient developed profound encephalopathy without localising features leading to death two months later. These cases emphasise the atypical presentations of JCV: chronic relapsing, unusual symmetrical visual pathway disease, and non-localising encephalopathy without MRI evidence of PML.

MR spectroscopy in HIV associated neurocognitive disorder in the era of cART: a review.

Neuroimaging has been a critical tool for understanding the neuropathological underpinnings observed in HIV. The pathophysiology of HAND is chiefly driven by neuroinflammation. Despite adhering to cART, low levels of viraemia probably persist in the brain in some patients leading to chronic immune activation with resultant neuroinflammation and consequent neuronal injury. MR spectroscopy has been widely used as a biomarker for the presence and severity of HAND in several studies. By studying the MRS signatures, it is possible to characterise the presence of neuroinflammation and neural injury. Furthermore, metabolite concentrations measured by MRS could be used as a quantitative indicator of HIV cerebral involvement, thereby affording the opportunity to assess the efficacy of cART in HAND. However, currently there are three significant limitations in the MRS HIV research literature: the relative paucity of prospective studies, the small number of regions of interrogation due to current methodology (single voxel MRS), and the evolving understanding of the impact of co-morbidities (e.g. ageing, mood disorders, alcoholism etc.) on MRS measurements. This review critically addresses the current literature of MRS studies in people living with HIV (PWH) with HAND to determine its value, especially in the context of the current cART era. In addition, we discuss technical considerations related to the disease and the future direction in HAND using MRS.

Black blood imaging of intracranial vessel walls.

Traditional vascular imaging focuses on non-invasive cross-sectional imaging to assess luminal morphology; however, the vessel wall itself may be specifically involved in many diseases. Newer pulse sequences, and particularly black blood MRI of intracranial vessels, have brought a paradigm shift in understanding the pathophysiology of many vasculopathies. Black blood MRI of intracranial vessel walls can help in a range of pathologies with differing pathophysiology, including intracranial atherosclerosis, aneurysms, vasculitis and vasculopathy, moyamoya disease, dissection and vertebrobasilar hypoplasia. This review highlights how vessel wall imaging can contribute to the clinical diagnosis and management of patients with intracranial vascular pathology.

Recurrence of progressive multifocal leukoencephalopathy despite immune recovery in two HIV seropositive individuals.

We present two cases of recurrent progressive multifocal leukoencephalopathy (PML) in patients with long standing virally suppressed human immunodeficiency virus (HIV) and normal CD4+ T cell count who were taking stable regimens of highly active antiretroviral therapy (HAART). This has significant implications for other patients with a past history of PML, not just those with HIV but also those on medications such as natalizumab or fumarates.

Compressive Optic Neuropathy from Allergic Fungal Sinusitis.

Ophthalmic manifestations of allergic fungal sinusitis (AFS) are rare, but can occur in advanced disease. A 32-year-old man with advanced AFS presented with severe bilateral vision loss and restricted ocular motility. Magnetic resonance imaging and histological analysis confirmed active chronic AFS. Functional endoscopic sinus surgery was performed, with adjunctive steroid therapy. Although AFS is a reasonably well-recognised entity, severe disease causing bilateral visual deficits is rarely encountered. This can confound the diagnosis and appropriate treatment. Ophthalmologists should thus be aware of compressive optic neuropathy as a complication of advanced AFS to prompt early treatment and mitigate visual loss.

Antisocial behaviour and lying: a neuropsychiatric presentation of agenesis of the corpus callosum.

OBJECTIVE: The purpose of this case study is to describe the case of a person with agenesis of the corpus callosum (ACC), intellectual disability and features of antisocial behaviour and lying. METHODS: A 26-year-old woman with a mild intellectual disability who presented with antisocial behaviour and chronic lying was found to have ACC and associated cerebral abnormalities. RESULTS: Psychiatric, radiological and neuropsychological assessment of this patient provided convergent evidence of the importance of the corpus callosum in enabling understanding of social situations and appropriate social behaviour, particularly via its connectivity with the frontal regions of the brain. CONCLUSION: Antisocial behaviour and lying may be more commonly associated with callosal dysgenesis than is currently realised.

Infectious leukoencephalopathies.

Leukoencephalopathy from infectious agents may have a rapid course, such as human simplex virus encephalitis; however, in many diseases, it may take months or years before diagnosis, such as in subacute sclerosing panencephalitis or Whipple disease. There are wide geographic distributions and susceptible populations, including both immunocompetent and immunodeficient patients. Many infections have high mortality rates, such as John Cunningham virus and subacute sclerosing panencephalitis, although others have effective treatments if suspected and treated early, such as herpes simplex encephalitis. This chapter will describe viral, bacterial, and protozoal infections, which predominantly cause leukoencephalopathy. We focus on the clinical presentation of these infectious agents briefly covering epidemiology and subtypes of infections. Next, we detail current pathophysiologic mechanisms causing white matter injury. Diagnostic and confirmatory tests are discussed. We cover predominantly MRI imaging features of leukoencephalopathies, and in addition, summarize the common imaging features. Additionally, we detail how imaging features may be used to narrow the differential of a leukoencephalopathy clinical presentation. Lastly, we present an outline of common treatment approaches where available.

Blood brain barrier disruption and glutamatergic excitotoxicity in post-acute sequelae of SARS COV-2 infection cognitive impairment: potential biomarkers and a window into pathogenesis.

Objective: To investigate the association between blood-brain barrier permeability, brain metabolites, microstructural integrity of the white matter, and cognitive impairment (CI) in post-acute sequelae of SARS-COV-2 infection (PASC). Methods: In this multimodal longitudinal MRI study 14 PASC participants with CI and 10 healthy controls were enrolled. All completed investigations at 3 months following acute infection (3 months ± 2 weeks SD), and 10 PASC participants completed at 12 months ± 2.22 SD weeks. The assessments included a standard neurological assessment, a cognitive screen using the brief CogState battery and multi-modal MRI derived metrics from Dynamic contrast enhanced (DCE) perfusion Imaging, Diffusion Tensor Imaging (DTI), and single voxel proton Magnetic Resonance Spectroscopy. These measures were compared between patients and controls and correlated with cognitive scores. Results: At baseline, and relative to controls, PASC participants had higher K-Trans and Myo-inositol, and lower levels of Glutamate/Glutamine in the frontal white matter (FWM) (p < 0.01) as well as in brain stem (p < 0.05), and higher FA and lower MD in the FWM (p < 0.05). In PASC participants, FA and MD decreased in the FWM at 12 months compared to baseline (p < 0.05). K-Trans and metabolite concentrations did not change significantly over time. Neurocognitive scores did not correlation with the increased permeability (K trans). Interpretation: PASC with CI is associated with BBB impairment, loss of WM integrity, and inflammation at 3 months which significantly but not uniformly improved at 12 months. The loss of WM integrity is possibly mediated by BBB impairment and associated glutamatergic excitotoxicity.

Magnetization Transfer Contrast - Is it Sensitive Enough to Differentiate Demyelination from Axonal Loss?

Background and Objective: Magnetization transfer contrast imaging (MTC) exploits the principle of exchange of energy between the bound and free protons and was shown to be pathologically informative. There is, however, controversy as to whether it correlates with axonal loss (AL), demyelination (DM), or both. This study addresses the pathophysiological process that underlies the white matter injury using the metric derivative of MTC, magnetization transfer ratio (MTR), and defines the role of MTR in identifying the different stages of inflammation, that is, edema, DM, and AL, using optic nerve as the model. Materials and Methods: One hundred and forty-two patients with a single, unilateral episode of optic neuritis (ON) were included in the study. Patients were divided into three groups - those with AL, those with DM, and those who were clinically optic neurites but without any electrophysiological changes suggestive of either AL or DM. MTR and electrophysiological studies were performed in the post-acute stage of ON and the results were compared to those obtained from the unaffected optic nerve. Results: MTR was significantly reduced in the optic nerves of both DM and AL groups when compared to that in normal optic nerves (P < 0.001). The difference in MTR between the AL and DM groups did not reach statistical significance. Patient group with acute ON did not show any change in the MTR values compared to the normal controls. Conclusions: MTR is a sensitive technique to identify neuronal injury, whether it is DM or AL. It, however, cannot differentiate these two pathological processes. MTR is not sensitive to identify acute ON.

Novel magnetic resonance KTRANS measurement of blood-brain barrier permeability correlated with covert HE.

BACKGROUND: Using dynamic contrast-enhanced (DCE) MR perfusion and MR spectroscopy this study aimed to characterize the blood-brain barrier permeability and metabolite changes in patients with cirrhosis and without covert HE. METHODS: Covert HE was defined using psychometric HE score (PHES). The participants were stratified into 3 groups: cirrhosis with covert HE (CHE) (PHES<-4); cirrhosis without HE (NHE) (PHES≥-4); and healthy controls (HC). Dynamic contrast-enhanced MRI and MRS were performed to assess KTRANS, a metric derivative of blood-brain barrier disruption, and metabolite parameters. Statistical analysis was performed using IBM SPSS (v25). RESULTS: A total of 40 participants (mean age 63 y; male 71%) were recruited as follows: CHE (n=17); NHE (n=13); and HC (n=10). The KTRANS measurement in the frontoparietal cortex demonstrated increased blood-brain barrier permeability, where KTRANS was 0.01±0.02 versus 0.005±0.005 versus 0.004±0.002 in CHE, NHE, and HC patients, respectively (p = 0.032 comparing all 3 groups). Relative to HC with a value of 0.28, the parietal glutamine/creatine (Gln/Cr) ratio was significantly higher in both CHE 1.12 mmoL (p < 0.001); and NHE 0.49 (p = 0.04). Lower PHES scores correlated with higher glutamine/Cr (Gln/Cr) (r=-0.6; p < 0.001) and lower myo-inositol/Cr (mI/Cr) (r=0.6; p < 0.001) and lower choline/Cr (Cho/Cr) (r=0.47; p = 0.004). CONCLUSION: The dynamic contrast-enhanced MRI KTRANS measurement revealed increased blood-brain barrier permeability in the frontoparietal cortex. The MRS identified a specific metabolite signature with increased glutamine, reduced myo-inositol, and choline, which correlated with CHE in this region. The MRS changes were identifiable in the NHE cohort.

Differentiation of Primary Central Nervous System Lymphoma and High-Grade Glioma with Dynamic Susceptibility Contrast-Derived Metrics: Pilot Study.

OBJECTIVE: Preoperative differentiation of lymphoma from other aggressive intracranial neoplasms is important as the surgical and adjuvant therapy may be fundamentally different between the 2 types of tumors. The purpose of this study was to assess the ability of the dynamic susceptibility contrast-derived metrics, percentage signal recovery (PSR) ratio, and relative cerebral blood volume (rCBV) to distinguish between primary central nervous system lymphoma (PCNSL) and high-grade glioma (HGG). METHODS: Twenty-six patients (15 with HGG and 11 with PCNSL) with histologically confirmed diagnoses were retrospectively analyzed. Mean PSR and rCBV were calculated from dynamic susceptibility contrast imaging. The 2 groups were compared using an independent samples t-test. Receiver operating characteristic analyses were performed to determine the area under the curve and identify threshold values to differentiate PCNSL from GBM. RESULTS: Both rCBV and PSR values were significantly different, at both the group level and subject level, between the PCNSL and HGG patients. The mean rCBV was significantly lower in PCNSL (1.38 ± 0.64) compared with HGG (5.19 ± 2.21, df = 11.24, P < 0.001). The mean PSR ratio was significantly higher in PCNSL (1.04 ± 0.11) compared with HGG (0.72 ± 0.16, df = 17.23, P < 0.001). An rCBV threshold value of 2.67 provided a 100% sensitivity and 100% specificity (area under the curve 1.0) for differentiating PCNSL from HGG. A PSR ratio threshold value of 0.9 was 100% sensitive and 90.91% specific for differentiating PCNSL from HGG. CONCLUSIONS: The findings of our study show that rCBV and PSR ratio are different in HGG and PCNSL at both the group level and subject level. Incorporation of perfusion in routine magnetic resonance imaging of contrast-enhancing lesions can have a significant impact on patient management.

An observational study to determine volume changes in the functional liver remnant following portal vein embolization.

BACKGROUND AND AIM: Portal vein embolization (PVE) prior to hepatic resection reduces the risk of hepatic insufficiency in the postoperative period by redistributing blood from the embolized unhealthy liver to the healthy liver, termed the functional liver remnant (FLR). A retrospective analysis of liver volumes after embolization in a single institution was performed to identify change in volume of the FLR and determine factors affecting this change. METHODS: Between 2013 and 2015, 21 patients undergoing PVE followed by hepatic resection for varied indications (colorectal metastases, hepatocellular carcinoma, cholangiocarcinoma, etc.) were included in this study. n-butyl cyanoacrylate glue diluted with Lipiodol (35-45% strength) along with 75-100 µm of polyvinyl alcohol particles were used for embolization. Liver volumetric determination was performed before and after PVE and volume changes in the FLR were analyzed. Biochemical factors and factors affecting FLR hypertrophy were also analyzed. RESULTS: Majority of the patients (n = 18) underwent right-lobe embolization. All were performed using the ipsilateral approach. No major complications occurred with only one patient developing post-procedural ascites requiring percutaneous draining. A significant increase in the mean volume of the FLR by 63.7% ± 91.6%, P = 0.001 was noted after PVE. The FLR/total liver volume (TLV) increased significantly by 17% ± 18%. No significant demographic factors affected FLR hypertrophy and no significant biochemical changes were noted. Thirteen patients were successfully operated on after embolization. CONCLUSIONS: PVE is effective in inducing significant hypertrophy of the future FLR, prior to hepatic resection in our institution.

Association of Immunosuppression and Viral Load With Subcortical Brain Volume in an International Sample of People Living With HIV.

Importance: Despite more widely accessible combination antiretroviral therapy (cART), HIV-1 infection remains a global public health challenge. Even in treated patients with chronic HIV infection, neurocognitive impairment often persists, affecting quality of life. Identifying the neuroanatomical pathways associated with infection in vivo may delineate the neuropathologic processes underlying these deficits. However, published neuroimaging findings from relatively small, heterogeneous cohorts are inconsistent, limiting the generalizability of the conclusions drawn to date. Objective: To examine structural brain associations with the most commonly collected clinical assessments of HIV burden (CD4+ T-cell count and viral load), which are generalizable across demographically and clinically diverse HIV-infected individuals worldwide. Design, Setting, and Participants: This cross-sectional study established the HIV Working Group within the Enhancing Neuro Imaging Genetics Through Meta Analysis (ENIGMA) consortium to pool and harmonize data from existing HIV neuroimaging studies. In total, data from 1295 HIV-positive adults were contributed from 13 studies across Africa, Asia, Australia, Europe, and North America. Regional and whole brain segmentations were extracted from data sets as contributing studies joined the consortium on a rolling basis from November 1, 2014, to December 31, 2019. Main Outcomes and Measures: Volume estimates for 8 subcortical brain regions were extracted from T1-weighted magnetic resonance images to identify associations with blood plasma markers of current immunosuppression (CD4+ T-cell counts) or detectable plasma viral load (dVL) in HIV-positive participants. Post hoc sensitivity analyses stratified data by cART status. Results: After quality assurance, data from 1203 HIV-positive individuals (mean [SD] age, 45.7 [11.5] years; 880 [73.2%] male; 897 [74.6%] taking cART) remained. Lower current CD4+ cell counts were associated with smaller hippocampal (mean [SE] ß = 16.66 [4.72] mm3 per 100 cells/mm3; P < .001) and thalamic (mean [SE] ß = 32.24 [8.96] mm3 per 100 cells/mm3; P < .001) volumes and larger ventricles (mean [SE] ß = -391.50 [122.58] mm3 per 100 cells/mm3; P = .001); in participants not taking cART, however, lower current CD4+ cell counts were associated with smaller putamen volumes (mean [SE] ß = 57.34 [18.78] mm3 per 100 cells/mm3; P = .003). A dVL was associated with smaller hippocampal volumes (d = -0.17; P = .005); in participants taking cART, dVL was also associated with smaller amygdala volumes (d = -0.23; P = .004). Conclusions and Relevance: In a large-scale international population of HIV-positive individuals, volumes of structures in the limbic system were consistently associated with current plasma markers. Our findings extend beyond the classically implicated regions of the basal ganglia and may represent a generalizable brain signature of HIV infection in the cART era.

The Case of the Disappearing Colloid Cyst.

BACKGROUND: The natural history of colloid cysts is imperfectly understood, and controversies remain in defining broad management strategies for incidental colloid cysts. The gradual asymptomatic regression of a colloid cyst has not been reported. CASE DESCRIPTION: We present a unique case demonstrating the clinically silent, gradual regression of a colloid cyst over many years. CONCLUSIONS: Gradual regression of a colloid cyst is possible. The philosophical and practical implications of this case on the neurosurgeon's approach to managing patients with colloid cysts are discussed.

Meta-analysis of magnetic resonance spectroscopy in the diagnosis of hepatic encephalopathy.

OBJECTIVE: Various imaging modalities have been used to explore pathogenic mechanisms and stratify the severity of hepatic encephalopathy (HE). The hypothesis of this meta-analysis was that there is a progressive identifiable derangement of imaging measures using magnetic resonance spectroscopy (MRS) related to the severity of the HE. METHODS: Studies with more than 10 cases and HE diagnosis were identified from the electronic databases PubMed, EMBASE, Cumulative Index to Nursing and Allied Health Literature (CINAHL), Literatura Latino Americana em Ciências da Saúde (LILACS), and Cochrane Central Register of Controlled Trials (CENTRAL) through July 25, 2018. Participants were stratified into healthy controls and patients with non-HE (NHE) (cirrhosis without HE), minimal HE (MHE), and overt HE (OHE). Analyses were organized by metabolite studied and brain region examined. Statistical meta-analysis was performed using the metafor package in R (v3.4.1). Pooled standardized mean differences between patient groups were calculated using a random effects model. RESULTS: We identified 31 studies (1,481 patients) that included data for cirrhosis-related HE. We found the parietal region to be the most reliable in differentiating between patients with and without MHE, with standard mean differences of +0.82 (95% confidence interval [CI] +0.49 to +1.15, p < 0.0001, I 2 = 37.45%) for glutamine/glutamate, -0.36 (95% CI -0.61 to -0.10, p = 0.007, I 2 = 20.00%) for choline, and-0.77 (95% CI -1.19 to -0.34, p = 0.0004, I 2 = 67.48%) for myo-inositol. We also found that glutamine/glutamate was the metabolite that reliably correlated with HE grade in all brain regions. CONCLUSIONS: The meta-analysis reveals that MRS changes in glutamine/glutamate, choline, and myo-inositol, particularly in the parietal lobe, correlate with the severity of HE. MRS may be of value in the assessment of HE.