CNS efficacy parameters of combination antiretroviral therapy in chronic HIV infection: A multi-voxel magnetic resonance spectroscopy study.

This study aimed to determine the correlations of combination antiretroviral therapy (cART) efficacy parameters in the central nervous system (CNS) with a neurometabolic profile on magnetic resonance spectroscopy (MRS) in virally suppressed, neurologically asymptomatic HIV+ individuals. In total, 32 HIV+ individuals on stable cART with an average age of 41.97 ± 10.12 years and with available clinical data, CNS penetration effectiveness (CPE), and monocyte efficacy (ME) scores underwent multi-voxel MRS. The parameters of neuronal number/function (NAA/Cr), membrane turnover (Cho/Cr), and glial proliferation (mI/Cr) were analyzed in supratentorial white and gray matter. Correlations of CPE and ME with neurometabolic ratios were performed using Pearson's correlation test. Statistical significance was set at p < 0.05. A strong positive correlation was observed between Cho/Cr and CPE in the left parietal subcortical white matter (r = 0.577, p = 0.001). A strong positive correlation between NAA/Cr and ME was obtained in the left (r = 0.521, p = 0.003) and the right (r = 0.494, p = 0.005) posterior cingulate. A strong negative correlation between ME and Cho/Cr ratios was observed in the right frontal deep white matter (r = -0.569, p = 0.001). Indices designed to assess cART efficacy in CNS failed to present significant correlations with the neurometabolic profile obtained using MRS. There is a need to define more potent non-invasive tools for neuroinflammation assessment given the prolonged life expectancy in the HIV+ population.

Gradient Patterns of Age-Related Diffusivity Changes in Cerebral White Matter.

The current concept of brain aging proposes three gradient patterns of changes in white matter that occur during healthy brain aging: antero-posterior, supero-inferior, and the myelodegeneration-retrogenesis (or the "last-in-first-out") concept. The aim of this study was to correlate white matter diffusivity measures (fractional anisotropy-FA, mean diffusivity-MD, radial diffusivity-RD, and axial diffusivity-AD) in healthy volunteers with chronological age and education level, in order to potentially incorporate the findings with proposed patterns of physiological brain aging. The study was performed on 75 healthy participants of both sexes, with an average age of 37.32 ± 11.91 years underwent brain magnetic resonance imaging (MRI) with diffusion tensor imaging (DTI). DTI was performed using tract-based spatial statistics (TBSS), with the analysis of four parameters: FA, MD, RD, and AD. Skeletonized measures were averaged in 29 regions of interest in white matter. Correlations between age and DTI measures and between education-level and DTI measures were performed using Pearson's correlation test. To correct for multiple comparisons, we applied a Bonferroni correction to the p-values. Significance was set at p ≤ 0.001. A significant negative correlation of FA with age was observed in posterior thalamic radiation (PTR) (p< 0.001). A significant positive correlation between age and MD was observed in sagittal stratum (SS) (p< 0.001), between age and RD in PTR, SS, and retrolenticular internal capsule (p< 0.001), and between age and AD in the body of the corpus callosum (p< 0.001). There were no significant correlations of DTI parameters with educational level. According to our study, RD showed the richest correlations with age, out of all DTI metrics. FA, MD, and RD showed significant changes in the diffusivity of projection fibers, while AD presented diffusivity changes in the commissural fibers. The observed heterogeneity in diffusivity changes across the brain cannot be explained by a single aging gradient pattern, since it seems that different patterns of degradation are true for different fiber tracts that no currently available theory can globally explain age-related changes in the brain. Additional factors, such as the effect of somatosensory decline, should be included as one of the important covariables to the existing patterns.

[Long COVID: long-term symptoms and morphological/radiological correlates]. / Long-COVID: Langzeitsymptome und morphologische/radiologische Korrelate.

BACKGROUND: Neurologic, pulmonary, cardiac and gastrointestinal functional disorders can persist in the post-acute phase and constitute a long COVID syndrome, also known as post-acute sequelae of SARS-CoV­2 infection (PASC). Some patients develop persistent and debilitating symptoms despite a relatively mild illness at onset and they are known as COVID-19 long haulers. OBJECTIVE: Presentation of symptoms, signs and biomarkers present in patients previously affected by COVID-19 and discussion of possible underlying mechanisms and consequences. METHODS: Existing literature and reported cases as well as expert opinions are analyzed and discussed. RESULTS: Long COVID affects survivors of COVID-19 at all levels of disease severity, even in mild to moderate cases and younger adults who did not require respiratory support, hospitalization or intensive care. A challenging aspect is that many long haulers never had laboratory confirmation of COVID-19, raising skepticism that the persistent symptoms have a physiological basis. On the other hand, some symptoms seen in post-acute COVID-19 may occur as a consequence of critical illness or as a side effect of treatment. CONCLUSION: Given that COVID-19 is a new disease, it is not possible to determine how long these effects will last. Long-term monitoring of post-acute COVID-19 symptoms and screening for frequent comorbid conditions are essential.

Distinct pattern of microsusceptibility changes on brain magnetic resonance imaging (MRI) in critically ill patients on mechanical ventilation/oxygenation.

PURPOSE: Over the years, interesting SWI abnormalities in patients from intensive care units (ICU) were observed, not attributable to a specific cause and with uncertain clinical significance. Recently, multiple SWI-hypointense foci were mentioned related to neurological complications of SARS-COV-2 infection. The purpose of the study was to describe the patterns of susceptibility brain changes in critically-ill patients who underwent mechanical ventilation and/or extracorporeal membrane oxygenation (ECMO). METHODS: An institutional board-approved, retrospective study was conducted on 250 ICU patients in whom brain MRI was performed between January 2011 and May 2020. Out of 48 patients who underwent mechanical ventilation/ECMO, in fifteen patients (median age 47.7 years), the presence of SWI abnormalities was observed and described. RESULTS: Microsusceptibilities were located in white-gray matter interface, in subcortical white matter (U-fibers), and surrounding subcortical nuclei in 13/14 (92,8%) patients. In 8/14 (57,1%) patients, SWI foci were seen infratentorially. The corpus callosum was affected in ten (71,4%), internal capsule in five (35,7%), and midbrain/pons in six (42,8%) patients. CONCLUSION: We showed distinct patterns of diffuse brain SWI susceptibilities in critically-ill patients who underwent mechanical ventilation/ECMO. The etiology of these foci remains uncertain, but the association with mechanical ventilation, prolonged respiratory failure, and hypoxemia seems probable explanations.

Susceptibility-weighted Imaging: Technical Essentials and Clinical Neurologic Applications.

Susceptibility-weighted imaging (SWI) evolved from simple two-dimensional T2*-weighted sequences to three-dimensional sequences with improved spatial resolution and enhanced susceptibility contrast. SWI is an MRI sequence sensitive to compounds that distort the local magnetic field (eg, calcium and iron), in which the phase information can differentiate. But the term SWI is colloquially used to denote high-spatial-resolution susceptibility-enhanced sequences across different MRI vendors and sequences even when phase information is not used. The imaging appearance of SWI and related sequences strongly depends on the acquisition technique. Initially, SWI and related sequences were mostly used to improve the depiction of findings already known from standard two-dimensional T2*-weighted neuroimaging: more microbleeds in patients who are aging or with dementia or mild brain trauma; increased conspicuity of superficial siderosis in Alzheimer disease and amyloid angiopathy; and iron deposition in neurodegenerative diseases or abnormal vascular structures, such as capillary telangiectasia. But SWI also helps to identify findings not visible on standard T2*-weighted images: the nigrosome 1 in Parkinson disease and dementia with Lewy bodies, the central vein and peripheral rim signs in multiple sclerosis, the peripheral rim sign in abscesses, arterial signal loss related to thrombus, asymmetrically prominent cortical veins in stroke, and intratumoral susceptibility signals in brain neoplasms.

Neurometabolic Remodeling in Chronic Hiv Infection: a Five-Year Follow-up Multi-Voxel Mrs Study.

There is a lack of data about the long-term follow-up changes in neurometabolic profile and neuropsychological performance of HIV-positive subjects under continuous antiretroviral therapy (cART). The aim of the study was to assess changes in neurometabolic profile in chronically-infected, HIV-positive subjects during a five-year follow-up period, using multi-voxel proton magnetic resonance spectroscopy (1H-MRS). Nineteen neurologically asymptomatic, aviremic, HIV-positive subjects, underwent multi-voxel 2D MRS on a 3 T MR unit and synchronous neurocognitive assessment in a five-year follow-up period. Twelve voxels were placed in prefrontal cortices, anterior and posterior cingulate gyrus, intraparietal sulci, and frontal centrum semiovale white matter, to identify peaks of N-acetyl-aspartate (NAA), creatine (Cr), choline (Cho), and myoinositol (mI). Ratios of NAA/Cr, NAA/Cho, NAA/mI, mI/Cr, and Cho/Cr were analyzed. Longitudinal differences in ratios and neurocognitive scores were tested with the Wilcoxon signed-rank-test. Statistical significance was set at p ≤ 0.004 significant, and 0.05 > p > 0.004 trending toward significance. A significant longitudinal increase in NAA/Cr ratio was observed in 5/12 voxels, while there was a trend toward significance in an additional three. The increase in Cho/Cr reached statistical significance in one voxel. Changes in the mI/Cr ratio demonstrated a significant increase in 4/12 voxels. A progressive increase in NAA/Cr, followed by better neurocognitive performance, may be an indicator of brain plasticity in the setting of chronic HIV-related neuronal injury. A progressive mI/Cr increase could be partly explained by glial proliferation due to functional compartment remodeling and partly attributable to insufficient control of persistent neuroinflammation by cART.

Early Introduction of cART Reverses Brain Aging Pattern in Well-Controlled HIV Infection: A Comparative MR Spectroscopy Study.

Introduction: The aim of this study was to compare age-related changes in chronically infected, asymptomatic HIV-positive patients under combination antiretroviral therapy (cART), with age-, gender-, and educational-level-matched healthy subjects, using multi-voxel magnetic-resonance spectroscopy (MRS). Methods: There were 66 chronically infected HIV-positive subjects and 65 age-, gender-, and educational-level-matched control subjects, divided into four groups according to the age: group 1 (20-29 years old), group 2 (30-39), group 3 (40-49) and group 4 (50-59). MRS was performed and ratios of N-acetyl-aspartate (NAA)/creatine (Cr) were analyzed in ten locations of the supracallosal gray matter. For the comparison of NAA/Cr ratios in healthy and HIV-positive subjects, ANCOVA with age and education as covariates was performed. Correlations of NAA/Cr ratios with duration of cART were performed using Pearson's correlation test. Statistical significance was set at p < 0.05. Results: The NAA/Cr ratios were decreased in the 20-29-year-old HIV-positive subjects in 8/10 locations (p < 0.005) compared to the healthy controls, while in the 50-59-year-old groups they were significiantly lower only in one location (p = 0.004). There were significant positive correlations of NAA/Cr levels with the duration of cART in the oldest group of HIV-positive subjects, while in the youngest group there were no significant correlations. Conclusion: The aging pattern in chronic HIV infection under cART is accentuated rather than accelerated. There is an initial HIV-related neuronal damage with a significant decline in NAA/Cr ratios; after the initiation of cART, however, NAA/Cr ratios increase continuously to become similar to healthy aging individuals, probably due to beneficial effect of long-standing cART. Summary: Brain aging in chronic HIV infection under cART is accentuated, with an initial HIV-related neuronal damage followed by a subtle NAA/Cr increase after the initiation of cART. Under cART, in advanced age, NAA/Cr ratios become similar to healthy aging individuals.

Apparent diffusion coefficient reproducibility in brain tumors measured on 1.5 and 3 T clinical scanners: A pilot study.

BACKGROUND: Gradient and coil systems, pulse sequence design, and imaging parameters, as well as different scanners, can influence apparent diffusion coefficient (ADC) values. The aim of this study was to evaluate the effect of two different field strengths on the reproducibility of mean absolute ADC measurements in various primary and secondary brain tumors. METHODS: Fifty patients with histologically proven brain tumors were prospectively examined on two MR scanners from the same vendor, with different field strengths-1.5T and 3T-on the same day. Absolute ADC values were compared using the Wilcoxon matched-pairs signed-rank test. Inter-scanner agreement between two different fields in the same tumor was examined using correlation coefficients, and the discrepancy between the highest and the lowest mean absolute ADC values between scanners was tested using a one-way analysis of variance. Statistical significance was set at p < 0.05. RESULTS: There was no statistically significant difference between mean absolute ADC values obtained on 1.5T and 3T scanners for all patients and all brain tumor types. The intratumoral difference in ADC values, averaged from two scanners in the same tumor type, ranged from 1.58 to 4.5% for 1.5T, and from 1.18 to 4.37% for 3T.Inter-scanner agreement was high, and the kappa coefficient ranged from 0.88 to 0.99, with no significant difference between obtained values on different field strengths. CONCLUSION: Based on the results obtained in our study, there is no significant difference between mean absolute ADC values measured in various primary and secondary brain tumors at different field strengths (1.5 and 3.0T MR systems), in the same patient, and in the same tumor, measured on the same day.

Leptomeningeal form of Immunoglobulin G4-related hypertrophic meningitis with perivascular spread: a case report and review of the literature.

PURPOSE: Immunoglobulin G4 (IgG4)-related disease represents a spectrum of fibro-inflammatory disorders that affects various organ systems, including the central nervous system. METHODS: Here we present the case of lgG4-related hypertrophic meningitis with exclusively leptomeningeal involvement and spread via perivascular spaces. RESULTS: A 58-year-old male patient presented with complex partial seizures. Initial computed tomography examination showed left frontal sulcal hyperdensity. Subsequent magnetic resonance examination revealed FLAIR hyperintensity in the central sulcus, with post-contrast enhancement in the form of "dotted line." Physical examination, routine laboratory, and cerebrospinal fluid analyses were unremarkable. Meningeal biopsy confirmed IgG4-related meningitis. After corticosteroid treatment, a complete resolution of imaging findings was observed. Two months later, the patient presented with relapsing neurological symptoms and radiological findings in postcentral, precentral, and temporal sulci, resembling the form of "dotted line" contrast enhancement. In addition, linear intraparenchymal enhancement that followed perivascular spaces was seen in the left parietal lobe. After repeated steroid therapy, all lesions resolved completely. CONCLUSION: We reported the first case of isolated IgG4-related leptomeningeal involvement with a "dotted line" enhancement and perivascular intraparenchymal spread. Although IgG4-related meningitis represents a rare disease, both clinicians and radiologists should include this condition in the differential diagnosis of unclear leptomeningeal disease.

Infections of the spine and spinal cord.

Predisposing factors for developing spinal infections include: immunodeficiency; drug abuse; the widespread use of broad-spectrum antibiotics, corticosteroids, and immunosuppressive drugs; diabetes mellitus; and spinal surgery. Infections can be bacterial, fungal, parasitic, or viral in origin. This chapter reviews current knowledge in clinical and imaging findings in the most common spinal infections divided according to the compartment primarily involved.

Neuroimaging of Spinal Tumors.

Intradural tumors are relatively rare neoplasms; however, when unrecognized in a timely manner, they can result in serious deficits and disability. These tumors lack obvious clinical symptoms until compression of the cord or neurologic deficits occur. The most common intramedullary lesions are ependymomas, astrocytomas, and hemangioblastomas. Meningiomas and nerve sheath tumors (schwannomas and neurofibromas) comprise most intradural-extramedullary tumors. Less common tumors are hemangiopericytoma, paraganglioma, melanocytoma, melanoma, metastases, and lymphoma. MR imaging is the imaging method of choice, helpful for localization and characterization of these lesions before treatment and for follow-up after treatment.

Differentiation of pyogenic and fungal brain abscesses with susceptibility-weighted MR sequences.

INTRODUCTION: Conventional magnetic resonance imaging (MRI) techniques are insufficient to determine the causative agent of brain abscesses. We investigated: (1) the value of susceptibility-weighted MR sequences (SWMRS) in the differentiation of fungal and pyogenic brain abscesses; and (2) the effect of different SWMRS (susceptibility-weighted imaging (SWI) versus venous blood oxygen level dependent (VenoBOLD)) for the detection of specific imaging characteristics of pyogenic brain abscesses. METHODS: We studied six patients with fungal and ten patients with pyogenic brain abscesses. Imaging characteristics on conventional MRI, diffusion-weighted imaging (DWI) and SWMRS were recorded in all abscesses. All lesions were assessed for the presence of a "dual-rim sign" on SWMRS. RESULTS: Homogenously hyperintense lesions on DWI were present in 60 % of patients with pyogenic abscesses, whereas none of the patients with fungal abscesses showed such lesions. On SWMRS, 90 % of patients with pyogenic abscesses and 60 % of patients with fungal abscesses had only lesions with a low-signal-intensity rim. On SWI, the dual-rim sign was apparent in all pyogenic abscesses. None of the fungal abscesses on SWI (P = 0.005) or any of the pyogenic abscesses on VenoBOLD (P = 0.005) were positive for a dual-rim sign. CONCLUSIONS: In fungal abscesses, the dual-rim sign is not present but a prominent peripheral rim or central susceptibility effects on SWI will be seen. The appearance of pyogenic abscesses on SWMRS depends on the used sequence, with the dual-rim sign a specific feature of pyogenic brain abscesses on SWI.

Atypical idiopathic inflammatory demyelinating lesions (IIDL): conventional and diffusion-weighted MR imaging (DWI) findings in 42 cases.

INTRODUCTION: The purpose of this study was to evaluate MR imaging characteristics with conventional and advanced MR imaging techniques in patients with IIDL. METHODS: MR images of the brain in 42 patients (20 male, 22 female) with suspected or known multiple sclerosis (MS) from four institutions were retrospectively analyzed. Lesions were classified into five different subtypes: (1) ring-like lesions; (2) Balo-like lesions; (3) diffuse infiltrating lesions; (4) megacystic lesions; and (5) unclassified lesions. The location, size, margins, and signal intensities on T1WI, T2WI, and diffusion-weighted images (DWI), and the ADC values/ratios for all lesions, as well as the contrast enhancement pattern, and the presence of edema, were recorded. RESULTS: There were 30 ring-like, 10 Balo-like, 3 megacystic-like and 16 diffuse infiltrating-like lesions were detected. Three lesions were categorized as unclassified lesions. Of the 30 ring-like lesions, 23 were hypointense centrally with a hyperintense rim. The mean ADC, measured centrally, was 1.50 ± 0.41 × 10(-3) mm(2)/s. The mean ADC in the non-enhancing layers of the Balo-like lesions was 2.29 ± 0.17 × 10(-3) mm(2)/s, and the mean ADC in enhancing layers was 1.03 ± 0.30 × 10(-3) mm(2)/s. Megacystic lesions had a mean ADC of 2.14 ± 0.26 × 10(-3)mm(2)/s. Peripheral strong enhancement with high signal on DWI was present in all diffuse infiltrating lesions. Unclassified lesions showed a mean ADC of 1.43 ± 0.13 mm(2)/s. CONCLUSION: Restriction of diffusion will be seen in the outer layers of active inflammation/demyelination in Balo-like lesions, in the enhancing part of ring-like lesions, and at the periphery of infiltrative-type lesions.

Imaging findings in seven cases of congenital infantile myofibromatosis with cerebral, spinal, or head and neck involvement.

INTRODUCTION: Congenital infantile myofibromatosis (IM) is a rare mesenchymal disease, presenting with tumors in the skin, muscle, viscera, bone, and subcutaneous tissue. It can present as (a) a solitary form with subcutaneous, erythematous nodules, (b) a multicentric form with subcutaneous, muscle, and/or bony lesions, and (c) a multicentric form with visceral involvement. Cerebral or spinal involvement in myofibromatosis has been reported rarely. METHODS: We report seven cases of histology-proven infantile myofibromatosis with brain, spine, and/or head and neck involvement. RESULTS: In three patients with multiple subcutaneous nodules, a multicentric form of IM with visceral involvement was diagnosed. In three patients, a multicentric form without visceral involvement was found. Two patients had brain involvement, and four patients had vertebral body involvement. CONCLUSION: In a newborn presenting with intraparenchymal brain lesions, epidural spinal masses, and/or vertebra plana or lytic lesions of the calvarium and spine, infantile myofibromatosis should be considered as a possible differential diagnosis. The presence of subcutaneous or muscular nodules facilitates the diagnosis.