Peak Resembling N-acetylaspartate (NAA) on Magnetic Resonance Spectroscopy of Brain Metastases.

Background and Objectives: Differentiating between a high-grade glioma (HGG) and solitary cerebral metastasis presents a challenge when using standard magnetic resonance imaging (MRI) alone. Magnetic resonance spectroscopy (MRS), an advanced MRI technique, may assist in resolving this diagnostic dilemma. N-acetylaspartate (NAA), an amino acid found uniquely in the central nervous system and in high concentrations in neurons, typically suggests HGG over metastatic lesions in spectra from ring-enhancing lesions. This study investigates exceptions to this norm. Materials and Methods: We conducted an MRS study on 49 histologically confirmed and previously untreated patients with brain metastases, employing single-voxel (SVS) techniques with short and long echo times, as well as magnetic resonance spectroscopic imaging (MRSI). Results: In our cohort, 44 out of 49 (90%) patients demonstrated a typical MR spectroscopic profile consistent with secondary deposits: a Cho peak, very low or absent Cr, absence of NAA, and the presence of lipids. A peak at approximately 2 ppm, termed the "NAA-like peak", was present in spectra obtained with both short and long echo times. Among the MRS data from 49 individuals, we observed a peak at 2.0 ppm in five brain metastases from mucinous carcinoma of the breast, mucinous non-small-cell lung adenocarcinoma, two metastatic melanomas, and one metastatic non-small-cell lung cancer. Pathohistological verification of mucin in two of these five cases suggested this peak likely represents N-acetyl glycoproteins, indicative of mucin expression in cancer cells. Conclusions: The identification of a prominent peak at 2.0 ppm could be a valuable diagnostic marker for distinguishing single ring-enhancing lesions, potentially associated with mucin-expressing metastases, offering a new avenue for diagnostic specificity in challenging cases.

Case Report: Labor induced coccydynia associated with Modic I changes successfully treated with platelet-rich plasma.

Imaging can aid in determining potential causes of coccygeal pain and therefore guide clinicians to carry out individualized treatment. We represent a case of postpartum coccydynia treated by platelet-rich plasma (PRP) which was assessed and followed by MRI. A primipara with uncomplicated labor developed coccygeal pain after delivery that significantly limited her postpartum recovery. On the first MR scan, recorded 6 months after delivery, there were edematous changes of the vertebral endplates of Co1-4 level (Modic type I) with the presence of pronounced precoccygeal venous drainage. Degenerative changes with signs of edema in the area of the pubic symphysis were recorded. The sacroiliac joints had regular morphological features. Since the patient was breastfeeding, PRP therapy was applied with a total of three injections in the area of the coccyx subcutaneously, once every 3 months. The subjective feeling of pain reduction after each injection was about 30%, with the complete withdrawal of pain after one year and still pain-free at the two-year follow-up. One year after the initial MR imaging, a follow-up MR examination was performed, where almost complete resolution of edematous changes in the previously present zones was observed, with residual minor edema of the vertebral endplates at the Co2-3 level. Edema of the pubic bones in the area of the pubic symphysis also subsided. A case of labor-induced coccydynia that was represented as Modic type I changes without neither fracture or luxation was successfully treated with PRP with complete resolution of symptoms.

Diagnostic value of the apparent diffusion coefficient in differentiating malignant from benign endometrial lesions.

Introduction: Magnetic resonance imaging (MRI) with its innovative techniques, such as diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC), increases the diagnostic accuracy in distinguishing between malignant and benign lesions of the endometrium. The aim of the study was MRI differentiation between malignant and benign endometrial lesions and correlation with histopathological findings with a special emphasis on quantitative analysis. An additional aim was to correlate the ADC values and histological tumor grades. Methods: The prospective study included 119 female patients with or without vaginal bleeding and pathological values of endometrial thickness, who underwent MRI examinations. According to MRI reports the patients were divided into 45 suspicious malignant and 74 suspicious benign endometrial lesions. The radiological diagnosis was compared to the histopathological evaluation, which confirmed 37 malignant lesions while the rest were benign. Results: The mean ADC value for malignant lesions was 0.761 ± 0.13×10-3 mm2/s and for benign lesions was 1.318 ± 0.20×10-3 mm2/s. The ADC values for malignant lesions were expectedly lower than those of benign lesions (p<0.001). The ADC cut-off value was 1.007×10-3 mm2/s with a sensitivity of 100%, specificity of 92.7%, a positive predictive value of 60.3%, and a negative predictive value of 100%. In comparison with the histopathological findings, the sensitivity of MRI was 100%, specificity 90.2%, positive predictive value was 82.2%, and negative predictive value was 100%. Observing the histological grades 1, 2, and 3 of endometrial carcinoma, no statistically significant differences of mean ADC values were found. The mean ADC values for histological tumor grades 1,2 and 3 were 0.803 ± 0.13×10-3 mm2/s, 0.754 ± 0.12×10-3 mm2/s and 0.728 ± 0.13×10-3 mm2/s, respectively. Conclusion: DWI and ADC values represent clinically useful tools for the differentiation between malignant and benign endometrial lesions with high sensitivity and good specificity, but the results failed to demonstrate their usefulness in differentiating histological grades of endometrial cancer.

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.

An integrative survival analysis and a systematic review of the cerebellopontine angle glioblastomas.

Glioblastomas presenting topographically at the cerebellopontine angle (CPA) are exceedingly rare. Given the specific anatomical considerations and their rarity, overall survival (OS) and management are not discussed in detail. The authors performed an integrative survival analysis of CPA glioblastomas. A literature search of PubMed, Scopus, and Web of Science databases was performed per PRISMA guidelines. Patient data including demographics, clinical features, neuroimaging, management, follow-up, and OS were extracted. The mean age was 39 ± 26.2 years. The mean OS was 8.9 months. Kaplan-Meier log-rank test and univariate Cox proportional-hazards model identified hydrocephalus (log-rank, p = 0.034; HR 0.34; 95% CI 0.12-0.94; p = 0.038), chemotherapy (log-rank, p < 0.005; HR 5.66; 95% CI 1.53-20.88; p = 0.009), and radiotherapy (log-rank, p < 0.0001; HR 12.01; 95% CI 3.44-41.89; p < 0.001) as factors influencing OS. Hydrocephalus (HR 3.57; 95% CI 1.07-11.1; p = 0.038) and no adjuvant radiotherapy (HR 0.12; 95% CI 0.02-0.59; p < 0.01) remained prognostic on multivariable analysis with fourfold and twofold higher risk for the time-related onset of death, respectively. This should be considered when assessing the risk-to-benefit ratio for patients undergoing surgery for CPA glioblastoma.

Case Report: Atypical Solitary Brain Metastasis: The Role of MR Spectroscopy In Differential Diagnosis.

Background: Metastatic brain tumors are typically located at the cerebral hemispheres or the cerebellum and most frequently originate from primary breast or lung tumors. Metastatic lesions are usually associated with blood-brain barrier disruption, solid or ring-like contrast enhancement, and perilesional vasogenic edema on brain imaging. Even in cases where metastases are predominantly cystic, enhancement of the minor solid component can be detected. In contrast, non-enhancing secondary brain tumors were only reported in a patient after antiangiogenic treatment with bevacizumab. Case report: We report a case of a 54-year-old male who presented with left-sided weakness and multiple seizures. Brain magnetic resonance imaging revealed a T2-weighted heterogeneous solid tumor in the right frontoparietal parasagittal region, with no apparent enhancement on T1-weighted post-contrast images and no evident perilesional edema. Further MRS analysis revealed markedly increased choline and lipid peaks. The patient underwent craniotomy for tumor removal. Histopathology revealed findings consistent with metastatic non-microcellular neuroendocrine lung cancer. positron emission tomography/computed tomography (PET/CT) revealed a stellate lesion within the right upper lung lobe, compatible with primary lung cancer. Conclusion: Non-enhancing brain metastatic tumors are rarely reported in the literature, usually following antiangiogenic treatment. Here, we report the first ever case of a non-enhancing metastatic brain tumor with no prior history of antiangiogenic treatment, with particular emphasis on the importance of MRS analysis in atypical brain lesions.

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.

Case Report: Malignant Primary Sellar Paraganglioma With Unusual Genetic and Imaging Features.

BACKGROUND: Paraganglioma occurs rarely in the sellar/parasellar region. Here, we report a patient with malignant paraganglioma with primary sellar location with unusual genetic and imaging features. CASE PRESENTATION: A 31-year-old male presented with mild hypertension, headache, nausea, and vomiting. A sellar/parasellar tumor mass was revealed by magnetic resonance imaging (MRI), while an endocrine work-up found partial hypopituitarism, suggesting that it was a non-functioning pituitary tumor. Antihypertensive therapy and hormone replacement were initiated. Tumor reduction was achieved with transsphenoidal neurosurgery. However, histological diagnosis was not possible due to extensive tissue necrosis. After 4 years of stable disease, the residual tumor showed re-growth requiring gamma knife radiosurgery. Four years after the radiosurgery, MRI showed a significant tumor progression leading to a second neurosurgery. This time, pathological and immunohistochemical findings revealed paraganglioma. Plasma levels of metanephrine and normetanephrine were normal. A gene sequencing panel performed on DNA extracted from blood excluded germline mutations in 17 susceptibility genes. The patient developed new tumor masses in the neck, and the third surgery was performed. Immunohistochemistry demonstrated lack of ATRX (alpha thalassemia/mental retardation syndrome X-linked) protein in tumor cells, indicating an ATRX gene mutation. Molecular genetic analysis performed on tumor DNA revealed a combination of ATRX and TP53 gene abnormalities; this was not previously reported in paraganglioma. MRI and 68Ga-DOTANOC PET/CT revealed the full extent of the disease. Therapy with somatostatin LAR and 177Lu-DOTATATE Peptide Receptor Radionuclide Therapy (PRRT) was initiated. CONCLUSION: Although rare, paraganglioma should be considered in the differential diagnosis of sellar/parasellar tumor lesions, even in the absence of typical imaging features. ATRX gene mutation in paraganglioma is an early predictor of malignant behavior and a potential novel therapeutic marker when pharmacological therapy targeting mutated ATRX becomes available.

Is Elevated Choline on Magnetic Resonance Spectroscopy a Reliable Marker of Breast Lesion Malignancy?

BACKGROUND: Contemporary magnetic resonance imaging (MRI) of the breast represents a powerful diagnostic modality for cancer detection, with excellent sensitivity and high specificity. Magnetic resonance spectroscopy (MRS) is being explored as an additional tool for improving specificity in breast cancer detection, using multiparametric MRI. The aim of this study was to examine the possibility of 1H-MRS to discriminate malignant from benign breast lesions, using elevated choline (Cho) peak as an imaging biomarker. METHODS: A total of 60 patients were included in this prospective study: 30 with malignant (average age, 55.2 years; average lesion size, 35 mm) and 30 with benign breast lesions (average age, 44.8 years; average lesion size, 20 mm), who underwent multiparametric MRI with multivoxel 3D 1H-MRS on a 1.5-T scanner in a 3-year period. Three patients with benign breast lesions were excluded from the study. All lesions were histologically verified. Peaks identified on 1H-MRS were lipid (0.9, 2.3, 2.8, and 5.2 ppm), choline (3.2 ppm), and water peaks (4.7 ppm). Sensitivity and specificity, as well as positive and negative predictive values, were defined using ROC curves. Cohen's Kappa test of inter-test reliability was performed [testing the agreement between 1H-MRS and histologic finding, and 1H-MRS and MR mammography (MRM)]. RESULTS: Choline peak was elevated in 24/30 malignant lesions and in 20/27 benign breast lesions. The sensitivity of 1H-MRS was 0.8, specificity was 0.741, positive predictive value was 0.774, and negative predictive value was 0.769. Area under ROC was 0.77 (CI 0.640-0.871). Inter-test reliability between 1H-MRS and histologic finding was 0.543 (moderate agreement) and that between 1H-MRS and MRM was 0.573 (moderate agreement). False-negative findings were most frequently observed in invasive lobular cancers, while false-positive findings were most frequently observed in adenoid fibroadenomas. CONCLUSION: Although elevation of the choline peak has a good sensitivity and specificity in breast cancer detection, both are significantly lower than those of multiparametric MRM. Inclusion of spectra located on tumor margins as well as analysis of lipid peaks could aid both sensitivity and specificity. An important ratio of false-positive and false-negative findings in specific types of breast lesions (lobular cancer and adenoid fibroadenoma) suggests interpreting these lesions with a caveat.

Primary Intraparenchymal Meningiomas: A Case Report and a Systematic Review.

BACKGROUND: Primary intraparenchymal meningiomas are exceedingly rare and often challenging to diagnose, given their misleading radiologic features. It is hypothesized that they arise from the cap cells of the pia mater that enter the brain via penetrating blood vessels during brain development. We systematically reviewed and analyzed previously reported features of primary intraparenchymal meningiomas in terms of radiography, presenting symptoms, and histopathology. METHODS: A literature search of the Web of Science and PubMed databases and crossed references was performed in March 2021, per PRISMA guidelines, with no restrictions regarding publication date. Data regarding demographic features, clinical, radiographic, and histopathologic characteristics were extracted. RESULTS: A total of 52 patients (including the reported case) were included in this review. The mean age was 21.1 years (range, 0.3-66 years) with a male/female ratio of 1.9:1. The most common localizations of intraparenchymal meningiomas were in the frontal (30.8%) and temporal (21.2%) lobes. Cyst formation was more readily observed and was noted in 51.4% of patients. Histopathology showed a higher incidence of World Health Organization grade II (14/52, 26.9%) and World Health Organization grade III (7/52, 13.5%) of primary intraparenchymal meningiomas. CONCLUSIONS: We present a comprehensive analysis of every reported primary intraparenchymal meningioma. Because of their rarity and capacity to mimic other more common intra-axial tumors, they represent a diagnostic challenge. This systematic review highlights the importance of paying attention to atypical intra-axial lesions, with a particular reflection on the discrepancy between clinical characteristics and imaging features.

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.

Thalamic volume loss as an early sign of amnestic mild cognitive impairment.

The aim of this study was to compare brain volume reduction in patients with Alzheimer's disease (AD) and amnestic mild cognitive impairment (aMCI) with age-related changes in age- and gender-matched healthy individuals. Sixty-six patients were divided in three groups based on medical history, neurological and neurocognitive assessment: 26 patients with AD, 20 patients with aMCI and 20 healthy controls. All participants underwent high-resolution magnetic resonance (MR) imaging on 3 T unit. MR volumetry of cerebral cortex, white matter and lateral ventricles volumes, as well as volumes of subcortical nuclei (hippocampus, amygdala, thalamus) was performed. Global cerebral and grey matter volumes were lower in AD patients compared to aMCI (p = 0.023 and p = 0.001, respectively) and controls (p < 0.001 and p < 0.001, respectively). Volume of lateral ventricles was significantly higher in AD patients compared to controls (right p = 0.007, left p = 0.007). Volumes of thalamus were lower in AD patients (right p < 0.001, left p < 0.001), and in aMCI patients (right p = 0.004, left p = 0.015), compared to controls. Hippocampal volume was lower in AD patients compared to both aMCI patients (right p = 0.047, left p = 0.003) and controls (right p < 0.001, left p < 0.001). In aMCI patients, hippocampal volume was lower than in controls (right p = 0.004, left p = 0.007). Volumes of amygdala were lower in AD patients compared to controls (righ p = 0.003, left p = 0.001). Our results show that thalamic volume loss could be an early sign associated with poorercognitiveperformance in aMCI, preceeding the atrophy of amygdala, global grey and white matter volume loss, and cerebrospinal fluid spaces dilatation.

Impaired dynamic cerebral autoregulation in trained breath-hold divers.

Breath-hold divers (BHD) experience repeated bouts of severe hypoxia and hypercapnia with large increases in blood pressure. However, the impact of long-term breath-hold diving on cerebrovascular control remains poorly understood. The ability of cerebral blood vessels to respond rapidly to changes in blood pressure represents the property of dynamic autoregulation. The current investigation tested the hypothesis that breath-hold diving impairs dynamic autoregulation to a transient hypotensive stimulus. Seventeen BHD (3 women, 11 ± 9 yr of diving) and 15 healthy controls (2 women) completed two or three repeated sit-to-stand trials during spontaneous breathing and poikilocapnic conditions. Heart rate (HR), finger arterial blood pressure (BP), and cerebral blood flow velocity (BFV) from the right middle cerebral artery were measured continuously with three-lead electrocardiography, finger photoplethysmography, and transcranial Doppler ultrasonography, respectively. End-tidal carbon dioxide partial pressure was measured with a gas analyzer. Offline, an index of cerebrovascular resistance (CVRi) was calculated as the quotient of mean BP and BFV. The rate of the drop in CVRi relative to the change in BP provided the rate of regulation [RoR; (∆CVRi/∆T)/∆BP]. The BHD demonstrated slower RoR than controls (P ≤ 0.001, d = 1.4). Underlying the reduced RoR in BHD was a longer time to reach nadir CVRi compared with controls (P = 0.004, d = 1.1). In concert with the longer CVRi response, the time to reach peak BFV following standing was longer in BHD than controls (P = 0.01, d = 0.9). The data suggest impaired dynamic autoregulatory mechanisms to hypotension in BHD. NEW & NOTEWORTHY Impairments in dynamic cerebral autoregulation to hypotension are associated with breath-hold diving. Although weakened autoregulation was observed acutely in this group during apneic stress, we are the first to report on chronic adaptations in cerebral autoregulation. Impaired vasomotor responses underlie the reduced rate of regulation, wherein breath-hold divers demonstrate a prolonged dilatory response to transient hypotension. The slower cerebral vasodilation produces a longer perturbation in cerebral blood flow velocity, increasing the risk of cerebral ischemia.

N-Acetylaspartate-to-creatine ratio in twelve brain locations among healthy men and women with different levels of education.

Brain bioenergetics could be affected by many intrinsic and extrinsic factors, yet no link has been established between markers of bioenergetics in specific brain regions and educational level. In this cross-sectional study, we evaluated N-acetylaspartate-to-creatine ratio (NAA/Cr), a biomarker of brain functionality, using multivoxel proton magnetic resonance spectroscopy in twelve brain locations among healthy volunteers (n = 51; 30 females; age 47.8 ± 16.3 years) who earned either a high school diploma (36 out of 51) or a college degree (15 out of 51). Hierarchical multiple regression analysis revealed that our model as a whole (including level of education as a predictor variable, and age and gender as control variables) explained significant percentage of the variance in the NAA/Cr levels at 8 out of 12 specific brain locations (P< 0.05). This was highlighted in left anterior mesial cortex where the model explained 63.1% of the variance in brain NAA/Cr, with education and age make significant contributions (72.6% and 48.5%, respectively) to our model (P< 0.05). Having superior brain N-acetylaspartate-to-creatine ratio appears to be related with higher education in healthy men and women.

Self-confidence and clinical skills: the case of students who study medicine in English in a non-English speaking setting.

BACKGROUND: An increasing number of international students has been enrolling in medical studies in the English language offered by the countries of Eastern Europe. Development of practical skills is likely more challenging when students learn in the English language, while their patients are non-English speaking persons. AIMS: To evaluate self-perception of practical skills of medical students in the English language program. METHODS: From December 2016 to December 2017, a total of 52 students from the Studies in English program of two universities in Serbia were included in the study. Data were obtained by a previously validated questionnaire. RESULTS: Participants were most confident when measuring blood pressure, checking the arterial pulse, and taking history. Students were the least confident when placing urinary catheters, performing rectal examinations, and suturing wounds. Male students reported higher confidence in "Major interventions" compared to females (p = 0.004), and no difference between male and female students was found in the total skill score of "knowledge of Serbian language" (p = 0.339). Adjusted analysis showed that a higher grade point average remains associated with a more confident perception of one's practical skills (B 26.48, 95% confidence interval 8.98-43.98). Rasch analysis showed that because the scores were distributed around the mean value between "not confident at all" and "quite confident," the majority of students had similar perceptions of their skills. CONCLUSION: Active supervision by teaching staff is also recommended in an attempt to rectify the lack of confidence at performing a range of clinical procedures which is present among international students.

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.

Executive Functions Rating Scale and Neurobiochemical Profile in HIV-Positive Individuals.

The set of complex cognitive processes, that are necessary for the cognitive control of behavior, known as executive functions (EF), are traditionally associated with the prefrontal cortex and commonly assessed with laboratory based tests and conventional neuroimaging. In an effort to produce a more complete and ecologically valid understanding of executive functioning, the rating scales have been developed in order to assess the behavioral aspects of EF within an everyday real-world context. The main objective of this study was to examine the relationship between behavioral aspects of EF measured by rating scale and neurometabolic profile in neurologically asymptomatic HIV-positive individuals under cART, measured using multi-voxel magnetic resonance spectroscopy (mvMRS). The sample comprised 39 HIV-positive adult male participants, stable on cART and 39 healthy HIV-negative volunteers. Both groups completed the Behavior Rating Inventory of Executive Function-Adult Version (BRIEF-A). HIV-positive group additionally underwent long-echo three-dimensional mvMRS to determine neurobiochemical profile in the anterior cingulate gyrus (ACG) of both hemispheres. Three dominant neurometabolites were detected: N-acetyl aspartate (NAA), the neuronal marker; choline (Cho), the marker of membrane metabolism and gliosis and creatine (Cr), the reference marker. Ratios of NAA/Cr and Cho/Cr were analyzed. The initially detected significant correlations between age, current CD4, BRIEF-A subscales Inhibit, Shift, Emotional Control, Plan/Organize, Self Monitoring and ratios of NAA/Cr and Cho/Cr in the dorsal and ventral part of the ACG, were lost after the introduction of Bonferroni corrections. Also, there were no significant differences between HIV-positive and HIV-negative group on any of BRIEF-A subscales. Such results possibly imply that stable cART regimen contributes to preservation of behavioral aspects of EF in asymptomatic HIV-positive individuals. Even though a subtle deficit in some aspects of EF might exist, it would not be manifest if behavioral aspect was assessed using EF rating scale. Further explanation might be that expected HIV-related changes in neurometabolic profile of the ACG under cART are not reflected in those behavioral aspects that are measurable by EF rating scale.

Basal ganglia shrinkage without remarkable hippocampal atrophy in chronic aviremic HIV-positive patients.

Conventional magnetic-resonance (MR) imaging is not sensitive enough in depicting subtle neurodegenerative changes that occur during chronic HIV infection with good peripheral viral suppression. The aim of this study was to compare brain volumes in HIV-positive subjects with age- and education-matched healthy controls with regard to influence of aging and immunologic parameters. An overall of 65 subjects (40 HIV-positive and 25 age-, gender-, and education-matched healthy subjects) underwent conventional MR imaging with three-dimensional sequence adequate for volumetric measurements. Volumes of specific brain regions were measured and compared between HIV-positive and healthy subjects using Student t test. Correlations between obtained brain volumes and immunologic parameters were determined using Pearson's correlation test. Influence of age as a covariate was determined using ANCOVA test. Statistical value was set at p < 0.05. Volumes of nucleus accumbens (p = 0.003), putamen (p = 0.003), and thalamus (p = 0.046) were significantly decreased in HIV-positive subjects compared with healthy, while volumes of lateral ventricles were significantly increased (p = 0.043). However, influence of age on atrophy was greater than presence of HIV infection in all observed volumes. Positive correlation of nadir CD4+ count and nucleus accumbens volume was obtained, as well as of therapy with lateral ventricle volumes. Volumes of putamen correlated negatively with duration of therapy. HIV-associated atrophic changes are visible in nucleus accumbens, putamen, and thalamus in neurocognitively asymptomatic stage, while no changes can be observed in the hippocampus, affected by other types of dementias. Under therapy, the influence of physiological aging on HIV-associated atrophy is greater than the presence of HIV infection per se.

A prominent lactate peak as a potential key magnetic resonance spectroscopy (MRS) feature of progressive multifocal leukoencephalopathy (PML): Spectrum pattern observed in three patients.

Progressive multifocal leukoencephalopathy (PML) is a rare, often fatal, opportunistic infection, associated with demyelinating process. PML is caused by John Cunningham (JC) polyomavirus, and predominantly affects patients with human immunodeficiency virus (HIV) infection or other immunocompromised patients. The purpose of this study was to determine the role of magnetic resonance spectroscopy (MRS) in establishing the diagnosis of PML. MRS with long and short echo time was performed in two patients with PML associated with HIV infection and in one PML patient associated with chronic lymphocytic leukemia. The most prominent peak on the obtained spectra was for lactate; it showed 2-3 times higher concentration of lactate compared to choline, almost 4-6 times higher lactate concentration compared to creatine, and 4-11 times higher lactate in comparison to N-acetylaspartate concentration. Similar spectrum pattern was observed in all patients. To the best of our knowledge, this is a new finding that might be useful in early diagnosis of PML. Nevertheless, further confirmation of our results is needed, since we analyzed the spectrum pattern only in three patients. Overall, our results could help in early detection of PML, especially in non-HIV patients, and thus prevent the fatal outcome of the disease. MRS could also be useful in detecting "tumefactive" demyelinating lesions in PML patients, associated with immune reconstitution inflammatory syndrome, to avoid misdiagnosis of neoplasm.