Quantitative magnetic resonance assessment of brain atrophy related to selected aspects of disability in patients with multiple sclerosis: preliminary results.

PURPOSE: The aim of this volumetric study was to evaluate the relationship between brain atrophy quantification in multiple sclerosis (MS) patients and the progression of disability measured by neurological standardised tests. MATERIAL AND METHODS: Seventeen patients (mean age 40.89 years) with clinically definite MS and 24 control subjects (mean age 38.45 years) were enrolled in the study. Brain examinations were performed on a 1.5T MR scanner. Automatic brain segmentation was done using FreeSurfer. Neurological disability was assessed in all patients in baseline and after a median follow-up of two years, using EDSS score evaluation. RESULTS: In MS patients we found significantly (p < 0.05) higher atrophy rates in many brain areas compared with the control group. The white matter did not show any significant rate of volume loss in MS patients compared to healthy controls. Significant changes were found only in grey matter volume in MS subjects. At the follow-up evaluation after two years MS patients with deterioration in disability revealed significantly decreased cerebral volume in 14 grey matter areas at baseline magnetic resonance imaging (MRI) compared to MS subjects without disability progression. CONCLUSIONS: Grey matter atrophy is associated with the degree of disability in MS patients. Our results suggest that morphometric measurements of brain volume could be a promising non-invasive biomarker in assessing the volumetric changes in MS patients as related to disability progression in the course of the disease.

Evaluation of early cerebral metabolic, perfusion and microstructural changes in HCV-positive patients: a pilot study.

BACKGROUND & AIMS: The aim of the study was to evaluate early metabolic perfusion, and microstructural cerebral changes in patients with the hepatitis C virus (HCV) infection and normal appearing brain on plain MR using advanced MR techniques, as well as to assess correlations of MR measurements with the liver histology activity index (HAI). METHODS: Fifteen HCV-positive patients and 18 control subjects underwent single voxel MR spectroscopy (MRS), perfusion weighted imaging (PWI), and diffusion tensor imaging (DTI), using a 1.5T MR unit. MRS metabolite ratios (NAA/Cr, Cho/Cr, mI/Cr) were calculated. PWI values of relative cerebral blood volume (rCBV) were assessed from 8 areas including several cortical locations, basal ganglia, and fronto-parietal white matter. DTI fractional anisotropy (FA) and apparent diffusion coefficient (ADC) values were obtained from 14 white matter tracts. RESULTS: Compared to controls, HCV-positive patients showed significantly (p < 0.05) lower NAA/Cr ratios within frontal and parietal white matters, lower rCBV values within frontal and temporo-parietal cortices, decreased FA values, as well as increased ADC values in several white matter tracts. We also found elevated rCBV values in basal ganglia regions. The increase in mI/Cr and Cho/Cr ratio was correlated with a higher HAI score. CONCLUSIONS: The results of advanced MR techniques indicate neurotoxicity of HCV reflected by neuronal impairment within white matter, cortical hypoperfusion, and disintegrity within several white matter tracts. Hyperperfusion in basal ganglia may be an indicator of brain inflammation in HCV patients. Our findings may suggest a biologic link between HCV-related liver disease and cerebral dysfunction.

Analysis of metabolic changes of brain in HIV-1 seropositive patients with proton magnetic resonance spectroscopy.

BACKGROUND: Asymptomatic central nervous system involvement may occur in the early stages of the HIV infection. The aim of the study was to evaluate early brain metabolic changes by means of proton MR spectroscopy (H1MRS) in the HIV-1 seropositive patients without neurological deficits or significant abnormalities in the plain MR study. MATERIAL/METHODS: The H1MRS examinations were performed with the use of a MR GE Signa 1,5T system. There were 39 subjects examined, aged 21 to 57 years (mean age 35 years) were examined, including 25 patients infected with HIV-1 and 14 healthy volunteers who constituted a control group. The examinations were performed using the Single Voxel Spectroscopy technique with the PRESS sequence, with following parameters: TR=1500 ms, TE=35 ms, number of acquisitions =128, time of acquisition =3 min. 43 sec. Voxels of 8 cm(3) (20×20×20 mm) in size were located in the following 5 regions: posterior cingulate gyrus, grey matter of the frontal area, left basal ganglia, white matter of the left parietal area and white matter of the frontal area. The NAA/Cr, Cho/Cr, mI/Cr ratios in the defined regions of interest were statistically analyzed. RESULTS: There was a statistically significant decrease (p<0.05) in the NAA/Cr ratios in the posterior cingulate area and white matter of the left parietal area in HIV-1 seropositive patients, as compared to the control group. Other metabolite ratios in all the above mentioned locations showed no statistically significant differences, as was also the case for NAA/Cr ratios in grey matter of the frontal area, left basal ganglia and white matter of the frontal area. CONCLUSIONS: The reduction of NAA/Cr values revealed in H1MRS studies suggests loss of neurons/neuronal activity in the posterior cingulate area and white matter of the left parietal area, in patients with HIV-1 at the stage before clinical manifestations of retroviral infection and structural changes in the plain MR study. This may reflect a direct neurotropic activity of HIV.

Diffusion tensor imaging of normal-appearing cervical spinal cords in patients with multiple sclerosis: Correlations with clinical evaluation and cerebral diffusion tensor imaging changes. Preliminary experience.

BACKGROUND: Several studies have identified changes in the spinal cord DTI measurements in patients with multiple sclerosis (MS). However, correlations between changes in DTI parameters in normal appearing cervical spine and neurological findings have not been clearly established. OBJECTIVES: To determine whether diffusion tensor imaging (DTI) measurements such as fractional anisotropy (FA) and apparent diffusion coefficient (ADC) are sufficiently sensitive in detecting microstructure alterations in normal-appearing spinal cords in patients with MS and whether they reflect these patients' clinical disability. MATERIAL AND METHODS: Fifteen patients diagnosed with relapsing-remitting MS (RRMS) with normal-appearing cervical spinal cords on plain MRI and 11 asymptomatic volunteers were enrolled in the study. Overall, 75 cervical spinal segments were analyzed. The regions of interest were drawn from the entire spinal cord cross-section and in the normal-appearing white matter tracts: the superior and inferior cerebellar peduncles and the posterior limbs of the internal capsules. Neurological deficit and the level of disability were evaluated using the Expanded Disability Status Scale (EDSS), the timed 25-foot walk test (T25FW) and the 9-hole peg test (9HPT) for manual dexterity. RESULTS: A significant difference (p < 0.05) in FA values between patients with MS and the control group was found at levels C2 (p = 0.047) and C3 (p = 0.023). No significant changes in ADC values were found. There was correlation between FA and ADC values in selected white matter tracts and at particular spinal cord levels. We also observed significant correlations between diffusion tensor imaging parameters and manual dexterity. CONCLUSIONS: Our preliminary results may suggest that the spinal cord's structural loss is the dominant factor in the inflammatory/demyelinating component in patients with MS. Diffusion tensor imaging changes in the spinal cord correlate with brain DTI changes. Manual functioning seems to be more affected than walking.

Single median maxillary central incisor syndrome and variant in SMO gene associated with SHH pathway.

Solitary median maxillary central incisor syndrome (SMMCI) is a rare congenital oronasal-dental midline anomaly. The aim of this paper is a presentation of a patient with SMMCI without other visible dentofacial anomalies, with a potentially new molecular etiology consisting of a gene-gene reaction and conservative therapeutic approach to nasal obstruction. Potentially pathogenic variants in the SMO gene (p.Gly422Glu) and in P2RY13 gene (p.Trp205*) inherited from the probant's father, and in the PLD2 gene (p.Gln319fs), inherited from the mother were found. A multidisciplinary approach is necessary for the management of patients with SMMCI, including a genetic consultation with genetic tests.

Apparent diffusion coefficient measurements in normal appearing white matter may support the differential diagnosis between multiple sclerosis lesions and other white matter hyperintensities.

AIMS: The objectives of the study were to assess the usefulness of measurements of apparent diffusion coefficient (ADC) in normal appearing white and grey matter (NAWM, NAGM) in differential diagnosis between patients with hyperintense demyelinating plaques in the course of multiple sclerosis (MS) and other conditions presenting white matter hyperintensities (WMHs), as well as to evaluate the relationship between clinical data and ADC values in MS patients. MATERIAL AND METHODS: The study comprised 66 patients with MS before treatment, 66 patients with WMHs and 64 control subjects (control group, CG), who underwent MRI (magnetic resonance imaging) examination including diffusion weighted imaging (DWI) with a 1.5 T MR unit. ADC measurements were obtained from NAWM of the cerebellum, pons as well as frontal, fronto-parietal and temporal regions bilaterally, and from NAGM of thalami and heads of caudate nuclei, using round region of interest (ROI) sized 200mm2. RESULTS: The mean ADC values in frontal, fronto-parietal and temporal NAWM were significantly higher in the MS group than in subjects with WMHs and CG (p < .001), whereas the mean ADC value in pons was higher in MS than in CG (p < .05). In the MS group we observed a positive correlation between the Expanded Disability Status Scale (EDSS) and lesion load, between duration of the disease and mean ADC values and between lesion load and mean ADC values. CONCLUSION: Our results suggest that ADC measurements may support the differential diagnosis between MS and other conditions associated with white matter hyperintensities. The most significant changes were observed in temporal white matter regions.

Value of perfusion-weighted MR imaging in the assessment of early cerebral alterations in neurologically asymptomatic HIV-1-positive and HCV-positive patients.

BACKGROUND AND PURPOSE: Asymptomatic central nervous system (CNS) involvement occurs in the early stage of the human immunodeficiency virus (HIV) infection. It has been documented that the hepatitis C virus (HCV) can replicate in the CNS. The aim of the study was to evaluate early disturbances in cerebral microcirculation using magnetic resonance (MR) perfusion-weighted imaging (PWI) in asymptomatic HIV-1-positive and HCV-positive patients, as well as to assess the correlation between PWI measurements and the clinical data. MATERIALS AND METHODS: Fifty-six patients: 17 HIV-1-positive non-treated, 18 HIV-1-positive treated with combination antiretroviral therapy (cART), 7 HIV-1/HCV-positive non-treated, 14 HCV-positive before antiviral therapy and 18 control subjects were enrolled in the study. PWI was performed with a 1.5T MR unit using dynamic susceptibility contrast (DSC) method. Cerebral blood volume (CBV) measurements relative to cerebellum (rCBV) were evaluated in the posterior cingulated region (PCG), basal ganglia (BG), temporoparietal (TPC) and frontal cortices (FC), as well as in white matter of frontoparietal areas. Correlations of rCBV values with immunologic data and liver histology activity index (HAI) were analyzed. RESULTS: Significantly lower rCBV values were found in the right TPC and left FC as well as in PCG in HIV-1-positive naïve (p = 0.009; p = 0.020; p = 0.012), HIV-1 cART treated (p = 0.007; p = 0.009; p = 0.033), HIV-1/HCV-positive (p = 0.007; p = 0.027; p = 0.045) and HCV-positive patients (p = 0.010; p = 0.005; p = 0.045) compared to controls. HIV-1-positive cART treated and HIV-1/HCV-positive patients demonstrated lower rCBV values in the right FC (p = 0.009; p = 0.032, respectively) and the left TPC (p = 0.036; p = 0.005, respectively), while HCV-positive subjects revealed lower rCBV values in the left TPC region (p = 0.003). We found significantly elevated rCBV values in BG in HCV-positive patients (p = 0.0002; p<0.0001) compared to controls as well as to all HIV-1-positive subjects. There were no significant correlations of rCBV values and CD4 T cell count or HAI score. CONCLUSIONS: PWI examination enables the assessment of HIV-related as well as HCV-related early cerebral dysfunction in asymptomatic subjects. HCV-infected patients seem to reveal the most pronounced perfusion changes.

Evaluation of metabolic changes within the normal appearing gray and white matters in neurologically asymptomatic HIV-1-positive and HCV-positive patients: magnetic resonance spectroscopy and immunologic correlation.

OBJECTIVE: The aim of the study was to evaluate early metabolic changes using proton MR spectroscopy (MRS) in asymptomatic HIV-1-positive and HCV-positive patients without abnormalities in the structural MR examination. METHODS: Sixty-five asymptomatic patients: 21 HIV-1-positive naive, 20 HIV-1-positive with combination antiretroviral therapy (cART), 9 HIV-1/HCV-positive naive, 15 HCV-positive naive and 18 normal subjects were enrolled in the study. The MRS examinations were performed with a 1.5T MR scanner. Voxels were located in the following regions: posterior cingulate gyrus (PCG), anterior cingulate gyrus (ACG), parietal white matter (PWM), left basal ganglia (BG) and frontal white matter (FWM). The NAA/Cr, Cho/Cr, mI/Cr ratios and correlations of MRS measurements with the immunologic data were analyzed. RESULTS: There was a significant decrease (p<0.05) of the NAA/Cr ratios in PCG, ACG and PWM regions in HIV-1-positive cART treated patients compared to the normal subjects. The significantly decreased NAA/Cr ratios in PWM and FWM were observed in HCV infected patients. The subjects with HIV-1/HCV co-infection revealed significantly lower NAA/Cr ratios in the ACG area. Other metabolite ratios in all analyzed regions, as well as the NAA/Cr ratios in BG showed no significant differences. The decrease of CD4n T cell count was associated with the decease of the NAA/Cr ratio in the PCG area and the increase of Cho/Cr ratio in the FWM region. CONCLUSIONS: The metabolic changes - reduction of NAA/Cr ratios are most pronounced in HIV-1-positive patients using cART. The low CD4n T cell count is a risk factor for neurocognitive impairment in HIV-1-positive patients.