Safety and efficacy of simple training protocol in patients after mild traumatic brain injury.

AIMS: Mild Traumatic Brain Injury (mTBI) is the most common type of craniocerebral injury. Proper management appears to be a key factor in preventing post-concussion syndrome. The aim of this prospective study was to evaluate the effect and safety of selected training protocol in patients after mTBI. METHODS: This was a prospective study that included 25 patients with mTBI and 25 matched healthy controls. Assessments were performed in two sessions and included a post-concussion symptoms questionnaire, battery of neurocognitive tests, and magnetic resonance with tractography. Participants were divided into two groups: a passive subgroup with no specific recommendations and an active subgroup with simple physical and cognitive training. RESULTS: The training program with slightly higher initial physical and cognitive loads was well tolerated and was harmless according to the noninferiority test. The tractography showed overall temporal posttraumatic changes in the brain. The predictive model was able to distinguish between patients and controls in the first (AUC=0.807) and second (AUC=0.652) sessions. In general, tractography had an overall predictive dominance of measures. CONCLUSION: The results from our study objectively point to the safety of our chosen training protocol, simultaneously with the signs of slight benefits in specific cognitive domains. The study also showed the capability of machine learning and predictive models in mTBI patient recognition.

Proton magnetic resonance spectroscopy changes in the brainstem in patients after mild traumatic brain injury with loss of consciousness.

INTRODUCTION: Loss of consciousness (LOC) is used as a diagnostic feature of mild traumatic brain injury (MTBI). However, only 10% of concussions result in LOC. There are only a limited number of in-vivo studies dealing with unconsciousness and structural and functional integrity of the brainstem in patients with MTBI. The aim of our pilot study was to assess the sensitivity of proton magnetic resonance spectroscopy (1H-MRS) to detect metabolic changes in the brainstem in patients after MTBI with unconscioussness. METHODS: Twenty-four patients (12 with LOC, and 12 without LOC) within 3 days of MTBI and 19 healthy controls were examined. All subjects underwent single-voxel 1H-MRS examination of the upper brainstem. Spectra were evaluated using LCModel software. Ratios of total N-acetylaspartate (tNAA), total choline-containing compounds (tCho) and glutamate plus glutamine (Glx) to total creatine (tCre) were used for calculations. RESULTS: We found a significant decrease in tNAA/tCre and tCho/tCre ratios in the patient group with LOC when compared with the control group of healthy volunteers (P=0.002 and P=0.041, respectively), and a significant decrease in the tNAA/tCre ratio in the LOC group when compared with patients without LOC (P=0.04). Other metabolite ratios in the brainstem did not show any significant group differences. CONCLUSION: Our findings indicate that decrease of tNAA/tCre ratio in the upper brainstem using single-voxel 1H-MRS may provide a potential biomarker for MTBI associated with LOC.

Virtual Reality Visual Training in an Adult Patient with Anisometropic Amblyopia: Visual and Functional Magnetic Resonance Outcomes.

A case of an adult with anisometropic amblyopia who underwent a successful vision therapy program playing videogames in a virtual reality environment is described, reporting changes in conventional visual clinical data, as well as in brain activity. The patient was a 22 year old man on baseline examination that never previously wore correction for his anisometropia. After prescribing contact lens correction for the anisometropia and after 44 h of virtual reality-based vision therapy over a period of 1.5 years, the best corrected distance visual acuity (BCDVA) in the amblyopic eye improved from 0.05 to 0.5 (Sloan chart). One year after finishing the visual training, the BCDVA experienced a slight decrease to 0.4 (Sloan chart). Through the visual training, the patient gradually developed stereopsis. Likewise, changes were also detected after visual therapy on functional magnetic resonance imaging while the patient was viewing 2D and 3D stimuli. The preliminary results of this case show the potential of using virtual reality-based visual training as a treatment for adult amblyopia.

Altered hypothalamic metabolism in early multiple sclerosis - MR spectroscopy study.

Multiple sclerosis (MS) is a disease characterized by overlapping processes of neuroinflammation and neuro-axonal degeneration. Disturbances of the hypothalamo-pituitary axis in MS are supposed to modulate neuroinflammatory circuits, however, there is insufficient knowledge about the hypothalamic metabolism alterations in early MS. This 1H MRS study performed on a 1.5 T MR-scanner was focused on the hypothalamus of 31 pre-treatment patients after their first clinical MS episode/s, compared to 31 healthy controls. The metabolite ratios of N-acetyl-aspartate &N-acetyl-aspartyl-glutamate (tNAA), glutamate & glutamine (Glx), myo-Inositol (mIns), choline- and creatine-containing compounds (tCho, tCr) were further correlated with the Expanded Disability Status Scale (EDSS). In the hypothalamus of early MS patients compared to controls, we found decreased tNAA/tCr and increased tCho/tNAA, mIns/tNAA, Glx/tCr, and Glx/tNAA. In addition, tCho/tNAA, Glx/tNAA, and mIns/tNAA were positively and tNAA/tCr was negatively correlated with EDSS. Results suggest that the decline of the tNAA ratio, indicating neuro-axonal dysfunction in the hypothalamus, may be linked with glutamate excitotoxicity. Excessive glutamate concentrations may cause microglial activation and myelinated tracts degradation with subsequent gliosis, paralleled by increased mIns and tCho ratios. This indicates that glutamate excitotoxicity can play an important role in MS from its earliest stages.

Metabolic and histopathological changes in the brain and plasma of rats exposed to fractionated whole-brain irradiation.

In the present study we investigated the correlation between radiation-induced metabolic and histopathological changes in the brain under experimental conditions. Adult male Wistar rats received fractionated whole-brain irradiation (fWBI) with a total dose of 40 Gy administered in 5 fractions (dose 8 Gy per fraction) once a week on the same day for 5 consecutive weeks. Radiation-induced alteration in plasma and brain metabolites were measured by proton nuclear magnetic resonance (1H NMR)-based metabolomics and proton magnetic resonance spectroscopy (1HMRS). Histopathological changes in the brain were evaluated to determine alteration of neurogenesis and glial cell responses in 2 neurogenic regions: the hippocampal dentate gyrus (DG) and the subventricular zone-olfactory bulb axis (SVZ-OB axis). Evaluation of brain metabolites 15 weeks after irradiation performed with 1H MRS showed a significant decrease in the total N-acetylaspartate to total creatine (tNAA/tCr) ratio in the striatum, hippocampus, and OB, while gamma-aminobutyric acid to tCr (GABA/tCr) ratio in the hippocampus as well as OB and total choline to tCr (tCho/tCr) in striatum and OB. Magnetic resonance imaging (MRI) volumetric analysis showed a significant reduction in total brain volume and atrophy of dorsal hippocampus and OB. 1H NMR in plasma of irradiated animals displayed decreased citrate and increased bile acids. Image analysis of the brain sections 16 weeks after fWBI showed an increase in neurodegeneration and inhibition of neurogenesis. Results showed that fWBI led to metabolic alterations associated with histopathological findings, suggesting a subacute and development of late radiation-induced changes.

Anaplastic astrocytoma mimicking progressive multifocal leucoencephalopathy: a case report and review of the overlapping syndromes.

BACKGROUND: Co-occurrence of multiple sclerosis (MS) and glial tumours (GT) is uncommon although occasionally reported in medical literature. Interpreting the overlapping radiologic and clinical characteristics of glial tumours, MS lesions, and progressive multifocal leukoencephalopathy (PML) can be a significant diagnostic challenge. CASE PRESENTATION: We report a case of anaplastic astrocytoma mimicking PML in a 27-year-old patient with a 15-year history of MS. She was treated with interferon, natalizumab and finally fingolimod due to active MS. Follow-up MRI, blood and cerebrospinal fluid examinations, and biopsy were conducted, but only the latter was able to reveal the cause of progressive worsening of patient's disease. CONCLUSIONS: Anaplastic astrocytoma misdiagnosed as PML has not yet been described. We suppose that the astrocytoma could have evolved from a low grade glioma to anaplastic astrocytoma over time, as the tumour developed adjacent to typical MS plaques. The role of the immunomodulatory treatment as well as other immunological factors in the malignant transformation can only be hypothesised. We discuss clinical, laboratory and diagnostic aspects of a malignant GT, MS lesions and PML. The diagnosis of malignant GT must be kept in mind when an atypical lesion develops in a patient with MS.

Proton MR spectroscopic imaging of human glioblastomas at 1.5 Tesla.

In this study we evaluated clinical feasibility of proton magnetic resonance spectroscopy metabolite mapping (1H MRSI) by using 1.5 Tesla MR-scanner in 10 patients with high-grade glioblastoma. In vivo 1H MRSI performed with a relatively short scan time of 20 minutes enabled to obtain comprehensive information about metabolic changes in glioblastoma and adjacent tissues namely in the peritumoral edema, in the middle and solid part of the tumor, and in the normal-appearing brain tissue. Spectroscopically it was possible to identify initiation of neuronal cell death in the solid tumorous tissue via decreased N-acetyl-aspartate to creatine ratio (↓ tNAA/tCr) and expanding carcinogenesis reflected in elevated choline ratios (↑ tCho/tCr and tCho/tNAA). We showed also the central necrosis of glioblastoma accompanied by the tissue hypoxia, which were apparent as increased lactate and lipids ratios (↑ Lac/tCr and lip/Lac). Metabolic changes were noticeable also in the peritumoral area, showing the glioblastoma infiltration into the surrounding tissues. In intracranial tumors, 1H MRSI performed on 1.5 Tesla field strength was sufficient to provide information about the stage of carcinogenesis, tumor expansion or necrotization and thus it could be considered as a useful diagnostic tool in oncology.

Prefrontal grey and white matter neurometabolite changes after atomoxetine and methylphenidate in children with attention deficit/hyperactivity disorder: a (1)H magnetic resonance spectroscopy study.

Attention deficit/hyperactivity disorder (ADHD) is the most common neurobehavioral childhood disorder. Dysfunction of prefrontal neural circuits which are responsible for executive and attentional functions has been previously shown in ADHD. We investigated the neurometablite changes in areas included in dorsolateral prefrontal neural circuits after 2 months of long-acting methylphenidate or atomoxetine medication in children with ADHD who were responders to treatment. Twenty-one ADHD children were examined by single voxel (1)H-magnetic resonance spectroscopy (MRS) before and after 2 months of medication with OROS methylphenidate (n=10) or atomoxetine (n=11). The spectra were taken from the dorsolateral prefrontal cortex (DLPFC, 8ml) and white matter behind the DLPFC (anterior semioval center, 7.5ml), bilaterally. NAA and NAA/Cr (N-acetylaspartate/creatine) decreased in the left DLPFC and Cho/Cr (choline/creatine) increased in the right DLPFC after atomoxetine medication. Glu+Gln and Glu+Gln/Cr (glutamate/glutamine) increased in the left white matter after methylphenidate medication. We hypothesize that atomoxetine could decrease hyperactivation of DLPFC neurons and methylphenidate could lead to increased activation of cortical glutamatergic projections with the consequences of increased tonic dopamine release in the mesocortical system.

Hippocampal neurometabolite changes in depression treatment: a (1)H magnetic resonance spectroscopy study.

Previous studies using magnetic resonance spectroscopy have related abnormalities in hippocampal metabolism to depression. Current evidence is consistent with the conclusion that the hippocampal formation plays an important role in the presentation of depressive symptoms. Eighteen adult patients with major depressive disorder, aged 20 to 60 years, underwent magnetic resonance spectroscopy of the hippocampus during a period of depressive symptomatology and after 7-11 weeks of antidepressant medication with at least 50% reduction in the Montgomery-Åsberg Depression Rating Scale ()MADRS score. During therapy, we found a significantly decreased Lac/Cr ratio in the left hippocampus. The Ins/Cr ratio showed a significant negative correlation with the severity of depression as assessed by the MADRS at baseline. Moreover, we found a negative association of NAA/Cho with age and a positive association of Cho/Cr with age, both on the left and right sides at baseline. In light of our findings and previous studies results we hypothesize that mitochondrial dysfunction leading to predominantly anaerobic glycolysis in connection with the intracellular signaling pathways disturbances and decreased astrocytic function/number might subsequently lead to decreased brain neuroplasticity in depression. These mechanisms could be positively influenced by antidepressant treatment with selective serotonin or norepineprine reuptake inhibitors, with potential effects on untimely neuronal aging in depression.

Proton magnetic resonance spectroscopy and its diagnostically important metabolites in the brain.

This review provides a brief summary of the physical basis of magnetic resonance spectroscopy ((1)H MRS) and its application in the human brain. We discuss the chemical structure, signal properties, biological function, normal spatial distribution and diagnostic potential of the more significant metabolites detectable in brain tissue: N-acetylaspartate, N-acetylaspartylglutamate, choline-containing substances, creatine, phosphocreatine, myo-inositol, glutamine and glutamate. We also present a few notes on the importance of proper spectral quantification and contemporary trends in ¹H MRS. [corrected].

Proton magnetic resonance spectroscopy in patients with early stages of amyotrophic lateral sclerosis.

INTRODUCTION: Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disorder primarily affecting upper and lower motor neurons. Due to relative fast progression of the disease, early diagnosis is essential. Proton magnetic resonance spectroscopy ((1)H-MRS) is used for objectivization of upper motor neuron (UMN) lesions. The aim of this study was to assess the use of (1)H-MRS in the early stages of ALS. METHODS: Eleven patients with clinically definite (n=2), probable (n=7), and probable laboratory-supported (n=2) diagnosis of ALS with disease duration of less than 14 months were studied. Control group consists of 11 sex- and age-matched healthy subjects. All subjects underwent assessment of functional disability using revised ALS Functional Rating Scale (ALSFRS-R) and single-voxel (1)H-MRS examination of both precentral gyri, pons, medulla oblongata, and occipital lobe. Spectra were evaluated with LCModel software. RESULTS: The mean disease duration was 6.5 ± 3.5 months. The median ALSFRS-R was 42. Significant decrease between patient and control groups was found in the NAA/Cre ratio in the left and right precentral gyri (p=0.008, p=0.040). Other metabolite ratios in other areas did not show significant differences. Total ALSFRS-R score weakly positively correlated with NAA/Cre ratio in the left precentral gyrus (p=0.047). CONCLUSIONS: (1)H-MRS is sensitive to detect metabolic changes caused by neurodegeneration processes during ALS and can be used for detection of UMN dysfunction. These MRS changes in the early stages of ALS are most prominent in motor cortex.

In vitro determination of biomechanical properties of human articular cartilage in osteoarthritis using multi-parametric MRI.

The objective of this study was to evaluate the correlations between MR parameters and the biomechanical properties of naturally degenerated human articular cartilage. Human cartilage explants from the femoral condyles of patients who underwent total knee replacement were evaluated on a micro-imaging system at 3T. To quantify glycosaminoglycan (GAG) content, delayed gadolinium-enhanced MRI of the cartilage (dGEMRIC) was used. T(2) maps were created by using multi-echo, multi-slice spin echo sequences with six echoes: 15, 30, 45, 60, 75, and 90 ms. Data for apparent diffusion constant (ADC) maps were obtained from pulsed gradient spin echo (PGSE) sequences with five b-values: 10.472, 220.0, 627.0, 452.8, 724.5, and 957.7. MR parameters were correlated with mechanical parameters (instantaneous (I) and equilibrium (Eq) modulus and relaxation time (tau)), and the OA stage of each cartilage specimen was determined by histological evaluation of hematoxylin-eosin stained slices. For some parameters, a high correlation was found: the correlation of T(1Gd) vs Eq (r=0.8095), T(1Gd) vs I/Eq (r=-0.8441) and T(1Gd) vs tau (r=0.8469). The correlation of T(2) and ADC with selected biomechanical parameters was not statistically significant. In conclusion, GAG content measured by dGEMRIC is highly related to the selected biomechanical properties of naturally degenerated articular cartilage. In contrast, T(2) and ADC were unable to estimate these properties. The results of the study imply that some MR parameters can non-invasively predict the biomechanical properties of degenerated articular cartilage.

Decrease of NAA with aging outside the seizure focus in mesial temporal lobe epilepsy--a proton-MRS study at 3 Tesla.

There is evidence that chronic pharmacoresistant temporal lobe epilepsy (TLE) is a progressive disorder accompanied by mental deterioration. We investigated effects of aging on cerebral N-acetyl-aspartate (NAA) concentrations in the temporal lobe of 12 patients with pharmacoresistant mesial TLE (mTLE) and 22 healthy controls by means of proton-magnetic resonance spectroscopy ((1)H-MRS) at 3 T. Furthermore, we calculated correlations between NAA concentrations and measures of verbal and figural memory in patients. In mTLE patients but not in healthy controls the concentration of NAA in the lateral temporal lobe was negatively correlated with age. In patients with mTLE NAA in left lateral temporal voxels correlated with verbal memory. NAA in medial temporal voxels did not correlate with age or neuropsychological measures. Significant decrease of NAA with age in the lateral temporal lobe of patients with mTLE provides evidence for progressive neuronal dysfunction with aging. NAA is a marker of neuronal integrity since it correlates with verbal memory.

1H magnetic resonance spectroscopy at 3 T in cryptogenic and mesial temporal lobe epilepsy.

The objectives of this work were to compare concentrations of N-acetylaspartate (NAA), glutamate (Glu), glutamine (Gln), Glx (=Glu + Gln), myo-inositol (mI), total creatine (Cre) and other metabolites in the temporal lobes of patients with mesial temporal lobe epilepsy (mTLE), cryptogenic TLE (cTLE), who show no abnormalities in high-resolution MRI, and healthy controls using single voxel (1)H MRS at 3 T. Twelve patients with mTLE, nine with cTLE and 22 controls were investigated using a short echo time STEAM protocol. Voxels were positioned bilaterally in the medial and lateral temporal lobes. Spectra were processed with LCModel. Significantly lower mean NAA were detected in mTLE patients (P < 0.001) and a trend towards lower NAA in cTLE patients compared to controls (P = 0.053). Glx was not different between groups. Estimates of Glu showed a different metabolic pattern in mTLE with elevated Glu in lateral compared with medial voxels on the ipsilateral side to seizure onset (P = 0.019). MI concentrations were significantly lower in cTLE (P < 0.001) and in mTLE patients (P = 0.005) compared with healthy controls. MI/Cre was significantly reduced in cTLE patients only (P = 0.004). The results confirm low NAA in mTLE and to a lesser extent in cTLE patients. MI and mI/Cre were identified as potential metabolic indicators of the epileptogenic area in cTLE.

Investigation of apparent diffusion constant as an indicator of early degenerative disease in articular cartilage.

PURPOSE: To investigate the apparent diffusion constant (ADC) as a prospective magnetic resonance imaging (MRI) marker of early degeneration in articular cartilage. MATERIALS AND METHODS: Early degenerative changes were studied using in vitro MRI on cartilage-bone specimens excised from human femoral condyles. The loss of proteoglycans developed in vivo due to a degenerative process was compared with a gadolinium diethylenetriamine pentaacetate anion (Gd-DTPA(2-)) enhanced decrease of T(1) relaxation times, and with an increase of ADCs and T(2) relaxation times. RESULTS: Contrast enhanced T(1) values decreased and the diffusion constants increased in cartilage regions with depleted proteoglycans. The relative changes in diffusion constants were smaller than those of Gd-DTPA(2-) enhanced T(1), and in some proteoglycan-depleted regions no changes in the diffusion constants were detected. T(2) relaxation times showed considerable spatial variability that did not correlate with proteoglycan concentration. CONCLUSION: In contrast to Gd-DTPA(2-) enhanced T(1), which reflects changes in chemical composition, diffusion constants may reflect structural degradation of the cartilage matrix.