Intracranial yolk sac tumor in an adult patient: MRI, diffusion-weighted imaging and 1H MR spectroscopy features

Introduction. Yolk sac tumors represent only 5%-7% of intracranial germ cell tumors, which comprise about 1% of all primary brain tumors in adults. Literature data about nonspecific imaging characteristics of these tumors are scant. We presented magnetic resonance imaging findings with diffusion-weighted imaging and proton magnetic resonance spectroscopy of this rare type of tumor in an adult patient. Case report. A 55-year-old man with progressive left side weakness, headache, dizziness and ataxia, underwent preoperative magnetic resonance imaging, diffusion-weighted imaging and proton magnetic resonance spectroscopy. After surgical resection and histological analysis, the final diagnosis of yolk sac tumor was established. Retrospective imaging analysis were performed in order to determine imaging and biochemical parameters that could be useful in the diagnostic evaluation of this tumor type. Conclusion. Though the imaging features of yolk sac tumor are not specific, morphoanatomical and metabolic imaging could offer the information that provides new insights into this tumor that may facilitate further therapeutic decision process and potentially provides better information regarding the disease prognosis

Genetic risk factors in patients with Myasthenia gravis

Myasthenia gravis (MG) is a rare autoimmune disease mediated by antibodies against components of the neuromuscular junction, particularly the acetylcholine receptor (AChR). The prevalence of MG in Belgrade has been estimated at 189 cases per 1,000,000 inhabitants, which is among the highest prevalence reported to date. Genetic studies have mainly pointed to specific HLA alleles associated with MG. However, CTLA-4 and TNFRSF11A, playing a role in the immune response, have recently been associated with MG in genome-wide association studies. Since CTLA-4 and TNFRSF11A promote other autoimmune diseases, the main objective of this casecontrol study was to determine the association between these candidate genes and the risk for developing MG in Serbian population. Genotyping of rs231735 and rs231770 within the CTLA-4 gene and rs4263037 within TNFRSF11A in 447 AChR-MG patients and 447 individually sex- and age-matched controls revealed no association with MG (p=0.344, p=0.923 and p=0.557, respectively). However, when stratifying patients into those with early-onset (n=183) and late-onset MG (n=264), we found an association of minor rs231735 allele T with early-onset MG under the recessive genetic model (OR=0.548, 95% CI=0.339-0.888, p=0.014, p10e6 permutation=0.014). Haplotype analysis revealed that individuals with the GC haplotype rs231735-rs231770 had a higher risk for developing earlyonset MG (OR =1.360, p=0.027, p10e6 permutation =0.027). Considering the sufficient statistical power of the study (>90%) and the selection criteria for controls, our results suggest that the CTLA-4 may be associated with early-onset MG in Serbian population. Analysis of additional variants is needed to understand the association of CTLA-4 with MGBOOK OF ABSTRACTS: 8th CONGRESS OF SERBIAN NEUROSCIENCE SOCIETY with international participation 31 May – 2 June 2023. Belgrade, Serbi

Significance of magnetic resonance imaging in differential diagnosis of nontraumatic brachial plexopathy

Background/Aim. Nontraumatic brachial plexopathies may be caused by primary or secondary tumors, radiation or inflammation. The aim of this study was to present the significance of MRI in revealing the cause of nontraumatic brachial plexopathy. Methods. A two-year retrospective study included 22 patients with nontraumatic brachial plexopathy. In all the patients typical clinical findings were confirmed by upper limb neurophysiological studies. In all of them MRI of brachial plexus was performed by 1.5 T scanner in T1 and T1 FS sequence with and without contrast, as well as in T2 and T2 FS sequences. Results. Seven (32%) patients had brachial plexopathy with signs of inflammatory process, 5 (23%) patients had secondary tumors, in 4 (18%) patients multifocal motor neuropathy was established and in the same number (18%) of the patients postradiation fibrosis was found. Two patients (9%) had primary neurogenic tumors. Conclusion. According to the results of this study MRI is a method which may determine localization and cause of brachial plexopathy. MRI can detect focal nerve lesions when other methods fail to find them. Thus, MRI has a direct impact on further diagnostic and therapeutical procedures

Changes in thymopoiesis in myasthenia gravis

This study was undertaken to investigate T-cell maturation ill hyperplastic thymi of patients suffering from myasthenia gravis (MG). For this purpose, the expression of the major differentiational molecules (CD4, CD8, and CD3/TCRalphass) and that of the regulator. v and activation molecules oil thymocytes from MG patients and control subjects were estimated by flow cytometric analysis. In the MG patients the increase in relative proportion of immature (CD4-8- TCRalphass-) and the most mature (CD4+8- TCRalphass(high) and CD4-8- TCRhigh encompassing immunoregulatory NKT) thymocytes followed by a decrease in that of CD4+8+CD3 /TCRalphass- cells was found. Furthermore, in these patients the relative proportion of CD4+HLA-DR+ and CD4+71+ cells was increased, whereas that of CD4+25+ cells was slightly, but significantly, decreased (reflecting, most likely, decreased contribution of T reg cells bearing this phenotype). Moreover. in MG thymi the percentage of CD45RA+ cells was reduced indicating changes in the selection processes. In keeping with this finding the reduced thymocyte apoptotic index and percentage of cells bearing apoptosing (CD4-8- TCRalphass(low)) phenotype were detected. In conclusion, the study demonstrates substantial changes in intrathymic differentiation of T cells in hyperplastic MG thymi and suggests alterations in selection events providing an increased escape of potentially? autoreactive T-cell clones, on one side, and all altered maturation and/or selection of immunoregulatory cells (NKT and CD4+8-25+ T reg cells) keeping these cell clones under control, on the other side

The effect of benfothiamine in the therapy of diabetic polyneuropathy

Introduction. Diabetic polyneuropathy (DPN) is one of the most common diabetic complications, which can result in a significant functional impairment and reduction of the quality of life in affected individuals. It occurs due to alterations in different biochemical mechanisms which require the presence of thiamine, which is why this vitamin is used in the therapy of DPN. Due to the low bioavailability of the hydrosolubile forms of thiamine, its liposolubile preparations (benfotiamine) are preferentially used. Objective. The aim of this study was to determine the efficacy of benfotiamine in combination with vitamin B6 in the therapy of DPN. Methods. The study group comprised of 22 patients with DPN who were treated with the combination of benfotiamine and vitamin B6 during 45 days. The effect of the therapy was evaluated by the analysis of different clinical, laboratory and electrophysiological parameters before and after conducted treatment. Results. After the treatment period, a statistically highly significant reduction of pain (p<0.01) was noted with the reduction of pain score on visual analogue scale in 86.4% of patients. A significant reduction of subjective complaints was also noted, with decreased modified total symptom score in 95.5% of patients (p<0.01). The presence of alodynia was reported at the beginning of the study in 77.3%, and after the benfotiamine therapy only in 22.7% of patients, while hyperpathy was initially present in 90.9%, and after treatment in 31.8% of patients (p<0,01). Neurophysiological parameters of polyneuropathy also significantly improved, with the improvement of the compound muscle action potential amplitude in 68.2% (p<0.01) and motor conduction velocity of the peroneal nerve in 45.5% of patients (p<0.01). The improvement of the sensory nerve action potential amplitude (p<0.01) and sensory conduction velocity (p=0.05) of the sural nerve was found in 45.5% of patients. After the treatment period, there was a highly statistically significant lowering of the glycosylated haemoglobin (p<0.01), with improved findings in 63.6% of patients. After completed study treatment protocol 86.4% of patients rated their overall condition as improved. Conclusion. Our results showed that the conducted treatment resulted in significant subjective and objective improvement of the disease signs symptoms, which confirmed that benfotiamine was good starting choice for the treatment of diabetic polyneuropathy

Correlation of clinical and neurophysiological findings with health related quality of life in patients with diabetic polyneuropathy

Background/Aim. Diabetic polyneuropathy is defined as the presence of clinical or subclinical symptoms and/or signs of peripheral nerve damage in patients with diabetes mellitus in the absence of the other causes of peripheral neuropathy. The aim of this study was to assess healthrelated quality of life (HRQoL) in patients with diabetic polyneuropathy and its correlation with clinical and neurophysiological findings. Methods. This study comprised 60 patients with distal, symmetric, sensorimotor diabetic polyneuropathy and type 2 diabetes mellitus. For evaluation of clinical findings the following scales were used: Medical Research Council strenth score (MRC sum score), Inflammatory Neuropathy Cause and Treatment (INCAT) disability scale (arm disability and leg disability scales), INCAT sensory sum score, Hamilton depression and anxiety rating scales. Nerve conduction study (NCS) was performed on the motor part of the median and peroneal nerves, the sensory part of the median nerve and sural nerve. All the patients completed the Serbian version of the SF-36 questionnaire as a measure of HRQoL. Results. Our results showed mild to moderate QoL impairment in the patients with diabetic polyneuropathy with no difference in physical and mental composite scores (p > 0.05). The age of the patients, mean MRC sum score, arm disability scale score, leg disability scale score and mean INCAT sensory sum score correlated with scores in the SF-36 questionnaire (p < 0.01). The patients with higher scores of anxiety and depression had significantly worse health perception for all QoL domains, for both composite scores and for the total SF-36 score (p < 0.01). Both motor and sensory NCS parameters of the median nerve showed significant correlations with QoL scores (p < 0.05). Conclusion. Our results showed mild to moderate QoL impairment in the patients with diabetic polyneuropathy. HRQoL significantly correlated with the age of the patients, muscle strength, disability, sensory complaints, depressiveness and anxiety of the patients. Electrophysiological examination of median nerve significantly correlated with QoL in the patients with diabetic polyneuropathy. [Projekat Ministarstva nauke Republike Srbije, br. 175087 and 175083

Impairment of cardiac autonomic control in patients with amyotrophic lateral sclerosis

The aim of this study was to investigate autonomic cardiac control in patients with amyotrophic lateral sclerosis (ALS). Fifty-five patients with sporadic ALS (28 female and 27 male; average age 56.00 +/- 10.34 years) were compared to 30 healthy controls (17 female and 13 male; average age 42.87 +/- 11.91 years). Patients with previous history of cardiac disease, diabetes mellitus, and impaired respiratory function were excluded from the study. Cardiovascular autonomic tests according to Ewing, power spectrum analysis of RR variability (low- and high-frequency bands - LF and HF, LF/HF index), real-time beat-to-beat ECG signal monitoring with heart rate variability analysis and baroreflex function analysis were carried out in all patients. Time-domain parameters of heart rate variability (mean RR interval, SDNN, SDANN, SDNN index, rMSSD and pNN50%) were obtained from 24-h ECG monitoring. ALS patients had a significantly higher score of sympathetic (p lt 0.01) and parasympathetic (p lt 0.001) dysfunction, as well as of the overall score of autonomic dysfunction (p lt 0.001). LF/HF index was significantly increased; baroreflex sensitivity and time-domain parameters of heart rate variability were highly significantly decreased in ALS patients (p lt 0.001). Our results demonstrated impaired cardiac autonomic control in ALS with marked parasympathetic dysfunction and sympathetic predominance

Proton magnetic resonance spectroscopy and apparent diffusion coefficient in evaluation of solid brain lesions

Background/Aim. Advanced magnetic resonance techniques can provide insight in physiological changes within pathological canges and contribute to better distinquishing between different tumor types and their discrimination from non-neoplastic lesions. The aim of this study was to evaluate the role of proton magnetic resonance spectroscopy (1H-MRS) and apparent diffusion coefficients (ADC) in distinguishing intracranial glial tumors from tumor like nonneoplastic lesions, as well as for differentiating high- from low-grade gliomas. Methods. This retrospective study included 47 patients with solid brain lesions (25 nonneoplastic, 14 low-grade and 8 anaplastic glial tumors). In all patients 1H-MRS (at a TE of 135 ms and 30 ms) and diffusion- weighted imaging (DWI) were performed. The choline to creatine (Cho/Cr), choline to N-acetyl aspartate (Cho/NAA), N-acetyl aspartate to creatine (NAA/Cr) and myoinositol to creatine (mIn/Cr) ratios and the apparent diffusion coefficient (ADC) were determined. Results. The Cho/Cr ratio was significantly higher in glial tumors grade II than in non-neoplastic lesions (p = 0.008) and in glial tumors grade III than in non-neoplastic lesions (p = 0.001). The Cho/NAA ratio was significantly higher in glial tumors grade II than in non-neoplastic lesions (p = 0.037). ΔADC/ADC between glial tumors grade II and glial tumors grade III showed a statistical significance (p = 0.023). Conclusion. Our study showed that 1H-MRS and apparent diffusion coefficients can help in evaluation and differentiation of solid brain lesions

Inappropriately chelated iron in the cerebrospinal fluid of amyotrophic lateral sclerosis patients

ALS is characterized by oxidative damage in the brain and cerebrospinal fluid, which is exerted by pro-oxidative activity of iron. Such activity of iron can be drastically increased in the presence of inappropriate iron ligands that catalyze redox cycling of iron, thereby promoting hydroxyl radical generation. The aim of our study was to determine the relative level of inappropriate iron ligands in the cerebrospinal fluid of ALS patients. To determine the levels of inappropriate iron ligands and redox activity of iron in cerebrospinal fluid (10 samples from ALS patients and 10 controls), we applied electron paramagnetic resonance spectroscopy. We have shown that cerebrospinal fluid of ALS patients comprises twofold increased level of inappropriate iron ligands, proportionally increasing iron redox activity and hydroxyl radical production compared to controls. In conclusion, our results strongly support the pro-oxidative/detrimental role of inappropriately chelated iron in ALS pathophysiology. The identification of biomolecules that form such iron complexes and their therapeutic targeting may represent the future of ALS treatment.Ministry of Education and Science of the Republic of Serbia [175083, 173014