Background Neurodegeneration due to cerebral folate transport deficiency is a rare autosomal recessive disorder caused by biallelic pathogenic variants in FOLR1 . Onset typically occurs in late infancy and is characterized by psychomotor regression, epilepsy, and a hypomyelinating leukodystrophy on magnetic resonance imaging. If left untreated, progressive neurodegeneration occurs. However, early treatment with folinic acid has been shown to stabilize or reverse neurological features. Approximately thirty patients have been described worldwide. Here, we report the first two cases with genetically proven cerebral folate transport deficiency from South-Eastern Europe, describe the effect of oral folinic acid therapy on clinical and neuroradiological features and review the literature. Results Two siblings presented in childhood with clinical and radiological findings consistent with a hypomyelinating leukodystrophy. Exome sequencing revealed a novel homozygous pathogenic variant in FOLR1 (c.465_466delinsTG; p.W156G), confirming the diagnosis of neurodegeneration due to cerebral folate transport deficiency. Folinic acid treatment was promptly initiated in both patients. The younger sibling was treated early in disease course at 2 years of age, and demonstrated complete recovery in clinical and MRI features. The older sibling, who was 8 years of age at the time of diagnosis and treatment, demonstrated partial but substantial improvements. Conclusion We present the first account in the literature that early treatment initiation with oral folinic acid alone can result in complete neurological recovery of both clinical and radiological abnormalities in neurodegeneration due to cerebral folate deficiency. Moreover, through the report of these patients along with review of the literature, we provide information about the natural history of the disease with comparison of treatment effects at different stages of disease progression. This report also reinforces the importance of universal access to genetic testing to ensure prompt diagnoses for treatable disorders.

Introduction We evaluated whether 12-week intake of molecular hydrogen (H2) in 5 overweight adults (3 women; age: 50.2 ±11.9 years, body mass index: 29.4 ±2.1 kg/m2) affects brain levels of the glutamate-glutamine-GABA cycle, critical amino acid neurotransmitters in the mechanism of neuronal activation during appetite regulation. Methods A 1.5-T single-voxel proton magnetic resonance spectroscopy was used to assess the tissue concentrations of relevant metabolites. Results The mean glutamate and glutamate-plus-glutamine levels at the posterior cingulate gyrus decreased significantly during the study; this was accompanied by a significant drop in GABA levels at left prefrontal white matter, and glutathione levels at anterior cingulate gyrus. No changes in the brain metabolites were found in the comparable group of overweight individuals (n = 4, 2 women; age: 41.0 ±13.9, BMI 26.8 ±1.3 kg/m2) followed-up in the past without this treatment. Conclusions We showed a possible hydrogen-driven upregulation of neurotransmitters involved in appetite stimulation leading to hunger suppression and weight loss. Further studies analyzing appetite-controlling metabolic pathways affected by H2 would require monitoring of additional biomarkers of satiation and satiety during different feeding regimens.

The aim of this randomized controlled trial was to analyze the effects of medium-term supplementation with hydrogen-rich water on brain metabolism, appetite-regulating hormones, body composition, and safety biomarkers in overweight adults. Twenty (n = 20, 10 females) apparently healthy adults with a body mass index >24.9 kg/m2 were assigned to receive 0.5 L per day of hydrogen-rich water (7.5 mg of hydrogen) or hydrogen-free water (tap water) for 12 weeks. Two-way analysis of variance with repeated measures revealed a significant difference between the two interventions in several body composition indices (P ≤ 0.05), with hydrogen-rich water superior to placebo to reduce waist circumference and mid-upper arm circumference by 1.31 cm (95% confidence interval, from –0.23 to 2.85) and 0.65 cm (95% confidence interval, from –0.10 to 1.40), respectively. Hydrogen-rich water outcompeted placebo to raise serum ghrelin levels, as the mean difference from the placebo group was 17.28 pmol/L (95% confidence interval, from 1.81 to 32.75) (P = 0.02). A non-significant strong positive trend (P = 0.10) was reported toward hydrogen-rich water being superior to placebo in augmenting total serum short-chain fatty acid levels, with a mean difference from the control group of 195.6 μmol/L (95% confidence interval, from –64.55 to 275.85). The mean fecal calprotectin levels were significantly reduced after hydrogen-rich water intervention for 19.7 μg/mg (95% confidence interval, from 0.31 to 39.09) (P = 0.03). Our findings advance hydrogen-rich water as a promising metabolic intervention in overweight adults, but further validation via multicentric longitudinal randomized controlled trials in metabolic and nutritional disorders is required.

The severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) caused a global pandemic and one group of patients has developed a severe form of COVID-19 pneumonia with an urgent need for hospitalization and intensive care unit (ICU) admission. The aim of our study was to evaluate the prognostic role of MDW, CRP, procalcitonin (PCT), and lactate in critically ill COVID-19 patients. The primary outcome of interest is the 28 day mortality of ICU patients with confirmed SARS-CoV-2 infection and sepsis (according to Sepsis 3 criteria with acute change in SOFA score ≥ 2 points). Patients were divided into two groups according to survival on the 28th day after admission to the ICU. Every group was divided into two subgroups (women and men). Nonparametric tests (Mann–Whitney) for variables age, PCT, lactate, and MDW were lower than alpha p < 0.05, so there was a significant difference between survived and deceased patients. The Chi-square test confirmed statistically significant higher values of MDW and lactate in the non-survivor group. We found a significant association between MDW, lactate, procalcitonin, and fatal outcome, higher values were reported in the deceased group.

Acute secondary progressive multiple sclerosis (SPMS) is characterized by escalating neurological disability, with limited disease-modifying therapeutic options. A 48-year-old woman with acute SPMS being treated with interferon beta-1a and oral corticosteroids presented as a clinical outpatient with no disease-modifying effects after treatment. A decision was made to treat her with a combination of guanidinoacetate and creatine for 21 days. She had made clinical progress at follow-up, with the intensity of fatigue dropping from severe to mild. Magnetic resonance spectroscopy revealed increased brain choline, creatine, N-acetylaspartate, and glutathione. Patients with SPMS may benefit from guanidinoacetate–creatine treatment in terms of patient- and clinician-reported outcomes; this requires additional study.

Background: Pretreatment differentiation between glioblastoma and metastasis is a frequently encountered dilemma in neurosurgical practice. Distinction is required for precise planning of resection or radiotherapy, and also for defining further diagnostic procedures. Morphology and spectroscopy imaging features are not specific and frequently overlap. This limitation of magnetic resonance imaging and magnetic resonance spectroscopy was the reason to initiate this study. The aim of the present study was to determine whether the dataset of diffusion tensor imaging metrics contains information which may be used for the distinction between primary and secondary intra-axial neoplasms. Methods: Two diffusion tensor imaging parameters were measured in 81 patients with an expansive, ring-enhancing, intra-axial lesion on standard magnetic resonance imaging (1.5 T system). All tumors were histologically verified glioblastoma or secondary deposit. For qualitative analysis, two regions of interest were defined: intratumoral and immediate peritumoral region (locations 1 and 2, respectively). Fractional anisotropy and mean difusivity values of both groups were compared. Additional test was performed to determine if there was a significant difference in mean values between two locations. Results: A statistically significant difference was found in fractional anisotropy values among two locations, with decreasing values in the direction of neoplastic infiltration, although such difference was not observed in fractional anisotropy values in the group with secondary tumors. Mean difusivity values did not appear helpful in differentiation between these two entities. In both groups there was no significant difference in mean difusivity values, neither in intratumoral nor in peritumoral location. Conclusion: The results of our study justify associating the diffusion tensor imaging technique to conventional morphologic magnetic resonance imaging as an additional diagnostic tool for the distinction between primary and secondary intra-axial lesions. Quantitative analysis of diffusion tensor imaging metric, in particular measurement of fractional anisotropy in peritumoral edema facilitates accurate diagnosis.

In this randomized controlled pilot trial, we investigated the effects of a 6-month intake of hydrogen-rich water (HRW) on several molecular and phenotypic biomarkers of aging in older adults aged 70 years and over. Forty older adults (20 women) were randomly allocated in a parallel-group design to receive 0.5 L per day of HRW (15 ppm of hydrogen) or control drink (0 ppm of hydrogen) during a 6-month intervention period. The biomarkers assessed at baseline and 6-month follow up were molecular markers in the blood (DNA and chromosomes, nutrient sensing, protein, and lipid metabolism, oxidative stress and mitochondria, cell senescence, inflammation), brain metabolism, cognitive functioning, physical function and body composition, resting blood pressure, facial skin features, sleep outcomes, and health-related quality of life. The mean age, weight, and height of study participants were 76.0 ± 5.6 years, 78.2 ± 16.1 kg, height 167.5 ± 11.5 cm, respectively. A significant treatment vs. time interaction was found for telomere length (P = 0.049), with the length increased after HRW intervention (from 0.99 ± 0.15 at baseline to 1.02 ± 0.26 at follow up) and decreased after drinking control water (from 0.92 ± 0.27 to 0.79 ± 0.15). A marker of DNA methylation (Tet methylcytosine dioxygenase 2, TET2) expression at 6-month follow-up increased in both groups, yet the degree of elevation was significantly higher in HRW (from 0.81 ± 0.52 at baseline to 1.62 ± 0.66 at follow up) comparing to the control water (from 1.13 ± 0.82 to 1.76 ± 0.87) (P = 0.040). A strong trend for treatment vs. time interaction was found for a degree of DNA methylation (P = 0.166), with the methylation increased in the HRW group (from 120.6 ± 39.8 ng at baseline to 126.6 ± 33.8 ng at follow up) and decreased after taking control water (from 133.6 ± 52.9 ng to 121.2 ± 38.4 ng). HRW was superior to control water to increase brain choline and NAA levels in the left frontal grey matter, brain creatine at the right parietal white matter, and brain NAA at the right parietal mesial grey matter (P < 0.05). No significant differences were found between interventions for other outcomes (P > 0.05), except for a significantly improved chair stand performance after HRW intervention compared to the control water (P = 0.01). Owing to pleiotropic mechanisms of hydrogen action, this simple biomedical gas could be recognized as a possible anti-aging agent that tackles several hallmarks of aging, including loss of function and telomere length shortening. The study was registered at ClinicalTrials.gov (NCT04430803).