Brain MRI Results Research Articles

Insights From Minnesota on Newborn Screening for Adrenoleukodystrophy: A 5-Year Update.

Our objectives are to report on the outcomes of adrenal insufficiency (AI) and cerebral ALD (cALD) in children diagnosed with X-linked adrenoleukodystrophy (ALD) identified by newborn screening (NBS) in Minnesota in the first 5 years following initiation of NBS in 02/2017. A retrospective chart review was conducted for children diagnosed with ALD via Minnesota NBS from 02/06/2017 through 02/06/2022. Data reviewed included newborn screening data, diagnostic very long chain fatty acid levels, ABCD1 molecular testing results, serial measurements of ACTH and cortisol, and serial brain MRI results. Thirty-two boys and 11 girls were molecularly and/or biochemically confirmed to have ALD. Of these 32 boys, six (2-7 years; median age:18 months) developed AI. Two boys developed cALD and underwent stem cell transplantation, one of whom also has been diagnosed with AI. All the pathogenic/likely pathogenic variants detected during the first 5 years had initial C26:0 lysophosphatidylcholine (C26:0 lysoPC) values over 0.3 μmol/L at the time of newborn screening. The addition of ALD to NBS in Minnesota has allowed for early detection of asymptomatic AI in six young patients and asymptomatic cALD in two patients. Data from our study shows a positive correlation between high newborn screening LysoPC levels and variant pathogenicity.

Fecal occult blood is associated with an increased risk of cerebral small vessel disease in elderly patients

Background and purposeStudies have shown that fecal occult blood is associated with an increased risk of ischemic stroke, but the relationship between fecal occult blood and cerebral small vessel disease (CSVD) remains largely unknown. This study aimed to identify predictors for CSVD, with fecal occult blood and its proxies as potential influencing factors in elderly patients. MethodPatients aged 65 years or older with various chronic diseases were enrolled. The presence of CSVD was evaluated by brain MRI results. Fecal occult blood was measured by fecal immunochemical test. Logistic regression analysis was used for the association between the presence of fecal occult blood and the risk of CSVD. ResultsLogistic regression analysis indicated that a prevalence of positive fecal occult blood was related to CSVD (Model 1, adjusted OR=1.63, 95% CI: 1.15–2.29, P=0.006). We subsequently grouped all subjects as positive fecal occult blood (259, 16.48%) and negative fecal occult blood (1313, 83.52%), and logistic regression analysis indicated that a prevalence of CSVD was related to positive fecal occult blood (Model 2, adjusted OR=1.50, 95% CI: 1.08–2.08, P=0.015). In addition, the ratios of lacunes (67.18% vs. 53.85%, P<0.001) and enlarged perivascular spaces (43.63% vs. 34.42%, P=0.005) were higher in patients with positive fecal occult blood than in controls. ConclusionsThe presence of fecal occult blood is probably related to the risk of CSVD in elderly patients and could be used as a screening tool for CSVD in elderly populations.

Investigation of patients with childhood epilepsy in single center: Comprehensive genetic testing experience.

Epilepsy is a common multifactorial neurological disease usually diagnosed during childhood. In this study, we present the contribution of consecutive genetic testing to the genetic diagnostic yield of childhood epilepsy. In 100 children (53 female, 47 male) with epilepsy, targeted sequencing (TS) and clinical exome sequencing (CES) were performed. All cases (n= 100) included in the study were epilepsy patients. In addition, we investigated the genetic diagnosis rates according to the associated co-occurring findings (including developmental delay/intellectual disability, brain malformations, macro-/microcephaly, and dysmorphic features). The overall diagnostic rate in this study was 33% (n= 33 patients). We identified 11 novel variants in WDR45, ARX, PCDH19, SCN1A, CACNA1A, LGI1, ASPM, MECP2, NF1, TSC2, and CDK13. Genetic diagnosis rates were as follows: cases with developmental delay/intellectual disability 38.7% (24/62) and without developmental delay/intellectual disability 23.6% (9/38); cases with brain malformations 46.8% (15/32) and without brain malformations 25% (16/64); cases with macro-/microcephaly 50% (6/12) and without macro-/microcephaly 28.4% (25/88); and cases with dysmorphic features 48.2% (14/29) and without dysmorphic features 23.9% (17/71). Genotype-phenotype correlation is even more important in diseases such as epilepsy, which include many genes and variants of these genes in etiopathogenesis. We presented the clinical findings of the cases carrying 11 novel variants in detail, including dysmorphic features, accompanying neurodevelopmental disorders, EEG results, and brain MRI results.

The clinical and predictive value of 18F-FDG PET/CT metabolic patterns in a clinical Chinese cohort with autoimmune encephalitis.

To investigate the diagnostic and predictive role of 18F-FDG PET/CT in patients with autoimmune encephalitis (AE) as a whole group. Thrty-five patients (20 females and 15 males) with AE were recruited. A voxel-to-voxel semi-quantitative analysis based on SPM12 was used to analyze 18F-FDG PET/CT imaging data compared to healthy controls. Further comparison was made in different prognostic groups categorized by modified Rankin Scale (mRS). In total, 24 patients (68.6%) were tested positive neuronal antibodies in serum and/or CSF. Psychiatric symptoms and seizure attacks were major clinical symptoms. In the acute stage, 13 patients (37.1%) demonstrated abnormal brain MRI results, while 33 (94.3%) presented abnormal metabolism patterns. 18F-FDG PET/CT was more sensitive than MRI (p < 0.05). Patients with AE mainly presented mixed metabolism patterns compared to the matched controls, demonstrating hypermetabolism mainly in the cerebellum, BG, MTL, brainstem, insula, middle frontal gyrus, and relatively hypometabolism in the frontal cortex, occipital cortex, temporal gyrus, right parietal gyrus, left cingulate gyrus (p < 0.05, FWE corrected). After a median follow-up of 26 months, the multivariable analysis identified a decreased level of consciousness as an independent risk factor associated with poor outcome of AE (HR = 3.591, p = 0.016). Meanwhile, decreased metabolism of right superior frontal gyrus along with increased metabolism of the middle and upper brainstem was more evident in patients with poor outcome (p < 0.001, uncorrected). 18F-FDG PET/CT was more sensitive than MRI to detect neuroimaging abnormalities of AE. A mixed metabolic pattern, characterized by large areas of cortical hypometabolism with focal hypermetabolism was a general metabolic pattern. Decreased metabolism of right superior frontal gyrus with increased metabolism of the middle and upper brainstem may predict poor long-term prognosis of AE.

Nailfold capillary measurements correlated to NOTCH3 R544C mutation in preclinical CADASIL patients

BackgroundCerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL) is a hereditary disease caused by NOTCH3 mutation. Nailfold capillaroscopy is a non-invasive technique typically used for rheumatic diseases. It has potential in other conditions linked to vascular pathology. However, capillaroscopy in CADASIL has not been explored. This study aims to investigate whether capillaroscopy measurements can correlate with brain vascular changes in preclinical CADASIL patients, specifically those with NOTCH3 mutation. MethodsThis study included 69 participants from the Taiwan Precision Medicine Initiative (TPMI) dataset who visited Taichung Veterans General Hospital from January to December 2022. All individuals underwent genetic studies, brain imaging and nailfold capillaroscopy. The Mann-Whitney U test was used to compare results of brain imaging between carriers and controls. It was also used to compare measurements in nailfold capillaroscopy within each group. Spearman Rank Correlation Analysis was used to explore the relationship between capillary measurements and brain MRI results. ResultsWhite matter hyperintensities (WMH) expression was positively correlated with capillary dimension and negatively correlated with density. Our results presented that R544C carriers exhibited a diffuse increase in WMH (p < 0.001) and a global reduction in gray matter volume but preserved in specific areas. The white matter lesion scores in all brain regions were higher in the mutation carriers than the controls. (p < 0.001). ConclusionThis research highlights the association of nailfold capillaroscopy findings with white matter lesions in preclinical CADASIL patients. Capillaroscopy guides an effective screening strategy in individuals with NOTCH3 mutations.

Long-term efficacy and safety of divozilimab during 2-year treatment of multiple sclerosis patients in randomized double-blind placebo-controlled clinical trial BCD-132-4/MIRANTIBUS

To evaluate the efficacy and safety of the anti-CD20 monoclonal antibody divozilimab (DIV) used as an intravenous infusion at a dose of 500 mg every 24 weeks during 100 weeks for the treatment of patients with multiple sclerosis (MS), including relapsing-remitting multiple sclerosis (RRMS) and secondary progressive MS (SPMS) with relapses. The multicenter, randomized, double-blind and double-masked phase III clinical trial (CT) BCD-132-4/MIRANTIBUS (NCT05385744) included 338 adult patients with MS distributed in a 1:1 ratio into two groups: DIV 500 mg and teriflunomide (TRF) 14 mg. After screening, subjects were included in the main CT period, which consisted of two cycles of therapy over 48 weeks, then entered an additional period from weeks 49 to 100, which included three cycles of therapy. The efficacy was assessed based on the results of brain MRI and registration of data on relapses. 308 subjects completed 5 therapy cycles according to the study protocol. An analysis of the effectiveness of DIV therapy over 2 years showed a persistent suppression of MRI and clinical activity of the disease in comparison with TRF, which was confirmed by all the studied MRI indicators (including CUA; total number of gadolinium-enhancing (GdE) lesions on T1-weighted scans ; number of new or enlarged lesions on T2-weighted scans; lesions volume change on T2-weighted scans; change in the volume of hypointense lesions on T1-weighted scans). The use of DIV was associated with a statistically significant decrease in ARR compared to TRF (p=0.0001). The ARR in the DIV group was 0.057, in the TRF group - 0.164 with 95% confidential interval for the frequency ratio [0.202; 0.593]. The incidence of GdE lesions on T1-weighted scans in the DIV group was significantly lower than in the TRF group. The average number of such lesions was 0.0±0.08 and 1.0±4.46 in the DIV and TRF groups, respectively (p<0.0001). Progression of EDSS was detected in 18 (10.7%) and 36 (21.3%) patients in the DIV and TRF groups, respectively (p=0.0075). The proportion of patients with relapses was 11.2% (n=19) in the DIV group and 23.1% (n=39) in the TRF group (p=0.0039). In the subpopulation of patients with SPMS, no cases of increase in EDSS were detected, and not a single case of exacerbation was recorded over 2 years of using DIV. Also, DIV has shown a favorable safety profile. Among the adverse reactions (AR), infusion reactions and laboratory abnormalities, such as a decrease in the number of leukocytes, neutrophils, and lymphocytes, were most often recorded. Identified AR were expected, had mild to moderate severity, and resolved without any negative consequences. The results of the BCD-132-4/MIRANTIBUS CT indicate a high sustained efficacy and safety of long-term use of DIV in comparison with TRF during 2 years of therapy.

Transient global amnesia as a clinical manifestation of unilateral hippocampal infarction. Case report

Transient global amnesia (TGA) is a rare symptom complex characterized by a brief episode of severe fixation, anterograde and retrograde amnesia. The prevalence of TGA increases with age. Risk factors for this disease include physical overexertion, severe emotional stress, exposure to cold or hot water, hypothermia and pain. The diagnosis of TGA is based on the Kaplan and Hodges–Warlow criteria, according to which TGA is characterized by: complete resolution of mnestic disturbances within 24 hours; absence of other neurological and cognitive impairments; absence of previous head trauma or seizures. In cases where the clinical picture of TGA does not meet the criteria for the disease, a differential diagnosis should be performed, especially with cases of ischemic stroke in the vertebrobasilar region and transient epileptic amnesia. If acute ischemia is confirmed by the brain MRI results, further comprehensive diagnostic investigation must be performed to determine the subtype of acute cerebrovascular accident with further appropriate secondary prevention of cardiovascular complications. If a non-cardioembolic stroke type is identified, antiplatelet therapy has a crucial role. The clinical case of a patient with a left-sided hippocampal infarction clinically manifested by a TGA is presented.

Analysis of Genetic and MRI Changes, Blood Markers, and Risk Factors in a Twin Pair Discordant of Progressive Supranuclear Palsy.

Background and Objectives: Progressive supranuclear palsy (PSP) is a neurodegenerative disease, a tauopathy, which results in a wide clinical spectrum of neurological symptoms. The diagnosis is mostly based on clinical signs and neuroimaging; however, possible biomarkers for screening have been under investigation, and the role of the gut microbiome is unknown. The aim of our study was to identify potential blood biomarkers and observe variations in the gut microbiome within a PSP discordant monozygotic twin pair. Materials and Methods: Anthropometric measurements, neuropsychological tests, and the neurological state were evaluated. Blood was collected for metabolic profiling and for the detection of neurodegenerative and vascular biomarkers. Both the gut microbiome and brain MRI results were thoroughly examined. Results: We found a relevant difference between alpha-synuclein levels and moderate difference in the levels of MMP-2, MB, Apo-A1, Apo-CIII, and Apo-H. With respect to the ratios, a small difference was observed for ApoA1/SAA and ApoB/ApoA1. Using a microbiome analysis, we also discovered a relative dysbiosis, and the MRI results revealed midbrain and frontoparietal cortical atrophy along with a reduction in overall brain volumes and an increase in white matter lesions in the affected twin. Conclusions: We observed significant differences between the unaffected and affected twins in some risk factors and blood biomarkers, along with disparities in the gut microbiome. Additionally, we detected abnormalities in brain MRI results and alterations in cognitive functions.

High sensitivity of asymmetric 18F-THK5351 PET abnormality in patients with corticobasal syndrome

Corticobasal syndrome (CBS) is characterized by symptoms related to the asymmetric involvement of the cerebral cortex and basal ganglia. However, early detection of asymmetric imaging abnormalities can be challenging. Previous studies reported asymmetric 18F-THK5351 PET abnormalities in CBS patients, but the sensitivity for detecting such abnormalities in larger patient samples, including early-stage cases, remains unclear. Patients clinically diagnosed with CBS were recruited. All patients displayed asymmetric symptoms in the cerebral cortex and basal ganglia. Asymmetric THK5351 PET abnormalities were determined through visual assessment. Brain MRI, perfusion SPECT, and dopamine transporter (DAT) SPECT results were retrospectively reviewed. The 15 patients had a median age of 72 years (59–86 years) and a disease duration of 2 years (0.5–7 years). Four patients met the probable and 11 met the possible CBS criteria according to Armstrong criteria at the time of PET examination. All patients, including early-stage cases, exhibited asymmetric tracer uptake contralateral to their symptom-dominant side in the cerebral cortex/subcortical white matter and striatum (100%). The sensitivity for detecting asymmetric imaging abnormalities contralateral to the symptom-dominant side was 86.7% for brain MRI, 81.8% for perfusion SPECT, and 90% for DAT SPECT. White matter volume reduction was observed in the subcortical region of the precentral gyrus with increased THK5351 uptake, occurring significantly more frequently than gray matter volume reduction. THK5351 PET may be a sensitive imaging technique for detecting asymmetric CBS pathologies, including those in early stages.

Intrauterine Blood Transfusion for Parvo B19-Induced Fetal Anemia: Neuroimaging Findings and Long-Term Neurological Outcomes

Introduction: We aimed to evaluate the neuroimaging findings and long-term neurodevelopmental outcomes of fetuses and children following intrauterine blood transfusion (IUT) for parvo B19 infection-induced anemia compared to those with RBC alloimmunization. Methods: We conducted a retrospective cohort study including women who underwent an IUT due to fetal anemia between 2006 and 2019 in a tertiary, university-affiliated medical center. The cohort was divided into two groups: a study group – fetuses affected by congenital parvo B19 infection; and a control group – fetuses affected by RBC alloimmunization. Retrospective data such as antenatal sonographic evaluations, fetal brain MRI results, and short-term fetal and neonatal outcomes were collected. All children underwent a neurodevelopmental evaluation after birth using a Vineland questionnaire. Primary outcome was defined as the presence or absence of neurodevelopmental delay. Secondary outcome was defined as the presence of abnormal fetal neuroimaging findings such as cerebellar hypoplasia, polymicrogyria, intracranial hemorrhage, or severe ventriculomegaly. Results: Overall, 71 fetuses requiring at least one IUT were included in the study. Of these, 18 were affected by parvo B19 infection and 53 by RBC alloimmunization with various associated antibodies. Fetuses in the parvo B19 group presented at an earlier gestational age (22.91 ± 3.36 weeks vs. 27.37 ± 4.67 weeks, p = 0.002) and were more affected by hydrops (93.33% vs. 16.98%, p < 0.001). Three fetuses out of the 18 (16.67%) fetuses in the parvo B19 group died in utero following the IUT. Abnormal neuroimaging findings were detected in 4/15 (26.7%) of the parvo B19 survivors versus 2/53 (3.8%) of fetuses affected by RBC alloimmunization (p = 0.005). There was no difference in long-term neurodevelopmental delay rates between the children in the study and control groups, as assessed at the average age of 3.65 and 6.53 years, accordingly. Conclusion: Fetal anemia due to parvo B19, treated with IUT, might be associated with increased rates of abnormal neurosonographic findings. The correlation between those findings and long-term adverse neurodevelopmental outcomes requires further investigation.

Efficiency of Nanoparticles (Micromage-B) in the Complex Treatment of Multiple Sclerosis

Multiple sclerosis (MS) is a serious neurological problem because of its high prevalence, chronic course, frequent disability, and propensity to affect young people. The immunopathogenesis hypothesis underlies the origin of MS. Selective sorption activity of biocompatible magnetite nanoparticles against surface proteins of cell membranes, circulating immune complexes, lymphocytotoxic antibodies, complement system, the effect of increasing phagocytic activity and leukocyte phagocytosis completion index allows the effective use of these nanodevices for immunocorrection. The main goal of the study is to slow down the progression of MS, improve the neurological status and general condition of the patient, and reduce the dynamics of the spread of demyelinating foci in the brain. Materials and methods: a patient diagnosed with multiple sclerosis, secondary progressive type of course, cerebro-spinal form, clinical aggravation stage; EDSS neurological status and disability assessment scales; contrast-enhanced MRI of the brain. An oral form of the nanodevice Micromage-B was used as an immunosorbent and immunomodulator. The choice of the regimen and dosage of Micromage-B was personalized. Assessment of the general condition and neurological status was performed every 7 days for 6 months. Contrast-enhanced MRI of the brain was performed at the 5th month of the study. As a result of using Micromage-B in MS treatment, objective improvement of neurological status, reduction of stiffness and rapid fatigability of the lower extremities were observed. Gait and coordination improved, hand tremors decreased, depression and signs of concentration disorders disappeared, appetite restored, and speech improved. During the entire period of Micromage-B application, positive dynamics in the normalization of the neurological status was observed. After 6 months of treatment, the total score dropped by 165 to 35. It was found that the maximum positive effect was observed in the evaluation of the pyramidal system and coordination. The EDSS Disability Scale score decreased from 6.0 to 5.0. Contrast-enhanced MRI brain examination for the first time showed a decrease in the number of new foci of demyelination in the brain by the 4th month of Micromage-B administration. The positive dynamics of normalization of the neurological status correlated with the results of brain MRI. The process of recovery of central nervous system activity in MS is not only due to the immunosuppressive properties of magnetite nanoparticles, but is probably caused by the activation of remyelination mechanisms and oligodendrocyte differentiation through enzymatic methylation. Considering the above, the use of biocompatible nanodevices in the complex treatment of MS is a promising direction. The scheme and method of using biocompatible magnetite nanoparticles to improve the effectiveness of MS treatment require further improvement and study.

Hybrid 18F-Fluoroethyltyrosine PET and MRI with Perfusion to Distinguish Disease Progression from Treatment-Related Change in Malignant Brain Tumors: The Quest to Beat the Toughest Cases.

Conventional MRI has important limitations when assessing for progression of disease (POD) versus treatment-related changes (TRC) in patients with malignant brain tumors. We describe the observed impact and pitfalls of implementing 18F-fluoroethyltyrosine (18F-FET) perfusion PET/MRI into routine clinical practice. Methods: Through expanded-access investigational new drug use of 18F-FET, hybrid 18F-FET perfusion PET/MRI was performed during clinical management of 80 patients with World Health Organization central nervous system grade 3 or 4 gliomas or brain metastases of 6 tissue origins for which the prior brain MRI results were ambiguous. The diagnostic performance with 18F-FET PET/MRI was dually evaluated within routine clinical service and for retrospective parametric evaluation. Various 18F-FET perfusion PET/MRI parameters were assessed, and patients were monitored for at least 6 mo to confirm the diagnosis using pathology, imaging, and clinical progress. Results: Hybrid 18F-FET perfusion PET/MRI had high overall accuracy (86%), sensitivity (86%), and specificity (87%) for difficult diagnostic cases for which conventional MRI accuracy was poor (66%). 18F-FET tumor-to-brain ratio static metrics were highly reliable for distinguishing POD from TRC (area under the curve, 0.90). Dynamic tumor-to-brain intercept was more accurate (85%) than SUV slope (73%) or time to peak (73%). Concordant PET/MRI findings were 89% accurate. When PET and MRI conflicted, 18F-FET PET was correct in 12 of 15 cases (80%), whereas MRI was correct in 3 of 15 cases (20%). Clinical management changed after 88% (36/41) of POD diagnoses, whereas management was maintained after 87% (34/39) of TRC diagnoses. Conclusion: Hybrid 18F-FET PET/MRI positively impacted the routine clinical care of challenging malignant brain tumor cases at a U.S. institution. The results add to a growing body of literature that 18F-FET PET complements MRI, even rescuing MRI when it fails.

Anatomical Variations of the Willis Circle: A Risk Factor for Brain Lesions in Sickle Cell Patients

<i>Background and objective</i>: The brain lesions observed in sickle cell patients are often known to be due to vessels occlusions. But other factors could be associated with the genesis of these lesions. The objective of this study was to assess the association between the presence of anatomical variations in the Willis circle and that of brain lesions found on MRI in sickle cell patients. <i>Methods</i>: We conducted a bicentric cross-sectional study with retrolective analysis of images at the medical imaging departments of the HUDERF in Brussels (Belgium) and the Yaoundé General Hospital (Cameroon), over a period of 12 months from November 2020 to October 2021. We included 187 homozygous sickle cell patients with documented electrophoresis and brain MRI results. The MRI were carried out in T1, T2, T2*, FLAIR, Diffusion and 3D TOF sequences on Siemens^® 1.5 Tesla devices. The collected data were analyzed using SPSS^® software version 20.0 for Windows^® with a significant p<0.05. <i>Results</i>: The mean age of patients was 8.76 years with no significant difference between the sexes. Variations in the Willis circle were present in 20 cases (10.70%) with a predominance in the posterior hemicircle (6.96% versus 3.74% for the anterior hemicircle; p=0.04). The most common variation was type G corresponding to hypoplasia or absence of the anterior communicating artery in the anterior hemicircle, and hypoplasia or unilateral absence of a posterior communicating artery in the posterior hemicircle. At the parenchymal level, brain lesions were found in 11 cases (5.88%) including ischemic lesions (3.21%) and leukopathies (1.07%). In general, the existence of these lesions was significantly associated with the presence of the Willis circle variations (p=0.01). <i>Conclusion and recommendation</i>: The presence of anatomical variations of the Willis arterial circle in sickle cell patients is associated with the existence of brain lesions. We therefore conclude that anatomical variations of the Willis circle could be an unknown factor increasing the risk of brain damages and therefore morbidity in these patients. We recommend that a larger sample study be conducted to verify our findings.

The Use of a Nanotechnological Drug (MICROMAGE-B) in the Complex Treatment of Multiple Sclerosis

Multiple sclerosis (MS) is a serious neurological problem because of its high prevalence, chronic course, frequent disability, and propensity to affect young people. The immunopathogenesis hypothesis underlies the origin of MS. Selective sorption activity of biocompatible magnetite nanoparticles against surface proteins of cell membranes, circulating immune complexes, lymphocytotoxic antibodies, complement system, the effect of increasing phagocytic activity and leukocyte phagocytosis completion index allows the effective use of these nanodevices for immunocorrection. The main goal of the study is to slow down the progression of MS, improve the neurological status and general condition of the patient, and reduce the dynamics of the spread of demyelinating foci in the brain. Materials and methods: a patient diagnosed with multiple sclerosis, secondary progressive type of course, cerebro-spinal form, clinical aggravation stage; EDSS neurological status and disability assessment scales; contrast-enhanced MRI of the brain. An oral form of the nanodevice Micromage-B was used as an immunosorbent and immunomodulator. The choice of the regimen and dosage of Micromage-B was personalized. Assessment of the general condition and neurological status was performed every 7 days for 6 months. Contrast-enhanced MRI of the brain was performed at the 5th month of the study. As a result of using Micromage-B in MS treatment, objective improvement of neurological status, reduction of stiffness and rapid fatigability of the lower extremities were observed. Gait and coordination improved, hand tremors decreased, depression and signs of concentration disorders disappeared, appetite restored, and speech improved. During the entire period of Micromage-B application, positive dynamics in the normalization of the neurological status was observed. After 6 months of treatment, the total score dropped by 165 to 35. It was found that the maximum positive effect was observed in the evaluation of the pyramidal system and coordination. The EDSS Disability Scale score decreased from 6.0 to 5.0. Contrast-enhanced MRI brain examination for the first time showed a decrease in the number of new foci of demyelination in the brain by the 4th month of Micromage-B administration. The positive dynamics of normalization of the neurological status correlated with the results of brain MRI. The process of recovery of central nervous system activity in MS is not only due to the immunosuppressive properties of magnetite nanoparticles, but is probably caused by the activation of remyelination mechanisms and oligodendrocyte differentiation through enzymatic methylation. Considering the above, the use of biocompatible nanodevices in the complex treatment of MS is a promising direction.

Brain MRI and Neuropsychological Findings at Long-Term Follow-Up After COVID-19 Hospitalisation: An Observational Cohort Study

<h3>Research Objectives</h3> To report findings on brain MRI and neurocognitive function, as well as persisting fatigue at long-term follow-up after COVID-19 hospitalisation in patients identified as high risk for affection of the central nervous system. <h3>Design</h3> Ambidirectional observational cohort study. <h3>Setting</h3> All patients (n=734) previously hospitalized with a laboratory-confirmed COVID-19 in a total regional population in Sweden during the period March 1st to May 31st 2020. <h3>Participants</h3> A subgroup (n=185) with persisting symptoms still interfering with daily life at a telephone follow-up 4 months after discharge were invited for a medical and neuropsychological evaluation. Thirty-five of those who were assessed with a neurocognitive test battery at the clinical visit, and presented a clinical picture concerning for COVID-19-related brain pathology, were further investigated by brain MRI. <h3>Interventions</h3> N/A. <h3>Main Outcome Measures</h3> Findings on brain MRI, neurocognitive test results and reported fatigue. <h3>Results</h3> Twenty-five patients (71%) had abnormalities on MRI; multiple white matter lesions were the most common finding. Six patients had had MRI performed in the acute phase during their hospitalisation, and all of these patients had additional white matter lesions at the follow-up MRI. Sixteen patients (46%) demonstrated impaired neurocognitive function, of which 10 (29%) had severe impairment. Twenty-six patients (74%) reported clinically significant fatigue. Patients with abnormalities on MRI had a lower Visuospatial Index (p=0.031) compared with the group with normal MRI findings. <h3>Conclusions</h3> A majority in this group of patients selected to undergo MRI after a clinical evaluation, showed signs of possible COVID-19 related brain affection detectable by brain MRI and/or neurocognitive test results. Even in a previously fairly healthy group of patients, COVID-19 might have a substantial negative impact on cognition in several domains, persisting several months post discharge. Abnormal findings were not restricted to patients with severe disease. Thus, for clinicians it is important to consider post-covid related changes when facing patients' reports of neuropsychological deficiency, regardless of severity of disease. <h3>Author(s) Disclosures</h3> The authors declare no competing interests.

Regression of deep left-sided hemiparesis after kinesitherapy in a patient with severe post-traumatic destruction of the right hemisphere: a clinical case

According to the results of brain MRI, it seemed that the motor deficit in the left limbs was irreversible due to the absence of brain tissue in the right hemisphere. This clinical case is indisputably unique and not standard and contains inexplicable changes that contradict the laws of anatomy and physiology and require further study. A young patient diagnosed with post-traumatic encephalopathy after suffering a severe open craniocerebral injury, subarachnoid hemorrhage, and intracerebral hematoma in the right hemisphere, complicated by purulent meningoencephalitis, developed severe sensorimotor aphasia, gaze paresis, left-sided plegia, hypesthesia, and hemianopsia. The patient was discharged from the hospital with a very poor prognosis. However, parents and close relatives continued to activate the patient with the help of passive and active kinesiotherapy. The result was unexpected for doctors, since the neurological sensory and motor deficit gradually partially regressed with the improvement of the cognitive brain functions. In our opinion, the regression of the neurological deficit in the absence of a morphological substrate and neurophysiological recovery in the affected hemisphere is due to the high plasticity of the brain, represented by compensatory activation and reorganization of the ipsilateral sensory and pyramidal tracts.

A case of retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations: Long‐term treatment with repeated courses of immunotherapy

AbstractWe present here the case of a 48‐year‐old man who first developed retinopathy, and motor deficit and aphasia occurred 8 years later. A tumor‐like lesion was seen by brain MRI. He was diagnosed with retinal vasculopathy with cerebral leukoencephalopathy and systemic manifestations (RVCL‐S) because a three prime repair exonuclease 1 (TREX1) gene abnormality was identified. After intravenous methylprednisolone pulse (IVMP) and intravenous immunoglobulin (IVIg) therapy, cerebrospinal fluid (CSF) test results and clinical manifestations improved. However, a new lesion appeared 3 years later. Immunotherapy became ineffective, and repeated relapses occurred. We evaluated the results of laboratory tests and brain MRI for 6 years after the first treatment. Coagulation tests, including measurements of vWF activity, remained high, so immunotherapy was thought to have a limited effect.

LGI1 antibody-associated encephalitis without evidence of inflammation in CSF and brain MRI.

This study aimed to explore the frequency and distinct characteristics of adult patients with LGI1 antibody-associated encephalitis in the absence of inflammatory abnormalities in both routine CSF analysis and brain MRI. We conducted a retrospective study of adult patients with antibodies targeting LGI1 and then screened patients with no evidence of inflammation in brain MRI and normal results in routine CSF analysis, including white blood cell count, protein concentration, IgG, and oligoclonal bands. Among 80 patients with LGI1 antibody-associated encephalitis in our center, 31 (38.8%) fulfilled the screening criteria. For these patients, the onset age was 57.0 ± 14.7years, and 19 (61.3%) were female. Viral prodrome occurred in 5 patients (16.1%). Faciobrachial dystonic seizures (FBDS) were the most predominant symptom (38.7%), followed by seizure onset (22.6%) and memory deficits (19.4%). The sensitivity of antibody detection in serum was higher than CSF (96.8% vs. 48.4%, p < 0.001). Most patients (30/31, 96.8%) benefited from the first-line immunotherapy, and 23 patients (74.2%) achieved complete recovery, yet 3 patients (9.7%) had clinical relapses in 2-year follow-up after discharge. The patients had a higher prevalence of females (61.9% vs. 26.7%, p = 0.003) and were more frequently associated with FBDS during the disease course (38.7% vs. 10.2%, p = 0.004). However, there was no difference in treatment outcomes and recurrence ratio between the two groups (p = 0.144 and p = 0.515). Moreover, we divided all 80 patients into four groups according to antibody titer levels in serum and CSF at the time of diagnosis, respectively. WBC and protein concentrations in CSF showed no difference among the four groups. The absence of evidence of inflammation in routine CSF analysis and brain MRI did not rule out anti-LGI1 associated encephalitis. FBDS and the subacute onset of cognitive dysfunction should push forward with autoantibody testing for patients even without inflammatory abnormalities. The routine inflammatory indicators in CSF seemed to be unrelated to antibody titer levels.

Effect of MIND diet intervention on cognitive performance and brain structure in healthy obese women: a randomized controlled trial

Previous studies suggested adherence to recently developed Mediterranean-DASH Intervention for Neurodegenerative Delay (MIND) associated with cognitive performance. This study aimed to examine the effect of MIND dietary pattern on cognitive performance features and changes in brain structure in healthy obese women. As a total of 50 obese women were assessed for eligibility, we randomly allocated 40 participants with mean BMI 32 ± 4.31 kg/m2 and mean age 48 ± 5.38 years to either calorie-restricted modified MIND diet or a calorie-restricted standard control diet. Change in cognitive performance was the primary outcome measured with a comprehensive neuropsychological test battery. We also performed voxel-based morphometry as a secondary outcome to quantify the differences in brain structure. All of the measurements were administered at baseline and 3 months follow-up. Thirty-seven participants (MIND group = 22 and control group = 15) completed the study. The results found in the MIND diet group working memory + 1.37 (95% CI 0.79, 1.95), verbal recognition memory + 4.85 (95% CI 3.30, 6.40), and attention + 3.75 (95% CI 2.43, 5.07) improved more compared with the control group (ps < 0.05). Results of brain MRI consist of an increase in surface area of the inferior frontal gyrus in the MIND diet group. Furthermore, the results showed a decrease in the cerebellum-white matter and cerebellum-cortex in two groups of study. Still, the effect in the MIND group was greater than the control group. The study findings declare for the first time that the MIND diet intervention can reverse the destructive effects of obesity on cognition and brain structure, which could be strengthened by a modest calorie restriction.Clinical trial registration ClinicalTrials.gov ID: NCT04383704 (First registration date: 05/05/2020).

Analysis on the MRI and BAEP Results of Neonatal Brain With Different Levels of Bilirubin.

BackgroundTo explore whether there is abnormality of neonatal brains' MRI and BAEP with different bilirubin levels, and to provide an objective basis for early diagnosis on the bilirubin induced subclinical damage on brains.MethodsTo retrospectively analyze the clinical data of 103 neonatal patients, to conduct routine brain MRI examination and BAEP testing, and to analyze BAEP and MRI image results of the neonatal patients, who were divided into three groups based on the levels of total serum bilirubin concentration (TSB): 16 cases in mild group (TSB: 0.0–229.0 ěmol/L), 49 cases in moderate group (TSB: 229.0–342.0 ěmol/L), and 38 cases in severe group (TSB ≥ 342.0 ěmol/L).ResultsWe found the following: A. Comparison of the bilirubin value of the different group: The bilirubin value of the mild group is 171.99 ± 33.50 ěmol/L, the moderate group is 293.98 ± 32.09 ěmol/L, and the severe group is 375.59 ± 34.25 ěmol/L. The comparison of bilirubin values of the three groups of neonates (p < 0.01) indicates the difference is statistically significant (p < 0.01). B. The weight value of the <2,500 g group is 2.04 ± 0.21 and the ≥2,500 g group is 3.39 ± 0.46; the weight comparison of the two groups indicates that the difference is statistically significant (p < 0.01). C. Comparison of the abnormal MRI of the different groups: The brain MRI result's abnormal ratio of the mild group is 31.25%, the moderate group is 16.33%, and the severe group is 21.05%, but the comparison of brain MRI results of the three neonates groups indicates that the difference is not statistically significant (p > 0.05). D. Comparison of abnormal MRI signal values of globus pallidus on T1WI in different groups: 1. The comparison of normal group signal values with that of mild group (p < 0.05), with that of moderate group, and with that of severe group (p < 0.01) indicates that the difference is statistically significant.ConclusionAt low level of bilirubin, central nervous system damage may also occur and can be detected as abnormality by MRI and BAEP. Meanwhile, MRI and BAEP can also provide early abnormal information for the judgment of central nervous system damage of the children with NHB who have no acute bilirubin encephalopathy (ABE) clinical features, and provide clues for early treatment and early intervention.