Gray Matter Involvement Research Articles

Subtypes and location of (juxta)cortical lesions relate to cognitive dysfunction in people with multiple sclerosis

Background: Cortical lesion subtypes’ occurrence and distribution across networks may shed light on cognitive impairment (CI) in multiple sclerosis (MS). Methods: In 332 people with MS, lesions were classified as intracortical, leukocortical or juxtacortical based on artificially generated double inversion-recovery images. Results: CI-related leukocortical lesion count increases were greatest within sensorimotor and cognitive networks (p < 0.001). Only intracortical lesion count could distinguish between cognitive groups (p = 0.024). Effect sizes were two- to four-fold larger than differences between MS phenotypes. Conclusion: In CI-MS, leukocortical lesions predominate, whereas intracortical lesions distinguish cognitive groups. Lesions’ grey matter (GM) involvement might be decisive for cognition in MS, surpassing overall disease burden.

DC-CRP: Deep Cerebral Venous Thrombosis, Clinicoradiological Profile, and Treatment Outcome in Indian Population-A Tertiary Care Experience.

Deep cerebral venous thrombosis (DCVT) is an uncommon cause of stroke with diverse predisposing factors, clinical presentations, imaging findings, and functional outcomes, which makes the diagnosis of DCVT even more challenging. Retrospective observational study (December 2018 to January 2023). Cases with imaging data suggestive of DCVT were included. The neuroradiological assessment was performed using multimodality imaging to determine the location of parenchymal changes and the number of deep veins involved in isolation or with the superficial dural venous system. Clinical variables were tabulated. Of the 206 cases with CVT in the study period, 27 had DCVT (13.1%), of which four (14.8%) had isolated DCVT (male-to-female ratio 13:14; mean age = 33.4 years). Hyperhomocysteinemia (n = 11) is the most common risk factor associated with it. The most common presentations were headaches (n = 27) and focal motor deficits (n = 13). Raised intracranial tension (ICT) was present in almost half of the study population (n = 14). Mean and median modified Rankins score (mRS) at the time of discharge were 2.0 and 1, respectively. The most common deep vein involved was the straight sinus (SS) (n = 25), followed by the internal cerebral vein (n = 23). The mean and median mRS after 3 months from discharge were 0.3 and 0, respectively. A knowledge of diverse clinical presentations in DCVT, its neurovascular anatomy, and imaging characteristics with prompt diagnosis and timely interventions can assist in attenuating the risk of acute complications and long-term sequelae. Extensive deep grey matter involvement in DCVT is associated with neurological manifestations like altered sensorium and motor deficits, with increased severity of illness as measured by the mRS score.

Clinical prognostication in acute necrotizing encephalopathy of childhood: the role of magnetic resonance imaging severity assessment.

Acute necrotizing encephalopathy of childhood is a unique entity with bilateral gray and white matter involvement. The aim of this study is to explore whether the severity of findings on imaging scans is indicative of the prognosis and clinical outcomes for pediatric patients with acute necrotizing encephalopathy. A retrospective cross-sectional study was conducted on 42 patients diagnosed with acute necrotizing encephalopathy. A severity score based on MR imaging was computed for each patient, utilizing a point system determined by the existence of factors such as hemorrhage, cavitation, enhancement, diffusion restriction, and lesion location. The scoring was categorized into mild, moderate, and severe. Clinical outcomes were determined at the time of discharge and at follow-ups as mild disability, moderate disability, severe disability, and death according to the modified Rankin Scale. Associations were determined by Fisher's exact test, chi-square test, and one-way ANOVA. The study included 21 boys and 21 girls with a mean age of 71.5months. A statistically significant connection (P=0.027) was found between the severity score from MR imaging and the clinical outcome. A statistically significant relationship was also observed between diffusion restriction (P=0.008), cerebellar involvement (P=0.048), and an unfavorable clinical outcome. Additionally, individuals who experienced shock exhibited a correlation with adverse outcomes (P=0.01). In predicting the outcome of acute necrotizing encephalopathy, cerebellar involvement and presence of diffusion restriction were associated with worse clinical outcomes in our study. Developing a comprehensive MR-based severity score is crucial for improving diagnostic accuracy and patient outcomes. Our findings underscore the importance of including diffusion restriction and cerebellar involvement in the scoring system.

MOG-antibody-associated transverse myelitis with the H-sign and unusual MRI enhancement: a case report and literature review.

Transverse myelitis is the second most common symptoms in myelin oligodendrocyte antibody-associated diseases (MOGAD), causing obvious clinical manifestation. T2-hyperintense lesions mainly restricted to the gray matter in the spinal cord on axial magnetic resonance imaging, produce the H-sign, which is thought to be the typical finding of MOGAD. Contrast enhancement can be observed in some cases of myelin oligodendrocyte antibody-associated transverse myelitis (MOG-TM). However, reports on the enhancement pattern associated with the H-sign are rarely seen. In this report, we describe a case of pediatric MOG-TM in which the H-sign was observed without enhancement, while the surrounding white matter exhibited enhancement. This pattern contradicts the previously observed gray matter involvement. Then we reviewed the literatures of myelin oligodendrocyte antibody-positive myelitis to focus on the neuroimaging features and discuss the implications of our finding.

Magnetic resonance imaging pattern recognition of metabolic and neurodegenerative encephalopathies in dogs and cats.

Metabolic/neurodegenerative encephalopathies encompass a wide list of conditions that share similar clinical and magnetic resonance imaging (MRI) characteristics, challenging the diagnostic process and resulting in numerous tests performed in order to reach a definitive diagnosis. The aims of this multicentric, retrospective and descriptive study are: (I) to describe the MRI features of dogs and cats with metabolic/neurodegenerative encephalopathies; (II) to attempt an MRI recognition pattern classifying these conditions according to the involvement of grey matter, white matter or both; and (III) to correlate the MRI findings with previous literature. A total of 100 cases were recruited, comprising 81 dogs and 19 cats. These included hepatic encephalopathy (20 dogs and three cats), myelinolysis (five dogs), intoxications (seven dogs and one cat), thiamine deficiency (two dogs and seven cats), hypertensive encephalopathy (three dogs and two cats), neuronal ceroid lipofuscinosis (11 dogs and one cat), gangliosidosis (three dogs and two cats), fucosidosis (one dog), L-2-hydroxyglutaric aciduria (13 dogs and one cat), Lafora disease (11 dogs), spongiform leukoencephalomyelopathy (one dog) and cerebellar cortical degeneration (four dogs and two cats). None of the hepatic encephalopathies showed the previously described T1-weighted hyperintensity of the lentiform nuclei. Instead, there was involvement of the cerebellar nuclei (8/23), which is a feature not previously described. Dogs with myelinolysis showed novel involvement of a specific white matter structure, the superior longitudinal fasciculus (5/5). Thiamine deficiency affected numerous deep grey nuclei with novel involvement of the oculomotor nuclei (3/9), thalamic nuclei, subthalamus and cerebellar nuclei (1/9). Cats with hypertensive encephalopathy had a more extensive distribution of the white matter changes when compared to dogs, extending from the parietal and occipital lobes into the frontal lobes with associated mass effect and increased brain volume. Lysosomal storage disease showed white matter involvement only, with neuronal ceroid lipofuscinosis characterised by severe brain atrophy when compared to gangliosidosis and fucosidosis. All patients with L-2-hydroxyglutaric aciduria had a characteristic T2-weighted hyperintense swelling of the cerebral and cerebellar cortical grey matter, resulting in increased brain volume. Lafora disease cases showed either normal brain morphology (5/11) or mild brain atrophy (6/11). Dogs with cerebellar cortical degeneration had more marked cerebellar atrophy when compared to cats. This study shows the important role of MRI in distinguishing different metabolic/neurodegenerative encephalopathies according to specific imaging characteristics.

Increased prevalence of vertebrobasilar dolichoectasia in Parkinson's disease and its effect on white matter microstructure and network.

This study aimed to investigate the prevalence of vertebrobasilar dolichoectasia (VBD) in Parkinson's disease (PD) patients and analyze its role in gray matter changes, white matter (WM) microstructure and network alterations in PD. This is a cross-sectional study including 341 PD patients. Prevalence of VBD in these PD patients was compared with general population. Diffusion tensor imaging and T1-weighted imaging analysis were performed among 174 PD patients with or without VBD. Voxel-based morphometry analysis was used to estimate gray matter volume changes. Tract-based spatial statistics and region of interest-based analysis were used to evaluate WM microstructure changes. WM network analysis was also performed. Significantly higher prevalence of VBD in PD patients was identified compared with general population. Lower fractional anisotropy and higher diffusivity, without significant gray matter involvement, were found in PD patients with VBD in widespread areas. Decreased global and local efficiency, increased hierarchy, decreased degree centrality at left Rolandic operculum, increased betweenness centrality at left postcentral gyrus and decreased average connectivity strength between and within several modules were identified in PD patients with VBD. VBD is more prevalent in PD patients than general population. Widespread impairments in WM microstructure and WM network involving various motor and nonmotor PD symptom-related areas are more prominent in PD patients with VBD compared with PD patients without VBD.

Dual Inversion Recovery Magnetic Resonance Imaging's Diagnostic Value for Estimating the Overall Load of Multiple Sclerosis Lesions and its Anatomical Distribution

B Background: In young adults, multiple sclerosis is a prevalent chronic inflammatory demyelinating condition. It is characterized by white matter affection, but many individuals also have significant gray matter involvement. A double inversion recovery pulse pattern was recently proposed to improve the detectability of multiple sclerosis lesions. Objectives: To evaluate the diagnostic value of double inversion recovery sequence in the detection of cortical and white matter multiple sclerosis plaques in different brain anatomical locations. Subjects and methods: A total of 37 patients with an established diagnosis of multiple sclerosis were included in this cross-sectional study. Brain MRI was done using double inversion recovery, T2 and FLAIR sequences. The number of lesions was counted and compared in the three sequences. Results: Dual Inversion Recovery sequence was highly significant and superior to both T2 and FLAIR sequences (P &lt; 0.001) in depicting the lesions regardless of anatomical distribution. Dual Inversion Recovery was significantly superior to T2 (P =&lt;0.001) and FLAIR (P =&lt;0.001) in detecting lesions in cortical and juxtacortical. However, Dual Inversion Recovery shows less periventricular and deep white matter lesions in comparison to T2 and FLAIR sequences. Conclusion: The Dual Inversion Recovery sequence detected more multiple sclerosis lesions in cortical, subcortical and infratentorial than the traditional T2W and FLAIR sequences. It also demonstrated greater delineation between the white matter, grey matter, and multiple sclerosis lesions, which became more easily visualized.

Influence of Infarct Morphology and Patterns on Cognitive Outcomes After Endovascular Thrombectomy.

To assess the association of qualitative and quantitative infarct characteristics and 3 cognitive outcome tests, namely the Montreal Cognitive Assessment (MOCA) for mild cognitive impairment, the Boston Naming Test for visual confrontation naming, and the Sunnybrook Neglect Assessment Procedure for neglect, in large vessel occlusion stroke. Secondary observational cohort study using data from the randomized-controlled ESCAPE-NA1 trial (Safety and Efficacy of Nerinetide in Subjects Undergoing Endovascular Thrombectomy for Stroke), in which patients with large vessel occlusion undergoing endovascular treatment were randomized to receive either intravenous Nerinetide or placebo. MOCA, Sunnybrook Neglect Assessment Procedure, and 15-item Boston Naming Test were obtained at 90 days. Total infarct volume, gray matter, and white matter infarct volumes were manually measured on 24-hour follow-up imaging. Infarcts were also visually classified as either involving the gray matter only or both the gray and white matter and scattered versus territorial. Associations of infarct variables and cognitive outcomes were analyzed using multivariable ordinal or binary logistic regression models. Of 1105 patients enrolled in ESCAPE-NA1, 1026 patients with visible infarcts on 24-hour follow-up imaging were included. MOCA and Sunnybrook Neglect Assessment Procedure were available for 706 (68.8%) patients and the 15-item Boston Naming Test was available for 682 (66.5%) patients. Total infarct volume was associated with worse MOCA scores (adjusted common odds ratio per 10 mL increase, 1.05 [95% CI, 1.04-1.06]). After adjusting for baseline variables and total infarct volume, mixed gray and white matter involvement (versus gray matter-only adjusted common odds ratio, 1.92 [95% CI, 1.37-2.69]), white matter infarct volume (adjusted common odds ratio per 10 mL increase 1.36 [95% CI, 1.18-1.58]) and territorial (versus scattered) infarct pattern (adjusted common odds ratio, 1.65 [95% CI, 1.15-2.38]) were associated with worse MOCA scores. Results for Sunnybrook Neglect Assessment Procedure and 15-item Boston Naming Test were similar, except for the territorial infarct pattern, which did not reach statistical significance in multivariable analysis. Besides total infarct volume, infarcts that involve the white matter and that show a territorial distribution were associated with worse cognitive outcomes, even after adjusting for total infarct volume.

Development of statistical auto-segmentation method for diffusion restriction gray matter lesions in patients with newly diagnosed sporadic Creutzfeldt–Jakob disease

Quantification of diffusion restriction lesions in sporadic Creutzfeldt-Jakob disease (sCJD) may provide information of the disease burden. We aim to develop an automatic segmentation model for sCJD and to evaluate the volume of disease extent as a prognostic marker for overall survival. Fifty-six patients (mean age ± SD, 61.2 ± 9.9 years) were included from February 2000 to July 2020. A threshold-based segmentation was used to obtain abnormal signal intensity masks. Segmented volumes were compared with the visual grade. The Dice similarity coefficient was calculated to measure the similarity between the automatic vs. manual segmentation. Cox proportional hazards regression analysis was performed to evaluate the volume of disease extent as a prognostic marker. The automatic segmentation showed good correlation with the visual grading. The cortical lesion volumes significantly increased as the visual grade aggravated (extensive: 112.9 ± 73.2; moderate: 45.4 ± 30.4; minimal involvement: 29.6 ± 18.1 mm3) (P < 0.001). The deep gray matter lesion volumes were significantly higher for positive than for negative involvement of the deep gray matter (5.6 ± 4.6 mm3 vs. 1.0 ± 1.3 mm3, P < 0.001). The mean Dice similarity coefficients were 0.90 and 0.94 for cortical and deep gray matter lesions, respectively. However, the volume of disease extent was not associated with worse overall survival (cortical extent: P = 0.07; deep gray matter extent: P = 0.12).

A comprehensive study of mutation and phenotypic heterogeneity of childhood mitochondrial leukodystrophies

ObjectiveMitochondrial leukodystrophies (MLs) are mainly caused by impairments of the mitochondrial respiratory chains. This study reports the mutation and phenotypic spectrum of a cohort of 41 pediatric patients from 39 distinct families with MLs among 320 patients with a molecular diagnosis of leukodystrophies. MethodsThis study summarizes the clinical, imaging, and molecular data of these patients for five years. ResultsThe three most common symptoms were neurologic regression (58.5%), pyramidal signs (58.5%), and extrapyramidal signs (43.9%). Because nuclear DNA mutations are responsible for a high percentage of pediatric MLs, whole exome sequencing was performed on all patients. In total, 39 homozygous variants were detected. Additionally, two previously reported mtDNA variants were identified with different levels of heteroplasmy in two patients. Among 41 mutant alleles, 33 (80.4%) were missense, 4 (9.8%) were frameshift (including 3 deletions and one duplication), and 4 (9.8%) were splicing mutations. Oxidative phosphorylation in 27 cases (65.8%) and mtDNA maintenance pathways in 8 patients (19.5%) were the most commonly affected mitochondrial pathways. In total, 5 novel variants in PDSS1, NDUFB9, FXBL4, SURF1, and NDUSF1 were also detected. In silico analyses showed how each novel variant may contribute to ML pathogenesis. ConclusionsThe findings of this study suggest whole-exome sequencing as a strong diagnostic genetic tool to identify the causative variants in pediatric MLs. In comparison between oxidative phosphorylation (OXPHOS) and mtDNA maintenance groups, brain stem and periaqueductal gray matter (PAGM) involvement were more commonly seen in OXPHOS group (P value of 0.002 and 0.009, respectively), and thinning of corpus callosum was observed more frequently in mtDNA maintenance group (P value of 0.042).

Detection of Multiple Sclerosis Lesions in Supra- and Infra-Tentorial Anatomical Regions by Double Inversion Recovery, Flair, and T2 MRI Sequences: A Comparative Study in Iraqi Patients

Background: In young adults, multiple sclerosis is a prevalent chronic inflammatory demyelinating condition. It is characterized by white matter affection, but many individuals also have significant gray matter involvement. A double-inversion recovery pulse (DIR) pattern was recently proposed to improve the visibility of multiple sclerosis lesions. Objective: To find out how well a DIR sequence, FLAIR, and T2-weighted pulse sequences can find MS lesions in the supratentorial and infratentorial regions. Methods: A total of 37 patients with established diagnoses of multiple sclerosis were included in this cross-sectional study. Brain MRI was done using double inversion recovery, T2, and FLAIR sequences. The number of lesions was counted and compared in the three sequences. Results: The DIR sequence detected more infratentorial lesions when compared to the T2 and FLAIR sequences. In the supratentorial region, DIR detected more lesions than T2 and FLAIR. Conclusion: The DIR sequence is highly superior to both the T2 and FLAIR sequences in depicting the lesions, regardless of their anatomical distribution. Moreover, the DIR sequence detected more multiple sclerosis lesions in the infratentorial region than the traditional T2W and FLAIR sequences.

Sjogren-Larsson syndrome brain volumetric reductions demonstrated with an automated software.

Sjogren-Larsson syndrome (SLS) is a neurocutaneous disease with an autosomal recessive inheritance, caused by mutations in the gene that encodes fatty aldehyde dehydrogenase (ALDH3A2), clinically characterized by ichthyosis, spastic diplegia, and cognitive impairment. Brain imaging plays an essential role in the diagnosis, demonstrating a nonspecific leukoencephalopathy. Data regarding brain atrophy and grey matter involvement is scarce and discordant. We performed a volumetric analysis of the brain of two siblings with SLS with the aim of detecting deep grey matter nuclei, cerebellar grey matter, and brainstem volume reduction in these patients. Volume data obtained from the brain magnetic resonance imaging (MRI) of the two patients using an automated segmentation software (Freesurfer) was compared with the volumes of a healthy control group. Statistically significant volume reduction was found in the cerebellum cortex, the brainstem, the thalamus, and the pallidum nuclei. Volume reduction in grey matter leads to the hypothesis that SLS is not a pure leukoencephalopathy. Grey matter structures affected in the present study suggest a dysfunction more prominent in the thalamic motor pathways.

Evaluation of the correlation between thalamic area and cognitive functions in patients with early-stage relapsing-remitting multiple sclerosis

Background: The aim of this study is to investigate the presence of cognitive dysfunction and deep gray matter involvement in the early-stages of Relapsing-Remitting Multiple Sclerosis(RRMS) disease and examine the relationship between them.&#x0D; Materials and Methods: Thirty-four patients and 23 healthy individuals were included in the study. Patients diagnosed with RRMS according to the Revised 2010 and 2017 McDonald criteria, aged between 18-50, were enrolled in the study. The control group consisted of 23 healthy individuals with normal neurological examination, cranial magnetic resonance imaging(MRI), and cognitive functions. All participants underwent a neuropsychological test battery that covers memory, executive functions, language, and visuospatial domains, and the results of these tests were compared among the study groups. The data on MRI parameters, including the areas of the thalamus and corpus callosum as well as the width of the third ventricle, were compared among the study groups. Finally, the relationship between neuropsychological test results and MRI parameters was investigated in patients with early-stage RRMS.&#x0D; Results: The mean duration of the disease for MS patients was 3.53 years, and their median EDSS score was 2. It was observed that memory, executive functions, and fine motor skills were affected in early-stage RRMS patients. This impairment correlated with a decrease in the thalamus and corpus callosum areas and an increase in the third ventricle width.&#x0D; Conclusion: The MRI parameters defined as biomarkers for potential cognitive impairments in RRMS have critical importance in predicting the prognosis of the disease and taking early measures against future cognitive dysfunction.

Presymptomatic grey matter alterations in ALS kindreds: a computational neuroimaging study of asymptomatic C9orf72 and SOD1 mutation carriers

BackgroundThe characterisation of presymptomatic disease-burden patterns in asymptomatic mutation carriers has a dual academic and clinical relevance. The understanding of disease propagation mechanisms is of considerable conceptual interests, and defining the optimal time of pharmacological intervention is essential for improved clinical trial outcomes.MethodsIn a prospective, multimodal neuroimaging study, 22 asymptomatic C9orf72 GGGGCC hexanucleotide repeat carriers, 13 asymptomatic subjects with SOD1, and 54 “gene-negative” ALS kindreds were enrolled. Cortical and subcortical grey matter alterations were systematically appraised using volumetric, morphometric, vertex, and cortical thickness analyses. Using a Bayesian approach, the thalamus and amygdala were further parcellated into specific nuclei and the hippocampus was segmented into anatomically defined subfields.ResultsAsymptomatic GGGGCC hexanucleotide repeat carriers in C9orf72 exhibited early subcortical changes with the preferential involvement of the pulvinar and mediodorsal regions of the thalamus, as well as the lateral aspect of the hippocampus. Volumetric approaches, morphometric methods, and vertex analyses were anatomically consistent in capturing focal subcortical changes in asymptomatic C9orf72 hexanucleotide repeat expansion carriers. SOD1 mutation carriers did not exhibit significant subcortical grey matter alterations. In our study, none of the two asymptomatic cohorts exhibited cortical grey matter alterations on either cortical thickness or morphometric analyses.DiscussionThe presymptomatic radiological signature of C9orf72 is associated with selective thalamic and focal hippocampal degeneration which may be readily detectable before cortical grey matter changes ensue. Our findings confirm selective subcortical grey matter involvement early in the course of C9orf72-associated neurodegeneration.

Longitudinal Changes of Functional Connectivity Dynamism Are Relevant for Disability Worsening in Multiple Sclerosis: A 2.5-Year Study (P10-3.018)

<h3>Objective:</h3> To investigate changes in time-varying functional connectivity (TVFC) over 2.5 years of follow-up in multiple sclerosis (MS) patients and their association with disability progression. <h3>Background:</h3> In MS patients, TVFC analysis showed abnormalities of the main functional networks, correlated with more severe clinical and cognitive disability. Preliminary evidence showed that MS-related cognitive decline was associated with progressive TVFC destabilization. However, the clinical relevance of longitudinal TVFC changes has not been investigated yet. <h3>Design/Methods:</h3> 3T-MRI scans and clinical evaluations were obtained at baseline and at median follow-up of 2.5 years from 129 right-handed MS patients (103 relapsing-remitting [RR] and 26 progressive [P]) and 28 matched healthy controls (HC). At 2.5-year follow-up, patients were classified as clinically stable/worsened according to their disability change. TVFC was quantified at voxel-wise level as the coefficient of variation (CoV) across sliding-windows of degree centrality. <h3>Results:</h3> At follow-up, 25/129 (19.3%) MS patients worsened clinically. At baseline, MS patients showed reduced TVFC <i>vs</i> HC in the bilateral orbitofrontal cortex (p&lt;0.05, family-wise error corrected), left cerebellum, right precuneus and left thalamus. At 2.5-year follow-up, a widespread reduction of TVFC over time (p&lt;0.05, family-wise error corrected) was found in MS patients in temporal, parietal, occipital and frontal lobes, as well as in the cerebellum. Such a pattern of TVFC reduction was also found when looking at clinically stable MS patients. Clinically worsened MS presented peculiar TVFC reductions in areas of the default-mode network and basal ganglia. Reduced TVFC in the left putamen in clinically worsened <i>vs</i> stable MS patients was significant at time <i>x</i> group interaction analysis. <h3>Conclusions:</h3> After 2.5 years of follow-up, MS patients showed widespread TVFC reduction in cortical lobes and cerebellum. A peculiar involvement of deep grey matter was found in clinically worsened MS patients. Accrual of TVFC abnormalities in deep grey matter regions may represent a biological substrate of disability worsening. <b>Disclosure:</b> Dr. D’Amore has nothing to disclose. Paola Valsasina has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for ACCMED. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bristol Myers Squibb . Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Sanofi Genzyme. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Novartis. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Roche. Mr. Preziosa has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Merck. Monica Margoni has received research support from MAGNIMS. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving on a Speakers Bureau for Bayer, Biogen Idec, Merck-Serono, Novartis, Roche, Sanofi Genzyme, Takeda, and Teva Pharmaceutical Industries. Dr. Filippi has received personal compensation in the range of $5,000-$9,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Springer Nature. The institution of Dr. Filippi has received research support from Biogen Idec, Merck-Serono, Novartis, Roche, Teva Pharmaceutical Industries, Italian Ministry of Health, Fondazione Italiana Sclerosi Multipla, and ARiSLA (Fondazione Italiana di Ricerca per la SLA). Maria Assunta Rocca has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Bayer, Biogen, Bristol Myers Squibb, Celgene, Genzyme, Merck Serono, Novartis, Roche, and Teva. The institution of Maria Assunta Rocca has received research support from Italian Ministry of Health, MS Society of Canada and Fondazione Italiana Sclerosi Multipla.

Myelitis and Myelopathies in the Era of COVID-19 (P4-10.003)

<h3>Objective:</h3> To characterize the clinical presentations of myelitis and myelopathies following SARS-CoV2 infection (COVID-19) or vaccination for COVID-19. <h3>Background:</h3> Neurologic complications of COVID-19 are well-described; however, myelopathies associated with COVID-19 are comparatively rarer events. Myelopathies associated with vaccination are even rarer than those seen with infection. There is a need to recognize and document these rare cases as the number of infections and vaccinations increase to refine diagnosis and treatment. <h3>Design/Methods:</h3> We reviewed the clinical profiles of 15 patients referred to the Johns Hopkins Myelitis &amp; Myelopathy Center between April 2020 and June 2022 for myelopathic syndromes suspected to be triggered by SARS-CoV-2 infection or COVID-19 vaccination. Each patient’s etiology was classified as vascular, inflammatory, unmasking of neurological disease, or unknown. <h3>Results:</h3> All vascular myelopathies (n=5) were associated with COVID-19 and presented as acute and subacute progressive bladder dysfunction and weakness with non-enhancing lesions on MRI. Inflammatory myelopathies were associated with vaccination (n=3) and COVID-19 (n=2) and were notable for CSF pleocytosis, elevated protein, and involvement of white matter tracts and grey matter on MRI. COVID-19 and vaccination were associated with unmasking underlying myelopathic disease (e.g., demyelinating or metabolic) in 4 patients. Among the vaccination group (n=5), 2 received one dose of the mRNA-1273 vaccine and 3 received one dose of the Ad26.COV2.S vaccine. One patient could not be classified. <h3>Conclusions:</h3> Initial imaging in vascular patients had subtle findings recognized in hindsight–early recognition on imaging could refine differential diagnosis. Patients with inflammatory etiologies generally only saw improvement in their symptoms after PLEX; early initiation can halt progression and improve outcomes. Among the unmasked group, patients had heterogeneous clinical presentations. Imaging in this group showed chronic lesions, unlike the other two groups. It is critical to identify the etiological factors in subjects with myelopathies in the setting of COVID-19 or vaccination to establish an appropriate treatment. <b>Disclosure:</b> Ms. Hao has nothing to disclose. Dr. Dominguez Penuela has nothing to disclose. Dr. Reyes-Mantilla has nothing to disclose. The institution of Dr. Barreras has received research support from Foundation for Sarcoidosis Research. The institution of Dr. Pardo-Villamizar has received research support from National Institutes of Health. The institution of Dr. Pardo-Villamizar has received research support from Bart McLean Fund for Neuroimmunology Research .

Post Infectious Triggered Anti-Myelin Oligodendrocyte Glycoprotein Antibody-Associated Disease (MOGAD) via CMV in an Immunocompetent Host (P10-5.030)

<h3>Objective:</h3> N/A <h3>Background:</h3> A previously healthy, immunocompetent 38-year-old female presented with initial complaints of subacute, waxing and waning high grade fevers, general malaise, and muscle aches for two weeks. Acutely she developed severe lumbar radiculopathy with significant urinary retention and bilateral lower extremity weakness leading to ED presentation. The patient was subsequently admitted with rapidly progressive lower extremity paraplegia and brisk reflexes over a 24-hour span. MRI imaging was notable for longitudinally extensive transverse myelitis (LETM) over continuous cervical and thoracic segments with significant gray matter involvement and left parahippocampal FLAIR hyperintensities Serum subsequently demonstrated positive anti-CMV IgM/IgG antibodies with a PCR load of 61 copies/mL indicative of a CMV infection with low viremia. LP CSF was CMV PCR negative with mildly elevated opening pressures and trace neurotrophic pleocytosis. Given stagnant clinical changes after five days of IV steroids, plasmapheresis was initiated with marked improvements in functional lower extremity strength. Soon afterwards, initial presenting lab work resulted, demonstrating high serum titers (1:2560) of anti-MOG antibodies. <h3>Design/Methods:</h3> N/A <h3>Results:</h3> N/A <h3>Conclusions:</h3> In immunocompetent hosts, CMV infection itself is a rarely described cause of inflammatory myelopathy with only 14 prescribed cases. With both deep gray matter FLAIR hyperintensities and cervical and thoracic LETM, a concomitant para-infectious CMV and new MOGAD is unlikely in our clinical setting. Additionally, systemic findings typically indicative of severe CMV infections such as retinitis, pericarditis/myocarditis, transaminitis, thrombocytopenia, and leukopenia were absent. Given prior reports of sequence similarities between MOG T-cell epitopes and a major capsid protein of CMV, molecular mimicry between antigen presenting cells has been hypothesized. Here we detail a first described case report of a possible post-infectious MOG antibody transverse myelitis triggered presumptively via CMV infection. Furthermore, presenting in an immunocompetent host, our case report highlights a further wrinkle into the pathophysiology and presence of post infectious triggered autoimmunity for MOGAD. <b>Disclosure:</b> Dr. Chen has nothing to disclose. Dr. Kwon has nothing to disclose.

Phenotyping mitochondrial DNA-related diseases in childhood: A cohort study of 150 patients.

Mitochondrial diseases (MDs) are heterogeneous disorders caused by mutations in nuclear DNA (nDNA) or mitochondrial DNA (mtDNA) associated with specific syndromes. However, especially in childhood, patients often display heterogeneity. Several reports on the biochemical and molecular profiles in children have been published, but studies tend not to differentiate between mtDNA- and nDNA-associated diseases, and focus is often on a specific phenotype. Thus, large cohort studies specifically focusing on mtDNA defects in the pediatric population are lacking. We reviewed the clinical, metabolic, biochemical, and neuroimaging data of 150 patients with MDs due to mtDNA alterations collected at our neurological institute over the past 20 years. mtDNA impairment is less frequent than nDNA impairment in pediatric MDs. Ocular involvement is extremely frequent in our cohort, as is classical Leber hereditary optic neuropathy, especially with onset before 12 years of age. Extraneurological manifestations and isolated myopathy appear to be rare, unlike adult phenotypes. Deep gray matter involvement, early disease onset, and specific phenotypes, such as Pearson syndrome and Leigh syndrome, represent unfavorable prognostic factors. Phenotypes related to single large scale mtDNA deletions appear to be very frequent in the pediatric population. Furthermore, we report for the first time an mtDNA pathogenic variant associated with cavitating leukodystrophy. We report on a large cohort of pediatric patients with mtDNA defects, adding new data on the phenotypical characterization of mtDNA defects and suggestions for diagnostic workup and therapeutic approach.

Bagel sign in neuro Behçet's disease myelitis: neuroimages.

Neuro-Behçet's disease (NBD) is a chronic heterogenous autoimmune disorder. It may involve central or pripheral nervous system but rarely shows spinal cord involvement (SCI). Bagel Sign is a unique sign of SCI due to NBD. It is a central T2W hyperintense lesion with a hypointense core on axial magnetic resonance imaging (MRI). This sign may be a complete or an incomplete ring with or without post-contrast enhancement. Here we report a patient with NBD whose primary presentaion was transverse myelitis. A 14-year-old patient was admitted due to triparesis and urinary retention. He had T2W hyperintensities from the left basal ganglion down to the T10 level. A similar anteromedial spot has been described in anterior spinal cord infarction which favors an ischemic pathogenesis for NBD. To our knowledge this is the first report of Bagel Sign and longitudinally extensive transverse myelitis with gray matter involvement.

Prevalence, and Pattern of Hypoxic Ischemic Encephalopathy on Magnetic Resonance Imaging among Pediatric patients

Background: Hypoxic Ischemic Encephalopathy is a frequently encountered occurrence in a pediatric setting and more prevalent in the low middle income countries. Magnetic resonance imaging (MRI) is considered a reliable source of investigation. Our study determined the imaging findings and cause of Hypoxic ischemic encephalopathy in children referred for MR Imaging to our radiology department. Study design: A prospective cross-sectional study. Place and duration of study: Our prospective cross-sectional study was conducted at a pediatric tertiarycare hospital, of Karachi Pakistan from 1st November 2021 to 30th October 2022. Methods: Our study included children from newborns to 16 years of age who either had a history of fits, abnormal APGAR score, delayed cry or delayed milestones. The brain MRI was performed on 1.5 tesla scanner with a standard protocol and interpreted by Experienced Radiologists Findings were recorded on anExcel Sheet and data was analyzed on SPSS version 26. Our study included children from newborns to 16 years of age who were at risk of hypoxic insult and were born to mothers who had hypertension, diabetes milletus, history of maternal substance abuse and maternal history of fits history of fits and children who had a history of fits, abnormal APGAR score, delayed cry and/or delayed milestones. Children who were born via instrumental delivery were excluded from our study. Result: A total number of 187 patients were included in our study with 98 males and 89 females. The most common age group involved was from age &gt;1 year to 5 years (50.3%). The most common presenting complaints included delayed milestones (63.6%) and fits (59.9%), delayed cry (52.4). On examination 42.2% had microcephaly. One-third of the patients had a positive maternal history for diabetes mellitus, hypertension and anemia. APGAR score was checked at 1 minute and 5 minute which showed the most common APGAR score of 3-6 which was seen in 81.8% of the patients. On MR Imaging 54.5% had periventricular leukomalacia, 35.3% had deep gray matter involvement, 3.7% had germinal matrix hemorrhage, and only 1.6% had watershed infarcts. A statically significant association was seen between gestation at birth and periventricular leukomalacia (P=&lt;0.5). Conclusion: Hypoxic Ischemic Encephalopathy is a common occurrence in our society and MRI is the recommended modality due to its sensitivity and superior soft-tissue resolution. In developing countries due to a lack of proper facilities and awareness, there is an increased incidence of HIE which leads to increased morbidity therefore increasing awareness and early diagnosis is of utmost importance. Keywords: Hypoxic ischemic encephalopathy, Magnetic Resonance Imaging, Pediatric population