Hearing loss and dementia: radiologic and biomolecular basis of their shared characteristics. A systematic review.

Dementia and hearing loss share radiologic and biologic findings that might explain their coexistence, especially in the elderly population. Brain atrophy has been observed in both conditions, as well as the presence of areas of gliosis. The brain atrophy is usually focal; it is located in the temporal lobe in patients with hearing loss, while it involves different part of brain in patients with dementia. Radiological studies have shown white matter hyperintensities (WMHs) in both conditions. WMHs have been correlated with the inability to correctly understand words in elderly persons with normal auditory thresholds and, the identification of these lesion in brain magnetic resonance imaging studies has been linked with an increased risk of developing cognitive loss. In addition to WMHs, some anatomopathological studies identified the presence of brain gliosis in the elderly's brain. The cause-effect link between hearing loss and dementia is still unknown, despite they might share some common findings. The aim of this systematic review is to analyze radiologic and biomolecular findings that these two conditions might share, identify a common pathological basis, and discuss the effects of hearing aids on prevention and treatment of cognitive decline in elderly patients with hearing loss.

Approved and Emerging Disease Modifying Therapies on Neurodegeneration in Multiple Sclerosis.

Multiple sclerosis (MS) is an autoimmune, chronic, progressive disease leading to a combination of inflammation, demyelination, and neurodegeneration throughout the central nervous system (CNS). The outcome of these processes can be visualized in magnetic resonance imaging (MRI) scans as brain atrophy, or brain volume loss (BVL), as well as lesions, "black holes" and spinal cord atrophy. MRI outcomes such as BVL have been used as biomarkers of neurodegeneration and other measures of MS disease progression in clinical research settings. Several FDA-approved medications seek to alleviate disease progression by reducing the impact of such factors as demyelination and neurodegeneration, but there are still many shortcomings that current clinical research aims to mitigate. This review attempts to provide an overview of the FDA-approved medications available for treating multiple sclerosis and their effect on neurodegeneration, measured by BVL.

Choroid plexus volume as a marker of retinal atrophy in relapsing remitting multiple sclerosis.

OBJECTIVE: To evaluate choroid plexus (CP) volume as a biomarker for predicting clinical disability and retinal layer atrophy in relapsing remitting multiple sclerosis (RRMS). METHODS: Ninety-five RRMS patients and 26 healthy controls (HCs) underwent 3 T whole brain MRI, expanded disability status scale (EDSS) and optical coherence tomography (OCT). Fully automated intra-retinal segmentation was performed to obtain the volumes of the retinal nerve fiber layer (RNFL), combined ganglion cell layer -inner plexiform layer (GCIPL), inner nuclear layer (INL), outer plexiform layer (OPL), outer nuclear layer (ONL), retinal pigment epithelium (RPE), total macular volume (TMV) and papillomacular bundle (PMB). Automated segmentation of the CP within the lateral ventricles was performed and the choroid plexus volume (CPV) was normalized by total intracranial volume (TIV). Linear regression analysis and generalized estimating equation (GEE) models were applied to evaluate relationships between nCPV and EDSS, T2 lesion volume, disease duration, and retinal layer volumes, followed by Bonferroni correction analysis for multiple comparisons. RESULTS: RRMS patients had larger tChPV compared to HCs (p < 0.001). After Bonferroni correction, there was a significant positive correlation between tChPV and EDSS (r2 = 0.25, p = 0.0002), disease duration (r2 = 0.30, p = 0.01), and T2 lesion volume (r2 = 0.39, p = 0.0000). A robust negative correlation was found between tChPV and RNFL (p < 0.001), GCIPL (p = 0.003), TMV (p = 0.0185), PMB (p < 0.0001), G (p = 0.04), T(p = 0.0001). CONCLUSIONS: Our findings support the association of tChPV with disability and altered retinal integrity in RRMS.

Characterization of white matter lesions in multiple sclerosis using proton density and T1-relaxation measures.

PURPOSE: Although lesion dissemination in time is a defining characteristic of multiple sclerosis (MS), there is a limited understanding of lesion heterogeneity. Currently, conventional sequences such as fluid attenuated inversion recovery (FLAIR) and T1-weighted (T1W) data are used to assess MS lesions qualitatively. Estimating water content could provide a measure of local tissue rarefaction, or reduced tissue density, resulting from chronic inflammation. Our goal was to utilize the proton spin density (PD), derived from a rapid, multi-contrast STAGE (strategically acquired gradient echo) protocol to characterize white matter (WM) lesions seen on T2W, FLAIR and T1W data. MATERIALS AND METHODS: Twenty (20) subjects with relapsing-remitting MS were scanned at 3 T using T1W, T2-weighted, FLAIR and strategically acquired gradient echo (STAGE) sequences. PD and T1 maps were derived from the STAGE data. Disease severity scores, including Extended Disability Status Scale (EDSS) and Multiple Sclerosis Functional Composite (MSFC), were correlated with total, high PD and high T1 lesion volumes. A probability map of high PD regions and all lesions across all subjects was generated. Five perilesional normal appearing WM (NAWM) bands surrounding the lesions were generated to compare the median PD and T1 values in each band with the lesional values and the global WM. RESULTS: T1W intensity was negatively correlated with PD as expected (R = -0.87, p < 0.01, R2 = 0.756) and the FLAIR signal was suppressed for high PD volumes within the lesions, roughly for PD ≥ 0.85. The threshold for high PD and T1 regions was set to 0.909 and 1953.6 ms, respectively. High PD regions showed a high probability of occurrence near the boundary of the lateral ventricles. EDSS score and nine-hole peg test (dominant and non-dominant hand) were significantly correlated with the total lesion volume and the volumes of high PD and T1 regions (p < 0.05). There was a significant difference in PD/T1 values between the high PD/T1 regions within the lesions and the remaining lesional tissue (p < 0.001). In addition, the PD values of the first NAWM perilesional band directly adjacent to the lesional boundary displayed a significant difference (p < 0.05) compared to the global WM. CONCLUSION: Lesions with high PD and T1s had the highest probability of occurrence at the boundary of the lateral ventricles and likely represent chronic lesions with significant local tissue rarefaction. Moreover, the perilesional NAWM exhibited subtly increasing PD and T1 values from the NAWM up to the lesion boundary. Unlike on the T1 maps, the perilesional band adjacent to the lesion boundary possessed a significantly higher PD value than the global WM PD values. This shows that PD maps were sensitive to the subtle changes in NAWM surrounding the lesions.

Reduced oxygen extraction fraction in deep cerebral veins associated with cognitive impairment in multiple sclerosis.

Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89% vs 72.4 ± 2.23%) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.508, p = 0.031) and the SvO2 (r = -0.498, p = 0.036) exhibited a moderate correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS. .

The effect of ocrelizumab on Balo's tumefactive lesion: A case report.

Balo's concentric sclerosis (BCS) is a rare subtype of multiple sclerosis. Advanced MRI metrics, such as magnetization transfer ratio (MTR), fractional anisotropy (FA), mean diffusivity (MD), and the ratio of total N-acetylaspartate concentration/total creatine concentration (tNAA/tCr) using proton magnetic resonance spectroscopy (1H-MRS), are commonly used in research studies to investigate the effect of a disease modifying therapy (DMT). We report a patient diagnosed with BCS, receiving ocrelizumab, and provide a comparison of the lesion volume, T1-gadolinium lesion volume, MTR, FA, MD, and MRS metrics at baseline, 6- and 12-month follow-up. There was a reduction in Balo's lesion volume on fluid-attenuated inversion recovery (FLAIR) imaging observed in our patient from baseline (23.925 mL) to 12-month follow-up (2.391 mL), with the largest decrease from baseline to 6-month follow-up (3.650 mL). There was no T1-gadolinium enhancement seen at month 6 and 12. The MTR of the lesion did not change significantly (baseline = 50.9%, 6-month = 49.9%, 12-month =50.1%) but the FA increased from 0.188 (at baseline) to 0.304 (at 6 months), while the 12-month follow-up FA was 0.297. We also noted a reduction in MD from baseline (1.333 × 10-3 mm2/s) to 6-month follow-up (1.037 × 10-3 mm2/s), while the 12-month follow-up MD was 1.086 × 10-3 mm2/s. There was a 10.3% increase in tNAA/tCr from 1.583 (at month 0) to 1.747 (at month 12). Our results demonstrate for the first time a direct effect of ocrelizumab on BCS lesions. To validate our findings, more observations are needed in a larger group of BCS patients.

Reduced Oxygen Extraction Fraction in Deep Cerebral Veins Associated with Cognitive Impairment in Multiple Sclerosis.

Studying the relationship between cerebral oxygen utilization and cognitive impairment is essential to understanding neuronal functional changes in the disease progression of multiple sclerosis (MS). This study explores the potential of using venous susceptibility in internal cerebral veins (ICVs) as an imaging biomarker for cognitive impairment in relapsing-remitting MS (RRMS) patients. Quantitative susceptibility mapping derived from fully flow-compensated MRI phase data was employed to directly measure venous blood oxygen saturation levels (SvO2) in the ICVs. Results revealed a significant reduction in the susceptibility of ICVs (212.4 ± 30.8 ppb vs 239.4 ± 25.9 ppb) and a significant increase of SvO2 (74.5 ± 1.89 % vs 72.4 ± 2.23 %) in patients with RRMS compared with age- and sex-matched healthy controls. Both the susceptibility of ICVs (r = 0.646, p = 0.004) and the SvO2 (r = -0.603, p = 0.008) exhibited a strong correlation with cognitive decline in these patients assessed by the Paced Auditory Serial Addition Test, while no significant correlation was observed with clinical disability measured by the Expanded Disability Status Scale. The findings suggest that venous susceptibility in ICVs has the potential to serve as a specific indicator of oxygen metabolism and cognitive function in RRMS.

Exploring Inner Ear and Brain Connectivity through Perilymph Sampling for Early Detection of Neurological Diseases: A Provocative Proposal.

Recent evidence shows that it is possible to identify the elements responsible for sensorineural hearing loss, such as pro-inflammatory cytokines and macrophages, by performing perilymph sampling. However, current studies have only focused on the diagnosis of such as otologic conditions. Hearing loss is a feature of certain neuroinflammatory disorders such as multiple sclerosis, and sensorineural hearing loss (SNHL) is widely detected in Alzheimer's disease. Although the environment of the inner ear is highly regulated, there are several communication pathways between the perilymph of the inner ear and cerebrospinal fluid (CSF). Thus, examination of the perilymph may help understand the mechanism behind the hearing loss observed in certain neuroinflammatory and neurodegenerative diseases. Herein, we review the constituents of CSF and perilymph, the anatomy of the inner ear and its connection with the brain. Then, we discuss the relevance of perilymph sampling in neurology. Currently, perilymph sampling is only performed during surgical procedures, but we hypothesize a simplified and low-invasive technique that could allow sampling in a clinical setting with the same ease as performing an intratympanic injection under direct visual check. The use of this modified technique could allow for perilymph sampling in people with hearing loss and neuroinflammatory/neurodegenerative disorders and clarify the relationship between these conditions; in fact, by measuring the concentration of neuroinflammatory and/or neurodegenerative biomarkers and those typically expressed in the inner ear in aging SNHL, it could be possible to understand if SNHL is caused by aging or neuroinflammation.

From Animal Models to Clinical Trials: The Potential of Antimicrobials in Multiple Sclerosis Treatment.

Multiple sclerosis (MS) is a chronic, autoimmune, demyelinating disease of the central nervous system (CNS). Microbes, including bacteria and certain viruses, particularly Epstein-Barr virus (EBV), have been linked to the pathogenesis of MS. While there is currently no cure for MS, antibiotics and antivirals have been studied as potential treatment options due to their immunomodulatory ability that results in the regulation of the immune process. The current issue addressed in this systematic review is the effect of antimicrobials, including antibiotics, antivirals, and antiparasitic agents in animals and humans. We performed a comprehensive search of PubMed, Google Scholar, and Scopus for articles on antimicrobials in experimental autoimmune encephalomyelitis animal models of MS, as well as in people with MS (pwMS). In animal models, antibiotics tested included beta-lactams, minocycline, rapamycin, macrolides, and doxycycline. Antivirals included acyclovir, valacyclovir, and ganciclovir. Hydroxychloroquine was the only antiparasitic that was tested. In pwMS, we identified a total of 24 studies, 17 of them relevant to antibiotics, 6 to antivirals, and 1 relevant to antiparasitic hydroxychloroquine. While the effect of antimicrobials in animal models was promising, only minocycline and hydroxychloroquine improved outcome measures in pwMS. No favorable effect of the antivirals in humans has been observed yet. The number and size of clinical trials testing antimicrobials have been limited. Large, multicenter, well-designed studies are needed to further evaluate the effect of antimicrobials in MS.

Impact of Disease Modifying Therapy on MS-Related Fatigue: A Narrative Review.

Multiple sclerosis (MS) is a chronic autoimmune disease that affects the central nervous system by causing inflammation, demyelination and neurodegeneration. Fatigue is the most prevalent and one of the most disabling symptoms among people with MS (pwMS). Due to its complexity and subjective character, fatigue is still little understood despite its frequent occurrence and severe impact. The potential causes, effects, and treatments of fatigue associated with MS have been extensively studied in recent years. Though the benefits of such a variety of contributions are obvious, there have not been many attempts to evaluate the effect of disease modifying therapies (DMTs) on MS-related fatigue. In this review, we summarize clinical trials and research studies, and we discuss the effect of different DMTs on MS-related fatigue.

Role of white matter in cognitive impairment among relapsing remitting multiple sclerosis patients.

BACKGROUND: Multiple Sclerosis (MS) associated cognitive impairment is believed to be mostly connected with damage to gray matter. The contribution of white matter is still poorly understood. We aim to examine the relationship between cognition and white matter tracts among relapsing remitting MS (RRMS) patients. METHODS: Thirty RRMS patients were selected undergo the (3-seconds-interstimulus-interval paced auditory serial addition test) PASAT-3, the (symbol digit modalities test (SDMT) and full-brain MRI scans on a SIEMENS 3 Tesla Verio scanner. Diffusion Tensor Imaging (DTI) parameters, such as fractional anisotropy (FA) and mean diffusivity (MD) were examined in 37 white matter (WM) tracts. WM tracts were selected from the association pathways, projection pathways, commissural pathways by applying Human Connectome project (HCP)842 tractography atlas after DTI data reconstruction and registration to HCP1065 diffusion template in DSI Studio (version March 2021) In SPSS v26, Spearman's rank correlation analysis was used to examine the connection between DTI WM tracts and cognitive scores. The power of the study was increased by using false discovery rate (FDR) software. RESULTS: The mean scores on the PASAT-3 and SDMT were 31.5 ± 12.8 and 46.9 ± 16.7 respectively. Better cognitive performance was correlated to higher FA values, while lower cognitive function was correlated to higher MD values. There was a positive correlation between FA values in the right medial lemniscus and superior cerebellar peduncle and SDMT scores (p 0.05). Additionally, there was a trend for significance between the FA values in the left corticothalamic tract and SDMT scores. MD values in the superior cerebellar peduncle, left arcuate Fasciculus and left extreme capsule were negatively correlated with SDMT scores (p<0.05). PASAT-3 scores were negatively correlated with MD values in the right cerebellum, however, there was no significant correlation between PASAT-3 and FA values. CONCLUSIONS: White matter tracts, particularly the superior cerebellar peduncle, contribute to the cognitive impairment in RRMS. Larger sample sizes for longitudinal research are necessary.

Cognitive enrichment and education quality moderate cognitive dysfunction in black and white adults with multiple sclerosis.

OBJECTIVE: To examine the extent to which three sociobehavioral proxies of cognitive reserve-years of education, education quality, and cognitive enrichment-differ in their prediction of cognitive performance among Black and White people with MS (PwMS). METHODS: 82 PwMS (Black n = 41, White n = 41) underwent a neurological examination and a neuropsychological evaluation that included tests of word recognition (Wechsler Test of Adult Reading) as well as measures of verbal memory, visuospatial memory, and processing speed (the Brief International Cognitive Assessment for MS; BICAMS). Participants rated their lifetime engagement in various cognitively-enriching activities (Cognitive Reserve Scale). RESULTS: For the full sample, education quality and cognitive enrichment were more strongly associated with cognitive performance than were years of education. Cognitive enrichment was not associated with cognitive performance among participants with high education quality. In contrast, among participants with low education quality, cognitive enrichment was strongly associated with cognitive performance, suggesting that high engagement in cognitively-enriching activities provided similar protection to high education quality. Furthermore, among Black participants, cognitive enrichment and educational quality moderated the relationship between disability level and cognitive performance. In contrast, among White participants, cognitive enrichment did not provide additional protection beyond the buffering effect of education quality. CONCLUSIONS: PwMS can successfully build reserve through multiple routes, including formal education or informal cognitive enrichment. Treatment for MS should incorporate cognitively-enriching activities to build resilience against cognitive decline, particularly for members of marginalized racial/ethnic groups, who are at greatest risk for poor health outcomes, and for whom years of education may not best reflect education quality.

Targeting Neuroinflammation to Alleviate Chronic Olfactory Dysfunction in Long COVID: A Role for Investigating Disease-Modifying Therapy (DMT)?

Chronic olfactory dysfunction after SARS-CoV-2 infection occurs in approximately 10% of patients with COVID-19-induced anosmia, and it is a growing public health concern. A regimen of olfactory training and anti-neuroinflammatory therapy with co-ultramicronized palmitoylethanolamide with luteolin (um-PEA-LUT) has shown promising results in clinical trials; however, approximately 15% of treated patients do not achieve full recovery of a normal olfactory threshold, and almost 5% have no recovery. Disease-modifying therapies (DMTs), which are used to treat autoimmune neuroinflammation in multiple sclerosis (MS), have not been studied for treating persistent inflammation in refractory post-COVID-19 smell disorder. This study evaluated COVID-19-related smell loss and MS-related smell loss, comparing the responses to different therapies. Forty patients with MS and 45 reporting post-COVID-19 olfactory disorders were included in the study. All patients underwent nasal endoscopy and were evaluated by using validated Sniffin' Sticks testing. The patients with long COVID were treated for three months with um-PEA-LUT plus olfactory training. The patients with MS were treated with DMTs. Olfactory functions before and after treatment were analyzed in both groups. At the experimental endpoint, 13 patients in the COVID-19 group treated with um-PEA-LUT had residual olfactory impairment versus 10 patients in the MS group treated with DMTs. The severity of the persistent olfactory loss was lower in the MS group, and the patients with MS treated with IFN-beta and glatiramer acetate had the preservation of olfactory function. These data provide a rationale for considering prospective trials investigating the efficacy of DMTs for post-COVID-19 olfactory disorders that are refractory to um-PEA-LUT with olfactory training. This study is the first to consider the role of DMT in treating refractory post-viral olfactory loss in patients with long COVID.

Communicating the relevance of neurodegeneration and brain atrophy to multiple sclerosis patients: patient, provider and researcher perspectives.

Central nervous system (CNS) atrophy provides valuable additional evidence of an ongoing neurodegeneration independent of lesion accrual in persons with multiple sclerosis (PwMS). However, there are limitations for interpretation of CNS volume changes at individual patient-level. Patients are receiving information on the topic of atrophy through various sources, including media, patient support groups and conferences, and discussions with their providers. Whether or not the topic of CNS atrophy should be proactively discussed with PwMS during office appointments is currently controversial. This commentary/perspective article represents perspectives of PwMS, providers and researchers with recommendations for minimizing confusion and anxiety, and facilitating proactive discussion about brain atrophy, as an upcoming routine measure in evaluating disease progression and treatment response monitoring. The following recommendations were created based on application of patient's and provider's surveys, and various workshops held over a period of 2 years: (1) PwMS should receive basic information on understanding of brain functional anatomy, and explanation of inflammation and neurodegeneration; (2) the expertise for atrophy measurements should be characterized as evolving; (3) quality patient education materials on these topics should be provided; (4) the need for standardization of MRI exams has to be explained and communicated; (5) providers should discuss background on volumetric changes, including references to normal aging; (6) the limitations of brain volume assessments at an individual-level should be explained; (7) the timing and language used to convey this information should be individualized based on the patient's background and disease status; (8) a discussion guide may be a very helpful resource for use by providers/staff to support these discussions; (9) understanding the role of brain atrophy and other MRI metrics may elicit greater patient satisfaction and acceptance of the value of therapies that have proven efficacy around these outcomes; (10) the areas that represent possibilities for positive self-management of MS symptoms that foster hope for improvement should be emphasized, and in particular regarding use of physical and mental exercise that build or maintain brain reserve through increased network efficiency, and (11) an additional time during clinical visits should be allotted to discuss these topics, including creation of specific educational programs.

Demographics and baseline disease characteristics of Black and Hispanic patients with multiple sclerosis in the open-label, single-arm, multicenter, phase IV CHIMES trial.

BACKGROUND: Black/African American patients with multiple sclerosis (BpwMS) and Hispanic/Latino patients with multiple sclerosis (HpwMS), who historically have been underrepresented in multiple sclerosis (MS) clinical trials, exhibit greater disease severity and more rapid disease progression than White patients with MS (WpwMS). The lack of diversity and inclusion in clinical trials, which may be due to barriers at the system, patient and study levels, impacts the ability to effectively assess risks, benefits and treatment responses in a generalized patient population. METHODS: CHIMES (Characterization of Ocrelizumab in Minorities With Multiple Sclerosis), an open-label, single-arm, multicenter, phase IV study of self-identified BpwMS and HpwMS aged 18-65 years with relapsing MS and an Expanded Disability Status Score (EDSS) of ≤5.5, was developed in collaboration with patients with MS, national advocacy groups and clinical researchers. Patients were enrolled at study centers across the US, including Puerto Rico, and 1 site in Kenya. RESULTS: A total of 182 patients enrolled in CHIMES: 113 (62.1%) were BpwMS, and 69 (37.9%) were HpwMS; the mean (SD) baseline EDSS score was 2.4 (1.4), and 62.6% of patients were treatment naive. Using the pooled non-BpwMS/HpwMS group in the OPERA ocrelizumab trials as a reference population, patients enrolled in CHIMES were younger, had a higher mean body mass and had a greater T2 lesion volume but similar T2 lesion number on MRI. CONCLUSION: BpwMS and HpwMS have been consistently underrepresented in clinical trials, limiting the understanding of disease biology and response to treatment in this population. Data from the CHIMES study revealed differences in demographics and some baseline disease characteristics and disease burden between BpwMS and HpwMS vs WpwMS. These differences could have an impact when assessing clinical outcomes in BpwMS and HpwMS. GOV IDENTIFIER: NCT04377555.

Optical Coherence Tomography in Chronic Relapsing Inflammatory Optic Neuropathy, Neuromyelitis Optica and Multiple Sclerosis: A Comparative Study.

Purpose: To examine the optical coherence tomography (OCT) features of the retina in patients with chronic relapsing inflammatory optic neuropathy (CRION) and compare them with those of neuromyelitis optica spectrum disorder (NMOSD), relapsing-remitting multiple sclerosis (RRMS) with and without optic neuritis (ON), and healthy controls (HC). Methods: In this retrospective cross-sectional study, we used spectral domain OCT to evaluate the retinal structure of 14 participants with CRION, 22 with NMOSD, 40 with RRMS with unilateral ON, and 20 HC. The peripapillary retinal nerve fiber layer (pRNFL), total macular volume (TMV), and papillomacular bundle (PMB) were measured, and intra-retinal segmentation was performed to obtain the retinal nerve fiber (RNFL), ganglion cell (GCL), inner plexiform (IPL), inner nuclear (INL), outer plexiform (OPL) and outer nuclear (ONL) layer volumes. Results: The global pRNFL [39.33(±1.8) µm] and all its quadrants are significantly thinner in CRION compared with all other groups (p < 0.05). CRION patients have decreased volumes of TMV, RNFL, GCL, and IPL compared with all other groups (p < 0.05). Conclusion: Severe thinning in pRNFL and thinning in intra-retinal segments of IPL, GCL, RNFL, and TMV could be helpful in differentiating CRION from NMOSD and RRMS.

Neuromyelitis Optica in a Young Woman With Tuberous Sclerosis: Is There an Association?

Tuberous sclerosis complex (TSC) is a genetic neurocutaneous disorder that presents with multi-organ involvement, including but not limited to hamartomas in the brain, eyes, heart, lung, liver, kidney, and skin. Neuromyelitis optica spectrum disorder (NMOSD) is an inflammatory, autoimmune, demyelinating, central nervous system disorder, targeting the optic nerves and spinal cord. We report a 30-year-old woman with TSC who developed tingling in the legs that gradually involved her abdomen. Additional symptoms included severe vomiting that lasted for a week and spasms in her legs. One month later, she was hospitalized due to difficulty ambulating and tingling in her hands. Magnetic resonance imaging (MRI) of her spine showed longitudinally extensive upper cervical and lower thoracic cord signal changes. MRI scan of her brain showed few non-specific T2 signal changes along with cortical and subcortical tubers. Aquaporin (AQP4) IgG antibody was found to be positive in both serum and cerebrospinal fluid. Accordingly, she was diagnosed with NMOSD, treated with a 5-day course of intravenous steroids, followed by 5 sessions of plasma exchange. After her initial improvement, she was started on rituximab as maintenance therapy. Two years later, she is clinically stable, and her follow-up MRI showed marked improvement.

Olfactory Dysfunction, Headache, and Mental Clouding in Adults with Long-COVID-19: What Is the Link between Cognition and Olfaction? A Cross-Sectional Study.

Smell alteration and cognitive impairment are common features of the Long-COVID Syndrome. Mental clouding, often described as brain fog, might affect smell by altering recollection of odors or through a share mechanism of neuroinflammation. We investigated mental clouding, headache, and cognitive function in adult patients with persistent COVID-19 olfactory dysfunction. This multi-center cross-sectional study enrolled 152 adults with self-reported olfactory dysfunction from 3 tertiary centers specialized in COVID-19 olfactory disorders. Inclusion criteria were smell alterations after COVID-19 persisting over 6 months from infection, age >18 and < 65. Exclusion criteria included smell alterations, headache, or memory problems prior to COVID-19 infection. The patients were evaluated by olfactometry, nasal endoscopy, headache scale, cognitive assessment, Mini Mental State Examination (MMSE), and self-reported measures. Smell dysfunction was stratified and classified based on olfactory deficit severity and presence of olfactory distortion (parosmia, cacosmia). Data on smell disorder, mental clouding, MMSE, and headache were analyzed to assess correlations. Among the 152 patients studied, 50 (32.8%) presented with anosmia, 25 (16.4%) with hyposmia, 10 (6.6%) with parosmia/cacosmia, and 58 patients (38.2%) with a combination of hyposmia and parosmia; seven (4.6%) patients suffered from headache exclusively, and two (1.4%) had headache and mental clouding as their primary symptom. Headache was reported by 76 (50%) patients, and mental clouding by 71 (46.7%). The patients reporting headache, mental clouding, or both, had significantly increased risk of suffering from anosmia and/or hyposmia when compared with their counterparts without these neurological symptoms. No patients had reduced MMSE scores. In our cohort of adult patients with post-COVID-19, smell alterations persisting over 6 months, cognitive impairment and headache were associated with more severe olfactory loss, consistent with neuroinflammatory mechanisms mediating a variety of Long-COVID symptoms.

The Emerging Role of Scalogram-Based Convolutional Neural Network in the Diagnosis of Epileptic Seizures.

Epilepsy, a common disorder affecting 1-2% of the population, can significantly impact a person's quality of life and can lead to disability or even death [...].