Brain Involvement Research Articles

Short intravenous amphotericin B followed by oral posaconazole using a simple, stratified treatment approach for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis: a prospective cohort study

ObjectivesTo evaluate the efficacy and safety of short-course intravenous amphotericin B followed by sustained release posaconazole tablets for diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. MethodsThis prospective, pragmatic study included adults with diabetes or COVID-19-associated rhino-orbito-cerebral mucormycosis. Patients received short (7–14 days) or long (15–28 days) intravenous antifungal therapy (short intravenous antifungal treatment [SHIFT] or long intravenous antifungal treatment [LIFT], respectively) depending on the presence or absence of brain involvement. All patients received step-down posaconazole tablets, debridement, and glycemic control. The primary outcome was the treatment success at week 14, which was determined by assessing survival and the absence of disease progression through clinical evaluation and nasal endoscopy. Log-binomial regression analysis (risk ratio and 95% CI) was performed to assess factors associated with the primary outcome. ResultsIntravenous therapy was administered to 251 participants: SHIFT, 205 (median duration, 13 days); LIFT, 46 (median duration, 22 days). Treatment success at 3 months was 88% (217/248; 95% CI, 83–91%): SHIFT group, 93% (189/203; 89–96%); LIFT group, 62% (28/45; 47–76%). All-cause mortality was 12% (30/251): SHIFT group, 6% (13/205); LIFT group, 37% (17/46). Age (aRR [95% CI]: 1.02 [1.00–1.05]; p 0.027), diabetic ketoacidosis at presentation (2.32 [1.20–4.46]; p 0·012), glycated haemoglobin A1c (1.19 [1.03–1.39]; p 0.019), stroke (3.93 [1.94–7.95]; p 0·0001), and brain involvement (5.67 [3.05–10.54]; p < 0.0001) were independently associated with unsuccessful outcomes. Discussion: Short intravenous amphotericin B with step-down posaconazole tablets should be further studied as primary treatment option for diabetes or COVID-19-associated mucormycosis in randomized controlled trials.

Identification of an 85-kb Heterozygous 4p Microdeletion With Full Genome Analysis in Autosomal Dominant Charcot-Marie-Tooth Disease.

Charcot-Marie-Tooth disease (CMT) is a syndrome of a hereditary neurodegenerative condition affecting the peripheral nervous system and is a single gene disorder. Deep phenotyping coupled with advanced genetic techniques is critical in discovering new genetic defects of rare genetic disorders such as CMT. We applied multidisciplinary investigations to examine the neurophysiology and nerve pathology in a family that fulfilled the diagnosis of CMT2. When phenotype-guided first-tier genetic tests and whole-exome sequencing did not yield a molecular diagnosis, we conducted full genome analysis by examining phased whole-genome sequencing and whole-genome optical mapping data to search for the causal variation. We then performed a systematic review to compare the reported patients with interstitial microdeletion in the short arm of chromosome 4. In this family with CMT2, we reported the discovery of a heterozygous 85-kb microdeletion in the short arm of chromosome 4 (4p16.3)[NC_000004.12:g.1733926_1819031del] spanning 3 genes [TACC3 (intron 6-exon 16), FGFR3 (total deletion), and LETM1 (intron 10-exon14)] that cosegregated with disease phenotypes in family members. The clinical features of peripheral nerve degeneration in our family are distinct from the well-known 4p microdeletion syndrome of Wolf-Hirschhorn syndrome, in which brain involvement is the major phenotype. In summary, we used the full genome analysis approach to discover a new microdeletion in a family with CMT2. The deleted segment contains 3 genes (TACC3, FGFR3, and LETM1) that likely play a role in the pathogenesis of nerve degeneration.

AQP4-IgG NMOSD, MOGAD, and double-seronegative NMOSD: is it possible to depict the antibody subtype using magnetic resonance imaging?

There is clinical and radiological overlap among demyelinating diseases. However, their pathophysiological mechanisms are different and carry distinct prognoses and treatment demands. To investigate magnetic resonance imaging (MRI) features of patients with myelin-oligodendrocyte glycoprotein associated disease (MOGAD), antibody against aquaporin-4(AQP-4)-immunoglobulin G-positive neuromyelitis optica spectrum disorder (AQP4-IgG NMOSD), and double-seronegative patients. A cross-sectional retrospective study was performed to analyze the topography and morphology of central nervous system (CNS) lesions. Two neuroradiologists consensually analyzed the brain, orbit, and spinal cord images. In total, 68 patients were enrolled in the study (25 with AQP4-IgG-positive NMOSD, 28 with MOGAD, and 15 double-seronegative patients). There were differences in clinical presentation among the groups. The MOGAD group had less brain involvement (39.2%) than the NMOSD group (p = 0.002), mostly in the subcortical/juxtacortical, the midbrain, the middle cerebellar peduncle, and the cerebellum. Double-seronegative patients had more brain involvement (80%) with larger and tumefactive lesion morphology. In addition, double-seronegative patients showed the longest optic neuritis (p = 0.006), which was more prevalent in the intracranial optic nerve compartment. AQP4-IgG-positive NMOSD optic neuritis had a predominant optic-chiasm location, and brain lesions mainly affected hypothalamic regions and the postrema area (MOGAD versus AQP4-IgG-positive NMOSD, p= 0 .013). Furthermore, this group had more spinal cord lesions (78.3%), and bright spotty lesions were a paramount finding to differentiate it from MOGAD (p = 0.003). The pooled analysis of lesion topography, morphology, and signal intensity provides critical information to help clinicians form a timely differential diagnosis.

A phase 1, open-label, dose escalation and dose expansion study to evaluate the safety, tolerability, pharmacokinetics, and antitumor activity of PF-07799933 (ARRY-440) as a single agent and in combination therapy in participants 16 years and older with advanced solid tumors with BRAF alterations.

TPS3164 Background: Approved BRAF inhibitors (BRAFi) are inactive against RAF dimers. Accordingly, the acquisition of BRAF dimers ( e.g., through drug-acquired splice variants or BRAF amplification) may lead to therapy resistance. Non-V600 (class II and III) BRAF alterations that occur de novo in diverse tumor types also signal as dimers and therefore have no approved targeted therapeutic options. Additional liabilities of approved BRAFi include toxicity from paradoxical activation of wild-type (WT) RAF and limited brain penetration, a common primary and metastatic site for BRAF-altered cancers. In contrast to approved agents, investigational BRAFi inhibit WT and mutant RAF proteins (A, B, and C-RAF, monomers, dimers), and therefore may be limited by on-target toxicity from “pan-RAF” inhibition. PF-07799933 is an oral selective ATP-competitive small-molecule RAF kinase inhibitor that suppresses BRAF signaling in BRAF V600-mutant and non-V600- BRAF mutant tumors. It displays significantly less paradoxical activation than approved BRAFi and is not “pan RAF” as it spares non-BRAF-containing RAF dimers. We describe here the Phase 1 study of PF-07799933 as monotherapy or in combination with binimetinib or cetuximab in participants with BRAF-altered advanced solid tumors. Methods: The purpose of this first-in-human study is to investigate the safety, tolerability, pharmacokinetics (PK), pharmacodynamics, and potential clinical benefits of PF-07799933 administered as a single agent and in combination in participants with BRAF Class I, II and III mutated solid tumors with or without brain involvement. Part 1 (monotherapy dose escalation) and Part 2 (combination dose escalation) will enroll participants with BRAF V600 mutation who have progressed on a approved BRAFi or with de novo Class II or III alterations who have progressed on standard of care therapy. The primary objective of Part 1 is to determine monotherapy MTD/RDE of PF-07799933. Participants in Part 1 will be allowed to add on rational combination with either binimetinib or cetuximab at the time of disease progression. Once PK measurements indicate the potential for significant BRAF inhibition in the brain, participants with untreated and symptomatic brain metastases will be allowed to enroll. The primary objective of Part 2 is combination MTDc/RDEc of PF-07799933 with binimetinib or cetuximab. The primary objective of Part 3 is efficacy in defined cohorts (total ~120 participants): Cohort 1-2: BRAF V600 mutant melanoma; Cohort 3: BRAF Class II altered melanoma; Cohorts 4-5: BRAF V600 and Class II altered CRC; Cohort 6: other BRAF V600, Class II/III altered solid tumor not qualifying for Cohorts 1-5. Clinical trial information: NCT05355701 .

Providing Suggested Rules for Multiple Primary Cancer Recording, Coding and Registering in Population-based Cancer Registry.

Multiple primary cancers (MPC) present many coding difficulties, while a distinction should be made between new cases and those with metastasis and/or extension and recurrence of the primary ones. We aimed to reflect on the experiences and results of data quality control of the East Azerbaijan/Iran Population-Based Cancer Registry and present our suggested rules for reporting, recording and registering multiple primary cancer. Comparability, validity, timeliness, and completeness of data assessment were performed. As a result, we created a consulting team including expert oncologists, pathologists, and gastroenterologists to discuss for multiple primary tumors recording, identifying, coding and registering. In case of confirmed Blood malignancies with definite BMB results, Brain and/or Bone involvements are always metastatic. In most cases of multiple cancers with the same morphological types, the earlier should be registered as primary tumor. In most of the synchronous multiple cancers, familial cancer syndromes should be considered and rules out. In case of two tumors diagnosed at the same time in colon and rectum, primary site should be detected by T stage or tumor sizes. In case of multiple tumors in Recto-sigmoid, Colon , and Rectum the earlier history of tumor should be considered as primary site. This rule was applied for Female Genital tumors, as earlier site is always the Primary cancer and other tumors should be registered as metastatic sites. Conclusion: Given the complexity of coding MPCs, we suggested some additional rules for identifying, recording, coding, and registering multiple primary cancers in the context of the EA-PBCR program.

Microstructural Changes in Normal-Appearing White Matter in Pediatric X-Linked Adrenoleukodystrophy: A Diffusion Tensor Imaging Study

Abstract Objective Diffusion tensor imaging (DTI) is an advanced magnetic resonance imaging (MRI) technique that provides quantitative diffusion data of water molecules in tissue. Usage of DTI in pediatric X-linked adrenoleukodystrophy (X-ALD) may adjunct earlier detection of brain involvement. This study aimed to analyze the normal-appearing white matter in pediatric patients with X-ALD using DTI. Materials and Methods A retrospective database search was performed. Children with genetically diagnosed X-ALDs with a reportedly normal brain MRI between January 2010 and September 2021 were included. Fractional anisotropy (FA), radial diffusivity (RD), axial diffusivity (AD), and apparent diffusion coefficient were serially measured in 8 regions of the brain, and these measurements were compared with those in control patients. Results The study group included 21 X-ALD patients and 11 control patients. The mean age was 6.64 ± 5.14 years. FA values of the genu and body of the corpus callosum were significantly lower in the ALD group than controls. There was also a statistically significant difference in FA, AD, and RD values of cerebellar white matter in the two groups. Conclusion There is evidence of white matter damage on DTI in X-ALD patients with the normal-appearing white matter on conventional MRI sequences. The inclusion of DTI in routine MRI examinations of X-ALD patients may provide additional insight into possible white matter damage in that population.

Brain and eye involvement in McCune-Albright Syndrome: clinical and translational insights.

McCune-Albright Syndrome (MAS) is a rare mosaic (post-zygotic) genetic disorder presenting with a broad continuum clinical spectrum. MAS arises from somatic, activating mutations in the GNAS gene, which induces a dysregulated Gsα-protein signaling in several tissues and an increased production of intracellular cyclic adenosine monophosphate (cAMP). Overall, MAS is a rare disorder affecting less than 1/100,000 children and, for this reason, data establishing genotype-phenotype correlations remain limited. Affected individuals clinically present with a variable combination of fibrous dysplasia of bone (FD), extra-skeletal manifestations (including cafeí-au-lait spots) and precocious puberty which might also be associated to broad hyperfunctioning endocrinopathies, and also gastrointestinal and cardiological involvement. Central nervous system (CNS) and eye involvement in MAS are among the less frequently described complications and remain largely uncharacterized. These rare complications mainly include neurodevelopmental abnormalities (e.g., delayed motor development, cognitive and language impairment), CNS anomalies (e.g., Chiari malformation type I) and a wide array of ophthalmological abnormalities often associated with vision loss. The pathophysiological mechanisms underlying abnormal neurological development have not been yet fully elucidated. The proposed mechanisms include a deleterious impact of chronically dysregulated Gsα-protein signaling on neurological function, or a secondary (damaging) effect of (antenatal and/or early postnatal) hypercortisolism on early pre- and post-natal CNS development. In this Review, we summarize the main neurological and ophthalmological features eventually associated with the MAS spectrum, also providing a detailed overview of the potential pathophysiological mechanisms underlying these clinical complications.

High tumor burden in patients with non-small-cell lung cancer: a Delphi survey among Spanish oncologists.

Aim: To define high tumor burden (HTB) in non-small-cell lung cancer. Methods: A total of fiveoncologists initiated the project, selecting 66 participants, and elaborated a questionnaire with 26 statements using the Delphi method with a 9-point Likert scale of agreement. Results: Factors with moderate strength of consensus wereidentified, including a sum of the longest diameter of lesions ≥10cm, elevatedLDH, hepatic involvement, lymphangitis carcinomatosis, brain involvement unapproachable with local techniques and pericardial effusion. There was a consensus against increases intumor markers and asymptomatic brain involvement being related to HTB. HTB was considered a relevant factor for treatment selection supporting thechoice of combination regimens versus immunotherapy only. Conclusion: In this Delphi study, experts defined several factors associated with HTB in non-small cell lung cancer.

Rare diagnosis of coexistent antiphospholipid syndrome and systemic lupus erythematosus in a male patient with successful management: a case report.

A 28-year-old male, referred to our hospital for the assessment of chest pain. Past medical history was significant for extensive deep venous thrombosis despite the appropriate management with a therapeutic dose of direct-acting oral anticoagulant. Prolonged partial thromboplastin time was not corrected by mixing study along with positive lupus anticoagulant, anticardiolipin, and B-2 glycoprotein antibodies. In addition, antinuclear antibodies, anti-DNA antibodies, and direct Coombs were positive with decreased levels of C3. The patient was diagnosed with SLE with brain, heart, and kidney involvement in the setting of antiphospholipid antibody syndrome. He was treated successfully with full recovery. SLE and APS both have sneaky ways of manifestation. Ineffective diagnosis and therapy could cause irreversible organ damage. Clinicians should have a high index of suspicion for APS, particularly in young patients who approach with spontaneous or unprovoked thromboses or unexplained recurrent early or late pregnancy loss. Anticoagulation, modifying cardiovascular risk factors, and identifying and treating any underlying inflammatory diseases are all part of the multidisciplinary care that is needed for management. Although male affection is rare, SLE and APS should be considered in male patients as these conditions tend to be more aggressive than in the female.

Intranasal infection by SARS-CoV-2 Omicron variants can induce inflammatory brain damage in newly weaned hamsters

ABSTRACT Children infected by SARS-CoV-2 Omicron variant may develop neurological complications. To study the pathogenesis in the growing brain, we intranasally challenged newly-weaned or mature hamsters with SARS-CoV-2 Omicron BA.2, BA.5, or Delta variant. Omicron BA.2 and Delta infection produced a significantly lower viral load in the lung tissues of newly-weaned than mature hamsters despite comparable histopathological damages. Newly-weaned hamsters had higher brain viral load, significantly increased cerebrospinal fluid concentration of TNF-α and CXCL10 and inflammatory damages including mild meningitis and parenchymal vascular congestion, despite sparse expression of nucleocapsid antigen in brain cells. Furthermore, 63.6% (28/44) of all SARS-CoV-2 infected newly-weaned hamsters showed microgliosis in olfactory bulb (OB), cerebral cortex, and hippocampus. In infected mature hamsters, microgliosis was observed mainly in OB and olfactory cortex of 35.3% (12/34) of their brains. Neuronal degeneration was found in 75% (33/44) of newly-weaned hamsters affecting multiple regions including OB, olfactory cortex, midbrain cortex, and hippocampus, while such changes were mainly observed in the hippocampus of mature hamsters. Importantly, similar brain histopathology was also observed in Omicron BA.5-infected newly-weaned hamsters. Our study suggested that SARS-CoV-2 may affect the brain at a young age. This kind of brain involvement and histological changes are not virus variant or subvariant specific. Incidentally, a moderate amount of eosinophilic infiltration was observed in the mucosa of nasal turbinate and trachea of newly-weaned hamsters infected by Omicron BA.2 and BA.5 but not Delta variant. This histological finding is consistent with the higher incidence of laryngotracheobronchitis in young children infected by the Omicron variant. Summary Intranasal infection of newly-weaned Syrian hamsters by SARS-CoV-2 Omicron variants can lead to brain inflammation and neuron degeneration with detectable low level of viral load and sparse expression of viral nucleoprotein.

A diagnostic conundrum in the time of a pandemic: a subtle, isolated myelopathy. (P10-5.028)

<h3>Objective:</h3> NA <h3>Background:</h3> Anti-CV2/collapsin response-mediator protein 5 (CRMP5) antibodies are considered “high-risk” markers, frequently associating with paraneoplastic syndromes (PNS). <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 44-year-old woman was recovering from a mild case of COVID-19 when she presented with a single episode of urinary retention and a subacute paraparesis with prominent sensory disturbances and girdle-like pain. Since a spinal cord MRI did not show any lesions and EMG did not detect any conduction defects, she refused further examinations and underwent empiric antimicrobial and steroid therapy, along with physical treatment. However, almost two months later she was still suffering from dysesthesia, dysuria, dyschezia and gait disturbance. A second MRI revealed multiple, asymmetric, short-segment lesions in the spinal cord, with persistent contrast-enhancement (despite the previous steroid treatment), but no brain involvement. Cerebrospinal fluid (CSF) analysis and infectious workup were unremarkable, detecting only a slight increase in CSF proteins and a mirror pattern. An extensive screening for autoimmune and paraneoplastic diseases disclosed anti-CV2/CRMP5 antibodies in the serum; however, antibody titer and confirmatory tests were not available at that time and there was no corresponding reactivity in her CSF. After 3 months the antibodies were still present, arguing for a PET scan, which was uneventful. In the meanwhile the woman was treated with IV steroids, followed by a slow oral tapering with gradual but significant improvement. Indeed, after 6 months the MRI showed a diffuse reduction of the spinal cord swelling and T2 signal change, with no contrast enhancement; her neurological exam still remains strikingly normal. <h3>Conclusions:</h3> This remarkable response to immunotherapy, along with the atypical clinical phenotype and radiographic findings (when compared to reported anti-CV2/CRMP-5 myelopathies), argues for an alternative diagnosis, contemplating a post-infectious etiology rather than a PNS. The case also underlines how commercial line blots should always be confirmed by alternative and more reliable techniques. <b>Disclosure:</b> Federica Boso has nothing to disclose. Dr. Giometto has nothing to disclose.

Outcome of Brain Lymphoma in a High Epstein-Barr Virus–Prevalence Country After Kidney Transplantation

The incidence of post-transplant lymphoproliferative disorder (PTLD) in adult kidney transplant (KTx) recipients is less common in Taiwan. In our institute, we observed that brain lymphoma was the most notorious type. The study describes the clinical, histologic, and radiological features of primary central nervous lymphoma (PCNSL) and the outcomes and associations with Epstein-Barr virus (EBV) infection in our center. Among 1470 KTx recipients, 5 patients had tissue-proven brain lymphoma (0.34%). The brain pathology disclosed diffuse large B-cell lymphoma in all patients. EBV was detected through in situ hybridization for Epstein-Barr encoding region (EBER) to disclose the EBV inclusion in the nuclei of lymphoma cells. The first treatment step was the reduction of immunosuppressants; 4 patients received whole-brain radiotherapy after complete resection of PCNSL, and 1 received concurrent chemoradiotherapy. Only one patient had poor performance status at the time of diagnosis and had a poor response to treatment with steroids. Four patients survived (mean 36.5 months, range 8.6 to 57.6 months), but one died after rapid neurologic deterioration. Epstein-Barr virus inclusion was found in PCNSL in our patients; however, the role of EBV in PCNSL remains to be clarified. Post-transplant lymphoproliferative disorder is a rare malignancy after KTx with a predilection of brain involvement in Taiwan. We report a successful care experience in a patient with primary CNS lymphoma with better survival.

Patient-Reported Outcomes in Myotonic Dystrophy Type 2: Correlations with Motor and Cognitive Endpoints (S7.007)

<h3>Objective:</h3> To characterize patient-reported outcomes (PROs) and evaluate relationships between PROs and clinical endpoints in patients with myotonic dystrophy type 2 (DM2). <h3>Background:</h3> Although muscle weakness is the key feature in DM2, two-thirds of patients report that impaired cognition is among the most disabling symptoms and affects their quality of life. PROs of physical and mental status are extremely limited in DM2 but could serve as measures for clinical trial development. <h3>Design/Methods:</h3> Ten individuals with DM2 and ten age and gender-matched controls were enrolled. All participants underwent brain MRIs and a comprehensive battery of cognitive and motor measures. Additionally, they completed PROs, including the 36-Item Short Form (SF-36), PRO Measurement Information System (PROMIS-10), Beck Depression and Anxiety Inventory (BDI and BAI), and Apathy Evaluation Scale (AES). Paired t-test and Spearman’s correlation were used to determine group differences and correlations between PROs and clinical endpoints. <h3>Results:</h3> Of 20 participants (60% female), mean age and education were similar between groups. Compared to controls, the DM2 group showed a significant difference in BAI, AES, and SF-36 physical functioning (PF) subscale (<i>p</i>=0.004–0.024) and impaired PROMIS-Global Physical (GPH) and Mental Health (GMH). We found a strong correlation between SF-36 (PF) and PROMIS-GPH with a 6-minute walk test and gait speed (<i>rho</i>=0.68–0.75, <i>p</i>=0.02–0.04). Moderate correlations were observed between 1) BDI and verbal fluency test; 2) BAI and processing speed; 3) AES and a test of executive function and cerebral white matter integrity. <h3>Conclusions:</h3> Our pilot study demonstrates that changes in mental and physical health status are of significance for DM2 patient’s quality of life. The relationships between PROs (BAI, BDI, and AES) and cognitive endpoints suggest brain involvement. PROs, as measured by SF-36 and PROMIS-10, are associated with motor endpoints. These results support the use of PROs as a tool to measure disease burden in DM2. <b>Disclosure:</b> Dr. Jain has nothing to disclose. Dr. Olszewski has nothing to disclose. Dr. Flashman has received personal compensation in the range of $500-$4,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Archives of Clinical Neuropsychology. The institution of Dr. Flashman has received research support from NIH/NINDS. The institution of Dr. Flashman has received research support from Michael J Fox Foundation. Mrs. Burgos-Aguilar has nothing to disclose. Dr. Duncan has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for BrainQ Technologies. Dr. Duncan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for University of Pittsburg Pepper Center. Dr. Duncan has stock in CareDirections. The institution of Dr. Duncan has received research support from PCORI. The institution of Dr. Duncan has received research support from NIA and NINDS. The institution of Dr. Duncan has received research support from AHRQ. Dr. Duncan has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Nopoulos has received personal compensation in the range of $500-$4,999 for serving as a Consultant for norvartis. The institution of Dr. Puwanant has received research support from Muscular Dystrophy Association. The institution of Dr. Puwanant has received research support from NIH/NINDS. The institution of Dr. Puwanant has received research support from NIH/NINDS.

Choroid Plexus Enlargement In Systemic Lupus Erythematosus: Relationship With Auto-Antibody Status And Neuropsychiatric Involvement (P10-3.016)

<h3>Objective:</h3> To evaluate whether choroid plexus (CP) enlargement occurs in patients with systemic lupus erythematosus (SLE) compared to healthy controls (HC) and is associated with auto-antibody status, neuropsychiatric involvement (NP-SLE) and structural brain damage. <h3>Background:</h3> CP enlargement has been suggested as a marker of neuroinflammation in multiple sclerosis, being associated with disease activity and clinical disability. CP involvement in SLE immunopathology has been recently hypothesized, however, the associations between CP enlargement, auto-antibody status, clinical manifestations and brain structural damage have not been fully explored yet. <h3>Design/Methods:</h3> Brain 3T dual-echo and 3D T1-weighted sequences were acquired from 32 SLE patients and 32 age- and sex-matched HC. CP volume was manually obtained from 3D T1-weighted scans and normalized by head size. CP volumes were compared between HC and SLE patients stratified according to auto-antibody status (anti-antiphospholipid [APA] and anti-double-stranded DNA [ADNA] antibodies) and NP involvement using linear models. Associations between CP volume and clinical and structural MRI variables were explored using linear regression analyses. <h3>Results:</h3> Compared to HC, only SLE patients with positive autoantibody status (APA [n=18] or ADNA [n=24) showed significantly higher white matter (WM) lesion volume (LV) (p=0.020 and 0.033), whereas only SLE patients with APA antibodies had a significant CP enlargement (p=0.013). Compared to HC, both non-NP-SLE (n=20) and NP-SLE patients (n=12) showed significantly higher CP volume (p=0.002 and &lt;0.001), whereas WM LV was significantly higher only in NP-SLE (p=0.001). Compared to non-NP-SLE, NPSLE patients had significantly higher CP volume (p=0.024) and WM LV (p=0.015). No between-group volumetric brain differences were found. No significant associations of CP volume with disease duration and activity, WM LV and normalized brain volume were found. <h3>Conclusions:</h3> CP enlargement occurs in SLE patients, especially in those with APA and NP involvement, suggesting its potential role in the pathophysiology of SLE related brain involvement. <b>Disclosure:</b> Dr. Gueye has nothing to disclose. 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. Giuseppe A. Ramirez has nothing to disclose. Enrica Bozzolo has nothing to disclose. Valentina Canti has nothing to disclose. Monica Margoni has received research support from MAGNIMS. Alessandro Meani has nothing to disclose. Patrizia Rovere-Querini has nothing to disclose. Angelo Manfredi 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 Clinical &amp; Experimental Immunology. 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. 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).

Use of disease assessment tools to increase the value of case reports on Susac syndrome: two case reports

BackgroundSusac syndrome is an immune-mediated, ischemia-producing, occlusive microvascular endotheliopathy that threatens the brain, retina, and inner ear. There is a need for disease assessment tools that can help clinicians and patients to more easily, accurately, and uniformly track the clinical course and outcome of Susac syndrome. Ideally, such tools should simultaneously facilitate the clinical care and study of Susac syndrome and improve the value of future case reports. To meet this need, two novel clinical assessment tools were developed: the Susac Symptoms Form and the Susac Disease Damage Score. The former is a comprehensive self-report form that is completed by patients/families to serially document the clinical status of a patient. The latter documents the extent of damage perceived by individual patients/families and their physicians. Both forms were initially trialed with two particularly representative and instructive patients. The results of this trial are shared in this report.Case presentationPatient 1 is a 21-year-old Caucasian female who presented with an acute onset of headache, paresthesias, cognitive dysfunction, and emotional lability. Patient 2 is a 14-year-old Caucasian female who presented with an acute onset of headache, cognitive dysfunction, urinary incontinence, ataxia, and personality change. Both patients fulfilled criteria for a definite diagnosis of Susac syndrome: both eventually developed brain, retinal, and inner ear involvement, and both had typical “snowball lesions” on magnetic resonance imaging. The Susac Symptoms Form documented initial improvement in both patients, was sufficiently sensitive in detecting a subsequent relapse in the second patient, and succinctly documented the long-term clinical course in both patients. The Disease Damage Score documented minimal disease damage in the first patient and more significant damage in the second.ConclusionsThe Susac Symptoms Form and the Disease Damage Score are useful disease assessment tools, both for clinical care and research purposes. Their use could enhance the value of future case reports on Susac syndrome and could improve opportunities to learn from a series of such reports.

A Deep Learning-based Approach for Colorization of Grayscale Images and Videos

Colorization is the process of converting grayscale photos into colorful ones that are more visually appealing. Previously, a wide range of colorization techniques has been developed, which require the involvement of the human brain which consumes a lot of time and energy. In today’s world, there are many procedures that will automatically convert the grayscale image to a color image. Most of the conversion techniques incorporate elements of deep learning, machine learning, and art. This study gives a novel technique for coloring grayscale images that makes use of GAN and U-Net model characteristics. By using this technique, the model is able to learn how to colorize images from a trained U- Net. Additionally, the Fusion layer is used to combine the global priors for each class with the local information finds for each class, which are based on small image patches. This produces colorization outcomes that are more attractive on a visual level. Finally, the results of the method were obtained by doing an evaluation based on user research and comparing it to the state-of-the-art

A CASE REPORT OF ASYMMETRIC BRACHIAL PLEXUS INVOLVEMENT IN LEPROSY NEUROPATHY DEMONSTRATED BY MAGNETIC RESONANCE IMAGING

Leprosy is a is a chronic granulomatous disease primarily affects the peripheral nerves and skin .Sometimes, the disease has an unusual presentation, crippling complications, and can be contagious, so its timely diagnosis and management are extremely important. In this case report 29-years-old male a case of biopsy proven Hansens disease-borderline tuberculoid type on MDT. Patient with complains of weakness of left upper limb and pain in the neck radiating to left upper limb since 1 month . MRI is commonly used for evaluating the plexus,brain and spinal cord Brachial plexus involvement is commonly seen in borderline tuberculoid variant .Thickening may be due to cell mediated immune response. A possibility of drug resistant leprosy was considered and adviced to continue MDT.Patient was treated as a case of bilateral brachial plexitis and transverse myelitis secondary to IRIS .Patient was managed with medication then improved

Sturge-Weber Syndrome: A Review of Pathophysiology, Genetics, Clinical Features, and Current Management Approache.

Sturge-Weber syndrome (SWS) is a congenital, sporadic, and rare neurocutaneous disorder, characterized by the presence of a facial port-wine birthmark (PWB), glaucoma, and neurological manifestations including leptomeningeal angiomatosis and seizures. It is caused by a postzygotic, somatic, gain-of-function variant of the GNAQ gene, and more recently, the GNA11 gene in association with distinctive clinical features. Neuroimaging can help identify and stratify patients at risk for significant complications allowing closer follow-up; although no presymptomatic treatment has been demonstrated to be effective to date, these patients could benefit from early treatment and/or supportive interventions. Choroid plexus (CP) thickness measurements in brain magnetic resonance imaging (MRI) have a high sensitivity and specificity for early and incipient changes in SWS. In contrast, the absence of pathologic findings makes it possible to rule out associated neurological involvement and leads to periodical observation, with new imaging studies only in cases of new clinical signs/symptoms. Periodic ophthalmological examination is also recommended every 3 months during the first year and yearly afterwards to monitor for glaucoma and choroidal hemangiomas. Treatment for SWS depends on the extent and areas that are affected. These include laser surgery for PWB, anticonvulsants in the case of brain involvement, with either seizures or abnormal EEG, and medical treatment or surgery for glaucoma. Sirolimus has been used in a limited number of patients and appears to be a safe and potentially effective treatment for cutaneous and extra-cutaneous features, however controlled clinical studies have not been carried out. Better knowledge of GNAQ/GNA11 molecular pathways will help to develop future targeted treatments.

Partial restoration of brain dystrophin by tricyclo-DNA antisense oligonucleotides alleviates emotional deficits in mdx52 mice

The mdx52 mouse model recapitulates a frequent mutation profile associated with brain involvement in Duchenne muscular dystrophy. Deletion of exon 52 impedes expression of two dystrophins (Dp427, Dp140) expressed in brain, and is eligible for therapeutic exon-skipping strategies. We previously showed that mdx52 mice display enhanced anxiety and fearfulness, and impaired associative fear learning. In this study, we examined the reversibility of these phenotypes using exon 51 skipping to restore exclusively Dp427 expression in the brain of mdx52 mice. We first show that a single intracerebroventricular administration of tricyclo-DNA antisense oligonucleotides targeting exon 51 restores 5%-15% of dystrophin protein expression in the hippocampus, cerebellum, and cortex, at stable levels between 7 and 11week after injection. Anxiety and unconditioned fear were significantly reduced in treated mdx52 mice and acquisition of fear conditioning appeared fully rescued, while fear memory tested 24h later was only partially improved. Additional restoration of Dp427 in skeletal and cardiac muscles by systemic treatment did not further improve the unconditioned fear response, confirming the central origin of this phenotype. These findings indicate that some emotional and cognitive deficits associated with dystrophin deficiency may be reversible or at least improved by partial postnatal dystrophin rescue.

Radiographic predictors of occult intracranial involvement in olfactory neuroblastoma patients.

Traditional management of olfactory neuroblastoma (ONB) includes margin-negative resection with removal of cribriform plate, dura, and olfactory bulb, regardless of intracranial disease. This approach may be overtreating certain patients. Our investigation examines risk factors associated with occult intracranial disease to optimize therapeutic outcomes. This retrospective, multi-institutional cohort study examined clinical covariates associated with occult intracranial involvement. Patient demographics, staging, Hyam's grade, and pathologic involvement of dura, olfactory bulb/tract, and brain were collected. Diagnostic imaging was reviewed. Positive and negative predictive value (NPV) were estimated along with effect size estimates. Cox hazard regression examined associations with overall survival (OS) and disease-free survival (DFS). A total of 224 subjects with new diagnoses of ONB (2005-2021) were identified. Skull base bone involvement on computed tomography (CT) had the highest NPV for pathologic dura (88.0%), olfactory bulb (88%), and brain involvement (97.3%). Hyam's grade category was significantly associated with dural involvement (φC =0.26; 95% confidence interval [CI]: 0.16, 0.42). Subjects without radiologic skull base involvement (n=66) had pathologic positivity of 12.1%. Within this subgroup, Hyam's grade was clinically significant for dural positivity (φ=0.34; 95% CI: -0.12, 0.71) with 28.6% involvement in high grade tumors. Neither clinical nor pathologic positivity of intracranial structures were associated with significantly different OS or DFS. Both CT and magnetic resonance imaging (MRI) had reasonably good NPV for involvement of dura and olfactory bulb. Higher Hyam's grade was associated with dural involvement. Patients with low-grade tumors not involving the skull base may be suitable for avoiding skull base resection; however, further investigation is warranted.