Central Nervous System Manifestations Research Articles

Chronic graft-versus-host disease myelitis successfully treated with rituximab.

Chronic graft-versus-host disease (cGVHD) is a major serious complication after allogeneic stem-cell transplantation (allo-HSCT), and often mimics autoimmune diseases. Central nervous system (CNS) symptoms are rare manifestations of cGVHD, and are difficult to diagnose. CNS manifestations of cGVHD were discussed in the 2020 National Institutes of Health cGVHD Consensus Project as one of the "atypical cGVHD manifestations" with involvement of various organ systems other than classical cGVHD organs. We experienced a case of myelitis after allo-HSCT diagnosed as cGVHD of the CNS. The neurological symptoms progressed after corticosteroid pulse therapy, resulting in severe paralysis and paresthesia of the lower extremities. The clinical course and magnetic resonance imaging findings showed some similarities with multiple sclerosis. We decided to use rituximab after the patient became refractory to corticosteroids because rituximab has been reported to be effective in multiple sclerosis by suppressing B cells on both sides of the blood-brain barrier. Rituximab was effective for the neurologic symptoms in our case. In atypical cGVHD, treatments used in corresponding autoimmune diseases may be reasonable and effective.

P-2294. Listeriosis in cancer patients: Uncommon and protean

Abstract Background Historically cancer patients (pts) are considered to be at an increased risk of Listeria monocytogenes infection (listeriosis, LT), especially those with ongoing chemotherapy or receipt of glucocorticoids (GCs). However, the features of this uncommon infection have not been described in contemporary cohorts of cancer pts. Methods We performed a 12-year retrospective chart review of cancer pts with LT as confirmed by positive culture from blood or other sterile clinical samples at MD Anderson Cancer Center (2011-2023). Results We identified 20 cancer pts with LT. Twelve (60%) had an underlying hematologic malignancy (Figure 1). Lymphopenia < 1000/µL (17, 85%, severe < 200/µL in 20%) and monocytopenia < 1000/µL (18, 90%, severe < 200/µL in 35%) were common at diagnosis, as well as chemotherapy (13, 65%) and GC use (11, 55%) within 30 days prior to LT diagnosis. Most (15 pts) were < 65 years old. Fever was seen in 10 pts. Vomiting/diarrhea were common (50%), while 45% of pts had headache or altered mental status. LT most often presented with bacteremia (17, 85%) and gastroenteritis (9, 45%) (Figure 2). 7/9 pts with gastroenteritis were bacteremic. Central nervous system (CNS) manifestations (meningitis, brain abscess) were documented in 2 pts who had a lumbar puncture. Focal non-CNS infections were seen in 30% of pts in unusual sites: cellulitis, abscess, endocarditis, cholangitis, urinary tract infection, and peritonitis. Of interest, 11pts (55%) had low SOFA score at presentation and were given antibiotics only after blood cultures were positive for Listeria. In fact, most pts (17, 85%) either did not receive empiric (n=11) or had inappropriate empiric antibiotics (n=6) until LT diagnosis. The 30-day mortality from LT diagnosis was 25% and correlated with high SOFA score ≥ 5 (5/8 pts, P = 0.0005). Delayed appropriate antibiotics were not significantly associated with increased 30-day mortality in this small cohort (Table 1). Conclusion Although uncommon, LT in cancer pts has pleotropic manifestations and variable morbidity, from non-bacteremic gastroenteritis to septicemia, CNS and non-CNS focal infections. Consider LT in ill cancer pts with lymphopenia/monocytopenia and recent chemotherapy or GCs, especially if they have GI symptoms, even in the absence of fever or CNS involvement. Disclosures Sebastian Wurster, MD, MSc, Astellas Pharma: Grant/Research Support|Gilead Sciences: Grant/Research Support Dimitrios P. Kontoyiannis, MD, AbbVie: Advisor/Consultant|Astellas Pharma: Advisor/Consultant|Astellas Pharma: Grant/Research Support|Astellas Pharma: Honoraria|Cidara Therapeutics: Advisor/Consultant|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Knight: Advisor/Consultant|Merck: Advisor/Consultant|Scynexis: Advisor/Consultant

P-147. Exploring the Complexity of Brucellosis: Findings from a Prospective Observational Study at AIIMS, Jodhpur

Abstract Background Brucellosis, a global health concern, is often misidentified due to diagnostic complexities. In India, its prevalence is estimated at 13.5%. This study examines its microbiological and clinical spectrum for improved management. Methods AIIMS, Jodhpur, conducted a prospective observational study from April 2021 to March 2024, examining patient records for demographic data, clinical presentations, laboratory and microbiological findings, treatment approaches, outcomes, and excluding alternative causes of pyrexia of unknown origin (PUO) Results Among 1142 cases analyzed, 43 were confirmed positive for brucellosis subsequent to thorough exclusion criteria. The most common age group affected by brucellosis, intriguingly, was those under 20 years, comprising 53.49% of the cases, followed by individuals aged 21 to 50 years at 30.23%, with those over 50 years representing 16.27% of the cases. The study unveiled a spectrum of clinical presentations, including 34 cases of PUO, 3 instances of spinal involvement, 5 cases with Central Nervous System (CNS) manifestations, as well as isolated occurrences of Endocarditis and Kikuchi Disease, underscoring the diverse clinical manifestations associated with brucellosis. Noteworthy clinical indicators included a high prevalence of unpasteurized milk consumption (76.74%), fever (88.37%), and joint pain (62.79%). Predominantly, B. Melitensis accounted for 30 cases, followed by B. Abortus with 11 cases and B. Suis with 2 cases. Conclusion This study reaffirms the significant diagnostic challenge posed by brucellosis, particularly within the spectrum of PUO. Blood culture emerges as a cornerstone in the reliable diagnosis of the infection. Disclosures All Authors: No reported disclosures

Choroid plexus-targeted viral gene therapy for alpha-mannosidosis, a prototypical neurometabolic lysosomal storage disease.

The choroid plexuses (CP) are highly vascularized structures that project into the ventricles of the vertebrate brain. The polarized epithelia of the CP produce cerebrospinal fluid by transporting water and ions into the ventricles from the blood and normally secrete a large number of proteins. We assessed the feasibility of selective CP transduction with recombinant adeno-associated virus (rAAV) gene therapy vectors for treatment of lysosomal storage disease (LSD), a broad category of neurometabolic illness associated with significant burdens to affected patients and their families. There are no ideal or complete therapeutic options currently available, especially for the central nervous system manifestations of LSDs. Alpha-mannosidosis (AMD) is an autosomal recessive prototypical LSD caused by deficiency of lysosomal alpha-mannosidase and characterized by cerebellar ataxia, neurocognitive disability, facial and skeletal abnormalities, hearing impairment, and mild immune deficiency. In a murine model of AMD, we compared the biochemical effects of CSF-directed rAAV serotypes 1, 4, 5, 6, and 9. Recombinant AAV1 and rAAV6, two closely related serotypes whose capsid sequences differ by only six amino acids, showed the most robust transduction of CP in mouse brain, consistent with their transduction of CPE in nonhuman primates and cats, as well as in other structures. We found restoration of LAMAN enzyme activity comparable to or higher than AMD heterozygote levels in the brain globally (olfactory bulb, cortex, cerebellum, brainstem). Further IND-generating preclinical experiments will advance rAAV6-LAMAN, which appears to be the most promising choroid plexus-targeting candidate serotype for future clinical translation to treat AMD.

Emerging concepts and treatments in autoinflammatory interferonopathies and monogenic systemic lupus erythematosus.

Over the past two decades, the number of genetically defined autoinflammatory interferonopathies has steadily increased. Aicardi-Goutières syndrome and proteasome-associated autoinflammatory syndromes (PRAAS, also known as CANDLE) are caused by genetic defects that impair homeostatic intracellular nucleic acid and protein processing respectively. Research into these genetic defects revealed intracellular sensors that activate type I interferon production. In SAVI and COPA syndrome, genetic defects that cause chronic activation of the dinucleotide sensor stimulator of interferon genes (STING) share features of lung inflammation and fibrosis; and selected mutations that amplify interferon-α/β receptor signalling cause central nervous system manifestations resembling Aicardi-Goutières syndrome. Research into the monogenic causes of childhood-onset systemic lupus erythematosus (SLE) demonstrates the pathogenic role of autoantibodies to particle-bound extracellular nucleic acids that distinguishes monogenic SLE from the autoinflammatory interferonopathies. This Review introduces a classification for autoinflammatory interferonopathies and discusses the divergent and shared pathomechanisms of interferon production and signalling in these diseases. Early success with drugs that block type I interferon signalling, new insights into the roles of cytoplasmic DNA or RNA sensors, pathways in type I interferon production and organ-specific pathology of the autoinflammatory interferonopathies and monogenic SLE, reveal novel drug targets that could personalize treatment approaches.

INNV-02. BRAINMETS: A CLINICIAN-FRIENDLY SOFTWARE TO MANUALLY SEGMENT BRAIN METASTASES AND DETECT PRIMARY TUMOR ORIGIN USING DEEP LEARNING

Abstract Estimates suggest that around 20%-40% of cancer patients are affected by brain metastases. A subset of these patients first present with central nervous system manifestations with an unknown primary. The issue then arises regarding which region of the body should be imaged, if not the entire body, exposing the patient to more radiation. To address this issue, streamline workflows, and save precious time, we developed a software clinicians can use to identify primary tumor locus. “BrainMets” is a user-friendly software that handles a DICOM input, allows the user to segment the region(s) of interest manually, and uses a deep learning model to predict the most likely tumor origin. The model is a mixed-effects neural network pre-trained on radiomic features from open-source data by Ocaña-Tienda et al. (2023) using 637 high-resolution imaging studies from 10 different medical centers with an accuracy of 90.5%, precision of 92.7%, recall of 87.8%, and F1 score of 90.2%. The software leverages the open-source software 3D-Slicer to help segment regions of interest, extract radiomic features, and make predictions. It is built using Flask, a Python package for backend development. The frontend user interface is created using HTML/CSS and Bootstrap. The “BrainMets” software thus strives to enhance diagnostic workflow significantly, reduce appointment times for scans, and improve patient experience. Future enhancements include integrating more AI models, improving healthcare IT system compatibility, and updating datasets to boost predictive accuracy and generalizability. This tool sets a new standard in personalized medicine, optimizing treatment strategies for cancer patients with brain metastases. As adoption increases, it could substantially improve patient outcomes and reduce healthcare costs associated with misdiagnosis and overtreatment. Further research and development will focus on expanding its applicability across various types of cancers.

Neurological manifestations of lysosomal storage diseases.

Lysosomal storage diseases (LSDs) encompass a group of rare inherited metabolic disorders characterized by the accumulation of undegraded substrates within lysosomes, leading to multisystemic manifestations, including profound neurological involvement. This article provides a concise overview of the neurological manifestations of LSDs, with a focus on central nervous system (CNS) involvement and treatment strategies. While the paper intricacies of each LSD subtype and its associated CNS manifestations, it aims to provide a summary of the essential findings and implications. The neurological manifestations of LSDs encompass a spectrum of symptoms, including cognitive impairment, motor dysfunction, seizures, and sensory deficits, which significantly impact patients' quality of life and pose therapeutic challenges. Current treatment strategies primarily aim to alleviate symptoms and slow disease progression, with limited success in reversing established neurological damage. Enzyme replacement therapy, substrate reduction therapy, and emerging gene therapies hold promise for addressing CNS involvement in LSDs. However, challenges such as blood-brain barrier penetration and long-term efficacy remain. In addition to discussing treatment modalities, this article highlights the importance of early diagnosis, multidisciplinary care, and patient advocacy in optimizing outcomes for individuals affected by LSDs. Ethical considerations are also addressed, including equitable access to emerging treatments and integrating personalized medicine approaches. Overall, this article underscores the complex interplay between genetics, neuroscience, and clinical care in understanding and managing the neurological manifestations of LSDs while emphasizing the need for continued research and collaboration to advance therapeutic interventions and improve patient outcomes.

Central nervous system manifestations of tuberous sclerosis complex: A single centre experience in Qatar.

To review the clinical and radiological correlation of the central nervous system manifestations of tuberous sclerosis complex (TSC). All patients under the age of 18 years with TSC seen at the Department of Pediatrics, Sidra Medicine, Doha, Qatar, between January 2003 and February 2021 were included in this retrospective study. Severity of epilepsy was determined using the early childhood epilepsy severity score (E-CHESS) tool. The study sample included 38 patients (50% male), 8 (21%) of whom were native to Qatar. The median age at diagnosis was 4 (range: 0-72) months. A family history of TSC was present in 10 (26%) cases, while 33 (86%) patients had a TSC2 gene mutation. Common presentations included seizures (79%), rhabdomyoma (26%), and developmental delay (13%). On MRI scans, cortical tubers were seen in all patients, subependymal nodules in 37 (97%), and subependymal giant cell astrocytoma was diagnosed in 8 (21%) cases. A total of 30 children developed epilepsy, 9 of whom had favorable and 21 had unfavorable E-CHESS scores, and 6 required pharmaceutical management. A total of 13 children were diagnosed with autistic spectrum disorder and 12 with attention deficit hyperactivity disorder. Multidisciplinary management and further research is needed to optimize the care and quality of life of TSC affected individuals and their families.

Central nervous system manifestations in acute and chronic graft-versus-host disease.

Despite the growing evidence supporting the existence of CNS involvement in acute and chronic graft-versus-host disease (CNS-GvHD), the characteristics and course of the disease are still largely unknown. In this multicenter retrospective study, we analyzed the clinical, biological, radiological, and histopathological characteristics, as well as the clinical course of 66 patients diagnosed with possible CNS-GvHD (pCNS-GvHD), selected by predetermined diagnostic criteria. Results were then contrasted depending on whether pCNS-GvHD occurred before or after day 100 following allogeneic hematopoietic stem cell transplantation. Median time between hematopoietic stem cell transplantation and pCNS-GvHD onset was 149 days (IQ25-75 48-321), and pCNS-GvHD onset occurred before day 100 following transplantation in 44% of patients. The most frequent findings at presentation were cognitive impairment (41%), paresis (21%), altered consciousness (20%), sensory impairment (18%), and headache (15%). Clinical presentation did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Brain MRI found abnormalities compatible with the clinical picture in 57% of patients, while CT detected abnormalities in only 7%. Seven patients had documented spinal cord MRI abnormalities, all of them with pCNS-GvHD occurring after day 100 following transplantation. In the cerebrospinal fluid, white blood cell count was increased in 56% of the population (median 18 cells/μL). Histopathological analyses were performed on 12 specimens and were suggestive of pCNS-GvHD in 10. All compatible specimens showed parenchymal and perivascular infiltration by CD3+ and CD163+ cells. Immunosuppressive therapy was prescribed in 97% of patients, achieving complete clinical response in 27%, partial improvement in 47% and stable disease in 6%. Response to immunosuppressive therapy did not significantly differ between patients with pCNS-GvHD occurring before or after day 100 following transplantation. Clinical relapse was observed in 31% of patients who initially responded to treatment. One-year overall survival following pCNS-GvHD onset was 41%. Onset before day 100 following hematopoietic stem cell transplantation (HR [95%CI]: 2.1 [1.0-4.5]; P=0.041) and altered consciousness at initial presentation (HR [95%CI]: 3.0 [1.3-6.7]; P=0.0077) were associated with a reduced one-year overall survival probability. Among surviving patients, 61% had neurological sequelae. This study supports that immune-mediated CNS manifestations may occur following allo-HSCT. These can be associated with both acute and chronic GvHD and carry a grim prognosis. The clinical presentation as well as the radiological and biological findings appear variable.

Tumefactive Demyelination Lesions: Report on Three Cases

Abstract Purpose: Tumefactive demyelination (TD) lesion and its subtype Balo’s concentric sclerosis (BCS), are rare manifestations of central nervous system demyelinating disease. Because of its rarity, physicians might hesitate in reaching a diagnosis or initiating steroid pulse therapy. This study aims at pinpointing the key neuroimaging features to distinguish TD lesions from surgical conditions, and illustrating the clinical outcomes of patients with TD lesions. Case report: Two of the three patients had solitary TD lesions, one 47-year-old man presenting with newly onset seizure and another 54-year-old women suffering from progressive hemiparesis. The male patient underwent craniotomy for mass excision without further steroid therapy, while the female patient received methylprednisolone pulse therapy only. Both patients remained free of clinical and radiological relapses over the past 6-7 years, leading to the diagnosis of clinically isolated syndrome. The third case is a 30-year-old woman with subacute onset of dysarthria and hemiparesis. She had two BCS lesions along with other demyelinating lesions in the juxtacortical and periventricular regions, cerebellar peduncles, and spinal cord, fulfilling dissemination in time and space. Her neurological deficits resolved after pulse therapy, and she received long-term disease modifying therapy for multiple sclerosis. Conclusion: This study underscores the diverse neuroimaging and clinical presentations of patients with TD lesions, and emphasizes the importance of clinical vigilance regarding this rare condition.

A Histopathological Study on the Changes in the Central Nervous System of Dead Cats With Neurological Symptoms

Background: Neurological conditions constitute approximately 10% of feline cases referred to veterinary clinics. Such cases often present manifestations of central nervous system (CNS) damage, including inflammatory lesions, neoplastic growth and structural and cellular transformations. Objectives: This study aimed at identifying histopathological changes in the CNS of cats that had succumbed to neurological symptoms. Methods: Microscopic evaluation of different sections within the CNS was conducted on 20 cats that had either died naturally or were euthanized due to neurological signs. After performing a necropsy, we examined the CNS tissues and conducted PCR testing to screen for possible viral infections, including feline infectious peritonitis (FIP), feline immunodeficiency virus (FIV) and feline leukemia virus (FeLV). Results: The majority of cases showed characteristic histopathologic lesions, notably mononuclear and suppurative meningoencephalitis, perivascular cuffing, disseminated intravascular coagulation (DIC), granulomatous meningoencephalitis, acute neuronal necrosis, liquefactive necrosis, epididymitis, thrombosis and demyelination. Among the 20 cats studied, 12 tested positive for FIP by PCR analysis, while 5 cats exhibited positive results for FIV. Also, FeLV PCR tests displayed positive results in 4 cats. No evidence of feline spongiform encephalopathy (FSE) was observed. Conclusion: This study is the first of its kind conducted in Iran. Based on the results, the most prevalent viral agents infecting cats’ CNS were FIP, FIV and FeLV. The investigation revealed no evidence of FSE in cats with neurological signs.

Critical Pertussis: “Prevention is better than cure”

Abstract The global incidence of pertussis has increased in the last two decades. Critical pertussis (cases necessitating intensive care unit admission or resulting in death) is a major health concern, especially among infants. Inadequately transferred maternal immunity, high susceptibility to disease before completion of the primary immunization schedule, and differential expression of pertussis toxins are some of the proposed reasons for higher disease burden in infancy. Adolescent children with waning immunity and susceptible adults contribute to the transmission of the disease. Siblings and parents are a major source of infection in infants. Multisystem involvement includes respiratory failure, central nervous system manifestations, shock, and pulmonary artery hypertension. Hyperleukocytosis, a characteristic feature of critical pertussis, is a proven risk factor for increased mortality. Other predictors of mortality include pulmonary artery hypertension, requirement of mechanical ventilation, and vasoactive requirements. Early macrolide antibiotics and organ support measures are the major domains of management. Intensive care needs include mechanical ventilation, inotropic support, and leukodepletion measures. Studies regarding optimal management strategies are scarce, and strategies like leukapheresis or ECMO have shown variable mortality benefit in literature. Routine immunization along with adolescent booster dose and immunization of pregnant mothers have shown promising impacts on reducing pertussis-related morbidity and mortality. We describe the updates regarding the risk factors for resurgence, disease morbidity, and management strategies in children with critical pertussis.

Behçet's disease modifies the gingival inflammatory response.

Behçet's disease (BD) pathogenesis involves severe outcomes such as blindness, central nervous system manifestations, and deep venous thrombosis that impacts systemic and local inflammatory changes. We tested the hypothesis that BD negatively affects gingival health and increases the severity of gingivitis. The study included 37 BD patients with gingivitis without any sign of periodontitis. Systemically healthy 19 patients with gingivitis (G) and 20 periodontally and systemically healthy individuals (C) were recruited as controls. BD patients were further grouped as stable and unstable based on their responses to BD treatment. Clinical periodontal parameters were measured to determine the impact of BD on gingival health. Serum and saliva levels of ELA-2 (neutrophil elastase-2), SLPI (secretory leukocyte protease inhibitor), α1-AT (alpha1-anti-trypsin), VEGF (vascular endothelial growth factor), IL-6 (interleukin-6), IL-8 (interleukin-8), and TNF-α (tumor necrosis factor alpha) were analyzed using multiplex immunoassay to measure the systemic and local inflammatory impact of BD. Plaque index (PI), probing pocket depth (PPD), and bleeding on probing (BOP) were significantly higher in the BD group than in the controls (p<0.05). IL-6 was higher in both serum and saliva in the BD group than in the G group (p<0.05). ELA-2 levels in saliva were higher in the stable BD group than in the controls, while TNF-α and SLPI were statistically significantly higher in BD than in the control (p<0.05). Salivary α1-AT level was statistically lower in the BD group compared to the control group. Our study suggested that the gingival inflammatory profile was impaired in patients with BD.

Neuroinflammatory Disorders of the Central Nervous System Associated with Monkeypox Virus Infection: A Systematic Review and Call to Action.

The Monkeypox virus, a zoonotic pathogen of the Orthopoxvirus genus, has shown a marked global spread, resulting in cases of neuroinflammatory disorders. This systematic review aims to summarize the central nervous system manifestations linked to monkeypox virus infection. We conducted a systematic review according to PRISMA guidelines. Databases such as PubMed, EMBASE, Cochrane Library, and Web of Science were searched up to September 2024. Inclusion criteria focused on monkeypox virus-positive patients with confirmed central nervous system inflammatory disorders, including encephalitis, meningitis, myelitis, and related neuroimmune diseases. From 770 screened articles, 38 studies were included. Of the 20 reported monkeypox virus-infected cases with central nervous system involvement, the most common manifestations were encephalitis (40%), encephalomyelitis (30%), and meningoencephalitis (10%). Additional rarer presentations included Guillain-Barré syndrome (5%) and transverse myelitis (5%). The mean age of affected individuals was 27.9±13.69 years, and 75% were male. Fever, fatigue, and myalgia were the predominant systemic symptoms, with neurological complications often appearing within 4.6±2.5 days post-infection. Diagnoses were confirmed by quantitative reverse transcription polymerase chain reaction, magnetic resonance imaging, and cerebrospinal fluid analysis. Treatment strategies varied, with antivirals (e.g., tecovirimat) and immunomodulatory therapies (e.g., methylprednisolone, immunoglobulins, and rituximab) utilized. Monkeypox virus infection is associated with severe neuroinflammatory disorders, with varying outcomes from complete recovery to mortality. Increased awareness, comprehensive diagnostic approaches, and targeted therapeutic interventions are critical in managing these cases. Further research is required to elucidate the mechanisms of neuroinflammation in the monkeypox virus and establish standardized treatment protocols.

Tuberous Sclerosis Complex and the kidneys: what nephrologists need to know.

Tuberous sclerosis complex (TSC) is an autosomal dominant disease characterized by the development of hamartomas in the central nervous system, heart, skin, lungs, and kidneys and other manifestations including seizures, cortical tubers, radial migration lines, autism and cognitive disability. The disease is associated with pathogenic variants in the TSC1 or TSC2 genes, resulting in the hyperactivation of the mTOR pathway, a key regulator of cell growth and metabolism. Consequently, the hyperactivation of the mTOR pathway leads to abnormal tissue proliferation and the development of solid tumors. Kidney involvement in TSC is characterized by the development of cystic lesions, renal cell carcinoma and renal angiomyolipomas, which may progress and cause pain, bleeding, and loss of kidney function. Over the past years, there has been a notable shift in the therapeutic approach to TSC, particularly in addressing renal manifestations. mTOR inhibitors have emerged as the primary therapeutic option, whereas surgical interventions like nephrectomy and embolization being reserved primarily for complications unresponsive to clinical treatment, such as severe renal hemorrhage. This review focuses on the main clinical characteristics of TSC, the mechanisms underlying kidney involvement, the recent advances in therapy for kidney lesions, and the future perspectives.

Central and Peripheral Nervous System Manifestations Associated with Dengue Illness.

Dengue illness, caused by the dengue viruses, continues to be a major global health concern, with increasing incidence and the emergence of severe manifestations such as neurological complications. An overview of the current understanding of dengue epidemiology, clinical manifestations, and research priorities is presented here. Dengue transmission has escalated in recent years, exacerbated by factors such as vector expansion, climate change, and socioeconomic challenges. The clinical spectrum of dengue ranges from mild febrile illness to severe manifestations, including hemorrhagic fever and neurological complications. Neurological manifestations of dengue, once considered rare, are now increasingly reported, encompassing encephalitis, myelitis, and Guillain-Barré Syndrome, among others. Diagnosis primarily relies on laboratory methods such as RT/PCR, NS1 antigen detection, and serological assays. Despite advancements in understanding the dengue pathogenesis, there remains a critical need for effective vaccines, antiviral drugs, improved surveillance methods, predictive models for disease severity, and long-term studies on post-Dengue sequelae. Integrated programs and holistic approaches to dengue control are essential for mitigating its impact. Addressing these research priorities will be pivotal in combating dengue and reducing its global burden.

Central Nervous System Involvement in Systemic Autoimmune Rheumatic Diseases-Diagnosis and Treatment.

Central nervous system (CNS) involvement in autoimmune rheumatic diseases represents a significant challenge for clinicians across all specialties. While most reviews on the subject focus on neurological manifestations within a specific rheumatic disease, few descriptions shift from neurological clinical syndromes to achieve rheumatological diagnoses. This narrative review aims to synthesize current knowledge on the diagnosis and management of CNS manifestations occurring in the most prevalent rheumatic conditions in adults. We searched the MEDLINE database using the terms "central nervous system", "rheumatic diseases", "systemic lupus erythematosus", "rheumatoid arthritis", "Sjögren syndrome", and "vasculitis". The search strategy included review articles from 2019 to 2024, published in English, Spanish, or Portuguese. We explored the pathophysiological mechanisms linking autoimmunity to CNS pathology, emphasizing the role of syndromic reasoning, autoantibody profiles, and imaging modalities as tools for diagnosis and determination of inflammatory activity. The review also discusses differential diagnoses through a stepwise approach to neurological syndromes, summarized in diagnostic flowcharts, and presents updated treatment options. Although our approach is primarily semiology-based, the complexity of the subject invites future endeavors involving new technologies, such as functional MRI, MR spectroscopy, and nuclear medicine.

COVID-19 related acute necrotizing encephalopathy and acute myocarditis in an adult female: a novel case report of brain injury and myocarditis

BackgroundAcute necrotizing encephalopathy (ANE) and myocarditis are both acute, life-threatening conditions that can be triggered by COVID-19. We report a case of sequential ANE and myocarditis following a COVID-19 infection.Case presentationA 27-year-old female patient was brought to the emergency department due to episodes of fever for two days and a 9-h altered state of consciousness. Her condition rapidly developed into stuporous and hemodynamic instability within serval hours. Veno-arterial extracorporeal membrane oxygenation (ECMO) was rapidly initiated with other supportive treatments. The following-up MRI showed bilateral, symmetrically distributed lesions in the brainstem, bilateral hippocampal regions, and bilateral basal ganglia, consistent with ANE. The diagnosis was confirmed through the detection of SARS-CoV-2 and the exclusion of other potential causes. After weeks of medical treatment, her condition stabilized, and she was transferred for further rehabilitation treatment.ConclusionsThis case study indicates that COVID-19 may simultaneously and rapidly affect the central nervous system and cardiovascular system, leading to poor outcomes. Accurate diagnosis and timely invasive bridging therapy, when necessary, can be lifesaving. Further exploration of potential mechanisms underlying COVID-19 central nervous system (CNS) and cardiovascular system manifestations will be important.

Synergistic effects of resveratrol and enzyme replacement therapy in the Mucopolysaccharidosis type I

Mucopolysaccharidosis type I (MPS I) is a rare genetic disorder caused by mutations in the IDUA gene, leading to alpha-L-iduronidase enzyme deficiency and resulting in the accumulation of glycosaminoglycans (GAG; heparan and dermatan sulfate) in lysosomes. The consequent GAG accumulation within cells leads to organ dysfunction and a range of debilitating symptoms. Enzyme replacement therapy (ERT) is the prevailing treatment, but its limitations (including high cost, time requirements, inefficiency in treatment of central nervous system (CNS), and immunogenicity) necessitate exploration of alternative therapeutic strategies. This research propose a novel approach leveraging the synergistic effects of ERT and resveratrol-induced autophagy. Resveratrol, with its immunomodulatory and GAG degradation-stimulating properties, holds a promise in mitigating immune responses triggered by ERT. Moreover, its ability to penetrate the blood–brain barrier presents a potential solution for addressing CNS manifestations. This study employed cells from MPS I patients to investigate the combined effects of resveratrol and the enzyme. Evaluation of the therapeutic impact involved assessing GAG accumulation, enzyme testing, and examining lysosome functionality and the autophagy process through fluorescence microscopy and Western blotting. The combined therapy stimulated the lysosomal mannose-6-phosphate receptor (M6PR) and lysosome biogenesis through the transcription factor EB (TFEB). Additionally, initial block of autophagy in autophagosome formation was relieved after the combined therapy and resveratrol alone. Together with increased enzyme activity through stimulation of the receptor, this synergistic therapy can be considered a new potential treatment for MPS I patients, improving their overall quality of life.

Neurologic Manifestations of Rheumatologic Disorders.

This article provides an overview of the neurologic manifestations of sarcoidosis and select rheumatologic disorders. An approach to the assessment and differential diagnosis of characteristic clinical presentations, including meningitis and vasculitis, is also reviewed. A review of treatment options is included as well as discussion of distinct areas of overlap, including rheumatologic disease in the setting of neuromyelitis spectrum disorder and demyelinating disease in the setting of tumor necrosis factor-α inhibitors. An increased understanding of the immune mechanisms involved in sarcoidosis and rheumatologic diseases has resulted in a greater diversity of therapeutic options for their treatment. Evidence directing the treatment of the central nervous system (CNS) manifestations of these same diseases is lacking, with a paucity of controlled trials. It is important to have a basic knowledge of the common CNS manifestations of rheumatologic diseases and sarcoidosis so that they can be recognized when encountered. In the context of many systemic inflammatory diseases, including systemic lupus erythematosus, IgG4-related disease, and sarcoidosis, CNS disease may be a presenting feature or occur without systemic manifestations of the disease, making familiarity with these diseases even more important.