Synthesis, characterization, and anti-inflammatory activity of tetrahydropiperine, piperic acid, and tetrahydropiperic acid via down regulation of NF-κB pathway.

The present study describes the synthesis, characterization, and evaluation of tetrahydropiperine (THP), piperic acid (PA), and tetrahydropiperic acid (THPA) as anti-inflammatory agents. THPA demonstrated potent anti-inflammatory activity among all the compounds. The anti-inflammatory potential was investigated in both in-vitro and in-vivo experimental models. Our findings demonstrated that THPA effectively suppressed the production of pro-inflammatory mediators, including nitric oxide and pro-inflammatory cytokines (TNF-α, IL-6, and IL-1ß) in both in vitro and in vivo. Additionally, THPA attenuated the expression of i-NOS and COX-2 in RAW 264.7 macrophages. The oral administration of THPA significantly reduced carrageenan induced paw edema thickness and alleviated liver, lung, and kidney injury induced by LPS. THPA also reduced the infiltration of inflammatory cells, prevented the occurrence of significant lesions, and mitigated tissue damage. Moreover, THPA significantly improved the survival rate of mice challenged with LPS. Our western blot studies also found that LPS induced NF-κB activation was downregulated by treatment with THPA in an in vivo system. These results collectively illustrated the potential of THPA as a therapeutic agent for treating inflammatory diseases.

Comparative analysis of late-stage rheumatoid arthritis and osteoarthritis reveals shared histopathological features.

OBJECTIVES: Osteoarthritis (OA) is a debilitating and heterogeneous condition, characterized by various levels of articular cartilage degradation, osteophytes formation, and synovial inflammation. Multiple evidences suggest that synovitis may appear early in the disease development and correlates with disease severity and pain, therefore representing a relevant therapeutic target. In a typical synovitis-driven joint disease, namely rheumatoid arthritis (RA), several pathotypes have been described by our group and associated with clinical phenotypes, disease progression, and response to therapy. However, whether these pathotypes can be also observed in the OA synovium is currently unknown. METHODS: Here, using histological approaches combined with semi-quantitative scoring and quantitative digital image analyses, we comparatively characterize the immune cell infiltration in a large cohort of OA and RA synovial tissue samples collected at the time of total joint replacement. RESULTS: We demonstrate that OA synovium can be categorized also into three pathotypes and characterized by disease- and stage-specific features. Moreover, we revealed that pathotypes specifically reflect distinct levels of peripheral inflammation. CONCLUSIONS: In this study, we provide a novel and relevant pathological classification of OA synovial inflammation. Further studies investigating synovial molecular pathology in OA may contribute to the development of disease-modifying therapies.

Semisynthesis of Novel Dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione Natural Product Hybrids of Parthenin Followed by Their Cytotoxicity Evaluation.

Natural products possess unique and broader intricacies in the chemical space and have been essential for drug discovery. The crucial factor for drug discovery success is not the size of the library but rather its structural diversity. Although reports on the number of new structurally diverse natural products (NPs) have declined recently, researchers follow the next logical step: synthesizing natural product hybrids and their analogues using the most potent tool, diversity-oriented synthesis (DOS). Here, we use weed Parthenium hysterophorus as a source of parthenin for synthesis of novel dispiro-pyrrolizidino/thiopyrrolizidino-oxindolo/indanedione natural product hybrids of parthenin via chemo-, regio-, and stereoselective azomethine ylide cycloaddition. All synthesized compounds were characterized through a detailed analysis of one-dimensional (1D) and two-dimensional (2D) NMR and HRMS data, and the stereochemistries of the compounds were confirmed by X-ray diffraction analysis. All compounds were evaluated for their cytotoxicity against four cell lines (HCT-116, A549, Mia-Paca-2, and MCF-7), and compound 6 inhibited the HCT-116 cells with an IC50 of 5.0 ± 0.08 µM.

Gold nanoblackbodies-based multifunctional nanocomposite for multimodal cancer therapy.

Multifunctional nanocomposites are of potential use to achieve complete tumor elimination and, thus, to avoid tumor recurrence. Herein, polydopamine (PDA)-based gold nanoblackbodies (AuNBs) loaded with indocyanine green (ICG) and Doxorubicin (DOX) termed as A-P-I-D nanocomposite were investigated for multimodal plasmonic photothermal-photodynamic-chemotherapy. Upon near-infrared (NIR) irradiation, A-P-I-D nanocomposite showed enhanced photothermal conversion efficiency of 69.2% compared to bare AuNBs (62.9%) due to the presence of ICG, along with ROS (1O2) generation as well as enhanced DOX release. On assessment of therapeutic effects on breast cancer (MCF-7) and melanoma (B16F10) cell lines, A-P-I-D nanocomposite showed significantly lower cell viabilities of 45.5% and 24% compared to 79.3% and 76.8% for AuNBs. Fluorescence images of stained cells revealed characteristic signs of apoptotic mode of cell death, with almost complete damage on A-P-I-D nanocomposite + NIR treated cells. Further, on evaluation of photothermal performance through breast tumor-tissue mimicking phantoms, A-P-I-D nanocomposite provided required thermal ablation temperatures within the tumor along with the potential for the elimination of residual cancerous cells through photodynamic therapy and chemotherapy. Overall, this study demonstrates that A-P-I-D nanocomposite + NIR provides better therapeutic outcome on cell lines and enhanced photothermal performance on breast tumor-tissue mimicking phantoms to be a promising agent for multimodal cancer therapy.

Do environmental technology and banking sector development matter for green growth? Evidence from top-polluted economies.

Pursuing green growth is imperative to cope with the climate change battle. Green growth in top-polluting economies is being encouraged. The underlying work is aiming to investigate the impact of environmental technology and banking sector on green growth. More precisely, the study employs CS-ARDL and PMG-ARDL methods for empirical assessment. The FMOLS and DOLS techniques have been used to perform the sensitivity analysis for CS-ARDL and PMG-ARDL results. Empirical evidence of both the CS-ARDL and PMG-ARDL models reveals that banking sector development and environmental technology promote green growth. In detail, the insights reveal the significant and positive effect of environmental innovations and technology on green growth in both long-run as well as in short-run. Moreover, the findings of the study also disclose the significant and positive effect of banking sector and stock market developments on green growth in both long-run and short-run. Sensitivity analysis confirmed and improved our findings. Based on these effects, the study delivers policy implications for the promotion of environmental-based technological innovations and financial sector development to enhance green growth in top-polluted economies.

Rituximab versus tocilizumab in rheumatoid arthritis: synovial biopsy-based biomarker analysis of the phase 4 R4RA randomized trial.

Patients with rheumatoid arthritis (RA) receive highly targeted biologic therapies without previous knowledge of target expression levels in the diseased tissue. Approximately 40% of patients do not respond to individual biologic therapies and 5-20% are refractory to all. In a biopsy-based, precision-medicine, randomized clinical trial in RA (R4RA; n = 164), patients with low/absent synovial B cell molecular signature had a lower response to rituximab (anti-CD20 monoclonal antibody) compared with that to tocilizumab (anti-IL6R monoclonal antibody) although the exact mechanisms of response/nonresponse remain to be established. Here, in-depth histological/molecular analyses of R4RA synovial biopsies identify humoral immune response gene signatures associated with response to rituximab and tocilizumab, and a stromal/fibroblast signature in patients refractory to all medications. Post-treatment changes in synovial gene expression and cell infiltration highlighted divergent effects of rituximab and tocilizumab relating to differing response/nonresponse mechanisms. Using ten-by-tenfold nested cross-validation, we developed machine learning algorithms predictive of response to rituximab (area under the curve (AUC) = 0.74), tocilizumab (AUC = 0.68) and, notably, multidrug resistance (AUC = 0.69). This study supports the notion that disease endotypes, driven by diverse molecular pathology pathways in the diseased tissue, determine diverse clinical and treatment-response phenotypes. It also highlights the importance of integration of molecular pathology signatures into clinical algorithms to optimize the future use of existing medications and inform the development of new drugs for refractory patients.

COVID-Related Leukoencephalopathy: Unusual MRI Features and Comparability to Delayed Post Hypoxic Ischemic Encephalopathy.

COVID-19 related leukoencephalopathy can be multifactorial given the systemic effects of the viral disease. We present couple of cases with typical clinico-imaging stigmata of COVID-19 resulting in severe respiratory insufficiency. MR brain imaging revealed confluent diffuse supratentorial white matter T2 hyperintensity with restricted diffusion during the sub-acute course of the disease. The MR imaging pattern of leukoencephalopathy was non-specific but more comparable to delayed post-hypoxic leukoencephalopathy (DPHL) as also previously reported in COVID-19. Interestingly, T2 imaging showed unusual but peculiar finding of "accentuated medullary veins" in the superficial zones. No dural venous sinus thrombosis or micro-hemorrhages were present to explain "dots and stripes" due to dilated medullary veins. The patho-mechanism of this findings is not clear but may possibly be related to demyelination as DPHL has shown to be a demyelinating process. We present a review of COVID-related leukoencephalopathy with discussion on hypoxia-induced demyelinating process with accentuated medullary veins as possible associated marker.

The role of lymphoid tissue SPARC in the pathogenesis and response to treatment of multiple myeloma.

Background: Despite the significant progress in the treatment of multiple myeloma (MM), the disease remains untreatable and its cure is still an unmet clinical need. Neoplastic transformation in MM is initiated in the germinal centers (GCs) of secondary lymphoid tissue (SLT) where B cells experience extensive somatic hypermutation induced by follicular dendritic cells (FDCs) and T-cell signals. Objective: We reason that secreted protein acidic and rich in cysteine (SPARC), a common stromal motif expressed by FDCs at the origin (SLTs) and the destination (BM) of MM, plays a role in the pathogenesis of MM, and, here, we sought to investigate this role. Methods: There were 107 BM biopsies from 57 MM patients (taken at different time points) together with 13 control specimens assessed for SPARC gene and protein expression and compared with tonsillar tissues. In addition, regulation of myeloma-promoting genes by SPARC-secreting FDCs was assessed in in vitro GC reactions (GCRs). Results: SPARC gene expression was confirmed in both human primary (BM) and secondary (tonsils) lymphoid tissues, and the expression was significantly higher in the BM. Sparc was detectable in the BM and tonsillar lysates, co-localized with the FDC markers in both tissues, and stimulation of FDCs in vitro induced significantly higher levels of SPARC expression than unstimulated controls. In addition, SPARC inversely correlated with BM PC infiltration, ISS staging, and ECOG performance of the MM patients, and in vitro addition of FDCs to lymphocytes inhibited the expression of several oncogenes associated with malignant transformation of PCs. Conclusion: FDC-SPARC inhibits several myelomagenic gene expression and inversely correlates with PC infiltration and MM progression. Therapeutic induction of SPARC expression through combinations of the current MM drugs, repositioning of non-MM drugs, or novel drug discovery could pave the way to better control MM in clinically severe and drug-resistant patients.

Biomedical Applications of Scutellaria edelbergii Rech. f.: In Vitro and In Vivo Approach.

In the current study, in vitro antimicrobial and antioxidant activities and in vivo anti-inflammatory and analgesic activities of Scutellaria edelbergii Rech. f. (crude extract and subfractions, i.e., n-hexane, ethyl acetate (EtOAc), chloroform, n-butanol (n-BuOH) and aqueous) were explored. Initially, extraction and fractionation of the selected medicinal plant were carried out, followed by phytochemical qualitative tests, which were mostly positive for all the extracts. EtOAc fraction possessed a significant amount of phenolic (79.2 ± 0.30 mg GAE/g) and flavonoid (84.0 ± 0.39 mg QE/g) content. The EtOAc fraction of S. edelbergii exhibited appreciable antibacterial activity against Gram-negative (Escherichia coli and Klebsiella pneumoniae) strains and significant zones of inhibition were observed against Gram-positive bacterial strains (Bacillus subtilis and Staphylococcus aureus). However, it was found inactive against Candida Albicans and Fusarium oxysporum fungal strains. The chloroform fraction was the most effective with an IC50 value of 172 and 74 µg/mL against DPPH (1,1-Diphenyl-2-picryl-hydrazyl) and ABTS assays, in comparison with standard ascorbic acid 59 and 63 µg/mL, respectively. Moreover, the EtOAc fraction displayed significant in vivo anti-inflammatory activity (54%) using carrageenan-induced assay and significant (55%) in vivo analgesic activity using acetic acid-induced writing assay. In addition, nine known compounds, ursolic acid (UA), ovaul (OV), oleanolic acid (OA), ß-sitosterol (BS), micromeric acid (MA), taraxasterol acetate (TA), 5,3',4'-trihydroxy-7-methoxy flavone (FL-1), 5,7,4'-trihydroxy-6,3'-dimiethoxyflavone (FL-2) and 7-methoxy catechin (FL-3), were isolated from methanolic extract of S. edelbergii. These constituents have never been obtained from this source. The structures of all the isolated constituents were elucidated by spectroscopic means. In conclusion, the EtOAc fraction and all other fractions of S. edelbergii, in general, displayed a significant role as antibacterial, free radical scavenger, anti-inflammatory and analgesic agents which may be due to the presence of these constituents and other flavonoids.

Comparison Of Anaesthetic Efficacy Of Articaine And Lidocaine In Nonsurgical Endodontic Treatment Of Permanent Mandibular Molars With Symptomatic Irreversible Pulpitis. A Randomized Clinical Trial.

BACKGROUND: Inferior Alveolar Nerve Block (IANB) with Buccal Infiltration (BI) anaesthesia is required to completely anesthetize the mandibular molars with symptomatic irreversible pulpitis. 4% Articaine and 2% Lidocaine provide local anaesthesia during the nonsurgical endodontic treatment of mandibular molars with symptomatic irreversible pulpitis. Objective of the study was to compare the effect of Articaine and Lidocaine in the combination of Inferior alveolar nerve block with buccal infiltration anaesthesia during the nonsurgical endodontic treatment of mandibular molars with symptomatic Irreversible Pulpitis. METHODS: One hundred and sixty participants with Symptomatic Irreversible Pulpitis of permanent mandibular molars were divided randomly in two groups. Group A was given Articaine 4% IANB along with BI whereas group B was given Lidocaine 2%. Pain was assessed after 15 minutes of administration of local anaesthesia. Anaesthetic success of the agents is defined as, absence of pain or mild pain first during the access cavity preparation then instrumentation of the canals of tooth. Chi-square test was applied to analyse data for statistical significance. RESULTS: Anaesthetic success of Articaine was 96.2% during access cavity preparation compared to Lidocaine (86.2%). Success during instrumentation of canals was also found to be high in Articaine (90.2%) compared to Lidocaine (76.2%). This difference of anaesthetic efficacy between Articaine and Lidocaine was found statistically significant. (p=0.02). CONCLUSIONS: Articaine is found to be better than Lidocaine regarding anaesthetic efficacy and hence, it can be a safer alternative to Lidocaine.

Neuro-imaging manifestations of COVID-19: Predilection for PICA infarcts.

COVID-19 has been an ever-evolving viral pandemic which can cause systemic disturbance especially in some of the critically ill patients. Neurologic or Neuro-imaging manifestations of COVID-19 are being increasingly reported in these patients and mainly consist of ischemic strokes, hypoxic ischemic injury and non-specific encephalopathy. Ischemic strokes as expected more commonly afflict major vascular territories, likely due to accentuated hypercoagulability in these patients. Certain vascular territories may be more susceptible to ischemic infarcts. We observed higher predilection for infarcts in posterior inferior cerebellar artery (PICA). This may represent another peculiarity of this pandemic.

Streamlined Subpopulation, Subtype, and Recombination Analysis of HIV-1 Half-Genome Sequences Generated by High-Throughput Sequencing.

High-throughput sequencing (HTS) has been widely used to characterize HIV-1 genome sequences. There are no algorithms currently that can directly determine genotype and quasispecies population using short HTS reads generated from long genome sequences without additional software. To establish a robust subpopulation, subtype, and recombination analysis workflow, we amplified the HIV-1 3'-half genome from plasma samples of 65 HIV-1-infected individuals and sequenced the entire amplicon (∼4,500 bp) by HTS. With direct analysis of raw reads using HIVE-hexahedron, we showed that 48% of samples harbored 2 to 13 subpopulations. We identified various subtypes (17 A1s, 4 Bs, 27 Cs, 6 CRF02_AGs, and 11 unique recombinant forms) and defined recombinant breakpoints of 10 recombinants. These results were validated with viral genome sequences generated by single genome sequencing (SGS) or the analysis of consensus sequence of the HTS reads. The HIVE-hexahedron workflow is more sensitive and accurate than just evaluating the consensus sequence and also more cost-effective than SGS.IMPORTANCE The highly recombinogenic nature of human immunodeficiency virus type 1 (HIV-1) leads to recombination and emergence of quasispecies. It is important to reliably identify subpopulations to understand the complexity of a viral population for drug resistance surveillance and vaccine development. High-throughput sequencing (HTS) provides improved resolution over Sanger sequencing for the analysis of heterogeneous viral subpopulations. However, current methods of analysis of HTS reads are unable to fully address accurate population reconstruction. Hence, there is a dire need for a more sensitive, accurate, user-friendly, and cost-effective method to analyze viral quasispecies. For this purpose, we have improved the HIVE-hexahedron algorithm that we previously developed with in silico short sequences to analyze raw HTS short reads. The significance of this study is that our standalone algorithm enables a streamlined analysis of quasispecies, subtype, and recombination patterns from long HIV-1 genome regions without the need of additional sequence analysis tools. Distinct viral populations and recombination patterns identified by HIVE-hexahedron are further validated by comparison with sequences obtained by single genome sequencing (SGS).

COVID-19-associated encephalopathy: Neurological manifestation of COVID-19.

Coronavirus disease 2019 (COVID-19) is a viral disease, also known as severe acute respiratory syndrome coronavirus 2, was first reported in Wuhan, China, December 2019. Respiratory manifestations from the induced acute lung injury were the most common reported findings. Few cases showed extrapulmonary manifestations. COVID-19-associated neurological manifestations have not been widely reported. In this report, we describe a case of encephalopathy in a patient with COVID-19 infection.

Isolated hemorrhagic arterialized DVAs: revisiting symptomatic DVAs.

We aim to present here a small case series of symptomatic isolated hemorrhagic arterialized developmental venous anomalies (sDVAs) with a larger goal of revisiting the classification based on patho-mechanisms plus emphasizing angiographic features coupled with CT and MRI. Typically, DVA is an incidental and silent abnormality on neuroimaging. Understanding its morphology in terms of arterialization and relationship with other entities is crucial for management. One adult and two pediatric cases presented with acute or sub-acute hemorrhage in the cerebellum or thalamus. Morphologic characterization on cross-sectional imaging and catheter angiography confirmed the integrated diagnosis of "symptomatic isolated hemorrhagic arterialized DVAs with deeper or superficial venous drainage". Conservative management was adopted in all cases. We emphasize the following classification and approach for symptomatic DVAs: (1) congestive isolated arterialized sDVAs, (2) congestive isolated resistive sDVAs, (3) coexisting sDVAs (with AVM or cavernous malformation), (4) compressive sDVAs (compressive effects), and (5) idiopathic DVAs. Like our three cases, ganglionic and infratentorial DVAs have higher propensity of hemorrhage, compressive effects, and usually harbor deeper venous drainage. Typical "caput medusae" as dominant collector vein on cross-sectional imaging is crucial to complement and even confirm the diagnosis of DVA before catheter angiography in sDVAs. Capillary stain or early opacification of DVAs is a marker of arteriovenous shunting in arterialized sDVAs. Recognition of this entity is crucial as treatment is usually conservative.

Multiple Sclerosis in the Emirati Population: Onset Disease Characterization by MR Imaging.

BACKGROUND AND OBJECTIVES: Multiple Sclerosis (MS) epidemiology is on the path of globalization mainly due to changing environmental factors. The prevalence of MS is on the rise in the Middle East and Persian Gulf region. Our observations has led us to hypothesize a heavy MRI lesion load at the onset of disease in a relatively younger native population. We aimed to estimate and characterize the onset disease on MRI using McDonald's criteria while applying its terms of "Dissemination in Space (DIS) and Dissemination in Time (DIT)". MATERIALS AND METHODS: Retrospective review of onset MRI studies of 181 Emirati (native) individuals. Basic demographics were captured. Only 47 patients with Clinically Definite MS (CDMS) were included who had onset diagnostic MRI available. Lesion load was quantified using the specific zones of involvement designated for DIS: (1) Periventricular (PVZ) (I), (2) Juxta-cortical (II) (3) Infra-tentorial (III) and, (4) Spinal cord (IV). PVZ was sub-classified and lesions were quantified. A single enhancing lesion was required for DIT. RESULTS: Average age of onset was about 26 years with female dominance of about 2 : 1. About 50% had all 4 zones and about 85% had at least 3 zones involved at the onset. Involvement of only 1 zone was rare. Dissemination in time (DIT) in brain and/or cord was present in approximately 50%. Each of the 4 zones were involved in at least 70% of cases. PVZ was not spared in any case with at least 3 lesions present in approx. 95% and ≥12 lesions in approx. half of the patients. Spinal cord specifically cervical cord was involved in up to 80% with typical patchy lesions. CONCLUSION: Onset disease characterization using MRI in a young Emirati cohort showed a heavy lesion load in the brain and spinal cord at the onset, signifying cumulative disease before presentation. Disseminated disease also facilitated early diagnosis of MS. The findings have significant potential ramifications for local environmental and cultural factors, as well as disease course and disability progression.

Stenotrophomonas skull base osteomyelitis presenting as necrotizing otitis externa: Unmasking by CT and MRI-case report and review.

Necrotizing or malignant otitis externa in patients presenting with mild clinical findings can pose as a tip of the iceberg; computed tomography (CT) and/or magnetic resonance imaging (MRI) unveils the clinical-imaging discrepancy and unmasks the presence of skull-base osteomyelitis (SBO). Pseudomonas aeruginosa is the most common causative pathogen of SBO, followed by fungal and other rare bacterial organisms. This report presents a rare case in an elderly diabetic patient, where the pathogen Stenotrophomonas maltophilia was isolated. There have been no previous reported cases in the literature of SBO caused by this pathogen. The hallmark of SBO on computed tomography or magnetic resonance imaging is soft tissue inflammatory changes under the central skull base with associated bone erosion. This may result in the peculiar appearance of the "Ovoid Gap" sign. SBO can be due to nonotogenic sources, namely: sinogenic, rhinogenic, pharnygogenic, or odontogenic infections. Low threshold for imaging is advised in immunosuppressed and elderly diabetic patients.

Comparisons of Onlay versus Sublay Mesh Fixation Technique in Ventral Abdominal Wall Incisional Hernia Repair.

OBJECTIVE: To compare the results of onlay with sublay mesh repair technique for ventral incisional hernia. STUDY DESIGN: Comparative study. PLACE AND DURATION OF STUDY: Surgical Unit IV, Sandeman (Provincial) Hospital, Quetta and Mohtarma Shaheed Benazir Bhutto Hospital, Quetta, from July 2016 to December 2017. METHODOLOGY: Sixty-five patients, diagnosed by clinical examination as ventral incisional hernia, were included in the study. Patients were divided randomly into two groups. Group 1 had onlay mesh repair while group 2 were subjected to Sublay mesh fixation technique. Results of the procedures done in terms of operative time, wound infection, seroma formation, hospital stay, and follow-up. The data was analysed by the SPSS. RESULTS: The age ranges from 18-65 years, mean 39.13 +11.76 years. There were 42 males (64.61%) and 23 females (35.4%). The distribution of ventral incisional hernia was 42 (64.61%) in midline, followed by subcostal incision in 10 (15.38%) patients. In group 1, a total of 33 (50.76%) patients underwent onlay mesh repair, while 32 (49.23%) patients had underwent sublay mesh repair in group 2 (p=0.007). The wound infection and dehiscence was less in group 2. The seroma formation was prevalent in group1 (p-value 0.005). The hospital stay in group 2 was less (p=0.003).The follow up for 6 months revealed no recurrence in 20 patients of group 1 and 12 patients of group 2. CONCLUSION: Group 2 has a definitive edge over group 1 in the management of incisional hernia. The morbidity of the patient in group 2 was lower than group 1.

TB Meningitis and TB Peritonitis: Abdominal Pseudocyst and VP-Shunt Link.

TB meningitis (TBM) carries high morbidity and mortality and is a relatively common extrapulmonary TB in the third world countries. TBM as thick exudative disease manifests on MRI and CT as nodular basal leptomeningitis, hydrocephalus, basal infarcts, and tuberculomas. Hydrocephalus is treated with ventriculoperitoneal shunting (VPS). Shunt malfunction and revision are common. We report a case of multidrug-resistant TBM with spinal involvement and dissemination of the disease via VPS causing TB peritonitis (TBP). TBP presented as a large abdominal pseudocyst around the catheter tip with shunt malfunction. There was no evidence for any other site of extra-CNS disease. TBP per se is relatively less common. This is the first case reporting VPS as a means of TB spread.

Antiphospholipid syndrome and neurofibromatosis type I: a coincidence or new association? / Síndrome antifosfolípide e neurofibromatose tipo I: uma coincidência ou nova associação?

ABSTRACT - Numerous studies have reported on structural vascular anomalies and ischemia associated with neurofibromatosis type 1 that are thought to stem from dysfunction of neurofibromin, the neurofibromatosis type 1 protein. Documented cases of associated antiphospholipid syndrome fulfilling the accepted diagnostic criteria are exceptionally rare, with only three cases reported in the literature. Here, we report on a patient with neurofibromatosis type 1 and a history of spontaneous abortions presenting with sudden vision loss in the right eye and swelling of the optic nerve head. Fluorescein angiography indicated anterior ischemic optic neuropathy. Brain magnetic resonance imaging revealed findings consistent with left cavernous sinus meningioma. Serologic testing demonstrated persistently elevated anti-b2-glycoprotein antibodies. Her findings suggested antiphospholipid syndrome with concomitant clinical and laboratory evidence of antiphospholipid syndrome: frequent abortions, a vaso-occlusive episode, and persistently elevated antiphospholipid syndrome antibodies. To our knowledge, this case represents the first neuro-ophthalmic manifestation of antiphospholipid syndrome associated with neurofibromatosis type 1.

RESUMO - Inúmeros estudos têm relatado anomalias vasculares estruturais e isquemia associada com à neurofibromatose tipo 1 que, acredita-se, resultam da disfunção da neurofibromina, a proteína tipo 1 da neurofibromatose. Casos documentados de síndrome antifosfolípide associada que atendem aos critérios diagnósticos aceitos são excepcionalmente raros, com apenas três casos relatados na literatura. Aqui, relatamos um paciente com neurofibromatose tipo 1 e histórico de abortos espontâneos apresentando perda repentina de visão no olho direito e edema de cabeça do nervo óptico. A angiofluoresceínografia indicou neuropatia óptica isquêmica anterior. Ressonância magnética cerebral revelou achados compatíveis com meningioma do seio cavernoso esquerdo. O teste sorológico demonstrou anticorpos anti-b2 glicoproteína persistentemente elevados. Seus achados sugerem síndrome antifosfolípide com evidências clínicas e laboratoriais concomitantes de síndrome antifosfolipídica: abortos frequentes, episódio vaso-oclusivo e anticorpos antifosfolípides persistentemente elevados. Pelo nosso conhecimento, este caso pode representar a primeira manifestação neuro-oftálmica da síndrome antifosfolípide associada à neurofibromatose tipo 1.