CNS Manifestations Research Articles

P081 Unravelling SLE in a young male child

Abstract Background Juvenile-onset systemic lupus erythematosus (jSLE)) is a rare but severe multisystem autoimmune, inflammatory disease that can affect any organ system and cause significant morbidity and mortality. The disease onset occurs before the age of 18, however the peak age of onset is between 12 and 14 years and it affects ∼15–20% of all SLE patients. Patients with disease onset before 5 years of age are very uncommon and may be referred to as early-onset SLE. They commonly present with fever and general malaise, rash and arthritis. In addition, cases of jSLE, tend to have more severe organ manifestations and greater damage at the time of diagnosis as well as a higher incidence of renal, cardiovascular and neuropsychiatric involvement. Compared with adult-onset SLE, it is more aggressive, with higher medication burden including corticosteroids and other immunosuppressive drugs. Method and results This case report reviews the journey of a 5-year-old boy, who developed recurrent skin rashes, fever and generalised lymphadenopathy in his second year of life. After multiple hospital admissions and various investigations at different facilities spanning a year, he was admitted to the paediatric emergency unit at a tertiary hospital on account of an acute infection. On presentation, he was pyrexial. There were hypo- and hyperpigmented lesions extending over his scalp, face and upper arms as well as vasculitic lesions in his palms and soles; lip ulcers, sparse brown hair and multiple, non-tender lymph nodes in the cervical, supraclavicular and axillary regions. Respiratory examination revealed a right lobar pneumonia. Heart rate was 112 bpm and heart sounds were normal, however an echocardiogram showed a moderate pericardial effusion with no signs of tamponade. His abdomen was distended with a non-tender hepatomegaly. There was no synovitis. He was lethargic, but had no focal neurological signs. Laboratory results were as follows: normocytic anaemia (8.5 g/dl); ESR (120 mm/h); deranged transaminases; albumin (32 g/dl); Creatinine (12umol/l); urinalysis was normal, positive antinuclear antibody (1:320); positive double-stranded DNA (1:40); positive anti-smith, anti-Ro and anti-RNP antibodies; low C3, C4. A lymph node biopsy showed reactive changes only, with no evidence of haematological malignancy. The diagnosis of jSLE was confirmed at age 3yrs. The acute illness due to pneumonia was treated with antibiotics. Prednisolone 10 mg, Hydroxychloroquine (HCQ) 80 mg daily, Azathioprine 25 mg daily, calcium supplementation and gastric protection were added to manage the jSLE. He made an initial recovery and was managed in the outpatient clinic for months. However, his illness flared up again around age 4 years when he developed generalized seizures, facial and pedal oedema, low urine output, proteinuria 3+, low albumin (25 g/dl), creatinine (252umol/l) and high urine albumin-creatinine ratio (278.62 mg/mmol) reflecting new renal and CNS involvement. A renal biopsy was not available. He received pulse iv methylprednisolone 250 mg daily for 3 days followed by monthly iv cyclophosphamide therapy 500 mg (NIH Regime) which was discontinued after the 5th cycle due to haemorrhagic cystitis. He eventually continued treatment with mycophenolate mofetil 125 mg daily, HCQ 80 mg daily, Prednisolone 10 mg daily, Nifedipine and Enalapril and a year later, has low activity from the cutaneous, renal and CNS manifestations. There is renal damage (creatinine 180 μmol/l) and hypertension, as well as treatment complications from prednisolone causing bilateral cataracts. Conclusion Early diagnosis of jSLE is still a challenge and a high index of suspicion is required especially in the very young. Severe presentation and aggressive clinical course is associated with tissue damage, as in the case presented. Management is complex and we were challenged by the choice and availability of treatment suitable for the severity of his disease, bearing in mind that damage can occur early especially in a male child. In addition, it is important to consider his young age and long-term exposure to drug toxicity and complications.

SARS-CoV-2 promotes RIPK1 activation to facilitate viral propagation

Coronavirus disease 2019 (COVID-19), caused by severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2), is the ongoing global pandemic that poses substantial challenges to public health worldwide. A subset of COVID-19 patients experience systemic inflammatory response, known as cytokine storm, which may lead to death. Receptor-interacting serine/threonine-protein kinase 1 (RIPK1) is an important mediator of inflammation and cell death. Here, we examined the interaction of RIPK1-mediated innate immunity with SARS-CoV-2 infection. We found evidence of RIPK1 activation in human COVID-19 lung pathological samples, and cultured human lung organoids and ACE2 transgenic mice infected by SARS-CoV-2. Inhibition of RIPK1 using multiple small-molecule inhibitors reduced the viral load of SARS-CoV-2 in human lung organoids. Furthermore, therapeutic dosing of the RIPK1 inhibitor Nec-1s reduced mortality and lung viral load, and blocked the CNS manifestation of SARS-CoV-2 in ACE2 transgenic mice. Mechanistically, we found that the RNA-dependent RNA polymerase of SARS-CoV-2, NSP12, a highly conserved central component of coronaviral replication and transcription machinery, promoted the activation of RIPK1. Furthermore, NSP12 323L variant, encoded by the SARS-CoV-2 C14408T variant first detected in Lombardy, Italy, that carries a Pro323Leu amino acid substitution in NSP12, showed increased ability to activate RIPK1. Inhibition of RIPK1 downregulated the transcriptional induction of proinflammatory cytokines and host factors including ACE2 and EGFR that promote viral entry into cells. Our results suggest that SARS-CoV-2 may have an unexpected and unusual ability to hijack the RIPK1-mediated host defense response to promote its own propagation and that inhibition of RIPK1 may provide a therapeutic option for the treatment of COVID-19.

Relevance of CSF, Serum and Neuroimaging Markers in CNS and PNS Manifestation in COVID-19: A Systematic Review of Case Report and Case Series.

Background: The data on neurological manifestations in COVID-19 patients has been rapidly increasing throughout the pandemic. However, data on CNS and PNS inflammatory disorders in COVID-19 with respect to CSF, serum and neuroimaging markers is still lacking. Methods: We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords “SARS-CoV-2 and neurological complication”, “SARS-CoV-2 and CNS Complication” and “SARS-CoV-2 and PNS Complication” looking for transverse myelitis, vasculitis, acute disseminated encephalomyelitis, acute hemorrhagic necrotizing encephalitis (AHNE), cytotoxic lesion of the corpus callosum (CLOCC) and Guillain-Barré syndrome (GBS), published between 1 December 2019 to 15 July 2021. Results: Of the included 106 CNS manifestations in our study, CNS inflammatory disorders included transverse myelitis (17, 14.7%), AHNE (12, 10.4%), ADEM (11, 9.5%), CLOCC/MERS (10, 8.6%) and vasculitis (4, 3.4%). Others were nonspecific encephalopathy, encephalitis, seizures and stroke. Most patients were >50 years old (75, 70.8%) and male (64, 65.3%). Most (59, 63.4%) were severe cases of COVID-19 and 18 (18%) patients died. Of the included 94 PNS manifestations in our study, GBS (89, 92.7%) was the most common. Most of these patients were >50 years old (73, 77.7%) and male (59, 64.1%). Most (62, 67.4%) were non-severe cases of COVID-19, and ten patients died. Conclusion: Our comprehensive review of the clinical and paraclinical findings in CNS and PNS manifestations of COVID-19 provide insights on the pathophysiology of SARS-CoV-2 and its neurotropism. The higher frequency and severity of CNS manifestations should be noted by physicians for increased vigilance in particular COVID-19 cases.

Phenotypic characterization of Cdkl5-knockdown neurons establishes elongated cilia as a functional assay for CDKL5 Deficiency Disorder

CDKL5 Deficiency Disorder (CDD) is a severe encephalopathy characterized by intractable epilepsy, infantile spasms, and cognitive disabilities. The detrimental CNS manifestations and lack of therapeutic interventions represent unmet needs, necessitating identification of CDD-dependent phenotypes for in vitro disease modeling and therapeutic testing. Here, we optimized a high-content assay to quantify cilia in CDKL5-deficient neurons. Our work shows that Cdkl5-knockdown neurons have elongated cilia and uncovers cilium lengthening in hippocampi of Cdkl5 knockout mice. Collectively, our findings identify cilia length alterations under CDKL5 activity loss in vitro and in vivo and reveal elongated cilia as a robust functional phenotype for CDD.

PULMONARY CRYPTOCOCCOSIS COMPLICATING POST-COVID-19 PULMONARY FIBROSIS

TOPIC: Chest Infections TYPE: Medical Student/Resident Case Reports INTRODUCTION: Pulmonary cryptococcosis (PC) is an opportunistic invasive mycosis common in immunocompromised patients, presenting as dyspnea and cough(1). Studies have shown opportunistic infections such as pulmonary aspergillosis, candida and pneumocystis pneumonia in critically ill patients with COVID-19. However data on incidence of PC in this subset of patients is sparse(2). We discuss a patient with post-COVID-19 pulmonary fibrosis(PF) who developed PC. CASE PRESENTATION: A 62-year-old lifelong non-smoker male presented with worsening dyspnea and cough. One month prior to this, he was treated for new hypoxic respiratory failure secondary to COVID-19 pneumonia and pulmonary embolism and was on baseline oxygen therapy 4L/min since. On presentation, he was noted to be afebrile, tachycardic HR of 114/min, tachypneic with RR 24/min, and saturating 93% on 6L O2. He had bilateral crackles on chest auscultation. Initial labs were unremarkable except ABG showing normal pH of 7.38, with hypoxia pO2 58 and hypercarbia pCo2 65. COVID-19 PCR remained positive. Chest X-ray was suggestive of multifocal pneumonia. Chest CT revealed severe multifocal pneumonia with interval development of bronchiectasis. Patient was initiated on IV linezolid, meropenem, remdesivir and dexamethasone;he required BiPAP support due to respiratory failure. Worsening respiratory failure despite completion of antibiotic course, prompted initiation of ceftazidime. He was also started on trial of IV methylprednisolone 125mg every six hourly in view of suspected post-COVID-19 PF, administered for two weeks. Patient's hospitalization was further complicated by critical illness myopathy, atrial fibrillation and flutter. Subsequently fungal serology returned positive for cryptococcal antigen and fluconazole therapy was initiated. He had no history of immunocompromise such as HIV, Diabetes, ESRF etc. CSF analysis was deferred since he had no CNS manifestations. Patient showed clinical improvement into second week of hospitalization and repeat CT scan done 18 days after starting fluconazole showed interval improvement of multifocal infiltrate. DISCUSSION: Post-COVID-19 pulmonary fibrosis is increasingly identified with evolving clinical data. Dysregulated release of matrix metalloproteinases, epithelial injury, and fibroproliferation are all implicated in the pathogenesis of post infective PF(3). CONCLUSIONS: High dose steroids used in the management of PF pose serious risk of complications related to immunosuppression and subsequent opportunistic infections such as pulmonary cryptococcosis and pneumocystis pneumonia. As the pandemic is still evolving, it will be interesting to see if PF and opportunistic infections become an established post-COVID-19 sequela. REFERENCE #1: Setianingrum F, Rautemaa-Richardson R, Denning DW. Pulmonary cryptococcosis: A review of pathobiology and clinical aspects. Med Mycol. 2019 Feb 1;57(2):133-150. doi: 10.1093/mmy/myy086. PMID: 30329097. REFERENCE #2: Salehi M, Ahmadikia K, Badali H, Khodavaisy S. Opportunistic Fungal Infections in the Epidemic Area of COVID-19-19: A Clinical and Diagnostic Perspective from Iran. Mycopathologia. 2020;185(4):607-611. doi:10.1007/s11046-020-00472-7 REFERENCE #3: Tale S, Ghosh S, Meitei SP, Kolli M, Garbhapu AK, Pudi S. Post-COVID-19-19 pneumonia pulmonary fibrosis. QJM. 2020;113(11):837-838. doi:10.1093/qjmed/hcaa255 DISCLOSURES: No relevant relationships by Sangeetha Isaac, source=Web Response No relevant relationships by Shalom Isaac, source=Web Response No relevant relationships by Evans Kyei-Nimako, source=Admin input No relevant relationships by Amos Lal, source=Web Response No relevant relationships by Mohammed Afraz Pasha, source=Web Response

RARE INVASIVE FUNGAL SPECIES IN SUSCEPTIBLE HOSTS

TOPIC: Critical Care TYPE: Medical Student/Resident Case Reports INTRODUCTION: We present a case of a 31 year old immunocompromised patient secondary to lupus complicated by renal failure on hemodialysis who presented with fever diagnosed with a rare invasive fungal infection. CASE PRESENTATION: Patient presented due to an ongoing fever of 2 months after recently being treated with empiric antibiotics for presumed pneumonia and septic arthritis of his knee at an outside hospital. Work up for fever of unknown origin was obtained and started on empiric antibiotics. On day 4 of admission, CT head was obtained due to an acute focal neurologic deficit (Image 1) which showed a lesion in the left basal ganglia and subsequently had to be intubated fur acute hypoxic respiratory failure. Due to his immunocompromised state, CNS targeting empiric antibiotics and antifungals were initiated. Biopsy of the lesion and repeat brain imaging was delayed due to thrombocytopenia and hemodynamic instability. All work up for his fever was negative except for a positive fungitell and his subsequent imaging showed rapidly progressing lesion to encompass the left cerebral hemisphere and extending to the right cerebral hemisphere (Image 2). Urgent frontal craniotomy with biopsy initially reported high grade glioblastoma but final culture of the sample grew Scedosporium boydii. Voriconazole was started; however, due to the extensive spread of the fungi the patient passed away shortly after. DISCUSSION: Clinical spectrum of Scedosporiosis in immunocompromised hosts range from keratitis, endophthalmitis, otitis, sinusitis, pulmonary infections and rarely, CNS infections [1-8]. Risk factors include diabetes, transplant recipients, leukemia, lupus, lymphoma and drowning [1,3]. Brain abscess, meningitis and mycotic aneurysms are common CNS manifestations and diagnosis are usually delayed due to difficulty isolating the Scedosporium spp [1-3]. Histopathology showing hyaline hyphae with regular septation and dichotomous branching can be confused with Aspergillus or Fusarium spp [1,2,4,5]. Isolation of the fungus with appropriate culture and media is crucial in accuracy of diagnosis and for subsequent treatment plan. Scedosporium spp are resistance to amphotericin B and has wide variability of susceptibility to itraconazole, voriconazole, posaconazole and micafungin [1-3]. If diagnosed early, surgical resection of the abscess is preferred treatment option with voriconazole depending on susceptibility[1-3]. Therefore, early diagnosis with appropriate mode of isolation is crucial in treating invasive fungal infection due to high morbidity and mortality associated. CONCLUSIONS: Accuracy of sample isolation is difficult for Scedosporium and usually leads to delay in treatment. In our patient, only the biopsy of the brain abscess showed histopathological evidence of Scedosporium spp., reminding us of the importance of early recognition of possible rare causes of infection in susceptible hosts. REFERENCE #1: Ramirez-Garcia A, Pellon A, Rementeria A, Buldain I, Barreto-Bergter E, Rollin-Pinheiro R, de Meirelles JV, Xisto MIDS, Ranque S, Havlicek V, Vandeputte P, Govic YL, Bouchara JP, Giraud S, Chen S, Rainer J, Alastruey-Izquierdo A, Martin-Gomez MT, López-Soria LM, Peman J, Schwarz C, Bernhardt A, Tintelnot K, Capilla J, Martin-Vicente A, Cano-Lira J, Nagl M, Lackner M, Irinyi L, Meyer W, de Hoog S, Hernando FL. Scedosporium and Lomentospora: an updated overview of underrated opportunists. Med Mycol. 2018 Apr 1;56(suppl_1):102-125. doi: 10.1093/mmy/myx113. PMID: 29538735. REFERENCE #2: Tortorano AM, Richardson M, Roilides E, van Diepeningen A, Caira M, Munoz P, Johnson E, Meletiadis J, Pana ZD, Lackner M, Verweij P, Freiberger T, Cornely OA, Arikan-Akdagli S, Dannaoui E, Groll AH, Lagrou K, Chakrabarti A, Lanternier F, Pagano L, Skiada A, Akova M, Arendrup MC, Boekhout T, Chowdhary A, Cuenca-Estrella M, Guinea J, Guarro J, de Hoog S, Hope W, Kathuria S, Lortholary O, Meis JF, Ullmann AJ, Petrikkos G, Lass-Flörl C; European Society of Clinical Microbiology and Infectious Diseases Fungal Infection Study Group; European Confederation of Medical Mycology. ESCMID and ECMM joint guidelines on diagnosis and management of hyalohyphomycosis: Fusarium spp., Scedosporium spp. and others. Clin Microbiol Infect. 2014 Apr;20 Suppl 3:27-46. doi: 10.1111/1469-0691.12465. PMID: 24548001. REFERENCE #3: Seidel D, Meißner A, Lackner M, Piepenbrock E, Salmanton-García J, Stecher M, Mellinghoff S, Hamprecht A, Durán Graeff L, Köhler P, Cheng MP, Denis J, Chedotal I, Chander J, Pakstis DL, Los-Arcos I, Slavin M, Montagna MT, Caggiano G, Mares M, Trauth J, Aurbach U, Vehreschild MJGT, Vehreschild JJ, Duarte RF, Herbrecht R, Wisplinghoff H, Cornely OA. Prognostic factors in 264 adults with invasive Scedosporium spp. and Lomentospora prolificans infection reported in the literature and FungiScope®. Crit Rev Microbiol. 2019 Feb;45(1):1-21. doi: 10.1080/1040841X.2018.1514366. Epub 2019 Jan 10. Erratum in: Crit Rev Microbiol. 2019 Feb 18;:1. PMID: 30628529. DISCLOSURES: No relevant relationships by Chandni Bheeman, source=Web Response No relevant relationships by Sung Hong, source=Web Response No relevant relationships by Karan Omidvari, source=Web Response No relevant relationships by Anuja Pradhan, source=Web Response No relevant relationships by Ronak Shah, source=Web Response

Adverse events associated with antimicrobial compounds in a general hospital in Chile.

Antimicrobial compounds are associated with a wide range of adverse events (AE) and some of them can be potentially preventable. To characterize AE associated with antimicrobial compounds. Retrospective analysis of AEs reported to the National Pharmacological Surveillance System from 2014 to 2017 in a regional hospital. Severity, causality and preventability were analyzed. Sixty events were observed in 56 patients aged 2 months to 96 years. Cases were registered mostly in hospitalized patients. The most frequent AEs were skin disorders (56.7%), followed by hepatobiliary (13.3%), and CNS events (10%). Blood, kidney, respiratory gastrointestinal and immunological disorders were less frequently registered, including cases with anaphylactic shock and Stevens-Johnson syndrome (SJS). Causal analysis indicated a definitive association in 8.3%, probable in 70% and possible in 22%. Skin lesions were mostly associated with beta-lactams, hepatobiliary disorders with antituberculosis drugs and CNS manifestations with carbapenems. Cutaneous, neurological, and hepatobiliary events appeared at a median of 4, 2.5 and 10.5 days after starting the medication, respectively. AEs were managed with withdrawal of the suspected drug (83.3%) and other auxiliary therapies. AEs were categorized as severe in 22% and one case with SJS had a fatal outcome (1.7%). Preventability analysis revealed 25% of potentially avoidable events. Antimicrobial AE involved a wide diversity of compounds, occurred in different hospitalization units, affected patients of a wide age range and attacked different systems or organs. An important fraction was potentially avoidable.

Differences in MPS I and MPS II Disease Manifestations.

Mucopolysaccharidosis (MPS) type I and II are two closely related lysosomal storage diseases associated with disrupted glycosaminoglycan catabolism. In MPS II, the first step of degradation of heparan sulfate (HS) and dermatan sulfate (DS) is blocked by a deficiency in the lysosomal enzyme iduronate 2-sulfatase (IDS), while, in MPS I, blockage of the second step is caused by a deficiency in iduronidase (IDUA). The subsequent accumulation of HS and DS causes lysosomal hypertrophy and an increase in the number of lysosomes in cells, and impacts cellular functions, like cell adhesion, endocytosis, intracellular trafficking of different molecules, intracellular ionic balance, and inflammation. Characteristic phenotypical manifestations of both MPS I and II include skeletal disease, reflected in short stature, inguinal and umbilical hernias, hydrocephalus, hearing loss, coarse facial features, protruded abdomen with hepatosplenomegaly, and neurological involvement with varying functional concerns. However, a few manifestations are disease-specific, including corneal clouding in MPS I, epidermal manifestations in MPS II, and differences in the severity and nature of behavioral concerns. These phenotypic differences appear to be related to different ratios between DS and HS, and their sulfation levels. MPS I is characterized by higher DS/HS levels and lower sulfation levels, while HS levels dominate over DS levels in MPS II and sulfation levels are higher. The high presence of DS in the cornea and its involvement in the arrangement of collagen fibrils potentially causes corneal clouding to be prevalent in MPS I, but not in MPS II. The differences in neurological involvement may be due to the increased HS levels in MPS II, because of the involvement of HS in neuronal development. Current treatment options for patients with MPS II are often restricted to enzyme replacement therapy (ERT). While ERT has beneficial effects on respiratory and cardiopulmonary function and extends the lifespan of the patients, it does not significantly affect CNS manifestations, probably because the enzyme cannot pass the blood–brain barrier at sufficient levels. Many experimental therapies, therefore, aim at delivery of IDS to the CNS in an attempt to prevent neurocognitive decline in the patients.

RBD in pure autonomic failure

Pure autonomic failure is considered to be a degenerative condition of the autonomic nervous resulting from accumulation of alpha-synuclein in autonomic ganglia [1,2]. Lack of CNS involvement distinguishes this disorder from other synucleopathies with CNS involvement like MSA, DLB and PD. However, long term follow-up of PAF patients has shown that some of these cases convert to one of these disorders most commonly MSA [3]. Also, recent data, albeit limited in nature has shown the association of REM sleep disorder in PAF patients challenging the previous notion that PAF is a disease restricted to autonomic nervous system. This data has led to the discovery of a clinical syndrome with a position in the middle of the spectrum of these disorders with PAF at one end of the spectrum and MSA, DLB and PD at the other end. We hereby present a case report of one such patient with PAF associated with RBD but without any other CNS manifestations.

Neurological manifestations and pathophysiological mechanisms of Covid-19

Background - Severe acute respiratory syndrome coronavirus-2 is a novel, highly infectious coronavirus and the etiologic agent of Covid-19. The course of Covid-19 can range from mild flu-like symptoms to severe, life-threatening symptoms, especially when comorbidities are present. Increasing studies have reinforced the association between SARS-CoV-2 and various neurological manifestations, although the pathophysiological mechanisms remain uncertain. Objective - The aim of this paper was to briefly describe current findings on the relationship between SARS-CoV-2 pathophysiology and major CNS and Peripheral Nervous System (PNS) manifestations. Methods and Material - This work consists of a literature review based on the study of academic papers. To this end, the Pubmed platform was used to search for scientific articles, using the keywords: covid-19, coronavirus, physiopathology, neuronal symptoms. Results - out of 114,660 articles found, 94 were selected for this review. Conclusions - Periodic reviews collaborate in the constant updating and summarization of findings. Understanding the pathophysiology of SARS-CoV-2 on the SN and the link between the systems may lead to earlier and earlier diagnoses of neurological involvement, guide therapeutic management, prevent sequelae, and preserve lives.

Postpartum Psychosis Masking the Diagnosis of Neuropsychiatric Lupus

Systemic Lupus Erythematosus (SLE) is a chronic, relapsing, and remitting systemic disease. Autoimmunity and protean clinical manifestations affecting almost all the systems are the hallmarks of SLE. Systemic lupus can affect the central nervous system. The severity of CNS manifestations varies from less severe subclinical neurocognitive dysfunction affecting memory, intellect, and learning to more severe manifestations such as seizure, stroke, or transverse myelitis [1]. The psychotic features of primary psychiatric disorders overlap with Neuropsychiatric SLE (NPSLE) and often mask and delay the diagnosis of NPSLE.

Acute Toxic Effects of AB-CHMINACA on Lung, Heart and Liver: An Experimental Pilot Study

Background: Synthetic cannabinoid (SCs) substances are intended for drug addiction while they cannot be easily detected on a regular drug screen. The danger of these substances is not only being undetected, but also their health effects are not well studied and cannot be predicted. This is one of the recent major health problems that threaten populations around the world. Aim of the study: This study is an experimental study to detect the toxic effect of acute exposure to a synthetic cannabinoid substance “AB-CHMINACA’ clinically and histopathologically in different organs in adult male albino rats. Material and methods: AB-CHMINACA was tested for dissolution in different solvents to choose the best vehicle. Doses were selected according to Guidance on dose level selection for regulatory general toxicology studies for pharmaceuticals. Animals were injected intraperitoneal and after 24 hours, animals were sacrificed and the lung, heart, and liver were examined for histopathological changes. Results: AB-CHMINACA dissolves best in organic solvents like ethanol and DMSO. The most suitable vehicle for intraperitoneal injection of animals was ethanol-saline. After injection, animals showed CNS manifestations; depression or excitation followed by depression according to the dose. Histopathological examination of the lung, heart, and liver tissues showed generalized congestion, hemorrhage, inflammatory cell infiltration and degeneration, which increased by increasing the dose. Conclusion: AB-CHMINACA has toxic histopathological effects on the lung, heart, and liver on single-dose exposure even with minimal clinical manifestations. These effects are dose-related.

Multicenter Case Series of Primary Adrenal Lymphoma (PAL)

Introduction: Primary adrenal lymphoma (PAL) is a rare malignancy, with only around 250 cases reported. It is defined as histologically proven lymphoma that involves one or both adrenal glands and presents with no prior history of lymphoma. In case of simultaneous involvement of other organs and lymph nodes, the diagnosis requires unequivocal dominant involvement of the adrenal gland. In order to investigate the genetic landscape and molecular pathology of PAL, we initiated an international collaboration to collect clinical data as well as tumor samples. Here we give an overview of the clinical features in the largest series of PAL patients so far.Methods: We collected histopathologic information on 80 cases from 11centers in Europe and the USA. Imaging data was available in 64, patient history in 54, treatment outcome in 50, and survival data in 41 patients. Overall survival (OS) was calculated with the non-parametric method of Kaplan-Meier, considering the date of first diagnosis and either the time of death from any cause (complete data), or the time of last follow-up (censored data). Comparison between survival curves was made using the log-rank test. Progression-free survival (PFS) was defined as the time from diagnosis until progression or death, irrespective of cause. Clinical and laboratory data at first diagnosis were compared with the Chi-Square test (χ2) test. Statistical significance was defined as a p-value < 0.05.Results: Median age at diagnosis was 67 yrs (range: 25-89), with a male/female ratio of 2.4. The most common presentation was with B symptoms (56%). In 7 patients (13%) PAL was detected incidentally. Imaging studies showed bilateral adrenal involvement in 52%, which in contrast to previous studies had no prognostic impact. Isolated adrenal masses were detected in 30 of 64 patients on CT scans (47%), the other 34 (53%) showed additional extra-adrenal manifestations. 18FDG-PET scans, performed in 19 pts, revealed extra-adrenal involvement not detected by CT scans in 9 cases. The left and right adrenals were affected with similar frequency. Mean tumor size (largest diameter) was 80 mm (27-180), with no prognostic impact. Serum lactate dehydrogenase was elevated (LDH >250 U/l) in 44 of 49 patients tested and was >500 U/l in 67%. Adrenal insufficiency (AI) was detected in 11 of 16 (69%) bilateral PALs evaluated endocrinologically. None of the 14 evaluated unilateral PALs showed AI. Detection of AI had no significant effect on overall survival. B cell Non-Hodgkin lymphoma (NHL) was the most common histopathological diagnosis (90%). About 86% of analyzed samples were positive for the B-cell marker CD20. Ki-67 expression was more than 70% in 33 of 38 evaluated patients (87%), confirming the highly proliferative nature of this lymphoma. CNS involvement was present in 13 patients, surprisingly without significant impact on prognosis. 2-year OS was 61.5%. Median PFS was 11 months (range: 1-140), with a mean follow-up of 39.4 months. Information about response was available for 50 pts after first-line chemo- or immunochemotherapy: 40% (20/50) reached complete remission (CR), 36% (18/50) partial remission (PR), and 24% (12/50) showed disease progression (DP). Seven responding patients (5 in CR, 2 in PR) underwent autologous stem cell transplantation (aSCT). After an initial response to first-line therapy, 16/50 patients (29%) relapsed. Five patients (2 in CR and 3 with DP after first-line therapy) developed secondary CNS manifestation (one of them despite prophylactic brain irradiation). Patients receiving immunochemotherapy according to the R-CHOP protocol survived longer than patients receiving other therapies but the difference did not reach statistical significance (HR: 0.79, 95%CI: 0.32-1.96; p=0.6). The longest survival was seen in patients treated with conventional chemotherapy followed by aSCT in CR.Conclusion: Treatment of PAL is a challenge. Adrenal insufficiency can occur as potentially life-threatening complication in cases with bilateral involvement. It is thus disconcerting that endocrinological workup was only performed in a minority of cases. R-CHOP has been widely used, but longest survival with conventional chemotherapy was 108 months. Additional aSCT in complete remission increased the likelihood of long-term survival (PFS 72-140 mo.). It remains to be seen whether therapies targeting the B cell receptor pathway will be effective in patients with PAL. DisclosuresMajidi:Takeda Pharmaceutical International Co.: Research Funding. Casasnovas:Sanofi: Consultancy, Honoraria; Roche: Consultancy, Honoraria, Research Funding; Gilead: Consultancy, Honoraria, Research Funding; Takeda: Consultancy, Honoraria; BMS: Consultancy, Honoraria; Abbvie: Consultancy, Honoraria. Germing:Janssen: Honoraria; Novartis: Honoraria, Research Funding; Celgene: Honoraria, Research Funding. Gattermann:Celgene: Honoraria; Novartis: Honoraria, Other: Travel support; Takeda Pharmaceutical International Co.: Research Funding.

Idiopathic Thrombocytopenic Purpura in Patients Admitted to Benghazi Children Hospital

Introduction: Childhood immune thrombocytopenia (ITP) is an acquired autoimmune disorder characterized by isolated thrombocytopenia (peripheral blood platelet count &lt;100 x 109/L). ITP is one of the most common bleeding disorders in children, with an incidence of approximately four per 100.000 per year. Aim: Aim is to review presenting features, response to therapy, and natural history of ITP treated at Benghazi medical center, department of pediatric. Methods: Cross-sectional descriptive study was carried out at the Pediatric Department of Benghazi medical center. Results: The study included 86 patients their mean age was 4.2±2.7years,with minimum age 11months and maximum age 12years.Male to female ratio was 1:1.15, female constitute to more than half (53.5%) .Mean duration of hospital stay was 5.2± 4.3 days , minimum duration was one day and maximum was 23 days. Bruise was presented by 84.9% of patients, 67.4% was presented by history of upper respiratory tract infection and 30.2% presented with bleeding from different site. Repeated admission was recorded in 93% of the patients. Family history of ITP was recorded in 4.7%. Respiratory manifestation was present in 4.8%, CNS manifestation present in 2.4%, hepatosplenomegaly in 2.4%, Lymphoadnopathy in 2.4%, renal manifestation in 1.2% and musculoskeletal manifestation in 1.2%. WBC count was &gt;4 in 1.2% , 4-11 in 73.3% and 25.5% had level &gt; 11 x103/ml, mean level was 9.7± 3.4 x103/ ml. Sever decrease of platelets was recorded in 54.7% of the patients , 36% had moderate decrease , mild recorded in 9.3% and no one had normal count .Peripheral blood smear, 26.7% of patients had normocytic normochromic. 25.5%was microcytic hypochromic 4.7% had microcytic normochromic, 1.2% had atypical lymphocyte with decrease plat, 1.2% had Normocytic hypochromic, 14% were normal and 15.5% not done. Bone marrow was normal in 68.5% of the patients, 1.2% of patients had thrombocytopenia, 1.2% of them had aplastic anemia, 1.2% of .........

CLINICO-BIOCHEMICAL STUDY OF SAFETY AND TOLERABILITY OF SELECTIVE SEROTONIN REUPTAKE INHIBITORS (SSRIs) IN A TERTIARY MEDICAL COLLEGE IN WEST BENGAL

INTRODUCTION:Selective serotonin reuptake inhibitors (SSRIs) are a class of drugs that selectively increase the levels of serotonin in the synaptic cleft by blocking its uptake by serotoninergic neurons. They are now extensively used to treat various psychiatric disorders like depression, panic disorders, obsessive compulsive disorders and are now being evaluated in the treatment of a number of other psychiatric disorders like bulimia nervosa and social phobia. In this scenario we try to elucidate the serum electrolyte level, serum serotonin level, renal function test and platelet count to check out the changes as in different papers demonstrated that there are variations in different parameters of renal function occurred with chronic administration of SSRI. Objectives: To evaluate serum electrolyte level, serum serotonin level, renal function tests and platelet count of patients with major depressive disorder on chronic SSRI therapy and screen for any adverse drug reactions (if any) Materials and Methods: A cross-sectional observational study conducted in the Department of Psychiatry, Department of Biochemistry and Department of Pharmacology of Medical College and Hospital, Kolkata . The study protocol was approved by the Institutional Ethics Committee. Written consent was obtained from the subjects included in the study. Results and Discussion: After evaluating the biochemical parameters, it was observed that long term (more than 6 months) SSRI therapy can cause decline Platelet count (29.76%) and Serum Sodium Levels i.e. Hyponatremia (29.76%); whereas the serum serotonin levels (17.86%) were found to be elevated. Further, a negative correlation of -0.605 was observed between the serum sodium levels (in subjects with hyponatremia) and the duration for which the subjects were taking SSRI whereas a positive correlation of +0.407 was observed between the serum serotonin levels (in subjects with above normal serum serotonin levels) and the duration for which the subjects were taking SSRI. A number of adverse drug effects were reported. 28 subjects (33.33%) reported at least any one of the following symptoms like Headache, Sedation, Dizziness, Anxiety, Agitation. 12 subjects (14.28%) reported having recurring suicidal thoughts. 21 subjects (25.00%) reported GIT Problems like nausea/ vomiting/ constipation/ dyspepsia. 13 subjects (15.48%) reported reduction in sleep time while 20 subjects (23.81%) reported reduction in appetite. Sexual Problems like decreased libido, ejaculation difculty or impotence was reported by 19 subjects (22.62%). 25 subjects (29.76%) reported that they had gained weight after the therapy. Discontinuation Symptoms were reported by 59 subjects (70.24%). Conclusion: The hemogram of patients on SSRI therapy should be monitored from time to time and their biochemical parameters should be evaluated to prevent any untoward adverse effects in the subjects. The patients on SSRI therapy should be closely monitored for adverse effects like sexual problems, GITproblems, CNS manifestations, suicidal thoughts, discontinuation symptoms among others.

Neonatal Brain Injury From SARS-CoV-2: Fact or Fiction?

Neonatal Brain Injury From SARS-CoV-2: Fact or Fiction?

The value of bone marrow biopsy for staging of patients with primary CNS lymphoma.

BackgroundIn patients with presumed primary CNS lymphoma (PCNSL), a systemic manifestation is found only in a small minority. Although bone marrow biopsy (BMB) is recommended for staging, its diagnostic value is unclear.MethodsA retrospective analysis of 392 patients with presumed PCNSL from 3 university hospitals and 33 patients with secondary CNS lymphoma (SCNSL) and initial CNS involvement from a multicenter Germany-wide prospective registry was performed.ResultsA BMB was performed and documented in 320/392 patients with presumed PCNSL; 23 had pathologic results. One harbored the same lymphoma in the brain and bone marrow (BM), 22 showed findings in BM discordant to the histology of brain lymphoma; n = 12 harbored a low-grade lymphoma in the BM, the other showed B-cell proliferation but no proof of lymphoma (n = 5), monoclonal B cells (n = 3), or abnormalities not B-cell-associated (n = 2). In the group of SCNSL with initial CNS manifestation, 32/33 patients underwent BMB; 7 were documented with bone marrow involvement (BMI); 1 had concordant results in the brain and BM with no other systemic manifestation. Six had additional systemic lymphoma manifestations apart from the brain and BM.ConclusionsIn only 2 out of 352 (0.6%) patients with CNS lymphoma (320 presumed PCNSL and 32 SCNSL), BMB had an impact on diagnosis and treatment. While collected in a selected cohort, these findings challenge the value of BMB as part of routine staging in presumed PCNSL.

Behçet's Syndrome Apart From the Triple Symptom Complex: Vascular, Neurologic, Gastrointestinal, and Musculoskeletal Manifestations. A Mini Review.

Behçet‘s Syndrome (BS) is a variable vessel vasculitis according to the Chapel Hill Consensus Nomenclature (1) and may thus affect any organ, including major and minor arterial and venous vessels to a varying degree and with varying frequency. Although the main features of BS are recurrent oral and genital aphthous ulcers, cutaneous lesions, ocular inflammation and arthritis—major vessel and life—or organ threatening involvement of internal organs and the central and peripheral nervous system occur. In general, BS in Europe appears to form six phenotypes of clinical manifestations (2), which are (1) mucocutaneous only, (2) predominant arthritis/articular involvement, (3) vascular phenotype, (4) ocular manifestations, which are most likely associated with CNS manifestations and HLA-B51, (5) dominant parenchymal CNS manifestations (being associated with the ocular ones), and (6) gastrointestinal involvement. Mucocutaneous manifestations are present in almost all patients/all phenotypes. In the following review, we summarize the current knowledge concerning vascular, neurologic, gastrointestinal and musculoskeletal manifestations of the disease.

Computerized tomographic brain findings of CNS manifestations in HIV/AIDS patients receiving HAARTS treatment

Background: Despite current availability of highly active antiretroviral therapy (HAART) in our hospital, neurologic complications of HIV are common. Aim: The aim of this study was to document brain computed tomography (CT) findings in HIV patients receiving HAART who developed neurological complications and to examine the relationship of these findings with CD4 cell counts. Materials and Methods: Twenty patients with central nervous system symptoms out of 200 HIV/AIDS patients receiving HAART at the HIV Clinic of Federal Teaching Hospital, Gombe, were retrospectively studied. The findings were reviewed alongside their clinical features, CD4 + count, and HAART history. Results: CT findings were positive in 12 (60%) of the patients, while no abnormality was seen in 8 (40%). The most common brain abnormality was atrophy (35%). Two out of five patients (40%) with CD4 counts &gt;200 had abnormal CT findings compared with 9 out of 14 patients (64%) with CD4 counts &lt;200 cells who had CT abnormalities. This finding was statistically significant (R = 0.864, P = 0.00). Conclusion: There is high incidence of neurological complications and positive brain CT scan among the patients who defaulted from HAART treatment and with CD4 cell counts of &lt;200 cells/microliter.

Renal Transplants COVID-19 Infection with Different Presentations, Clinical Courses and Outcomes

We report five cases with different clinical presentations of COVID-19 infection in renal transplant patients. Initially a typical clinical presentation, in the form of CNS manifestations (amnesia, behavior change followed by left sided paresis) for the 1st case, GIT manifestations for the 2nd case and chest and cardiac manifestations for the 3rd case were presented. The other two cases similarly presented with chest manifestations but with different clinical courses. Our patients had a favorable outcome, which may provide a reference value for treating COVID-19 patients. © 2021, Ain Shams University Faculty of Medicine. All rights reserved.