Enhanced inflammasome-mediated inflammation and impaired autophagy in peripheral blood mononuclear cells is associated with non-alcoholic fatty liver disease severity.

AIMS: Identification of the progress of non-alcoholic fatty liver disease (NAFLD) is crucial for their effective treatment. Circulating peripheral blood mononuclear cells (PBMC) could be a surrogate monitor instead of complicated and expensive biopsies. Changes in immuno-metabolic status in NAFLD patients may be reflected by an expression of different PBMC-specific molecular markers. It was hypothesized that impaired autophagy with enhanced inflammasome activation is a critical molecular event in PBMC that could contribute to systemic inflammation associated with NAFLD progression. MAIN METHODS: A cross-sectional study with a sample size of 50 subjects were undertaken from a governmental facility in Kolkata, India. Major anthropometric, biochemical, and dietary parameters were recorded. Cellular and serum samples of NAFLD patients were analyzed for oxidative stress, inflammation, inflammasome activation, and autophagic flux by western blot, flow cytometry, immunocytochemistry. KEY FINDINGS: Baseline anthropometric and clinical parameters were found associated with NAFLD severity. Elevated systemic inflammation was reflected by higher proinflammatory markers like iNOS, Cox-2, IL-6, TNF-α, IL-1ß, hsCRP in the serum of NAFLD subjects (p < 0.05). ROS-induced NLRP3 inflammasomes marker proteins were upregulated (p < 0.05) in PBMC along with NAFLD severity. Expression of autophagic markers such as LC3B, Beclin-1 and its regulator pAMPKα were found diminished (p < 0.05) with a concomitant rise of p62. Colocalization of NLRP3 with LC3B proteins in PBMC was found diminished along NAFLD severity. SIGNIFICANCE: Present data provide mechanistic evidence of impaired autophagy and intracellular ROS triggered inflammasome activation in PBMC, which could potentially exacerbate NAFLD severity.

Is Serum Creatine Phosphokinase Level Useful to Predict the Severity of Organophosphate Poisoning?

Background and aim: Organophosphate poisoning is a global health burden due to intentional and occupational exposure, particularly in Asian countries. Patients are usually monitored through serum acetylcholinesterase levels. Still, it is non-specific, does not correlate well with the severity of poisoning, and is not widely available in laboratory settings in developing countries. This study aims to assess serum baseline creatine phosphokinase (CPK) levels as a prognostic biomarker in acute organophosphate poisoning. Materials and methods: We recruited all patients older than 12 years who were admitted to the wards of the Indoor Medicine Ward in Burdwan Medical College and Hospital in West Bengal (India) because of ingestion or inhalation of organophosphorus compounds within the previous 12 hours between May 1, 2019, and November 1, 2020. Clinical severity was categorized according to Peradeniya organophosphorus poisoning (POP) scale. Serum CPK, pseudocholinesterase levels, and pH were measured. Levels were reassessed on days three and seven, and patients were followed-up until death or discharge. Results: 100 patients (68 men and 32 women) were included in the study. Most of them presented with miosis (98%), followed by abdominal pain (96%), diarrhea (78%), and vomiting (52%). In the multivariate analysis, the patients with a higher risk of being intubated were younger. Of the analytical levels, the one that showed a better relationship with the risk of intubation was the pseudocholinesterase level, although without statistical significance. Initial CPK levels, time of admission, or stratification on the POP severity scale, offered poor performance after adjustment. Conclusion: The analytical values of CPK or the POP severity scale at the time the patient presents in the emergency room have limited value to predict the final severity of the picture. The amount of the poison consumed should be collected for future studies to elucidate these differences.

Rare neurological and neuropsychiatric manifestations of scrub typhus: a case series of 10 cases.

INTRODUCTION: Scrub typhus is a potentially life-threatening but curable disease that can produce multi-organ failure. Neurological manifestations in scrub typhus have gained attention recently, where the entire neural axis except the myoneural junction can be involved. Although the pathogenesis of neurological involvement has not been established, immune-mediated mechanisms are suspected. This article reports the clinicopathological features of scrub typhus cases presenting several rare neurological and neuropsychiatric manifestations. METHODS: Three hundred fifty-four serologically confirmed scrub typhus cases were admitted to the Department of General Medicine of Burdwan Medical College and Hospital (West Bengal, India) between May 2018 and May 2022. There were 50 patients who had predominantly neurological manifestations. Of these 50 cases, ten patients presented with extremely rare neurological manifestations. RESULTS: We report 10 cases of scrub typhus (four men and six women) who presented with complex neurological pictures (posterior reversible encephalopathy syndrome, Opalski syndrome, parkinsonism, cerebellitis, isolated opsoclonus, acute transverse myelitis, myositis, polyradiculoneuropathy with cranial neuropathy, acute transient behavioral changes, and fibromyalgia). Immune-mediated mechanisms might have mediated the pathogenesis of most cases following scrub typhus infection. CONCLUSION: From a clinicopathological point of view, each case was unique in its presentation and treatment response. In any acute onset neurological disorders associated with febrile illness in the tropics or subtropics, scrub typhus infection should be included in the differential diagnosis, despite the absence of eschar and unremarkable neuroimaging findings. This otherwise curable disease may result in multi-organ dysfunction syndrome and death if the diagnosis is delayed.

Scrub Typhus Presenting as Unilateral Abducens Nerve Palsy.

Scrub typhus, an acute febrile infectious disease prevalent in the "Tsutsugamushi Triangle", is a mite-born rickettsial zoonosis, caused by Orientia tsutsugamushi. Although the clinical presentation is protean, it rarely causes abducens nerve palsy. We report a 14-year-old previously healthy Indian girl who presented with a recent onset right abducens nerve palsy and headache, but without fever and without the classic dermatological manifestation ("eschar") of the disease. After exclusion of common infectious, autoimmune, and neoplastic causes, she was finally diagnosed with scrub typhus associated with an abducens nerve palsy, which responded to doxycycline therapy.

COVID-19 Induced Miller Fisher Syndrome Presenting With Autonomic Dysfunction: A Unique Case Report and Review of Literature.

A plethora of neurological manifestations are associated with the 2019 coronavirus infectious disease (COVID-19). We hereby report the first case of a patient infected with SARS-CoV-2 who acutely presented with autonomic dysfunction preceding the onset of complete clinical picture of Miller Fisher syndrome. She was finally diagnosed to be a case of anti-ganglioside antibody positive post-COVID-19 Miller Fisher syndrome with dysautonomia and treated with intravenous immunoglobulin with an excellent response. We also discuss the plausible pathogenic mechanisms of COVID-19 induced Miller Fisher syndrome and furnish a review of the post-COVID-19 Miller Fisher syndrome cases reported.

Complex movement disorders in SARS-CoV-2 infection induced acute disseminated encephalomyelitis.

Movement disorders are extremely rare in acute disseminated encephalomyelitis (ADEM) and in the novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) infection. We herein report a 34-years-old previously healthy woman who presented with a febrile illness and a constellation of movement disorders (predominantly myoclonus) followed by encephalopathy. After exclusion of common infectious, autoimmune and paraneoplastic etiologies, she was diagnosed to have COVID-19 induced ADEM, which responded to intravenous methylprednisolone and intravenous immunoglobulin. Our case adds to the tally of cases of post-SARS-CoV-2 infection related movement disorders and to the exceedingly rare list of cases in which movement disorders preceded ADEM.

Tubercular longitudinally extensive transverse myelitis (LETM): An enigma for primary care physicians.

Albeit, all forms of tuberculosis (TB) are endemic in India, spinal intramedullary TB and tubercular longitudinally extensive transverse myelitis (LETM) is deemed extremely rare. With recent advances in the field of neurology, autoimmune astrocytopathy (neuromyelitis optica spectrum disorders, NMOSD), myelin-oligodendrocyte glycoprotein associated encephalomyelitis (MOG-EM), metabolic myelopathy, connective tissue diseases and viral infections have gained considerable focus in the list of differentials of LETM whereas tubercular association is often forgotten. This report presents a rare case of acute transverse myelopathy which unveiled previously undiagnosed pulmonary tuberculosis in an adult rural Indian male. The patient responded well to anti-tubercular therapy and corticosteroids. Exact pathogenesis of LETM in TB remains elusive. Association of TB with MOG-EM has been one of the recent hot-cakes. However, an ill-defined immune-inflammatory response to the infectious agent is the likely cause of tubercular LETM. Hence, the primary care physicians who are the first medical contacts of acute LETM cases and in most cases due to diagnostic dilemma there is an unavoidable delay in accurate diagnosis and initiation of therapy. Primary care doctors should nurture a high index of suspicion to diagnose this potentially lifetime-debilitating yet absolutely treatable clinical condition i.e. tubercular LETM.

Hemifacial Spasm as the Presenting Manifestation of Type 3c Diabetes Mellitus.

Background: Type 3c diabetes mellitus (T3cDM) usually occurs because of a variety of exocrine pancreatic diseases with varying mechanisms, which eventually lead to secondary pancreatic endocrine insufficiency i.e. hyperglycemia. Phenomenology: A man suffering from previously undiagnosed T3cDM presenting with subacute onset hemifacial spasm. Educational value: This case emphasizes the importance of rapid bedside measurement of capillary blood glucose in patients presenting with acute to subacute onset movements disorders irrespective of their past glycemic status.

Seizure as a presenting manifestation of Wernicke's encephalopathy induced by hyperemesis gravidarum.

Wernicke's encephalopathy (WE) is an acute neurological condition characterized by the triad of ophthalmoparesis with nystagmus, ataxia, and global confusion. WE is a life-threatening illness caused by thiamine deficiency, primarily affecting the peripheral and central nervous systems. Thiamine deficiency is predominantly associated with chronic alcoholism, but various other causes have also been reported, including severe malnutrition, prolonged parenteral nutrition, malignancies, immunodeficiency syndromes, liver disease, hyperthyroidism and severe anorexia nervosa, and hyperemesis gravidarum. We, hereby, report a unique case of WE induced by hyperemesis gravidarum that presented in mid-trimester of pregnancy in a rather extremely unusual way with focal seizures and secondary generalization but fortunately ended up with a good feto-maternal outcome.

Cerebral venous thrombosis in COVID-19.

BACKGROUND AND AIMS: Initially, novel severe acute respiratory syndrome coronavirus (SARS-CoV-2) was considered primarily a respiratory pathogen. However, with time it has behaved as a virus with the potential to cause multi-system involvement, including neurological manifestations. Cerebral venous sinus thrombosis (CVT) has increasingly been reported in association with coronavirus infectious disease of 2019 (COVID-19). Here, we have shed light upon CVT and its possible mechanisms in the backdrop of the ongoing COVID-19 pandemic. METHODS: In this review, data were collected from PubMed, EMBASE and Web of Science, until March 30, 2021, using pre-specified searching strategies. The search strategy consisted of a variation of keywords of relevant medical subject headings and keywords, including "COVID-19", "SARS-CoV-2", "coronavirus", and "cerebral venous sinus thrombosis". RESULTS: COVID-19 has a causal association with a plethora of neurological, neuropsychiatric and psychological effects. CVT has gained particular importance in this regard. The known hypercoagulable state in SARS-CoV-2 infection is thought to be the main mechanism in COVID-19 related CVT. Other plausible mechanisms may include vascular endothelial dysfunction and altered flow dynamics. CONCLUSIONS: Although there are no specific clinical characteristics, insidious or acute onset headache, seizures, stroke-like, or encephalopathy symptoms in a patient with, or who has suffered COVID-19, should prompt the attending physician to investigate for CVT. The treatment of COVID-19 associated CVT does not differ radically from the therapy of CVT without the infection, i.e. urgent initiation of parenteral unfractionated heparin or low molecular weight heparin followed by conventional or mostly newer oral anticoagulants.

A case of primary disseminated rhinosporidiosis and dapsone-induced autoimmune hemolytic anemia: A therapeutic misadventure.

Rhinosporidiosis, a chronic inflammatory disease, which is caused by the aquatic microorganism Rhinosporidium seeberi, is endemic in India and in many other regions of the tropics. It primarily infects mucocutaneous surfaces of nose, nasopharynx, and conjunctiva through transepithelial invasion. However, over the centuries, atypical involvement of other body parts, especially viscera, bone, subcutaneous layers, genitals, the tracheobronchial tree, and even the skull has been, though rarely, reported. This chronic granulomatous infection is notorious for its propensity for recurrence following autoinoculation and poor response to most of the anti-microbials except dapsone. Surgical excision followed by cauterization remains the treatment of choice when an operation is feasible. We herein report a case of an immunocompetent person with primary disseminated dermato-pulmonary rhinosporidiosis, which created significant diagnostic dilemma at the beginning, got complicated due to dapsone-induced direct anti-globulin test-positive autoimmune hemolytic anemia, and finally responded to prolonged multidrug therapy with liposomal amphotericin B, ketoconazole and cycloserine. This report establishes the importance of tissue diagnosis in rhinosporidiosis and even, in resource-poor set-ups, a simple histopathological diagnosis can promote an early and affordable accurate diagnosis, and subsequently, a proper therapeutic intervention.

A Rare Case of SARS-CoV-2 Infection Associated With Pituitary Apoplexy Without Comorbidities.

Pituitary apoplexy is a medical and surgical emergency caused by hemorrhage or infarction of the hypophysis, which typically occurs within a pituitary adenoma. It is usually characterized by severe (often thunderclap) headache, visual disturbances, cranial nerve impairments, and hormonal deficiencies. We herein report a case of a previously healthy woman with severe acute respiratory syndrome coronavirus 2 infection associated with pituitary apoplexy. The plausible pathophysiological mechanisms of pituitary apoplexy in infectious coronavirus disease 2019 are discussed.

A case of area postrema variant of neuromyelitis optica spectrum disorder following SARS-CoV-2 infection.

Neuromyelitis optica spectrum disorder (NMOSD) is a disabling autoimmune astrocytopathic channelopathy, characterized by the presence of pathogenic antibodies to aquaporin-4 (AQP-4) water channels. Several viral infections including HIV, influenza virus, varicella zoster virus, and Epstein Barr virus, among others, have been alleged to trigger NMOSD in both immunocompetent and immunocompromised individuals. Neurological manifestations of coronavirus infectious disease of 2019 (COVID-19) have been ever evolving and the spectrum of neuraxial involvement is broadening. Albeit it may affect any area of the neural axis, the involvement of the spinal cord is rare compared to that of the brain and of the peripheral nervous system. Cases with acute longitudinally extensive transverse myelitis (LETM) have been recently reported in SARS-CoV-2 infection but did not fulfill the international consensus diagnostic criteria for NMOSD. AQP-4-antibody-seropositive NMOSD following SARS-CoV-2 infection had not yet been reported. We herein report a novel case of a previously healthy man who presented with a clinical picture of bouts of vomiting and hiccoughs (area postrema syndrome), which rapidly evolved to acute LETM, all following SARS-CoV-2 infection. He was finally diagnosed to be a case of seropositive NMOSD which presented as area postrema syndrome. The response to immunomodulatory drugs was excellent.

Rabeto plus: a valuable drug for managing functional dyspepsia.

The aim of the study was to evaluate and document the efficacy and tolerability of rabeto plus (FDC of rabeprazole and itopride) in management of functional dyspepsia. It was an open, prospective, non-comparative, multidose study. The patients with functional dyspepsia (NERD or non-erosive reflux disease) attending OPD of a leading, tertiary care, teaching hospital in West Bengal (BS Medical College, Bankura) were inducted in the study. A total of 46 adult patients of either sex with functional dyspepsia and a clinical diagnosis of NERD were given 1 capsule of rabeto plus before breakfast, for up to 4 weeks. Primary efficacy variables were relief from symptoms of heartburn, nausea, vomiting, waterbrash and fullness. Secondary efficacy variables were global assessment of efficacy and toleration by patients and treating physicians. The tolerability was assessed on the basis of record of spontaneously reported adverse events with their nature, intensity and outcome. Out of 55 patients enrolled in the study, 46 completed the study as planned, while 9 patients were lost to follow-up (dropped). Most patients reported near total symptom relief by the end of study. Total symptom score showed remarkable and significant improvement from baseline to end of the study. Importantly, none of the patients reported any side-effect. All participants tolerated the drug well. Moreover, response to study drug was rated as excellent or good by over 93% patients and their treating physicians. This means that 9 out 10 patients receiving rabeto plus reported desired symptom relief from dyspepsia. Thus it was concluded that rabeto plus is a valuable drug for treatment of functional dyspepsia or NERD.