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Schmidt's syndrome, or autoimmune polyendocrine syndrome type 2 (APS-2), is an uncommon disorder characterized by the co-occurrence of autoimmune thyroiditis and adrenalitis. APS-2 is defined as a combination of Addison's disease, autoimmune thyroid disease, and/or type 1 diabetes mellitus. It is an autosomal dominantly inherited polygenic disorder with incomplete penetrance; the candidate genes include but are not limited to HLA-DR3, HLA-DR4, CTLA-4, PTPN22, and CD25-IL-2. Autoimmune thyroiditis, often Hashimoto's disease, results in hypothyroidism. Primary adrenal failure results in enhanced secretion of adrenocorticotrophic hormone melanocyte and co-secretion of melanocyte-stimulating hormone, contributing to hyperpigmentation. Mineralocorticoid deficiency results in salt wasting, fatigue and cramps, postural hypotension, and hyperkalemia. Cortisol, an insulin counter-regulatory hormone, plays a pivotal role in maintaining euglycemia; deficiency predisposes to the development of hypoglycemia. We here report a rare presentation of Schmidt's syndrome as hypoinsulinemic hypoglycemia in a middle-aged male patient. Management includes treatment of acute hypoglycemic episodes with glucose or glucagon, long-term glucocorticoids and mineralocorticoids for adrenal insufficiency, and thyroid hormone supplements for hypothyroidism. This case report and brief overview aim to contribute to the scientific understanding of Schmidt's syndrome/APS-2. Additionally, here we briefly outline the diagnostic challenges in hypoglycemia evaluation, including the utilization of Whipple's triad and the gold standard supervised 72-hour fast and evaluation for primary adrenal and thyroid insufficiencies.

Abstract Introduction Inconvenient administration and side effects of some disease-modifying therapies (DMTs) for relapsing multiple sclerosis (RMS) can deter adherence. We evaluated treatment satisfaction with cladribine tablets (CladT) for RMS in the Arabian Gulf. Methods This was a non-interventional, multicentre, prospective observational study in non-pregnant/lactating adults (aged ≥ 18 years) with RMS eligible for 1st treatment with CladT (EU labelling). The primary outcome was overall treatment satisfaction at 6 months (Treatment Satisfaction Questionnaire for Medication [TSQM]-14, v. 1.4), Global Satisfaction subscale. Secondary endpoints were TSQM-14 scores for convenience, satisfaction with side effects and satisfaction with effectiveness. Patients provided written informed consent. Results Of 63 patients screened, 58 received CladT and 55 completed the study. Mean age was 33 ± 9 years; mean weight 73 ± 17 kg; 31% male/69% female; mostly from the United Arab Emirates (52%) or Kuwait (30%). All had RMS (mean 0.9 ± 1.1 relapses in the past year), mean Expanded Disability Status Scale (EDSS) 1.4 ± 1.2; 36% were DMT-naïve. Mean [95% CI] score was high for overall treatment satisfaction (77.8 [73.0–82.6]), ease of use (87.4 [83.7–91.0]), tolerability (94.2 [91.0–97.3]) and effectiveness (76.2 [71.6–80.7]). Scores were similar irrespective of DMT history, age, gender, relapse history or EDSS. No relapses or serious treatment-emergent adverse events (TEAE) occurred. Two severe TEAE occurred (fatigue, headache) and 16% reported lymphopenia (two cases of grade 3 lymphopenia). Absolute lymphocyte counts at baseline and 6 months were 2.2 ± 0.8 × 109/L and 1.3 ± 0.3 × 109/L, respectively. Conclusions Treatment satisfaction, ease of use, tolerability and patient-perceived effectiveness for CladT were high, irrespective of baseline demographics, disease characteristics and prior treatment.

The clean energy demand and limited fossil fuel reserves require an alternate source that is sustainable and eco-friendly. This demand for clean energy steered the introduction of biofuels such as bioethanol and biodiesel. The third-generation biodiesel is promising as it surpasses the difficulties associated with food security and land usage. The third-generation biodiesel comprises biodiesel derived from oil produced by oleaginous microbes. The term oleaginous refers to microbes with the ability to accumulate lipids to about 20% of the biomass and is found in the form of triacylglycerols. Yeasts can be grown easily on a commercial scale and are amenable to modifications to increase single-cell oil (SCO) productivity. The oleaginous yeast L. starkeyi is a potential lipid producer that can accumulate up to 70% of SCO of its cell dry weight under optimum conditions. Compared to other oleaginous organisms, it can be grown on a wide range of feedstock and a good part of the lipid produced can be converted to biodiesel. This review presents the recent advances in single-cell oil production from L starkeyi and strategies to increase lipid production are analyzed.

Schistosomiasis is a parasitic infection caused by the trematodes of the Schistosoma genus. It is one of the neglected tropical diseases, contributing significantly to health-care costs, morbidity, and mortality in the developing world. The resultant disease is broadly classified as urogenital and gastrointestinal schistosomiasis. Intestinal schistosomiasis manifests as altered bowel habits, tenesmus, rectal bleeding, and or abdominal pain. Mucosal lesions include erythema, nodularity, and inflammatory polyps of the colon. Colonic polyps are mucosal lesions, benign or malignant, sporadic or inherited, and have been in the limelight for many years owing to their malignant potential. Inflammatory lesions in schistosomiasis can morphologically resemble neoplastic polyps and pose a diagnostic dilemma. We here report a rare case of intestinal schistosomiasis masquerading as colonic polyps, diagnosed on biopsy and effectively treated with praziquantel.

Background: Intravenous immunoglobulin (IVIg) and therapeutic plasma exchange (TPE) are among the main immunotherapies for neurological disorders. Their benefit is greatest in immune-mediated conditions, but their distinct efficacy cannot be simply explained. Objectives: This review aimed to systematically identify studies comparing the efficacy of TPE and IVIg treatments for selected autoimmune neurological disorders and identify optimal therapies for each condition. Data Sources and Methods: PubMed, MEDLINE and Embase databases were searched for original publications from 1990 to 2021. Additional publications were identified via expert recommendations. Conference abstracts older than 2017, review articles and articles without information on TPE and IVIg comparison in title and abstract were excluded. Risks of bias were descriptively addressed, without a meta-analysis. Results: Forty-four studies were included on Guillain–Barré syndrome (20 studies – 12 adult, 5 paediatric, 3 all ages), myasthenia gravis (11 studies –8 adult, 3 paediatric), chronic immune–mediated polyradiculoneuropathy (3 studies –1 adult, 2 paediatric), encephalitis (1 study in adults), neuromyelitis optica spectrum disorders (5 studies –2 adult, 3 all ages) and other conditions (4 studies – all ages). TPE and IVIg were mostly similarly efficacious, measured by clinical outcomes and disease severity scores. Some studies recommended IVIg as easy to administer. TPE procedures, however, have been simplified and the safety has been improved. TPE is currently recommended for management of neuromyelitis optica spectrum disorder relapses and some myasthenia gravis subtypes, in which rapid removal of autoantibodies is crucial. Conclusion: Despite some limitations (e.g. the low evidence levels), this review provides an extensive 30-year-long overview of treatments for various conditions. Both IVIg and TPE are usually comparably efficacious options for autoimmune neurological disorders, with few exceptions. Treatment choices should be patient-tailored and based on available clinical resources. Better designed studies are needed to provide higher-level quality of evidence regarding clinical efficacy of TPE and IVIg treatments.

Abstract Background Neuromyelitis optica spectrum disorder (NMOSD) is a rare, neurological disease that places a significant burden on patients, their carers, and healthcare systems. Objectives To estimate patient and carer health utilities and costs of NMOSD within the UK setting. Methods Patients with NMOSD and their carers, recruited via a regional specialist treatment centre, completed a postal questionnaire that included a resource use measure, the EuroQoL (EQ)-5D-5L, EQ-5D-VAS, Vision and Quality of Life Index (VisQoL), Carer Experience Survey (CES) and the Expanded Disability Status Scale (EDSS). The questionnaire asked about respondents’ use of health and community care services, non-medical costs, informal care and work capacity. Data were analysed descriptively. Uncertainties in costs and utilities were assessed using bootstrap analysis. Results 117 patients and 74 informal carers responded to the survey. Patients’ mean EQ-5D-5L and VisQoL health utilities (95% central range) were 0.54 (− 0.29, 1.00) and 0.79 (0.11, 0.99), respectively. EQ-5D-5L utility decreased with increasing EDSS score bandings, from 0.80 (0.75, 0.85) for EDSS ≤ 4.0, to 0.20 (− 0.29, 0.56) for EDSS 8.0 to 9.5. Mean, 3-month total costs were £5623 (£2096, £12,156), but ranged from £562 (£381, £812) to £32,717 (£2888, £98,568) for these EDSS bandings. Carer-reported EQ-5D-5L utility and CES index scores were 0.85 (0.82, 0.89) and 57.67 (52.69, 62.66). Mean, 3-month costs of informal care were £13,150 to £24,560. Conclusions NMOSD has significant impacts on health utilities and NHS and carer costs. These data can be used as inputs to cost-effectiveness analyses of new medicines for NMOSD.

Cellulases are commercially important enzymes with application in various industries such as biofuel, detergent, food processing, brewery, pulp and paper. To make its production cost-effective, a preferred method is to use solid-state fermentation and with use of inexpensive substrates. Solid-state fermentation is an alternative culturing method and yields higher enzymes compared to submerged fermentation. In the current study, Aspergillus niger was isolated and further developed as inoculum for solid-state fermentation. Agroindustrial discards like banana pseudostem, jackfruit waste were used as the substrates. The substrates were pretreated by acid and were characterized by FTIR analysis to confirm the presence of cellulosic content. Different concentrations of the substrates were attempted for fermentation and the yield of the enzyme was compared. The solid-state fermentation was stable for enzyme production as well as microbial growth. The cellulase activity per gram of the substrate (U/g) was obtained maximum for jackfruit waste-based media (17±1.1 U/g). Both the lignocellulosic substrates were potential substrates for the production of cellulase enzyme. With further optimization and scale-up, this could be a cheap and sustainable process. This study has validated agro-industrial waste’s bioconversion into value-added products that have a remarkable environmental and economic advantage.

Abstract Improvements in assays for detecting serum antibodies against myelin oligodendrocyte glycoprotein (MOG) have led to the appreciation of MOG‐antibody‐associated disease (MOGAD) as a novel disorder. However, much remains unknown about its etiology. We performed human leukocyte antigen (HLA) analysis in 82 MOGAD patients of European ancestry in the UK population. No HLA class II associations were observed, thus questioning the mechanism of anti‐MOG antibody generation. A weak protective association of HLA‐C*03:04 was observed (OR = 0.26, 95% CI = 0.10‐0.71, pc = 0.013), suggesting a need for continued efforts to better understand MOGAD genetics and pathophysiology.

Abstract Background Common variable immunodeficiency (CVID) is a group of heterogeneous primary immunodeficiencies characterised by a dysregulated and impaired immune response. In addition to an increased susceptibility to infection, it is also associated with noninfectious autoimmune and lymphoproliferative complications. CVID is rarely associated with neurological complications. Pulmonary involvement is more common, and patients can develop an interstitial lung disease known as granulomatous-lymphocytic interstitial lung disease (GLILD). Case presentation A 50-year-old Caucasian female with a history of Evans syndrome (idiopathic thrombocytopaenic purpura and autoimmune haemolytic anaemia) and hypogammaglobulinaemia initially presented to the neurology clinic with marked cerebellar ataxia and headaches. Following extensive investigation (which included brain biopsy), she was diagnosed with neuro-sarcoidosis and her symptoms resolved following treatment with immunosuppressive therapy. Over the following 10 years, she was extensively investigated for recurrent pulmonary infections and abnormal radiological findings, which included pulmonary nodules, infiltrates and splenomegaly. Subsequently, she was referred to an immunology clinic, where immunoglobulin replacement treatment was started for what was ultimately considered to be CVID. Shortly afterwards, evaluation of her clinical, radiological and histological findings at a specialist interstitial lung disease clinic led to a diagnosis of GLILD. Conclusion CVID is a condition which should be suspected in patients with immunodeficiency and recurrent infections. Concomitant autoimmune disorders such as haemolytic anaemia and immune thrombocytopenia may further support the diagnosis. As illustrated in this case, there is a rare association between CVID and inflammatory involvement of the neurological system. Respiratory physicians should also suspect CVID with associated GLILD in patients with apparent pulmonary granulomatous disease and recurrent infections. In addition, this case also highlights the challenge of diagnosing CVID and its associated features, and how the definitive exclusion of other pathologies such as malignancy, mycobacterial infection and lymphoma is required as part of this diagnostic process.

Objective To identify factors predictive of relapse risk and disability in myelin oligodendrocyte glycoprotein associated disease (MOGAD).Setting Patients were seen by the neuromyelitis optica spectrum disorders (NMOSD) service in Liverpool, UK, a national referral centre for adult patients with MOGAD, NMOSD and related conditions.Participants Patients with MOGAD=76 from England, Northern Ireland and Scotland were included in this cohort study.Results Relapsing disease was observed in 55% (42/76) of cases. Steroid treatment >1 month (OR 0.2, 95% CI 0.05 to 0.80; p=0.022), transverse myelitis (TM) at first attack (OR 0.03, 95% CI 0.004 to 0.23; p=0.001) and male sex (OR 0.16, 95% CI 0.04 to 0.68; p=0.014) were associated with monophasic disease (area under the curve=0.85). Male sex (HR 0.46, 95% CI 0.24 to 0.89; p=0.011) and TM at disease onset (HR 0.42, 95% CI 0.22 to 0.82; p=0.011) were also associated with an increased latency to first relapse. 45% (32/71) of patients became MOG-antibody negative and in relapsing patients negative seroconversion was associated with a lower relapse risk (relative risk 0.11 95% CI 0.05 to 0.26; p

Purpose Optical coherence tomography (OCT) captures retinal damage in neuromyelitis optica spectrum disorders (NMOSD). Previous studies investigating OCT in NMOSD have been limited by the rareness and heterogeneity of the disease. The goal of this study was to establish an image repository platform, which will facilitate neuroimaging studies in NMOSD. Here we summarise the profile of the Collaborative OCT in NMOSD repository as the initial effort in establishing this platform. This repository should prove invaluable for studies using OCT to investigate NMOSD.Participants The current cohort includes data from 539 patients with NMOSD and 114 healthy controls. These were collected at 22 participating centres from North and South America, Asia and Europe. The dataset consists of demographic details, diagnosis, antibody status, clinical disability, visual function, history of optic neuritis and other NMOSD defining attacks, and OCT source data from three different OCT devices.Findings to date The cohort informs similar demographic and clinical characteristics as those of previously published NMOSD cohorts. The image repository platform and centre network continue to be available for future prospective neuroimaging studies in NMOSD. For the conduct of the study, we have refined OCT image quality criteria and developed a cross-device intraretinal segmentation pipeline.Future plans We are pursuing several scientific projects based on the repository, such as analysing retinal layer thickness measurements, in this cohort in an attempt to identify differences between distinct disease phenotypes, demographics and ethnicities. The dataset will be available for further projects to interested, qualified parties, such as those using specialised image analysis or artificial intelligence applications.

Neuromyelitis Optica Spectrum Disorder (NMOSD) is an inflammatory demyelinating disease of the central nervous system (CNS) primarily affecting the optic nerves and spinal cord, but also involving other regions of the CNS including the area postrema, periaqueductal gray matter, and hypothalamus. Knowledge related to pediatric manifestations of NMOSD has grown in recent years, particularly in light of newer information regarding the importance of not only antibodies to aquaporin 4 (AQP4-IgG) but also myelin oligodendrocyte glycoprotein (MOG-IgG) in children manifesting clinically with this syndrome. In this review, we describe the current state of the knowledge related to clinical manifestations, diagnosis, and chronic therapies for children with NMOSD, with emphasis on literature that has been published in the last 5 years. Following the review, we propose recommendations for the assessment/follow up clinical care, and treatment of this population.

Neuromyelitis optica spectrum disorder (NMOSD) is an uncommon inflammatory disease of the central nervous system, manifesting clinically as optic neuritis, myelitis, and certain brain and brainstem syndromes. Cases clinically diagnosed as NMOSD may include aquaporin 4 (AQP4)-antibody-seropositive autoimmune astrocytopathic disease, myelin oligodendrocyte glycoprotein (MOG)-antibody-seropositive inflammatory demyelinating disease, and double-seronegative disease. AQP4-antibody disease has a high female-to-male ratio (up to 9:1), and its mean age at onset of ~40 years is later than that seen in multiple sclerosis. For MOG-antibody disease, its gender ratio is closer to 1:1, and it is more common in children than in adults. Its clinical phenotypes differ but overlap with those of AQP4-antibody disease and include acute disseminated encephalomyelitis, brainstem and cerebral cortical encephalitis, as well as optic neuritis and myelitis. Double-seronegative disease requires further research and clarification. Population-based studies over the past two decades report the prevalence and incidence of NMOSD in different populations worldwide. One relevant finding is the varying prevalence observed in different racial groups. Consistently, the prevalence of NMOSD among Whites is ~1/100,000 population, with an annual incidence of

Abstract. Introduction:. Autoantibody-mediated autoimmunity directed against targets within the voltage-gated potassium channel complex (VGKCC autoantibodies) has been implicated in causing neuropathic pain. Methods:. We report the case of a 76-year-old, United Kingdom male who was diagnosed with contactin-associated protein 2 (CASPR2) autoantibody–associated Morvan syndrome, a rare neurological condition. Results:. He had previously worked in a swine abattoir; exposure to aerosol within swine abattoirs has been reported to elicit an immune response resulting in the production of these autoantibodies; however, unusually, his manifestations emerged with several years' latency. Although this patient's Morvan syndrome–associated seizures were well-controlled with antiepileptic drugs, his neuropathic pain and painful muscle fasciculations did not respond to pharmacological interventions. He refused pain management program treatment, but high-dose immunoglobulin treatment or treatment with rituximab, reported to be sometimes effective in this group, was not initiated because of concerns regarding his general frailty. Discussion and Conclusion:. This case highlights issues around the identification and treatment of rare patients with chronic pain who have voltage-gated potassium channel complex autoantibodies; it also emphasizes the possibility that former swine abattoir workers might be at risk of developing neuropathic pain even years after their vocational exposure.

Three patients with the clinical and investigation features of facial onset sensory and motor neuronopathy (FOSMN) syndrome are presented, one of whom came to a post-mortem examination. This showed TDP-43-positive inclusions in the bulbar and spinal motor neurones as well as in the trigeminal nerve nuclei, consistent with a neurodegenerative pathogenesis. These data support the idea that at least some FOSMN cases fall within the spectrum of the TDP-43 proteinopathies, and represent a focal form of this pathology.

Background: Transverse myelitis (TM) is an immune-mediated disorder of the spinal cord that affects adults and children and that causes motor, sensory and autonomic dysfunction. There is a prolonged recovery phase, which may continue for many years. Neuromyelitis optica (NMO) is an uncommon relapsing inflammatory central nervous system condition in which TM can be the first presenting symptom. As TM and NMO affect many patients in the prime of their working life, the disorder can impose a significant demand on health resources. There are currently no robust controlled trials in children or adults to inform the optimal treatment of TM. However, treatment with intravenous immunoglobulin (IVIG) is being effectively used in the management of a range of neurological conditions. Although other interventions such as plasma exchange (PLEX) in addition to intravenous (IV) methylprednisolone therapy can be beneficial in TM, PLEX is costly and technically challenging to deliver in the acute setting. IVIG is more readily accessible and less costly. Objective: To evaluate whether additional and early treatment with IVIG is of extra benefit in TM compared with standard therapy with IV steroids. Design: A multicentre, single-blind, parallel-group randomised controlled trial of IVIG compared with standard therapy for the treatment of TM in adults and children. Participants: Patients aged ≥ 1 year diagnosed with either acute first-onset TM or first presentation of NMO. Target recruitment was 170 participants (85 participants per arm). Interventions: Participants were randomised 1 : 1 to treatment with IV methylprednisolone only or treatment with IV methylprednisolone plus 2 g/kg of IVIG in divided doses within 5 days of the first commencement of steroid therapy. Main outcome measures: Primary outcome measure – American Spinal Injury Association (ASIA) Impairment Scale at 6 months post randomisation, with a good outcome defined by a two-grade change. Secondary and tertiary outcome measures – ASIA motor and sensory scales, Expanded Disability Status Scale, health outcome, quality of life, Client Service Receipt Inventory and International Spinal Cord Injury Pain, Bladder and Bowel Basic Data Sets. Results: In total, 26 participants were screened and two were randomised into the study. With the limited sample size, treatment effect could not be determined. However, we identified barriers to accrual that included strict inclusion criteria, the short enrolment window, challenges associated with the use of the ASIA Impairment Scale as an outcome measure and estimation of the incidence of TM. Conclusions: The study did not reach the end point and the effect of IVIG in TM/NMO could not be determined. Investigators should be aware of the potential challenges associated with carrying out a rare disease trial with a short enrolment window. The study question is one that still necessitates investigation. Preliminary work to ameliorate the effect of the barriers encountered in this study is vital. Trial registration: EudraCT 2014-002335-34, ClinicalTrials.gov NCT02398994 and Current Controlled Trials ISRCTN12127581. Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 21, No. 31. See the NIHR Journals Library website for further project information. Funding was also received from Biotest AG, Germany (supply of IVIG) and the Transverse Myelitis Society (excess research cost to facilitate study initiation).

Retinoblastoma patients have excellent survival following primary treatment by enucleation, radiotherapy or chemotherapy. Patients receiving chemotherapy or radiotherapy may develop second malignancies years later due to DNA damage or genetic mutations. Urinary bladder leiomyosarcoma is one among them and most such cases have been reported after chemotherapy. We report the third case occurring after isolated radiotherapy.

A large proportion of "encephalitis" is caused by unknown agents. Of late, a new category of disorders, "autoimmune encephalitis," has been described, which present with features similar to viral encephalitides. A well-delineated and common entity among this group is the recently described anti-NMDAR encephalitis (NMDARE). Although this entity was initially described in young women harboring ovarian teratomas, it is now characterised as well in children and men. Approximately 60% of the patients have an underlying tumor, usually an ovarian teratoma. In 40% of the patients, no cause can be found (idiopathic NMDARE). NMDARE typically presents with psychiatric features followed by altered level of consciousness, severe dysautonomia, hyperkinetic movement disorders, seizures and central hypoventilation. Orofacial dyskinesias resulting in lip and tongue mutilation are quite common. Seizures, are common and may be difficult to treat. The disease can be confirmed by serum and cerebrospinal fluid anti-NMDAR antibodies. Titers of these antibodies can also guide response to treatment. Tumor removal is necessary if identified, followed by immunological treatment. Intravenous methylprednisolone and immunoglobulins aim to suppress/modulate immune response while plasma exchange attempts to remove antibodies and other inflammatory cytokines. Rituximab and cyclophosphamide aim to suppress antibody production. Recovery is slow and often with neurological deficits if treatment is delayed. With many distinctive clinical features, a specific antibody that aids diagnosis, and early effective treatment with commonly available drugs leading to good outcomes, NMDARE is a diagnosis that should be considered early in any case of "unexplained encephalitis."