A case report of COVID-19 in refractory myasthenia: Outcome with remdesivir and dexamethasone.

RATIONALE: Myasthenia gravis (MG) patients are at increased risk of COVID-19 infection and its complications due to chronic immunosuppression. COVID-19 infection can also increase the risk of myasthenia exacerbation. PATIENT CONCERNS: The patient presented with respiratory distress, fever and chills and was diagnosed with COVID-19 pneumonia. His past medical history includes seropositive generalized MG diagnosed in 2019, hypertension, atrial fibrillation and congestive heart failure with reduced ejection failure. DIAGNOSES: Refractory seropositive generalized MG having COVID-19 pneumonia and respiratory failure (needing mechanical ventilation) with sepsis. INTERVENTION: Use of intravenous remdesivir and dexamethasone and patient's myasthenic exacerbation (due to COVID-19 and its complications) was successfully treated with plasmapheresis. OUTCOMES: Patient was successfully weaned off ventilator to trach collar and was discharged to inpatient rehabiliation. He was followed up 1 month post hospital discharge and was on trach collar. LESSONS: This case report illustrates early use of the combination therapy might be beneficial in refractory myasthenia gravis cases even with chronic immunosuppression and severe COVID-19 infection.

COVID-19 in Refractory Myasthenia Gravis- A Case Report of Successful Outcome.

This is a brief report of a patient who has refractory Myasthenia Gravis, on multiple long-term immunosuppressive therapies and contracted COVID-19 during this 2020 pandemic. She was quarantined for total of 14 days and recovered successfully without any complications (no myasthenia exacerbation or crisis, no COVID-19 related complications), with no changes to her immunosuppressive therapy. Treatment of MG patients with COVID-19 needs to be tailored to individual patient.

Are Tanycytes the Missing Link Between Type 2 Diabetes and Alzheimer's Disease?

Tanycytes are highly specialized bipolar ependymal cells that line the ventrolateral wall and the floor of the third ventricle in the brain and form a blood-cerebrospinal fluid barrier at the level of the median eminence. They play a pivotal role in regulating metabolic networks that control body weight and energy homeostasis. Due to the glucosensing function of tanycytes, they could be considered as a critical player in the pathogenesis of type 2 diabetes. Genetic fate mapping studies have established the role of tanycytes for the newly detected adult hypothalamic neurogenesis with important implications for metabolism as well as pathophysiology of various neurodegenerative diseases. We believe that a comprehensive understanding of the physiological mechanisms underlying their neuroplasticity, glucosensing, and cross talk with endothelial cells will enable us to achieve metabolic homeostasis in type 2 diabetes patients and possibly delay the progression of Alzheimer's disease and hopefully improve cognitive function.

Glia Maturation Factor in the Pathogenesis of Alzheimer's disease.

Alzheimer's disease (AD) is a neurodegenerative and neuroinflammatory disease characterized by the presence of extracellular amyloid plaques (APs) and intracellular neurofibrillary tangles (NFTs) in the brain. There is no disease modifying therapeutic options currently available for this disease. Hippocampus, entorhinal cortex (Broadmann area 28), perirhinal cortex (Broadmann area 35) and insular cortices are areas within the brain that are first ones to be severely affected in AD. Neuroinflammation is an important factor that induces neurodegeneration in AD. Glia maturation factor (GMF), a proinflammatory factor plays a crucial role in AD through activation of microglia and astrocytes to release proinflammatory mediators in the brain. Through immunohistochemical studies, we have previously shown that GMF is highly expressed in the vicinity of APs and NFTs in AD brains. Glial fibrillary acidic protein (GFAP), reactive astrocytes, ionized calcium binding adaptor molecule-1 (Iba-1) labelled activated microglia and GMF immunoreactive glial cells are increased in the entorhinal cortical layers especially at the sites of APs and Tau containing NFTs indicating a role for GMF. Overexpression of GMF in glial cells leads to neuroinflammation and neurodegeneration. Inhibition of GMF expression reduces neurodegeneration. Therefore, we suggest that GMF is a novel therapeutic target not only for AD but also for various other neurodegenerative diseases.

Co-Expression of Glia Maturation Factor and Apolipoprotein E4 in Alzheimer's Disease Brain.

Apolipoprotein E4 (ApoE4) is a major genetic risk factor for Alzheimer's disease (AD). The E4 allele of ApoE plays a crucial role in the inflammatory and neurodegenerative processes associated with AD. This is evident from the multiple effects of the ApoE isoforms in amyloid-ß (Aß) aggregation. Glia maturation factor (GMF) is a brain-specific neuroinflammatory protein that we have previously demonstrated to be significantly upregulated in various regions of AD brains compared to non-AD control brains and that it induces neurodegeneration. We have previously reported that GMF is predominantly expressed in the reactive astrocytes surrounding amyloid plaques (APs) in AD brain. In the present study, using immunohistochemical and dual immunofluorescence staining, we show the expression and colocalization of GMF and ApoE4 in AD brains. Our results show that ApoE4 is present within the APs of AD brain. Further, we found that GMF and ApoE4 were strongly expressed and co-associated in APs and in the reactive astrocytes surrounding APs in AD. An increased expression of GMF in APs and neurofibrillary tangles in the AD brain, and the co-localization of GMF and ApoE4 in APs suggest that GMF and ApoE4 together should be contributing to the neuropathological changes associated with AD.