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Background: Acute disseminated encephalomyelitis (ADEM) is classically considered as a monophasic immune-mediated demyelinating disorder. A relapse can occur in children but extremely rare in adults. Case-report: A 57-year-old man presented with fulminant ADEM-like episode without proceeding viral illness. Neurological deficits rapidly developed associated with extensive demyelinating brain lesions with vasogenic edema. After the initiation of aggressive immunotherapy, his symptoms resolved, but he relapsed twice during 26-month observation period;one was a mild episode characterized by rapidly evolving MRI lesions without development of symptoms, and the other was a fulminant ADEM-like episode similar to the first one. The second fulminant episode occurred only 2 days after getting a flu shot despite no clinical or radiological relapse when he received COVID-19 vaccinations. The patient's symptoms and extensive brain MRI lesions improved after the initiation of aggressive immunotherapy at the early stage. No autoantibodies against neuronal surface (such as GABA A receptor) or glial surface antigens (aquaporin 4, or myelin oligodendrocyte glycoprotein) were identified in either serum or CSF. Conclusion(s): Extensive white matter lesions can occur without neuronal or glial surface antibodies, recurrent fulminant ADEM-like episode can develop even in an adult patient, and flu shot may provoke fulminant ADEM-like episode.Copyright © 2022
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Case Report: Although the coronavirus disease 2019 (COVID-19) affects the respiratory system, neurological complications in children have been reported. Neurological manifestations in children with acute COVID-19 infection are rare and range from headaches, transverse myelitis, strokes, and encephalitis which presents as a part of Multisystem Inflammatory Syndrome in Children (MIS-C). However, encephalitis presenting post-COVID-19 in the absence of MIS-C in children has not been described. Case presentation: A 9-year-old Hispanic female with no past medical history presented with altered mental status and seizures. Associated symptoms prior to seizures included worsening headaches and vomiting. Initial labs were significant for an elevated erythrocyte sedimentation rate of 32 mm/hr, C-reactive protein of 2 mg/dL, and white blood cell (WBC) count of 28 000 cells/mcl with neutrophilia. Comprehensive metabolic panel was normal. Computed tomography of the head and urine drug screen were normal. Magnetic resonance imaging of the brain demonstrated diffusion restriction in the left frontal lobe as well as mild leptomeningeal enhancement concerning for meningoencephalitis. Lumbar puncture (LP) showed pleocytosis (WBC 169 cells/mcl, 76% neutrophils), elevated glucose 77 mg/dl, normal protein 56 mg/dl, and elevated myelin basic protein indicative of a demyelinating disease. Infectious workup was significant for a positive COVID-19 immunoglobulin (Ig) G (19.66), positive Mycoplasma pneumoniae (M. pneumoniae) IgM (0.87 units/L), with an equivocal IgG (0.11 units/L). Autoimmune workup was negative. She received dexamethasone 0.15 mg/kg/dose for 1 day, followed by methylprednisolone (10 mg/kg/dose) for 3 days and oral prednisone for 5 days resulting in significant improvement. Although CSF cultures returned negative, she received a 7-day course of doxycycline for a possible coexisting M. pneumoniae infection. Repeat LP showed improving pleocytosis, and lymphocytic predominance. Discussion: In this case report, rapid neurological recovery after administration of corticosteroids in the presence of positive COVID-19 IgG and demyelinating disease was suggestive of encephalitis presenting post- COVID-19 infection. Although M. pneumoniae can present with neurological symptoms (e.g., encephalitis), repeat titers at follow-up after recovery did not show the expected 4-fold increase in IgG, making it less likely the cause of this presentation. The proposed pathophysiology of COVID-19-mediated encephalitis includes direct invasion of the nervous system, immune-mediated cytokine response, and molecular mimicry between coronaviruses and neuronal proteins causing demyelination. The mainstay treatment includes immunomodulators such as corticosteroids, Intravenous Immunoglobulin, monoclonal antibodies (eg., rituximab), or plasma exchange. Conclusion: COVID-19 infection should be considered when evaluating a patient with meningoencephalitis or post-infectious encephalitis.
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Case Report: A 4-year-old African American male presented to an outside emergency department (ED) following sudden inability to move left upper extremity. Past medical history was unremarkable and routine vaccinations were up to date. Radiograph of affected extremity ruled out fractures and patient was discharged to follow up with primary care physician. Two days later mother brought him to our ED due to persistent left upper extremity paralysis, poor appetite, and subjective fever. On exam his left arm was warm and tender to dull and sharp touch;he had definite loss of active movement, hypotonia and absence of deep tendon reflexes. The patient had winging of left scapula and could not shrug left shoulder. MRI of cervical and thoracic spine showed enlargement of spinal cord from C2-C6 level with gray matter hyperintensity, slightly asymmetric to the left. Laboratory studies showed leukocytosis (14 000/mcL) and CSF studies showed pleocytosis of 89 WBC/mcL (93.3% mononuclear cells and 6.7% polymorphonuclear cells), 0 RBCs, normal glucose and protein, and a negative CSF meningoencephalitis multiplex PCR panel. Due to high suspicion of demyelinating or autoimmune condition he was treated with high dose steroids and IVIG. Subsequently neuromyelitis optica was ruled out as aquaporin-4 receptor antibodies (AB) and myelin oligodendrocyte glycoprotein AB were normal. CSF myelin basic protein and oligoclonal bands were absent ruling out demyelinating disorders. CSF arboviruses IgM and West Nile IgM were negative. He showed minimal improvement in left upper extremity movement but repeat spinal cord MRI one week later showed improved cord thickness with less hyperintensity. Respiratory multiplex PCR was negative including enteroviruses. Repeat CSF studies after IVIG showed increased IgG index and IgG synthesis suggestive of recent spinal cord infection, consistent with acute flaccid myelitis (AFM). Pre-IVIG blood PCR was invalid for enteroviruses due to PCR inhibitors found in the sample. Blood post-IVIG was negative for mycoplasma IgM, West Nile IgM, and arboviruses IgM. Enterovirus panel titers (post-IVIG) were positive for coxsackie A (1:32), coxsackie B type 4 (1:80) and 5 (1:320), echovirus type 11 (1:160) and 30 (1:80) as well as positive for poliovirus type 1 and 3. These titers could not distinguish acute infection from patient's immunity or false-positives as a result of IVIG. He was discharged with outpatient follow-up visits with neurology, infectious disease, occupational and physical therapy, showing only mild improvement after discharge. Discussion(s):With the anticipated resurgence of AFM after the peak of COVID-19 pandemic, our case illustrates the need to consider this diagnostic possibility in patients with flaccid paralysis. It is important to remember CSF IgG synthesis is not affected by IVIG. In addition when treatment plans include IVIG, appropriate samples should be collected before IVIG to facilitate accurate work-up for infectious diseases. Copyright © 2023 Southern Society for Clinical Investigation.
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CASE: A 44 year old female with history of depression and recent suicide attempt presents with one week of cognitive and functional decline. One month prior to presentation, patient attempted suicide with opioids requiring intubation for respiratory depression and stroke sequelae. She was discharged from this stay after 12 days having returned to mental and functional baseline. Two weeks later, she demonstrated decreased focus and concentration, progressing to decreased mobility and akinesis, eventually presenting to our hospital. Admission metabolic and toxic workup was negative. CT head redemonstrated findings of previously known stroke. MRI demonstrated new increased T2 Flair of the parietal lobes and the cerebral white matter. LP was without evidence of infection or inflammation. Encephalitis panel and autoimmune workup were negative. Neurology consult suggested delayed post-hypoxic leukoencephalopathy as a possible diagnosis, given clinical course of improvement and subsequent decline, along with akinetic mutism and deep cortical white matter flair abnormalities. After failed trial of lorazepam, she was started on amantadine and her cognitive and functional status improved slowly. IMPACT/DISCUSSION: Delayed post-hypoxic leukoencephalopathy (DPHL) is a rare syndrome characterized by biphasic time course with initial recovery and subsequent cognitive and functional decline. DPHL can follow any event of prolonged cerebral hypoxia most frequently CO poisoning. It can occur with more common causes of hypoxia including overdose, cardiac arrest, and seizures;recent case reports have reported DPHL following severe covid infection. The clinical course involves a hypoxic event followed by a return to functional baseline typically lasting 7-21 days, after which progressive physical and mental decline occur. Signs include neuropsychiatric symptoms like amnesia and disorientation, as well as parkinsonism or akinetic mutism (1). The mechanism of DPHL is unclear. One possible mechanisms involves diffuse demyelination. The half life of myelin basic proteins is approximately 20 days, the length of the lucid interval. Hypoxia may abruptly halt the myelination process but symptoms may not emerge until a critical threshold of loss was achieved. Evaluation of DPHL involves considering other causes of encephalopathy, such as infection, substance use, stroke, catatonia, and toxins. In the absence of other causes, diagnosis of DPHL is based on characteristic time course following hypoxic event, symptoms, and MRI findings of diffuse T2 hyperintensity of cerebral white matter are pathognomonic (1). Treatment of DPHL is generally supportive. Limited evidence suggests amantadine may be of benefit. CONCLUSION: Physicians should consider DPHL in patients who have experienced cerebral hypoxia and present with the characteristic time course and imaging findings.
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Many studies conducted after the pandemic period revealed that, while COVID-19 primarily injured the lungs, it also affects other organs in the form of cardiovascular complications, metabolic derangements, renal damage, and so on. Although we know that inflammatory cascades, complement activation, and pro-inflammatory cytokines are all involved in vasculitic processes that cause organ damage, we do not know the exact mechanism of complications such as acute respiratory distress syndrome (ARDS), cardiovascular ischemia, deep vein thrombosis, pulmonary thromboembolism, and brain injuries (embolism) that are frequently observed in COVID 19. The currently available biomarkers do not predict the severity of the aforementioned complications. As a result, more specific biomarkers such as serum calcium binding protein (S100B), glial fibrillary acid protein (GFAP), myelin basic protein (MBP), neuron-specific enolase (NSE), hs-TNI, (highly sensitive cardiac troponin) - HBDH, (Hydroxybutyrate Dehydrogenase), CK-MB (creatine kinase myocardial band), ST2 (suppression of tumorigenicity 2) are in need for early detection & improved clinical outcome.
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Human coronaviruses have been recently implicated in neurological sequelae by insufficiently understood mechanisms. We here identify an amino acid sequence within the HCoV-OC43 p65-like protein homologous to the evolutionarily conserved motif of myelin basic protein (MBP). Because MBP-derived peptide exposure in the sciatic nerve produces pronociceptive activity in female rodents, we examined whether a synthetic peptide derived from the homologous region of HCoV-OC43 (OC43p) acts by molecular mimicry to promote neuropathic pain. OC43p, but not scrambled peptides, induces mechanical hypersensitivity in rats following intrasciatic injections. Transcriptome analyses of the corresponding spinal cords reveal upregulation of genes and signaling pathways with known nociception-, immune-, and cellular energy-related activities. Affinity capture shows the association of OC43p with an Na+ /K+ -transporting ATPase, providing a potential direct target and mechanistic insight into virus-induced effects on energy homeostasis and the sensory neuraxis. We propose that HCoV-OC43 polypeptides released during infection dysregulate normal nervous system functions through molecular mimicry of MBP, leading to mechanical hypersensitivity. Our findings might provide a new paradigm for virus-induced neuropathic pain.
Subject(s)
Coronavirus OC43, Human , Neuralgia , Amino Acid Sequence , Animals , Coronavirus OC43, Human/physiology , Female , Humans , Peptides , Rats , Spinal CordABSTRACT
We investigated the carboxylated conjugated polymer poly 3-(3-carboxypropyl)thiophene-2,5-diyl as a nanosized (200-350 nm) biomolecule receptor layer on the channel of organic electrochemical transistor (OECT) devices. Myelin basic protein, SARS-CoV-2 spike glycoprotein S1, and their antibodies (10 nm size scale) were alternately used in the attached molecule form as receptors and analytes. Sub-ng detection in buffer was observed, and response to S1 was also obtained in clinical serum. Changes in threshold voltage and current output from OECT transfer curves and measurements of open circuit potential between receptor layers and a reference electrode provided complementary responses and insight into the response mechanisms, guiding further development of electrochemical field-effect and voltammetric protein sensors based on polymeric active layers with nanoscale functionality. ©