Progressive encephalomyelitis with rigidity and myoclonus (PERM) associated with anti-glycine receptor antibodies and urothelial carcinoma: a case report.

BACKGROUND: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare neurological condition with paraneoplastic etiology in about 20% of cases, usually presenting before or shortly after the oncological diagnosis is established. PERM associated with anti-glycine receptor antibodies is not previously reported in a patient with bladder cancer. CASE PRESENTATION: A 72-years-old Caucasian male was admitted with acute onset of dysarthria, dysphagia and trismus three years after initial surgical treatment for bladder cancer. The condition was initially diagnosed as tetanus and treated accordingly, but the diagnosis was reconsidered because of progression despite adequate treatment. Diagnostic workup on readmission revealed lung and paraaortal metastases from bladder cancer and anti-glycine receptor (anti-GlyR) antibodies both in the cerebrospinal fluid and in serum, which supplemented with the clinical presentation led to the diagnosis of PERM, presumably related to bladder cancer. The patient showed improvement and stabilization after treatment with intravenous immunoglobulin and chemotherapy against metastatic bladder cancer. CONCLUSION: To the best of our knowledge, this is the first reported case of anti-GlyR antibody positive PERM related to urothelial carcinoma. The symptoms mimicked tetanus, and responded to chemotherapy and immunotherapy.

Evaluation of real-time polymerase chain reaction for the diagnosis of protozoal myeloencephalitis in horses using cerebrospinal fluid.

BACKGROUND: Equine protozoal myeloencephalitis (EPM) caused by Sarcocystis neurona remains an antemortem diagnostic challenge in some horses. Recent work suggested the use of real-time PCR (rtPCR) on cerebrospinal fluid (CSF) as a promising diagnostic tool. OBJECTIVE: To evaluate the sensitivity and specificity of S. neurona rtPCR on CSF for EPM diagnosis using horses with EPM and S. neurona-seropositive horses with other neurologic conditions. ANIMALS: Ninety-nine horses with neurologic disease that underwent complete neurologic examination, CSF collection, and, if euthanized, necropsy including the central nervous system (CNS). METHODS: Retrospective case-control study using banked CSF samples. Samples from horses with neurologic abnormalities and necropsy-confirmed EPM diagnosis, presumptive EPM diagnosis using strict criteria (SnSAG2/4/3 ELISA serum:CSF titer ratios <50) and horses diagnosed with other neurologic diseases were used. RESULTS: Fifty-two horses had EPM; 23 were confirmed on necropsy, and 29 were presumptive clinical diagnoses. The other 47 horses all had necropsy-confirmed diagnoses. Four of the 47 horses had normal neurologic findings on necropsy and the remaining 43 horses had neurologic diseases including equine degenerative myeloencephalopathy (EDM), cervical vertebral stenotic myelopathy, trauma, and other miscellaneous conditions. One CSF sample was weakly positive for S. neurona by rtPCR, this sample was obtained from a horse with confirmed EDM. Samples from the other 98 horses were negative for S. neurona by rtPCR. CONCLUSIONS AND CLINICAL IMPORTANCE: Our study contradicts previous conclusions that S. neurona rtPCR is potentially useful for EPM diagnosis, because our results indicate that the assay has a low sensitivity (0%) for EPM.

Relapsing Encephalomyelitis After COVID-19 Infection and Vaccination: From the National MS Society Case Conference Proceedings.

Prior case studies suggest that severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) and its vaccines may unmask CNS neuroinflammatory conditions. We present a case of relapsing steroid-responsive encephalomyelitis after SARS-CoV-2 infection and subsequent COVID-19 vaccination. We also characterize the frequency of CNS neuroinflammatory events reported in the literature after both SARS-CoV-2 infection and COVID-19 vaccination.

Orofacial Dyskinesia and Intractable Hiccups in a Patient with Varicella-zoster Virus Encephalomyelitis.

A 73-year-old Japanese man with diabetic complications presented with involuntary lip movements and long-lasting hiccups after developing zoster rash. Magnetic resonance imaging revealed lesions involving the medial temporal lobe and C1 level of the spinal cord. Varicella-zoster virus (VZV) encephalomyelitis was diagnosed. We considered attributing the orofacial dyskinesia, a very rare symptom of VZV central nervous system (CNS) complications, to the temporal lobe lesion. Although the culprit lesion for the hiccups was unclear, further examinations may have clarified this issue. As immunocompromised patients with herpes zoster may develop CNS complications with a wide variety of symptoms, special care is needed.

A case of EBV encephalomyelitis with positive anti-GFAP-IgG antibody with recurrent fever and dysuresia as the main symptoms: Case report and retrospective analysis.

RATIONALE: Due to neuronal destruction caused by Epstein-Barr virus (EBV) infection, exposure to neuronal surface antigens may lead to an imbalance in immune tolerance, which in turn triggers an autoimmune response. In addition, due to the involvement of nonspecific B-cell activation or molecular mimicry, EBV and Glial Fibrillary Acidic Protein (GFAP) receptors may have common epitopes. Viral infection triggers activation of B-cell and cross-reaction with viral antibodies, resulting in autoimmune encephalomyelitis. The clinical presentation may be complex or even atypical. A small number of patients may develop autoimmune reactions. PATIENT CONCERNS: Most patients with EBV encephalomyelitis have a good prognosis, with the disease generally having a short course, few complications, and a good prognosis. In most patients, after treatment, their neurological function basically recovers within a few weeks or months. DIAGNOSIS INTERVENTIONS: The patient had fever and headache. His 3 tests for cerebral spinal fluid (CSF) are consistent with the features of viral encephalomyelitis. Pathogenic examination of CSF confirmed EBV, and imaging suggested brain and spinal cord involvement. After antiviral treatment, the patient's symptoms relieved. The diagnosis of EBV encephalomyelitis was considered. However, the patient's temperature continued to increase. He was transferred to a superior hospital and was given GFAP-Ab in CSF, which was strongly positive. The patient was given immunoglobulin and antiviral therapy. This supports the diagnosis of GFAP-IgG antibody positive with EBV encephalomyelitis. OUTCOMES: After treatment with antiviral drugs and immunoglobulins, the patient's symptoms improved and he was able to function. LESSONS: EBV encephalomyelitis is a rare clinical disease. Therefore, more attention should be paid to the early diagnosis and treatment of similar patients to avoid misdiagnosis. CSF tests, genetic tests, and imaging tests can confirm the diagnosis.

Myeloencephalitis as the only presentation of Omicron SARS-CoV-2 infection.

SARS-CoV-2 is now a major global health issue and manifests mainly as a respiratory disorder. Several other complications involving hypercoagulability, cardiovascular system and central nervous system have been described in the literature. Among these atypical presentations, encephalopathy associated with SARS-CoV-2 is a rare entity with heterogenous clinical and radiological findings. The direct presence of SARS-CoV-2 in cerebrospinal fluid (CSF) was rarely found in encephalopathy patients with acute SARS-Cov-2 infection.Here, we report a case of myeloencephalitis with positive real-time PCR for SARS-CoV-2 in CSF in a young woman presenting exclusively with neurological symptoms. Other differential diagnosis were extensively pursued by a comprehensive aetiological workup. To our knowledge, this is the first case report in the Omicron era. In the context of recent global explosion of SARS-Cov-2 infections, clinicians should consider this pathogen among other possible neurotropic agents and be familiar with its radiological and clinical presentations.

Serological biomarkers in autoimmune GFAP astrocytopathy.

Autoimmune glial fibrillary acidic protein astrocytopathy (GFAP-A) is a newly defined meningoencephalomyelitis. The pathogenesis of GFAP-A is not well understood. The present study measured the expression levels of 200 serological cytokines in GFAP-A patients, NMOSD patients and healthy controls (HCs). The correlations between serum cytokine levels and clinical information in GFAP-A patients were analyzed. A total of 147 serological proteins were differentially expressed in GFAP-A patients compared to HCs, and 33 of these proteins were not observed in NMOSD patients. Serum levels of EG-VEGF negatively correlated with GFAP antibody titers, MIP-3 alpha positively correlated with clinical severity in GFAP-A patients, and LIGHT positively correlated with WBC counts and protein levels in the CSF of GFAP-A patients. These results suggest that GFAP and AQP4 astrocytopathy share some common pathology related to TNF signaling. Serum MIP 3 alpha may be a biomarker to assess clinical severity and a potential target for therapy of autoimmune GFAP astrocytopathy.

[GFAp astrocytopathy - a new form of encephalomyelitis]. / GFAP-astrocytopati ­ ovanlig och nyupptäckt form av encefalomyelit.

In recent years several previously unknown autoimmune disorders that affect the central nervous system have been described. Antibodies against glial fibrillary acidic protein (GFAp) were identified in a new form of encephalomyelitis, where the clinical phenotype differs from neuromyelitis optica spectrum disorders. The clinical picture includes headache, encephalopathy, optic neuritis and myelitis. GFAp is a structural component of the cytoskeleton of astrocytes, and an elevated concentration of GFAp in the cerebrospinal fluid, together with antibodies, is a marker of astrocytopathy. The prognosis is good with immunosuppressive treatment.

Acute demyelinating encephalomyelitis and transverse myelitis in a child with COVID-19.

BACKGROUND: Corona virus disease 2019 (COVID-19) includes a wide range of diseases with varying pathophysiology in children and adults. Although the disease mainly affects the respiratory tract, neurological involvement is also reported in the literature. The most common neurological complaints due to COVID-19 are headache, dizziness and anosmia. Acute necrotizing myelitis, acute demyelinating encephalomyelitis (ADEM), acute axonal neuropathy, acute transverse myelitis, and Guillian-Barre syndrome have been reported as neurological dysfunctions associated with COVID-19. CASE: A ten-year-old male patient presented with complaints of fever, headache and generalized muscle pain. The patient developed inability to walk and significant muscle weakness during the disease course, and he was diagnosed with ADEM and transverse myelitis on magnetic resonance imaging (MRI). As the etiological agent, COVID-19 was detected in both the respiratory panel sample and the cerebrospinal fluid (CSF) sample by the polymerase chain reaction (PCR) technique. Pulse steroid, IVIG, and plasmapheresis treatment were administered. He started to stand with support during follow-up. CONCLUSION: We presented a case of COVID-19 related ADEM and transverse myelitis who responded to pulse steroid, IVIG, and plasmapheresis.

Clinical, neuroradiological, diagnostic and prognostic profile of autoimmune glial fibrillary acidic protein astrocytopathy: A pooled analysis of 324 cases from published data and a single-center retrospective study.

Autoimmune glial fibrillary acidic protein (GFAP) astrocytopathy is a recently defined autoimmune meningoencephalomyelitis, associated with GFAP-IgG antibody. A pooled analysis of 324 cases from published literature and a retrospective single-center study were performed, firstly reveals the possibility that patients with myelitic lesions respond better to initial immunotherapy, but are prone to relapse, suggesting a more aggressive and long-term immunosuppressive medication for them. Moreover, our results showed using tacrolimus at maintenance stage exhibited a less tendency to relapse, providing a possibly new choice to future clinical treatments.

Autopsy Case of Meningoencephalomyelitis Associated With Glial Fibrillary Acidic Protein Antibody.

BACKGROUND AND OBJECTIVES: To describe the autopsy findings and neuropathologic evaluation of autoimmune meningoencephalomyelitis associated with glial fibrillary acidic protein (GFAP) antibody. METHODS: We reviewed the clinical course, imaging, laboratory, and autopsy findings of a patient with autoimmune meningoencephalomyelitis associated with GFAP antibody who had a refractory course to multiple immunosuppressive therapies. RESULTS: The patient was a 70-year-old man who was diagnosed as GFAP antibody-associated autoimmune meningoencephalomyelitis. MRI of the head showed linear perivascular enhancement in the midbrain and the basal ganglia. Despite treatment with high-dose corticosteroids, plasma exchange, IV immunoglobulins, and cyclophosphamide, he died with devastating neurologic complications. Autopsy revealed a coexistent neuroendocrine tumor in the small intestine and diffuse inflammation in the brain parenchyma, perivascular spaces, and leptomeninges, with predominant T-cells, macrophages, and activated microglia. B-cells and plasma cells were absent. There was no astrocyte involvement with change in GFAP immunostaining. DISCUSSION: This case illustrates autoimmune meningoencephalomyelitis associated with GFAP antibody in the CSF and coexistent neuroendocrine tumor. The autopsy findings were nonspecific and did not demonstrate astrocyte involvement. Further accumulation of cases is warranted to delineate the utility and pathogenic significance of the GFAP autoantibody.

Progressive encephalomyelitis with rigidity: A Taiwanese case and review of literature.

INTRODUCTION: Progressive encephalomyelitis with rigidity and myoclonus (PERM) is a rare disorder. However, the outcome is still variable with different serological and tumor associations, and the elements to good response with less relapse is yet to be elucidated. METHOD: We present a case and obtain a literature review of patients with PERM and make comparisons based on different serological groups. We also analyze patients with idiopathic PERM that had detailed medical records. RESULTS: 81 patients were collected and analyzed. The largest group were glycine receptor-antibody (GlyR-Ab)-positive (70%), and the seropositive-GlyR-Ab-negative group had better response to immunotherapy. Malignancy can occur up to 2 years from the presentation of PERM. Among the 18 cases with detailed records, the patients who had good outcome initiate immunotherapy within 2 months from presentation. 9 of the 12 patients who experienced no relapse had non-steroid immunotherapy. The maximal interval time of relapse was 24 months. CONCLUSION: We recommend tumor surveillance up to 2 years in patients with PERM and early administration of immunotherapies and maintain with non-steroid immunotherapy with or without oral corticosteroid for a minimum of 2 years to reduce the risk of relapse in GlyR-Ab-positive patients.

[Aquaporin 4 antibody-positive neuromyelitis optica spectrum disorders and myelin oligodendrocyte glycoprotein antibody-associated encephalomyelitis. A brief review]. / Aquaporin-4-Antikörper-positive-Neuromyelitis-optica-Spektrum-Erkrankungen und Myelinoligodendrozytenglykoprotein-Antikörper-assoziierte Enzephalomyelitis. Eine Kurzübersicht.

Aquaporin 4 (AQP4) immunoglobulin (Ig)G-associated neuromyelitis optica spectrum disorders (NMOSD) and myelin oligodendrocyte glycoprotein immunoglobulin (Ig)G-associated encephalomyelitis (MOG-EM, also termed MOG antibody-associated disease, MOGAD) are important autoimmune differential diagnoses of multiple sclerosis (MS), which differ from MS with respect to optimum treatment and prognosis. AQP4 IgG-positive NMOSD take a relapsing course in virtually all cases and MOG-EM in at least 80% of adult cases. Both diseases can quickly lead to permanent disability if left untreated, although MOG-EM is associated with a better overall long-term prognosis. Antibody testing must be carried out by means of so-called cell-based assays. A number of red flags have been defined that must be checked prior to making a diagnosis of NMOSD or MOG-EM. Acute attacks are treated using high-dose glucocorticoids and plasma exchange or immunoadsorption. Rituximab and other immunosuppressants are used off-label for attack prevention. Recently, eculizumab, a C5 complement inhibitor, has been approved in the European Union (EU) for the treatment of patients with AQP4 IgG-positive NMOSD. This article gives a brief overview of the clinical and paraclinical features, pathology, treatment and prognosis of these rare disorders.

Progressive Encephalomyelitis with Rigidity and Myoclonus (PERM)-like Symptoms Associated with Anti-ganglionic Acetylcholine Receptor Antibodies.

This report describes a 59-year-old woman who presented with progressive encephalomyelitis with rigidity and myoclonus (PERM)-like symptoms and severe dysautonomia, including orthostatic hypotension, sinus bradycardia, dysuria, and prolonged constipation. Her neurological symptoms improved after immunotherapy, but the dysautonomia persisted. Anti-ganglionic acetylcholine receptor (gAChR) α3 subunit antibodies, which are frequently identified in patients with autoimmune autonomic ganglionopathy, were detected in the pre-treatment serum. The central distribution of the nicotinic acetylcholine receptors, a target of anti-gAChR antibodies, and immunotherapeutic efficacy observed in this case indicate that anti-gAChR α3 subunit antibodies are associated with the PERM-like features accompanied by autonomic manifestations.

A novel orally infected hamster model for Coxsackievirus A16 hand-foot-and-mouth disease and encephalomyelitis.

Coxsackievirus A16 (CV-A16) is one of the major causes of mild and self-limiting hand-foot-and-mouth disease (HFMD) in young children, which may occasionally leads to serious neurological complications. In this study, we had developed a novel, consistent, orally infected CV-A16 HFMD hamster model with encephalomyelitis. Four groups of 7-day-old hamsters in a kinetic study were orally infected with mouse-adapted CV-A16 strains and sacrificed at 1-4 days post infection (dpi), respectively. Tissues were studied by light microscopy, immunohistochemistry to detect viral antigens, in situ hybridization to detect viral RNA, and by viral titration. In a separate transmission experiment, orally infected index hamsters were housed together with contact hamsters to investigate oral and fecal viral shedding by virus culture and reverse transcription polymerase chain reaction (RT-PCR). At severe infection/death endpoints, index and contact hamster infection were also histopathologically analyzed. In the kinetic study, infected hamsters developed signs of infection at 4 dpi. Viral antigens/RNA were localized to brainstem (medulla/pons; reticular formation and motor trigeminal nucleus) and spinal cord anterior horn neurons, oral squamous epithelia and epidermis from 3 to 4 dpi. Salivary and lacrimal glands, myocardium, brown adipose tissue, intestinal smooth muscle, and skeletal muscle infection was also demonstrated. Viremia at 1 dpi and increasing viral titers in various tissues were observed from 2 dpi. In the transmission study, all contact hamsters developed disease 3-5 days later than index hamsters, but demonstrated similar histopathological findings at endpoint. Viral culture and RT-PCR positive oral washes and feces confirmed viral shedding. Our hamster model, orally infected by the natural route for human infection, confirmed CV-A16 neurotropism and demonstrated squamous epitheliotropism reminiscent of HFMD, attributes not found in other animal models. It should be useful to investigate neuropathogenesis, model person-to-person transmission, and for testing antiviral drugs and vaccines.

Multiple intracranial lesions with lung adenocarcinoma: A rare case of MOG-IgG-associated encephalomyelitis.

BACKGROUND: Myelin oligodendrocyte glycoprotein (MOG) is an important marker on the surface of oligodendrocytes and is associated with many demyelinating diseases. Recently, MOG-IgG-associated encephalomyelitis (MOG-EM) has been proposed as a disease entity with a preliminary diagnosis standard. Some patients with lung cancer have been reported to be seropositive for onconeural antibodies; however, lung cancer cases with MOG-EM have not been previously reported. METHODS: We report the case of a patient with lung adenocarcinoma with multiple intracranial lesions found during molecular targeted therapy. RESULTS: The patient tested positive for MOG antibody in her cerebrospinal fluid, and the therapeutic effect of steroids was excellent. CONCLUSION: This is the first reported case of MOG-EM coincident with lung cancer in a patient with multiple intracranial lesions. When patients present with a history of malignant tumors or suspected paraneoplastic neurological syndrome, clinicians should also be alert to the presence of other autoimmune antibodies such as MOG-IgG to avoid treatment delay.