Recurrent Anti-AMPA Receptor Limbic Encephalitis: A Case Report and Literature Review.
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SUBMITTER: Fang Y
PROVIDER: S-EPMC8690251 | biostudies-literature |
REPOSITORIES: biostudies-literature
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Project description:AimsAMPA receptor (AMPAR) and CRMP5 antibodies are relatively uncommon in limbic encephalitis, and patients with both antibodies are rare. We recently treated such a patient, but the patient died after active treatment. To further understand this disease, we conducted a case report and literature review.DiscussionsTo date, five encephalitis patients, including our patient, have been found to be positive for AMPAR and CRMP5 antibodies. The male-to-female ratio of the reported cases is 4:1, and the age range is 26 and 62 years old. All five patients presented with various neuropsychiatric symptoms, including insomnia, abnormal behavior, seizures, extrapyramidal symptoms, and autonomic dysfunction. Four patients had tumors (three invasive thymomas and one suspected lymphoma), and three cases died within a short period of time. No tumor was detected in one of the patients during the follow-up period; however, after active treatment, the outcome was poor, and the patient developed cachexia. One patient had good response to immunotherapy and tumor therapy and successfully returned to work.ConclusionsThe prognosis of encephalitis associated with AMPAR and CRMP5 antibodies is worse than that of the encephalitis associated with AMPAR antibodies alone. The most likely cause is that this encephalitis is more likely to be accompanied by malignant tumors, leading to a poor prognosis. In addition, it may also be due to some synergistic mechanisms between the two antibodies. Further studies aimed at the prognosis of this type of encephalitis are warranted.
| S-EPMC7066334 | biostudies-literature
Project description:Introduction:Paraneoplastic limbic encephalitis (PLE) is a rare disease that presents as rapid onset dementia characterized by short-term memory loss (STM), anxiety, and behavioral changes. Anti-NMDAR antibodies are unfrequently reported in PLE associated with small-cell lung cancer (SCLC). Given that PLE can precede the diagnosis of cancer, it is very important that once infectious, metabolic, nutritional, or structural disorders associated with short-term memory loss are ruled out that vigorous effort must be made to rule out underlying malignancy. Case:We report a rare case of PLE as the presenting symptom of SCLC. A 72-year-old male with history of COPD was brought to the ED by his wife after he was found to have short-term memory loss, including forgetfulness of his wedding anniversary the day before, and anxiety. Neurological exam showed impaired short-term recall on MOCA. CT head showed no evidence of infarct. Lumbar puncture was performed which showed lymphocytic pleocytosis, a nonspecific inflammatory change. CSF panel was negative for HSV, Neisseria, Hemophilus, E. coli, and HIV. Initial EEG was unremarkable, though a repeat EEG showed mild slowing of the posterior dominant rhythm consistent with mild encephalopathy. MRI showed equivocal increased FLAIR on T2-weighted images in the bilateral temporal lobes, left greater than right. CTA thorax showed bulky mediastinal and right hilar LAD. FNA of the R4 lymph node revealed SCLC. The NM bone scan showed no osteoblastic lesions. While the serum autoantibody panel was positive for anti-NMDAR, the CSF autoantibody panel returned entirely negative. Chemotherapy with etoposide and cisplatin was started on Day 4 of admission. The patient's neurological symptoms showed improvement following chemotherapy. Conclusion:This case highlights the importance of recognizing short-term memory loss as a feature of PLE.
| S-EPMC7288224 | biostudies-literature
Project description:RationaleNeurosyphilis presenting as limbic encephalitis (LE) is an important differential diagnosis of autoimmune LE (ALE) defined by Graus in 2016. However, data on the clinical differences and similarities between neurosyphilis presenting as LE and ALE are limited. Herein, we report neurosyphilis presenting as ALE that fulfilled the main items of the Graus ALE criteria. Moreover, a literature review of neurosyphilis presenting as LE was performed.Patient concernsA 66-year-old Japanese man developed nonconvulsive status epilepticus. He presented with progressive personality change and working memory deficits within 3 months prior to admission. A hyperintense lesion localized in the bilateral medial temporal area was observed on T2-weighted fluid-attenuated inversion recovery brain magnetic resonance imaging. Cerebrospinal fluid analysis showed mild pleocytosis and the presence of oligoclonal band. However, in-house assays did not detect antineuronal antibodies. Electroencephalogram showed lateralized rhythmic delta activity in the right temporal area. The serum and cerebrospinal fluid serological and antigen tests for syphilis had positive results.DiagnosisALE was initially suspected based on the patient's symptoms and ancillary test findings that fulfilled the Graus ALE criteria. However, based on the positive confirmatory test results for syphilis, a diagnosis of neurosyphilis was eventually made.InterventionThe patient received intravenous midazolam, oral levetiracetam, and lacosamide to control nonconvulsive status epilepticus. In addition, he was treated with intravenous benzylpenicillin at a dose of 24 million units/day for 14 days.OutcomesThe patient's cognitive function relatively improved after antibiotic treatment. However, he presented with persistent mild working memory deficit, which was evaluated with the Wechsler Adult Intelligence Scale, 3rd edition. Therefore, on day 103 of hospitalization, he was transferred to another hospital for rehabilitation and long-term care due to limitations in performing activities of daily living.LessonsThe present case was diagnosed with neurosyphilis presenting as ALE, but meanwhile, in most case, neurosyphilis presenting as LE developed at a slower progressive rate, and it had a broader or restricted involvement on brain MRI than ALE based on the literature review. Therefore, an appropriate differential diagnosis of LE can be obtained by identifying clinical differences between the 2 conditions.
| S-EPMC9388039 | biostudies-literature
Project description:Anti-α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid (AMPA) receptor encephalitis is a rare autoimmune disease that is characterized by acute cognitive impairment, mental symptoms, and seizures. The high comorbidity rate between anti-AMPA receptor (AMPAR) encephalitis and other somatic diseases, such as malignancy, has revealed the possibility of potential copathogenesis. However, there have not yet been reports about anti-AMPAR encephalitis with concomitant cerebrospinal fluid (CSF) biomarkers consistent with Alzheimer disease (AD). Herein, we present the case of an elderly male patient with autoimmune encephalitis (AE) presenting with anti-AMPA1-R and anti-AMPA2-R antibodies, as well as CSF biomarkers of AD. The patient was hospitalized with acute memory decline for 1 week. Anti-AMPA1-R and anti-AMPA2-R antibodies were positively detected in CSF, and the anti-AMPA2-R antibody was also present in the serum. Additionally, the biomarkers of AD were concurrently present in CSF (Aβ1-42 = 245.70 pg/mL, t-Tau = 894.48 pg/mL, p-Tau = 78.66 pg/mL). After administering a combined treatment of intravenous immunoglobulin and glucocorticoids, the patient recovered significantly, and his cognitive function achieved a sustained remission during 2 months' follow-up. This case raises the awareness of a possible interaction between AE and changes of CSF biomarkers. We speculated that the existence of AMPAR antibodies can induce changes of CSF, and other pathological alterations. This present report highlights that a potential relationship exists among AE and provides a warning when making the diagnosis of AD.
| S-EPMC8283122 | biostudies-literature
Project description:To report the clinical and immunological features of a novel autoantigen related to limbic encephalitis (LE) and the effect of patients' antibodies on neuronal cultures.We conducted clinical analyses of 10 patients with LE. Immunoprecipitation and mass spectrometry were used to identify the antigens. Human embryonic kidney 293 cells expressing the antigens were used in immunocytochemistry and enzyme-linked immunoabsorption assay. The effect of patients' antibodies on cultures of live rat hippocampal neurons was determined with confocal microscopy.Median age was 60 (38-87) years; 9 were women. Seven had tumors of the lung, breast, or thymus. Nine patients responded to immunotherapy or oncological therapy, but neurological relapses, without tumor recurrence, were frequent and influenced the long-term outcome. One untreated patient died of LE. All patients had antibodies against neuronal cell surface antigens that by immunoprecipitation were found to be the glutamate receptor 1 (GluR1) and GluR2 subunits of the alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor (AMPAR). Human embryonic kidney 293 cells expressing GluR1/2 reacted with all patients' sera or cerebrospinal fluid, providing a diagnostic test for the disorder. Application of antibodies to cultures of neurons significantly decreased the number of GluR2-containing AMPAR clusters at synapses with a smaller decrease in overall AMPAR cluster density; these effects were reversed after antibody removal.Antibodies to GluR1/2 associate with LE that is often paraneoplastic, treatment responsive, and has a tendency to relapse. Our findings support an antibody-mediated pathogenesis in which patients' antibodies alter the synaptic localization and number of AMPARs.
| S-EPMC2677127 | biostudies-literature
Project description:Bullous pemphigoid (BP) is a rare, life-threatening autoimmune blistering disease with pruritus and tension blisters/bullous as the main clinical manifestations. Glucocorticosteroids are the main therapeutic agents for it, but their efficacy is poor in some patients. Tofacitinib, a small molecule agent that inhibits JAK1/3, has shown incredible efficacy in a wide range of autoimmune diseases and maybe a new valuable treatment option for refractory BP. To report a case of refractory BP successfully treated with tofacitinib, then explore the underlying mechanism behind the treatment, and finally review similarities to other cases reported in the literature. Case report and literature review of published cases of successful BP treatment with JAK inhibitors. The case report describes a 73-year-old male with refractory BP that was successfully managed with the combination therapy of tofacitinib and low-dose glucocorticoids for 28 weeks. Immunohistochemistry and RNA sequencing were performed to analyze the underlying mechanism of tofacitinib therapy. A systematic literature search was conducted to identify other cases of treatment with JAK inhibitors. Throughout the 28-week treatment period, the patient experienced clinical, autoantibody and histologic resolution. Immunohistochemical analysis showed tofacitinib significantly decreased the pSTAT3 and pSTAT6 levels in the skin lesions of this patient. RNA sequencing and immunohistochemical testing of lesion samples from other BP patients identified activation of the JAK-STAT signaling pathway. Literature review revealed 17 previously reported cases of BP treated with four kinds of JAK inhibitors successfully, including tofacitinib (10), baricitinib (1), upadacitinib (3) and abrocitinib (3). Our findings support the potential of tofacitinib as a safe and effective treatment option for BP. Larger studies are underway to better understand this efficacy and safety.
2024-11-13 | GSE278926 | GEO
Project description:Introduction18 F-fluorodeoxyglucose (FDG)-PET metabolic patterns of brain differ among autoimmune encephalitis with different neuronal surface antigens. In this case report, we compared the topographical relationship of cerebral glucose metabolism and antigen distribution in the patients with anti-NMDAR and anti-AMPAR encephalitis. Literature review summarized the common features of brain metabolism of autoimmune encephalitis.MethodsThe cerebral glucose metabolism was evaluated by FDG-PET/CT during acute-to-subacute stage of autoimmune encephalitis and after treatment. The stereo and quantitative analysis of cerebral metabolism used standardized z-score and visualized on three-dimensional stereotactic surface projection. To map NMDAR and AMPAR in human brain, we adopted genetic atlases from the Allen Institute and protein atlases from Zilles's receptor densities.ResultsThe three-dimensional stereotactic surface projection displayed frontal-dominant hypometabolism in a 66-year-old female patient with anti-AMPAR encephalitis and occipital-dominant hypometabolism in a 29-year-old female patient with anti-NMDAR encephalitis. Receptor density maps revealed opposite frontal-occipital gradients of AMPAR and NMDAR, which reflect reduced metabolism in the correspondent encephalitis. FDG-PET hypometabolic areas possibly represent receptor hypofunction with spatial correspondence to receptor distributions of the autoimmune encephalitis. The reversibility of hypometabolism was in line with patients' cognitive improvement. The literature review summarized six features of metabolic anomalies of autoimmune encephalitis: (a) temporal hypermetabolism, (b) frontal hypermetabolism and (c) occipital hypometabolism in anti-NMDAR encephalitis, (d) hypometabolism in association cortices, (e) sparing of unimodal primary motor cortex, and (e) reversibility in recovery.ConclusionsThe distinct cerebral hypometabolic patterns of autoimmune encephalitis were representative for receptor hypofunction and topographical distribution of antigenic receptors. The reversibility of hypometabolism marked the clinical recovery of autoimmune encephalitis and made FDG-PET of brain a valuable diagnostic tool.
| S-EPMC7066351 | biostudies-literature
Project description:Anti-Ma2 encephalitis is a rare neurological disorder with a predominant involvement of brainstem, limbic and diencephalic structures. Although an unspecific encephalopathy is the usual form of presentation, acute-onset neurologic symptoms and other atypical manifestations have been described and account for the challenging diagnosis of this entity. Despite being usually detected as a paraneoplastic syndrome in patients with early-stage tumors or without a previous history of malignancy, a growing concern has arisen from several cases reported in metastatic patients under treatment with immune checkpoint inhibitors. We report what to our knowledge is the first known case of anti-Ma2 encephalitis associated to pembrolizumab and presenting as an acute-onset focal neurological syndrome, consisting on acute global aphasia, right upper limb paresia, hypoacusia, sleep disorder, decreased conscious level and a motor focal status that was refractory to anticonvulsant therapy. A brain MRI scan showed a focal alteration of the cortical-subcortical signal on the left parietal lobe. CSF study found a significant hyperproteinorrhachia and electroencephalography showed lateralized periodic discharges (LPDs), suggestive of a diffuse encephalopathy. A positive result for anti-Ma2 antibodies was obtained both in blood and CSF samples through indirect immune-fluorescence (IFI) and later confirmed by western-blot technique. Our patient obtained a mild response to steroid therapy and a significant improvement after the administration of intravenous immunoglobulins. The hypothesis that checkpoint inhibitors may trigger the expression of previously subclinical paraneoplastic events, through the strengthening of cytotoxic T cells-mediated immune response, is supported by our finding of preexisting anti-Ma2 antibodies in preserved blood samples obtained before the initiation of pembrolizumab in our patient. Further research is needed to reveal if the detection of onconeural antibodies prior to a treatment with checkpoint inhibitors may be used as a predictive biomarker of neurologic immune-related high-grade toxicity.
| S-EPMC8350103 | biostudies-literature
Project description:Hemoptysis caused by Parvimonas micra: case report and literature review
| PRJEB72347 | ENA
Project description:Anti-leucine-rich glioma-inactivated1 (Anti-LGI1) autoimmune encephalitis is a rare autoimmune disease discovered in recent years. It is generally not defined as an inherited disease, though its etiology is still unclear. Herein, we report the first case of adult patients with familial anti-LGI1 encephalitis. Two biological siblings who worked in different regions were successively diagnosed with anti-LGI1 encephalitis in their middle age. The two patients had similar clinical manifestations including imaging results. Their clinical symptoms improved after immunotherapy and antiepileptic therapy. Given that some unique human leukocyte antigen (HLA) subtypes appear at a high frequency, multiple recent studies have revealed that anti-LGI1 encephalitis is associated with genetic susceptibility. One of the patients underwent HLA genotyping and whole-exome sequencing (WES), revealing the same HLA typing as in previous studies and two rare HLA variants. Therefore, further studies involving larger samples and more populations should be conducted to explore the possibility of other influencing factors such as environmental impacts.
| S-EPMC9047818 | biostudies-literature