A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review.
Ontology highlight
ABSTRACT:
SUBMITTER: Sapana T
PROVIDER: S-EPMC10703372 | biostudies-literature | 2023
REPOSITORIES: biostudies-literature
Publications
A case report of anti-GAD65 antibody-positive autoimmune encephalitis in children associated with autoimmune polyendocrine syndrome type-II and literature review.
Sapana Tamang T Li Wei W Tian Fengyan F Yan Wenhao W Dou Binghua B Hua Shuang S Zhuo Zhihong Z
Frontiers in immunology 20231122
<h4>Background</h4>Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA), the major inhibitory neurotransmitter in the central nervous system. Antibodies against glutamic acid decarboxylase (GAD) are associated with various neurologic conditions described in patients, including stiff person syndrome, cerebellar ataxia, refractory epilepsy, and limbic and extra limbic encephalitis. While there are few case reports and research on anti-GA ...[more]
Similar Datasets
Project description:Human papillomavirus (HPV) infection is a sexually transmitted disease that may lead to cervical cancer. HPV vaccines have been implemented widely to prevent this. While generally few complications of vaccination are reported, there have been occasional reports of adverse reactions post-vaccination. The safety profile of the HPV vaccine is reassuring. However, since its introduction, several serious post-vaccination central nervous system complications have been reported; however, causality has not been established. Herein, we describe a 39-year-old woman who developed seizures and experienced a rapid decline in memory shortly after her first dose of the HPV vaccine. Cranial magnetic resonance imaging and cerebrospinal fluid analysis were performed, and the patient was diagnosed with anti-glutamic acid decarboxylase 65 (anti-GAD65) antibody-associated autoimmune encephalitis. She responded well to high-dose glucocorticoids. Four-month follow-up revealed full recovery and absence of recurrence. Since the HPV vaccine is administered worldwide, this case should raise clinicians' awareness regarding the possible CNS complications related to vaccinations, such as anti-GAD65 antibody-associated AE.
| S-EPMC9579373 | biostudies-literature
Project description:Autoimmune polyendocrine syndromes (APS) is a rare group of disorders caused by impaired function of multiple endocrine glands due to disruption of immune tolerance. Of which, type 2 (APS-2) is the most common. Glutamic acid decarboxylase (GAD) is the rate-limiting enzyme for the synthesis of gamma-aminobutyric acid (GABA). Anti-GAD antibodies are associated with various neurological disorders, including stiff person syndrome (SPS). SPS is characterized by axial muscle stiffness, rigidity, and intermittent painful muscle spasms, with a prevalence of one to two in a million, making it an extremely rare neurological disorder. The comorbidity of APS-2 with SPS is even rarer. Most practicing neurologists encounter only one or two cases of APS-2 combined with anti-GAD65 antibody-associated SPS in their careers, resulting in underdiagnosis and undertreatment, leading to severe disability and suffering. This case report describes a young male who initially exhibited hair loss, vitiligo, and previously unreported eosinophilia. Before his diagnosis, he was admitted multiple times, with symptoms improving following the addition of intravenous immunoglobulin (IVIG) therapy to a poor treatment regimen. This paper aims to increase physicians' awareness of this condition, enhancing the likelihood of early diagnosis and treatment.
| S-EPMC11746041 | biostudies-literature
Project description:BACKGROUND:Autoimmune polyendocrine syndrome type II (APS-2) is a rare constellation of autoimmune hypoadrenalism, thyroid dysfunction and/or type 1 diabetes (T1DM), usually occurring in the 3rd or 4th decades and associated with a human leukocyte antigen (HLA) DR3 or DR4 serotype. We detail the first report of an elderly woman developing the full triad of APS-2 shortly after commencing anti-programmed cell death protein 1 (anti-PD1) immune checkpoint inhibition for unresectable melanoma and review the literature for similar presentations secondary to anti-PD1 axis therapy. CASE:A 78-year-old female with advanced unresectable BRAF wild-type melanoma was treated with pembrolizumab (2 mg/kg 3-weekly). Three weeks following the first dose she developed fulminant autoimmune diabetes, with an initially low C-peptide denoting rapid destruction of ß-islet cells. Following stabilisation of her diabetes, two further doses of pembrolizumab was administered. She then represented with symptomatic hypoadrenalism and hypothyroidism, consistent with APS-2. Her HLA class II genotype was HLA-DRB1*04.16 (DR4 serotype), a recognised association with this syndrome. Her melanoma responded rapidly to anti-PD1 therapy, and a complete response (CR) was attained after four doses of pembrolizumab. Treatment was discontinued and her CR is ongoing. CONCLUSION:This is the first report of the full triad of APS-2 developing in a genetically susceptible individual at the age of 78 after treatment with an anti-PD1 agent. Although scarcely reported, a literature review of similar reports seems to indicate a predilection for this syndrome in patients with HLA-DR4 serotypes. HLA Class II typing is not routinely recommended, but may provide useful predictive information for patients at risk of poly-endocrinopathy even in patients without a relevant personal or family history. Additional studies are required to determine if such testing would be useful and/or cost effective.
| S-EPMC6729071 | biostudies-literature
Project description:Anti-contactin-associated protein-like 2 (CASPR2) antibody-associated autoimmune encephalitis is commonly characterized by limbic encephalitis with clinical symptoms of mental and behavior disorders, cognitive impairment, deterioration of memory, and epilepsy. The classical lesions reported are located at the medial temporal lobe or hippocampus, whereas prominent brainstem lesions have not been addressed to date. Herein, we reported two patients mimicking progressive brainstem infarction with severe neurological manifestations. On brain magnetic resonance imaging (MRI), prominent brainstem lesions were noted, although multifocal lesions were also shown in the juxtacortical and subcortical white matters, basal ganglia, hippocampus, and cerebellar hemisphere. Unexpectedly and interestingly, both cases had detectable CASPR2 antibodies in sera, and an exclusive IgG1 subclass was documented in the further analysis. They were treated effectively with aggressive immunosuppressive therapies including corticosteroids, intravenous immunoglobulin G, and rituximab, with the first case achieving a rapid remission and the other undergoing a slow but gradual improvement. To the best of our knowledge, this is the first report on prominent brainstem involvement with definite MRI lesions in anti-CASPR2 antibody-associated autoimmune encephalitis, which helps to expand the clinical spectrum of this rare autoimmune disease and update the lesion patterns in the CNS.
| S-EPMC8631873 | biostudies-literature
Project description:The enzyme glutamate decarboxylase (GAD) produces the neurotransmitter GABA, using pyridoxal-5'-phosphate (PLP). GAD exists as two isoforms, GAD65 and GAD67. Only GAD65 acts as a major autoantigen, frequently implicated in type 1 diabetes and other autoimmune diseases. Here we characterize the structure and dynamics of GAD65 and its interaction with the autoimmune polyendocrine syndrome type 2-associated autoantibody b96.11. Using hydrogen-deuterium exchange mass spectrometry (HDX), X-ray crystallography, cryo-electron microscopy, and computational approaches, we examine the conformational dynamics of apo- and holoGAD65 and the GAD65-autoantibody complex. HDX reveals local dynamics accompanying autoinactivation, with the catalytic loop promoting collective motions at the CTD-PLP domain interface. In the GAD65-b96.11 complex, heavy chain CDRs dominate the interaction, with a long CDRH3 bridging the GAD65 dimer via electrostatic interactions with the 260PEVKEK265motif. This bridging links structural elements controlling GAD65's conformational flexibility to its autoantigenicity. Thus, intrinsic dynamics, rather than sequence differences within epitopes, appear to be responsible for the contrasting autoantigenicities of GAD65 and GAD67. Our findings elucidate the structural and dynamic factors that govern the varying autoantibody reactivities of GAD65 and GAD67, offering a revised rationale for the autoimmune response to GAD65.
| S-EPMC11889217 | biostudies-literature
Project description: Not available
| S-EPMC11240285 | 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: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
Project description:BackgroundTakotsubo cardiomyopathy (TCM) is a rare disease entity characterized by acute, non-ischemic, reversible myocardial dysfunction that mimics acute myocardial infarction. Activation and excessive outflow of sympathetic nervous system are believed to be central to the figure in the disease pathogenesis. Adrenocortical hormones potentiate the systemic actions of sympathetic nervous system and accordingly are essential for regulation of myocardial function. We present an unusual case of a middle-aged woman with primary adrenal insufficiency who presented paradoxically with TCM.Case presentationA 50-year-old woman with past history of hypothyroidism presented to emergency department with history of acute chest pain and syncope. There was no significant drug history or history of an emotional or physical stimulus prior to admission. Prominent pigmentation over the tongue and skin creases of hands were noted. On presentation, she was in shock and had ventricular tachycardia which required electrical cardioversion. The subsequent electrocardiogram demonstrated diffuse T-wave inversions with prolonged QTC. There was apical hypokinesia on echocardiogram, and cardiac biomarkers were elevated. There was persistent inotropic requirement. She had marked postural symptoms, and a postural blood pressure drop of 50 mm Hg was present. Initial laboratory parameters were significant for hyperkalemia (7.8 mEq/L) and hyponatremia (128 mEq/L). These findings prompted evaluation for adrenal insufficiency which was confirmed with appropriate tests. Autoimmune polyendocrine syndrome II was thus diagnosed based on the above findings. Coronary angiography revealed normal coronaries. The diagnoses of TCM was established in accordance with the International Takotsubo Diagnostic Criteria. She was started on stress dose steroid replacement therapy and improved dramatically. At one month of follow-up, the patient is asymptomatic, and there was normalization of her left ventricular function.ConclusionsIntricate relationship and interplay exist between the steroid hormones and catecholamines in the pathogenesis of TCM. Steroid hormones not only potentiate the actions of catecholamines, but they also regulate and channelize catecholaminergic actions preventing their deleterious effects on the cardiac tissue. Hence, both steroid deficiency and exogenous steroid replacement may precipitate TCM. Evidence from more such cases and larger perspective studies in future will further improve our understanding of this complex disease process and its myriad associations.
| S-EPMC9748007 | 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