Aug 2026· Frontiers in Veterinary Science· Vol 13· 0 citations· 26 references
Medicine
TL;DR
The first detection of mGluR1 antibodies in a cat with neurological disease is described and a potential association between mGluR1 autoimmunity and epileptic seizures and episodic behavioral abnormalities in a cat is suggested.
Abstract
Autoimmune encephalitis associated with neuronal autoantibodies is increasingly recognized in veterinary medicine. In cats, previously reported antibodies have primarily targeted components of the voltage-gated potassium channel complex, such as leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2). Anti-metabotropic glutamate receptor 1 (mGluR1) antibodies are well described in human medicine but have not previously been reported in cats. A 5.5-month-old female domestic shorthair cat was presented for recurrent epileptic seizures and episodic behavioral abnormalities, including pica. Neurological examination revealed mild pelvic limb ataxia. Based on the history of epileptic seizures and behavioral abnormalities, the neuroanatomical localization was consistent with the forebrain. Magnetic Resonance Imaging (MRI) of the brain and cerebrospinal fluid (CSF) analysis were unremarkable. Infectious disease testing from CSF, including polymerase chain reaction (PCR) assays for Feline Coronavirus, Toxoplasma gondii, Feline Herpesvirus, and Rustrela virus, was negative. Neural antibody testing using tissue-based and cell-based assays identified an elevated serum mGluR1 antibody titer (1:80; reference <1:20), whereas cerebrospinal fluid and tissue-based assays were negative. Testing for other neuronal autoantibodies, including LGI1 and CASPR2, was negative. Following optimization of antiseizure therapy, the cat showed clinical improvement, accompanied by a decrease in the serum mGluR1 antibody titer. This report describes the first detection of mGluR1 antibodies in a cat with neurological disease and suggests a potential association between mGluR1 autoimmunity and epileptic seizures and episodic behavioral abnormalities in a cat.
Anti–metabotropic glutamate receptor 1 (mGluR1) encephalitis is a rare form of autoimmune encephalitis that typically presents with cerebellar dysfunction. Predominant brainstem involvement has seldom been reported. We report an 87-year-old man who presented with a subacute onset of fever, dysarthria, limb weakness, and altered mental status. Comprehensive diagnostic evaluation revealed anti-mGluR1 antibodies in both serum and cerebrospinal fluid using a cell-based assay, while cerebrospinal fluid next-generation sequencing (NGS) was negative for infectious pathogens. Brain MRI demonstrated extensive T2-weighted and fluid-attenuated inversion recovery (T2/FLAIR) hyperintensity involving the midbrain, pons, and medulla, without diffusion restriction. These findings support the possibility that anti-mGluR1 encephalitis may, in rare instances, present with predominant brainstem involvement. Testing for anti-mGluR1 antibodies may be considered in patients with otherwise unexplained subacute inflammatory brainstem syndromes.
Abstract Autoimmune epilepsy, once regarded as a rare and poorly understood subset of seizure disorders, has now emerged as a clinically significant and potentially reversible cause of epilepsy. Advances in neuroimmunology have substantially broadened the spectrum of neural autoantibodies implicated in epileptogenesis—particularly those directed against neuronal cell surface and synaptic proteins, such as the N-methyl-D-aspartate receptor (NMDAR), leucine-rich glioma-inactivated protein 1 (LGI1), contactin-associated protein-like 2 (CASPR2), and glutamic acid decarboxylase 65 (GAD65). Distinct autoantibody profiles are now recognized to correlate with characteristic clinical syndromes, facilitating earlier and more targeted diagnosis. For instance, faciobrachial dystonic seizures are highly suggestive of LGI1 antibody-mediated encephalitis, while neuropsychiatric manifestations and movement disorders are typical of NMDAR antibody encephalitis, and chronic temporal lobe epilepsy frequently accompanies GAD65 autoimmunity. Early identification of these immune-mediated forms is critical, as antibody-mediated epilepsies involving cell surface antigens often respond favorably to immunotherapy, leading to substantial recovery. In contrast, epilepsies associated with intracellular antigen targets or cytotoxic T-cell–driven mechanisms, such as Rasmussen encephalitis, typically show poor therapeutic response due to irreversible neuronal injury. Some autoimmune encephalitides also occur as paraneoplastic syndromes, underscoring the importance of comprehensive oncological evaluation in affected patients. Moreover, immune dysregulation has been implicated in catastrophic epileptic conditions such as new-onset refractory status epilepticus and febrile infection-related epilepsy syndrome, further broadening the clinical spectrum of autoimmune-mediated seizures. Although seizures may arise from diverse etiologies, immune mechanisms have gained increasing recognition as an important and potentially modifiable contributor to epileptogenesis. This recognition has been formally endorsed by the International League Against Epilepsy, which classifies autoimmune epilepsy as a distinct diagnostic entity. Nevertheless, true autoimmune epilepsy, in which seizure susceptibility persists after resolution of encephalitic activity, remains relatively uncommon. In most cases, seizures associated with autoimmune encephalitis are acute and reversible with timely immunotherapy. Thus, precise terminology—differentiating acute symptomatic seizures from chronic autoimmune-associated epilepsy—is essential for appropriate management, prognostication, and research standardization.
Monika Singla, Abhishek Dixit, M. Mehndiratta· International Journal of Epi...· 0 citations
Background Paraneoplastic autoimmune encephalitis (PAE) is most commonly associated with small cell lung cancer (SCLC). Anti–γ-aminobutyric acid B receptor (GABABR) antibodies underlie a treatable limbic syndrome, whereas anti–SRY-box transcription factor 1 (SOX1) antibodies serve as high-specificity onconeural biomarkers of SCLC-driven autoimmunity. The sequential emergence of these two antibodies during the longitudinal course of a single patient has rarely been documented. Case presentation A 75-year-old man presented with episodic impaired consciousness, behavioural disturbance and rapid cognitive decline. Brain MRI showed bilateral hippocampal signal abnormalities. A cell-based assay (CBA) detected anti-GABABR antibodies at high titre in serum (1:3200) and cerebrospinal fluid (CSF; 1:1000), while a tissue-based assay (TBA) on rat brain confirmed a neuronal cell-surface staining pattern; the full paraneoplastic panel, including anti-SOX1, was negative, and initial tumour screening was unrevealing. A diagnosis of anti-GABABR encephalitis (initially regarded as non-paraneoplastic) was made and the patient improved with intravenous immunoglobulin (IVIG), high-dose corticosteroids and maintenance mycophenolate mofetil. During a refractory second relapse 5 months later, repeat CBA showed rising anti-GABABR titres (serum 1:10,000; CSF 1:1000) and newly positive anti-SOX1 antibodies (serum 1:100; CSF 1:1); a previously occult right superior mediastinal mass radiologically compatible with SCLC was identified on repeat chest CT. The diagnosis was revised to anti-GABABR/anti-SOX1 dual-antibody PAE (probable PNS by 2021 PNS-Care criteria). The family declined biopsy, PET/CT and antitumour therapy because of advanced age and frailty; repeated IVIG with continued immunosuppression achieved partial clinical stabilisation with persistent cognitive impairment. Conclusion Apparently isolated anti-GABABR encephalitis can evolve into dual anti-GABABR/anti-SOX1 paraneoplastic disease, with the second antibody heralding an occult SCLC. Repeating both CBA-based and intracellular antibody panels at every clinical relapse, together with repeat thoracic imaging, is essential to avoid missing an evolving paraneoplastic aetiology.
Feng Liu, Ye-Han Jiang, Yu-fang Hu et al.· Frontiers in Cellular Neuros...· 0 citations
Background N-methyl-d-aspartate (NMDA) autoantibody encephalitis is a rare autoimmune condition affecting approximately 1.5 per million people per year [1]. It predominantly occurs in young women and is often associated with tumors, particularly teratomas [3]. The diagnosis is aided by testing cerebrospinal fluid (CSF) or serum for NMDA receptor antibodies along with careful evaluation of symptoms. Misdiagnosis is common, as its symptoms can mimic other more prevalent conditions, such as upper respiratory illnesses or psychiatric disorders like acute psychosis or schizophrenia. Case report We present the case of a 34-year-old man who was initially incarcerated and subsequently developed decreased communication and mild agitation over several days, leading to his transfer to a psychiatric institute with a presumed diagnosis of schizophrenia. As his encephalopathy worsened over weeks, he exhibited catatonic symptoms and was referred to our facility for further evaluation after an unrevealing workup, including an initial lumbar puncture. Upon re-evaluation, a lumbar puncture was repeated with an autoimmune panel, returning positive for anti-NMDA antibodies, confirming the diagnosis. The patient was initially treated with steroids and plasma exchange, resulting in minimal improvement. He later received intravenous immunoglobulin (IVIG) and concomitant rituximab, leading to some functional improvement to a non-verbal but alert state. Conclusion This case highlights the importance of considering rare autoimmune encephalitis' in patients presenting with worsening encephalopathy in the setting of a new psychiatric diagnosis, despite its rare nature.
Unknown authors· Journal of Community Hospita...· 0 citations
Although significant progress has been made in identifying antigen targets in autoimmune encephalitis (AIE), in a substantial proportion of patients with presumed AIE no known autoantibodies can be detected. Herein, we describe a novel autoantibody reactivity, directed against copine-5 (CPNE5), in patients with AIE and melanoma. Patients were identified through routine clinical testing for anti-neural autoantibodies by indirect immunofluorescence on neuronal tissue sections. The antigen was identified by immunoprecipitation and mass spectrometry and confirmed by recombinant protein assays. Serum and cerebrospinal fluid (CSF) immunoglobulin G (IgG) from four patients was found to exhibit distinct binding to cerebellar and hippocampal neurons. Copine-5 was identified as the target antigen. Clinical manifestations included cognitive decline, confusion/disorientation, psychosis, seizures and signs and symptoms compatible with basal ganglia involvement (movement disorders, including secondary parkinsonism, and/or abulia/akinetic mutism), alongside pain (including painful tonic spasms and focal allodynia), dysarthria, dysphagia, and abducens nerve palsy. Brain magnetic resonance imaging disclosed hyperintense lesions in the basal ganglia and the temporal lobe. CSF analysis revealed mild pleocytosis, intrathecal IgG synthesis, and blood/CSF barrier dysfunction. Of particular note, all four patients had melanoma, with an occult primary in three. In one patient, melanoma diagnosis and immunotherapy with the anti-PD-1 immune checkpoint inhibitor nivolumab preceded the onset of AIE by 9 months. Glucocorticoid treatment and/or intravenous immunoglobulins led to transient improvement in at least three patients; however, all relapsed and three progressed to hypoactive delirium or mutism. Plasma exchange and cyclophosphamide treatment were followed by clinical improvement and stabilization in one patient, but potentially contributed to fatal infectious complications. Copine-5-IgG belonged to the strongly complement-activating IgG1 subclass and was produced intrathecally. Serum titers ranged between 1:1000 and 1:100,000. Copine-5 is a novel autoantibody target in AIE. Testing for anti-copine-5 autoantibodies should be included in the diagnostic workup of patients with AIE, especially, but not exclusively, if associated with melanoma or positive melanoma-associated tumor markers. Further studies investigating the immunopathogenesis of copine-5-related autoimmunity and the potential significance of anti-copine-5 as a novel paraneoplastic serological marker and of copine-5 as a histopathological tumor marker in patients with suspected melanoma are highly warranted.
M. Elstner, S. Jarius, B. Wildemann et al.· Journal of Neuroinflammation· 0 citations
Glutamate receptors in the CNS sensitive to the analog AMPA regulate neuronal excitability and synaptic plasticity. AMPA receptors are usually hetero-tetramers and the human GRIA3 gene and GluA3 protein product have been implicated in various CNS abnormalities including epilepsy, multiple sclerosis, schizophrenia, and cognitive disorders. Although not generally found in the immune system, GRIA3 has recently been demonstrated in a highly specialized group of immune system cells–plasmacytoid dendritic cells (pDCs). These are among the first cells to be activated by infecting viruses and they express GRIA3 in the absence of other AMPA receptor subunits, suggesting a possible role for the subunit in those neuroimmune disorders. The potential for molecular interactions between pDCs and neurons or glia is discussed, with the implications for linking viral infections, pDC activation, and chronic diseases. With growing evidence that the tryptophan metabolite kynurenic acid—an AMPA antagonist—is involved with a similar range of disorders, its role in those links is also discussed.
Trevor W Stone, F. Clanchy, Richard O. Williams· Frontiers in Cellular Neuros...· 0 citations