Antineuronal Antibodies Research Articles

Subacute Horizontal Diplopia, Jaw Dystonia, and Laryngospasm.

Jaw dystonia and laryngospasm in the context of subacute brainstem dysfunction have been described in a small number of diseases, including antineuronal nuclear antibody type 2 (ANNA-2, also known as anti-Ri) paraneoplastic neurologic syndrome. Severe episodes of laryngospasms causing cyanosis are potentially fatal. Jaw dystonia can also cause eating difficulty, resulting in severe weight loss and malnutrition. In this report, we highlight the multidisciplinary management of this syndrome associated with ANNA-2/anti-Ri paraneoplastic neurologic syndrome and discuss its pathogenesis.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Stroke-like presentation of acute toxic leukoencephalopathy due to capecitabine treatment with extensive intramyelinic edema.

Main Syndrome and Antibody Effects of Autoimmune Encephalitis Caused by Antineuronal Surface Antibodies: An Update

Since the discovery of a series of antineuronal surface antibodies (NSAs), the diagnostic approach and management of patients with autoimmune encephalitis (AE) and related disorders have undergone a "paradigm shift." However, recent topics described below are also announcing the dawn of the next era in the practice of patients with AE. As the clinical spectrum of NSA-associated AE expands, some types of AE (e.g., anti-DPPX antibody-associated and anti-IgLON5 antibody-associated disorders) can be misclassified into reconsider diagnosis when using the previously published diagnostic criteria. Nobel active immunization animal models of NSA-associated disorders (e.g., anti-NMDAR encephalitis model) can remarkably emphasize the understanding of the pathophysiological effects and main syndrome induced by NSAs. Additionally, several international clinical trials (e.g., rituximab, inebilizumab, ocrelizumab, bortezomib, and rozanolixizumab) for AE treatments, including anti-NMDAR encephalitis, have been implemented. Data from these clinical trials can be used to establish the best treatment of AE.

Immune Checkpoint Inhibitor Associated Central Nervous System Autoimmunity.

Outcome and re-challenge data of central nervous system (CNS) autoimmunity triggered by immune checkpoint inhibitors (ICI) are limited. We aim to describe a large series of ICI-triggered CNS-autoimmunity, and to compare these patients with spontaneous paraneoplastic syndromes (PNS). Retrospective review of Mayo Clinic patients with ICI-triggered CNS-autoimmunity (2/2015-6/2021). Clinical characteristics were compared to spontaneous PNS patients (with antineuronal nuclear antibody [ANNA]-1 or (anti-Hu) and/or neuroendocrine tumors [NET] within the same period. Thirty-one patients were included, 55% female, median age 63 years (range 39-76). Median time from ICI initiation was 3.65 months (range 0.8-44.5). Most common associated malignancies were melanoma and small-cell lung cancer. CNS manifestations included encephalitis (16), meningoencephalitis (8), cerebellar ataxia (4), demyelinating syndrome (2), myelopathy (1). MRI was abnormal in 62%. CSF was inflammatory in 70%. Neural autoantibodies were identified in 47%, more frequently in patients with NET (P=0.046). ICI was discontinued in 97%; 90% received immunosuppressive treatment. After median 6.8 months follow-up (range 0.7-46), 39% had unfavorable outcomes (grade ≥3). This associated with higher severity degree at onset, shorter period from ICI to neurological onset, and encephalitis. Four patients were re-challenged with ICI and one relapsed. Patients with NET and with ANNA-1 ICI-triggered CNS autoimmunity had associated peripheral nervous system manifestations more frequently than their spontaneous counterparts (P=0.007 and P=0.028, respectively). One third of ICI-related CNS-autoimmunity patients have unfavorable outcomes related to their clinical presentation. Relapses may occur after ICI re-challenge. Neural autoantibodies are often present, more commonly in patients with NET.

Antineuronal autoantibodies induced paraneoplasic syndrome in schizophrenia spectrum disorders: case report.

Our case is about a woman aged 62 years old, with a history of mental disorder who presented psychiatric symptomatology after years of being stabilized by antipsychotics. She was later investigated due to a mass in her breast. Carcinoma was diagnosed, and her psychiatric symptomatology was resolved after the tumerectomy. The therapeutic difficulty is the major problem of psychic disorders in the context of paraneoplastic syndrome. Several literature review have suggested a relationship between schizophrenia and antineuronal antibodies in the context of paraneoplastic syndrome. Treating the tumor can solve psychiatric symptoms better than psychotic treatment. The aim of our study is to highlight the importance of a complete medical evaluation to identify the psychiatric presentations of organic disorders associated with psychiatric manifestation and to ensure an early diagnosis.

Peripheral Nerve Pathology in Antibody Positive Paraneoplastic Neurological Syndromes (P11-8.005)

<h3>Objective:</h3> To describe peripheral nerve histopathology in neuropathy patients with paraneoplastic neurological syndromes (PNS) supported by autoantibody testing. <h3>Background:</h3> Rare autopsy cases in PNS suggest an association with shared antigens of misdirected cytotoxic T-cells against cancers and neural tissues. Neuropathy may be the first manifestation but reports of peripheral nerve pathology are limited. We sought to review the pathologic findings within nerve biopsies of patients having neuropathies linked to cancer and high-risk paraneoplastic antibody seropositivity. <h3>Design/Methods:</h3> We retrospectively reviewed the clinical data and nerve biopsy reports of patients presenting with neuropathy and paraneoplastic syndromes reviewing their cancer diagnosis and peripheral onsets. <h3>Results:</h3> Twelve sural nerves and one radial nerve were biopsied from patients with the following antibodies: Amphiphysin (n=6); Antineuronal nuclear antibodies (ANNA)-1 (n=2); ANNA-2 (n=2); Collapsin response mediator protein-5 (CRMP-5) (n=2); and Purkinje cytoplasmic antibody (PCA1) (n=1). Antibody testing occurred typically after biopsy or concurrently, and all patients had subacute onsets. Patients had overlapping involvements: length-dependent neuropathies (n=5), cranial neuropathies (n=1), brachial plexopathy (n=1), multiple mononeuropathies (n=2), and lumbosacral radiculoplexus involvement (n=8). Time to diagnosis was prolonged; commonly after one year. Malignancies were diverse including breast, ovarian, bladder, non-small cell lung cancer, small cell lung cancer, and coexisting colon and breast cancer. Fiber density was reduced in all, with multifocality frequently seen. Perineurial injury was absent, but sub-perineurial edema was common (n=4). Significant inflammation was absent in all but 5 cases, where small to moderate-sized CD45 collections were seen with vessel wall involvement with clinical lumbosacral plexus neuropathy (Amphiphysin (n=2), ANNA-2, and CRMP5) or multiple mononeuropathies (PCA-1). <h3>Conclusions:</h3> The absence of inflammatory infiltrates with reduced fiber density in distal sensory nerve biopsies is common in paraneoplastic neuropathies. A proximal inflammatory process is theorized. Microvessel inflammatory infiltrates with vessel wall involvement also occurs especially among lumbosacral plexopathy phenotypes. <b>Disclosure:</b> Dr. Granger has nothing to disclose. Dr. Rajnauth has nothing to disclose. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for UCB. The institution of Dr. Dubey has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for Astellas. The institution of Dr. Dubey has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Argenx. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for AGRIMS. Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Advances in Neurology . Dr. Dubey has received personal compensation in the range of $0-$499 for serving on a Speakers Bureau for Moffit Cancer Center . Dr. Dubey has received research support from Department of Defense . Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Dubey has received intellectual property interests from a discovery or technology relating to health care. Dr. Mills has received intellectual property interests from a discovery or technology relating to health care. The institution of Dr. Mauermann has received research support from IONIS. The institution of Dr. Mauermann has received research support from Alnylam. Dr. Mauermann has received publishing royalties from a publication relating to health care. Dr. Berini has nothing to disclose. Dr. Dyck has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Akcea/Ionis. Dr. Klein has a non-compensated relationship as a Klein with Neurology Journal that is relevant to AAN interests or activities.

Clinical features and biomarkers of acute encephalitis with claustrum sign (P5-5.027)

<h3>Objective:</h3> To determine clinical features and biomarkers of acute encephalitis with claustrum sign on brain MRI and to clarify the pathogenetic mechanism. <h3>Background:</h3> The claustrum sign has been described as reversible bilateral claustrum MRI hyperintensity on a T2-weighted MRI image. This finding has been reported in acute encephalitis, including acute necrotizing encephalopathy, febrile infection–related epilepsy syndrome, a subcategory of new-onset refractory status epilepticus. <h3>Design/Methods:</h3> We retrospectively analyzed the clinical features and cerebrospinal fluid (CSF) findings of three patients with acute encephalitis with claustrum sign. <h3>Results:</h3> All patients had prior symptoms suspected of infection, including fever, cough, and general fatigue. Two patients had meningeal signs and refractory status epilepticus. One patient had pyramidal signs and tremor. Claustrum sign was noted at 8, 28, and 52 days after the onset. In CSF, a glial fibrillary acidic protein (GFAP) antibody was detected in one patient with pyramidal signs and tremor. The other two patients had no antineuronal antibodies detected by tissue-based immunofluorescence assay using frozen rat brain sections. Compared with GFAP antibody-negative patients, GFAP antibody-positive patients had increased levels of CSF cell counts (antibody-positive vs antibody-negative; 127/μL vs 13 and 32/μL), protein concentrations (157 mg/dL vs 39 and 58 mg/dL), and tumor necrosis factor α (25.3 pg/mL vs 2.82 and 2.95 pg/mL). Interleukin 6 (IL-6) in CSF with GFAP antibody-negative patients was significantly higher than those with antibody-positive patients (195 and 609 pg/mL vs. 19.2 pg/mL). All patients required ventilator management and received immunotherapies. Two GFAP antibody-negative patients had improved, but a GFAP antibody-positive patient had died due to pneumonia. <h3>Conclusions:</h3> Acute encephalitis with claustrum sign is associated with at least increased levels of IL6 and GFAP antibody (i.e., GFAP astrocytopathy). In addition to CSF cytokine measurements, it is considered that GFAP antibody measurements should be performed in this disorder. <b>Disclosure:</b> Dr. Shimohata has nothing to disclose. Akira Takekoshi has nothing to disclose. Kimihiko Kaneko has nothing to disclose. Juichi Fujimori has nothing to disclose. Dr. Ioku has nothing to disclose. Keisuke Imai has nothing to disclose. Dr. Kimura has nothing to disclose.

Cognitive impairment in MOGAD is associated with ADEM-like episodes and deep grey matter atrophy (S40.006)

Cognitive impairment in MOGAD is associated with ADEM-like episodes and deep grey matter atrophy (S40.006)

Lesional Antibody Synthesis and Complement Deposition Associate With De Novo Antineuronal Antibody Synthesis After Spinal Cord Injury.

Spinal cord injury (SCI) disrupts the fine-balanced interaction between the CNS and immune system and can cause maladaptive aberrant immune responses. The study examines emerging autoantibody synthesis after SCI with binding to conformational spinal cord epitopes and surface peptides located on the intact neuronal membrane. This is a prospective longitudinal cohort study conducted in acute care and inpatient rehabilitation centers in conjunction with a neuropathologic case-control study in archival tissue samples ranging from acute injury (baseline) to several months thereafter (follow-up). In the cohort study, serum autoantibody binding was examined in a blinded manner using tissue-based assays (TBAs) and dorsal root ganglia (DRG) neuronal cultures. Groups with traumatic motor complete SCI vs motor incomplete SCI vs isolated vertebral fracture without SCI (controls) were compared. In the neuropathologic study, B cell infiltration and antibody synthesis at the spinal lesion site were examined by comparing SCI with neuropathologically unaltered cord tissue. In addition, the CSF in an individual patient was explored. Emerging autoantibody binding in both TBA and DRG assessments was restricted to an SCI patient subpopulation only (16%, 9/55 sera) while being absent in vertebral fracture controls (0%, 0/19 sera). Autoantibody binding to the spinal cord characteristically detected the substantia gelatinosa, a less-myelinated region of high synaptic density involved in sensory-motor integration and pain processing. Autoantibody binding was most frequent after motor complete SCI (grade American Spinal Injury Association impairment scale A/B, 22%, 8/37 sera) and was associated with neuropathic pain medication. In conjunction, the neuropathologic study demonstrated lesional spinal infiltration of B cells (CD20, CD79a) in 27% (6/22) of patients with SCI, the presence of plasma cells (CD138) in 9% (2/22). IgG and IgM antibody syntheses colocalized to areas of activated complement (C9neo) deposition. Longitudinal CSF analysis of an additional single patient demonstrated de novo (IgM) intrathecal antibody synthesis emerging with late reopening of the blood-spinal cord barrier. This study provides immunologic, neurobiological, and neuropathologic proof-of-principle for an antibody-mediated autoimmunity response emerging approximately 3 weeks after SCI in a patient subpopulation with a high demand of neuropathic pain medication. Emerging autoimmunity directed against specific spinal cord and neuronal epitopes suggests the existence of paratraumatic CNS autoimmune syndromes.

Early-onset schizophrenia: an adolescent case report

IntroductionThis is the case of a girl, aged 13, starting on 2021 with a first psychotic episode. Before this episode, her psychiatric history was an adjustment disorder because of scholar bullying, fully recovered before the onset of the current symptoms.ObjectivesTo describe an interesting case of early-onset psychosis.MethodsWe have used the interviews with the patient and her profile in Diraya (the medical database software in Andalucía).ResultsThe first symptoms started 6 months before the first hospitalization, and consisted in mild behavioural disorders, with disobedience and rudenesses, which represented a significant change compared with the previous personality of the patient. 3 weeks before the first admission she abruptly started to experience disconnection, unmotivated laughs, decreaded academic performance and incoherent speech. Also, she showed motor symptoms, consisting in oral and right-hand stereotypies. Then, she was hospitalized in a Pediatric unit, in order to rule out organicity. The nuclear magnetic resonance showed an image suggestive of venous development anomaly, with no acute injuries. Her cerebral spinal fluid was widely studied, and all the results were negative, including: the technique of PCR for many virus and bacteria that can cause meningitis or encephalitis; a bacterial culture; a biochemical study; antineuronal antibodies; and a limbic encephalitis antibodies study. Besides, the blood count, the biochemistry, the gasometry and serology were also negative. No drugs were detected in the urinalysis. Once the organicity was ruled out, she was treated with Olanzapine and Diazepam, and destinated to my child and adolescent psychiatry unit. During the first hospitalization we observed that she looked very often to the mirror, showed soliloquies and took leaps. During the interviews she was desinhibited. She initiated a delusional speech, focused in sexual topics. She said that she’s had a baby in the future with his father, and talked a lot about things she had already made in the future. During this admission, we changed the treatment to Quetiapine and Valproate.The second hospitalization was was done due to a lack of efficacy with the previous treatment and the presence of autolytic thoughts. We switched from Quetiapine to Aripiprazole. After a few days, she showed again a desinhibited behaviour, and kept the delusional speech, that now was more complex, refering that she had more than 20 babies, with many different men. After this we tried Lurasidone and suspended Aripiprazole, she showed a clinical improvement, at the cost of many side effects, though. So we finally changed to Clozapine, in combination with Gabapentin. Since she got clinical levels of clozapine, the delusions have been encapsulated.ConclusionsThe differential diagnosis is set with an early-onset schizophrenia and a schizoaffective disorder. Obviously, the evolution of the sypmptoms in the following months and years will have the last word.Disclosure of InterestNone Declared

Opsoclonus-myoclonus syndrome: Clinical characteristics, therapeutic considerations, and prognostic factors in a Spanish paediatric cohort

Opsoclonus-myoclonus-ataxia syndrome is a rare neuroinflammatory disorder with onset during childhood; aetiology may be paraneoplastic, para-infectious, or idiopathic. No biomarkers have yet been identified, and diagnosis is clinical. Better cognitive prognosis appears to be related to early onset of immunomodulatory therapy. We describe the epidemiological, clinical, therapeutic, and long-term prognostic characteristics of a cohort of 20 Spanish patients. The mean age of onset was 21 months (range, 2-59). Ataxia and opsoclonus were the most frequent symptoms both at disease onset and throughout disease progression. The mean time from onset to diagnosis was 1.1 months. Neuroblast lineage tumours were detected in 45% of patients; these were treated with surgical resection in 7 cases and chemotherapy in 2. Cerebrospinal fluid analysis revealed pleocytosis in 4 cases (25%) and neither antineuronal antibodies nor oligoclonal bands were detected in any patient. Immunomodulatory drugs were used in all cases. Nine patients started combined immunomodulatory treatment at the time of diagnosis, and 5 patients after a mean of 2.2 months. In the long term, 6 of the 10 patients followed up for more than 5 years presented mild or moderate cognitive sequelae. Four patients presented relapses, generally coinciding with the decrease of corticosteroid doses. Early initiation of immunotherapy, as well as triple combination therapy, where needed, was associated with a lower frequency of cognitive impairment 2 years after onset.

Characterisation of novel anti-neuronal antibodies

Anti-neuronal antibodies are widely recognised for their association with paraneoplastic and non-paraneoplastic neurological syndromes. The most common detection method for these antibodies has been indirect immunofluorescence (IIF) on primate or rodent neuronal substrates. While this method can detect the presence of the majority of neuronal antibodies, it does require extensive training to develop competence. Compounding this, there is significant overlap in the clinical presentation of many paraneoplastic and non-paraneoplastic antibodies.

Immune Mechanisms in Epileptogenesis: Update on Diagnosis and Treatment of Autoimmune Epilepsy Syndromes.

Seizures and epilepsy can result from various aetiologies, yet the underlying cause of several epileptic syndromes remains unclear. In that regard, autoimmune-mediated pathophysiological mechanisms have been gaining attention in the past years and were included as one of the six aetiologies of seizures in the most recent classification of the International League Against Epilepsy. The increasing number of anti-neuronal antibodies identified in patients with encephalitic disorders has contributed to the establishment of an immune-mediated pathophysiology in many cases of unclear aetiology of epileptic syndromes. Yet only a small number of patients with autoimmune encephalitis develop epilepsy in the proper sense where the brain transforms into a state where it will acquire the enduring propensity to produce seizures if it is not hindered by interventions. Hence, the term autoimmune epilepsy is often wrongfully used in the context of autoimmune encephalitis since most of the seizures are acute encephalitis-associated and will abate as soon as the encephalitis is in remission. Given the overlapping clinical presentation of immune-mediated seizures originating from different aetiologies, a clear distinction among the aetiological entities is crucial when it comes to discussing pathophysiological mechanisms, therapeutic options, and long-term prognosis of patients. Moreover, a rapid and accurate identification of patients with immune-mediated epilepsy syndromes is required to ensure an early targeted treatment and, thereby, improve clinical outcome. In this article, we review our current understanding of pathogenesis and critically discuss current and potential novel treatment options for seizures and epilepsy syndromes of underlying or suspected immune-mediated origin. We further outline the challenges in proper terminology.

Association of cerebrospinal fluid brain-binding autoantibodies with cognitive impairment in post-COVID-19 syndrome

BackgroundNeurological symptoms, in particular cognitive deficits, are common in post-COVID-19 syndrome (PCS). There is no approved therapy available, and the underlying disease mechanisms are largely unknown. Besides others, autoimmune processes may play a key role. DesignWe here present data of a prospective study conducted between September 2020 and December 2021 and performed at two German University hospitals with specialized Neurology outpatient clinics. Fifty patients with self-reported cognitive deficits as main complaint of PCS and available serum and CSF samples were included. Cell-based assays and indirect immunofluorescence on murine brain sections were used to detect autoantibodies against intracellular and surface antigens in serum and CSF and analyzed for associations with cognitive screening assessment. ResultsClearly abnormal cognitive status (MoCA ≤ 25/30 points) was only seen in 18/50 patients with self-reported cognitive deficits. Most patients (46/50) had normal routine CSF parameters. anti-neuronal autoantibodies were found in 52 % of all patients: n = 9 in serum only, n = 3 in CSF only and n = 14 in both, including those against myelin, Yo, Ma2/Ta, GAD65 and NMDA receptor, but also a variety of undetermined epitopes on brain sections. These included cerebral vessel endothelium, Purkinje neurons, granule cells, axon initial segments, astrocytic proteins and neuropil of basal ganglia or hippocampus as well as a formerly unknown perinuclear rim pattern. Pathological MoCA results were associated with the presence of anti-neuronal antibodies in CSF (p = 0.0004). ConclusionsAutoantibodies targeting brain epitopes are common in PCS patients and strongly associate with pathological cognitive screening tests, in particular when found in CSF. Several underlying autoantigens still await experimental identification. Further research is needed to inform on the clinical relevance of these autoantibodies, including controlled studies that explore the potential efficacy of antibody-depleting immunotherapy in PCS.

Antineuronal antibodies in cerebrospinal fluid and serum of 104 patients with psychotic disorders compared to 104 individually matched healthy controls

BackgroundAntineuronal antibodies can cause psychotic symptoms, particularly NMDAR antibodies; however, studies on the prevalence of antineuronal antibodies in cerebrospinal fluid (CSF) and serum of patients with psychotic disorders compared to matched healthy controls are sparse. MethodsWe included 104 patients with a first-time diagnosis of a psychotic disorder within one year prior to inclusion (50 % outpatients) and 104 individually matched healthy controls, all without any known immunological conditions. CSF and serum were tested for IgG antibodies (Abs) against NMDAR NR1-subunit, GAD65, LGI1, CASPR2, AMPAR1, AMPAR2 and GABAb-receptor B1/B2 using commercial fixed cell-based assays (CBAs) (Euroimmun). Positive samples were retested with CBA twice, and tested with tissue-based assays (TBA). Primary outcomes were the presence of any of the seven anti-neuronal antibodies in CSF or serum. Secondarily, we analyzed the prevalence of each autoantibody. ResultsNo antineuronal IgG antibodies were consistently found in any CSF sample and NMDAR-antibodies were not consistently present in any of the 208 participants, neither in CSF nor serum. CASPR2-Abs were consistently found in the serum of one patient and one control, and one healthy control, without diabetes, was seropositive for GAD65-Abs. CASPR2 borderline seropositivity was additionally found in one patient and two controls. All samples positive on CBA were negative on TBA. ConclusionsWe found no significant differences between patients and controls. Antineuronal IgG antibodies are very rare when screening a broad group of individuals with recent-onset psychotic disorders without other indications of autoimmune encephalitis. Thus, much larger studies are needed to conclude on potential contrasts in prevalence compared to healthy controls.

Autoimmune Mechanisms in Focal Epilepsy of Unknown Cause

ABSTRACT The manifestation of immunological findings in diverse disorders presenting with seizures points to autoimmunity and inflammation in the etiology of epilepsy. Typical examples of autoimmunity-associated epilepsy are autoimmune encephalitis, Rasmussen encephalitis, and glutamic acid decarboxylase (GAD) antibody-positive temporal lobe epilepsy (TLE). The last entity is a typical example of antibody-positive focal epilepsy of unknown cause (FEUC). One of the most prominent findings emphasizing the coexistence of epilepsy and autoimmunity is the detection of anti-neuronal antibodies in patients manifesting with seizures. Emergence of antibody-producing plasma cells in the early course of GAD-antibody-positive TLE and induction of seizures in rodents upon intracerebral administration of N-methyl-D-aspartate receptor antibodies indicate that anti-neuronal antibodies may play a causal (rather than bystander) role in the induction of seizures. By contrast, innate immunity of the central nervous system (CNS) and infiltrating cytotoxic T-cells appear to participate in Rasmussen encephalitis and autoimmune encephalitis with antibodies to intracellular antigens. In addition, repetitive seizures may activate glial cells through the release of damage-associate molecular pattern mediators and activation of toll-like receptors, which in turn leads to disrupted blood–brain barrier and increased cerebral infiltration of peripheral blood immune cells. In conclusion, complex interactions of humoral and cellular immunity in the CNS appear to cause or at least contribute to seizure induction in FEUC. The nature of these interactions has recently started to be understood. Investigation of these mechanisms is substantial for the discovery of new treatment strategies and biomarkers in epilepsy.

Cerebellar antibodies in post-stroke sera of acute ischemic stroke patients

<p>Although serum anti-neuronal antibodies are found in acute ischemic stroke (AIS) patients, it is not completely clear whether they are already present before the cerebrovascular event or emerge thereafter.&nbsp;</p>. <p>Sera of 21 consecutive first-ever AIS patients were collected within the first day of AIS (baseline), as well as 1 and 6 months after AIS. Well-characterized and novel anti-neuronal antibodies were investigated by cell-based assays, immunoblotting and indirect immunohistochemistry.</p>. <p>None of the AIS sera collected at different time points showed well-characterized antibodies. In 7 patients, 1- and 6-month sera (but not baseline sera) showed IgG mostly reacting with soma and dendrites of cerebellar Purkinje cells. Antibody-positive patients did not differ in terms of clinical and etiological features.</p>. <p>Our results provide evidence for the antibody-triggering action of AIS. Although anti-cerebellar antibodies are not associated with the severity of stroke, they may potentially contribute to chronic post-stroke complications and disability.</p>.

Clinical characteristics and short-term outcomes of autoimmune encephalitis in adults

To characterize clinical, paraclinical features and short-term outcomes in different types of autoimmune encephalitis (AE) in a one-center cohort of Russian patients, as well as to evaluate the frequency and significance of the joint expression of antineuronal and anti-glial antibodies (Abs) in AE. Forty-one patients were diagnosed with AE at the Research Center of Neurology from November 2020 to December 2022. Demographic, clinical characteristics, results of laboratory tests, MRI of brain, treatment and outcomes of disease were analyzed. The analysis of Abs to glial antigens (myelin-oligodendrocyte glycoprotein - MOG, glial fibrillar acidic protein - GFAP, aquaporin 4 - AQP-4) was performed by indirect immunofluorescence assay (Euroimmun, Germany). In 24 (58.5%) patients was established definite AE, confirmed by specific Abs detection; in 2 (4.9%) - definite limbic encephalitis, in 15 (36.6%) - seronegative probable AE (including 3 cases of Hashimoto's encephalitis). GFAP-Abs in cerebrospinal fluid (CSF) were detected only in two patients - with clinical and MRI-picture of autoimmune GFAP-astrocytopathy (A-GFAP-A). GFAP- and MOG-Abs in the blood were detected in 25.7% and 6%, respectively, AQP-4-Abs were not detected. There were no correlations between co-expression with glial Abs and clinical characteristics. Systemic and antithyroid Abs were present in 15% and 31%, respectively. Paraneoplastic AE accounted for 22%. For the first time in the Russian population, 2 cases of A-GFAP-A, 6 cases of AE associated with COVID-19 were described. The most common first syndrome were epileptic seizure (34%), psychiatric (29%) and cognitive (14%) disorders. Relapses of AE was observed in 22%. Inflammatory changes in CSF were detected in 41%, focal changes on MRI in 68%. First-line immune therapy was performed in all patients, 85% of cases received pulse therapy with methylprednisolone. Second-line immune therapy (rituximab or cyclophosphamide intravenously) was performed in 19.5%, 78% of patients achieved significant improvement during treatment (scores ≤2 on the modified Rankin scale). The results allow us to consider COVID-19 as a trigger of AE. The absence of detection of GFAP-Abs in CSF in patients with other types of AE contributes to the confirmation of the specificity of GFAP-seropositivity of CSF for the diagnosis of A-GFAP-A. The expression of GFAP- and MOG-Abs in AE can serve as confirmation of the immuno-mediated etiology of the disease, which is especially important for the AE diagnosis in the absence of antineuronal Abs.

Various Phenotypes related with Epilepsy in Autoimmune Encephalitis

Aim: To observe and analyses the epileptic phenotypes in autoimmune encephalitis ranging from acute symptomatic-seizures to autoimmune related epilepsy. Study design: Retrospective-observational cohort study Place and duration of study: Ghulam Muhammad Mahar Medical College Sukkur and Shaheed Mohtarma Benazir Bhutto Medical University Larkana from 1st August 2020 to 30th September 2021. Methodology: One hundred and twenty seven patients who were enrolled with a new onset of seizures in reference to autoimmune encephalitis. Clinical as well as through para-clinical tests, including electroencephalogram, cerebrospinal fluid/neuroimaging techniques including magnetic resonance index or fluorine-18-fluorodeoxyglucose positron-emission tomography/computed tomography was used for confirming the cases. Each patient underwent anti-nuronal antibody test and was grouped as positive or negative for the test and clinically compared. Results: There were 66 (51.96%) females and 61 (48.04%) males with mean age was 54±5.5 years. There were 62.9% cases who were having anti-neuronal antibodies as positive while 37.1% had a negative result. Majority of the positive group had multiple type seizures whereas SE was more common in negative group cases. There were 111 (87.4%) cases were given immunotherapy. Within these 111 cases the immunotherapy was effective in 60% of the cases. There were 81% cases with psychological as well as cognitive disturbances with 43.75% having long term sequel. The most common phenotype for seizure was focal impaired awareness seizures followed by focal bilateral tonic clonic seizures. Conclusion: Early onset of immunotherapy and recognition of seizures may avoid long term irreversible outcomes of sequela. Key words: Epileptic phenotype, Autoimmune encephalitis, Acute symptomatic seizure, Autoimmune associated epilepsy

Circulating plasmablasts and follicular helper T-cell subsets are associated with antibody-positive autoimmune epilepsy.

Autoimmune epilepsy (AE) is an inflammatory disease of the central nervous system with symptoms that have seizures that are refractory to antiepileptic drugs. Since the diagnosis of AE tends to rely on a limited number of anti-neuronal antibody tests, a more comprehensive analysis of the immune background could achieve better diagnostic accuracy. This study aimed to compare the characteristics of anti-neuronal antibody-positive autoimmune epilepsy (AE/Ab(+)) and antibody-negative suspected autoimmune epilepsy (AE/Ab(-)) groups. A total of 23 patients who met the diagnostic criteria for autoimmune encephalitis with seizures and 11 healthy controls (HC) were enrolled. All patients were comprehensively analyzed for anti-neuronal antibodies; 13 patients were identified in the AE/Ab(+) group and 10 in the AE/Ab(-) group. Differences in clinical characteristics, including laboratory and imaging findings, were evaluated between the groups. In addition, the immunophenotype of peripheral blood mononuclear cells (PBMCs) and CSF mononuclear cells, particularly B cells and circulating Tfh (cTfh) subsets, and multiplex assays of serum and CSF were analyzed using flow cytometry. Patients with AE/Ab(+) did not show any differences in clinical parameters compared to patients with AE/Ab(-). However, the frequency of plasmablasts within PBMCs and CSF in patients with AE/Ab(+) was higher than that in patients with AE/Ab(-) and HC, and the frequency of cTfh17 cells and inducible T-cell co-stimulator (ICOS) expressing cTfh17 cells within cTfh subsets was higher than that in patients with AE/Ab(-). Furthermore, the frequency of ICOShighcTfh17 cells was positively correlated with that of the unswitched memory B cells. We also found that IL-12, IL-23, IL-6, IL-17A, and IFN-γ levels were elevated in the serum and IL-17A and IL-6 levels were elevated in the CSF of patients with AE/Ab(+). Our findings indicate that patients with AE/Ab(+) showed increased differentiation of B cells and cTfh subsets associated with antibody production. The elevated frequency of plasmablasts and ICOS expressing cTfh17 shift in PBMCs may be indicative of the presence of antibodies in patients with AE.