Autoimmune Encephalopathy Research Articles

Severe cerebral amyloid angiopathy related inflammation (CAA-ri) associated with vaccination: Case report and literature review

Cerebral amyloid angiopathy-related inflammation (CAA-ri) is a rapid but reversible autoimmune encephalopathy where spontaneous autoantibody reaction against amyloid beta deposited in cerebral blood vessels produces characteristic neuroinflammatory changes such as vasogenic edema and microhemorrhages on MRI. The term amyloid-related imaging abnormalities (ARIA) is sometimes used to describe these changes but are more often reserved for similar MRI signal abnormalities seen after administration of anti-amyloid immunotherapy, using treatment exposure as an antecedent. It is unclear if there is any biological basis for this dichotomized distinction. We report a case of severe CAA-ri after exposure to SARS-CoV-2 vaccine and performed a literature review of CAA-ri related to vaccination. CAA-ri precipitated by immunogenic triggers other than anti-amyloid therapy would lend support to the hypothesis that ARIA seen on MRI may represent the same disease underpinned by a shared anti-Aβ autoantibody response irrespective of etiology. A thorough history should be taken before labelling CAA-ri as spontaneous.

Longitudinal imaging for monitoring disease activity in late‐onset Rasmussen's encephalitis during multimodal rehabilitation and immune therapy

AbstractBackgroundRasmussen's encephalitis (RE) is a rare autoimmune encephalopathy typically manifesting in early childhood, causing unilateral autoimmune inflammation of the cerebral cortex, leading to progressive neurological deficits, notably focal epileptic seizures. The late‐onset variant of RE in adults progresses slower and presents atypical features. Despite extensive research, the etiology remains elusive, hindering accurate diagnosis and treatment options.Case PresentationWe present a biopsy‐confirmed late‐onset variant of RE case in a 71‐year‐old man with a disease course of 12 years. After the initiation of intravenous immunoglobulin therapy and immunosuppressive treatment, disease stabilization was achieved, as evidenced by clinical assessments and imaging. Initially, the affected hemisphere swelled hyperacutely, followed by years of atrophic encephalopathy stabilizing into a residual state, with emerging focal disease signs in the contralateral hemisphere. Multimodal rehabilitation and immune therapy attenuated brain atrophy and reduced signal enhancement.ConclusionsLate‐onset variant of RE rehabilitation remains underdeveloped, focusing on symptom management and functional recovery post‐surgery. Longitudinal imaging is crucial for monitoring immune therapy response in clinical practice.

Brain-targeting autoantibodies in patients with dementia.

Autoantibodies against proteins in the brain are increasingly considered as a potential cause of cognitive decline, not only in subacute autoimmune encephalopathies but also in slowly progressing impairment of memory in patients with classical neurodegenerative dementias. In this retrospective cohort study of 161 well-characterized patients with different forms of dementia and 34 controls, we determined the prevalence of immunoglobulin (Ig) G and IgA autoantibodies to brain proteins using unbiased immunofluorescence staining of unfixed murine brain sections. Autoantibodies were detected in 21.1% of dementia patients and in 2.9% of gender-matched controls, with higher frequencies in vascular dementia (42%), Alzheimer's disease (30%), dementia of unknown cause (25%), and subjective cognitive impairment (16.7%). Underlying antigens involved glial fibrillary acidic protein (GFAP), glycine receptor, and Rho GTPase activating protein 26 (ARHGAP26), but also a range of yet undetermined epitopes on neurons, myelinated fiber tracts, choroid plexus, glial cells, and blood vessels. Antibody-positive patients were younger than antibody-negative patients but did not differ in the extent of cognitive impairment, epidemiological and clinical factors, or comorbidities. Further research is needed to understand the potential contribution to disease progression and symptomatology, and to determine the antigenic targets of dementia-associated autoantibodies.

A Borderline Personnality Disorder and Autoimmue Thyroiditis: A Case Report

The association between autoimmune thyroiditis and encephalopathy is rare and well known. A case report of a patient with bordeline disoder (BLD) with fluctuanting mood and psychotic symptoms using double blind method shows a significant relationship between psychotic symptoms and fluctuanting antithyroid anto immnune antibody titers [1]. We report here a case of patient with BLD and autoimmune thyroiditis. Improvement of BLD traits is obtained after adding thyroid hormones replacement therapy to psychotropic medication.

Unraveling the Intricacies of OPG/RANKL/RANK Biology and Its Implications in Neurological Disorders-A Comprehensive Literature Review.

The OPG/RANKL/RANK framework, along with its specific receptors, plays a crucial role in bone remodeling and the functioning of the central nervous system (CNS) and associated disorders. Recent research and investigations provide evidence that the components of osteoprotegerin (OPG), receptor activator of NF-kB ligand (RANKL), and receptor activator of NF-kB (RANK) are expressed in the CNS. The CNS structure encompasses cells involved in neuroinflammation, including local macrophages, inflammatory cells, and microglia that cross the blood-brain barrier. The OPG/RANKL/RANK trio modulates the neuroinflammatory response based on the molecular context. The levels of OPG/RANKL/RANK components can serve as biomarkers in the blood and cerebrospinal fluid. They act as neuroprotectants following brain injuries and also participate in the regulation of body weight, internal body temperature, brain ischemia, autoimmune encephalopathy, and energy metabolism. Although the OPG/RANKL/RANK system is primarily known for its role in bone remodeling, further exploring deeper into its multifunctional nature can uncover new functions and novel drug targets for diseases not previously associated with OPG/RANKL/RANK signaling.

Gut microbiome alterations in Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections (PANDAS) suggests variation in the gut-brain axis and gut metabolic potential

PANDAS, or Pediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal Infections is a form of Children’s Post infectious Autoimmune Encephalopathy (CPAE), a neuropsychiatric condition characterized by the abrupt onset of diverse neuropsychiatric manifestations following streptococcal infection. It is an increasingly recognized neuropsychiatric disorder that affects a subset of children whose underlying etiology remains unclear. Gut microbiome plays a crucial role in its host brain development and is implicated throughout the life in neurobehavior and neurological disorders. Emerging evidence suggest gut dysbiosis resulting in altered intestinal flora can impair gut barrier and increase leakiness in the blood-brain barrier leading to inflammation. We aimed to investigate if the microbiome is altered in pediatric patients with PANDAS. Stool (n=19), oral (n=20) and nasal swabs (n=18) were collected from patients diagnosed with PANDAS or healthy controls (HC) and used for 16S analysis. 13 stool samples (7 HC and 6 PANDAS) samples were further used for shogun metagenomics and 17 for untargeted metabolomics (8 HC and 9 PANDAS). 16S rRNA gene sequencing identified significant difference in microbial α diversity, with lower Shannon H’ in PANDAS compared to HC (Welch’s t-test t(16.95)=-2.6, p=0.02), and in β-diversity (PERMANOVA R2=0.08 p=0.04) between PANDAS and HC fecal but not throat and nasal samples. Shotgun metagenomics identified a significant reduction in gene diversity (Welch’s t-test t(9.9)=-3.06, p=0.01) and changes in various KEGG ortholog modules involved in gut metabolism and gut-brain axis. Significant differences were also detected in metabolite composition (PERMANOVA R2=0.10, p=0.02). We also identified a set of microbial groups and metabolites enriched or depleted in CPAE patients, involved in different aspects of host physiology and gut metabolism. Our results show that PANDAS patients have an altered gut microbial community, which may exacerbate their behavioral symptoms and it should be taken into consideration in unveiling the complex pathogenesis and selection of treatment options. Arizona Department of Health Services RFGA2022-010-23 (PK) and ADHS17-00007403 (SR, MD); The Alex Manfull Fund (PK). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Steroid response encephalopathy associated with autoimmune thyroiditis

IntroductionSteroid-responsive encephalopathy associated with autoimmune thyroiditis (SREAT) is a rare autoimmune disorder affecting the central nervous system, characterized by a spectrum of neurological and psychiatric symptoms.AimThis case study aims to highlight the diagnostic challenges and the successful management of SREAT syndrome in a young woman with autoimmune thyroiditis.Case studyA 21-year-old woman with documented Hashimoto's thyroiditis and polycystic ovary syndrome was admitted to the Clinic of Neurology following a 5-minute tonic seizure and subsequent confusion state lasting several hours. Initial brain MRI showed no abnormalities, and EEG revealed generalized slowness. Comprehensive laboratory assessments, including a complete blood count, biochemical analysis, and electrolyte panels, all yielded normal results. Further investigation revealed a significantly elevated anti-thyroid peroxidase antibody (anti-TPO) titer exceeding 1000 IU/mL. The suspicion of SREAT syndrome was considered. Pulse therapy with methylprednisolone was associated with rapid recovery. The patient was discharged from the hospital with an oral corticosteroid tapering regimen.Results and discussionThe administration of pulse therapy with methylprednisolone resulted in a rapid and very good response in the patient, evidenced by the resolution of seizure activity and improvement in confusion. Laboratory investigations, particularly the markedly elevated anti-TPO titer, supported the diagnosis of SREAT syndrome. The subsequent management with an oral corticosteroid tapering regimen maintained the patient's clinical stability.ConclusionsThis case highlights the importance of considering autoimmune encephalopathy in patients with a history of autoimmune thyroiditis presenting with neurological and psychiatric symptoms. Further research is warranted to better understand the underlying pathomechanisms.

Off-label use of therapeutic plasma-exchange in postasymptomatic covid-19 autoimmune encephalopathy

Hypertensive tetraventricular hydrocephalus in association with polyradiculoneuritis and leptomeningitis in patients are very unusual conditions that can be related to viral infections. We report the case of a patient with severe post-covid 19 encephalopathy who underwent Therapeutic Plasma Exchange (TPE) as an “off-label” use.

Predicting disability and mortality in CV2/CRMP5-IgG associated paraneoplastic neurologic disorders.

We aimed to investigate the prognostic factors associated with clinical outcomes in CV2/Collapsin response-mediator protein 5 (CRMP5)-IgG paraneoplastic neurologic disorders (PND). This is a retrospective study of patients with CV2/CRMP5-IgG PND evaluated between 2002-2022. We examined the association of clinical variables (including age, clinical phenotype [autoimmune encephalopathy, myelopathy, polyneuropathy/radiculopathy, MG, cerebellar ataxia, chorea, optic neuropathy], cancer) with three clinical outcomes (wheelchair dependence, modified Rankin Scale [mRS], mortality) using univariate logistic regression and Cox proportional hazards modeling. Kaplan-Meier estimates were used to determine the probability of survival. Twenty-seven patients (56% female) with CV2/CRMP5-IgG PND were identified with a median follow-up of 54 months (IQR = 11-102). An underlying tumor was identified in 15 patients (56%) including small cell lung cancer (SCLC) (8, [53%]), thymoma (4, [27%]), and other histologies (3, [20%]). At last follow-up, 10 patients (37%) needed a wheelchair for mobility and this outcome was associated with myelopathy (HR = 7.57, 95% CI = 1.87-30.64, P = 0.005). Moderate-severe mRS = 3-5 was associated with CNS involvement (encephalopathy, myelopathy, or cerebellar ataxia) (OR = 7.00, 95% CI = 1.18-41.36, P = 0.032). The probability of survival 4 years after symptom onset was 66%. Among cancer subtypes, SCLC (HR = 18.18, 95% CI = 3.55-93.04, P < 0.001) was significantly associated with mortality, while thymoma was not. In this retrospective longitudinal study of CV2/CRMP5-IgG PND, patients with CNS involvement, particularly myelopathy, had higher probability of disability. SCLC was the main determinant of survival in this population.

Use of cerebrospinal fluid biomarkers for accurate diagnosis of Alzheimer’s disease in a tertiary care memory center

AbstractBackgroundAccurate clinical‐biological diagnosis of dementia and of Alzheimer’s disease (AD) is important for exclusion of treatable modifiable conditions, to differentiate AD from conditions with similar clinical manifestations, and for consideration of novel disease‐modifying therapeutic agents. Recently, it has become possible to measure protein biomarkers that reflect the pathology of AD. Our aim was to examine our initial experience of running a “cognitive” CSF biomarker service and bank at our institute.MethodThe service operates since June 2020. All subjects underwent physical, neurological and cognitive evaluation, imaging and laboratory work‐up. Consenting patients presenting at young age or with atypical or unclear manifestations of cognitive and/or behavioral deterioration underwent lumbar puncture for CSF examination, tailored according to the clinical differential diagnosis [cells, protein, glucose, chloride, cytology, AD biomarkers‐ total tau (tTau), 181‐phosphorylated tau (pTau181), amyloid‐β42 (Aβ42)]. When appropriate, antibody analysis and microbiological studies were added.ResultAD biomarkers results were available for 63 subjects presenting with cognitive/behavioral impairment, mean age 59 (range 31‐78) years, 34 (54%) were men. Mean MMSE score was 21/30 (range 6‐30), mean MoCA score was 18/30 (range 6‐28). Pre CSF analysis, 27 (43%) subjects were clinically diagnosed with possible AD (CDAD) and 36 (57%) with clinically diagnosed possible non‐AD (CDNAD) (FTD, LBD, CBD, vascular disease, autoimmune encephalopathy, unclear etiology). In our sample 28 (44%) were biomarkers positive for AD. Among 27 subjects with CDAD in 5 AD was excluded and among 36 with CDNAD 6 were biomarker positive AD (clinical sensitivity 78%, false positive 18.5%, false negative 16.6%).ConclusionOur study emphasizes the added value of biomarker supported diagnosis in subjects with cognitive/behavioral impairment, to avoid incorrectly labeling AD or misdiagnosis and for disclosure recommendation in the era of disease‐modifying therapies.

ARIA‐E, ARIA‐H, and CAA‐related inflammation: time of reconsiderations?

AbstractBackgroundEvidence from published clinical trials suggests that high‐dose of monoclonal antibodies (mAbs) are needed to significantly remove parenchymal‐deposited Aβ plaques. However, high‐dosing mAbs resulted in a 25‐35% increased risk of amyloid‐related imaging abnormalities‐edema (ARIA‐E) and ARIA‐hemorrhage (ARIA‐H) side events. Although most ARIA‐E are incidentally recognized as clinically silent during pre‐planned safety monitoring MRI scans and suggested to be managed by dose reduction or suspension, it is noticeable that half of ARIA‐E progressed to symptomatic at continued dosing and to associate with late occurrence of ARIA‐H. Of particular importance, a few of them aggravated to potentially severe brain injury or death due to fatal CAA‐related events. Increased evidence from natural history studies suggests that ARIA‐E is the iatrogenic manifestation of cerebral amyloid angiopathy‐related inflammation (CAA‐ri), a rare autoimmune encephalopathy due to raised anti‐Aß autoAbs levels in the cerebrospinal fluid (CSF).MethodNatural history study of CAA‐ri demonstrated that immunotherapy‐related ARIA‐E share several commonalities with the spontaneous occurrence of autoAbs‐related ARIA‐E, including fluid, MRI, and PET biomarker changes and the potential response to treatment outcomes.ResultThe prospective longitudinal monitoring of patients with CAA‐ri provide evidence for a regional and temporal association of ARIA‐E on MRI with focal peaks of neuroinflammation on microglial‐PET imaging. This association was strong in patients with positive CSF markers of AD (ATN positive) and comorbid CAA pathology on MRI, while it was negligible in patients with CAA disease w/o AD (ATN negative). Raised CSF concentrations of anti‐Aß autoAbs were found in all patients at (sub)acute presentation, and reduced within 5 months from the ARIA‐E index event, in parallel with evidence of radiographic resolution of ARIA‐E. At follow‐up MRI scan, the occurrence of new hemorrhagic markers (aka ARIA‐H in trials) were found only in patients with coexisting CAA and AD comorbid pathology. The MRI scales for ARIA commonly used in clinical trials only partially paralleled the clinical, biological, and MRI findings.ConclusionThis suggests that to mitigate and monitor the risk of ARIA, more sensitive, specific, cost‐effective and easy to interpret diagnostic tools and biomarkers than MRI alone will be needed for precision drug‐dose tailoring.

An unbiased approach of individual tissue-specific autoantibody identification using Immunoprecipitation coupled to Mass-Spectrometry (IP-MS)

Abstract Background and aim Autoreactive antibodies have gained increasing recognition in autoimmune diseases of the central nervous system (CNS) serving as disease drivers and / or biomarkers. Identification of novel autoantibodies therefore is crucial to optimize diagnostic work and therapy of these diseases as well as understanding their pathogenesis. Hence, we aimed to develop an unbiased strategy to identify patients’ individual main autoantibodies directed against brain epitopes. Methods We used murine tissue-based assays to screen patients’ sera and cerebrospinal fluids (CSFs) for autoreactive IgGs with known and unknown antibody targets. IgGs from autoreactive patients’ samples were coupled to magnetic beads and used as a bait to pull down potential targets from homogenized brain tissue of wildtype mice. After precipitation and several washes to reduce unspecific binding, beads were subjected to on-bead tryptic digestion followed by mass spectrometry based proteomic analyses using liquid chromatography tandem mass-spectrometry (LC-MS/MS). For antibody targets identification the fold change enrichment compared to a negative control or to all other pulldown samples, as well as the protein abundance was used. Antibody target validation was done via recombinant expression of the target protein in HEK-293 cells and neutralization with the respective antigen in tissue-based immunofluorescence assays. Results As proof of principle, we were able to identify Grin1 Caspr2, Trim46 and Nf-h [MOU1] as main targets of patients’ sera or CSF with autoimmune encephalopathy. All four antigens showed highest enrichment and/or highest protein abundance in the respective samples and have been confirmed in cell-based assays. In addition, we identified one novel anti-neuronal antibody target in serum and CSF of a patient showing a speckled staining of the granular cerebellar layer. Preabsorbance of the serum and CSF with the recombinant protein fully neutralized the signal of the tissue-based immunofluorescence. Conclusions Our IP-MS approach is suitable to identify the main autoantibody targets in patients’ serum and CSF within murine CNS tissue thereby providing an unbiased and scalable technique allowing for tissue-specific autoantibody determination.

Expanding clinical spectrum from Hashimoto's encephalopathy to anti‐NAE antibody‐associated disorders (NAEAD)

AbstractUsing proteomic analysis, we identified anti‐NAE antibodies (autoantibodies against NH2‐terminal of alpha‐enolase) as a diagnostic marker for Hashimoto's encephalopathy (HE). As cases of HE with serum anti‐NAE antibodies accumulated, the clinical spectrum of HE with anti‐NAE antibodies became expanded. In addition, it is now known that antibodies can be detected in other diseases that differ from conventional HE. We recently reported the detection of anti‐NAE antibodies in patients with a clinical diagnosis of multiple system atrophy or corticobasal syndrome. These findings suggest that anti‐NAE antibodies indicate an immune mechanism in the pathogenesis of neurodegenerative diseases. We propose a novel disease concept for anti‐NAE antibody‐associated disorders (NAEAD). The clinical spectrum of NAEAD is not limited to HE but is a broad spectrum that partially shares several autoimmune neurological diseases, including autoimmune acute encephalopathy, autoimmune cerebellar ataxia, and autoimmune psychosis, and even extends to immune‐associated neurodegenerative diseases.

Therapeutic Plasma Exchange in Treatment of Autoimmune Encephalitis: A Case Report

The present study highlights the Therapeutic Plasma Exchange in treatment of Autoimmune Encephalitis. Due to the similarities in the clinical, imaging, and laboratory findings of many forms of autoimmune and infectious encephalitis, autoimmune encephalitis is frequently a difficult clinical diagnosis. Diagnosis of autoimmune encephalitis is based on the clinical course, serological evidence of autoimmunity, EEG changes, evidence of intrathecal inflammation in the cerebrospinal fluid and neuroimaging by MRI. In view of the suspected diagnosis of Autoimmune Encephalopathy with super refractory Status Epilepticus, Methylprednisolone was later added to the treatment. This case represents an interesting scenario of sero-negative encephalitis in which an early diagnosis could be made and treatment initiated in time.

Acute Fulminant Encephalitis in the Setting of Acute COVID-19 Infection (P12-3.008)

<h3>Objective:</h3> NA <h3>Background:</h3> Encephalitis in the setting of COVID-19 has been reported, however the mechanism by which SARS-CoV-2 causes encephalitis remains unclear. We aimed to describe a case of fulminant limbic encephalitis associated with acute COVID-19 infection. <h3>Design/Methods:</h3> NA <h3>Results:</h3> A 33-year-old COVID-19 positive female presented after being found unresponsive with seizure-like activity. On arrival, patient was comatose with intermittent left gaze deviation, weak gag and cough reflexes, and no movement to pain. She was intubated for airway protection (without hypoxia). Continuous EEG demonstrated generalized and bilaterally independent epileptiform discharges, with no electrographic or clinical seizures. Patient was prophylactically started on levetiracetam. Brain MRI revealed scattered DWI and T2 hyperintensities involving supratentorial and infratentorial areas more prominent in temporal lobes. CSF analysis showed mild neutrophilic pleocytosis; protein and glucose were normal. Infectious, autoimmune, and paraneoplastic encephalopathy in CSF/serum panels were negative. CSF COVID-19 PCR was negative. ESR, CRP and ferritin were mildly elevated. High-dose steroids and intravenous immunoglobulin were initiated. After 7 days repeated brain MRI demonstrated progression of T2 hyperintensities including midbrain, cerebral peduncles, and right hemispheric cortical ribboning. Patient continued to decline with gradual loss of brainstem reflexes and downward gaze deviation with ocular bobbing movements. Due to clinical deterioration the patient was transitioned to comfort care and deceased after extubating. <h3>Conclusions:</h3> There have been increasing reports of severe encephalitis subtypes among younger COVID-19 patients commonly associated with poor outcomes compared to other subtypes of encephalitis. To our knowledge this is the first case of encephalitis associated with COVID-19 infection with no response to immunomodulatory therapies. Other possible etiologies in this case include hypoxic injury, hypoglycemia, or toxic insults, which were considered less likely given clinical scenario. In our case, PCR of CSF was negative for COVID-19 which raises possibility of secondary hyperinflammation or molecular mimicry as potential causes. <b>Disclosure:</b> Dr. Kherallah has nothing to disclose. Dr. Manrique has nothing to disclose. Dr. Vennavaram has nothing to disclose. Dr. Samaha has nothing to disclose.

Autoimmune Encephalitis Criteria in Clinical Practice.

To assess the clinical practice applicability of autoimmune encephalitis (AE) criteria (2016). Medical records of 538 adults diagnosed with AE or related autoimmune encephalopathy at Mayo Clinic (not including pure movement disorders) were reviewed and AE guideline criteria applied. Of 538 patients, 288 were male (52%). The median symptom onset age was 55 years (range, 11-97 years; 16 had onset as children). All had other non-AE diagnoses reasonably excluded. Of 538 patients, 361 (67%) met at least possible criteria, having all 3 of subacute onset; memory deficits, altered mental status or psychiatric symptoms, and ≥1 supportive feature (new focal objective CNS finding, N = 285; new-onset seizures, N = 283; supportive MRI findings, N = 251; or CSF pleocytosis, N = 160). Of 361 patients, AE subgroups were as follows: definite AE (N = 221, 61%, [87% AE-specific IgG positive]), probable seronegative AE (N = 18, 5%), Hashimoto encephalopathy (N = 20, 6%), or possible AE not otherwise categorizable (N = 102, 28%). The 221 patients with definite AE had limbic encephalitis (N = 127, 57%), anti-NMDA-R encephalitis (N = 32, 15%), ADEM (N = 8, 4%), or other AE-specific IgG defined (N = 54, 24%). The 3 most common definite AE-IgGs detected were as follows: LGI1 (76, 34%), NMDA-R (32, 16%), and high-titer GAD65 (23, 12%). The remaining 177 patients (33%) not meeting possible AE criteria had the following: seizures only (65, 12% of all 538 patients), brainstem encephalitis without supratentorial findings (55, 10%; none had Bickerstaff encephalitis), or other (57, 11%). Those 57 "others" lacked sufficient supportive clinical, radiologic, or CSF findings (N = 26), had insidious or initially episodic onset of otherwise typical disorders (N = 21), or had atypical syndromes without clearcut memory deficits, altered mental status, or psychiatric symptoms (N = 10). Fifteen of 57 were AE-specific IgG positive (26%). Among the remaining 42, evidence of other organ-specific autoimmunity (mostly thyroid) was encountered in 31 (74%, ≥1 coexisting autoimmune disease [21, 50%] or ≥1 non-AE-specific antibodies detected [23, 53%]), and all but 1 had an objective immunotherapy response (97%). The 2016 AE guidelines permit autoimmune causation assessment in subacute encephalopathy and are highly specific. Inclusion could be improved by incorporating AE-IgG-positive patients with isolated seizures or brainstem disorders. Some patients with atypical presentations but with findings supportive of autoimmunity may be immune therapy responsive.

Determination of Clinical, Electrophysiological, and Radiological Characteristics of Pediatric Autoimmune Encephalopathy

AbstractAutoimmune encephalopathy (AE) is a group of diseases with subacute onset, that represents a wide clinical spectrum, manifested by complex neuropsychiatric symptoms and signs. In this study, the data of 27 patients diagnosed and followed up in our clinic with the diagnosis of AE between 2011 and 2021 were evaluated retrospectively. Out of 27 patients, 6 were definite seropositive AE, 2 of them met the diagnostic criteria for limbic encephalitis, and the remaining 19 were probable AE. Nowadays, we see AEs with increasing frequency. While there is a generally established approach in the diagnosis and treatment of seropositive patients, there are still hesitations and diagnostic difficulties in seronegative AEs. In this study, clinical, radiological, and prognostic features of definite and probable AE patients diagnosed in a tertiary pediatric neurology clinic were documented. It is thought that pediatric neurologists have an important responsibility to increase awareness about AE in pediatricians. In the future, it is predicted that AE will be diagnosed more frequently with new antibodies and one has to differentiate it from viral encephalitis and neuropsychiatric syndromes and diseases.

Neuropsychiatric Manifestations of Thyroid Diseases.

Thyroid disorders are known to cause neuropsychiatric manifestations. Variousneuropsychiatric manifestations are depression, dementia, mania, and autoimmune Hashimoto encephalopathy. Numerous investigations carried out in the previous 50-60 years have been evaluated critically.The pathophysiology of neuropsychiatric symptoms of thyroid diseases is described in the current studyand its link with autoimmune Hashimoto encephalopathy is also discussed. Furthermore, this paper also describes the association between thyroid-stimulating hormones and cognitive impairment. Hypothyroidism is associated with depression and mania, and hyperthyroidism is linked with dementia and mania. The association between Graves' disease and various mental disorders such as depressive and anxiety disorders is also discussed. The aim of this study is to review the relationship between various neuropsychiatric disorders and thyroid diseases. A literature search from the PubMed database to find various neuropsychiatric manifestations of thyroid disorders in the adult population was conducted. According to the review of the studies, cognitive impairment can result from thyroid disease. It has not been possible to demonstrate how hyperthyroidism can hasten the process of developing dementia. However, subclinical hyperthyroidism, thyroid-stimulating hormone (TSH) levels below the normal range, and high free thyroxine (T4) levels all raise the risk of dementia in the elderly. Additionally, the potential mechanisms underlying this associationhave been examined. A quick summary of the research on mania as a clinical symptom of hypothyroidism and its likely causes and pathogenesis is also reviewed. There is no dearth of evidence that describes variousneuropsychiatric manifestation in thyroid disorders.

RARE CASE REPORT -AUTOIMMUNE LGI1 LIMBIC ENCEPHALITIS IN ELDERLY

Autoimmune encephalitis is one of the main causes of noninfectious encephalitis. Can be broadly classied into non-paraneoplastic, paraneoplastic and vasculitis associated encephalopathy. It can be triggered by tumors and infections. Autoimmune encephalitis presents with variety of clinical features such as acute onset behavioral changes, psychiatric symptoms, memory loss, movement disorders, dystonia, mutism and seizures. Neuronal antibodies are directed against cell surface Ag(CSAab) ,synaptic antigen (SyAab), intraneuronal Ag(INAab). Anti LG1 and CASPR2 encephalitis are usually non-neoplastic autoimmune encephalopathy where antibodies are directed against proteins associated with Voltage gated k channel. About 50% patients with anti-VGKC encephalitis do not present antibodies against LGI1 or CASPR-2. Anually 1 case is detected amongst 100000 patients. This is a case report of a patient presented to Geriatrics OPD and the series of evaluation which led to diagnosis and treatment outcome.

Anti-AMPA Receptor Autoantibodies Reduce Excitatory Currents in Rat Hippocampal Neurons.

The GluR3 subunit of α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptors (AMPARs) has been identified as a target for autoantibodies (Aabs) in autoimmune encephalopathy and other diseases. Recent studies have proposed mechanisms by which these Aabs act, but their exact role in neuronal excitability is yet to be established. Patient Aabs have been shown to bind to specific regions within the GluR3 subunit. GLUR3B peptides were designed based on described (ELISA) immunogenic epitopes for Aabs and an immunisation strategy was used to generate novel anti-AMPAR Aabs. Target-specific binding and specificity of affinity-purified anti-AMPAR Aabs was confirmed using enzyme-linked immunosorbent assay, immunocytochemistry and Western blot. Functional anti-AMPAR Aab effects were determined on excitatory postsynaptic currents (EPSCs) from primary hippocampal neurons using whole-cell patch-clamp electrophysiology. Acute (10 or 30 min) or longer-term (24 h) application of anti-AMPAR Aabs caused a significant reduction in the mean frequency of spontaneous and miniature EPSCs in hippocampal neurons. Our data demonstrate that anti-AMPAR Aabs targeting peptides linked to auto-immune diseases mediate inhibitory effects on neuronal excitability at the synaptic level, such effects may lead to disruption of the excitatory/inhibitory balance at a network level.