Voltage-gated Potassium Channel Antibodies Research Articles

B - 111 The Role of Education, and Advocacy in Repeat Neuropsychological Evaluations of a Spanish Speaking Woman with Anti-LG-1 Encephalitis.

Anti-leucine-rich glioma-inactivated 1 limbic encephalitis (LGI1-LE) is a rare diagnosis but the second most common autoimmune encephalitis. While it has a growing body of neuropsychological literature, there is limited awareness by the lay public about this condition. As with all complex neurological conditions, caregiver/family understanding of the disorder and engagement in treatment is important for optimal recovery and dyad wellbeing. We present the case of a caregiver and patient dyad with confirmed LGI1-LE/ Voltage-Gated Potassium Channel antibodies seen for repeat neuropsychological evaluations to demonstrate the importance of education, advocacy, and multidisciplinary involvement as part of the neuropsychological assessment process. Repeat neuropsychological evaluations of a 72-year-old Spanish-speaking woman with limited formal education and complex medical history, including past strokes and recent autoimmune encephalitis. Initial evaluation revealed marked behavioral and cognitive fluctuations/variability with familial frustration secondary to poor understanding by caregiver until neuropsychological feedback session. Repeat evaluation was delayed four weeks due to caregiver factors but demonstrated improvement in global cognition and overall functioning. Follow up, six months later, demonstrated significant cognitive decline and new motoric symptoms with further difficulty coordinating appointments by the caregiver. In addition to assistance with medical management, neuropsychological involvement led to connection to case management, home evaluation, concrete solutions for food insecurity, and cognitive evaluation for the caregiver. This case adds to LG1-LE literature and demonstrates the importance of neuropsychology not only for disease tracking/ management but also as an important tool for advocacy and patient/caregiver education, specifically in culturally and educationally diverse populations with complex medical conditions.

#4583 NEUROLOGICAL DISEASES TREATED WITH PLASMAPHERESIS PERFORMED BY NEPHROLOGISTS

Abstract Background and Aims Apheresis is an extracorporeal technique whose objective is to eliminate pathological elements considered to be responsible for a disease or its clinical manifestations. Plasmapheresis is part of the nephrology activity that will precise to be promoted within clinical practice. It is a therapeutic alternative for a large number of diseases, with certain neurological pathologies being the most benefited of its use. The purpose of this study is to describe the experience with plasmapheresis performed by nephrologists on patients with neurological diseases. Method Descriptive-retrospective study of neurological diseases treated with plasmapheresis in our nephologist section between the years 2008-2023. We analyzed demographic data, underlying disease, procedure, complications, and clinical response of the patients. Results A total number of 31 plasmapheresis procedures have been performed, of which 16 procedures have been performed in neurological diseases with a total of 92 sessions. The average age was 47 years, with 69% of the female sex predominance. The most frequently disease treated was Multiple Sclerosis with 31%, followed by Acute demyelinating polyneuropathy in the form of Guillain Barré with 25%, Myasthenia Gravis and Voltage-Gated Potassium Channel Antibody Related antiLGi-1, both with 13%. Treatment prior to the technique was corticosteroids with 75%, immunoglobulins with 56% and immunosuppressants with 13%. All sessions were performed using the transmembrane filtration technique with plasmaFlux® and the Fresenius mulitiFiltrate® equipment. The median number of sessions per patient was 6. The mean exchange volume was 2.9 l/patient/session. The replacement fluid used was albumin on 100% of patients and 4 patients required albumin plus fresh frozen plasma. 75 percent of the patients had a positive response with partial remission or stability of the disease and 88 percent had no recurrences. Patients’ neurological response to the therapy was the expected, and similar to the one reported in the medical literature. Conclusion In our experience, plasmapheresis is a safe and effective therapy in patients with neurological diseases that should be required as a therapeutic option. We, as nephrologists must be aware of this and promote the management of this technique by publishing the joint experience in order to broaden the level of evidence in clinical practice. The importance of coordination in early referral by other different medical specialties may obtain better results.

A Rare Case of Thymoma-Associated Idiopathic Inflammatory Myopathy and Myasthenia Gravis (P1-5.009)

<h3>Objective:</h3> To describe the phenotype of and to support further research into the etiology and appropriate therapeutic management of thymoma-associated myasthenia gravis (MG)-inflammatory myopathy (IM) overlap syndrome. <h3>Background:</h3> While rare, the combination of MG and idiopathic IM has been previously documented. The prevalence of thymoma in patients with both IM and MG (70%) is significantly higher than in those with MG alone (10%). It has been postulated that thymoma-related immunopathogenic mechanisms, including dysregulation of the immune checkpoint pathway, may increase the risk of idiopathic IM and MG. <h3>Design/Methods:</h3> A 47-year-old male with a history of thymoma complicated by recent tumor recurrence presented to our tertiary referral center with rapid deterioration in bulbar and appendicular motor strength and a presumed diagnosis of amyotrophic lateral sclerosis. Prednisone, pyridostigmine, and IVIG previously provided no relief. Further workup was undertaken to elucidate the true etiology of his symptoms. <h3>Results:</h3> Electromyography/nerve conduction study was unremarkable. CSF studies revealed a normal protein and cell count. Creatine kinase was elevated at 2578 units/L. MRI of his cervical spine was remarkable for inflammatory changes along the myofascial planes of the posterior paraspinal muscles, concerning for myositis. Neural autoantibody testing, albeit after he had received IVIG, revealed multiple positive findings including acetylcholine receptor (AChR) blocking and modulating, smooth muscle, F-Actin, fibrillarin, and voltage-gated potassium channel antibodies. High dose methylprednisolone and plasmapheresis were initiated with marked clinical improvement. He has since been maintained on rituximab. On follow-up testing, continued positive antibodies include AChR binding, AChR blocking, and elevated striated muscle antibody. <h3>Conclusions:</h3> When presented with a patient with a history of recurrent thymoma and weakness of unclear etiology, MG-IM overlap syndrome should be considered in the differential diagnosis. Further study into the mechanism and appropriate management of this autoimmune dysregulation syndrome should be undertaken. <b>Disclosure:</b> Dr. Schmoll has nothing to disclose. Dr. Rodenbeck has nothing to disclose.

A Sharp Rise in Autoimmune Encephalitis in the COVID-19 Era: A Case Series.

Autoimmune encephalitis was very rare prior to the current pandemic. A sharp rise in cases has been observed from March to August of 2022 in Los Angeles. Such an increase, especially with certain types of antibodies, may point toward the possibility of post-infectious autoimmune encephalitis. While review articles on autoimmune encephalitisduring this pandemic have been published, a sharp rise in one geographic area within a short period of time has not been documentedyet. To report an alarming increase in autoimmune encephalitis with mostly positive glutamic acid decarboxylase (GAD) and/or voltage-gated potassium channel (VGKC) antibodies over six months during 2022 in Downtown Los Angeles. This is an observational case series from one neurocritical care practice in Downtown Los Angeles. Autoimmune encephalitis antibody panels were sent to patients with altered mental status or neurologic deficits of unclear etiology from March to August of 2022. Of the 29 patients tested, 12 reports came back positive. Ten had positive GAD and/or VGKC antibodies, one had a positive myelin oligodendrocyte glycoprotein antibody, and one had a positive leucine-richglioma-inactivated 1 protein antibody; a 41% positive rate. This observation has important implications: (1) We may be entering an era of heightened autoimmune encephalitis. (2) These occurrences may be post-infectious in nature at this point of the pandemic. (3) Mostly GAD and VGKC antibodies have been identified (10 of them), which may point toward a new direction of research from a molecular mimicry standpoint. (4) To benefit patients, clinicians need to be aware of such disease manifestations and increase testing; resources must be increased to improve test availability and shorten turnaround time; and treatment, which is expansive, must be made widely available for these potentially reversible diseases.

Neuropsychiatric Manifestations of Autoimmune Encephalitis in a Tertiary Hospital: A Case Series and Current Perspectives.

Importance:Autoimmune encephalitis (AE) refers to a group of neuropsychiatric conditions associated with specific circulating autoantibodies directed against synaptic receptors, neuronal cell surface proteins, and intracellular targets. Increased recognition of these disorders is of value, as affected patients prominently display cognitive impairment, behavioral disturbances, and seizures requiring multidisciplinary teams, with early recognition often impacting prognosis.Observations: This case series is based on a retrospective record review of adult patients diagnosed with AE between January 1, 2010- January 1, 2020. Cases 1 and 2, demonstrating anti- N-methyl-d-aspartate receptor (NMDAR) encephalitis with initial manifestations of neurologic and psychiatric symptoms, correlate with the literature describing a higher prevalence of this condition in young women. Case 3, despite being seronegative, exhibited classic features of anti-NMDAR encephalitis. Case 4 demonstrates a classic presentation of anti-leucine-rich glioma-inactivated 1 (LGI1) encephalitis: a middle-aged male with psychosis, altered mentation, and epilepsy. Case 5 had a more indolent neuropsychiatric presentation with mild elevation of N-type voltage-gated potassium channel (VGKC) antibody. Case 6, with glutamic acid decarboxylase 65 (GAD65) antibody, was an elderly female with speech dysfunction and altered mentation, and case 7 was an elderly male with GAD65 antibody who had stiff-person syndrome, ataxia, cognitive decline, and thymoma.Conclusions: This retrospective case series describes the clinical details of 7 individuals with AE and overlapping neuropsychiatric symptoms. This series is limited in scope, with a small number of cases and observational findings, which prevents specific conclusions from being drawn. Despite this limitation, the present article explores the nuances of variable presentations of this disease to inform better interdisciplinary management and emphasize the gap areas that need rigorous research.

Pediatric Autoimmune Encephalitis in Sri Lanka: A Single-Center Experience over 7 Years

AbstractPediatric autoimmune encephalitis (AE) remains a diagnostic and therapeutic challenge in resource-poor settings. Minimizing delay in diagnosis and appropriate escalation of treatment will help reduce both the short- and long-term neurodisabilities. A retrospective observational study was performed on children consecutively diagnosed with possible AE and then prospectively followed up in a single tertiary care children's hospital in Sri Lanka. Serum and cerebrospinal fluid were tested for neuroglial surface-binding autoantibodies using cell-based assays in majority of these children. Twenty-five children (mean age 7.6 years, standard deviation = 4) were recruited. In these children, presenting symptom was psychiatric in 11 children (44%), seizures in 10 (40%), language regression in 2 (8%), and combination of psychosis and convulsions in 2 (8%). Psychiatric presentations were more common in older (&gt;6 years) compared with young children (p = 0.001), while neurological presentations were more common in children aged ≤6 years (p = 0.001). N-methyl-D-aspartate receptor (NMDAR) antibodies were detected in 9 (45%) and unspecified voltage-gated potassium channel antibodies in 1 (5%) of the 20 tested. All received intravenous steroids and immunoglobulins; 19 (76%) plasma exchange; 7 (29%) rituximab. Complete/substantial improvement at 3 months occurred in 64%. Pediatric Cerebral Performance Category score at last review was 1 (normal function for age) in 43%. Higher proportion of younger children required less intense therapy and had better recovery (56%). Death (8%), incomplete recovery (71%), and relapses (8%) were more in older children. Clinical presentation and disease outcomes were different in children aged &lt;6 years compared with older age group. NMDAR antibody encephalitis was the commonest AE syndrome identified in this cohort.

Current Nosology of Neural Autoantibody-Associated Dementia.

BackgroundThe detection of neural autoantibodies in patients with cognitive decline is an increasingly frequent phenomenon in memory clinics, and demanding as it does a specific diagnostic approach and therapeutic management, it deserves greater attention. It is this review’s aim to present the latest nosology of neural autoantibody-associated dementia.MethodsA specific literature research via PubMed was conducted to describe the nosology of neural autoantibody-associated dementia.ResultsAn autoimmune dementia comprises with an early onset, atypical clinical presentation and rapid progression in conjunction with neural antibodies, signs of inflammation in the cerebrospinal fluid, and a non-neurodegenerative pattern in neuroimaging. An autoimmune dementia is probably present if the patient responds to immunotherapy. Atypical dementia involving neural autoantibodies with mostly N-methyl-D-aspartate receptor antibodies might not fulfill all the autoimmune-dementia criteria, thus it may constitute an independent disease entity. Finally, a neurodegenerative dementia such as the frontotemporal type also coincides with neural autoantibodies such as the subunit ionotropic glutamate receptors 3 of amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor antibodies, dementia with Lewy bodies with myelin oligodendrocytic protein, myelin basic protein antibodies, or Creutzfeldt-Jakob disease with Zic4 or voltage gated potassium channel antibodies. These dementia entities may well overlap in their clinical features and biomarkers, i.e., their neural autoantibodies or neuroimaging patterns.ConclusionThere are three main forms of neural autoantibody-associated dementia we can distinguish that might also share certain features in their clinical and laboratory presentation. More research is urgently necessary to improve the diagnosis and therapy of these patients, as the progression of their dementia might thus be improved or even reversed.

Voltage-gated potassium channel blanket testing in first-episode psychosis: Diagnostic nihilism?

Voltage-gated potassium channel antibodies are implicated in limbic encephalitis and currently included in first-episode psychosis organic screening guidelines. Individuals with high-positive voltage-gated potassium channel titres most commonly present with neurological symptoms as well as sleep, cognitive, behaviour, psychosis and mood disturbance. The significance of low-positive voltage-gated potassium channel antibody titres in psychiatric patients is unclear and has not been previously examined. We aim to describe a statewide cohort of psychiatric patients with low- and high-positive voltage-gated potassium channel titres and explore if this finding influenced clinical management and patient outcomes. A retrospective review of all voltage-gated potassium channel antibodies testing performed in public psychiatric services in Queensland, Australia, with comparison of the clinical presentation and long-term outcomes of low- and high-positive voltage-gated potassium channel titre cases. Specific antigen targets (leucine-rich glioma-inactivated protein 1 and contactin-associated protein 2 antibodies) were also assessed. The overall prevalence of voltage-gated potassium channel antibody positivity in Queensland, public, psychiatric service testing was 0.3% (14/4098), with 12 cases of low-positive voltage-gated potassium channel titre, 2 cases of high-positive (leucine-rich glioma-inactivated protein 1 antibody positive) cases and a voltage-gated potassium channel negative contactin-associated protein 2 antibody positive case. No low-positive case developed neurological abnormalities or had abnormal paraclinical investigations. In comparison, both high-positive voltage-gated potassium channel/leucine-rich glioma-inactivated protein 1 cases and the contactin-associated protein 2 antibody positive case rapidly developed neurological symptoms, had abnormal paraclinical testing and improved only with immunotherapy. There was no later development of encephalitic symptoms in the low-positive cases over an average of 1067 days follow-up. Voltage-gated potassium channel antibody-associated limbic encephalitis was rare, and always associated with high antibody titres. Low-positive titres were not associated with the development of encephalitis over a long period of follow-up. The value of universal voltage-gated potassium channel antibody screening is unclear, and further prospective studies in first-episode psychosis populations are required.

P.707 Voltage-gated potassium channel antibody–associated encephalitis presenting as suicidal behaviour: Case report

P.707 Voltage-gated potassium channel antibody–associated encephalitis presenting as suicidal behaviour: Case report

Autoimmune encephalitis as an increasingly recognised cause of non-convulsive status epilepticus: A retrospective, multicentre evaluation of patient characteristics and electroencephalography (EEG) results

PurposeStatus epilepticus (SE) is a severe condition of unrelenting seizures requiring urgent identification and treatment. SE may be unprovoked, occurring in someone with epilepsy, or may be provoked by acute intracranial disease or metabolic derangement. Increasingly encephalitis, particularly autoimmune types, is reported to cause refractory seizures. Whilst convulsive SE is readily identified, non-convulsive SE (NCSE) can be difficult to identify clinically, and electroencephalography (EEG) is required. Therefore, it is critical to identify the key clinical features associated with NCSE on EEG to inform future use of EEG. MethodsWe conducted a multicentre, retrospective analysis of EEG requests from four general and one specialist neurology hospital in the Northwest of England (2015–2018). Cases were identified from EEG requests for patients with suspected NCSE or other indications such as encephalopathy. We compared demographic and clinical characteristics between EEG-confirmed cases of NCSE and a randomly selected sample of negative controls. Results358 EEGs were reviewed, and 8 positive cases of NCSE were identified. Epilepsy was identified as the aetiology in 2 of these cases, and autoimmune encephalitis another 2 cases (one patient with N-methyl-d-aspartate receptor antibodies and another with voltage gated potassium channel antibodies). Previous alcohol excess (p = 0.005) and subtle motor signs (p = 0.047) on examination were observed more frequently in patients with NCSE compared to controls. ConclusionPhysicians should have a low threshold for urgent EEG in patients with suspected or previous encephalitis, especially if autoimmunity is suspected or subtle motor signs are present.

Autoimmune movement disorders

Autoimmune movement disorders (AMD) are increasingly recognized and include a wide spectrum of hyperkinetic, hypokinetic, sleep related and ataxic presentations. These range from chorea, tics, dystonic jerks, myoclonus, and neuromyotonia to hypo and akinetic rigid syndromes. The latter varieties encompass parkinsonism, stiff person syndrome (SPS) and progressive encephalomyelitis with rigidity and myoclonus (PERM). Ataxic syndromes include episodic ataxia associated with CASPR2 and post Herpes zoster cerebellitis and other rare paraneoplastic syndromes. The AMD have a broad spectrum of clinical phenotypes which are increasingly being recognized. They may present as an isolated movement disorder or as part of a wider clinical syndrome usually with encephalitic illnesses. They may follow infections, parainfectious, as in Paediatric Autoimmune Neuropsychiatric Disorders Associated with Streptococcal infection (PANDAS) and Sydenham chorea, or associate with an underlying occult malignancy (Leucine rich Glioma1 inactivated, Voltage Gated Potassium Channel Antibodies) associated Limbic encephalitis with brachio facial dystonic jerks and seizures linked with ovarian and testicular teratomas. In many instances no underlying cause is found, and ongoing research is revealing new markers and aetiologies for what was labelled idiopathic in the past. The autoimmune basis of these disorders is shown by the presence of antibodies or specific groups of CD8 cytotoxic cells mostly detected in the serum, cerebrospinal fluid and other tissues. Furthermore, their response to immunotherapies supports this notion and are the mainstay of current treatments. The latter include corticosteroids, therapeutic plasma exchange (TPE, PLEX), target specific biologicals (specific monoclonal antibodies mostly against B cells markers such as Ritixumab, anti CD20). Symptomatic therapies for the movement themselves and the associated presentation such as seizures, sleep and mood disturbances. The target antigens are diverse as mentioned above. They usually present subacutely and may deteriorate rapidly or follow a relapsing remitting course. Early positive recognition of these disorders is crucial as they are potentially treatable and in some case curable. This will avoid or reduce morbidity and improve long term outcomes.

343. Compliance to Standard of Care in the Diagnosis and Management of Suspected Encephalitis

BackgroundEncephalitis is associated with death or neurological disability in 50% with the majority of the patients having an unknown etiology. The IDSA guidelines on the management of encephalitis were published in August 2008 but compliance with their recommendations is unknown.MethodsA retrospective study was conducted at 17 hospitals in the Great Houston area from August 2008 through July 2015. All cases met the definition for possible or probable encephalitis as per the international encephalitis consortium recommendations. Data extraction from the medical record was done utilizing a standardized form. Extracted data included information on demographics, clinical presentation, diagnostic testing, and treatment.ResultsA total of 264 adults and children with encephalitis were enrolled. Compliance with IDSA guidelines was excellent for obtaining an MRI of the brain (92%), an electroencephalogram (92%) and obtaining a cerebrospinal fluid (CSF) bacterial culture (86.7%). Empirical antibiotic and acyclovir therapy was started in about 65% of patient with a CSF HSV PCR being done in 78.8%. A CSF VZV PCR was only done in 31.4% while an arboviral serology was done in 57.1% of patients. Compliance was lowest in ordering a CSF N-methyl-d-aspartate receptor antibody (NMDA) and voltage-gated potassium channel (VGKC) antibodies (19.3% and 5.6%, respectively). The tests with the highest yield were a CSF NMDA receptor antibody (39.2%) and a CSF VZV PCR (13.2%).ConclusionDiagnostic evaluation of patients with encephalitis and compliance with IDSA guidelines is suboptimal.Disclosures All authors: No reported disclosures.

GP.03 Immune deficiencies/dysregulations underpinning childhood limbic encephalitis: a case series and literature review

Background: Limbic encephalitis (LE) is a rare autoimmune syndrome affecting limbic system structures and causing variety of manifestations including memory changes, temporal epilepsies, and psychiatric symptoms. It is a rare disease in children but with a well-recognizable combination of clinical, neuroimaging and/or histological signature. Beyond the association with anti-neuronal auto-antibodies, no clear immune system phenotype has been associated with limbic encephalitis. Our aim is to characterize the clinical and paraclinical features of non-paraneoplasic limbic encephalitis and to correlate them with potential underlying immune deficiencies. Methods: Retrospective case series of seven patients with limbic encephalitis recruited at the Montreal Children’s Hospital (MCH) with a focus on the immune- and neuro-phenotypes, including anti-neuronal antibodies, lymphocyte sub-typing, key markers of immunoglobulin and complement systems. Literature review showed 77 cases of non-paraneoplastic non-NMDA limbic encephalitis. Results: Symptoms included temporal epilepsy (n=5), psychiatric symptoms such as ADHD or autistic symptoms (n=2), and memory changes (n=3). One patient was positive for both voltage gated potassium channel antibodies (VGKC) and anti-thyroid peroxidase antibodies (TPO) and two were positive only for anti TPO antibodies. One patient showed low CD19, and immunoglobulins. Three patients showed chronic low CD56 cell count. Conclusions: The study is still ongoing, but at least 3 patients already display some traits of immune dysregulation.

The prevalence and treatment outcomes of antineuronal antibody-positive patients admitted with first episode of psychosis.

Antineuronal antibodies are associated with psychosis, although their clinical significance in first episode of psychosis (FEP) is undetermined. To examine all patients admitted for treatment of FEP for antineuronal antibodies and describe clinical presentations and treatment outcomes in those who were antibody positive. Individuals admitted for FEP to six mental health units in Queensland, Australia, were prospectively tested for serum antineuronal antibodies. Antibody-positive patients were referred for neurological and immunological assessment and therapy. Of 113 consenting participants, six had antineuronal antibodies (anti-N-methyl-D-aspartate receptor antibodies [n = 4], voltage-gated potassium channel antibodies [n = 1] and antibodies against uncharacterised antigen [n = 1]). Five received immunotherapy, which prompted resolution of psychosis in four. A small subgroup of patients admitted to hospital with FEP have antineuronal antibodies detectable in serum and are responsive to immunotherapy. Early diagnosis and treatment is critical to optimise recovery. None.

Voltage-gated Potassium Channel Antibody Autoimmune Encephalopathy Presenting With Isolated Psychosis in an Adolescent.

Antibody-mediated encephalopathies associated with serum or cerebrospinal fluid antibodies directed against neuronal structures may present with a multitude of neuropsychiatric syndromes. Although some of the antibody-driven conditions are now well recognized in adults (eg, N-methyl-D-aspartate receptor antibody encephalitis), the spectrum of neuropsychiatric manifestations in the pediatric population is less clear. Psychosis, confusion, catatonia, and additional behavioral changes, along with seizures, encephalopathy, and movement disorders, may be initial manifestations or concurrent features in all age groups. Psychosis, when present, is often part of a broader spectrum of neurological and neuropsychiatric symptoms for which the diagnosis of autoimmune encephalitis is considered. The authors present the case of an adolescent with an acute and isolated psychotic presentation of voltage-gated potassium channel antibody encephalitis, further expanding the phenotypic spectrum of this specific antibody-mediated disease and raising the possibility that specific immune-mediated processes may define a biological subgroup of psychoses.

Sensory Polyneuropathies.

This article describes the methods of diagnosis and management of the sensory-predominant polyneuropathies. To simplify the approach to this category of patients, sensory-predominant polyneuropathies are divided broadly into either small fiber (or pain-predominant) neuropathies and large fiber (or ataxia-predominant) neuropathies, of which the sensory neuronopathies (dorsal root ganglionopathies) are highlighted. Physicians can now easily perform skin biopsies in their offices, allowing access to the gold standard pathologic diagnostic tool for small fiber neuropathies. Additional diagnostic techniques, such as corneal confocal microscopy, are emerging. Recently, small fiber neuropathies have been associated with a broader spectrum of diseases, including fibromyalgia, sodium channel mutations, and voltage-gated potassium channel antibody autoimmune disease. Despite advances in diagnosing small fiber neuropathies and sensory neuronopathies, many of these neuropathies remain refractory to treatment. In select cases, early identification and treatment may result in better outcomes. "Idiopathic" should be a diagnosis of exclusion and a thorough investigation for treatable causes pursued.

The value of LGI1, Caspr2 and voltage-gated potassium channel antibodies in encephalitis.

The discovery, in 2010, of autoantibodies against the extracellular proteins LGI1 and Caspr2 facilitated a change of view regarding the clinical importance of voltage-gated potassium channel (VGKC) antibodies. Currently, these antibodies are all classified as VGKC-complex antibodies, and are commonly considered to have a similar clinical value. However, studies from the past few years show that the immune responses mediated by these antibodies have differing clinical relevance. Here, we review the clinical importance of these immune responses in three settings: patients with anti-LGI1 antibodies, patients with anti-Caspr2 antibodies, and patients with antibodies against the VGKC complex that lack LGI1 and Caspr2 specificity. Antibodies against LGI1 and Caspr2 are associated with different but well-defined syndromes, whereas the clinical importance of VGKC-complex antibodies without LGI1 and Caspr2 specificity is questionable. We describe each of these syndromes, discuss the function of the target antigens and review the limited paediatric literature on the topic. The findings emphasize the importance of defining these disorders according to the molecular identity of the targets (LGI1 or Caspr2), and caution against the use of VGKC-complex antibodies for the diagnosis and treatment of patients without further definition of the antigen.

Autoimmune Voltage-Gated Potassium Channelopathy Presenting With Catecholamine Excess

BackgroundAutoimmune voltage-gated potassium channelopathies have been associated with a range of neurological presenting symptoms, including central, peripheral, and autonomic dysfunction. Patient DescriptionWe describe a 12-year-old boy who presented with nine months of pain, anxiety, and 30-pound weight loss. He was admitted for failure to thrive, then noted to be persistently hypertensive and tachycardic. Plasma metanephrines and urine metanephrines and catecholamines were elevated. Extensive investigation for causes of elevated catecholamines, such as hyperthyroidism or catecholamine-secreting tumor, was negative. A paraneoplastic panel was positive for voltage-gated potassium channel antibodies. Treatment with intravenous immunoglobulin and pulse methylprednisolone led to complete resolution of symptoms, weight gain, and normalization of vital signs and plasma metanephrines. ConclusionVoltage-gated potassium channel antibodies should be considered as part of the differential in patients presenting with elevated metanephrine and catecholamine secretion.

Voltage gated potassium channel antibody(VGKC)-associated encephalopathy and psychiatric symptoms (case report)

Introduction and ObjectivesThe limbic system is primarily responsible for modulating behaviour, emotions and neuro-endocrine functions. Limbic encephalopathy involves this part of the brain and is characterised by the acute or sub-acute onset of seizures, recent memory loss, confusion and psychiatric symptoms. Here we describe an unusual presentation of a well-functioning elderly man, who presented with sudden onset of confusion, cognitive impairment, treatment resistant hyponatremia, seizures and psychiatric symptoms.Methods (Presentation)This 79 year old gentleman, previously well and independent was admitted to the acute hospital with a 3 week history of sudden onset of confusion, odd behaviour and weight loss. On admission he was hyponatremic (Na-118), developed treatment resistant seizures and progressive cognitive impairment. He was referred to the Liaison Psychiatry team with increasing paranoia, agitation and persecutory delusions.ResultsMRI and CT brain remained normal. Lumbar puncture revealed a positive VGKC antibody and his blood titres for VGKC was more than 3000. His hyponatremia and seizures remained chronic, but improved with plasmapheresis, oral corticosteroids and cyclophosphamide. He was commenced on aripiprazole for psychiatric symptoms, but was transferred to the acute psychiatric unit after being detained under section 2 of the MHA due to risks of aggression and absconsion.ConclusionsPsychiatric symptoms related to this form of encephalitis have not been emphasised in literature. His aggression improved over time on aripiprazole, but was transferred to a residential care home setting due to persisting cognitive deficits and social care needs This case highlights the importance of recognising multimorbidity, joint working and more research required in the area.Disclosure of interestThe authors have not supplied their declaration of competing interest.

MOG antibody-positive, benign, unilateral, cerebral cortical encephalitis with epilepsy.

Objective:To describe the features of adult patients with benign, unilateral cerebral cortical encephalitis positive for the myelin oligodendrocyte glycoprotein (MOG) antibody.Methods:In this retrospective, cross-sectional study, after we encountered an index case of MOG antibody–positive unilateral cortical encephalitis with epileptic seizure, we tested for MOG antibody using our in-house, cell-based assay in a cohort of 24 consecutive adult patients with steroid-responsive encephalitis of unknown etiology seen at Tohoku University Hospital (2008–2014). We then analyzed the findings in MOG antibody–positive cases.Results:Three more patients, as well as the index case, were MOG antibody–positive, and all were adult men (median age 37 years, range 23–39 years). The main symptom was generalized epileptic seizure with or without abnormal behavior or consciousness disturbance. Two patients also developed unilateral benign optic neuritis (before or after seizure). In all patients, brain MRI demonstrated unilateral cerebral cortical fluid-attenuated inversion recovery hyperintense lesions, which were swollen and corresponded to hyperperfusion on SPECT. CSF studies showed moderate mononuclear pleocytosis with some polymorphonuclear cells and mildly elevated total protein levels, but myelin basic protein was not elevated. A screening of encephalitis-associated autoantibodies, including aquaporin-4, glutamate receptor, and voltage-gated potassium channel antibodies, was negative. All patients received antiepilepsy drugs and fully recovered after high-dose methylprednisolone, and the unilateral cortical MRI lesions subsequently disappeared. No patient experienced relapse.Conclusions:These MOG antibody–positive cases represent unique benign unilateral cortical encephalitis with epileptic seizure. The pathology may be autoimmune, although the findings differ from MOG antibody–associated demyelination and Rasmussen and other known immune-mediated encephalitides.