Anti-voltage Gated Potassium Channel Research Articles

Anti-voltage gated potassium channel antibodies (VGKC) – an audit

Anti-voltage gated potassium channel antibodies (VGKC) – an audit

75.1 AUTOIMMUNE ENCEPHALITIS: A CLINICAL PRACTICE OVERVIEW

In this portion of our broader presentation, we will provide a clinical overview of autoantibody-mediated brain diseases in children and adolescents, including autoimmune encephalitis (AE). This clinical overview will include a summarized review of the current literature describing the neurobiology, presentation, and treatment of the most common antibody-mediated autoimmune brain diseases affecting children and adolescents, including anti–N-methyl-D-aspartate receptor (anti-NMDAR) AE, anti–glutamic acid decarboxylase (anti-GAD65) AE, anti–voltage-gated potassium channel complex (anti-VGKC) AE, and anti–myelin oligodendrocyte glycoprotein (MOG)-associated AE. We will review the most common clinical presentations of these disorders with an emphasis on the symptoms of psychosis, delirium, and catatonia seen in children and adolescents with AE. Audience members will gain an understanding of the similarities and differences in the neurobiology, pathogenesis, and presentation of the most commonly diagnosed antibody-mediated autoimmune brain diseases affecting children and adolescents. The antineuronal autoantibodies implicated in AE in the pediatric population vary in their mechanisms of neurobiology, pathogenesis, and clinical presentation. It is essential for child and adolescent psychiatrists to understand the importance of testing for all known autoantibodies when evaluating patients with clinical presentations suspicious for AE and other antibody-mediated autoimmune brain diseases.

The Rare Case of Anti-VGKC Limbic Encephalitis Secondary to High-Grade Glioma

AbstractParaneoplastic limbic encephalitis secondary to a glial tumor is rare, and limited reports on this occurrence have been made in the pediatric population. This case involves a 13-year-old female patient with anti-voltage gated potassium channel (anti-VGKC) limbic encephalitis secondary to a high-grade glioma (HGG) in the suprasellar region. HHGs, associated with anti-VGKC antibodies, are a rare occurrence. This case highlights the need for the inclusion of glial neoplasms in the differential diagnosis for patients presenting with symptoms associated with paraneoplastic encephalitis.

Paraneoplastic Encephalopathy in a Patient With Metastatic Lung Cancer: A Case Study

Paraneoplastic Encephalopathy in a Patient With Metastatic Lung Cancer: A Case Study

A Case of Sensory Ataxia and Cardiac Hypertrophy Associated with Anti-Voltage Gated Potassium Channel (VGKC) Autoantibodies. (P2.208)

A Case of Sensory Ataxia and Cardiac Hypertrophy Associated with Anti-Voltage Gated Potassium Channel (VGKC) Autoantibodies. (P2.208)

Etiological associations and outcome predictors of acute electroencephalography in childhood encephalitis.

To examine EEG features in a retrospective 13-year cohort of children with encephalitis. 354 EEGs from 119 patients during their admission were rated blind using a proforma with demonstrated inter-rater reliability (mean k=0.78). Patients belonged to 12 etiological groups that could be grouped into infectious and infection-associated (n=47), immune-mediated (n=36) and unknown (n=33). EEG features were analyzed between groups and for risk of abnormal Liverpool Outcome Score and drug resistant epilepsy (DRE) at last follow up. 86% children had an abnormal first EEG and 89% had at least one abnormal EEG. 55% had an abnormal outcome, and 13% had DRE after median follow-up of 7.3years (2.0-15.8years). Reactive background on first EEGs (9/11, p=0.04) and extreme spindles (4/11, p<0.001) distinguished patients with anti-N-Methyl-d-Aspartate Receptor encephalitis. Non-reactive EEG background (48% first EEGs) predicted abnormal outcome (OR 3.8, p<0.001). A shifting focal seizure pattern, seen in FIRES (4/5), anti-voltage gated potassium channel (2/3), Mycoplasma (1/10), other viral (1/10) and other unknown (1/28) encephalitis, was most predictive of DRE after multivariable analysis (OR 11.9, p<0.001). Non-reactive EEG background and the presence of shifting focal seizures resembling migrating partial seizures of infancy are predictors of abnormal outcome and DRE respectively in childhood encephalitis. EEG is a sensitive but non-discriminatory marker of childhood encephalitis. We highlight the EEG features that predict abnormal outcome and DRE.

Autoantibody pain.

As autoantibodies bind to target tissues, Fc-region dependent inflammation can induce pain via mediators exciting nociceptors. But recently another possibility has emerged, where autoantibody binding to nociceptors can directly cause pain, without inflammation. This is thought to occur as a result of Fab-region mediated modification of nerve transduction, transmission, or neuropeptide release. In three conditions, complex regional pain syndrome, anti-voltage gated potassium channel complex autoimmunity, and chronic fatigue syndrome, all associated with no or only little inflammation, initial laboratory-, and clinical trial-results have suggested a potential role for autoantibody-mediated mechanisms. More research assessing the pathogenic roles of autoantibodies in these and other chronic pain conditions is required. The concept of autoantibody-mediated pain offers hope for the development of novel therapies for currently intractable pains.

Morvan Syndrome: A Case Report With Patient Narrative and Video.

A 74-year-old gentleman was admitted to the regional neurosciences center with encephalopathy, myokymia, and dysautonomia. Chest imaging had previously identified an incidental mass in the anterior mediastinum, consistent with a primary thymic tumor. Antivoltage-gated potassium channel (anti-VGKC) antibodies were positive (titer 1273 pmol/L) and he was hypokalemic. Electromyogram and nerve conduction studies were in keeping with peripheral nerve hyperexcitability syndrome, and an electroencephalogram was consistent with encephalopathy. A diagnosis of Morvan syndrome was made, for which he was initially treated with high-dose steroids, followed by a 5-day course of intravenous immunoglobulin (IVIG) therapy. He also underwent thymectomy, followed by a postexcision flare of his symptoms requiring intensive care management. Further steroids, plasmapheresis, and IVIG achieved stabilization of his clinical condition, enabling transfer for inpatient neurorehabilitation. He was commenced on azathioprine and a prolonged oral steroid taper. A subsequent presumed incipient relapse responded well to further IVIG treatment. This case report documents a thymoma-associated presentation of anti-VGKC-positive Morvan syndrome supplemented by patient and carer narrative and video, both of which provide valuable further insights into this rare disorder. There are a limited number of publications surrounding this rare condition available in the English literature. This, combined with the heterogenous presentation, association with underlying malignancy, response to treatment, and prognosis, provides a diagnostic challenge. However, the association with anti-VGKC antibody-associated complexes and 2 recent case series have provided some scope for both accurate diagnosis and management.

Acquired and genetic channelopathies: In vivo assessment of axonal excitability

Neuronal or axonal ion channel function can be impaired or altered in a number of disorders, such as acquired (autoantibody-mediated, toxic, and metabolic) and genetic channelopathies, and even neurodegenerative (motor neuron disease) or inflammatory diseases (multiple sclerosis, immune-mediated neuropathies). When specific channels are affected, axonal/neuronal excitability primarily alters according to original function of the corresponding channels. Separately, in the 1990s, axonal excitability testing was developed to assess ion channel function, membrane potential, and passive membrane properties non-invasively in human subjects. Using this technique, numerous papers on altered axonal excitability in a variety of disorders have been published since 2000. In a recent issue of Experimental Neurology, Park et al. demonstrated changes in peripheral axonal excitability in limbic encephalitis and acquired neuromyotonia with anti-voltage gated potassium channel antibodies. Unexpectedly, the results were not consistent with those caused by simple potassium channel blockade, suggesting that multiple other factors contribute to altered axonal excitability. In contrast it was reported that patients with episodic ataxia type 1 (genetic channelopathy with mutation of Kv1.1 channel gene) show prominent excitability changes exactly compatible with fast potassium channel blockade. This commentary aims to highlight findings of this study in a broader context, and provides possible explanations for the discrepancy of patterns of axonal excitability changes in acquired and genetic potassium channelopathies.

Two different presentations, one diagnosis

Acute confusion and hyponatraemia are common presentations in acute medicine. We report two cases of anti-voltage gated potassium channel (VGKC) antibody-related limbic encephalitis highlighting the variable presentation of this condition. Both patients were thoroughly investigated with MRI scan of brain, lumbar puncture, EEG as well as infective and autoimmune screens for encephalitis. Anti-VGKC antibodies were positive for both patients and prompt treatment with immunotherapy yielded good recovery. Patients presenting with confusion and seizures who have no demonstrable infectious or metabolic cause should have investigation for an autoimmune cause expedited. In addition, psychiatric presentations with atypical features such as drowsiness should prompt similar investigations. The outcome of anti-VGKCrelated limbic encephalitis is improved with early treatment employing steroids or immunotherapy.

Mitochondrial encephalomyopathy with lactic acidosis and stroke-like episodes (MELAS) in the older adult

A 70-year-old woman presented to the hospital's general physicians with a 3-week exacerbation of pre-existing migrainous headache, speech and behavioural change. There was a 20-year history of slowly progressive bilateral...

著明な筋痙攣・線維束性収縮をともない抗voltage gated potassium channel（VGKC）複合体抗体が高値であった筋萎縮性側索硬化症の1剖検例

The patient was a 55-year-old male who had prominent fasciculation and muscle cramps. Muscle weakness and atrophy of the trunk, respiratory system, and extremities gradually progressed. On the basis of these features, we diagnosed this patient as having amyotrophic lateral sclerosis (ALS), however, the upper motor neuron signs were not significant. Following the detection of the anti-voltage gated potassium channel (VGKC) complex antibody at 907.5 pM (normal < 100 pM) and repetitive discharge in a nerve conduction study, immunotherapy with intravenous immunoglobulin, methylprednisolone (mPSL), double filtration plasmapheresis (DFPP), ciclosporin, and rituximab was introduced. mPSL and DFPP showed only tentative effectiveness for fasciculation and muscle cramps, respectively. Thereafter, muscle weakness progressed. The patient died of type II respiratory failure at the age of 57 years, about 2 years after the onset of the disease. At autopsy, a histopathological diagnosis of ALS with lower-motor-predominant degeneration was made. Characteristic cellular features, including Bunina bodies in the remaining lower motor neurons and phosphorylated TAR DNA-binding protein 43-kDa (pTDP-43)-immunopositive inclusions in both upper and lower motor neuron systems, were evident. At present, an immunological role of the anti-VGKC complex antibody in the development of cramp-fasciculation syndrome has been speculated. In this ALS patient, the antibodies might be associated with pathomechanisms underlying the characteristic symptoms.

ANTI GLUTAMIC ACID DECARBOXYLASE ANTIBODY MEDIATED ENCEPHALOPATHY WHILE ON ETANERCEPT IN A PATIENT WITH MULTIPLE AUTOIMMUNE DISEASES

A 39 year old lady presented with an altered mental state and unsteadiness of gait. She had a history of juvenile idiopathic arthritis, autoimmune thyroiditis and alopecia, protein S deficiency...

Voltage-gated potassium channel complex antibodies in Creutzfeldt-Jakob disease

Clinical presentations of Creutzfeldt-Jakob disease (CJD) can be mimicked by those of immune-mediated encephalopathies, including limbic encephalitis with anti-voltagegated potassium channel (VGKC) complex antibodies [1, 2]. To date, anti-VGKC complex antibodies have been reported to be negative in CJD [1], thereby regarded as important to differentiate non-CJD dementia from CJD [3]. Here we report a patient with definite CJD who had serum anti-VGKC complex antibodies. A 60-year-old seaman acutely presented with blurred vision, disturbance in depth perception and light discrimination, difficulty recalling Chinese characters, and right-left disorientation. An ophthalmologist found no abnormality in his eyes. Two months later, he underwent a brain magnetic resonance imaging including diffusionweighted imaging, which showed hyperintensity signals in the bilateral occipital and parietal cortices. Neurologically, there were object agnosia, left hemineglect, dressing apraxia, Gerstmann syndrome, ideomotor apraxia, and instant memory disturbance. He also developed visual hallucinations such as flaming fire, and got agitated. Three months after onset, he got confused after taking one tablet of zolpidem and was admitted to a psychiatric department. Neurological examination on admission demonstrated the following findings: fluctuating levels of consciousness, difficulty in word recall, extinction; visual disturbance, poor pursuit eye movement, mild dysarthria; increased muscle tonus and myoclonus predominantly in the left; Myerson sign, snout reflex, increased jaw jerk and deep tendon reflexes predominantly in the left, bilateral Babinski and Chaddock signs; and he was bedridden. Serum antinuclear, anti-thyroid peroxidase, anti-thyroglobulin antibodies were negative and sodium levels were normal. No malignant tumors were found. Cell count was 2/mm, protein level was 27 mg/dl, 14-3-3 protein was positive, and total tau protein level was 3,420 pg/ml (cut-off value, 1,300 pg/ml) in the cerebrospinal fluid. Initial electroencephalography revealed slow waves, and periodic sharp wave complexes were present 23 weeks after onset. The analysis of PRNP revealed a substitution of methionine to arginine at codon 232. He received no immunotherapy. He died 8.5 months after onset and underwent necropsy of the left parietotemporal lobe. Neuropathological examination revealed neuronal loss, spongiform change, gemistocytic astrocytosis (Fig. 1a), and synaptic deposition of PrP (Fig. 1b) in the cerebral cortex, confirming the diagnosis of definite CJD. Western-blot analysis showed type 1 PrP. The titer of anti-VGKC complex antibodies, measured with radioimmunoassay using rabbit brain homogenates and K. Fujita (&) Y. Izumi R. Kaji Department of Clinical Neuroscience, The University of Tokushima Graduate School, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan e-mail: kof@clin.med.tokushima-u.ac.jp

067 Keys and locks

This case demonstrates two uncommon conditions presenting in a single patient. A 47-year-old male with a history since childhood of generalised tonic clonic seizures, well controlled, not on anti epileptic...

Acquired neuromyotonia following upper respiratory tract infection: a case report

We present a 37-year-old male subject who presented with burning sensations in his hands and feet with generalised twitching of his limbs, trunk and face. His symptoms developed 2 weeks after an upper respiratory tract infection. There was associated facial flushing and disturbed night sleep but no memory impairment or generalised sweating. Examination showed generalised myokymia and fasciculations and electromyography revealed widespread continuous semi-rhythmic doublets and triplets of low frequency with interspersed silent periods. Anti voltage gated potassium channel antibodies, antinuclear antibodies, anti-acetylcholine receptor antibodies and the anti-neuronal antibodies anti Hu, anti Yo and anti Ri were all negative. His symptoms improved slightly on lamotrigine and amitriptyline.

FC29.1 Anti-voltage gated potassium channel (VGKC) antibodies associated limbic encephalitis in Japan: Clinical presentation and patch-clamp study

FC29.1 Anti-voltage gated potassium channel (VGKC) antibodies associated limbic encephalitis in Japan: Clinical presentation and patch-clamp study

Strength‐duration properties of peripheral nerve in acquired neuromyotonia

The strength-duration time constant (SDTC) of a myelinated axon is a property of the nodal membrane and is sensitive to changes in membrane potential. Strength-duration time constants for motor axons and cutaneous afferents of the median nerve were measured in 9 patients with acquired neuromyotonia (NMT), a condition of peripheral nerve hyperexcitability, and 15 control patients. Mean motor axon time constants were significantly prolonged (344 ± 100 μs) in patients compared to healthy controls (264 ± 34 μs; P = 0.038), but sensory axon time constants were not significantly different. Motor axon time constants were longer than sensory axon time constants in 4 of the patients with neuromyotonia, suggesting that the nodal membrane was depolarized by an ectopic focus at the site of nerve stimulation at the wrist, ionic conductances were altered at the node, or that the size of the node was increased, possibly as a result of immune-mediated damage. The anti–voltage-gated potassium channel antibodies thought to generate peripheral nerve hyperexcitability in acquired neuromyotonia may be indirectly responsible for changes in motor axon nodal membrane properties. © 1999 John Wiley & Sons, Inc. Muscle Nerve 22: 823–830,1999

Strength-duration properties of peripheral nerve in acquired neuromyotonia.

The strength-duration time constant (SDTC) of a myelinated axon is a property of the nodal membrane and is sensitive to changes in membrane potential. Strength-duration time constants for motor axons and cutaneous afferents of the median nerve were measured in 9 patients with acquired neuromyotonia (NMT), a condition of peripheral nerve hyperexcitability, and 15 control patients. Mean motor axon time constants were significantly prolonged (344 +/- 100 micros) in patients compared to healthy controls (264 +/- 34 micros; P = 0.038), but sensory axon time constants were not significantly different. Motor axon time constants were longer than sensory axon time constants in 4 of the patients with neuromyotonia, suggesting that the nodal membrane was depolarized by an ectopic focus at the site of nerve stimulation at the wrist, ionic conductances were altered at the node, or that the size of the node was increased, possibly as a result of immune-mediated damage. The anti-voltage-gated potassium channel antibodies thought to generate peripheral nerve hyperexcitability in acquired neuromyotonia may be indirectly responsible for changes in motor axon nodal membrane properties.