scholarly journals Stop testing for autoantibodies to the VGKC-complex: only request LGI1 and CASPR2

2020 ◽  
Vol 20 (5) ◽  
pp. 377-384
Author(s):  
Sophia Michael ◽  
Patrick Waters ◽  
Sarosh R Irani
Keyword(s):  
Limbic Encephalitis ◽  
Target Surface ◽  
Double Negative ◽  
Healthy Controls ◽  
Patient Benefit ◽  
Pathogenic Potential ◽  
Voltage Gated ◽  
Morvan’S Syndrome ◽  
Change In Practice ◽  
Positive Results

Autoantibodies to leucine-rich glioma-inactivated 1 (LGI1) and contactin-associated protein like-2 (CASPR2) are associated with clinically distinctive syndromes that are highly immunotherapy responsive, such as limbic encephalitis, faciobrachial dystonic seizures, Morvan’s syndrome and neuromyotonia. These autoantibodies target surface-exposed domains of LGI1 or CASPR2, and appear to be directly pathogenic. In contrast, voltage-gated potassium channel (VGKC) antibodies that lack LGI1 or CASPR2 reactivities (‘double-negative’) are common in healthy controls and have no consistent associations with distinct syndromes. These antibodies target intracellular epitopes and lack pathogenic potential. Moreover, the clinically important LGI1 and CASPR2 antibodies comprise only ~15% of VGKC-positive results, meaning that most VGKC-antibody positive results mislead rather than help. Further, initial VGKC testing misses some cases that have LGI1 and CASPR2 antibodies. These collective observations confirm that laboratories should stop testing for VGKC antibodies and instead, test only for LGI1 and CASPR2 antibodies. This change in practice will lead to significant patient benefit.

scholarly journals Frontotemporal Dementia with Parkinsonism and Epilepsy Associated with VGKC Antibodies: Case Report and Literature Review

2021 ◽  
pp. 205-210
Author(s):  
Matthew Saint ◽  
Vafa Alakbarzade ◽  
Brendan McLean
Keyword(s):  
Case Report ◽  
Literature Review ◽  
Frontotemporal Dementia ◽  
Limbic Encephalitis ◽  
Poor Response ◽  
Double Negative ◽  
Aggressive Treatment ◽  
Voltage Gated ◽  
Negative Results ◽  
Autoimmune Conditions

Antibodies directed against the voltage-gated potassium channel complex (anti-VGKCs) are implicated in several autoimmune conditions including limbic encephalitis and epilepsy. However, emerging evidence suggests that only specific subtypes of anti-VGKCs are pathogenic. We present the case of a 55-year-old man who initially presented with focal unaware seizures and behavioural changes mimicking anti-VGKC-seropositive encephalitis that further progressed to parkinsonism with evidence of frontotemporal dementia and pre-synaptic dopaminergic deficit. Aggressive treatment with immunotherapy was ineffective, and antibody subtyping later revealed the anti-VGKC antibodies to be negative for leucine-rich glioma-associated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2) – the two known pathogenic subtypes. The clinical relevance of so-called “double-negative” anti-VGKCs (i.e., those not directed towards LGI1 or CASPR2) has been called into question in recent years, with evidence to suggest they may be clinically insignificant. Our case emphasises the importance of antibody subtyping in cases of anti-VGKC seropositivity; negative results, particularly when combined with a poor response to immunotherapy, should prompt a rapid reconsideration of the working diagnosis.

THUR 153 Antibodies against the voltage-gated potassium channel complex

2018 ◽  
Vol 89 (10) ◽  
pp. A18.2-A18
Author(s):  
Joyutpal Das ◽  
Vanisha Chauhan ◽  
Ryan Keh ◽  
Daniel Mills ◽  
Johal Nicholas ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Intravenous Immunoglobulins ◽  
Voltage Gated ◽  
Morvan’S Syndrome ◽  
Classic Phenotype ◽  
Antibody Titres ◽  
Peripheral Nerve Hyperexcitability ◽  
Clinical Phenotyping ◽  
Positive Results ◽  
Autoimmune Encephalopathy

Voltage-gated potassium channel (VGKC) complex antibodies have been associated with a spectrum of presentations including peripheral nerve hyperexcitability (PNH), Morvan’s syndrome, autoimmune encephalopathy, epilepsy and recently psychosis.We retrospectively reviewed the medical records of 70 patients from the Greater Manchester Neuroscience Centre, who had tested positive for VGKC-complex antibodies between 2012 and 2015 to identify the clinical relevance of positive results.The majority were diagnosed with autoimmune encephalopathy(19) followed by epilepsy(14), psychosis(10) and PNH(6). The remaining fifteen had other neurological presentations and six had no primary neurological disorder. 39/70 patients who had antibody titres>400 pM, were diagnosed with autoimmune encephalopathy(19), epilepsy(9), psychosis(4), PNH(3) and other disorders(4). 24/39 patients, who received treatment with one or a combination of corticosteroids, intravenous immunoglobulins, cyclophosphamide, plasma exchange, azathioprine or rituximab, had a diagnosis of autoimmune encephalopathy(18), epilepsy(2), psychosis(2) and malignancy(2). 16/24 were treatment responsive. 3/31 patients with lower titres were also treated, but only one with the classic phenotype (PNH) responded to treatment.The classic phenotype often had a titre >400 pM. PNH may have a titre ≤400 pM. The patients without classic presentations typically had titres≤400 pM. Consistent with previous studies, clinical phenotyping and antibody titre helped to determine the relevance of VGKC-complex antibodies.

Autoimmune limbic encephalitis and Morvan’s syndrome

2010 ◽  
pp. 5175-5176
Author(s):  
Camilla Buckle ◽  
Angela Vincent
Keyword(s):  
Cell Surface ◽  
Short Term Memory ◽  
Limbic Encephalitis ◽  
Memory Loss ◽  
Surface Proteins ◽  
Cell Surface Proteins ◽  
Term Memory ◽  
Voltage Gated ◽  
Morvan’S Syndrome ◽  
Autoimmune Limbic Encephalitis

Autoimmune limbic encephalitis—typical presentation is with acute or subacute onset of short term memory loss, seizures and disorientation. MRI characteristically shows striking abnormalities in the hippocampus. Antibodies against cell-surface proteins that are components of voltage-gated potassium channel (VGKC) complexes are found in a high proportion and are probably pathogenic. Aside from supportive care, treatment is with immunosuppression, often comprising corticosteroids with intravenous immunoglobulin and/or plasma exchange....

scholarly journals High Grade Glioma Mimicking Voltage Gated Potassium Channel Complex Associated Antibody Limbic Encephalitis

2014 ◽  
Vol 2014 ◽  
pp. 1-4 ◽  
Author(s):  
Dilan Athauda ◽  
R. S. Delamont ◽  
E. De Pablo-Fernandez
Keyword(s):  
Potassium Channel ◽  
Limbic Encephalitis ◽  
Immunosuppressive Treatment ◽  
High Grade Glioma ◽  
High Titre ◽  
High Grade ◽  
Voltage Gated ◽  
Primary Brain Tumours ◽  
Primary Brain Tumour ◽  
Morvan’S Syndrome

Though raised titres of voltage gated potassium channel (VGKC) complex antibodies have been occasionally associated with extracranial tumours, mainly presenting as Morvan's Syndrome or neuromyotonia, they have not yet been reported to be associated with an intracranial malignancy. This is especially important as misdiagnosis of these conditions and delay of the appropriate treatment can have important prognostic implications. We describe a patient with a high grade glioma presenting with clinical, radiological, and serological features consistent with the diagnosis of VGKC antibody associated limbic encephalitis (LE). This is the first association between a primary brain tumour and high titre of VGKC complex antibodies. Clinicoradiological progression despite effective immunosuppressive treatment should prompt clinicians to look for alternative diagnoses. Further studies to elucidate a possible association between VGKC complex and other surface antigen antibodies with primary brain tumours should be carried out.

Limbic encephalitis with voltage gated potassium channel antibodies in a child

2008 ◽  
Vol 39 (01) ◽  
Author(s):  
E Haberlandt ◽  
CG Bien ◽  
A Reiter ◽  
B Simma ◽  
R Crazzolara ◽  
...  
Keyword(s):  
Potassium Channel ◽  
Limbic Encephalitis ◽  
Voltage Gated

Voltage-gated potassium channel limbic encephalitis presenting as functional cognitive impairment

2020 ◽  
Vol 13 (12) ◽  
pp. e233179
Author(s):  
Eric Garrels ◽  
Fawziya Huq ◽  
Gavin McKay
Keyword(s):  
Cognitive Impairment ◽  
Case Report ◽  
Potassium Channel ◽  
Limbic Encephalitis ◽  
Psychiatric Symptoms ◽  
Differential Diagnoses ◽  
Visual Hallucinations ◽  
Voltage Gated ◽  
History Of ◽  
Impaired Cognition

Limbic encephalitis is often reported to present as seizures and impaired cognition with little focus on psychiatric presentations. In this case report, we present a 49-year-old man who initially presented to the Psychiatric Liaison Service with a several month history of confusion with the additional emergence of visual hallucinations and delusions. Due to the inconsistent nature of the symptoms in the context of a major financial stressor, a provisional functional cognitive impairment diagnosis was made. Investigations later revealed a positive titre of voltage-gated potassium channel (VGKC) antibodies, subtype leucine-rich glioma inactivated 1 accounting for his symptoms which dramatically resolved with steroids and immunoglobulins. This case highlighted the need for maintaining broad differential diagnoses in a patient presenting with unusual psychiatric symptoms.

scholarly journals Molecular detection of vector borne pathogens in anemic and thrombocytopenic dogs in southern Brazil

2018 ◽  
Vol 27 (4) ◽  
pp. 505-513 ◽  
Author(s):  
Anna Cláudia Baumel Mongruel ◽  
Priscila Ikeda ◽  
Keyla Carstens Marques de Sousa ◽  
Jyan Lucas Benevenute ◽  
Margarete Kimie Falbo ◽  
...  
Keyword(s):  
18S Rrna ◽  
Molecular Detection ◽  
Phylogenetic Analyses ◽  
Southern Brazil ◽  
Conventional Pcr ◽  
Pathogenic Potential ◽  
Vector Borne ◽  
Pcr Assays ◽  
Etiological Agents ◽  
Positive Results

Abstract Arthropod-borne pathogens are medically important because of their ability to cause diseases in their hosts. The purpose of this study was to detect the occurrence of Ehrlichia spp., piroplasmids and Hepatozoon spp. in dogs with anemia and thrombocytopenia in southern Brazil. EDTA-whole blood was collected from 75 domestic dogs presenting anemia or/and thrombocytopenia from Guarapuava, state of Paraná, Brazil. DNA samples were subjected to conventional PCR assays for Ehrlichia spp. (dsb), piroplasmids (18S rRNA) and Hepatozoon spp. (18S rRNA), followed by sequencing and phylogenetic analyses. Among the 75 dogs, one (1.33%) was positive for Hepatozoon sp. and six (8%) were positive for piroplasmids in 18S rRNA cPCR assays. None of the dogs showed positive results in Ehrlichia spp.-cPCR targeting dsb gene. The phylogenetic analyses revealed that three piroplasm sequences were clustered with Rangellia vitalii, while one sequence was grouped with B. vogeli. The only sequence obtained from Hepatozoon spp.-PCR protocol was pooled with H. canis. Therefore, there is urgent need for differential molecular diagnosis of the two piroplasm species cited as etiological agents in clinical cases of canine hemoparasitic diseases, given the higher pathogenic potential of R. vitalii than of B. vogeli.

Reversible Dementia: Two Nursing Home Patients With Voltage-Gated Potassium Channel Antibody-Associated Limbic Encephalitis

2015 ◽  
Vol 16 (9) ◽  
pp. 790-794 ◽  
Author(s):  
Wesley Reintjes ◽  
Marloes D.M. Romijn ◽  
Daan Hollander ◽  
Jan P. ter Bruggen ◽  
Rob J. van Marum
Keyword(s):  
Nursing Home ◽  
Potassium Channel ◽  
Limbic Encephalitis ◽  
Voltage Gated ◽  
Nursing Home Patients

Development and comparative evaluation of immunoblot assays for detecting autoantibodies to Scl 70 and Jo 1 antigens in serum

1990 ◽  
Vol 36 (12) ◽  
pp. 2053-2056 ◽  
Author(s):  
T Fonong ◽  
S M Evans ◽  
H A Homburger
Keyword(s):  
Comparative Evaluation ◽  
Clinical Laboratory ◽  
Connective Tissue Diseases ◽  
Positive Control ◽  
Analytical Sensitivity ◽  
Healthy Controls ◽  
Clinical Use ◽  
Immunoblot Assay ◽  
Negative Results ◽  
Positive Results

Abstract We developed rapid 24-h immunoblot assays for detecting autoantibodies to Scl 70 and Jo 1 antigens in serum. In comparative studies, we evaluated the analytical sensitivity of the immunoblot assays and commercial immunodiffusion assays for anti-Scl 70 and anti-Jo 1 autoantibodies with the use of positive control sera, and compared the frequencies of positive and negative results in a group of 116 sera, including specimens from 34 healthy controls and 82 patients with various connective-tissue diseases. The immunoblot assays were greater than 100-fold more sensitive than immunodiffusion for detecting both autoantibodies. Despite greater analytical sensitivity, there were no false-positive results by the immunoblot assay for anti-Scl 70 or anti-Jo 1 autoantibodies in sera from either the controls or the patients. The diagnostic sensitivity of the immunoblot assay for anti-Scl 70 autoantibodies in patients with scleroderma was greater than that of the immunodiffusion assay, 70% vs 20%, and was equivalent in patients with polymyositis, 43%. We conclude that rapid immunoblot assays for anti-Scl 70 and anti-Jo 1 autoantibodies are superior to immunodiffusion assays for clinical use and are suitable for routine use in the clinical laboratory.

scholarly journals A Patient with Double-Negative VGKC, Peripheral Nerve Hyperexcitability, and Central Nervous System Symptoms: A Postinfectious Autoimmune Disease

2020 ◽  
Vol 2020 ◽  
pp. 1-7
Author(s):  
Birte Eikeland
Keyword(s):  
Central Nervous System ◽  
Nervous System ◽  
Autoimmune Disease ◽  
Peripheral Nerve ◽  
Skin Lesions ◽  
Double Negative ◽  
Pathogenic Potential ◽  
Peripheral Nerve Hyperexcitability ◽  
Systemic Symptoms ◽  
Kinetics Of

Research in the last few years has indicated that most voltage-gated potassium channel- (VGKC-) complex antibodies without leucine-rich glioma-inactivated protein 1 or contactin-associated protein-like 2 antibody specificity lack pathogenic potential and are not clear markers for autoimmune inflammation. Here we report on a patient with double-negative VGKC who developed severe peripheral nerve hyperexcitability, central nervous system symptoms with agitation and insomnia, dysautonomia, and systemic symptoms with weight loss, itch, and skin lesions. The disease started acutely one month after an episode of enteroviral pericarditis and responded well to immunotherapy. The patient is presumed to have developed a postinfectious immunotherapy-responsive autoimmune disease. In the setting of anti-VGKC positivity, it seems likely that anti-VGKC contributed to the pathogenesis of the patient’s symptoms of nerve hyperexcitability and that the disease was caused by an acquired autoimmune effect on the neuronal kinetics of VGKC. It is still unknown whether or not there are unidentified extracellular molecular targets within the VGKC-complex, i.e., a novel surface antigen and a pathogenic antibody that can cause affected individuals to develop a peripheral nerve hyperexcitability syndrome. This case highlights the fact that less well-characterized autoimmune central and peripheral nervous system syndromes may have infectious triggers.

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