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Angela Vincent - One of the best experts on this subject based on the ideXlab platform.
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focal ca3 hippocampal subfield atrophy following lgi1 vgkc complex antibody Limbic Encephalitis
Brain, 2017Co-Authors: Thomas D Miller, Angela Vincent, Saiju Jacob, Sarosh R Irani, Trevor T J Chong, Anne Aimola M Davies, Michael R Johnson, Masud Husain, Paul MaddisonAbstract:Magnetic resonance imaging has linked chronic voltage-gated potassium channel (VGKC) complex antibody-mediated Limbic Encephalitis with generalized hippocampal atrophy. However, autoantibodies bind to specific rodent hippocampal subfields. Here, human hippocampal subfield (subiculum, cornu ammonis 1-3, and dentate gyrus) targets of immunomodulation-treated LGI1 VGKC-complex antibody-mediated Limbic Encephalitis were investigated using in vivo ultra-high resolution (0.39 x 0.39 x 1.0 mm³) 7.0T magnetic resonance imaging [n = 18 patients, 17 patients (94%) positive for LGI1 antibody and one patient negative for LGI1/CASPR2 but positive for VGKC-complex antibodies, mean age: 64.0 ± 2.55 years, median 4 years post-Limbic Encephalitis onset; n = 18 controls]. First, hippocampal subfield quantitative morphometry indicated significant volume loss confined to bilateral CA3 [F(1,34) = 16.87, P 3 months from symptom onset) were associated with CA3 atrophy. Third, whole-brain voxel-by-voxel morphometry revealed no significant grey matter loss. Fourth, CA3 subfield atrophy was associated with severe episodic but not semantic amnesia for postmorbid autobiographical events that was predicted by variability in CA3 volume. The results raise important questions about the links with histopathology, the impact of the observed focal atrophy on other CA3-mediated reconstructive and episodic mechanisms, and the role of potential antibody-mediated pathogenicity as part of the pathophysiology cascade in humans.
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eeg confirmed epileptic activity in a cat with vgkc complex lgi1 antibody associated Limbic Encephalitis
Epileptic Disorders, 2014Co-Authors: Akos Pakozdy, Peter Halasz, Ursula Glantschnigg, Michael Leschnik, Harald Hechinger, T Moloney, Bethan Lang, Angela VincentAbstract:A 5-year-old, female client-owned cat presented with acute onset of focal epileptic seizures with orofacial twitching and behavioural changes. Magnetic resonance imaging showed bilateral temporal lobe hyperintensities and the EEG was consistent with ictal epileptic seizure activity. After antiepileptic and additional corticosteroid treatment, the cat recovered and by 10 months of follow-up was seizure-free without any problem. Retrospectively, antibodies to LGI1, a component of the voltage-gated potassium channel-complex, were identified. Feline focal seizures with orofacial involvement have been increasingly recognised in client-owned cats, and autoimmune Limbic Encephalitis was recently suggested as a possible aetiology. This is the first report of EEG, MRI and long-term follow-up of this condition in cats which is similar to human Limbic Encephalitis.
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suspected Limbic Encephalitis and seizure in cats associated with voltage gated potassium channel vgkc complex antibody
Journal of Veterinary Internal Medicine, 2013Co-Authors: Akos Pakozdy, Peter Halasz, Michael Leschnik, Bethan Lang, Andrea Klang, Jan Bauer, Alexander Tichy, Johann G Thalhammer, Angela VincentAbstract:Background Treatment-resistant complex partial seizures (CPS) with orofacial involvement recently were reported in cats in association with hippocampal pathology. The features had some similarity to those described in humans with Limbic Encephalitis and voltage-gated potassium channel (VGKC) complex antibody. Hypothesis/Objectives The purpose of this pilot study was to evaluate cats with CPS and orofacial involvement for the presence of VGKC-complex antibody. Animals Client-owned cats with acute orofacial CPS and control cats were investigated. Methods Prospective study. Serum was collected from 14 cats in the acute stage of the disease and compared with 19 controls. VGKC-complex antibodies were determined by routine immunoprecipitation and by binding to leucine-rich glioma inactivated 1 (LGI1) and contactin-associated protein-like 2 (CASPR2), the 2 main targets of VGKC-complex antibodies in humans. Results Five of the 14 affected cats, but none of the 19 controls, had VGKC-complex antibody concentrations above the cut-off concentration (>100 pmol/L) based on control samples and similar to those found in humans. Antibodies in 4 cats were directed against LGI1, and none were directed against CASPR2. Follow-up sera were available for 5 cats in remission and all antibody concentrations were within the reference range. Conclusion and Clinical Importance Our study suggests that an autoimmune Limbic Encephalitis exists in cats and that VGKC-complex/LGI1 antibodies may play a role in this disorder, as they are thought to in humans.
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non paraneoplastic Limbic Encephalitis associated with nmdar and vgkc antibodies
Journal of Neurology Neurosurgery and Psychiatry, 2010Co-Authors: Hannah Pellkofer, Angela Vincent, Tania Kuempfel, Leslie Jacobson, Tobias DerfussAbstract:Limbic Encephalitis (LE) is characterised by seizures and impairment of short-term memory as well as behavioural and psychiatric symptoms such as anxiety, depression, personality change and hallucinations. Onset of these symptoms is typically subacute over a few weeks or months but may also evolve over a few days. In many patients, Limbic Encephalitis is a paraneoplastic syndrome usually preceding diagnosis of the malignancy. Associated tumours are most commonly small-cell lung cancer (SCLC), breast cancer, testicular tumour, teratoma, Hodgkin lymphoma and thymoma.1 Antineuronal autoantibodies can be detected in the sera of about 60% of patients. These autoantibodies are classically directed to intracellular antigens (eg, anti-Hu, anti-Ma1/2, anti-CRMP5/CV2, anti-amphiphysin). However, LE is now being recognised frequently in the absence of malignancy and can be associated with antibodies to voltage-gated potassium channel (VGKC-ab). More recently, a new type of immunotherapy-responsive severe LE was described by Dalmau and colleagues that is associated with antibodies to the n -methyl-d-aspartate-receptor (NMDAR) and ovarian teratoma. In rare instances, these NMDAR-ab also occur in men with testicular teratoma or SCLC.2 3 For the first time, we describe a male patient with non-paraneoplastic Limbic Encephalitis and with serum antibodies to both NMDAR and VGKC. This previously healthy 56-year-old man reported the first signs of disease …
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Limbic Encephalitis associated with antibodies to the nmda receptor in hodgkin lymphoma
Neurology, 2009Co-Authors: Michael S Zandi, Sarosh R Irani, G Follows, A M Moody, P Molyneux, Angela VincentAbstract:Convulsions, fever, and memory loss after chemotherapy are usually due to opportunistic infection, and often attributed to infection even if CSF viral PCR examination is negative. We describe a case of Limbic Encephalitis in a patient with relapsed Hodgkin lymphoma, in whom antibodies to the NMDA receptor were identified in serum and CSF, and whose anterograde memory improved with aggressive immunotherapy. Paraneoplastic Limbic Encephalitis in Hodgkin lymphoma has been reported before,1,2 but no target antigen identified. The case adds to the clinical associations of NMDA receptor antibodies. ### Case report. A 49-year-old man developed an amnesic syndrome temporally related to a second relapse of nodular sclerosing Hodgkin lymphoma. Eight years previously he had developed a large cervical lymph node and was successfully treated with mantle radiotherapy. He received chemotherapy to treat an abdominal relapse 2 years later, and maintained remission for 5 years. Last year he relapsed with a large abdominal para-aortic mass, and 3 weeks after his first cycle of treatment, with gemcitabine and cisplatin, he developed confusion and disorientation over 2 days, culminating in a generalized seizure while driving. Initial confusion and memory loss was assumed to be postictal, but his anterograde memory deficit persisted and worsened: at worst he could encode 4 of 7 parts of an address but could not recall or recognize any components at 5 minutes. He had no evidence of a movement disorder. There was no neutropenia. Erythrocyte …
Josep Dalmau - One of the best experts on this subject based on the ideXlab platform.
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Clinico-pathological correlation in adenylate kinase 5 autoimmune Limbic Encephalitis
Journal of Neuroimmunology, 2015Co-Authors: Adeline Sl L. Ng, Alejandro F. Centurion, Jennifer Cotter, Joel H. Kramer, Josep Dalmau, Eric J. Huang, Michael D GeschwindAbstract:Autoantibodies associated with autoimmune Limbic Encephalitis (ALE) have been well-characterized, with intracellular neuronal antibodies being less responsive to immunotherapy than antibodies to cell surface antigens. Adenylate kinase 5 (AK5) is a nucleoside monophosphate kinase vital for neuronal-specific metabolism and is located intracellularly in the cytosol and expressed exclusively in the brain. Antibodies to AK5 had been previously identified but were not known to be associated with human disease prior to the report of two patients with AK5-related ALE (Tuzun et al., 2007). We present the complete clinical picture for one of these patients and the first reported neuropathology for AK5 ALE.
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Treatment-responsive Limbic Encephalitis identified
2015Co-Authors: Josep DalmauAbstract:*These authors contributed equally to this work We report seven patients, six from a single institution, who developed subacute Limbic Encephalitis initially considered of uncertain aetiology. Four patients presented with symptoms of hippocampal dysfunction (i.e. severe short-term memory loss) and three with extensive Limbic dysfunction (i.e. confusion, seizures and suspected psychosis). Brain MRI and [18F]fluorodeoxyglucose (FDG)-PET complemented each other but did not overlap in 50 % of the patients. Combining both tests, all patients had temporal lobe abnormalities, five with additional areas involved. In one patient, FDG hyperactivity in the brainstem that was normal on MRI correlated with central hypoventilation; in another case, hyperactivity in the cerebellum anticipated ataxia. All patients had abnormal CSF: six pleocytosis, six had increased protein concentration, and three of five examined had oligoclonal bands. A tumour was identified and removed in four patients (mediastinal tera-toma, thymoma, thymic carcinoma and thyroid cancer) and not treated in one (ovarian teratoma). An immunohistochemical technique that facilitates the detection of antibodies to cell surface or synaptic proteins demonstrated that six patients had antibodies to the neuropil of hippocampus or cerebellum, and one to intraneuronal antigens. Only one of the neuropil antibodies corresponded to voltage-gated potassium channel (VGKC) antibodies; the other five (two with identical specificity) reacted with antigen
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serial brain 18fdg pet in anti ampa receptor Limbic Encephalitis
Journal of Neuroimmunology, 2014Co-Authors: Marianna Spatola, Josep Dalmau, Vesna Stojanova, John O Prior, Andrea O RossettiAbstract:Immunotherapy-responsive autoimmune CNS syndromes linked to antibodies targeting surface neuronal antigens lack reliable biomarkers of disease activity. We report serial cerebral (18)FDG PET studies in a woman with AMPA receptor (AMPA-R) autoimmune Limbic Encephalitis. During her follow-up, despite an aggressive immunotherapy, she displayed a persistent, predominantly left hippocampal FDG hypermetabolism, in the absence of CNS inflammatory signs. Brain metabolism abnormalities regressed after increasing antiepileptic treatment, correlating with a moderate clinical improvement. Brain (18)F-FDG PET could thus represent a useful complementary tool to orient the clinical follow-up.
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investigation of lgi1 as the antigen in Limbic Encephalitis previously attributed to potassium channels a case series
Lancet Neurology, 2010Co-Authors: Maartje G Huijbers, Eric Lancaster, Luis Bataller, Rita J Balicegordon, John K Cowell, Francesc Graus, Josep DalmauAbstract:Summary Background Voltage-gated potassium channels are thought to be the target of antibodies associated with Limbic Encephalitis. However, antibody testing using cells expressing voltage-gated potassium channels is negative; hence, we aimed to identify the real autoantigen associated with Limbic Encephalitis. Methods We analysed sera and CSF of 57 patients with Limbic Encephalitis and antibodies attributed to voltage-gated potassium channels and 148 control individuals who had other disorders with or without antibodies against voltage-gated potassium channels. Immunohistochemistry, immunoprecipitation, and mass spectrometry were used to characterise the antigen. An assay with HEK293 cells transfected with leucine-rich, glioma-inactivated 1 (LGI1) and disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) or ADAM23 was used as a serological test. The identity of the autoantigen was confirmed by immunoabsorption studies and immunostaining of Lgi1 -null mice. Findings Immunoprecipitation and mass spectrometry analyses showed that antibodies from patients with Limbic Encephalitis previously attributed to voltage-gated potassium channels recognise LGI1, a neuronal secreted protein that interacts with presynaptic ADAM23 and postsynaptic ADAM22. Immunostaining of HEK293 cells transfected with LGI1 showed that sera or CSF from patients, but not those from control individuals, recognised LGI1. Co-transfection of LGI1 with its receptors, ADAM22 or ADAM23, changed the pattern of reactivity and improved detection. LGI1 was confirmed as the autoantigen by specific abrogation of reactivity of sera and CSF from patients after immunoabsorption with LGI1-expressing cells and by comparative immunostaining of wild-type and Lgi1 -null mice, which showed selective lack of reactivity in brains of Lgi1 -null mice. One patient with Limbic Encephalitis and antibodies against LGI1 also had antibodies against CASPR2, an autoantigen we identified in some patients with Encephalitis and seizures, Morvan's syndrome, and neuromyotonia. Interpretation LGI1 is the autoantigen associated with Limbic Encephalitis previously attributed to voltage-gated potassium channels. The term Limbic Encephalitis associated with antibodies against voltage-gated potassium channels should be changed to Limbic Encephalitis associated with LGI1 antibodies, and this disorder should be classed as an autoimmune synaptic encephalopathy. Funding National Institutes of Health, National Cancer Institute, and Euroimmun.
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reversible Limbic Encephalitis with antibodies against the membranes of neurones of the hippocampus
Case Reports, 2009Co-Authors: Haruo Shimazaki, Yoshihito Ando, Imaharu Nakano, Josep DalmauAbstract:The authors report a patient with Limbic Encephalitis associated with an ovarian teratoma. An antibody against the membranes of neurones of the hippocampus was identified in both serum and CSF. Immunosuppressive treatments such as plasmapheresis and high-dose intravenous immunoglobulin administration resulted in a rapid clinical recovery.
Robert J Soiffer - One of the best experts on this subject based on the ideXlab platform.
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cord blood hematopoietic stem cell transplant confers an increased risk for human herpesvirus 6 associated acute Limbic Encephalitis a cohort analysis
Biology of Blood and Marrow Transplantation, 2012Co-Authors: Joshua A Hill, Joseph H Antin, Lindsey R Baden, Belisa Guzman Suarez, Corey Cutler, John Koreth, Philippe Armand, Edwin P Alyea, Vincent T Ho, Robert J SoifferAbstract:Human herpesvirus-6 (HHV-6) frequently reactivates after allogeneic hematopoietic stem cell transplantation (HSCT); its most severe manifestation is the syndrome of posttransplantation acute Limbic Encephalitis (HHV-6-PALE). The epidemiology, risk factors, and characteristics of HHV-6-PALE after unrelated cord-blood transplantation (UCBT) are not well characterized. We analyzed 1344 patients undergoing allogeneic HSCT between March 2003 and March 2010 to identify risk factors and characteristics of HHV-6-PALE. The cohort included 1243 adult-donor HSCT and 101 UCBT recipients. All patients diagnosed with HHV-6-PALE had HHV-6 DNA in cerebrospinal fluid (CSF) specimens in addition to symptoms and studies indicating Limbic Encephalitis. Nineteen cases (1.4%) of HHV-6-PALE were identified during this study: 10 after UCBT (9.9%) and 9 after adult-donor HSCT (0.7%), for an incidence rate of 1.2 cases/1000 patient-days compared to 0.08 cases/1000 patient-days ( P P P P = .04). Death from HHV-6-PALE occurred in 50% of affected patients undergoing UCBT and no recipients of adult-donor cells. Patients receiving UCBT have increased risk for HHV-6-PALE and greater morbidity from this disease.
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cord blood hematopoietic stem cell transplant confers an increased risk for human herpesvirus 6 associated acute Limbic Encephalitis a cohort analysis
Biology of Blood and Marrow Transplantation, 2012Co-Authors: Joshua A Hill, Joseph H Antin, Lindsey R Baden, Sophia Koo, Belisa Guzman Suarez, Corey Cutler, John Koreth, Philippe Armand, Edwin P Alyea, Robert J SoifferAbstract:Human herpesvirus-6 (HHV-6) frequently reactivates after allogeneic hematopoietic stem cell transplantation (HSCT); its most severe manifestation is the syndrome of posttransplantation acute Limbic Encephalitis (HHV-6-PALE). The epidemiology, risk factors, and characteristics of HHV-6-PALE after unrelated cord-blood transplantation (UCBT) are not well characterized. We analyzed 1344 patients undergoing allogeneic HSCT between March 2003 and March 2010 to identify risk factors and characteristics of HHV-6-PALE. The cohort included 1243 adult-donor HSCT and 101 UCBT recipients. All patients diagnosed with HHV-6-PALE had HHV-6 DNA in cerebrospinal fluid (CSF) specimens in addition to symptoms and studies indicating Limbic Encephalitis. Nineteen cases (1.4%) of HHV-6-PALE were identified during this study: 10 after UCBT (9.9%) and 9 after adult-donor HSCT (0.7%), for an incidence rate of 1.2 cases/1000 patient-days compared to 0.08 cases/1000 patient-days (P
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post transplant acute Limbic Encephalitis clinical features and relationship to hhv6
Neurology, 2007Co-Authors: William W Seeley, Francisco M Marty, T M Holmes, K Upchurch, Robert J Soiffer, Joseph H Antin, Lindsey R Baden, Edward B BromfieldAbstract:Background: Acute Limbic Encephalitis has been reported in the setting of treatment-related immunosuppression and attributed to human herpesvirus-6 (HHV6) infection. Clinical and laboratory features of the syndrome, however, have not been well characterized. Methods: We describe the clinical, EEG, MRI, and laboratory features of nine patients with acute Limbic Encephalitis after allogeneic hematopoietic stem cell transplantation (HSCT). To explore the relationship between HHV6 and this syndrome, we reviewed available CSF HHV6 PCR results from all HSCT patients seen at our center from March 17, 2003, through March 31, 2005. Results: Patients displayed a consistent and distinctive clinical syndrome featuring anterograde amnesia, the syndrome of inappropriate antidiuretic hormone secretion, mild CSF pleocytosis, and temporal EEG abnormalities, often reflecting clinical or subclinical seizures. MRI showed hyperintensities within the uncus, amygdala, entorhinal area, and hippocampus on T2, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) sequences. CSF PCR assays for HHV6 were positive in six of nine patients on initial lumbar puncture. All patients were treated with foscarnet or ganciclovir. Cognitive recovery varied among long-term survivors. The one brain autopsy showed Limbic gliosis and profound neuronal loss in amygdala and hippocampus. Among 27 HSCT patients with CSF tested for HHV6 over a 2-year period, positive results occurred only in patients with clinical Limbic Encephalitis. Conclusions: Patients undergoing allogeneic hematopoietic stem cell transplantation are at risk for post-transplant acute Limbic Encephalitis (PALE), a distinct neurologic syndrome. Treatment considerations should include aggressive seizure control and, possibly, antiviral therapy. PALE can be associated with the CSF presence of human herpesvirus-6, but the pathogenic role of the virus requires further exploration.
Francesc Graus - One of the best experts on this subject based on the ideXlab platform.
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opsoclonus myoclonus syndrome and Limbic Encephalitis associated with gabab receptor antibodies in csf
Journal of Neuroimmunology, 2014Co-Authors: Alicia Defelipemimbrera, Francesc Graus, Jaime Masjuan, Inigo Corral, Luisa M Villar, Nuria GarciabarraganAbstract:Abstract We report a case of a woman who had two consecutive autoimmune neurological disorders, including an opsoclonus–myoclonus syndrome (OMS) and Limbic Encephalitis (LE), with positive titers of GABA B receptor antibodies. The patient never developed seizures or had an underlying tumor after 4 years of follow-up.
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investigation of lgi1 as the antigen in Limbic Encephalitis previously attributed to potassium channels a case series
Lancet Neurology, 2010Co-Authors: Maartje G Huijbers, Eric Lancaster, Luis Bataller, Rita J Balicegordon, John K Cowell, Francesc Graus, Josep DalmauAbstract:Summary Background Voltage-gated potassium channels are thought to be the target of antibodies associated with Limbic Encephalitis. However, antibody testing using cells expressing voltage-gated potassium channels is negative; hence, we aimed to identify the real autoantigen associated with Limbic Encephalitis. Methods We analysed sera and CSF of 57 patients with Limbic Encephalitis and antibodies attributed to voltage-gated potassium channels and 148 control individuals who had other disorders with or without antibodies against voltage-gated potassium channels. Immunohistochemistry, immunoprecipitation, and mass spectrometry were used to characterise the antigen. An assay with HEK293 cells transfected with leucine-rich, glioma-inactivated 1 (LGI1) and disintegrin and metalloproteinase domain-containing protein 22 (ADAM22) or ADAM23 was used as a serological test. The identity of the autoantigen was confirmed by immunoabsorption studies and immunostaining of Lgi1 -null mice. Findings Immunoprecipitation and mass spectrometry analyses showed that antibodies from patients with Limbic Encephalitis previously attributed to voltage-gated potassium channels recognise LGI1, a neuronal secreted protein that interacts with presynaptic ADAM23 and postsynaptic ADAM22. Immunostaining of HEK293 cells transfected with LGI1 showed that sera or CSF from patients, but not those from control individuals, recognised LGI1. Co-transfection of LGI1 with its receptors, ADAM22 or ADAM23, changed the pattern of reactivity and improved detection. LGI1 was confirmed as the autoantigen by specific abrogation of reactivity of sera and CSF from patients after immunoabsorption with LGI1-expressing cells and by comparative immunostaining of wild-type and Lgi1 -null mice, which showed selective lack of reactivity in brains of Lgi1 -null mice. One patient with Limbic Encephalitis and antibodies against LGI1 also had antibodies against CASPR2, an autoantigen we identified in some patients with Encephalitis and seizures, Morvan's syndrome, and neuromyotonia. Interpretation LGI1 is the autoantigen associated with Limbic Encephalitis previously attributed to voltage-gated potassium channels. The term Limbic Encephalitis associated with antibodies against voltage-gated potassium channels should be changed to Limbic Encephalitis associated with LGI1 antibodies, and this disorder should be classed as an autoimmune synaptic encephalopathy. Funding National Institutes of Health, National Cancer Institute, and Euroimmun.
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neuronal surface antigen antibodies in Limbic Encephalitis clinical immunologic associations
Neurology, 2008Co-Authors: Francesc Graus, Jordi Bruna, A Saiz, M Lai, F Lopez, Lidia Sabater, Yolanda Blanco, Maria Jesus Rey, Teresa Ribalta, Josep DalmauAbstract:Objective: To report the frequency and type of antibodies against neuronal surface antigens (NSA-ab) in Limbic Encephalitis (LE). Methods: Analysis of clinical features, neuropathologic findings, and detection of NSA-ab using immunochemistry on rat tissue and neuronal cultures in a series of 45 patients with paraneoplastic (23) or idiopathic (22) LE. Results: NSA-ab were identified in 29 patients (64%; 12 paraneoplastic, 17 idiopathic). Thirteen patients had voltage-gated potassium channels (VGKC)-ab, 11 novel NSA (nNSA)-ab, and 5 NMDA receptor (NMDAR)-ab. nNSA-ab did not identify a common antigen and were more frequent in paraneoplastic than idiopathic LE (39% vs 9%; p = 0.03). When compared with VGKC-ab or NMDAR-ab, the nNSA associated more frequently with intraneuronal antibodies (11% vs 73%; p = 0.001). Of 12 patients (9 nNSA-ab, 2 VGKC-ab, 1 NMDAR-ab) with paraneoplastic LE and NSA-ab, concomitant intraneuronal antibodies occurred in 9 (75%). None of these 12 patients improved with immunotherapy. The autopsy of three of them showed neuronal loss, microgliosis, and cytotoxic T cell infiltrates in the hippocampus and amygdala. These findings were compatible with a T-cell mediated neuronal damage. In contrast, 13 of 17 (76%) patients with idiopathic LE and NSA-ab (8 VGKC-ab, 4 NMDAR-ab, 1 nNSA-ab) and 1 of 5 (20%) without antibodies had clinical improvement ( p = 0.04). Conclusions: In paraneoplastic Limbic Encephalitis (LE), novel antibodies against neuronal surface antigens (nNSA-ab) occur frequently, coexist with antibodies against intracellular antigens, and these cases are refractory to immunotherapy. In idiopathic LE, the likelihood of improvement is significantly higher in patients with NSA-ab than in those without antibodies. GLOSSARY: GAD = glutamic acid decarboxylase; LE = Limbic Encephalitis; NMDAR = N-methyl-D-aspartate receptor; NSA = neuronal surface antigens; nNSA = novel NSA; SCLC = small-cell lung cancer; VGKC = voltage-gated potassium channels; WBC = white blood cells.
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Limbic Encephalitis an expanding concept
Neurology, 2008Co-Authors: Francesc Graus, Albert SaizAbstract:Limbic Encephalitis (LE) was initially described as a paraneoplastic syndrome characterized by rapid development of confusion, seizures, short-term memory loss, and high MRI T2 and FLAIR signal involving one or both medial temporal lobes.1 No more than 5 years ago, LE was considered to invariably have a paraneoplastic origin mostly associated with lung or testicular cancer and with antibodies against intracellular neuronal antigens. Neuropathologic studies show dominant parenchymal infiltrates of T-cells supporting the hypothesis, not proven yet, that the disorder is mediated by a T cell driven immune response, presumably against the same antigens recognized by the antibodies.1 The concept of LE expanded with the description of patients with otherwise classic LE in association with antibodies to voltage-gated potassium channels (VGKC).2 This variant of LE infrequently associates with cancer, and often responds to immunotherapy along with a decrease of serum antibody titers, suggesting that the antibodies are pathogenic.2 More recently, a new Encephalitis was described in 12 women with ovarian teratomas.3 The syndrome predictably evolves in stages, including prodromal fever followed in a few days by prominent psychiatric symptoms or …
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paraneoplastic Limbic Encephalitis associated with potassium channel antibodies value of anti glial nuclear antibodies in identifying the tumour
Journal of Neurology Neurosurgery and Psychiatry, 2007Co-Authors: Luigi Zuliani, Angela Vincent, Albert Saiz, B Tavolato, Bruno Giometto, Francesc GrausAbstract:Limbic Encephalitis is characterised by subacute development of short-term memory loss, seizures, confusion and psychiatric features.1 Paraneoplastic Limbic Encephalitis is generally associated with small cell lung cancer (SCLC), and around 50% of patients harbour Hu, CV2/CRMP5 or amphiphysin antibodies.1 Recently, antibodies against voltage-gated potassium channels (VGKC-abs) were identified as a new marker of a non-paraneoplastic, immunotherapy-responsive form of Limbic Encephalitis.2,3 However, the presence of VGKC-ab does not exclude a paraneoplastic cause of Limbic Encephalitis.1 We described previously a new antibody called anti-glial nuclear antibody (AGNA), a marker of SCLC shown to be closely associated with paraneoplastic Lambert–Eaton myasthenic syndrome (LEMS).4 Here we report on two patients with paraneoplastic Limbic Encephalitis associated with SCLC and VGKC-ab who also presented AGNA. The presence of AGNA was assessed by immunohistochemistry on frozen sections of paraformaldehyde-fixed rat cerebellum in nine patients with Limbic Encephalitis and SCLC with (n = 2) or without (n = 7) VGKC-ab, and in seven patients with non-paraneoplastic Limbic Encephalitis and VGKC-ab. To confirm AGNA reactivity, an immunohistochemical competition assay was performed as described previously.4 VGKC-abs were detected by radioimmunoprecipitation (cutoff value: 100 pmol/l).2 A middle-aged man was admitted to hospital with a 2-week history of behavioural changes and generalised seizures. A neurological examination showed short-term memory loss, confusion and aphasia. Electroencephalography showed slowing in the left temporal lobe. Magnetic resonance …
Joseph H Antin - One of the best experts on this subject based on the ideXlab platform.
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cord blood hematopoietic stem cell transplant confers an increased risk for human herpesvirus 6 associated acute Limbic Encephalitis a cohort analysis
Biology of Blood and Marrow Transplantation, 2012Co-Authors: Joshua A Hill, Joseph H Antin, Lindsey R Baden, Belisa Guzman Suarez, Corey Cutler, John Koreth, Philippe Armand, Edwin P Alyea, Vincent T Ho, Robert J SoifferAbstract:Human herpesvirus-6 (HHV-6) frequently reactivates after allogeneic hematopoietic stem cell transplantation (HSCT); its most severe manifestation is the syndrome of posttransplantation acute Limbic Encephalitis (HHV-6-PALE). The epidemiology, risk factors, and characteristics of HHV-6-PALE after unrelated cord-blood transplantation (UCBT) are not well characterized. We analyzed 1344 patients undergoing allogeneic HSCT between March 2003 and March 2010 to identify risk factors and characteristics of HHV-6-PALE. The cohort included 1243 adult-donor HSCT and 101 UCBT recipients. All patients diagnosed with HHV-6-PALE had HHV-6 DNA in cerebrospinal fluid (CSF) specimens in addition to symptoms and studies indicating Limbic Encephalitis. Nineteen cases (1.4%) of HHV-6-PALE were identified during this study: 10 after UCBT (9.9%) and 9 after adult-donor HSCT (0.7%), for an incidence rate of 1.2 cases/1000 patient-days compared to 0.08 cases/1000 patient-days ( P P P P = .04). Death from HHV-6-PALE occurred in 50% of affected patients undergoing UCBT and no recipients of adult-donor cells. Patients receiving UCBT have increased risk for HHV-6-PALE and greater morbidity from this disease.
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cord blood hematopoietic stem cell transplant confers an increased risk for human herpesvirus 6 associated acute Limbic Encephalitis a cohort analysis
Biology of Blood and Marrow Transplantation, 2012Co-Authors: Joshua A Hill, Joseph H Antin, Lindsey R Baden, Sophia Koo, Belisa Guzman Suarez, Corey Cutler, John Koreth, Philippe Armand, Edwin P Alyea, Robert J SoifferAbstract:Human herpesvirus-6 (HHV-6) frequently reactivates after allogeneic hematopoietic stem cell transplantation (HSCT); its most severe manifestation is the syndrome of posttransplantation acute Limbic Encephalitis (HHV-6-PALE). The epidemiology, risk factors, and characteristics of HHV-6-PALE after unrelated cord-blood transplantation (UCBT) are not well characterized. We analyzed 1344 patients undergoing allogeneic HSCT between March 2003 and March 2010 to identify risk factors and characteristics of HHV-6-PALE. The cohort included 1243 adult-donor HSCT and 101 UCBT recipients. All patients diagnosed with HHV-6-PALE had HHV-6 DNA in cerebrospinal fluid (CSF) specimens in addition to symptoms and studies indicating Limbic Encephalitis. Nineteen cases (1.4%) of HHV-6-PALE were identified during this study: 10 after UCBT (9.9%) and 9 after adult-donor HSCT (0.7%), for an incidence rate of 1.2 cases/1000 patient-days compared to 0.08 cases/1000 patient-days (P
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post transplant acute Limbic Encephalitis clinical features and relationship to hhv6
Neurology, 2007Co-Authors: William W Seeley, Francisco M Marty, T M Holmes, K Upchurch, Robert J Soiffer, Joseph H Antin, Lindsey R Baden, Edward B BromfieldAbstract:Background: Acute Limbic Encephalitis has been reported in the setting of treatment-related immunosuppression and attributed to human herpesvirus-6 (HHV6) infection. Clinical and laboratory features of the syndrome, however, have not been well characterized. Methods: We describe the clinical, EEG, MRI, and laboratory features of nine patients with acute Limbic Encephalitis after allogeneic hematopoietic stem cell transplantation (HSCT). To explore the relationship between HHV6 and this syndrome, we reviewed available CSF HHV6 PCR results from all HSCT patients seen at our center from March 17, 2003, through March 31, 2005. Results: Patients displayed a consistent and distinctive clinical syndrome featuring anterograde amnesia, the syndrome of inappropriate antidiuretic hormone secretion, mild CSF pleocytosis, and temporal EEG abnormalities, often reflecting clinical or subclinical seizures. MRI showed hyperintensities within the uncus, amygdala, entorhinal area, and hippocampus on T2, fluid-attenuated inversion recovery (FLAIR), and diffusion-weighted imaging (DWI) sequences. CSF PCR assays for HHV6 were positive in six of nine patients on initial lumbar puncture. All patients were treated with foscarnet or ganciclovir. Cognitive recovery varied among long-term survivors. The one brain autopsy showed Limbic gliosis and profound neuronal loss in amygdala and hippocampus. Among 27 HSCT patients with CSF tested for HHV6 over a 2-year period, positive results occurred only in patients with clinical Limbic Encephalitis. Conclusions: Patients undergoing allogeneic hematopoietic stem cell transplantation are at risk for post-transplant acute Limbic Encephalitis (PALE), a distinct neurologic syndrome. Treatment considerations should include aggressive seizure control and, possibly, antiviral therapy. PALE can be associated with the CSF presence of human herpesvirus-6, but the pathogenic role of the virus requires further exploration.