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June 11, 2013; 80 (24) Article

Autoimmune limbic encephalopathy and anti-Hu antibodies in children without cancer

Jérôme Honnorat, Adrien Didelot, Evgenia Karantoni, Dorothée Ville, François Ducray, Laetitia Lambert, Kumaran Deiva, Marie Garcia, Phintip Pichit, Gaelle Cavillon, Véronique Rogemond, Jean-Yves DeLattre, Marc Tardieu
First published May 8, 2013, DOI: https://doi.org/10.1212/WNL.0b013e318296e9c3
Jérôme Honnorat
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Adrien Didelot
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Evgenia Karantoni
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Dorothée Ville
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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François Ducray
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Laetitia Lambert
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Kumaran Deiva
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Marie Garcia
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Phintip Pichit
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Gaelle Cavillon
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Véronique Rogemond
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Jean-Yves DeLattre
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Marc Tardieu
From the French Reference Center on Paraneoplastic Neurological Syndrome (J.H., A.D., F.D., G.C., V.R.), Hospices Civils de Lyon, Hôpital Neurologique, Neurologie B, Bron; Lyon Neuroscience Research Center (J.H., F.D., G.C., V.R.), INSERM U1028/CNRS UMR 5292, Lyon; Université de Lyon–Université Claude Bernard Lyon 1 (J.H., F.D., G.C., V.R.), Lyon; Service de Neurologie Mazarin (E.K., J.-Y.D.), Groupe Hospitalier Pitié-Salpêtrière, APHP, Université Pierre et Marie Curie-Paris 6, Centre de Recherche de l'Institut du Cerveau et de la Moelle Épinière, UMR S975, CNRS, UMR 7225, Paris; Department of Pediatric Neurology (D.V.), Centre de Reference Epilepsies Rares, Hôpital Femme Mère Enfant, Hospices Civils de Lyon, Lyon; Médecine Infantile 3 et Génétique Clinique (L.L.), CHU, Vandoeuvre-les-Nancy, France; Filière de Génétique Clinique (L.L.), Service de Médecine Néonatale, Maternité, Nancy; Hopitaux Universitaires Paris Sud (K.D., M.T.), AP-HP, Pediatric Neurology Department, National Referral Center for Neuroinflammatory Diseases in Children (NIE) and Inserm U1012, Le Kremlin Bicêtre, Bicêtre; Unité de Neuropédiatrie (M.G.), Centre Hospitalo-Universitaire d'Angers, Angers; and Unité d'Épileptologie (P.P.), Service de Neurologie 1, Hôpital la Pitié-Salpêtrière, Paris, France.
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Citation
Autoimmune limbic encephalopathy and anti-Hu antibodies in children without cancer
Jérôme Honnorat, Adrien Didelot, Evgenia Karantoni, Dorothée Ville, François Ducray, Laetitia Lambert, Kumaran Deiva, Marie Garcia, Phintip Pichit, Gaelle Cavillon, Véronique Rogemond, Jean-Yves DeLattre, Marc Tardieu
Neurology Jun 2013, 80 (24) 2226-2232; DOI: 10.1212/WNL.0b013e318296e9c3

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Abstract

Objective: The aim of this study was to describe the clinical presentation of children and adolescents with anti-Hu antibodies (Hu-Abs).

Methods: This was a retrospective study of children and adolescents with Hu-Abs collected by the French Paraneoplastic Neurological Syndrome (PNS) Reference Center between January 1, 2000 and December 31, 2011.

Results: The center identified 251 patients with Hu-Abs. Only 8 patients were younger than 18 years. All of the 243 adult patients had PNS. In contrast, of the 8 children, only 2 (25%, Fisher exact test p = 0.0003) had neuroblastoma and opsoclonus-myoclonus. The other 6 children (5 female and 1 male) presented with limbic encephalitis (progressive personality changes, memory loss, and seizure) and were free of cancer (mean follow-up time: 50 months; range: 34–72 months). Brain MRI scans were abnormal in 4 of the 6 patients, with left, right, or bitemporal T2/fluid-attenuated inversion recovery hyperintensity. Protein levels and cell counts in the CSF were normal in all patients, but numerous oligoclonal bands were observed in 4 patients. All 6 patients received antiepileptic drugs and immunotherapy, but management of epilepsy was difficult in all of them. Five of the children developed cognitive impairments.

Conclusion: In children, as in adults, Hu-Abs can be a marker of PNS. However, in contrast to adults, Hu-Abs in children are also associated with an aggressive form of autoimmune nonparaneoplastic limbic encephalitis. Future studies should be conducted to determine the incidence of this syndrome and whether earlier diagnosis and T-cell–directed immunotherapies may improve its prognosis.

GLOSSARY

FLAIR=
fluid-attenuated inversion recovery;
Hu-Abs=
anti-Hu antibodies;
PNS=
paraneoplastic neurologic syndromes

Footnotes

  • Go to Neurology.org for full disclosures. Funding information and disclosures deemed relevant by the authors, if any, are provided at the end of the article.

  • Received December 4, 2012.
  • Accepted in final form March 11, 2013.
  • © 2013 American Academy of Neurology
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