title: Motor cortex and hippocampus are the two main cortical targets in LGI1-antibody encephalitis.
abstract: Encephalitis associated with antibodies against leucine-rich glioma-inactivated 1 (LGI1) protein is increasingly recognized as an auto-immune disorder associated with characteristic tonic-dystonic seizures. The cortical or subcortical origin of these motor events is not clear. Some patients also present with different epileptic seizures and with cognitive impairment. The frequency of these features and their timing during the natural history of this encephalitis have not been fully described. We therefore reviewed data from 34 patients harbouring antibodies against LGI1 protein (21-81 years, median age 64) referred to the French Reference Centre for Neurological Paraneoplastic Syndrome. Three types of evidence suggested tonic-dystonic seizures were of cortical origin: (i) a slow, unilateral, frontal electroencephalographic wave, of duration ∼580 ms and amplitude ∼71 µV, preceded the contralateral tonic-dystonic seizures in simultaneous electroencephalographic and myographic records from seven of seven patients tested; (ii) 18-Fluorodeoxyglucose imaging revealed a strong hypermetabolism in primary motor cortex, controlateral to the affected limb, during encephalitis for five patients tested, as compared with data from the same patients after remission or from 16 control subjects; and (iii) features of polymyographic records of tonic-dystonic seizure events pointed to a cortical origin. Myoclonic patterns with brief, rhythmic bursts were present in three of five patients tested and a premyoclonic potential was identified in the cortex of one patient. Initially during encephalitis, 11 of 34 patients exhibited tonic-dystonic seizures (32%). Distinct epileptic syndromes were evident in 13 patients (38%). They were typically simple, focal seizures from the temporal lobe, consisting of vegetative symptoms or fear. At later stages, 22 of 32 patients displayed tonic-dystonic seizures (68%) and 29 patients presented frequent seizures (91%) including status epilepticus. Cognitive impairment, either anterograde amnesia or confusion was evident in 30 of 34 patients (88%). Brain imaging was normal in patients with isolated tonic-dystonic seizures; in patients with limbic symptoms it revealed initially a hippocampal hyperintensity in 8 of 19 patients (42%) and 17 of 24 patients (70%) at later stages. Our data suggest that the major signs of LGI1-antibody encephalitis can be linked to involvement of motor cortex and hippocampus. They occur in parallel with striatum involvement. One of these cortical targets is involved, often unilaterally at disease onset. As the encephalitis progresses, in the absence of immunomodulatory treatment, the second cortical target is affected and effects become bilateral. Progression to the second cortical target occurs with a variable delay of days to several months.
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Epilepsy Unit and Neurophysiology Department, Pitié-Salpêtrière Hospital, Paris, F-75013, France Institut du Cerveau et de la Moelle épinière (ICM; INSERM UMRS1127, CNRS UMR7225, UPMC), Paris, France French Reference Centre on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Bron, F-69677, France vincent.navarro@aphp.fr.
authors.forename: Vincent
authors.initials: V
authors.lastname: Navarro
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Nuclear Medicine Department, Pitié-Salpêtrière Hospital and CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, 75013, France.
authors.forename: Aurélie
authors.initials: A
authors.lastname: Kas
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Neurophysiology Department, Saint-Antoine Hospital, Paris, F-75011, France.
authors.forename: Emmanuelle
authors.initials: E
authors.lastname: Apartis
authors.affiliation: French Reference Centre on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Bron, F-69677, France Lyon Neuroscience Research Centre INSERM U1028/CNRS UMR 5292, Lyon, F-69372, France Université De Lyon - Université Claude Bernard Lyon 1, Lyon, F-69372, France.
authors.forename: Linda
authors.initials: L
authors.lastname: Chami
authors.affiliation: French Reference Centre on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Bron, F-69677, France Lyon Neuroscience Research Centre INSERM U1028/CNRS UMR 5292, Lyon, F-69372, France Université De Lyon - Université Claude Bernard Lyon 1, Lyon, F-69372, France.
authors.forename: Véronique
authors.initials: V
authors.lastname: Rogemond
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Inserm UMR S 1136 (EPAR team), Département de Santé Publique, GH Tenon-Saint Antoine, Paris, F-75020, France.
authors.forename: Pierre
authors.initials: P
authors.lastname: Levy
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM; INSERM UMRS1127, CNRS UMR7225, UPMC), Paris, France Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Neurology 2 Department, Pitié-Salpêtrière Hospital, Paris, F-75013, France.
authors.forename: Dimitri
authors.initials: D
authors.lastname: Psimaras
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Nuclear Medicine Department, Pitié-Salpêtrière Hospital and CNRS, INSERM, Laboratoire d'Imagerie Biomédicale, Paris, 75013, France.
authors.forename: Marie-Odile
authors.initials: MO
authors.lastname: Habert
authors.affiliation: Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Epilepsy Unit and Neurophysiology Department, Pitié-Salpêtrière Hospital, Paris, F-75013, France Institut du Cerveau et de la Moelle épinière (ICM; INSERM UMRS1127, CNRS UMR7225, UPMC), Paris, France.
authors.forename: Michel
authors.initials: M
authors.lastname: Baulac
authors.affiliation: Institut du Cerveau et de la Moelle épinière (ICM; INSERM UMRS1127, CNRS UMR7225, UPMC), Paris, France Sorbonne Universités, UPMC Univ Paris 06, AP-HP, Neurology 2 Department, Pitié-Salpêtrière Hospital, Paris, F-75013, France.
authors.forename: Jean-Yves
authors.initials: JY
authors.lastname: Delattre
authors.affiliation: French Reference Centre on Paraneoplastic Neurological Syndrome, Hospices Civils de Lyon, Hôpital Neurologique, Bron, F-69677, France Lyon Neuroscience Research Centre INSERM U1028/CNRS UMR 5292, Lyon, F-69372, France Université De Lyon - Université Claude Bernard Lyon 1, Lyon, F-69372, France.
authors.forename: Jérome
authors.initials: J
authors.lastname: Honnorat
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001323:Autoantibodies / Q000097:blood*; D015331:Cohort Studies; D004660:Encephalitis / Q000097:blood* / Q000175:diagnosis*; D005260:Female; D057809:HEK293 Cells; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D047908:Intracellular Signaling Peptides and Proteins; D008297:Male; D008875:Middle Aged; D009044:Motor Cortex / Q000473:pathology*; D011506:Proteins / Q000378:metabolism*; D012189:Retrospective Studies; D055815:Young Adult
chemical_list: D001323:Autoantibodies; D047908:Intracellular Signaling Peptides and Proteins; C116499:LGI1 protein, human; D011506:Proteins
keywords: LGI1; encephalitis; epilepsy; hippocampus; tonic seizure