title: Altered paired associative stimulation-induced plasticity in NMDAR encephalitis.
abstract: To determine whether neurophysiological mechanisms indicating cortical excitability, long-term potentiation (LTP)-like plasticity, GABAergic and glutamatergic function are altered in patients with anti-N-methyl-d-aspartate receptor (NMDAR) encephalitis and whether they can be helpful as markers of diagnostic assessment, disease progression, and potentially therapy response.
  
  
  
  Neurophysiological characterizations of patients with NMDAR encephalitis (n = 34, mean age: 28 ± 11 years; 30 females) and age/gender-matched healthy controls (n = 27, 28.5 ± 10 years; 25 females) were performed using transcranial magnetic stimulation-derived protocols including resting motor threshold, recruitment curve, intracortical facilitation, short intracortical inhibition, and cortical silent period. Paired associative stimulation (PAS) was applied to assess LTP-like mechanisms which are mediated through NMDAR. Moreover, resting state functional connectivity was determined using functional magnetic resonance imaging.
  
  
  
  PAS-induced plasticity differed significantly between groups (P = 0.0056). Cortical excitability, as assessed via motor-evoked potentials after PAS, decreased in patients, whereas it increased in controls indicating malfunctioning of NMDAR in encephalitis patients. Lower PAS-induced plasticity significantly correlated with the modified Rankin Scale (mRS) (r = -0.41; P = 0.0031) and was correlated with lower functional connectivity within the motor network in NMDAR encephalitis patients (P < 0.001, uncorrected). Other neurophysiological parameters were not significantly different between groups. Follow-up assessments were available in six patients and demonstrated parallel improvement of PAS-induced plasticity and mRS.
  
  
  
  Assessment of PAS-induced plasticity may help to determine NMDAR dysfunction and disease severity in NMDAR encephalitis, and might even aid as a sensitive, noninvasive, and well-tolerated "electrophysiological biomarker" to monitor therapy response in the future.
  
  
  
  ClinicalTrials.gov: Identifier: NCT01865578.
authors.affiliation: Department of Gastroenterology, Infectiology and Rheumatology Charité - Universitätsmedizin Berlin Germany.
authors.forename: Magdalena Sarah
authors.initials: MS
authors.lastname: Volz
authors.affiliation: Department of Neurology Charité - Universitätsmedizin Berlin Germany; Berlin School of Mind and Brain Humboldt - Universität zu Berlin Germany.
authors.forename: Carsten
authors.initials: C
authors.lastname: Finke
authors.affiliation: Department of Neurology Charité - Universitätsmedizin Berlin Germany; Center for Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Charité - Universitätsmedizin Berlin Germany.
authors.forename: Lutz
authors.initials: L
authors.lastname: Harms
authors.affiliation: German Center for Neurodegenerative Diseases (DZNE) Berlin Germany.
authors.forename: Betty
authors.initials: B
authors.lastname: Jurek
authors.affiliation: Department of Neurology Charité - Universitätsmedizin Berlin Germany; Neuro Cure Clinical Research Center and Experimental and Clinical Research Center and Max Delbrueck Center for Molecular Medicine Charité - Universitätsmedizin Berlin Germany.
authors.forename: Friedemann
authors.initials: F
authors.lastname: Paul
authors.affiliation: Department of Neurology Charité - Universitätsmedizin Berlin Germany; Neuro Cure Clinical Research Center and Experimental and Clinical Research Center and Max Delbrueck Center for Molecular Medicine Charité - Universitätsmedizin Berlin Germany; Center for Stroke Research Berlin Charité - Universitätsmedizin Berlin Germany.
authors.forename: Agnes
authors.initials: A
authors.lastname: Flöel
authors.affiliation: Department of Neurology Charité - Universitätsmedizin Berlin Germany; Center for Autoimmune Encephalitis and Paraneoplastic Neurological Syndromes Charité - Universitätsmedizin Berlin Germany; German Center for Neurodegenerative Diseases (DZNE) Berlin Germany.
authors.forename: Harald
authors.initials: H
authors.lastname: Prüss