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| Item Type: | Article |
|---|---|
| Title: | Altered paired associative stimulation-induced plasticity in NMDAR encephalitis |
| Creators Name: | Volz, M.S. and Finke, C. and Harms, L. and Jurek, B. and Paul, F. and Flöel, A. and Prüss, H. |
| Abstract: | Objective: 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. Methods: 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. Results: 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. Interpretation: 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.Clinical Trial Registration: ClinicalTrials.gov: Identifier: NCT01865578 |
| Keywords: | Transcranial Magnetic Stimulation, Human Motor Cortex, LTP-Like Plasticity, Cortical Excitability, Silent Period, Receptor Encephalitis, Levetiracetam, Mechanisms, Connectivity, Inhibition |
| Source: | Annals of Clinical and Translational Neurology |
| ISSN: | 2328-9503 |
| Publisher: | Wiley |
| Volume: | 3 |
| Number: | 2 |
| Page Range: | 101-113 |
| Date: | February 2016 |
| Official Publication: | https://doi.org/10.1002/acn3.277 |
| PubMed: | View item in PubMed |
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