Functional and structural brain changes in anti–N‐methyl‐D‐aspartate receptor encephalitis

Finke, Carsten; Kopp, Ute A.; Scheel, Michael; Pech, Luisa-Maria; Soemmer, Carina; Schlichting, Jeremias; Leypoldt, Frank; Brandt, Alexander U.; Wuerfel, Jens; Probst, Christian; Ploner, Christoph J.; Prüß, Harald; Paul, Friedemann

doi:10.1002/ana.23932

Cited by 182 publications

(266 citation statements)

References 41 publications

(64 reference statements)

Supporting

Mentioning

223

Contrasting

Unclassified

Order By: Relevance

“…Resting state functional MRI has been shown to reveal characteristic alterations of functional connectivity in NMDAR encephalitis patients despite normal routine MRI 29. Specifically, it was shown that patients have reduced functional connectivity of the hippocampus with the default mode network that correlated with individual memory performance.…”

Section: Discussionmentioning

confidence: 99%

“…Resting state functional connectivity data acquisition and analysis were performed as described previously in NMDAR encephalitis patients 29. Briefly, an echo‐planar imaging sequence (voxel size 3.4 mm isotropic, TR = 2250 msec, TE = 30 msec, 260 volumes) and a three‐dimensional 1 mm isotropic magnetization prepared rapid acquisition gradient echo sequences were acquired on a Siemens (Erlangen, Germany) Tim Trio 3T scanner.…”

Section: Methodsmentioning

confidence: 99%

“…Individual MEP changes (before and after PAS) were included as covariate of interest to investigate the correlation between PAS and motor network functional connectivity 29, 30, 31, 32…”

Section: Methodsmentioning

confidence: 99%

See 2 more Smart Citations

Altered paired associative stimulation‐induced plasticity in NMDAR encephalitis

Volz

Finke

Harms

et al. 2016

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

ObjectiveTo 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.MethodsNeurophysiological 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.InterpretationAssessment 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 RegistrationClinicalTrials.gov: Identifier: NCT01865578

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Methodsmentioning

confidence: 99%

See 1 more Smart Citation

Altered paired associative stimulation‐induced plasticity in NMDAR encephalitis

Volz

Finke

Harms

et al. 2016

Ann Clin Transl Neurol

Self Cite

View full text Add to dashboard Cite

show abstract

“…This cannot, however, be explained by gross brain tissue loss. Neither MRI studies [24] nor histopathology studies have provided evidence for neuronal or other brain tissue loss [27,32].…”

Section: Antibodies Against Nmdarmentioning

confidence: 99%

“…Second, there are studies focusing on the "the other side", that is the target organ. Such studies on the brains of patients with antibody-associated diseases have used positron emission tomography [23], resting state functional magnetic resonance imaging (MRI) [24], or neuropsychology tests [25,26] for functional studies, or MRI and histopathology for structural investigations [24,[27][28][29][30][31][32]. As far as possible, this review will consider the specific issue of epileptogenesis in the context of these encephalitides.…”

Section: Introductionmentioning

confidence: 99%

Autoimmune Epilepsies

Bien

Bauer

2014

Neurotherapeutics

View full text Add to dashboard Cite

In patients with immune-associated disorders of the gray central nervous system matter (including recurrent seizures), antibodies against intracellular antigens have been discovered since the 1980s/1990s. In recent years, new antibodies against surface antigens have also been discovered. In two respects, these antibodies are even more interesting than the ones to intracellular antigens as, first, they promise a better response to immunotherapy; and, second, these antibodies contribute greatly to the understanding of the disease mechanisms. Whereas in encephalitides with antibodies against intracellular antigens, a cytotoxic T-cell-mediated response seems to be responsible for neuronal cell loss, in encephalitides with autoantibodies against surface antigens these antibodies are probably the relevant pathogenic agents in the associated disease conditions. On the one hand, antibodies to the NR1 subunit of N-methyl-D-aspartate receptors have been suggested to cause internalization and loss of these receptors without any cell destruction. This mechanism can explain the reversible functional effects caused by these antibodies. On the other hand, antibody-and complement-mediated destructive, and the irreversible effects of antibodies against the voltage-gated potassium channel antigens have been noted. These emerging findings make it plausible that immunological therapies, preferably early after characterization of the antibodies, offer opportunities to restore the health of affected patients.

show abstract

Evaluation of Cognitive Deficits and Structural Hippocampal Damage in Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies

et al. 2017

Self Cite

View full text Add to dashboard Cite

IMPORTANCE Limbic encephalitis with leucine-rich, glioma-inactivated 1 (LGI1) antibodies is one of the most frequent variants of autoimmune encephalitis with antibodies targeting neuronal surface antigens. However, the neuroimaging pattern and long-term cognitive outcome are not well understood. OBJECTIVE To study cognitive outcome and structural magnetic resonance imaging (MRI) alterations in patients with anti-LGI1 encephalitis.

show abstract

Functional and structural brain changes in anti–N‐methyl‐D‐aspartate receptor encephalitis

Cited by 182 publications

References 41 publications

Altered paired associative stimulation‐induced plasticity in NMDAR encephalitis

Altered paired associative stimulation‐induced plasticity in NMDAR encephalitis

Autoimmune Epilepsies

Evaluation of Cognitive Deficits and Structural Hippocampal Damage in Encephalitis With Leucine-Rich, Glioma-Inactivated 1 Antibodies

Contact Info

Product

Resources

About