Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis

Gefferie, Silvano R; Maric, Angelina; Critelli, Hanne; Guéden, Sophie; Kurlemann, Gerhard; Kurth, Salomé; Nosadini, Margherita; Plecko, Barbara; Ringli, Maya; Rostásy, Kevin; Sartori, Stefano; Schmitt, Bernhard; Suppiej, Agnese; Bogaert, Patrick Van; Wehrle, Flavia M.; Huber, Reto; Bölsterli, Bigna K.

doi:10.1016/j.neuroimage.2021.118281

Cited by 8 publications

(5 citation statements)

References 54 publications

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“…In this respect, Nmethyl-D-aspartate (NMDA)-type glutamate receptors play an essential role in long-term synaptic plasticity 98 and are postulated to be involved in AD-related synaptic disruption [99][100][101] . In partial support of our hypothesis, a group recently observed a slower negative-to-positive slope of SW (considered here as negative half-waves) during the first hour of NREM sleep, as well as a smaller overnight reduction of the slope, in young participants with anti-NMDA receptor encephalitis (i.e., showing NMDA receptor deficiency) compared to age-matched healthy controls 102 . Additionally, idiopathic rapid eye movement sleep behavior disorder (iRBD) represents a prodromal stage for α-synucleinopathy neurodegeneration 103 .…”

Section: Cognitive Status Sw Characteristics and Cognitive Correlatessupporting

confidence: 69%

Sleep slow waves’ negative-to-positive-phase transition: a marker of cognitive and apneic status in aging

Lafrenière

Lina

Hernandez

et al. 2022

Sleep

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The sleep slow wave (SW) transition between negative and positive phases is thought to mirror synaptic strength and likely depends on brain health. This transition shows significant age-related changes but has not been investigated in pathological aging. The present study aimed at comparing the transition speed and other characteristics of SW between older adults with amnestic mild cognitive impairment (aMCI) and cognitively normal (CN) controls with and without obstructive sleep apnea (OSA). We also examined the association of SW characteristics with the longitudinal changes of episodic memory and executive functions and the degree of subjective cognitive complaints. aMCI (no/mild OSA=17; OSA=15) and CN (no/mild OSA=20; OSA=17) participants underwent a night of polysomnography (PSG) and a neuropsychological evaluation at baseline and 18 months later. Participants with aMCI had a significantly slower SW negative-to-positive-phase transition speed and a higher proportion of SW that are “slow-switchers” than CN participants. These SW measures in the frontal region were significantly correlated with memory decline and cognitive complaints in aMCI and cognitive improvements in CN participants. The transition speed of the SW that are “fast-switchers” was significantly slower in OSA compared to nOSA participants. The SW transition-related metrics showed opposite correlations with the longitudinal episodic memory changes depending on the participants' cognitive status. These relationships were particularly strong in participants with aMCI. As the changes of the SW transition-related metrics in pathological aging might reflect synaptic alterations, future studies should investigate whether these new metrics covary with biomarker levels of synaptic integrity in this population.

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Section: Cognitive Status Sw Characteristics and Cognitive Correlatessupporting

confidence: 69%

Sleep slow waves’ negative-to-positive-phase transition: a marker of cognitive and apneic status in aging

Lafrenière

Lina

Hernandez

et al. 2022

Sleep

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“…Alterations in sleep patterns have been observed on electroencephalography (EEG) in adults with NMDA receptor encephalitis. 25 Further studies could examine the association between sleep complaints and alterations in sleep stages. Insufficient data was available on whether sleep stages were captured on EEG in our cohort, and in a subset of our cohort (n = 11), we have previously demonstrated that loss of normal sleep architecture is associated with poor outcomes as defined by the modified Rankin Score (mRS ≥ 3) at 1 year.…”

Section: Discussionmentioning

confidence: 99%

Sleep Characteristics in Pediatric Anti–N-methyl-d-aspartate (NMDA) Receptor Encephalitis: A Retrospective Cohort Study

et al. 2023

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Background Rates of sleep problems in children with anti –N-methyl-d-aspartate (NMDA) receptor encephalitis are unknown. Methods: We used a retrospective observational cohort database of children with a diagnosis of NMDA receptor encephalitis at a single freestanding institution. One-year outcomes were assessed with the pediatric modified Rankin Score (mRS), with 0 to 2 as good and 3 or greater as poor outcome. Results: Ninety-five percent (39/41) of children with NMDA receptor encephalitis had sleep dysfunction at onset; 34% (11/32) reported sleep problems at 1 year. Sleep problems at onset and propofol use were not associated with poor outcomes at 1 year. Poor sleep at 1 year correlated with mRS scores (range 2-5) at 1 year. Discussion: High rates of sleep dysfunction occur in children with NMDA receptor encephalitis. Persistent sleep problems at 1 year may correlate with outcomes as assessed by mRS at 1 year. Further studies comparing the relationship of poor sleep with outcomes in NMDA receptor encephalitis are needed.

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“…Sleep data from three patient groups were gathered for the purpose of this study. Screening procedures and characteristics of patient groups have previously been published ( 22 , 32 , 33 ). All-night EEG, demographic, and clinical data from individuals with COS ( N = 17, 16.0 ± 3.6 years, 70.6% female), EOS ( N = 11, 16.4 ± 1.4 years, 36.4% female), NMDARE ( N = 8, 13.3 ± 4.5 years, 75.0% female), and 36 age- and sex-matched HC were pooled in this project.…”

Section: Methodsmentioning

confidence: 99%

“…Epoch-specific sleep staging and artifact rejection were available from previous analyses ( 22 , 32 , 33 ). Sleep stages were scored based on standard criteria by a sleep expert and either validated by a second sleep expert (COS, EOS, HC) or by one rater only to reduce inter-rater variability (NMDARE) ( 38 ).…”

Section: Methodsmentioning

confidence: 99%

“…A rare form of autoimmune encephalitis, anti-NMDAR encephalitis (NMDARE), is induced by autoantibodies that target the NMDAR leading to a functional deficit ( 20 ). The symptomatology of NMDARE and SZ also greatly overlap, often presenting with sleep and cognitive disturbances and culminating with a range of psychotic symptoms ( 21 , 22 ). This has encouraged research in the context of the glutamate hypothesis of SZ ( 23 – 28 ).…”

Section: Introductionmentioning

confidence: 99%

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Sleep spindles across youth affected by schizophrenia or anti-N-methyl-D-aspartate-receptor encephalitis

Dimitriades¹,

Markovic²,

Gefferie³

et al. 2023

Front. Psychiatry

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BackgroundSleep disturbances are intertwined with the progression and pathophysiology of psychotic symptoms in schizophrenia. Reductions in sleep spindles, a major electrophysiological oscillation during non-rapid eye movement sleep, have been identified in patients with schizophrenia as a potential biomarker representing the impaired integrity of the thalamocortical network. Altered glutamatergic neurotransmission within this network via a hypofunction of the N-methyl-D-aspartate receptor (NMDAR) is one of the hypotheses at the heart of schizophrenia. This pathomechanism and the symptomatology are shared by anti-NMDAR encephalitis (NMDARE), where antibodies specific to the NMDAR induce a reduction of functional NMDAR. However, sleep spindle parameters have yet to be investigated in NMDARE and a comparison of these rare patients with young individuals with schizophrenia and healthy controls (HC) is lacking. This study aims to assess and compare sleep spindles across young patients affected by Childhood-Onset Schizophrenia (COS), Early-Onset Schizophrenia, (EOS), or NMDARE and HC. Further, the potential relationship between sleep spindle parameters in COS and EOS and the duration of the disease is examined.MethodsSleep EEG data of patients with COS (N = 17), EOS (N = 11), NMDARE (N = 8) aged 7–21 years old, and age- and sex-matched HC (N = 36) were assessed in 17 (COS, EOS) or 5 (NMDARE) electrodes. Sleep spindle parameters (sleep spindle density, maximum amplitude, and sigma power) were analyzed.ResultsCentral sleep spindle density, maximum amplitude, and sigma power were reduced when comparing all patients with psychosis to all HC. Between patient group comparisons showed no differences in central spindle density but lower central maximum amplitude and sigma power in patients with COS compared to patients with EOS or NMDARE. Assessing the topography of spindle density, it was significantly reduced over 15/17 electrodes in COS, 3/17 in EOS, and 0/5 in NMDARE compared to HC. In the pooled sample of COS and EOS, a longer duration of illness was associated with lower central sigma power.ConclusionsPatients with COS demonstrated more pronounced impairments of sleep spindles compared to patients with EOS and NMDARE. In this sample, there is no strong evidence that changes in NMDAR activity are related to spindle deficits.

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Altered EEG markers of synaptic plasticity in a human model of NMDA receptor deficiency: Anti-NMDA receptor encephalitis

Cited by 8 publications

References 54 publications

Sleep slow waves’ negative-to-positive-phase transition: a marker of cognitive and apneic status in aging

Sleep slow waves’ negative-to-positive-phase transition: a marker of cognitive and apneic status in aging

Sleep Characteristics in Pediatric Anti–N-methyl-d-aspartate (NMDA) Receptor Encephalitis: A Retrospective Cohort Study

Sleep spindles across youth affected by schizophrenia or anti-N-methyl-D-aspartate-receptor encephalitis

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