Antibody-mediated NMDA Receptor Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Prolonged Recovery Stage

NCT06183788 | Recruiting

• 1 other identifier: HR22-00221
• Study Type: interventional
• Target: 20
• Locations: 1 country
• Sites: 1

Brief Summary

The encephalitis mediated by antibodies against the NMDA receptor (NMDARe) predominantly affects young adults and children resulting in severe neurologic and psychiatric deficits. After overcoming the acute stage, patients are left with long-lasting behavioral, cognitive, and psychiatric alterations with important socio-family-economical implications. Here investigators postulate that a better knowledge of this stage will improve treatment decisions and outcome. In Aim 1, the post-acute stage will be clinically characterized, tools to remotely follow cognitive, behavioral and psychiatric deficits will be provided, and the impact of cognitive rehabilitation will be assessed. In Aim 2, biomarkers (autoimmune, inflammatory, neuronal injury) will be identified as signatures of the acute and post-acute stages. In Aim 3, a mouse model of NMDARe will be used to determine the underlying mechanisms and treatment of the postacute stage.

Conditions

Anti-NMDA Receptor Encephalitis

Keywords

Cognitive Impairment; Encephalitis; Autoimmune; Cognitive rehabilitation

Outcome Measures

Primary Outcomes (69)

• Age

  Age measured in years

  18 months

• Gender

  Male or female

  18 months

• Vision condition

  Studied by optometer

  18 months

• Handedness

  Right- or Left-handed

  18 months

• General medical history

  Description of the most important issues compiled in the general medical history of the participant

  18 months

• Allergies

  List of allergies of each participant

  18 months

• Symptoms related to NMDARe

  Detailed description of symptoms experienced before, during and after the post-acute phase of NMDARe.

  18 months

• Treatments

  All treatments in which the participant is being involved.

  18 months

• Functional status

  Functional status according to Modified Rankin Scale (mRS) Modified Rankin Scale: \- Range: from 0 points (no symptoms) to 6 points (dead).

  18 months

• Intelligence Quotient

  Estimated through General Ability Index (GAI; from Weschler Adult Intelligence Scale - IV (WAIS-IV). This index is obtained through Verbal Comprehension Index (VCI) and Perceptual Reasoning Index (PRI). * Range of GAI: from 40 to 160. Higher is better. * Range of VCI: from 50 to 150. Higher is better. * Range of PRI: from 50 to 150. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Verbal working memory

  Verbal Working Memory: Working Memory Index (WMI) from WAIS-IV. \- Range of WMI: from 50 to 150. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Phonological loop

  Assessed by Forward order span of Digit span subtest from WAIS-IV. \- Range: from 0 to 9 Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Visual working memory

  Visual Working Memory: Spatial location subtest from Weschler Memory Scale - IV (WMS-IV). \- Range of Spatial Location subtest: from 0 to 32. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Verbal learning

  Assessed by: Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC); or Infants: España - Complutense Auditory-Verbal Learning Test for Children (Test de Aprendizaje Verbal España - Complutense Infantil; TAVECI) \- Total learning: range: from 0 to 80. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Proactive interference verbal memory

  Assessed by: Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC); or Infants: España - Complutense Auditory-Verbal Learning Test for Children (Test de Aprendizaje Verbal España - Complutense Infantil; TAVECI) \- Interference list: range: 0 to 15. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Short-term verbal memory

  Assessed by: Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC); or Infants: España - Complutense Auditory-Verbal Learning Test for Children (Test de Aprendizaje Verbal España - Complutense Infantil; TAVECI) \- Short-term memory free recall: range: 0 to 15. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Long-term verbal memory

  Assessed by: Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC); or Infants: España - Complutense Auditory-Verbal Learning Test for Children (Test de Aprendizaje Verbal España - Complutense Infantil; TAVECI) \- Long-term memory free recall: range: 0 to 15. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Verbal recognition memory

  Assessed by: Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC); or Infants: España - Complutense Auditory-Verbal Learning Test for Children (Test de Aprendizaje Verbal España - Complutense Infantil; TAVECI) \- Word-list Recognition: range: 0 to 15. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Verbal discrimination memory

  Assessed by: Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC); or Infants: España - Complutense Auditory-Verbal Learning Test for Children (Test de Aprendizaje Verbal España - Complutense Infantil; TAVECI) \- Discrimination index of word-list: False positives + omissions of recognition between 44 total words to recognize. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Verbal retention memory

  Assessed by: Adults: España - Complutense Auditory-Verbal Learning Test (Test de Aprendizaje Verbal España - Complutense; TAVEC); or Infants: España - Complutense Auditory-Verbal Learning Test for Children (Test de Aprendizaje Verbal España - Complutense Infantil; TAVECI) \- Retention index: percentatge of Long-term memory free recall between Short-term memory free recall. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Immediate visual memory

  Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R) \- Immediate visual memory: range: from 0 to 36. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Delayed visual memory

  Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R) \- Delayed visual memory: range: from 0 to 12. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Visual retention memory

  Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R) \- Retention index: percentatge of Long-term memory free recall between the Higher punctuation at Trial 2 or 3. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Visual recognition memory

  Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R) \- Figure Recognition: range: from 0 to 6. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Visual discrimination memory

  Assessed by: Brief Visuospatial Memory Test - Revised (BVMT-R) \- Discrimination index: figure recognized minus false positives. Range: from -6 to 6. Higher is better. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Processing speed

  Processing speed Index (PSI; from Weschler Adult Intelligence Scale - IV (WAIS-IV). Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• TMT-A

  Trail Making Test part A (TMT-A): \- Time in seconds: from 0 to infinity. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• TMT-B

  Trail Making Test part B (TMT-B): \- Time in seconds: from 0 to infinity. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Naming

  Assessed by: Boston Naming Test (BNT) \- Total correct: from 0 to 60 Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Naming with cues

  Assessed by: Boston Naming Test (BNT) \- Total correct with phonemic cue: from 0 to 60

  18 months

• Latency in naming

  Assessed by: Boston Naming Test (BNT) \- Time to complete test in seconds

  18 months

• Semantic fluency

  Number of name of animals recalled in 1 minute: range: from 0 to infinity. (Test Barcelona - Revised) (for ADULTS) Number of name of animals recalled in 1 minute + number of name of food and drinks recalled in 1 minute: from 0 to infinity (NEPSY - II) (for CHILDREN) Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Phonemic fluency

  Number of words started by letter "M" recalled in 1 minute: Range: from 0 to infinity. (Test Barcelona-Revised) (for ADULTS) Number of words started by letter "P" recalled in 1 minute + number of words started by letter "M" in 1 minute: range: from 0 to infinity (NEPSY-II) (for CHILDREN). Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Visuospatial skills

  Number location subtest of the Visual-Object Spatial and Perceptual battery. \- Range: from 0 to 10 Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Visuospatial skills - children

  Assessed by Arrows subtest of NEPSY-2 battery \- Range: from 0 to 20 Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Stroop test - word subtest

  \- Words: words read in 45 seconds Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Stroop test - color subtest

  \- Colour: colours distinguished in 45 seconds. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Stroop test - word-color subtest

  \- Word-colour: colours distinguished in 45 seconds. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Detectability - CPT3

  Assessed by Continuous Performance Test - 3rd Version. Measures the respondent's ability to differentiate non-targets (i.e. the letter X) from targets (i.e. all other letters). Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Omissions - CPT3

  Assessed by Continuous Performance Test - 3rd Version. Result from a failure to respond to targets. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Comissions - CPT3

  Assessed by Continuous Performance Test - 3rd Version. Comissions are made when responses are given to non-targets. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• HRT - CPT3

  Assessed by Continuous Performance Test - 3rd Version. Hit Reaction Time (HRT) is the mean response speed of correct responses from the whole administration. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• HRT-SD - CPT3

  Assessed by Continuous Performance Test - 3rd Version. Hit Reaction Time Standard Deviation (HRT-SD) is a measure of response speed consistency during the entire administration. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Variability- CPT3

  Assessed by Continuous Performance Test - 3rd Version. The amount of variability that the patient showed in 18 separate segments of the administration in relation to their own overall Hit Reaction Time Standard Deviation (HRT-SD). It is a measure of response consistency and a "within respondent" measure". Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• HRT Block Change - CPT3

  Assessed by Continuous Performance Test - 3rd Version. Hit Reaction Time Block Change indicates the change in mean response speed across blocks. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• HRT ISI Change - CPT3

  Assessed by Continuous Performance Test - 3rd Version. Hit Reaction Time Inter-Stimulus Interval Change (HRT ISI Change) indicates the change in mean response speed at various ISIs. Raw scores were transformed into standard T-scores (mean 50 ± standard deviation \[SD\] 10) and a score below 35 (≤ 1.5 SD below normative mean, or the equivalent ≤9th percentile) was considered significantly decreased.

  18 months

• Prensence of psychiatric symptoms or disorders in presential assessments

  Number of participants with psychiatric symptoms/disorders following DSM-IV-TR guidelines (psychotic symptoms, symptoms of depression, symptoms of mania, global functioning).

  18 months

• Sleep microstructure - Total study time

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Total sleep time: minutes

  18 months

• Sleep microstructure - Total sleep time

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Total sleep time: minutes

  18 months

• Sleep microstructure - Sleep efficiency

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Sleep efficiency: based on total study time and total sleep time

  18 months

• Sleep microstructure - Time to sleep onset

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Time to sleep onset: minutes

  18 months

• Sleep microstructure - Time in stage N1

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Time in stage N1: minutes

  18 months

• Sleep microstructure - Time in stage N2

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Time in stage N2: minutes

  18 months

• Sleep microstructure - Time in stage N3

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Time in stage N3: minutes

  18 months

• Sleep microstructure - Time in stage R

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Time in stage R: minutes

  18 months

• Sleep microstructure - First epoch of N1

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- First epoch of N1: minutes

  18 months

• Sleep microstructure - First epoch of N2

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- First epoch of N2: minutes

  18 months

• Sleep microstructure - First epoch of N3

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- First epoch of N3: minutes

  18 months

• Sleep microstructure - First epoch of REM

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- First epoch of REM: minutes

  18 months

• Sleep microstructure - REM/NREM time ratio

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- REM/NREM time ratio

  18 months

• Sleep microstructure - Number of arousals

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Number of arousals (total)

  18 months

• Sleep microstructure - Arousal Index

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Arousal Index

  18 months

• Sleep microstructure - Confusional arousals

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Confusional arousals: Yes or No

  18 months

• Sleep microstructure - Direct transition from N3 to W

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Direct transition from N3 to W: yes or no

  18 months

• Sleep microstructure - Delta arousals

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- "Delta arousals"?: yes, no or unknown

  18 months

• Sleep microstructure - Wake after sleep

  It will be adapted to patient's sleep habits (\~23:00 to 07:30) using a digital polygraph (Deltamed). This includes EEG in 43 scalp channels + 11 channels for electrooculography, electrocardiography, electromyography, and audiovisual recording (sampling rate 256 Hz). Sleep stages will be scored manually (AASM criteria) using 30-s epochs, with modifications depending on sleep alterations, as reported. Parameters: \- Wake after sleep: hour

  18 months

• Adherence to cognitive treatment - 6 months

  Number of sessions performed in 6 months

  6 months

• Adherence to cognitive treatment - 9 months

  Number of sessions performed in 9 months

  9 months

• Adherence to cognitive treatment - 12 months

  Number of sessions performed in 12 months

  12 months

Secondary Outcomes (83)

• Immune/inflammatory signaling-target gene expression pathways

  18 months

• Neurofilament light chain (NfL) levels in acute stage

  18 months

• Neurofilament light chain (NfL) levels in post-acute stage

  18 months

• Cell immunophenotyping - proportion of CD4

  18 months

• Cell immunophenotyping - proportion of CD8

  18 months

Study Arms (1)

Anti-NMDARe patients with remote cognitive rehabilitation

EXPERIMENTAL

Participants of a prospective cohort in post-acute phase of the Antibody-mediated NMDA Receptor Encephalitis that will received a behavioral treatment.

Behavioral: Remote cognitive rehabilitation program

Interventions

Remote cognitive rehabilitation program BEHAVIORAL

Remote cognitive rehabilitation program will be performed through an online validated platform (Guttmann NeuroPersonalTrainer: https://gnpt.es/) run by the psychologists team. This is a Sanitary Product with CE certification (Sanitary Product RPS/430/2014; International Patent \[PCT/ES2008/00677\]) and here will be used within its approved indications. The rehabilitation program will increase in difficulty and decrease in frequency during the first year of follow-up (V1-V3).

Anti-NMDARe patients with remote cognitive rehabilitation

Eligibility Criteria

• Age: 12 Years+
• Sex: all
• Healthy Volunteers: No
• Age Groups: Child (0-17), Adult (18-64), Older Adult (65+)

You may qualify if:

• Patients ≥12 years old with NMDARe in the post-acute stage of the disease;
• ≤6 months from hospital discharge (acute phase)

You may not qualify if:

• Inability to obtain informed consent;
• inability to travel to the center.

Sponsors & Collaborators

• Fundacion Clinic per a la Recerca Biomédica: lead
• Hospital Sant Joan de Deu: collaborator

Study Sites (1)

Hospital Clínic de Barcelona

Barcelona, Catalonia, 08036, Spain

RECRUITING

Related Publications (6)

• Guasp M, Rosa-Justicia M, Munoz-Lopetegi A, Martinez-Hernandez E, Armangue T, Sugranyes G, Stein H, Borras R, Prades L, Arino H, Planaguma J, De-La-Serna E, Escudero D, Llufriu S, Sanchez-Valle R, Santamaria J, Compte A, Castro-Fornieles J, Dalmau J; Spanish anti-NMDAR Encephalitis Study Group. Clinical characterisation of patients in the post-acute stage of anti-NMDA receptor encephalitis: a prospective cohort study and comparison with patients with schizophrenia spectrum disorders. Lancet Neurol. 2022 Oct;21(10):899-910. doi: 10.1016/S1474-4422(22)00299-X.

  PMID: 36115362 BACKGROUND

• Titulaer MJ, McCracken L, Gabilondo I, Armangue T, Glaser C, Iizuka T, Honig LS, Benseler SM, Kawachi I, Martinez-Hernandez E, Aguilar E, Gresa-Arribas N, Ryan-Florance N, Torrents A, Saiz A, Rosenfeld MR, Balice-Gordon R, Graus F, Dalmau J. Treatment and prognostic factors for long-term outcome in patients with anti-NMDA receptor encephalitis: an observational cohort study. Lancet Neurol. 2013 Feb;12(2):157-65. doi: 10.1016/S1474-4422(12)70310-1. Epub 2013 Jan 3.

  PMID: 23290630 BACKGROUND

• Arino H, Munoz-Lopetegi A, Martinez-Hernandez E, Armangue T, Rosa-Justicia M, Escudero D, Matos N, Graus F, Sugranyes G, Castro-Fornieles J, Compte A, Dalmau J, Santamaria J. Sleep disorders in anti-NMDAR encephalitis. Neurology. 2020 Aug 11;95(6):e671-e684. doi: 10.1212/WNL.0000000000009987. Epub 2020 Jun 23.

  PMID: 32576635 BACKGROUND

• Finke C, Kopp UA, Scheel M, Pech LM, Soemmer C, Schlichting J, Leypoldt F, Brandt AU, Wuerfel J, Probst C, Ploner CJ, Pruss H, Paul F. Functional and structural brain changes in anti-N-methyl-D-aspartate receptor encephalitis. Ann Neurol. 2013 Aug;74(2):284-96. doi: 10.1002/ana.23932. Epub 2013 Jul 8.

  PMID: 23686722 BACKGROUND

• Heine J, Kopp UA, Klag J, Ploner CJ, Pruss H, Finke C. Long-Term Cognitive Outcome in Anti-N-Methyl-D-Aspartate Receptor Encephalitis. Ann Neurol. 2021 Dec;90(6):949-961. doi: 10.1002/ana.26241. Epub 2021 Oct 21.

  PMID: 34595771 BACKGROUND

• Armangue T, Titulaer MJ, Malaga I, Bataller L, Gabilondo I, Graus F, Dalmau J; Spanish Anti-N-methyl-D-Aspartate Receptor (NMDAR) Encephalitis Work Group. Pediatric anti-N-methyl-D-aspartate receptor encephalitis-clinical analysis and novel findings in a series of 20 patients. J Pediatr. 2013 Apr;162(4):850-856.e2. doi: 10.1016/j.jpeds.2012.10.011. Epub 2012 Nov 16.

  PMID: 23164315 BACKGROUND

MeSH Terms

Conditions

Anti-N-Methyl-D-Aspartate Receptor Encephalitis; Cognitive Dysfunction; Encephalitis

Condition Hierarchy (Ancestors)

Paraneoplastic Syndromes, Nervous System; Nervous System Neoplasms; Neoplasms by Site; Neoplasms; Paraneoplastic Syndromes; Brain Diseases; Central Nervous System Diseases; Nervous System Diseases; Neurodegenerative Diseases; Neuroinflammatory Diseases; Autoimmune Diseases of the Nervous System; Autoimmune Diseases; Immune System Diseases; Cognition Disorders; Neurocognitive Disorders; Mental Disorders

Study Officials

• Josep Dalmau, MD, PhD

  Hospital Clínic

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Josep Dalmau, MD,PhD

CONTACT

34 93 227 1738; jdalmau@clinic.cat

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: NONE
• Purpose: SUPPORTIVE CARE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: SPONSOR

Study Record Dates

• First Submitted: May 19, 2023
• First Posted: December 28, 2023
• Study Start: January 16, 2023
• Primary Completion: January 1, 2025
• Study Completion: November 30, 2025
• Last Updated: May 6, 2024

Record last verified: 2024-05

Locations

ES (1)