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Anti-N-Methyl-D-Aspartate Receptor Encephalitis

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

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).

Remote cognitive rehabilitation program

Josep Dalmau, MD,PhD

Josep Dalmau, MD, PhD

Victor Patricio, MS

Thais Armanguè, MD, PhD

Mar Guasp, MD, PhD

Eugenia Martínez-Hernández, MD, PhD

Amaia Muñoz, MD

Laia Prades, MS

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.

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

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

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

All treatments in which the participant is being involved.

Functional status according to Modified Rankin Scale (mRS)

Modified Rankin Scale:

- Range: from 0 points (no symptoms) to 6 points (dead).

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Assessed by: Boston Naming Test (BNT)

- Total correct with phonemic cue: from 0 to 60

Assessed by: Boston Naming Test (BNT)

- Time to complete test in seconds

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.

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.

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.

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.

- 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.

- 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.

- 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.

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.

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.

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.

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.

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.

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.

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.

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.

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

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

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

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

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

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

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

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

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

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

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

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

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

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)

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

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

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

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

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

Number of sessions performed in 12 months

Whole blood/CSF will be collected using PAXgene® Blood RNA Tubes (Qiagen) shipped to the centers. Blood from healthy subjects and CSF from patients with normal pressure hydrocephalus will serve as controls.

Total RNA will be extracted using PAXgene® Blood RNA Kit (Qiagen). RNA samples are quantified using Qubit 2.0 Fluorometer (Life Technologies) and RNA integrity is determined with Agilent 2100 Bioanalyzer (Agilent Technologies).

Expression levels of 44 genes related to immune/inflammatory (or cytokine) pathways will be measured with the nCounter® Digital Analyzer (NanoString).

The raw copy number of mRNA transcripts of each gene will be standardized (stdGene) using the geometric mean of the 4 housekeeping genes for each subject.

Signature of molecular biomarkers in the acute stage

Signature of molecular biomarkers in the post-acute stages

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of CD4.

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of CD8.

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of CD8+CD45RA+.

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of CD8+CD45RO+.

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of iNKT.

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of CD19.

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of B naive (IgM+IgD+CD27-).

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of B memory (IgD-).

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of regulatory B cells.

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of plasmablasts.

Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of NK cells.

It will be conducted on a 3 Tesla Prisma scanner using a 32-channel head coil. Scanning takes \~50 min including 3D T1-weighted in sagittal plane; T2\*axial EPI; axial diffusion weighted EPI; 3D sagittal FLAIR; resting state functional MRI and glutamate and H2O univoxel spectroscopy in dorsolateral prefrontal cortex and hippocampus. There is no contrast used for the MRI scans

Outcome for MRI is normal or abnormal. Investigators will review all MRI sequences and determine if the MRI is abnormal and then describe the abnormality or abnormalities seen.

It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

- Normalcy: yes or no.

It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Parameters:

- Time awake: percentage

It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Parameters:

- Time in drowsiness: percentage

It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Parameters:

- Time asleep: percentage

It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Parameters:

- Epileptiform activity: yes or no

It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Parameters:

- Seizures: yes or no

It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Parameters:

- EEG slowing: yes or no

It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Parameters:

- Changes with Intermittent Light Stimulation: yes or no

It will include standard clinical EEG protocol (43 channels, 512 Hz18) (primary variables), and EEG reactivations of memories prior to new trials (secondary variables) while participants perform WM tasks, which will be synchronized with the task software in a laptop. The memory content from alpha power across electrodes will be related to the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Performances of the subjects produces a reactivation of memory prior to new trials while participants perform working memory tasks, and relate the decoding accuracy in different task periods to disease treatment and recovery and to behavioral parameters (WM precision, serial biases).

Parameters:

- Changes with hyperventilation: yes or no

Assessed by:

Digit subtest from WAIS-IV: obtained by Forward order, indirect order, increasing order subtests.

- Range: 0 - 48

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.

Assessed by:

Total learning List A subtest from Rey Auditory Verbal Learning Test (RAVLT)

- Range: 0 - 75

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.

Assessed by:

List B subtest from Rey Auditory Verbal Learning Test (RAVLT)

- Range: 0 - 15

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.

Assessed by:

Short-term verbal memory subtest from Rey Auditory Verbal Learning Test (RAVLT)

- Range: 0 - 15

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.

Assessed by:

Long-term verbal memory subtest from Rey Auditory Verbal Learning Test (RAVLT)

- Range: 0 - 15

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.

Assessed by:

Verbal recognition memory list subtest from Rey Auditory Verbal Learning Test (RAVLT)

- Range: 0 - 15

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.

Assessed by:

Verbal discrimination memory subtest from Rey Auditory Verbal Learning Test (RAVLT)

- Range: 0 - 1

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.

Assessed by:

Precision in the copy of the Rey-Osterrieth Complex Figure:

- Range: 0-36

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.

Assessed by:

Time to perform the copy of the Rey-Osterrieth Complex Figure: 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.

Assessed by:

Type of copy of the Rey-Osterrieth Complex Figure:

- Range: 1 to 4

Assessed by:

Short term memory subtest of the Rey-Osterrieth Complex Figure:

- Range: 0 - 36

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.

Assessed by:

Long-term memory subtest of the Rey-Osterrieth Complex Figure:

- Range: 0 - 36

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.

Assessed by:

Orientation in time subtest from Test Barcelona - Revised.

- Range: 0 - 5

Higher is better.

Assessed by:

Orientation in space subtest from Test Barcelona - Revised.

- Range: 0 -5

Assessed by:

Lecture subtest from 5 digit test: time

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.

Assessed by:

Counting subtest from 5 digit test: time

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.

Assessed by:

Choosing subtest from 5 digit test: time

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.

Assessed by:

Switching subtest from 5 digit test: time

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.

Assessed by:

Inhibition subtest from 5 digit test: time

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.

Assessed by:

Flexibility subtest from 5 digit test: time

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.

IED EDS Errors: The number of times that the subject failed to select the stimulus compatible with the current rule on the stage where the extra-dimensional shift occurs. This is a measure of the subject's ability to shift attentional set.

Assessed by:

Intra-Extra Dimensional test from CANTAB battery.

- Raw score range: 0 - 50. Lower 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.

IED Total Errors (Adjusted): The total number of times that the subject chose a wrong stimulus - i.e. one incompatible with the current rule, adjustment for every stage that was not reached. Lower is better. Total Errors Adjusted = Total Errors (problems reached) + \[(number of unreached problems) \* (25)\] This is a measure of the subject's efficiency in attempting the test. Subjects failing at any stage of the test will have had less opportunity to make errors. The adjustment is carried out to compensate for this missing data, and provide a more comparable error score to subjects completing all stages of the test..

Assessed by:

Intra-Extra Dimensional test from CANTAB battery.

- Raw score range: 0 - 402. Lower 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.

IED Stages Completed: This is the total number of stages the subject completed successfully. There are nine stages to be completed. Higher is better.

Assessed by:

Intra-Extra Dimensional test from CANTAB battery.

- Range: 0 - 9. Higher is better.

SWM Total Errors: The total number of times a box is selected that is certain not to contain a token and therefore should not have been visited by the subject, i.e. between errors + within errors - double errors. Calculated across all assessed four, six and eight token trials.

Assessed by:

Spatial Working Memory test from CANTAB battery.

- Range: 0 - 157. Lower is better

SWM Between Errors: The number of times the subject incorrectly revisits a box in which a token has previously been found. Calculated across all assessed four, six and eight token trials.

Assessed by:

Spatial Working Memory test from CANTAB battery:

- Raw score range: 0 - 153. Lower 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.

SWM Within Errors: The number of times a subject revisits a box already shown to be empty during the same search. Calculated across all assessed four, six and eight token trials.

Assessed by:

Spatial Working Memory test from CANTAB battery:

- Range: 0 - 153. Lower is better.

SWM Double Errors: The number of times a subject commits an error that is both a within error and a between error. Calculated across all assessed four, six and eight token trials.

Assessed by:

Spatial Working Memory test from CANTAB battery:

- Range: 0 - 147. Lower is better.

SWM Strategy (6-8 boxes): The number of times a subject begins a new search pattern from the same box they started with previously. If they always begin a search from the same starting point we infer that the subject is employing a planned strategy for finding the tokens. Therefore a low score indicates high strategy use (1 = they always begin the search from the same box), a high score indicates that they are beginning their searches from many different boxes. Calculated across assessed trials with 6 tokens or 8 tokens.

Assessed by:

Spatial Working Memory test from CANTAB battery:

- Range: 2 - 14. Lower 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

SWM Strategy (6-12 boxes): The number of times a subject begins a new search pattern from the same box they started with previously. If they always begin a search from the same starting point we infer that the subject is employing a planned strategy for finding the tokens. Therefore a low score indicates high strategy use (1 = they always begin the search from the same box), a high score indicates that they are beginning their searches from many different boxes. Calculated across assessed trials with 6 tokens or more.

Assessed by:

Spatial Working Memory test from CANTAB battery:

- Range: 3 - 26. Lower is better.

SWM Problem Reached: This measure reports the problem number that the subject reached, but did not necessarily complete.

Assessed by:

Spatial Working Memory test from CANTAB battery:

- Range: 2 - 6. Higher is better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total Hits: The total number of times the subject selected the correct emotion. Calculated across all assessed trials.

- Range: 0 - 90. Higher is Better

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total Hits Happiness: The total number of times the subject correctly selected the emotion 'Happiness'. Calculated across all assessed trials.

- Range: 0 - 15 . Higher is Better

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total Hits Sadness: The total number of times the subject correctly selected the emotion 'Sadness'. Calculated across all assessed trials.

- Range: 0 - 15 . Higher is Better

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total Hits Fear: The total number of times the subject correctly selected the emotion 'Fear'. Calculated across all assessed trials.

- Range: 0 - 15 . Higher is Better

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total Hits Anger: The total number of times the subject correctly selected the emotion 'Anger'. Calculated across all assessed trials.

- Range: 0 - 15 . Higher is Better

Assessed by:

Emotion Recognition Task from CANTAB battery

ERT Total Hits Surprise: The total number of times the subject correctly selected the emotion 'Surprise'. Calculated across all assessed trials.

- Range: 0 - 15 . Higher is Better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total Hits Disgust: The total number of times the subject correctly selected the emotion 'Disgust'. Calculated across all assessed trials.

- Range: 0 - 15 . Higher is Better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total False Alarms Happiness: The total number of times the subject incorrectly selected the emotion 'Happiness'. Calculated across all assessed trials.

- Range: 0 - 75 . Lower is Better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total False Alarms Sadness: The total number of times the subject incorrectly selected the emotion 'Sadness'. Calculated across all assessed trials.

- Range: 0 - 75 . Lower is Better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total False Alarms Fear: The total number of times the subject incorrectly selected the emotion 'Fear'. Calculated across all assessed trials.

- Range: 0 - 75 . Lower is Better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total False Alarms Anger: The total number of times the subject incorrectly selected the emotion 'Anger'. Calculated across all assessed trials.

- Range: 0 - 75 . Lower is Better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total False Alarms Surprise: The total number of times the subject incorrectly selected the emotion 'Surprise'. Calculated across all assessed trials.

- Range: 0 - 75 . Lower is Better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Total False Alarms Disgust: The total number of times the subject incorrectly selected the emotion 'Disgust'. Calculated across all assessed trials.

- Range: 0 - 75 . Lower is Better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Unbiased Hit Rate Happiness: The unbiased hit rate ensures that recognition accuracy of the Happiness emotion is not influenced by response guessing or response bias effects. It takes into consideration the joint probability of an individual making a correct response, based on the presentation of the correct stimulus out of the available possibilities. Calculated for assessed Happiness trials only.

- Range: 0 to 1. Higher is better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Unbiased Hit Rate Sadness: The unbiased hit rate ensures that recognition accuracy of the Sadness emotion is not influenced by response guessing or response bias effects. It takes into consideration the joint probability of an individual making a correct response, based on the presentation of the correct stimulus out of the available possibilities. Calculated for assessed Sadness trials only

- Range: 0 to 1. Higher is better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Unbiased Hit Rate Fear: The unbiased hit rate ensures that recognition accuracy of the Fear emotion is not influenced by response guessing or response bias effects. It takes into consideration the joint probability of an individual making a correct response, based on the presentation of the correct stimulus out of the available possibilities. Calculated for assessed Fear trials only.

- Range: 0 to 1. Higher is better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Unbiased Hit Rate Anger: The unbiased hit rate ensures that recognition accuracy of the Anger emotion is not influenced by response guessing or response bias effects. It takes into consideration the joint probability of an individual making a correct response, based on the presentation of the correct stimulus out of the available possibilities. Calculated for assessed Anger trials only.

- Range: 0 to 1. Higher is better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Unbiased Hit Rate Surprise: The unbiased hit rate ensures that recognition accuracy of the Surprise emotion is not influenced by response guessing or response bias effects. It takes into consideration the joint probability of an individual making a correct response, based on the presentation of the correct stimulus out of the available possibilities. Calculated for assessed Anger trials only.

- Range: 0 to 1. Higher is better.

Assessed by:

Emotion Recognition Task from CANTAB battery.

ERT Unbiased Hit Rate Disgust: The unbiased hit rate ensures that recognition accuracy of the Disgust emotion is not influenced by response guessing or response bias effects. It takes into consideration the joint probability of an individual making a correct response, based on the presentation of the correct stimulus out of the available possibilities. Calculated for assessed Disgust trials only.

- Range: 0 to 1. Higher is better.

Assessed by:

Semantic fluency test:

* Produce names of fruits and vegetables in 1 minute (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.

Assessed by:

Phonemic fluenct test:

* Produce words that start with letter M 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.

Assessed by:

Boston Naming Test (BNT):

- Range: 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.

Assessed by: Boston Naming Test (BNT): time to complete

Assessed by:

Benton Judgment of Line Orientation Test (JLO):

- Range: 0 to 30

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.

This is quantified from the participant responses in the working memory task. Errors in the report of memorized locations are multiplied by the sign of the difference in locations in the previous and current trials and then averaged over the whole session to obtain the index of serial bias. We expect increases in this index as patients improve clinically.

This is quantified by training decoders of memorized locations on EEG signals acquired over several electrodes during the working memory task. Reactivations are the average strength of the decoders during the fixation period of the next trial. We expect that EEG reactivations increase as patients improve clinically and correlate with the serial bias index.

This is quantified from EEG recorded during sleep, by detecting individual slow-waves and estimating their strength, and then computing the rate of growth of this strength in the first slow-wave periods in the night. We expect the rate of growth of slow waves to increase as patients improve.

Hospital Sant Joan de Deu

Fundacion Clinic per a la Recerca Biomédica

Rare Diseases

Glioma

Neurocognitive Disorders

Brain Neoplasms

Central Nervous System Neoplasms

Mental Disorders

Psychotic Disorders

Neoplasms, Neuroepithelial

Neuroectodermal Tumors

Neuroectodermal Tumors, Primitive

Neoplasms, Germ Cell and Embryonal

Neoplasms by Histologic Type

Neoplasms, Glandular and Epithelial

Neoplasms, Nerve Tissue

Neuroepithelioma

C-SMART intervention will be provided via telehealth. Participants will complete in-person neurocognitive testing (baseline, post-intervention) as well as surveys (baseline, post-session, post-intervention) via secure email link. Exit interviews will be conducted by Zoom.

The C-SMART intervention includes approximately 8 individual therapy sessions, each approximately 60 minutes in length, delivered weekly. C-SMART intervention components include cognitive rehabilitation and mindfulness training.

Study title	NCT ID	Conditions	Interventions	Eligibility	Organization
Antibody-mediated NMDA Receptor Encephalitis: Symptoms, Biomarkers, and Mechanisms of the Prolonged Recovery Stage	NCT06183788	Anti-NMDA Recep...	Remote cognitiv...	12 Years -	Fundacion Clinic per a la Recerca Biomédica
C-SMART: Cognitive Strategies, Mindfulness, and Rehabilitation Therapy for Patients With Primary Brain Tumors	NCT05984667	Glioma, Mixed Mild Neurocogni... Brain Tumor	C-SMART	18 Years -	Virginia Commonwealth University
Cognitive Rehabilitation of Glioma Patients	NCT00256425	Glioma Cognition Disor...	Cognitive rehab...	18 Years - 70 Years	UMC Utrecht
C-SMART: Cognitive Strategies, Mindfulness, and Rehabilitation Therapy for Patients With Primary Brain Tumors	NCT05984667	Glioma, Mixed Mild Neurocogni... Brain Tumor	C-SMART	18 Years -	Virginia Commonwealth University
Goal Management Training for Adult Survivors of Childhood Leukemia and Non-Hodgkins Lymphoma With Neurocognitive Sequelae	NCT04541056	Childhood Non-H... Childhood Acute... Childhood Acute...	Goal Management... Brain Health Wo...	18 Years - 40 Years	Norwegian University of Science and Technology
C-SMART: Cognitive Strategies, Mindfulness, and Rehabilitation Therapy for Patients With Primary Brain Tumors	NCT05984667	Glioma, Mixed Mild Neurocogni... Brain Tumor	C-SMART	18 Years -	Virginia Commonwealth University
Cognitive Rehabilitation of Glioma Patients	NCT00256425	Glioma Cognition Disor...	Cognitive rehab...	18 Years - 70 Years	UMC Utrecht
Effects of Computer-Assisted Cognitive Rehabilitation Programs With Breast Cancer Survivors	NCT04027400	Cognitive Impai... Breast Cancer	computer-assist...	18 Years - 99 Years	Texas Woman's University
Impact of Cognitive Rehab and Physical Activity on Cognition in Patients With Metastatic Brain Tumors Undergoing RT	NCT03096431	Metastatic Brai... Cerebral Metast...	Physical Activi... Cognitive rehab...	18 Years -	Virginia Commonwealth University

Spots Global Cancer Trial Database for cognitive rehabilitation