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.
Study Type
INTERVENTIONAL
Allocation
NA
Purpose
SUPPORTIVE_CARE
Masking
NONE
Enrollment
20
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).
Hospital Clínic de Barcelona
Barcelona, Catalonia, Spain
RECRUITINGAge
Age measured in years
Time frame: 18 months
Gender
Male or female
Time frame: 18 months
Vision condition
Studied by optometer
Time frame: 18 months
Handedness
Right- or Left-handed
Time frame: 18 months
General medical history
Description of the most important issues compiled in the general medical history of the participant
Time frame: 18 months
Allergies
List of allergies of each participant
Time frame: 18 months
Symptoms related to NMDARe
Detailed description of symptoms experienced before, during and after the post-acute phase of NMDARe.
Time frame: 18 months
Treatments
All treatments in which the participant is being involved.
Time frame: 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).
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 18 months
Naming with cues
Assessed by: Boston Naming Test (BNT) \- Total correct with phonemic cue: from 0 to 60
Time frame: 18 months
Latency in naming
Assessed by: Boston Naming Test (BNT) \- Time to complete test in seconds
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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.
Time frame: 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).
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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)
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 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
Time frame: 18 months
Adherence to cognitive treatment - 6 months
Number of sessions performed in 6 months
Time frame: 6 months
Adherence to cognitive treatment - 9 months
Number of sessions performed in 9 months
Time frame: 9 months
Adherence to cognitive treatment - 12 months
Number of sessions performed in 12 months
Time frame: 12 months
Immune/inflammatory signaling-target gene expression pathways
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.
Time frame: 18 months
Neurofilament light chain (NfL) levels in acute stage
Signature of molecular biomarkers in the acute stage
Time frame: 18 months
Neurofilament light chain (NfL) levels in post-acute stage
Signature of molecular biomarkers in the post-acute stages
Time frame: 18 months
Cell immunophenotyping - 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 CD4.
Time frame: 18 months
Cell immunophenotyping - 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.
Time frame: 18 months
Cell immunophenotyping - 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+CD45RA+.
Time frame: 18 months
Cell immunophenotyping - proportion of CD8+CD45RO+
This platform is for informational purposes only and does not constitute medical advice. Always consult a qualified healthcare professional.
Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of CD8+CD45RO+.
Time frame: 18 months
Cell immunophenotyping - 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 iNKT.
Time frame: 18 months
Cell immunophenotyping - 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 CD19.
Time frame: 18 months
Cell immunophenotyping - 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 naive (IgM+IgD+CD27-).
Time frame: 18 months
Cell immunophenotyping - 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 B memory (IgD-).
Time frame: 18 months
Cell immunophenotyping - 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 regulatory B cells.
Time frame: 18 months
Cell immunophenotyping - 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 plasmablasts.
Time frame: 18 months
Cell immunophenotyping - proportion of NK cells
Whole blood/CSF obtained in a EDTA tube will be analyzed in a FACS Canto II cytometer to assess the proportion of NK cells.
Time frame: 18 months
MRI
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.
Time frame: 18 months
EEG: normalcy
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.
Time frame: 18 months
EEG: time awake
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
Time frame: 18 months
EEG: time in drowsiness
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
Time frame: 18 months
EEG: time asleep
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
Time frame: 18 months
EEG: epileptiform activity
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
Time frame: 18 months
EEG: seizures
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
Time frame: 18 months
EEG: slowing
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
Time frame: 18 months
EEG: Changes with Intermittent Light Stimulation
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
Time frame: 18 months
EEG: Changes with hyperventilation
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
Time frame: 18 months
Verbal working memory - remote assessment
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.
Time frame: 18 months
Verbal learning - remote assessment
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.
Time frame: 18 months
Proactive interference verbal memory - remote assessment
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.
Time frame: 18 months
Short-term verbal memory - remote assessment
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.
Time frame: 18 months
Long-term verbal memory - remote assessment
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.
Time frame: 18 months
Verbal recognition memory - remote assessment
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.
Time frame: 18 months
Verbal discrimination memory - remote assessment
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.
Time frame: 18 months
Complex figure copy - remote assessment
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.
Time frame: 18 months
Time - Complex figure copy - remote assessment
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.
Time frame: 18 months
Type - Complex figure copy - remote assessment
Assessed by: Type of copy of the Rey-Osterrieth Complex Figure: \- Range: 1 to 4
Time frame: 18 months
Short-term visual memory - remote assessment
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.
Time frame: 18 months
Long-term visual memory - remote assessment
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.
Time frame: 18 months
Orientation in time - remote assessment
Assessed by: Orientation in time subtest from Test Barcelona - Revised. \- Range: 0 - 5 Higher is better.
Time frame: 18 months
Orientation in space - remote assessment
Assessed by: Orientation in space subtest from Test Barcelona - Revised. \- Range: 0 -5
Time frame: 18 months
5DT Lecture - remote assessment
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.
Time frame: 18 months
5DT counting - remote assessment
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.
Time frame: 18 months
5DT Choosing - remote assessment
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.
Time frame: 18 months
5DT Switching - remote assessment
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.
Time frame: 18 months
5DT Inhibition - remote assessment
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.
Time frame: 18 months
5DT Flexibility - remote assessment
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.
Time frame: 18 months
IEDEEDS - remote assessment
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.
Time frame: 18 months
IEDYERTA - remote assessment
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.
Time frame: 18 months
IEDYCOST - remote assessment
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.
Time frame: 18 months
SWM Total Errors - remote assessment
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
Time frame: 18 months
SWM Between Errors - remote assessment
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.
Time frame: 18 months
SWM Within Errors - remote assessment
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.
Time frame: 18 months
SWM Double Errors - remote assessment
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.
Time frame: 18 months
SWMS - remote assessment
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
Time frame: 18 months
SWMSX - remote assessment
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.
Time frame: 18 months
SWMPR - remote assessment
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.
Time frame: 18 months
ERTTH - remote assessment
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
Time frame: 18 months
ERTTHH - remote assessment
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
Time frame: 18 months
ERTTHS - remote assessment
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
Time frame: 18 months
ERTTHF - remote assessment
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
Time frame: 18 months
ERTTHA - remote assessment
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
Time frame: 18 months
ERTTHSU - remote assessment
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.
Time frame: 18 months
ERTTHD - remote assessment
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.
Time frame: 18 months
ERTTFAH - remote assessment
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.
Time frame: 18 months
ERTTFAS - remote assessment
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.
Time frame: 18 months
ERTTFAF - remote assessment
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.
Time frame: 18 months
ERTTFAA - remote assessment
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.
Time frame: 18 months
ERTTFASU - remote assessment
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.
Time frame: 18 months
ERTTFAD - remote assessment
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.
Time frame: 18 months
ERTUHRH - remote assessment
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.
Time frame: 18 months
ERTUHRS - remote assessment
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.
Time frame: 18 months
ERTUHRF - remote assessment
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.
Time frame: 18 months
ERTUHRA - remote assessment
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.
Time frame: 18 months
ERTUHRSU - remote assessment
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.
Time frame: 18 months
ERTUHRSD - remote assessment
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.
Time frame: 18 months
Semantic fluency - remote assessment
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.
Time frame: 18 months
Phonemic fluency - remote assessment
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.
Time frame: 18 months
Naming - remote assessment
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.
Time frame: 18 months
Naming with cues - remote assessment
Assessed by: Boston Naming Test (BNT) \- Total correct with phonemic cue: from 0 to 60
Time frame: 18 months
Time in Naming - remote assessment
Assessed by: Boston Naming Test (BNT): time to complete
Time frame: 18 months
Visuospatial skills - remote assessment
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.
Time frame: 18 months
Psychiatric symptoms/disorders in remote assessments
Number of participants with psychiatric symptoms/disorders following DSM-IV-TR guidelines (psychotic symptoms, symptoms of depression, symptoms of mania, global functioning).
Time frame: 18 months
Serial bias in working memory
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.
Time frame: 18 months
EEG reactivations in working memory
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.
Time frame: 18 months
Slow-wave rate of growth during slow-wave sleep period
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.
Time frame: 18 months