Table 2.
Studies investigating cognitive function in JME.
| References | Design | Patients/Controls (n) | Patient Age (sd) | Age of Epilepsy Onset (sd) | Disease Duration (sd) | AED Regimen | Impaired Cognitive Domains | Unimpaired Cognitive Domains | Imaging |
|---|---|---|---|---|---|---|---|---|---|
| Swartz et al. (85, 86) | C | 9/15 | 28.0 (4.0) | 9–20 | N/A | Mixed | 1. Working memory | 1. Attention | FDG-PET |
| Devinsky et al. (87) | C | 15/15 | 34.3 (N/A) | 14.6 (N/A) | 19.8 (N/A) | Mixed | 1. Processing Speed# 2. Abstract Reasoning* 3. Executive Functions (Concept Formation*, Cognitive Flexibility*, Perseverative Tendencies#, Planning#) |
1. Dexterity# | N/A |
| Sonmez et al. (88) | C | 35/35 | 21.7 (4.5) | <25 | 7.2 (4.7) | Polytherapy | 1. Visuo-spatial Perception (Cube Copying, Clock Drawing 2. Abstract Reasoning 3. Semantic Fluency 4. Verbal Learning and Memory 5. Non-verbal Learning and Memory 6. Executive Functions (Response Inhibition) |
1. IQ 2. Visuo-spatial Perception (Facial recognition) 3. Expressive Language (Naming) 4. Working Memory |
N/A |
| Kim et al. (89) | C | 27/27 | 16–29 | 12–23 | 0.4–9 | Drug-naïve | 1. Processing Speed 2. Semantic Fluency 3. Working Memory 4. Verbal Learning 5. Executive Functions (Cognitive Flexibility) |
1. General Cognitive Abilities 2. Verbal Memory 3. Non-verbal Memory |
N/A |
| Pascalicchio et al. (90) | C | 50/50 | 26.2 (7.4) | N/A | 13.8 (8.5) | Monotherapy (VPA) | 1. General Cognitive Abilities (IQ, VIQ, PIQ) 2. Processing Speed 3. Phonemic Fluency 4. Expressive Language (Naming) 5. Working Memory 6. Verbal Learning 7. Non-verbal Learning 8. Executive Functions (Cognitive Flexibility, Response Inhibition) |
1. Semantic Knowledge (Information, Similarities) 2. Visuo-spatial Perception 3. Abstract Reasoning (Block Design) |
N/A |
| Piazzini et al. (91) | C | 50/40 | 37.3 (10.5) | 19.0 (13.3) | 18.3 (9.9) | Mixed | 1. Phonemic Fluency 2. Executive Functions (Cognitive Flexibility) |
1. General Cognitive Abilities (IQ) | N/A |
| Iqbal et al. (92) | C | 8/16 | 28.1 (6.7) | N/A | N/A | Mixed | 1. Phonemic Fluency 2. Semantic Fluency 3. Executive Functions (self-reported, questionnaire-based) |
1. Processing Speed 2. Dexterity 3. Visuo-spatial Perception 4. Abstract Reasoning 5. Semantic Knowledge (Vocabulary) 6. Working Memory 7. Verbal Learning and Memory 8. Non-verbal Learning and Memory |
N/A$ |
| Roebling et al. (93) | C | 19/20 | 24.2 (9.9) | N/A | N/A | Mixed | 1. Phonemic Fluency 2. Semantic Fluency |
1. Processing Speed 2. Attention 3. Semantic Knowledge (Vocabulary) 4. Working Memory 5. Verbal Learning and Memory 6. Non-verbal Learning 7. Executive Functions (Response Inhibition, Figural Fluency) |
VBM and Working Memory fMRI |
| Wandschneider et al. (51) | C | 19/42 | 25.5 (9.6) | N/A | 11.1 (10.8) | Mixed | 1. Attention 2. Semantic Knowledge (Vocabulary) 3. Semantic Fluency 4. Working Memory (Non-verbal) 5. Prospective Memory 6. Executive Functions (Response Inhibition) |
1. Working Memory (Verbal) 2. Executive Functions (Cognitive Flexibility, Planning) |
N/A |
| O'Muircheartaigh et al. (94) | C | 28/55 | 33.6 (10.1) | 14.4 (3.4) | 20.2 (10.3) | Mixed | 1. Semantic Knowledge (Similarities) 2. Phonemic Fluency 3. Expressive Language (Naming) 4. Non-verbal Learning 5. Cognitive Flexibility |
1. General Cognitive Abilities 2. Semantic Knowledge (Vocabulary) 3. Semantic Fluency 4. Working Memory 5. Verbal Memory and Learning 6. Non-verbal Memory |
VBM |
| Kim et al. (95) | C | 25/30 | 25.3 (7.6) | 14.7 (3.1) | 10.6 (7.7) | Mixed | 1. Processing Speed 2. Phonemic Fluency 3. Working Memory 4. Executive Functions (Cognitive Flexibility, Response Inhibition) |
1. General Cognitive Abilities | Diffusion MRI |
| Moschetta and Valente (52) | C | 42/42 | 26.6 (8.4) | 14.0 (4.4) | 17.8 (N/A) | Monotherapy (VPA) | 1. Processing Speed 2. Phonemic Fluency 3. Working Memory 4. Executive Functions (Cognitive Flexibility, Response Inhibition) |
N/A | N/A |
| Jackson et al. (53) | C | 26/72 | 14.6 (3.1) | 13.2 (4.1) | 8.5 (3.5) (months) | 96% Monotherapy | 1. Processing Speed 2. Attention 3. Dexterity 4. Working Memory 5. Executive Functions (Problem Solving, Response Inhibition) |
1. General Cognitive Abilities (VIQ, PIQ) 2. Semantic Knowledge (Vocabulary) 3. Phonemic Fluency 4. Expressive Language (Naming) 5. Verbal Learning and Memory 6. Executive Functions (Task-switching) |
N/A |
| Lin et al. (96) | C | 56/42 | 26.5 (9.0) | 12.5 (4.6) | 14.3 (10.0) | Mixed | N/A | 1. General Cognitive Abilities 2. Vocabulary 3. Phonemic Fluency 4. Expressive Language (Naming) 5. Verbal Memory and Learning 6. Non-verbal Memory and Learning |
MRI |
| Wandschneider et al. (97) | C | 21/11 | 33.5 (22–64)** | N/A | N/A | Mixed | N/A | 1. Processing Speed 2. Phonemic Fluency 3. Semantic Fluency 4. Working Memory 5. Executive Functions (Cognitive Flexibility, Decision Making*) |
Working Memory fMRI |
| Zamarian et al. (98) | C | 22/33 | 26.0 (18–50)** | 14.0 (1–20)** | 11.5 (3–45)** | Mixed | 1. Processing Speed 1. Abstract Reasoning 2. Semantic Fluency 3. Executive Functions (Cognitive Flexibility, Planning, Decision Making) |
1. Attention 2. Phonemic Fluency 3. Working Memory |
N/A |
| Thomas et al. (99) | C | 60# | 31.0 (19–67)** | 12.0 (8–15)## | 21.0 (10–31)## | Mixed (Refractory to VPA) | 1. General Cognitive Abilities (FSIQ, VIQ, PIQ) 2. Processing Speed 3. Semantic Knowledge (Vocabulary) 4. Abstract Reasoning (Block Design) 5. Phonemic Fluency 6. Semantic Fluency 7. Expressive Language (Naming) 8. Working Memory 9. Verbal Memory 10. Non-verbal Learning and Memory 11. Executive Functions (Response Inhibition) |
1. Abstract Reasoning (Matrix Reasoning) 2. Verbal Learning 3. Executive Functions (Cognitive Flexibility) |
N/A |
| Iqbal et al. (100) | C | 22/44 | 26.7 (7.3) | N/A | N/A | Mixed | 1. Dexterity (dominant hand) 2. Phonemic Fluency 3. Semantic Fluency |
1. General Cognitive Abilities 2. Processing Speed 3. Dexterity (non-dominant hand) 4. Visuo-spatial Perception 5. Abstract Reasoning 6. Semantic Knowledge 7. Working Memory 8. Verbal Learning and Memory 9. Non-verbal Learning and Memory |
N/A$ |
| Giorgi et al. (101) | C | 20/20 | 26.7 (6.6) | 14.0 (3.8) | 12.7 (8.4) | Mixed | 1. Processing Speed 2. Semantic Fluency 3. Working Memory 4. Verbal Learning 5. Non-verbal Learning and Memory |
1. Phonemic Fluency 2. Verbal Memory 3. Executive Functions (Cognitive Flexibility, Response Inhibition) |
N/A |
| Valente et al. (102) | C | 57/44 | 27.4 (8.2) | N/A | N/A | Monotherapy (VPA) | 1. Processing Speed 2. Phonemic Fluency 3. Working Memory 4. Verbal Memory and Learning 5. Non-verbal Memory and Learning 6. Executive Functions (Cognitive Flexibility, Response Inhibition) |
N/A | N/A |
| Abarrategui et al. (73) | C | 19/21 | 33.0 (8.1) | 14.0 (12–16)** | 18.0 (14–25)** | Mixed | 1. Processing Speed | 1. General Cognitive Abilities 2. Semantic Knowledge (Information) 3. Visuo-spatial Perception/ Orientation 4. Abstract Reasoning 5. Phonemic Fluency 6. Expressive Language (Naming) 7. Working Memory 8. Verbal Memory 9. Non-verbal Memory 10. Executive Functions (Cognitive Flexibility, Response Inhibition, Planning) |
N/A$ |
| Rzezak et al. (103) | C | 79/69 | 27.3 (8.4) | N/A | N/A | Mixed | 1. Processing Speed 2. Phonemic Fluency 3. Semantic Fluency 4. Working Memory 5. Executive Functions (Cognitive Flexibility, Response Inhibition) |
N/A | |
| Sezikli et al. (104) | C | 45/15 | 22.9 (6.8) | 15.6 (4.1) | 7.2 (5.6) | Monotherapy (VPA) | 1. Processing Speed (Trail Making A) 2. Semantic Fluency 3. Working Memory 4. Non-verbal Memory 5. Executive Functions (Cognitive Flexibility, Figural Fluency) |
1. Processing Speed (Stroop CW) 2. Attention 3. Verbal Memory 4. Executive Functions (Response Inhibition) |
N/A |
| Unterberger et al. (105) | C | 36/38 | 25.3 (5.3) | 14.3 (3.4) | N/A | Mixed | 1. Processing Speed 2. Attention 3. Executive Functions (Risk taking) |
1. General Cognitive Abilities (VIQ) 2. Phonemic Fluency 3. Semantic Fluency 4. Executive Functions (Cognitive Flexibility, Response Inhibition) |
N/A |
| Paiva et al. (106) | C | 35/39 | 29.0 (9.1) | 15.7 (5.2) | 13.7 (9.4) | Mixed | 1. Executive Functions (Risk taking) | 1. Executive Functions (Decision Making under ambiguity) | N/A |
Studies are listed in chronological order. Unless specified otherwise, age, age of epilepsy onset and disease duration are reported as mean values in years, or as ranges, if provided in such format by the original reference.
**
Median (range).
##
Median (interquartile range).
$
Studies employing video-EEG during neuropsychological testing. C, Cross-sectional design; CW, Color-Word (Stroop test); IQ, Intelligence Quotient; PIQ, Performance Intelligence Quotient; VBM, Voxel-Based Morphometry; VIQ, Verbal Intelligence Quotient; VPA, Sodium Valproate.
In Devinsky et al. (87): *, reduced function in JME compared to TLE; #, comparisons against healthy controls. In Wandschneider et al. (97): *, shift toward more advantageous choices (i.e., task-associated learning) was impaired in JME patients with ongoing seizures, but not in those who were seizure-free. In the “AED Status” column, “Mixed” is given for studies where AED use was not restricted to a single regimen (i.e., monotherapy, polytherapy, or drug-naïve).