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Background
Tuberous sclerosis complex (TSC) is a genetic disease characterised by the growth of benign tumours. The Tuberous sclerosis Associated Neuropsychiatric Disorders (TAND) Checklist is used to identify patient-reported neurocognitive deficits. Patients may, however, under-recognise mild cognitive impairment. We aimed to determine the frequency of abnormal scores on three objective tests of cognitive function in people with and without diagnosed intellectual disability and examine associations between scores on these tests with self-reported TAND Checklist symptoms.
Methods
We conducted a cross-sectional study where people with TSC (PwTSC; n=46) completed the TAND Checklist and three cognitive tests: Symbol Digit Modalities Test (SDMT), Montreal Cognitive Assessment test and Trail Making Test—Parts A and B. We examined associations between cognitive test scores and the TAND Checklist using Pearson’s correlations (95% CI). Receiver operating characteristics (ROC) curves were plotted to determine the screening accuracy of each measure in identifying physician-diagnosed neurocognitive disorders.
Results
There were minimal correlations between the cognitive test scores and the TAND Checklist. More than 20% of PwTSC reported no cognitive issues on the TAND Checklist but had abnormal performance on at least one cognitive test. The ROC curves demonstrated similar results, with areas under the curve of 0.93 (95% CI 0.79 to 1.00) for the SDMT but only 0.70 (95% CI 0.45 to 0.95) for the TAND Checklist.
Conclusion
Objective tests of cognitive function are useful in identifying unrecognised neurocognitive deficits in PwTSC. Deficits likely have multifactorial origins, including undiagnosed intellectual disability and the impact of chronic epilepsy.
Full text
Correspondence to Dr Mark R Keezer; [email protected]
WHAT IS ALREADY KNOWN ON THIS TOPIC
Intellectual disability is present in many children with tuberous sclerosis complex (TSC).
WHAT THIS STUDY ADDS
Objective tests of cognitive function are useful in identifying neurocognitive deficits in adults and adolescents with TSC, even among those without a known history of intellectual disability.
HOW THIS STUDY MIGHT AFFECT RESEARCH, PRACTICE OR POLICY
The results of this study will sensitise healthcare providers and patients to the presence of more subtle neurocognitive deficits in adults and adolescents with TSC.
A clearer understanding of a person’s intellectual abilities allows for better planning of educational, social and clinical management strategies.
Introduction
Tuberous sclerosis complex (TSC) is a neurocutaneous genetic disease associated with the presence of hamartomas in the brain (eg, cortical tubers) and other vital organs, affecting one in 6000 live births.1 Approximately 85% of individuals have an autosomal dominant pathogenic variant in the TSC1 or TSC2 genes.2 People with TSC (PwTSC) often present with epilepsy, intellectual disability (ID) and autism spectrum disorder.1 The severity of these disease manifestations vary widely between individuals, even between members of the same family.3 The diagnosis of TSC can be made at any age.4 Neurocognitive impairments are frequent among PwTSC, with deficits in working memory, cognitive flexibility and divided attention being particularly prevalent.5 Prior studies have reported a negative association between the cerebral tuber count and the IQ of individuals.6 7
The TAND Checklist is recommended for screening PwTSC for behavioural and cognitive impairments.8 This checklist contains 12 sections, cataloguing patient-reported and physician-diagnosed neuropsychiatric and neurocognitive comorbidities.5 8 Many of these comorbidities, however, are often unrecognised by patients and under-diagnosed by physicians.9–11 This is especially the case when these manifestations are mild or when a person is diagnosed with TSC only as an adult. PwTSC, especially adults and older adolescents, would benefit from standardised screening tools specific to their age.12 13 To better identify and address the neurocognitive impairments in PwTSC, administration of an objective and validated screening tool, to be used in conjunction with the TAND Checklist, could facilitate the planning of educational, social and clinical management strategies.12 13
The first goal of our study was to describe the distribution of scores on selected tests of cognitive function (Symbol Digit Modalities Test (SDMT), Montreal Cognitive Assessment test (MoCA) and Trail Making Test (TMT)) in a cohort of adults and adolescents with TSC with no or only mild ID. Our second aim was to estimate the diagnostic accuracy of each cognitive tests for ID. Exploratory analyses included analysing the relationship between these tests and the tuber count in PwTSC, as well as to the results of these cognitive tests in PwTSC to a cohort of people with epilepsy but not TSC. We also describe the distribution of scores on a screening questionnaire for autism traits (Autism Spectrum Quotient (AQ)). We postulated that the SDMT, MoCA and TMT are clinical instruments that may be used to screen for mild neurocognitive impairments in adults and adolescents with TSC.
Methods
Study population
This study recruited participants from two Montreal-area TSC clinics. Adult participants (aged 18 years and older) were recruited from the TSC clinic for adults at the Centre hospitalier de l’Université de Montréal (CHUM) between 24 February 2022 and 9 February 2023. Adults without TSC, but with epilepsy, were additionally recruited as control participants from the epilepsy clinic at the CHUM during the same period. Adolescent participants (aged 14–17 years) were recruited from the TSC clinic for children at the Centre hospitalier universitaire Sainte-Justine (CHU Sainte-Justine) between 13 July 2023 and 12 October 2023. These were convenience samples. All diagnoses were made according to the most recent clinical and genetic criteria presented by the International Tuberous Sclerosis Complex Consensus Group,14 confirmed by physicians with expertise in TSC (MRK and PM). We excluded non-French-speaking individuals (fewer than 10% of patients seen in these clinics, done in order to standardise the cognitive testing procedures), and individuals with an ID severe enough to prevent them from completing the cognitive tests without the aid of another person (ie, moderate to severe ID), according to the judgement of the referring physician (MRK or PM).
Study design
This project was a cross-sectional validation study. It is reported as per the Strengthening the Reporting of Observational Studies in Epidemiology guidelines for cross-sectional studies. Clinical data were collected from the medical notes of study participants, including age at diagnosis, family history of TSC as well as genetic and imaging test results. Severity and control of epilepsy were assessed using the Global Assessment of Severity of Epilepsy (GASE), completed by their treating physician (MRK or PM). The GASE is a seven-level Likert scale on physician-perceived epilepsy severity.15 16 Participants were questioned by the recruiting research assistant on socio-demographic data. The presence of ID was judged according to the diagnoses retained in the medical notes, generally based on a prior neuropsychological evaluation.
Following a standard procedure and with training from a board-certified neuroradiologist with 12 years of experience (LL-G), the brain tuber count was assessed by two neurology residents (SB and FZ-E) who reviewed the last cerebral MRI available in the participant’s medical file. They reviewed the brain MRIs independently before combining their results. If their tuber counts did not match, discrepancies were resolved by consensus.
Test methods
The SDMT, MoCA and TMT were selected as cognitive assessment tools, alongside the AQ questionnaire for evaluating autistic traits. These tests were chosen based on their objectivity, their short administration time and their ease of administration by a person other than a neurologist or neuropsychologist, making them practical screening tools for PwTSC. The SDMT and TMT were additionally selected because they are well-established measures of cognitive functions that are thought to be especially impaired in PwTSC, and the MoCA was additionally selected as it is a well-known screening test of cognitive dysfunction often used in clinical medicine. All tests were administered, always in the same order, by a research assistant (MB, L-AB, FB or R-MD-E), following a training session with a neuropsychologist (OB), and after having completed the online training and certification for the MoCA test (https://mocacognition.com/training-certification/).
Tuberous sclerosis Associated Neuropsychiatric Disorders Checklist
The TAND Checklist is a qualitative questionnaire completed by the participant and/or their caregiver that consists of open-ended questions regarding previous diagnoses and symptoms. Of the 12 sections of the TAND, only sections 5 and 7, addressing ID and neuropsychological skills (subdomain ‘executive skills’), were considered in our study. For section 7, a point was attributed to each question where the participant answered ‘yes’, resulting in a maximum of six points for section 7, as previously described.17 The TAND Checklist possesses good content validity (ie, extent to which the test covers the range of neuropsychiatric deficits related to TSC) according to experts, as well as the relatives and caregivers of PwTSC.17 There are strong correlations between the TAND Checklist and the Strengths and Difficulties Questionnaire, the Social Communication Questionnaire, the Wessex Scale and the Behaviour Rating Inventory of Executive Functions.17 We used a validated French-language translation of the TAND Checklist.18 19
Symbol Digit Modalities Test
The SDMT is a rapid and sensitive screening tool to identify children and adults with cognitive deficits.20 It assesses information processing speed, motor speed and short-term memory.21 22 The SDMT is one of the most used tests among individuals with a number of neurological conditions including multiple sclerosis,23 24 Huntington’s disease25–27 and traumatic brain injury.28–32 The SDMT can be administered to individuals aged 8 years and older. It contains a key with nine distinct symbols, each associated with a digit. Beneath this key is a series of symbols whose corresponding digits are missing. The participant must complete the correspondences using the appropriate digits. The number of correctly filled boxes during a 90 s interval is recorded and the maximum score is 110. We calculated participant z-scores from normative data obtained as a function of sex and age.33 A z-score ≤−1.5 was considered our criterion for abnormal performance. The test-retest reliability of the SDMT is excellent (intraclass correlation coefficient=0.89).34
Montreal Cognitive Assessment test
The MoCA, initially developed for the screening of mild cognitive impairment, contains 13 sections aimed at detecting a range of cognitive impairments including executive function, attention, verbal fluency and memory.35 The sum of each section is computed to obtain a total score out of 30. A one point bonus is given for examinees with ≤12 years of education.35 Individuals that reach a score ≥26 are considered as unlikely to meet neuropsychological criteria for mild cognitive impairment.35 We used a validated French-language translation of the MoCA.36
Trail Making Test
The TMT evaluates attention, information processing speed and cognitive flexibility.20 The TMT contains two sections. Section A consists of connecting with a line the numbered circles from one to 25 in ascending order.20 Section B consists of connecting the circles by alternating between a number (1–13) and a letter (A–L) in ascending and alphabetical orders. The examiner indicates to the examinee when he/she makes an error. The time taken to complete each section, and the number of errors committed by the participant, are computed. Normative data are available, adjusting for a person’s age, educational level and IQ, which allows the differentiation between normal and abnormal.37 A z-score ≤−1.5 for time of completion was considered as our criterion for abnormal performance.
Autism Spectrum Quotient
The AQ is completed either by the participant or by the parent. It consists of 50 questions, each rated on a 4-point Likert scale. Individuals circle a response indicating their level of agreement or disagreement with each statement.38 39 Questions include social skills, redirection of attention and attention to detail. The evaluation grid on the Autism Research Center website was used to assign points based on the answers circled (https://docs.autismresearchcentre.com/tests/AQ_Scoring_Key.doc). A point is awarded each time an autistic behaviour is identified.39 The optimal threshold for distinguishing participants with versus without autistic characteristics is 26, with a sensitivity of 0.89 and a specificity of 0.98.38 We used a validated French-language translation of the AQ.40
Statistical analyses
The distribution of scores among PwTSC, and those among people with epilepsy but not TSC, was examined and checked for normality. We measured Pearson’s correlations (95% CI) between the TAND Checklist score and the three cognitive tests (SDMT, MoCA and TMT), after confirming the linearity of the associations. These correlations were characterised as very strong (0.9–1.0), strong (0.7–0.89), moderate (0.5–0.69), weak (0.3–0.49) and minimal or no correlation (0–0.29), as per published thresholds.41
We measured criterion diagnostic accuracy using receiver operating characteristics (ROC) curves to study the association among the scores of the SDMT, MoCA, TMT and the presence or absence of ID. We calculated the area under the curve (AUC) (95% CI) to summarise the overall diagnostic performance of each test.
We measured the associations between the scores of the three tests, epilepsy severity and cerebral tuber count using Pearson’s correlations (95% CI), again after confirming the normality of variable distributions and linear associations between the variables.
Our planned study size was 39 participants, aimed at detecting a statistically significant difference between a correlation coefficient of 0.2 and one of ≥0.7, with a power of 80% and an alpha level of 0.05. SupposingAssuming a prevalence of ID of 50%,42 43 we estimated that a study of 31 participants would be sufficient to measure an AUC of 0.80, with 95% CIs and widths no greater than 0.20.
Results
We recruited 46 PwTSC (40 adults and 6 adolescents) and 20 adults with epilepsy but without TSC (our control group).
Table 1 provides an overview of the participant demographics. Thirteen per cent of participants with TSC had physician-diagnosed ID. Approximately half of participants with TSC (54.3%) also had epilepsy, but only one of them was treated with topiramate, an antiseizure medication with an especially high risk of cognitive side effects, including cognitive slowing and reduced verbal fluency.44 45
Table 1Baseline characteristics of study participants
| Characteristics | Participants with TSC* N=46 | Controls with epilepsy* N=20 |
| Mean age in years (SD) | 35.4 (16.2) | 36.8 (15.3) |
| Age distribution (years) | ||
| 14–17 | 6 (13) | 0 (0) |
| 18–24 | 10 (21.7) | 5 (25) |
| 25–34 | 8 (17.4) | 5 (25) |
| 35–44 | 7 (15.2) | 5 (25) |
| 45–54 | 5 (10.9) | 2 (10) |
| 55–64 | 10 (21.7) | 2 (10) |
| 65 and over | 0 (0) | 1 (5) |
| Females | 23 (50) | 9 (45) |
| Level of education | ||
| No schooling | 0 (0) | 0 (0) |
| Elementary school | 1 (2.2) | 0 (0) |
| High school without diploma | 9 (19.6) | 5 (25) |
| High school with diploma or equivalent | 11 (23.9) | 1 (5) |
| Postsecondary school without university degree | 15 (32.6) | 12 (60) |
| Bachelor’s degree | 10 (21.7) | 2 (10) |
| Master’s degree | 0 (0) | 0 (0) |
| PhD | 0 (0) | 0 (0) |
| Epilepsy | 25 (54.3) | 20 (100) |
| GASE Scale | ||
| Not applicable, no epilepsy | 21 (45.7) | 0 (0) |
| 1 | 9 (36) | 3 (15) |
| 2 | 11 (44) | 2 (10) |
| 3 | 2 (8) | 6 (30) |
| 4 | 1 (4) | 2 (10) |
| 5 | 1 (4) | 6 (30) |
| 6 | 1 (4) | 1 (5) |
| 7 | 0 (0) | 0 (0) |
| SEGA | 10 (21.7) | N/A |
| Tubers | 16 (34.8) | N/A |
| ID, self-reported | 8 (17.4) | 4 (20) |
| ID, physician-diagnosed | 6 (13) | 3 (15) |
*All cells are n (%), unless indicated otherwise.
GASE, Global Assessment of Severity of Epilepsy; ID, intellectual disability; N/A, not applicable; SEGA, subependymal giant cell astrocytoma; TSC, tuberous sclerosis complex.
The distribution of test results is graphically represented in figure 1, stratified by the presence or absence of a known ID. For the SDMT, 17.4% of participants with TSC scored below the threshold (z-score ≤−1.5) indicating abnormal performance. This proportion increased to 41.3% for the MoCA (score <26). For TMT-A and TMT-B, 15.2% and 28.3% of individuals with TSC were below the threshold (z-score ≤−1.5). Among the individuals with ID, half of them had abnormal scores on all three cognitive tests. Among them, two had abnormal scores on all tests except the TMT-A, and one had no abnormal scores. Notably, several participants with TSC without known ID also had abnormal scores. Specifically, for the SDMT, 7% of participants without known ID fell below our threshold for a normal score, while for the MoCA the same was observed for nearly 30% of participants. These proportions were 10% and 20% for the TMT-A and TMT-B, respectively.
Figure 1. Stacked histograms showing the distribution of scores obtained for the various cognitive tests as well as for the TAND Checklist section 7 for participants with TSC and ID and control subjects with epilepsy and ID. (A) Stacked histograms showing score distribution for the SDMT. The threshold for the SDMT is set at -1.5, where a score >-1.5 is considered normal and a z-score <=-1.5 is considered abnormal. (B) Stacked histograms showing the score distribution for the MoCA. For the MoCA, the threshold is set at 26, where a score >=26 indicates normal intellectual capacity and a score <26 indicates cognitive dysfunction. (C, D) Stacked histograms showing score distribution for the TMT. For TMT-A and TMT-B, a score >-1.5 is considered normal and a z-score <=-1.5 is considered abnormal. (E) Stacked histograms showing score distribution for the TAND Checklist. Only positive responses are considered for the TAND Checklist. All results shown to the left of the red dotted line correspond to scores considered abnormal. MoCA, Montreal Cognitive Assessment test; SDMT, Symbol Digit Modalities Test;TAND, Tuberous sclerosis Associated Neuropsychiatric Disorders; TMT-A, Trail Making Test section A; TMT-B, Trail Making Test section B; TSC, tuberous sclerosis complex; ID, intellectual disability. *N=1.
Figure 1 also offers a comparison with the TAND Checklist evaluation. Most individuals responded affirmatively to ≥1 item presented by the checklist. Out of 46 participants, 22% with TSC, however, did not report any difficulties on the TAND Checklist (ie, a score of 0), while ≥1 of their cognitive test scores was abnormal. More specifically, three participants (6.5%) had a TAND Checklist score of 0 but their TMT-A score was abnormal. One participant with TSC had a TAND Checklist score of 0 but their SDMT, MoCA, TMT-A and TMT-B scores were all abnormal.
When comparing PwTSC with those with epilepsy but without TSC, their demographics were generally similar (table 1). The distribution of scores on the cognitive tests were also similar (figure 1).
Among participants with TSC, we found moderate to strong correlations between the three cognitive tests (table 2 and online supplemental figure 1). There were minimal to weak correlations between the TAND Checklist and these tests (table 2). The results were similar for control participants with epilepsy (online supplemental figure 2).
Table 2Pearson’s correlations (95% CI) between cognitive tests of people with TSC
| Tests | SDMT | MoCA | TMT-A | TMT-B | TAND |
| SDMT | N/A | 0.74 (0.57–0.85) | 0.56 (0.32–0.73) | 0.71 (0.53–0.83) | −0.18 (−0.45–0.11) |
| MoCA | 0.74 (0.57–0.85) | N/A | 0.37 (0.08–0.60) | 0.76 (0.59–0.86) | −0.16 (−0.44–0.14) |
| TMT-A | 0.56 (0.32–0.73) | 0.37 (0.08–0.60) | N/A | N/A | −0.16 (−0.43–0.13) |
| TMT-B | 0.71 (0.53–0.83) | 0.76 (0.59–0.86) | N/A | N/A | −0.23 (−0.49–0.06) |
| TAND | −0.18 (−0.45–0.11) | −0.16 (−0.44–0.14) | −0.16 (−0.43–0.13) | −0.23 (−0.49–0.06) | N/A |
MoCA, Montreal Cognitive Assessment test; N/A, not applicable; SDMT, Symbol Digit Modalities Test; TAND, Tuberous sclerosis Associated Neuropsychiatric Disorders; TMT-A, Trail Making Test section A; TMT-B, Trail Making Test section B.
Figure 2 presents the ROC curves of the cognitive tests, and table 3 displays the optimal sensitivity (95% CI) and specificity (95% CI), demonstrating their diagnostic potential in identifying people with ID. The SDMT had an AUC of 0.93 (95% CI 0.79 to 1.00), while the MoCA had 0.90 (95% CI 0.71 to 1.00) and TMT-B had 0.87 (95% CI 0.62 to 1.00). The TAND Checklist and TMT-A had AUCs of 0.70 (95% CI 0.45 to 0.95) and 0.58 (95% CI 0.26 to 0.90), respectively.
Figure 2. ROC curves and the table present different AUCs for cognitive tests in participants with TSC to detect an ID. The ROC curves for adults with TSC show the true positive rate (sensitivity) along the y-axis, and the false positive rate (1-specificity) along the x-axis. AUC, area under the curve; MoCA, Montreal Cognitive Assessment test; ROC, receiver operating characteristics; SDMT, Symbol Digit Modalities Test; TMT-A, Trail Making Test section A; TMT-B, Trail Making Test section B; TAND, Tuberous sclerosis Associated Neuropsychiatric Disorders.
Diagnostic accuracy for identifying individuals with intellectual disability
| Area under the curve (95% CI) | Optimal sensitivity (95% CI) | Optimal specificity (95% CI) | |
| SDMT | 0.93 (0.79 to 1.00) | 0.83 (0.44 to 0.97) | 0.97 (0.87 to 1.00) |
| MoCA | 0.90 (0.71 to 1.00) | 0.83 (0.44 to 0.97) | 1.00 (0.91 to 1.00) |
| TMT-A | 0.58 (0.26 to 0.90) | 0.33 (0.10 to 0.70) | 0.95 (0.83 to 0.99) |
| TMT-B | 0.87 (0.62 to 1.00) | 0.83 (0.44 to 0.97) | 1.00 (0.91 to 1.00) |
| TAND | 0.70 (0.45 to 0.95) | 0.50 (0.19 to 0.81) | 0.85 (0.71 to 0.93) |
The table presents the false positive rate (1−specifity) and the AUC of the ROC curves presented in figure 2, along with the optimal sensitivity and specificity for each test.
ACU, area under the curve; MoCA, Montreal Cognitive Assessment test; ROC, receiver operator characteristics; SDMT, Symbol Digit Modalities Test; TAND, Tuberous sclerosis Associated Neuropsychiatric Disorders; TMT-A, Trail Making Test section A; TMT-B, Trail Making Test section B.
The correlations between test results and the number of tubers in participants with TSC were generally minimal or weak (online supplemental figure 3 and online supplemental table 1).
Figure 3 provides the results of the AQ for participants with TSC, including their score distribution. Twenty-six per cent of PwTSC had an abnormal score (score ≥26). Pearson’s correlation between the AQ of participants with TSC and their number of tubers was minimal, at 0.18 (95% CI −0.44 to 0.69).
Figure 3. Distribution of scores obtained by participants with TSC for the AQ. Stacked histograms showing score distribution. The threshold is set at 26. A score <26: no signs of autistic behaviour, a score >=26: signs of autistic behaviour. The red line is the delimitation between signs of autistic behaviour and no autistic signs. Note that n=19 for the AQ completed by participants with TSC. AQ, Autism Spectrum Quotient; ID, intellectual disability; TSC, tuberous sclerosis complex. *N=1.
Discussion
Our first aim was to determine whether objective cognitive tests are effective instruments to screen for neurocognitive disorders in adults and adolescents with TSC, facilitating their referral for appropriate resources. We found that these cognitive tests were frequently abnormal in adults and adolescents with TSC. More specifically, one or more tests were abnormal in 70% of people who were not previously known for ID.
There were 10 individuals out of 46 (22%) who did not report any difficulties on the TAND Checklist but had abnormal scores for at least one of the cognitive tests. These inconsistencies highlight the difficulty in relying on self-reported outcomes. Patient answers do not always reflect their medical diagnosis but are rather subjective self-assessments of their abilities. Formal cognitive screening tests remain objective. There were minimal to weak correlations between the TAND Checklist and the SDMT, MoCA and TMT.
Some of the cognitive difficulties measured in PwTSC may be related to their epilepsy in addition to their TSC. Chronic epilepsy is known to impact cognition.46 However, among the 21 PwTSC without epilepsy, 67% were not known to have ID but had at least one abnormal cognitive test score.
The overall diagnostic performance of the screening cognitive tests was high, with the SDMT having an AUC of 0.93 (95% CI 0.79 to 1). There was a trend for SDMT and MoCA to perform better than other tests as well as the TAND Checklist, with overlapping 95% CI. Confirmatory studies with larger sample sizes are required.
Our study has limitations. One possible limitation is the presence of a response bias among participants who may be embarrassed or reluctant to openly declare their ID symptoms on the TAND Checklist (ie, social desirability bias). This could have negatively affected the ability of the checklist to identify intellectual impairements. Involving a caregiver to help complete the TAND checklist could enhance the identification of cognitive deficits that the patient is otherwise unaware of. Another issue raised by the study is the difficulty in differentiating whether the test results obtained are due to the participant’s TSC, to their epilepsy or to their medication. We relied on the medical chart and the diagnosis documented by the treated physician to determine if a person had ID or not. In participants known for TSC since childhood, these diagnoses were based on a neuropsychological evaluation in childhood. In this context, a subsequent study comparing our findings with more sophisticated assessments of intellectual functioning, such as the Wechsler Adult Intelligence Scale-IV,47 could provide valuable insights. This was not carried out in the current study, however, due to the additional resources required by such an endeavour.
In this study, we focused on the cognitive aspects of TANDs. While we briefly assessed the presence of autistic traits in adults using the AQ, future studies could consider more comprehensive assessments such as the Ritvo Autism Asperger Diagnostic Scale-Revised.48 Dysregulated behaviour, feeding/sleeping, mood/anxiety and hyperactivity/impulsivity are additional TAND aspects that should be further studied in adult populations, using tools similar to the Child Behaviour Checklist.49
Tests can be administered by their treating physician, as well as by a trained third party such as a nurse, medical student or research staff. Administering the tests during a patient’s initial assessment by a TSC healthcare provider would serve to establish a baseline, with occasional follow-up examinations to assess for any changes over time.
Neurocognitive screening tests may help detecting unrecognised neurocognitive deficits in adolescents and adults with TSC. These deficits likely have multifactorial origins, including mild and undiagnosed ID and the impact of chronic epilepsy. Our results are especially relevant for individuals with TSC who have yet to undergo a complete neuropsychological assessment. A clearer understanding of a person’s intellectual abilities allows for better planning of educational, social and clinical management strategies. This is especially common in PwTSC diagnosed during adulthood, an increasingly common occurrence.
The authors would like to thank the study participants who volunteered for this research.
Data availability statement
Data are available on reasonable request. De-identified data will be made available on reasonable request from academic investigators.
Ethics statements
Patient consent for publication
Not applicable.
Ethics approval
This study was approved by the Research Ethics Board of the Centre hospitalier de l’Université de Montréal (MP-02-2022-10250, 21.288—YP) and the Research Ethics Board of CHU Sainte-Justine (MEO-02-2024-5763, MP-02-2022-10250, 21.288—YP). Participants provided informed consent prior to their involvement in the study.
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MB and L-AB contributed equally.
Presented at Preliminary analyses of this work has been presented at the 2024 Canadian League Against Epilepsy annual conference.
Contributors MB, FB, OB, MRK contributed to the original concept and design of the study. MB, L-AB, FB, R-MD-E contributed to participant recruitment and assessment. SB, FZ-E, LL-G contributed to imaging assessment. JL carried out the statistical analyses. MB, L-AB, MRK contributed to the drafting of the manuscript. All authors critically revised the manuscript. MRK is the guarantor.
Funding The funding for this research was provided by the TD Bank Ready Commitment Programme.
Competing interests JL receives bursaries from the Fonds de Recherche du Québec—Santé. LL-G receives salary support from Fonds de Recherche Quebec Sante (FRQ-S)/Fondation de l’Association des Radiologistes du Quebec (FARQ) clinical research scholarship junior 1 salary award (311203) and research grants from the Fonds de Recherche Quebec Sante (FRQ-S)/Fondation de l’Association des Radiologistes du Quebec (FARQ), Quebec Bio-imaging Network and Radiological Society of North America. PM reports consulting fees from Eisai, UCB and Jazz Pharmaceuticals. MRK receives salary support from the Fonds de Recherche Québec—Santé (chercheur-clinicien junior 2), reports unrestricted educational grants from UCB, Jazz Pharmaceuticals, Paladin and Eisai, and research grants for investigator-initiated studies from UCB and Eisai, as well as research grants from TD Bank Ready Commitment Programme, TSC Alliance, the Quebec Bio-imaging Network, the Canadian Frailty Network, the Savoy Foundation and the Canadian Institutes of Health Research.
Provenance and peer review Not commissioned; externally peer reviewed.
Supplemental material This content has been supplied by the author(s). It has not been vetted by BMJ Publishing Group Limited (BMJ) and may not have been peer-reviewed. Any opinions or recommendations discussed are solely those of the author(s) and are not endorsed by BMJ. BMJ disclaims all liability and responsibility arising from any reliance placed on the content. Where the content includes any translated material, BMJ does not warrant the accuracy and reliability of the translations (including but not limited to local regulations, clinical guidelines, terminology, drug names and drug dosages), and is not responsible for any error and/or omissions arising from translation and adaptation or otherwise.
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