Health-related quality of life of adults with spinal muscular atrophy: insights from a nationwide patient registry in Germany.

PURPOSE: Spinal muscular atrophy (SMA) is a rare, autosomal-recessive disease characterized by progressive muscular atrophy and weakness resulting in substantial disability and short life expectancy. The objective of this cross-sectional study was to assess health-related quality of life (HRQoL) of adults with SMA in Germany in the era of disease-modifying therapy. METHODS: Adults with SMA were recruited via the German national TREAT-NMD SMA patient registry. HRQoL was measured using the EQ-5D-5L, the Health Utilities Index Mark III (HUI), and the Short Form (36) Health Survey (SF-36). Estimates were stratified by current best motor function of the lower limb and trunk (i.e., non-sitter, sitter, and walker) and SMA type (i.e., type I, II, and III). RESULTS: A total of 82 adults with SMA (mean age: 42 years, 51% female) self-completed the study questionnaire. The mean EQ-5D-5L utility was estimated at 0.5135 (range across subgroups: 0.31-0.99), mean EQ-VAS at 69.71 (64.67-90.00), mean HUI-derived utility at 0.3171 ( - 0.02-0.96), mean SF-6D utility at 0.6308 (0.58-0.65), and mean SF-36 Physical Component Summary and Mental Health Component Summary scores at 33.78 (9.92-53.10) and 53.49 (21.02-72.25), respectively. CONCLUSIONS: We show that adults with SMA experience considerable impairment across a wide range of health dimensions, including mobility, dexterity, pain, and emotional well-being. However, our results exhibit non-trivial variability across clinical subgroups and HRQoL measures. These data contribute to our understanding of the subjective impact of living with a severely debilitating neuromuscular disease, such as SMA.

Self-Reported Health-Related Quality of Life of Children with Spinal Muscular Atrophy: Preliminary Insights from a Nationwide Patient Registry in Germany.

BACKGROUND: Spinal muscular atrophy (SMA) is a rare, severely debilitating neuromuscular disease characterized by a wide spectrum of progressive muscular atrophy and weakness. OBJECTIVES: The objective of this pilot study was to estimate self-assessed health-related quality of life (HRQoL) of children with SMA. METHODS: Children with SMA were recruited via the German national TREAT-NMD SMA patient registry and asked to self-complete the following rating-scales: KIDSCREEN-27, KINDL, the PedsQL 3.0 Neuromuscular Module (PedsQL 3.0 NMM), EQ-5D-5L, and the Health Utilities Index (HUI). Estimates were stratified by current best motor function of the lower limb and trunk (i.e., non-sitter, sitter, and walker) and SMA type (i.e., type I, II, and III). RESULTS: In total, 17 children with SMA (mean age: 9.88 years, SD: 4.33 years, range: 5-16 years; 59% female) participated in the study. Across examined strata, the mean KIDSCREEN-27 total score was estimated at between 48.24 and 83.81; the mean KINDL total score at between 60.42 and 76.73; the mean PedsQL 3.0 NMM total score at between 58.00 and 83.83; the mean EQ-5D-5L utility at between 0.31 and 0.99; and the mean HUI-derived utility at between -0.02 and 0.96. CONCLUSIONS: The results from this pilot study show that German children with SMA, despite significant physical disability, have surprisingly good HRQoL as assessed using KIDSCREEN-27. Yet, many reside in health states associated with low utility. The disease burden was generally higher among non-sitters compared with walkers, and SMA type I compared with type III, but more research is needed to further delineate this variability. Our preliminary findings contribute to the understanding of HRQoL in pediatric patients with SMA and should be helpful to inform the design of future studies of this patient population.

Areas of improvement in the medical care of SMA: evidence from a nationwide patient registry in Germany.

BACKGROUND: Management and treatment of spinal muscular atrophy (SMA) has changed in recent years due to the introduction of novel transformative and potentially curative therapies resulting in the emergence of new disease phenotypes. Yet, little is known about the uptake and impact of these therapies in real-world clinical practice. The objective of this study was to describe current motor function, need of assistive devices, and therapeutic and supportive interventions provided by the healthcare system, as well as the socioeconomic situation of children and adults with different SMA phenotypes in Germany. We conducted a cross-sectional, observational study of German patients with genetically confirmed SMA identified and recruited via a nationwide SMA patient registry ( www.sma-register.de ) within the TREAT-NMD network. Study data was recorded directly from patient-caregiver pairs through a study questionnaire administered online via a dedicated study website. RESULTS: The final study cohort consisted of 107 patients with SMA. Of these, 24 were children and 83 adults. In total, about 78% of all participants were taking medication for SMA (predominantly nusinersen and risdiplam). All children with SMA1 were able to sit and 27% of children with SMA2 were able to stand or walk. Impaired upper limb function, scoliosis and bulbar dysfunction were observed more frequently in patients with reduced lower limb performance. Physiotherapy, occupational therapy, and speech therapy, as well as the use of cough assists were less common than indicated by care guidelines. Family planning and educational and employment status appear to be related to motor skill impairment. CONCLUSIONS: We show that the natural history of disease has changed in Germany following improvements in SMA care and the introduction of novel therapies. Yet, a non-trivial proportion of patients remain untreated. We also identified considerable limitations in rehabilitation and respiratory care, as well as low labour-market participation among adults with SMA, calling for action to improve the current situation.

Quality of life and psychological aspects in children with overactive bladder treated with parasacral transcutaneous electrical nerve stimulation - A prospective multicenter study.

OBJECTIVE: To assess the impact of parasacral transcutaneous electrical nerve stimulation (parasacral TENS) on quality of life (QoL) and psychological aspects in children treated for overactive bladder (OAB). METHODS: This international, multicenter, prospective cohort study involved individuals of 6-16 years of age under TENS treatment for OAB. The study was conducted between June 2016 and December 2019 in four participating centers: two in Australia, one in Germany and one in Brazil. Patients with anatomical and/or neurological abnormalities of the urinary tract were excluded. Questionnaires were applied before and after parasacral TENS treatment: the Dysfunctional Voiding Symptom Score (DVSS), used in Brazil, or the International Consultation on Incontinence Questionnaire - Pediatric Lower Urinary Tract Symptoms (ICIQ-CLUTS), used in Germany and Australia, to analyze urinary symptoms; the Strengths and Difficulties Questionnaire (SDQ) to assess emotional and behavioral aspects; and the Pediatric Incontinence Questionnaire (PinQ) for bladder-specific Qol. RESULTS: Fifty-three patients (28 girls and 25 boys) with a mean age of 8.64 ± 2.63 years were included. Median DVSS was 11 (range 6-13.5) and 3 (range 0-7), (p < 0.001), and median ICIQ-CLUTS was 12 (range 9-14) and 9 (range 5.7-12), (p < 0.001), before and after treatment, respectively. Median PinQ score decreased from 47.8 (range 38.9-59.7) to 39 (range 29-53.15) following treatment (p = 0.04). Median total SDQ score before and after treatment was 17 (range 13.5-21) and 15 (range 12-21), respectively (p = 0.939). CONCLUSION: Parasacral TENS was associated with a significant improvement in urinary symptoms and QoL; however, there was no change in psychological symptoms, as measured using the SDQ.

Anxiety disorders, depression and incontinence in preschool children-A population-based study.

OBJECTIVE: The aim was to examine associations of specific anxiety disorders, depressive symptoms, and incontinence in a representative, population-based sample of preschool children. METHODS: All preschool children of a defined geographical area examined before school-entry were included. Parents completed a questionnaire including the Preschool Feelings Checklist (PFC), eight questions referring to nocturnal enuresis (NE), daytime urinary incontinence (DUI), fecal incontinence (FI) and constipation, and 30 items regarding Diagnostic and Statistical Manual of Mental Disorders-Fifth Edition (DSM-5) diagnostic criteria of separation anxiety disorder (SAD), social phobia (SOC), specific phobia (PHOB), and generalized anxiety disorder (GAD). Data of 1206 children (mean age = 5.7 years; 53.5% boys) are presented. RESULTS: 34.6% of incontinent children had an anxiety disorder based on DSM-5 criteria and 13.3% had clinically relevant depressive symptoms (measured by the PFC). Rates of incontinence overall were 14.1% (11.9% NE, 3.1% DUI, and 1.8% FI) and 6.3% for constipation. Rates of SOC and PHOB were increased in NE (20.8% and 25.4%), DUI (39.3% and 34.5%) and FI (35.3% and 50.0%) compared to continent children (13.5% and 17.2%). Children with constipation had higher rates of SOC, PHOB, and GAD than those without. Compared to continent children (9.7%), depressive symptoms were more frequent in children with NE (26.8%), DUI (50.0%), and FI (61.9%). CONCLUSION: Anxiety disorders and depressive symptoms are common in children with incontinence. The most specific DSM-5 disorders associated with incontinence are SOC and PHOB, which can be incapacitating and may require treatment. Due to the high rates of anxiety disorders, it is important to screen all children with incontinence, for example, with specific questionnaires.

Mental Health and Health-Related Quality of Life in German Adolescents after the Third Wave of the COVID-19 Pandemic.

Evaluations after the first and second waves of the COVID-19 pandemic in Germany showed an increase in mental health problems and a reduction in health-related quality of life (HRQoL). The aim of the study was to assess those aspects after the third wave of COVID-19 in adolescents who decided to receive a vaccination. In students aged 12-17 years recruited from schools in one German region, mental health (by the strengths and difficulties questionnaire, SDQ) and HRQoL (by KIDSCREEN-10) were assessed by both a self- and parental report. Data from 1412 adolescents (mean age 14.3 years, SD = 1.64) and 908 parents were collected. The mean self-reported HRQoL was T = 53.7 (SD = 11.2), significantly higher in boys than in girls and higher in younger (12-14 years) than in older (15-17 years) adolescents. In total, 18.7% of adolescents reported clinically relevant psychological symptoms, especially peer problems (23.5%), emotional problems (17.4%), and hyperactivity (17.1%). Comparing the present data to evaluations after the first and second waves of COVID-19, adolescents rated a higher HRQoL and reported less mental health problems after the third wave. After 1.5 years of living with the pandemic, adolescents have adapted to the changes in everyday life. Further, the relaxation of restrictions, better school organization, and the prospect of the vaccination may have increased optimism, wellbeing, and contentment, leading to declining but still alarming rates of psychological symptoms.

Incontinence and sleep disturbances in young children: A population-based study.

AIMS: Nocturnal enuresis (NE), daytime urinary incontinence (DUI), fecal incontinence (FI), as well as sleep and behavioral problems are common in young children. The aim of this study was to analyze the association of sleep and psychological parameters for all types of incontinence in a representative sample of young children. METHODS: Six hundred thirty eight (of 1161) children with a mean age of 5.9 years (50.9% boys) were assessed during their mandatory school entry examination. The participation rate was 55%. Instruments included the Strengths and Difficulties Questionnaire, the Children's Sleep Habits Questionnaire and other clinical questions. Incontinence was diagnosed according to ICCS standards. Constipation was assessed by two questions. RESULTS: 17.1% of children had at least one type of incontinence, 14.8% had NE, 5.0% DUI, 2.1% FI, and 4.8% were constipated. 6.7% of children had clinically relevant psychological problems. 22.7% of children had sleep problems regularly (5-7 times/week). A wide variety of sleep problems were reported. Children with incontinence were not affected by a higher rate of sleep problems. Children with NE had fewer night wakings and those with constipation fewer parasomnias. Sleep and psychological problems were significantly associated, especially in children with DUI and FI. CONCLUSIONS: Sleep and behavioral problems are common in young children. Psychological problems have a clear impact on sleep. Young children with incontinence do not have more sleep problems than continent children. Therefore, both sleep and psychological problems should be addressed in young children with incontinence.

Neurodevelopmental disorders and incontinence in children and adolescents: Attention-deficit/hyperactivity disorder, autism spectrum disorder, and intellectual disability-A consensus document of the International Children's Continence Society.

AIMS: Neurodevelopmental disorders (NDs) are incapacitating disorders, which begin early in life, are mainly caused by genetic and neurobiological factors, and show a tendency to persist. They are associated with higher rates of incontinence in children and adolescents, including nocturnal enuresis, daytime urinary incontinence, fecal incontinence, and constipation. Without diagnosis and treatment, they will interfere with incontinence treatment leading to less favorable outcomes. The aim of this International Children's Continence Society (ICCS) document is to provide an overview of the three most important NDs, that is, attention-deficit/hyperactivity disorder, autism spectrum disorder (ASD), and intellectual disability (ID). METHODS: This consensus paper was commissioned by the ICCS. A selective, nonsystematic review was performed. Guidelines, reviews, and selected studies were included. The recommendations are consensus-based. RESULTS: ADHD is the most common ND with special relevance in clinical practice. ASD and ID are less common, but more severe disorders than ADHD. Basic principles of the assessment and treatment of NDs are provided. Incontinence is common among patients with NDs. Specific modifications and practical approaches in the treatment of incontinence in children with NDs are outlined. CONCLUSIONS: Incontinence in children and adolescents with NDs is common. Effective treatment of incontinence should be adapted and modified to the specific needs of patients with NDs. A multiprofessional approach is recommended.

State and trait anxiety in children with incontinence and their parents.

BACKGROUND: Maternal anxiety increases the risk for incontinence in children. The aim was to analyze anxiety in children with incontinence and their parents before (t1) and after 6 months of incontinence treatment (t2). METHODS: 40 children with incontinence and 40 controls completed the State-trait Anxiety Inventory for Children, their parents the Child Behavior Checklist (CBCL) and the State-trait Anxiety Inventory at baseline (t1) and 6 months later (follow-up, t2). Psychiatric disorders were assessed by a standardized parental diagnostic interview (Kinder-DIPS), IQ was tested by a one-dimensional test. All children were neurologically examined. Children with incontinence underwent a guideline-based treatment during the 6 months. RESULTS: At baseline, child and parental state and trait anxiety scores, as well as all CBCL scores were significantly higher in the patient group compared to the control group. At t2, parental anxiety, CBCL scores, and child trait anxiety were significantly higher in patients versus controls, whereas child state anxiety decreased, and parental state anxiety increased from t1 to t2. CONCLUSIONS: Incontinence and anxiety are associated. While state anxiety decreases, trait anxiety can remain stable over time. Higher levels of anxiety can influence incontinence treatment and should be assessed in every patient.

Psychopathology and Parental Stress in 3-6-Year-Old Children with Incontinence.

Objective: Incontinence and functional gastrointestinal disorders are common in young children and are associated with higher rates of psychological symptoms and mental disorders. This article focuses on the mutual association between incontinence and related toilet refusal syndrome, parental stress, and children's psychopathology especially in young children. Methods: Children's psychological symptoms, mental disorders, and parental stress levels were assessed in 38 parent-child dyads involving children with incontinence and 42 dyads of typically developing (TD) children. Results: Compared to TD children, patients had higher internalizing and externalizing CBCL scores and higher rates of clinically relevant externalizing problems. However, the rates of clinically relevant internalizing problems and mental disorders did not differ. The parents of children with incontinence reported significantly higher stress levels regarding child-related stress factors (PSI-CD) than did parents of TD children. However, there were no clinically relevant parental stress scores on a group level, which remained below the clinical range (T-value < 60). When simultaneously analyzed, children's (comorbid) mental disorders but not incontinence had a major impact on parental stress. Conclusions: Despite moderate stress levels, incontinence symptoms, urinary and fecal incontinence are highly prevalent in young children. However, stress among parents of young children was mainly elicited by any (comorbid) mental disorder.

Behavioral comorbidity, overweight, and obesity in children with incontinence: An analysis of 1638 cases.

AIMS: Children with nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI) are at risk for behavioral problems, overweight, and obesity. The aim of this study was to analyze the specific behavioral and weight comorbidity in subtypes of incontinence. METHODS: A total of 1638 consecutive patients presented to a tertiary incontinence clinic from 2012 to 2018 was examined prospectively according to ICCS criteria. Behavioral symptoms were measured with the Child Behavior Checklist (CBCL). Psychiatric disorders were diagnosed according to ICD-10 criteria. Weight categories were calculated according to WHO recommendations. RESULTS: The mean age was 7.8 years, 67% of patients were male. Fifty-seven percent had NE (n = 934), 33% DUI (n = 547), and 40% FI (n = 656). Boys had significantly higher rates of NE and FI than girls. Of all children, 39.2% (n = 539) had a clinically relevant CBCL total score. A total of 28.3% (n = 463) had an ICD-10 psychiatric diagnosis, mainly ODD and ADHD, and 28.6% (n = 463) were overweight or obese. Boys were more often affected by behavioral symptoms, psychiatric disorders, and overweight/obesity. Children with NE had the highest rate of overweight/obesity. Except for primary nonmonosymptomatic NE, subtypes of incontinence did not differ regarding behavioral symptoms and weight categories. However, overweight/obesity was significantly associated with behavioral and psychiatric parameters. CONCLUSIONS: Behavioral symptoms and psychiatric disorders, as well as overweight/obesity are important risk factors associated with incontinence, but the interaction between these factors is complex. In clinical settings, all children with incontinence should be screened with behavioral questionnaires. Also, weight should be measured, and overweight/obesity should be addressed.

Incontinence in persons with tuberous sclerosis complex.

AIMS: Tuberous sclerosis complex (TSC) is a multisystem genetic disorder caused by a mutation in the TSC1 or TSC2 gene with a broad spectrum of physical and psychological manifestations. The aim of the study was to examine incontinence, psychological problems, and adaptive behavior skills in patients with TSC. METHODS: Through a worldwide TSC support group, 26 children (4-17 years) and 15 adults (18-50 years) with TSC were recruited (38.1% male, mean age 16.4 years). Parents or care-givers completed the Developmental Behavior Checklist (DBC), the Parental Questionnaire: Enuresis/urinary Incontinence, and the Vineland Adaptive Behavior Scales (3rd edition). RESULTS: A total of 60.0% of the participants had nocturnal enuresis (NE), 51.3% daytime urinary incontinence (DUI) and 52.4% fecal incontinence (FI). 65.4% of children and 50.0% of adults had a clinically relevant DBC score. Psychological symptoms were associated with at least one subtype of incontinence. The mean adaptive behavior composite (ABC) score of the patients was 57.2 (SD = 26.1), with 38.1% in the average or below-average range (IQ >70), 26.2% with a mild, 11.9% with a moderate and 23.8% with a severe/profound intellectual disability. The incontinence rate was significantly higher in the groups with a lower ABC score. CONCLUSION: A substantial proportion of patients with TSC are affected by incontinence and psychological symptoms. Incontinence was higher in persons with lower adaptive skills and those with at least one type of incontinence showed a significantly higher DBC score. As incontinence and psychological problems affect daily functioning and well-being, assessment, and treatment are recommended.

Bladder and bowel control in a population-based sample: Associations to quality of life and behavioral problems of 4-6-year-old children participating in the German Health Interview and Examination Survey (KiGGS).

BACKGROUND: Prevalence rates for psychiatric comorbidities are high in incontinent children. We analyzed data from the KiGGS survey in order to assess the rate of preschool children with delayed or regular continence, the mean age of gaining continence, psychiatric problems, and quality of life in a nation-wide, representative sample. METHODS: Parental questionnaire data of 3875 preschool children (4-6 years) were analyzed. Percentages of children with daytime, nighttime, and complete continence, and mean ages of gaining continence were calculated. Psychological and behavioral problems (SDQ), as well as Quality of life (KINDL-R), were assessed. RESULTS: 16.9% showed delayed gaining of continence. Percentages of children with nighttime bladder continence were lower for boys (76.3%) than for girls (80.6%), and lower for children without (78.2%) than those with a migration status (79.2%). Complete continence was gained by more girls (83.9%) than boys (78.2%), more children from the former East Germany (82.4%) than former West Germany (81.1%), and by more migrants (82.7%) than nonmigrants (81.9%). Girls, children living in the former East of Germany, and migrants achieved continence consistently at an earlier age. Children with incontinence or continence ≥4 years showed significantly more psychological problems, less prosocial behavior and low quality of life. CONCLUSION: The age at gaining continence is moderated by gender, German region, and migration status. Delayed achievement of continence is associated with more psychological problems and a lower quality of life. The importance of effective treatment of incontinence is emphasized by the results of this study.

Incontinence and psychological symptoms in Phelan-McDermid syndrome.

AIMS: Phelan-McDermid syndrome (PMD) is a congenital syndrome caused by a deletion on chromosome 22q13.3. About 600 cases have been identified worldwide. PMD is characterized by neonatal hypotonia, moderate/severe intellectual impairment, impaired expressive language, and typical dysmorphic features. Psychological symptoms as hyperactivity, attention problems, restlessness, and stereotyped-repetitive behavior were reported. The aim of the study was to assess incontinence and associated psychological problems in PMD. METHODS: Forty-one individuals with PMD were recruited through a German support group (48.8% male; mean age 13.4 years; range, 4-55 years). Parents or caregivers completed the developmental behavior checklist (DBC), as well as the parental questionnaire: enuresis/urinary incontinence, including six questions on adaptive toileting skills. RESULTS: Rates of nocturnal enuresis (NE), daytime urinary incontinence, and fecal incontinence were 86%, 73%, and 79%. Rates were similar in all age groups (children, teens, adults). Constipation was present in 19%. Forty-two percent of the sample had a clinically relevant DBC score, with adults more affected than teens. Persons with NE had significantly higher "anxiety/depression" subscale scores. Toileting skills were more developed in adults than in children. Sixty-eight percent had further physical disabilities. CONCLUSIONS: Incontinence rates in PMD are high in all age groups. However, persons with PMD can improve their toilet skills. Therefore, the assessment and treatment of incontinence in persons with PMD is recommended. Constipation does not seem to be a major problem in PMD. Due to the high prevalence rates of somatic conditions, an assessment for organic and functional incontinence is recommended.

Incontinence and headache in preschool children.

AIMS: Headaches in preschool children are associated with behavioral and gastrointestinal symptoms. As the co-occurrence with incontinence is not known in young children, the aim of the study was to examine associations of headache, psychological symptoms and nocturnal enuresis (NE), daytime urinary incontinence (DUI), and fecal incontinence (FI) in a population-based sample of preschool children. METHODS: All preschool children of a defined geographical area were examined at school-entry. Parents completed a 22-item questionnaire, including 14 headache, 4 incontinence, and 25 items of the Strength and Difficulties Questionnaire (SDQ). Five hundred eighty-five children (50.4% males) with a mean age of 5.8 years were included. RESULTS: In total, 27.2% of all children had headaches. 15.7% had secondary and 11.3% primary headaches. Five children had migraine and five tension-type headaches, while all others were unclassifiable. 9.4% of children had incontinence (7.7% NE; 2.4% DUI, 1.2% FI) and 4.0% constipation. The rates of incontinence did not differ between children with primary and those without headache for NE (12.9% vs 7.5%), DUI (3.1% vs 2.7%) or FI (3.0% vs 1.0%), but for constipation (12.1% vs 2.6%). Incontinent children had significantly more behavioral and externalizing symptoms, children with headache more internalizing problems. Primary headache was a significant predictor for internalizing, while constipation and FI were predictors for externalizing symptoms. CONCLUSIONS: This population-based study showed that headache is associated with constipation, but not with incontinence in preschool children. Headache and incontinence are common risk factors for specific psychological symptoms and should be assessed in clinical practice.

Tuberous Sclerosis Complex Associated Neuropsychiatric Disorders and Parental Stress: Findings from a National, Prospective TSC Surveillance Study.

AIM: To assess the role of the TAND (tuberous sclerosis complex [TSC] associated neuropsychiatric disorders) checklist as a screening tool for neuropsychiatric pathology, to evaluate behavioral and psychiatric symptoms and related parental stress in children with TSC, and to analyze associations between parental stress, TAND findings, and TSC pathology. METHOD: This is a prospective cohort study including 22 individuals from a national TSC surveillance study in Germany using demographic and clinical data, the TAND checklist, the Child Behavior Checklist (CBCL), and the Parenting Stress Index (PSI). RESULTS: Mean (standard deviation) age at follow-up was 4 years (3 years 9 months), and 13/22 of patients were male. Seventeen children had epilepsy (focal: 9; generalized: 4; infantile spasms: 4). Developmental delay was diagnosed in 12/22 patients. The most prevalent TAND items were anxiety and mood swings in 10/22 children. At least one TAND item was reported by 17/22 patients, internalizing symptoms by 10/22, and externalizing symptoms by 11/22. In contrast, only one patient had a clinically relevant score in the CBCL scales. Of 22 parents, 12 reported clinically relevant parental stress due to both child and parenting factors. Higher total parental stress was associated with a higher TAND externalizing score (r = 0.49; p = 0.028) and TAND total score (r = 0.51; p = 0.016), a higher CBCL total score (r = 0.59; p = 0.005), and the number of antiepileptic drugs (r = 0.50; p = 0.017). Developmental delay was correlated with child stress factors (r = 0.48; p = 0.023). INTERPRETATION: The TAND checklist appears to be a promising screening tool for neuropsychiatric problems in very young children with TSC. Parental stress in children with TSC is modified by TSC-related pathology, both neuropsychiatric and neurological.