Pediatric Quality of Life Inventory Generic Core Scales SF15

The PedsQL SF15 version 4.0 was used to assess quality of life (QoL) in children with UCDs.^32–35 The PedsQL SF15 is typically reported using two forms: one self-reported component and one parent-reported component in children (aged five years to 18 years).

The PedsQL SF15 questionnaire consists of 15 questions that assess the following dimensions: physical functioning (five questions), emotional functioning (four questions), social functioning (three questions), and school functioning (three questions). Items are scored using a five-point Likert scale ranging from 0 (never) to 4 (almost always) or a three-point scale ranging from 0 (not at all) to 4 (a lot). Items are then reverse-scored and linearly transformed to a scale from 0 to 100 in the following manner: 0 = 100, 1 = 75, 2 = 50, 3 = 25, and 4 = 0. Higher scores indicate better QoL. Dimension scores are calculated as the mean of the items within the respective domain. In addition to the dimension scores, a psychosocial health summary score is also evaluated and consists of the emotional, social, and school-functioning dimensions. The physical health summary score is also evaluated as the average of the physical functioning scale scores. The total score was calculated as the sum of all the items over the number of items answered on all the scales.

Short Form (36) Health Survey

The SF-36 version 2.0 was used to assess QoL in adults with UCDs. SF-36 is a generic health assessment questionnaire that has been used in clinical trials to study the impact of chronic disease on health-related quality of life (HRQoL). SF-36 consists of eight domains: physical functioning, pain, vitality, social functioning, psychological functioning, general health perceptions, and role limitations due to physical and emotional problems. SF-36 also provides two component summaries: the physical component summary (SF-36-PCS) and the mental component summary (SF-36-MCS). The SF-36 PCS, SF-36-MCS, and eight domains are each measured on a scale of 0 to 100, with an increase in score indicating improvement in health status. In general use of SF-36, a change of two points to four points in each domain or two points to three points in each component summary indicates a clinically meaningful improvement as determined by the patient.³⁶

Wechsler Abbreviated Scale of Intelligence (WASI-II)

The WASI-II is a nationally standardized abbreviated general assessment of IQ based on the Wechsler Adult Intelligence Scale and is used in clinical, educational, and research settings. The WASI-II provides three scores based on verbal comprehension, perceptual reasoning, and full-scale IQ for children and adults from six to 89 years of age.^{32–34,37,38}

The WASI-II includes four subtests based on vocabulary (31 items), similarities (24 items), block design (13 items), and matrix reasoning (30 items) and can be administered in 30 minutes. The verbal comprehension score is based on the vocabulary and similarity subtests measuring knowledge, verbal concept formation, fund of knowledge, verbal reasoning, and concept formation. The perceptual reasoning score is based on the matrix reasoning and block design subtests measuring visual information processing, abstract reasoning skills, ability to analyze and synthesize abstract visual stimuli, non-verbal concept formation, visual perception and organization, simultaneous processing, visual-motor coordination, learning, and the ability to separate figure and ground in visual stimuli. An approximation of the full-scale IQ can be obtained based solely on the vocabulary and matrix reasoning subtests in 15 minutes.

Wechsler Preschool and Primary Scale of Intelligence, Third Edition (WPPSI-III)

The WPPSI-III is a measure of cognitive development for preschoolers and young children. The WPPSI-III provides five scores based on verbal IQ, performance IQ general language, processing speed index, and full-scale IQ for children from two to seven years of age.^39,40,41,42

The WPPSI-III includes 14 subtests in total that are composed of one item per subtest. Children under the age of four are typically evaluated based on five (receptive vocabulary, block design, information, object assembly, and picture naming) of the 14 subtests, whereas children older than four years of age are evaluated based on all 14 subtests, which include vocabulary, picture concepts, symbol search, word reasoning, coding, comprehension, picture completion, and similarities, and can be administered between 25 and 50 minutes depending on age (more time for older children). The verbal IQ score is based on the information, vocabulary, and word reasoning; the performance IQ is based on block design, matrix reasoning, and picture concepts; and the processing speed index is based on coding and symbol search. The full-scale IQ is established using the vocabulary and performance score summaries as well as the coding subtest.

Grooved Pegboard Test

The Grooved Pegboard Test is used to test motor and visual skills through manual dexterity in children five years of age and older as well as in adults and is typically used in neuropsychological test batteries, student labs, and as a screening technique in industrial environments.^33,43,44 The test requires manipulative dexterity and contains 25 holes with randomly positioned slots and pegs that have an accompanying key. Pegs are rotated to match their hole counterpart before they can be inserted. This task is performed and evaluated using both the patient’s dominant and non-dominant hand. Performance is measured based on the time required to complete the task, the number of unintentional peg drops, and the number of correct pegs inserted in the board upon completion. Results are then compiled and compared with tabulated means and standard deviations (SDs) in the local population categorized by age group.

Digit Span Test

The digit span test is a common measure of attention and short-term memory in both adults and children seven years of age and older.^33,45,46 The evaluations of both the forward and backward digit span are commonly used neuropsychological tests and are typically included in a component of the Wechsler memory scales and Wechsler intelligence scales. The patient is given a list of digits and then asked to recall them in correct sequential order (forward) and in reverse order (backward). Two trials are presented for each digit sequence and begin with a length of two digits per sequence. With every successful sequence, patients are presented with increasing digit sequence lengths. The digit span test ends when the patient fails to accurately report either of the two trials for a given sequence length or when the maximum sequence length is reached (nine digits forward and eight digits backward). The numbers of correct forward and backward sequences are combined to produce the Wechsler total correct score. Typically, three metrics can be used to assess the digit span test results: the maximum span, which consists of the longest sequence of digits correctly reported after two consecutive failures; the mean span, which is the mean of correctly reported digits; and the sequence length in which 50% of the digits were correctly reported.

California Verbal Learning Test

The CVLT-II assesses verbal memory abilities through testing immediate and delayed recall in adults and children 16 years of age and older. The CVLT-II provides seven scores based on the list A total recall, short delay free and cued recall, long delay free and cued recall, learning slope and total recognition discriminability.^33,47,48

Several lists containing 16 common words are read to the patients. Each word belongs to one of four categories, such as fruits and herbs. Patients are then asked to recall as many of these words as possible. The standard and alternative forms can be administered in 30 minutes of testing with a 30-minute delay, and the short form can be administered in 15 minutes of testing with a 15-minute delay. During the delay, patients are given other tasks to perform. The tester again asks the patients to recall the list. The number of correct answers is recorded for both immediate and delayed recall tasks. The list A total recall is based on the number of words in list A recalled in trials one through five. The short delay free recall is based on the number of words in list A recalled immediately after another trial using words from list B, whereas the short delay cued recall counterpart presents the category names of the words used in list A. The long delay free recall is based on the number of words in list A recalled after a delay of non-verbal testing is imposed following the short delay cued recall trial, whereas the long delay cued recall counterpart presents the category names of the words used in list A. The learning slope score is based on the slope of the least squares regression for correct response scores through trials one to five.

Child Behavior Checklist

The CBCL is an instrument used to rate a child’s problem behaviours and competencies. The preschool form is intended for children aged one year to five years, and the school-age form is intended for children under 18 years of age. The CBCL provides three summary scores categorized under internalizing problems, externalizing problems, and total problems.^{32,33,34,39,40,49,50}

The CBCL is completed by parents or teachers who are familiar with the patient. The first section of this questionnaire consists of 20 competence items, while the second section consists of 120 items on behaviour or emotional problems during the past six months. Items are scored using a three-point Likert scale in which 0 signifies “not true,” 1 signifies “somewhat or sometimes true,” and 2 signifies “very true or often true.” The CBCL is based on eight domains, which include the following: aggressive behaviour, anxious/depressed, attention problems, rule-breaking behaviour, somatic complaints, social problems, thought problems, and withdrawn/depressed. The internalizing problems summary score is based on the sum of the anxious/depressed, withdrawn/depressed, and somatic complaints domain scores, whereas the externalizing problems summary score is based on the sum of rule-breaking behaviour and aggressive behaviour domain scores. The total problem summary score is based on the sum of all domains.

Behavior Rating Inventory of Executive Function

The BRIEF is designed to assess executive functioning. The preschool form consists of 63 items and is intended for children aged two years to five years, whereas the standard form consists of 86 items and is intended for children aged five years to less than 18 years of age. The BRIEF provides three summary scores categorized under a behavioral regulation index, metacognition index, and global executive composite.^{32,33,34,39,40,51,52,53,54,55}

The BRIEF is completed by parents or teachers who are familiar with the patient. Items are scored using a three-point Likert scale — “never,” “sometimes,” and “often,” — in which higher scores reflect higher levels of reported problems. The BRIEF is based on eight domains, which include the following: inhibit, shift, emotional control, monitor, organization of materials, plan/organize, working memory, and initiate. The behavioural regulation index score is based on the inhibit, shift, and emotional-control domains, and the metacognition index score is based on the monitor, organization of materials, plan/organize, working memory, and initiate domains. The global executive composite score considers all domains and represents the child’s overall executive function.

The BRIEF can be assessed using t scores, with a score of 50 points typically considered the mean and a difference of 10 points from the mean as one SD. A clinically important difference for the BRIEF was identified as a change of 15 points (1.5 SDs) in the t score in a study by Waisbren et al. evaluating the validity of the BRIEF in a pediatric population with UCDs. However, the methodology used to establish the clinically important change in the study by Waisbren is unclear.⁵⁶