The GAIRS Checklist: a useful global assessment tool in patients with Rett syndrome

Abstract

Background

Rett Syndrome is a severe, neurodevelopmental disorder mainly caused by mutations in the MECP2 gene, affecting around 1 in 10,000 female births. Severe physical, language, and social impairments impose a wide range of limitations in the assessment of the abilities of Rett patients. This study proposes an analysis and first validation of a Global Assessment and Intervention in Rett syndrome (GAIRS) Checklist for assessing behavioral, intellectual, academic, neuropsychological and psychosocial manifestations in patients with Rett Syndrome. We administered the GAIRS Checklist to 113 Italian patients with Rett Syndrome aged 4–42.

Aims of this study

To examine the psychometric characteristics of the GAIRS Checklist. Moreover, the aim is also to examine the validity of GAIRS with test–retest correlation, convergent validity with similar functional measurements, such as the Vineland scales, and divergent validity with severity of disease scale, such as the RARS scale and severity of neuropsychiatric evaluations.

Results

All 10 subscales of GAIRS were positively and significantly related to each other and to the total GAIRS score, and the subscales showed high levels of Cronbach’s alpha values (from .77 to .95). Principal axis factoring suggested two factors that explain 60% of the variance. Test–retest reliability is 0.82. This means that psychometric properties are reliable. Correlation for Concurrent validity with Vineland score was high and Divergent Validity with RARS was also high.

Conclusion

The GAIRS Checklist used for Rett syndrome is acceptable and feasible to complete assessment in a clinical setting. Moreover, it can detect the complexity of this disease and may suggest the next step in terms of specific training in Rett syndrome.

Background

Rett syndrome (RTT) is a severe, neurodevelopmental disorder mainly caused by mutations in the MECP2 gene, affecting around 1 in 10,000 female births [1]. Clinical manifestations include severe linguistic and motor impairments that are the core of phenotype symptoms. A child affected by RTT initially appears to follow a typical development path, but at about 18 months of age a subtle regression in developmental acquisitions begins, opening the path to the clinical stages [2]. Loss of previously acquired language skills and of purposeful hand use, increasing difficulties in motor abilities (dyspraxia) and mental retardation are the clearest signs of regression involved in RTT. Other typical signs of RTT appear including hand stereotypies—such as handwashing, hand-wringing, hand-mouthing—breathing disorders (breath holding and hyperventilation), ataxia, agnosia, bruxism and epilepsy [3,4,5,6].

Several assessments on patients with RTT have been conducted on cognitive abilities, on communicational abilities and on motor abilities [7,8,9,10,11]; only few of these have carried out a global functional assessment of all the abilities of these patients. Assessment of the cognitive skills of patients with RTT, as well as other individuals with severe motor and communication limitations, is extremely challenging. [7] Neuropsychological and cognitive assessments are generally developed for and standardized with typically developing children who do not have physical impairments [12]. When standard assessment procedures requiring manual motor functioning for responding have been used to evaluate cognitive functioning, patients with RTT generally achieve age-equivalent performances close to young infants [13, 14]. Severe physical, language, and social impairments impose a wide range of limitations [2,3,4,5]. With reference to communication abilities, some studies [15, 16] have aimed to recognize any communicative acts (vocalizations, hand movement stereotypies, body movements, facial expressions, or eye gaze) that would represent a consistent and unequivocal response used by participants with RTT.

With reference to the assessment of motor abilities, available clinical scales do not comprehensively capture the variability of presentation of gait and postural abnormalities in Rett Syndrome patients. Griffiths scales [17] appear too specific to assess peculiar patterns of (loco-)motor derangements in RTT. In addition, the standardization sample included children aged 0–72 months and therefore, similar to the standardization sample of the Bayley scales [18], is not appropriate to test older children or adolescents. There is another motor scale specific for RTT and already validated: the Rett Syndrome Gross Motor Scale (RSGMS) [19]. Rodocanachi et al. [20], in a new standardized scale, the Rett Syndrome Motor Evaluation Scale (RESMES), added postural transitions and walking up or downstairs. RESMES items are centered on the International Classification of Functioning construct of patient’s capacity, which reflects what an individual can do in a semi-standardized environment and have been conceived to capture fine-grained characteristics of movement. Regarding a general assessment, there are two scales that can be used to assess children with special needs: the Portage Guide to Early Education Checklist [21] and the Bayley Scales of Infant Development [18]. The Portage Guide to Early Education Checklist [21] was developed by the Portage Project home intervention program which has been serving preschool multiple children with special needs in Wisconsin, USA. The guide has two parts: a developmental checklist which lists sequential behaviors from birth through five years of age in five learning areas and a set of curriculum cards which match each of the 450 behaviors listed on the checklist. The check-list has been used to pinpoint behaviors and measure change. The cards have been used in establishing individual home training prescriptions [21]. The Bayley Scales of Infant Development [18] consist of a mental scale of 103 items and a motor scale of 81 items. The scales have been designed to measure growth and development from birth to 30 months of age. The instrument was developed primarily for clinical and research use. According to Holden [18], the Bayley Scales have been invaluable in filling a longstanding need for a well standardized, reliable instrument to assess the developmental progress of infants.

With reference to the global assessment of the abilities in Rett syndrome, there are few instruments that can measures the global functional abilities of RTT patients. Some assessments have been carried out by interviewing the parents or caregivers using the Vineland Adaptive Behavior Scales-Interview second edition (VABS), and the Rett Assessment Rating Scales (RARS) [22]. VABS [23] is subdivided into four domains: communication; daily living; socialization; and motor skills. The interviewer asks general questions pertaining to the patient’s functioning in each domain and uses the responses to rate the examinee on each critical behavior item (2: always present, 1: sometimes present, 0: seldom or never present). Typical interviews require approximately one hour. A total score is computed by summing the individual ratings for each scale. Another general assessment scale has been created to evaluate level of severity in RTT patients—RARS [22]. This scale is organized into seven domains: cognitive, sensorial, motor, emotional, autonomy, typical characteristics of the disease and of behavior. A total of 31 items was generated as representative of the profile of RTT. Each item is provided with a brief glossary explaining its meaning in a few words. Each item is rated on a 4-point scale, where 1 = within normal limits, 2 = infrequent or low abnormality, 3 = frequent or medium–high abnormality, and 4 = strong abnormality. Intermediate ratings are possible; for example, an answer between 2 and 3 points is rated as 2.5. For each item, the evaluator circles the number corresponding to the best description of the patient. After a patient has been rated on all 31 items, a total score is computed by summing the individual ratings. This total score allows the evaluator to identify the level of severity of RTT, conceptualized as a continuum ranging from mild symptoms to severe deficits (Mild = 0–55; Moderate = 56–81; Severe =  > 81).

Summarizing, the main limitations of the scales presented here are firstly, in some scales like VABS and RARS parents and caregivers are requested to evaluate patients’ abilities through simple observation and not through direct evaluation by therapists; secondly, in some of these scales not all the areas of manifestations in RTT are considered (behavioral, intellectual, academic, neuropsychological and psychosocial); finally not all of these scales are presented hierarchically and they may not be valid for the assessment or for suggesting all the next level of the steps necessary for any eventual intervention.

In the present work, we proposed the Global Assessment and Intervention in Rett syndrome (GAIRS) to overcome all these limitations. The aim of this study is to examine the preliminary psychometric characteristics of the GAIRS Checklist. Furthermore, the aim is to examine the validity of GAIRS with test–retest correlation, convergent validity with similar functional measurements such as the Vineland scales, divergent validity with severity of disease scale such as the RARS scale and neuropsychiatric evaluations. A specific GAIRS Checklist has been developed to assess behavioral, intellectual, academic, neuropsychological and psychosocial manifestations in patients with Rett Syndrome. The purpose of the Checklist is to offer an easy-to-use, short and accessible tool for every health-care professional to assess all the abilities but also to identify patients needing next-step evaluation and treatment. Thanks to the hierarchical order of all the targets assessed in each area of GAIRS, this Checklist can be a useful instrument not only for assessment but also for any eventual intervention.

Methods

Patient characteristics

GAIRS was administered to 113 consecutively enrolled Rett patients (111 females, mean age 18.39 ± 10.19 years), from the Italian Rett Association. All 113 patients, aged from 4 to 45 years, met the diagnostic clinical criteria for Rett Syndrome and underwent specific genetic tests.

RTT patients were classified as clinical stage III (characterized by prominent hand apraxia/dyspraxia, apparently preserved ambulation ability, and some communicative ability, mainly eye contact) or stage IV (late motor deterioration, with progressive loss of ambulation ability), according to the criteria for classic RTT by Hagberg et al. [4]. Their demographic, developmental, clinical, behavioral, and genetic information, collected from all available sources (parent/caregiver reports of history and current behavior and features, previous clinical reports, and direct observation and examination of the patients) was entered into a database.

The Mecp2 mutation was seen in 80% of the sample; specific mutations of the Mecp2 gene were: 5% showed C7D3C, 10% showed R294X, 10% showed C965C, 10% showed R255X, 15% showed P152R and 30% showed T158M. Instead, for 20%, it was not possible to specify the type of gene mutation, but all the typical phenotypic characteristics of RTT were observed. We asked the reference neuropsychiatry of each patient to give a medical judgment of severity based on typical characteristics of the syndrome (epilepsy, mood swings, convulsions, aerophagia, scoliosis). The severity level ranges from 5 (mild severity) to 20 (severe severity). Mean severity index in relation to the typical characteristics of the syndrome is 9. Table 1 shows the clinical characteristics of the participants.

Table 1 Clinical characteristics

Materials

GAIRS is a global assessment and intervention rating scales checklist for Rett syndrome with items coming from the items of assessment in multi-disability disorders adapted to Rett syndrome [24,25,26,27,28]. Through a global analysis, it gives an overview of the different areas and is intended for use in a functional analysis of the overall abilities of the patient.

The GAIRS Checklist is composed of 10 macro-areas: basic or pre-requisite behavior, neuropsychological abilities, basic cognitive concepts, advanced cognitive concepts, communication abilities, emotional- affective abilities, hand motor skills, graphomotor skills, global motor abilities and level of autonomy in daily life. The 10 areas are described in Table 2. For each area, different sequential skills, hierarchically structured, are evaluated. Eighty-five skills in total are evaluated. Each skill has a numerical score ranging from 1 to 5, where 1 is the minimum level of capacity and 5 is the maximum level of capacity to perform a specific activity. Below, we present some examples. In the area of basic behavior, the first skill that is evaluated is spontaneous eye contact. The score of this skill is: 1 If the child is unable to establish spontaneous eye contact, 2 if the child can establish spontaneous eye contact 2/3 times out of 10, 3 if the child can establish spontaneous eye contact 4/6 times out of 10, 4 if the child can establish spontaneous eye contact 7/8 times out of 10, 5 if the child always establishes spontaneous eye contact. Instead, the sixth skill investigated in the hand motor area is grasping ability and its score is: 1 if the child cannot grasp an object on the table, 2 if the child can grasp a 5 cm object with palmar cubitus grip, 3 if the child can grasp a 5 cm object with palmar grip, 4 if the child can grasp a 1 cm object with pluri-digital grip, 5 if the child can grasp a 1 cm object with plier’s grip (thumb-index).

Table 2 Description of GAIRS checklist areas

VABS [23] is an assessment scale carried out by interviewing the parents and allow to highlight four domains: communication, daily living, socialization and motor skills. The reliability of the scales was established with reference to skewness, kurtosis and alpha values. Skewness is a measure of the asymmetry, kurtosis is a measure of the combined weight of a distribution's tails relative to the center of the distribution, Cronbach’s alpha is the measure of internal consistency. With reference to communication domain the reliability was established as follows: skewness = 0.38, kurtosis = 0.34, Cronbach’s alpha = 0.89; the reliability for daily living skills was: skewness = 0.34, kurtosis = 0.27, Cronbach’s alpha = 0.88; the reliability for socialization domain was: skewness = 0.69, kurtosis = 0.76, Cronbach’s alpha = 0.91; the reliability for motor skills domain was: skewness = 0.87, kurtosis = 0.67, Cronbach’s alpha = 0.94. The Cronbach’s alpha for the general scale was 0.89.

RARS [22] is a standardized scale used to evaluate the severity of the disease in patients with RTT. The total score allows to measure the severity of the disease along a continuum ranging from mild symptoms to severe ones. Skewness and kurtosis values, calculated for the distribution of the total score, are respectively 0.110 and 0.352. Distribution is found to be normal. Cronbach’s alpha is used to determine the internal consistency for the whole scale and subscales. Total alpha is 0.912, and the internal consistency of the sub-scales is high (from 0.811 to 0.934).

Procedure

Initially, Airett center professionals contacted the family by phone through a brief interview to collect their availability for GAIRS administration sessions. Then, parents were invited to a session in which they completed the RARS scale [22] that allows to identify the severity of the patients with Rett syndrome, and the Vineland questions [23] to identify behavioral features.

After these sessions, GAIRS Checklist was administered to the patients by the Airett team, composed of a physician, speech therapist and psychologist, during the evaluation sessions at the Rett Center. All professionals had certified, special training on Rett syndrome. Total administration time was around 4 h (range from 3 to 7) but for the most serious patients it was necessary to divide the administration into multiple sessions (2 or 3). Some skill scores that cannot be given directly during the evaluation, such as the item related to the ability to go to the bathroom, was evaluated through video or interview with parents. Every skill was requested ten times, but if the participant gave the first 3 correct answers, the skill was considered acquired; in the same way, if the participant gave the first 3 wrong answers, the skill was considered not acquired.

Results

Data were analyzed using the Statistical Package for the Social Sciences [29]. We used mean and standard deviation (SD) for the descriptive variables. Normality of the distributions of quantitative variables was verified by applying the Shapiro–Wilk test. Descriptive analysis of both demographic and clinical characteristics of Rett Syndrome patients was performed on the whole cohort. Results were discussed initially with reference to factorial structure of the GAIRS, afterwards, with reference to the internal reliability, and to the correlation for concurrent and divergent validity and finally, with reference to two examples of operational application of GAIRS and suggestions of intervention to two patients.

Factorial structure

To verify the factorial structure of the GAIRS, exploratory factor analysis (EFA) using principal axis factoring (PAF) was conducted with the Kaiser normalization promax rotation. Finally, we considered Internal Reliability (Cronbach alpha), test–retest reliability, and Correlations for Concurrent and Divergent Validity (Pearson correlations). We considered a two-tailed p value of 0.05 or less statistically significant.

Descriptive analyses and preliminary analyses

Tables 3, 4, 5, 6, 7, 8, 9, 10, 11 and 12 show the means and standard deviations for all the items for each subscale of GAIRS. Skewness and kurtosis for all the items were also determined and most items showed normal distribution, while few were positively or negatively skewed.

Table 3 Means, standard deviations, correct percentages and skewness and kurtosis values of the basic behavior area items

Table 4 Means, standard deviations, correct percentages and skewness and kurtosis values of the neuropsychological area items

Table 5 Means, standard deviations, correct percentages and skewness and kurtosis values of the basic cognitive area items

Table 6 Means, standard deviations, correct percentages and skewness and kurtosis values of the advanced cognitive area items

Table 7 Means, standard deviations, correct percentages and skewness and kurtosis values of the communication area items

Table 8 Means, standard deviations, correct percentages and skewness and kurtosis values of the emotional area items

Table 9 Means, standard deviations, correct percentages and skewness and kurtosis values of the hand motor area items

Table 10 Means, standard deviations, correct percentages and skewness and kurtosis values of the graphomotor area items

Table 11 Means, standard deviations, correct percentages and skewness and kurtosis values of the gross motor area items

Table 12 Means, standard deviations, correct percentages and skewness and kurtosis values of the autonomy in daily life area

Inter-subscale correlations were very high (Table 13). All 10 subscales of GAIRS were positively and significantly related to each other and to the total GAIRS score.

Table 13 Inter-subscale correlations among GAIRS’ areas

Exploratory factor analysis

To verify the factorial structure of GAIRS, PAF was conducted with the Kaiser normalization promax rotation. The use of an EFA approach in a first study testing a new construct such as GAIRS is suitable [30]. Furthermore, the use of PAF is recommended with a violation of the assumption of multivariate normality [31, 32].

The number of factors was determined through Velicer’s minimum average partial (MAP) test and parallel analysis [33]. Both the parallel analysis and the original MAP test suggested two factors, and for this reason, a PAF estimation using promax rotation with two-factor solutions was used to explore factor loadings. The two-factor solution was found to explain 60% of the variance. Almost all the items are loaded into the first factor (that explains 40% of variance) and provide evidence of a general level of abilities which are homogeneous in all subareas. The second factor explains 20% of the variance and can provide evidence of advanced formal learning abilities (Table 14).

Table 14 Exploratory factor analysis

Internal reliability, and correlation for concurrent and divergent validity

Since we obtained a single general factor explaining 40% of the variance of GAIRS, we decided to maintain the original sub areas to better describe the general functioning of patients with Rett Syndrome in each of them. For each subarea, we calculated the alpha levels for internal consistency. Cronbach’s alpha values for all the subscales and the total score were high with a range from 0.77 to 0.95. A test–retest correlation was applied on 58 patients with Rett syndrome 2 months after the first administration and the results were very high (r (58) = 0.82, p < 0.002).

All ten subscales of GAIRS were negatively related with the severity of symptoms of the RARS scale [22] and with neuropsychiatric symptom evaluations, while all the subscales of GAIRS were positively correlated with the concurrent measure of the Vineland (Table 15).

Table 15 Correlation among GAIRS score and other assessment instruments

Applications of GAIRS and suggestions of intervention

GAIRS scores have a mean of 2.28 and a standard deviation of 0.70. Based on this, we divided the scores on three levels: patient scores that fall in the 1–1.58 range (where the maximum is m-sd, i.e., 2.28–0.70) show basic competence, patient scores that fall in the 1.59–2.98 range (where the maximum is m + sd, i.e. 2.28 + 0.70) show an intermediate level of competence and, finally, patient scores that that fall in the 2.99–5.00 range show a high level of competence.

As an example, below, we present two patients (from our data file) that benefitted from the administration of GAIRS. Emma (name changed for anonymity) has a general score of 1.56, this means that she has a basic level of competence. This index told us nothing about intervention. We need to examine all areas of GAIRS: as we can see from Fig. 1, Emma has an intermediate level of gross motor abilities and participation and autonomy. She needs to improve prerequisites. For this reason, it is useful to go more in depth and to disaggregate prerequisite data, as shown in Fig. 2. We can see that while sometimes she looks for people with spontaneous eye contact, she is not able to show eye contact on request, neither look nor trace an object. Then we continue by examining the other areas. Once the hypothesis for each patient was developed, differential reinforcement procedures combined with extinction were designed in order to increase the identified behaviors. For example, the training with Emma has to have the aim of reaching a higher level of visual attention to faces and to objects. Additionally, she may benefit from starting functional communication training and motor training.

Fig. 1

GAIRS mean scores for each area

Fig. 2

Prerequisites subarea of GAIRS mean scores

Another example of application is the analysis of GAIRS with Anna. Anna (name changed) has a general score of 3.90, this means that she has a high level of competence. Again, we have to examine all areas of GAIRS: as we can see from Fig. 3, Anna has almost a master level in the prerequisites area of abilities and participation and autonomy. The disaggregation of prerequisites shows that she does not need to improve prerequisites (Fig. 4), just the ability to wait. We can continue and disaggregate the other areas and produce the hypothesis for the intervention.

Fig. 3

GAIRS mean scores for each area

Fig. 4

Prerequisites subarea of GAIRS mean scores

GAIRS scores have a mean of 2.28 and a standard deviation of 0.70. Based on this, we divided the scores on three levels: patient scores that fall in the 1–1.58 range (where the maximum is m-sd, i.e., 2.28–0.70) show basic competence, patient scores that fall in the 1.59–2.98 range (where the maximum is m + sd, i.e. 2.28 + 0.70) show an intermediate level of competence and, finally, patient scores that that fall in the 2.99–5.00 range show a high level of competence.

Discussion

The principal aim of this study was to examine the psychometric characteristics of the GAIRS Checklist. Moreover, the aim was to examine the validity of GAIRS with test–retest correlation, convergent validity with similar functional measurements such as the Vineland scales [23], divergent validity with severity of disease scale such as the RARS [22] scale and neuropsychiatric evaluations.

With reference to the validity of GAIRS, we decided to maintain the original subareas of the Checklist to better describe the general functioning of patients with Rett Syndrome in each of them. For these reasons, this study adds data on the use of the GAIRS Checklist in the global evaluation of patients with RTT. The results of the statistical analysis showed good internal reliability of the scale. Regarding the convergent validity with similar functional measurements such as the Vineland scales, all subscales of GAIRS were positively correlated with the concurrent measure of the Vineland and with neuropsychiatric symptom evaluation. With reference to the severity of disease scale such as the RARS scale and the neuropsychiatric evaluations, all ten sub-scales of GAIRS were negatively related with the severity of symptoms of the RARS scale [22]. All subscales of GAIRS were positively correlated with the concurrent measure of the Vineland and with neuropsychiatric symptom evaluation.

Our experience confirms the previously reported findings and suggests that the GAIRS Checklist can be used to assess behavioral, intellectual, academic, neuropsychological and psychosocial manifestations in patients with Rett Syndrome. The use of this Checklist can be extended to screen for neuropsychiatric involvement in RTT with complex needs. It can be integrated into routine medical appointments of individuals and conducted by all the therapists involved in the assessment and intervention with RTT patients. If the aim of the intervention is more related to motor abilities of the girls with Rett syndrome the GAIRS can be integrated with motor scales [19, 20].

Furthermore, the checklist can be easily re-administered during follow-up to detect behavioral and psychological changes over time and the efficacy of therapeutic intervention.

These results have interesting implications for future rehabilitation for deeply impaired clinical conditions as in the case of RTT [34,35,36,37]. First of all, this study may indicate a way to possibly modify RTT patients’ cognitive, motor and communicational structure, and improve their quality of life, as well as the quality of life in the people close to them.

GAIRS indeed is a descriptive assessment that involves completing direct observations in different environments and recording data as behaviors occur in order to determine the maintaining function of a behavior. It provides a structure for assimilation and integration of information leading to mastery of effective clinical reasoning in occupational therapy assessment and intervention. The model adheres to the World Health Organization in the International Classification of Functioning, Disability and Health (ICF) [38], in which both individual and environmental factors that enable or constrain participation in the community are considered in relation to health. The theoretical Model used here is the Applied Behavior Analysis (ABA). ABA is the science in which tactics derived from the principles of behavior are applied systematically to improve socially significant behaviors and experimentation is used to identify the variables responsible for behavior change [39]. ABA methods serve to identify the cause of a behavior and seek ways to improve behavior based on the identified function.

Despite the satisfactory psychometric characteristics, extension studies are warranted, also involving training in order to fully characterize the long-term evolution of GAIRS in Rett syndrome. Lastly, investigating the role intensive and low-frequency trainings on modifying GAIRS areas could provide further evidence about the ability of GAIRS checklist to discriminate between different clinical samples.

Conclusion

The GAIRS checklist was developed to provide healthcare professionals with a tool to easily screen neuro-psychiatric involvement in patients with RTT. The checklist explores the frequency of a wide range of neuropsychiatric manifestations and multiple dimensions of involvement on different levels: behavioral, psychiatric, intellectual, academic, neuropsychological and psychosocial. As these aspects can be impaired in RTT patients, we hypothesized that the checklist could be useful for screening neuropsychiatric needs in this population and for suggesting rehabilitation interventions.