[COMPLEX REGIONAL PAIN SYNDROME AND FUNCTIONAL NEUROLOGICAL DISORDER IN CHILDREN AND ADOLESCENTS: UNITY IN DIVERSITY].

INTRODUCTION: Functional neurological disorder (FND) and complex regional pain syndrome (CRPS) are disorders that affect quality of life. CRPS diagnosis is based on Budapest criteria that include various signs/symptoms. Despite the similarity in the etiology/pathophysiology of FND and CRPS, the joint prevalence of these two conditions in youth has not yet been reported. Given that both phenomena are less familiar among pediatric patients, it is crucial to thoroughly characterize them and establish a clear differential diagnosis. This, in turn, holds significant implications for guiding therapeutic interventions. OBJECTIVES: We aimed to examine: 1) the clinical profile of children with FND; 2) the prevalence of CRPS among children with FND; and 3) differences in clinical characteristics and in Budapest's symptoms/signs between children with FND and those with a co-diagnosis of FND and CRPS. METHODS: Sixty-one children (mean age: 13.70+2.93 years; 75.4% females) diagnosed with FND were studied. Sample's demographic, clinical characteristics and the Budapest CRPS classification criteria were collected from medical files. RESULTS: Most children with FND reported sensory (67%) and motor (88%) symptoms. Forty-four percent had a co-diagnosis of FND and CRPS. Among these children, 100% reported sensory and motor/tropical, 74% vasomotor, and 65% sudomotor symptoms. The prevalence of Budapest symptoms, except for motor-function impairment, was significantly higher among children with a co-diagnosis compared to children with FND alone. CONCLUSIONS: The high frequency of symptoms and clinical signs in children with co-incidence of CRPS and FND may indicate a shared developmental mechanism and is important for the development of appropriate rehabilitation interventions.

Gross motor proficiency deficits among children and adolescents post posterior fossa brain tumor removal vs. traumatic brain injury in the chronic phase of recovery: a cross-sectional study.

Introduction: Acquired brain injury (ABI) is a prevalent diagnosis in pediatric rehabilitation. Gross motor skills are often affected by ABI and limit the ability to participate in various physical activities. However, as ABI injury location is diverse, children and adolescents (youth) with localized ABI, such as ABI in the posterior fossa (ABI-PF) may present unique and different motor disabilities than youth with ABI on account of traumatic brain injury (TBI). Aims: The aims of the study were: (1) to compare gross motor deficits in youth with TBI vs. ABI-PF; and (2) to compare two methods on scoring BOT2 to determine which is better for identifying motor deficits. Methods: Participated in this study youth with TBI (N = 50) and ABI-PF (N = 30). Participants were tested on Bruininks-Oseretsky Test of Motor Proficiency-2nd Edition (BOT2) Upper-Limb Coordination, Balance, Strength, Running Speed and Agility, and Bilateral-Coordination subtests. Motor performance deficits were established using two-standard deviations (2SD) and age-equivalent methods. Between-group differences were assessed via independent t-tests and receiver operating characteristic curves (ROC). Results: According to the 2SD method, motor deficits in the ABI-PF group ranged from 20% to 66.66%, whereas in the TBI group 8%-16%. According to the age-equivalent method, in the TBI and ABI-PF groups 40%-66.0% and 46.66%-76.66% of the youth presented motor deficits, respectively. Moreover, ROC analysis showed that motor performance deficits of both groups in all sub-scales except for Bilateral Coordination differed enough to result in medium area under the curve. Conclusions: Motor deficits post-pediatric ABI are prevalent. In comparison to the TBI group, deficits are greater in the ABI-PF group. Moreover, compared to the 2SD method, the extent of motor deficiency is greater in the age-equivalent method. Therefore, using the later might provide a more valid classification of deficits in gross motor proficiency for youth post-ABI.

Pediatric Functional Neurological Symptoms Disorder: Walking Ability and Perceived Exertion Post-Pediatric Rehabilitation.

BACKGROUND: Adolescents with functional neurological symptoms disorder (FNSD) commonly present walking abnormalities. Walking is influenced by 'objective' (e.g., fitness) and 'subjective' (e.g., fear) components. Rate of perceived exertion (RPE) reflects the interaction between these two components. This study compared the walking ability and RPE before and after rehabilitation of adolescents with FNSD to adolescents with moderate-to-severe traumatic brain injury (TBI). Factors predicting walking and RPE were also examined. METHODS: Adolescents with FNSD (n = 31) and adolescents with moderate-to-severe TBI (n = 28) aged 6 to 18 years participated in the study. Participants received a multidisciplinary rehabilitation program. Six-minute walk test (6MWT) and RPE were assessed before and after rehabilitation. RESULTS: At pre-test, the TBI group presented lower RPE than the FNSD group (3.38 ± 2.49 and 6.25 ± 2.71, respectively). In the FNSD group, pre-test 6MWT was a significant predictor of post-test 6MWT (adjusted R2 = 0.17; p = 0.01). In the TBI group, post-test 6MWT was significantly predicted by both the pre-test 6MWT and age (adjusted R2 = 0.16; p = 0.04). CONCLUSIONS: Prior to the intervention, adolescents with FNSD perceived walking as a more difficult activity than adolescents with TBI. Post-intervention, although the intervention was effective in terms of changes in 6MWT and RPE, the 'subjective' component still contributed to the elevated RPE of the FNSD group.

A Behavioral Characteristics Observational Measure of Youth with Somatic Symptom Disorder during Physical Rehabilitation.

BACKGROUND: Youth with somatic symptom disorder (SSD) present unique behavioral characteristics. AIMS: To develop and examine the psychometric properties of an observational measure of behavioral characteristics for youth with SSD (the Somatization Behavioral Characteristics Questionnaire, SBCQ). METHODS: N = 80 youth with SSD and 31 with non-SSD impairments participated in this study (age = 13.91 ± 2.72, 14 ± 3.21, respectively; females: n = 61, 14, respectively). Symptom intensity (Children's Somatization Inventory-24; CSI-24), functional disability (Six-Minute Walk Test, walking rate of perceived exertion), and the SBCQ were assessed. SBCQ reliability and validity were examined. RESULTS: SBCQ had acceptable reliability in both groups (Cronbach's α > 0.7). Exploratory factor analysis in the SSD group revealed a three-cluster solution. Significant associations were found between the SBCQ, CSI-24, and functional disability. Both groups differed in the prevalence of all SBCQ behaviors. The greatest differences were in the mismatch between etiology and clinical presentation, and in the exhibited lack of trust in the therapist and "la belle indifference". Receiver operating characteristic analysis showed that the SBCQ has moderate accuracy in discriminating between the two groups (area under the curve = 0.80). Sensitivity and specificity were 82.5% and 73.3%, respectively. CONCLUSIONS: The SBCQ is psychometrically sound. Findings may aid in developing sensitive assessment tools for SSD and continuing education for therapists.

Functional neurological symptom disorder: Preliminary findings of factors associated with walking ability post integrative pediatric rehabilitation.

PURPOSE: The current study's aims were to (1) examine long-distance walking ability (6-minute walking test [6MWT]) and walking hemodynamic responses (i.e., heart rate) among youth with functional neurological symptom disorder (FNSD) before and after an integrative pediatric rehabilitation (IPR) program; and (2) explore factors predicting improvement in walking ability. METHODS: Thirty-one youth with FNSD participating in an IPR program were recruited. The IPR program was activated biweekly in an ambulatory format. Study measures included the 6MWT, hemodynamic characteristics, rate of perceived exertion (RPE), pain-intensity perception, and Child's Somatization Inventory-24 (CSI-24). All measures were conducted upon admission to the IPR and discharge. RESULTS: Findings indicated a significant increase in 6MWT distance, as well as decreases in heart rate, RPE, and pain-intensity perception from admission to discharge. At admission, CSI-24 and pain intensity predicted 6MWT distance (adjusted R2 = 0.68). Pain intensity predicted discharge 6MWT distance (adjusted R2 = 0.18). Initial 6MWT predicted changes in 6MWT distance from admission to discharge (adjusted R2 = 0.33). CONCLUSION: Using an integrative rehabilitation approach increases walking distance and decreases pain-related symptoms in youth with FNSD, emphasizing the need for collaboration between physical therapists and pediatric psychologists. Moreover, changes in walking ability may increase participation and thus should be the focus of IPR.

Mitochondrial augmentation of hematopoietic stem cells in children with single large-scale mitochondrial DNA deletion syndromes.

Patients with single large-scale mitochondrial DNA (mtDNA) deletion syndromes (SLSMDs) usually present with multisystemic disease, either as Pearson syndrome in early childhood or as Kearns-Sayre syndrome later in life. No disease-modifying therapies exist for SLSMDs. We have developed a method to enrich hematopoietic cells with exogenous mitochondria, and we treated six patients with SLSMDs through a compassionate use program. Autologous CD34+ hematopoietic cells were augmented with maternally derived healthy mitochondria, a technology termed mitochondrial augmentation therapy (MAT). All patients had substantial multisystemic disease involvement at baseline, including neurologic, endocrine, or renal impairment. We first assessed safety, finding that the procedure was well tolerated and that all study-related severe adverse events were either leukapheresis-related or related to the baseline disorder. After MAT, heteroplasmy decreased in the peripheral blood in four of the six patients. An increase in mtDNA content of peripheral blood cells was measured in all six patients 6 to 12 months after MAT as compared baseline. We noted some clinical improvement in aerobic function, measured in patients 2 and 3 by sit-to-stand or 6-min walk testing, and an increase in the body weight of five of the six patients suffering from very low body weight before treatment. Quality-of-life measurements as per caregiver assessment and physical examination showed improvement in some parameters. Together, this work lays the ground for clinical trials of MAT for the treatment of patients with mtDNA disorders.

Transition to Multidisciplinary Pediatric Telerehabilitation during the COVID-19 Pandemic: Strategy Development and Implementation.

Telerehabilitation offers a unique solution for continuity of care in pediatric rehabilitation under physical distancing. The major aims of this study were to: (1) describe the development of telerehabilitation usage guidelines in a large hospital in Israel, and to (2) evaluate the implementation of telerehabilitation from the perspectives of healthcare practitioners and families. An expert focus group developed guidelines which were disseminated to multidisciplinary clinicians. Following sessions, clinicians filled The Clinician Evaluation of Telerehabilitation Service (CETS), a custom-built feedback questionnaire on telerehabilitation, and parents completed the client version of the Therapist Presence Inventory (TPI-C) and were asked to rate the effectiveness of sessions on an ordinal scale. Four goals of telerehabilitation sessions were defined: (1) maintenance of therapeutic alliance, (2) provision of parental coping strategies, (3) assistance in maintaining routine, and (4) preventing functional deterioration. Principal Components Analysis was used for the CETS questionnaire and the relationships of CETS and TPI-C with child's age and the type of session were evaluated using Spearman's correlations and the Kruskal-Wallis H test. In total, sixty-seven telerehabilitation sessions, with clients aged 11.31 ± 4.8 years, were documented by clinicians. Three components (child, session, parent) explained 71.3% of the variance in CETS. According to therapists, their ability to maintain the therapeutic alliance was generally higher than their ability to achieve other predefined goals (p < 0.01). With younger children, the ability to provide feedback to the child, grade treatment difficulty and provide coping strategies to the parents were diminished. Families perceived the therapist as being highly present in therapy regardless of treatment type. These results demonstrate a potential framework for the dissemination of telerehabilitation services in pediatric rehabilitation.

Correction: Barak, S. et al. "Long-Term Outcomes of Early Enzyme Replacement Therapy for Mucopolysaccharidosis IV: Clinical Case Studies of Two Siblings". Diagnostics 2020, 10, 108.

The authors wish to make the following correction to this paper [...].

Long-Term Outcomes of Early Enzyme Replacement Therapy for Mucopolysaccharidosis IV: Clinical Case Studies of Two Siblings.

Enzyme replacement therapy (ERT) is one of the available therapies for mucopolysaccharidosis (MPS). This study presents a follow-up of two siblings with MPS IVA (Morquio A disease) that received ERT. Both siblings received weekly intravenous infusions of elosulfase alfa for 4.5 years. One sibling (patient 1, P1; male) started therapy at 54 months of age, and the other sibling (patient 2, P2; female) started at 11 months of age. ERT was well-tolerated. In comparison to P1, P2's growth curves deviated less from the norm. The orthopedic deformities of P1 were more severe than those of P2 and required several surgical corrections. P1's sleep test at 48 months revealed obstructive sleep apnea, while by the age of 102 months, parameters were normal. P2 never had sleep apnea. Only P1 demonstrated ear, nose, and throat clinical illnesses. In comparison to P1, P2's physical function was better maintained. In conclusion, ERT was safe in both patients during a 4.5-year follow-up. Although the typical characteristics of this disease were similar in both patients, P1 had a complex clinical course in comparison to P2, which influenced function and quality of life. Therefore, in order to make the most of ERT, it may be more beneficial when initiated at a relatively young age.

Parent-child Communication-centered Rehabilitative Approach for Pediatric Functional Somatic Symptoms.

BACKGROUND: Functional somatic symptoms (FSS) are a type of somatization phenomenon. Integrative rehabilitation approaches are the preferred treatment for pediatric FSS. Parental roles in the treatment process have not been established. STUDY AIMS: to present 1) a parent-focused treatment (PFT) for pediatric FSS and 2) the approach's preliminary results. METHODS: The sample included 50 children with physical disabilities due to FSS. All children received PFT including physical and psychological therapy. A detailed description of the program's course and guiding principles is provided. OUTCOME MEASURES: FSS extinction and age-appropriate functioning. RESULTS: Post-program, 84% of participants did not exhibit FSS and 94% returned to age-appropriate functioning. At one-year follow-up, only 5% of participants experienced symptom recurrence. No associations were found between pre-admission symptoms and intervention duration. CONCLUSION: PFT is beneficial in treating pediatric FSS. Therefore, intensive parental involvement in rehabilitation may be cardinal.

Discrepancies between mothers and clinicians in assessing functional capabilities and performance of children with cerebral palsy.

The current study is a cross-sectional study that aimed to investigate the concordance between health care professionals (HCPs) and mothers in rating capabilities and performance of children with cerebral palsy (CP), and the impact of CP gross motor severity on concordance. Seventy-three children with mild-to-severe CP (mean age 8.8 ± 2.10 years) and their mothers participated in this study. Two modes of Pediatric Evaluation Disability Inventory (PEDI) administration were used: mothers' interview by a social worker and HCPs' actual evaluation. Differences between raters were assessed by paired t-tests and intra-class correlation coefficients (ICCs). Agreement was defined as mean absolute difference of less than or equal to six points. The results indicated that in spite of excellent overall ICCs in PEDI (ICC>0.8), disagreement between raters was observed in all PEDI sub-domains: 38%, 56%, 72% and 59% disagreement in Functional Skills-Mobility, Functional Skills-Self Care, Caregiver Assistance-Mobility (CA-MO) and Caregiver Assistance-Self Care (CA-SC), respectively. In CA-SC and CA-MO disagreement mainly consisted of mothers rating their children lower in performance than HCPs. CP severity effected the agreement mostly in children with moderate CP severity. The implications of these results are that raters perceive child's activity differently, hence revealing hidden disability perceptions, with significant consequences for intended interventions.

Reliability and validity of Hebrew Pediatric Evaluation of Disability Inventory (PEDI) in children with cerebral palsy -- health care professionals vs. mothers.

AIM: To evaluate the reliability and validity of the PEDI in Hebrew (PEDI-H) in children with cerebral palsy (CP) using health care professionals' (HCP) and mothers' evaluations. METHODS: The sample comprised 73 participants (40 males, 33 females) with CP. Two modes of PEDI-H administration were used: interview of the mothers by a social worker and HCP evaluation. PEDI-H reliability was examined by two modes: 1) internal consistency via Cronbach's alpha and 2) overall absolute agreement within subject reliability via intraclass correlation coefficient (ICC). Discriminative validity using collapsed strata of the Gross Motor Functional Classification System (GMFCS) (area under the curve=AUC) were examined for each of the PEDI-H sub-domains. RESULTS: Participants' mean age was 8 years 8 months (standard deviation (SD) 2 years 10 months). The reliability of mothers' PEDI-H was good-to-excellent (Cronbach's alpha=0.889-0.964, ICC=0.845-0.938). The HCPs' reliability was excellent (Cronbach's alpha and ICCs > 0.90). The PEDI-H was also reliable in children with mild, moderate, and severe CP (GMFCS=I+II, III and IV+V, respectively), in younger (6-7 years) and older children (8-12 years), and in children with various CP distribution. Mothers and HCPs had low accuracy in Social-Function domains (AUC=0.538-0.686) and moderate-to-high accuracy in Mobility and Self-Care domains (AUC=0.887-0.967). PEDI-H was able to distinguish between children with various CP severities. CONCLUSION: The PEDI-H has good psychometric properties when administered by mothers and HCPs and can be used in older children with CP.