Gait analysis patterns and rehabilitative interventions to improve gait in persons with hereditary spastic paraplegia: a systematic review and meta-analysis.

Background: Hereditary spastic paraplegias (HSPs) are a group of inheritance diseases resulting in gait abnormalities, which may be detected using instrumented gait analysis. The aim of this systematic review was 2-fold: to identify specific gait analysis patterns and interventions improving gait in HSP subjects. Methods: A systematic review was conducted in PubMed, Cochrane Library, REHABDATA, and PEDro databases, in accordance with reporting guidelines of PRISMA statement and Cochrane's recommendation. The review protocol was recorded on the PROSPERO register. Patients with pure and complicated HSP of any age were included. All types of studies were included. Risk of bias, quality assessment, and meta-analysis were performed. Results: Forty-two studies were included: 19 were related to gait analysis patterns, and 24 were intervention studies. The latter ones were limited to adults. HSP gait patterns were similar to cerebral palsy in younger subjects and stroke in adults. Knee hyperextension, reduced range of motion at knee, ankle, and hip, reduced foot lift, and increased rapid trunk and arm movements were reported. Botulinum injections reduced spasticity but uncovered weakness and improved gait velocity at follow-up. Weak evidence supported intrathecal baclofen, active intensive physical therapy (i.e., robot-assisted gait training, functional exercises, and hydrotherapy), and functional electrical stimulation. Some improvements but adverse events were reported after transcranial magnetic stimulation, transcutaneous spinal direct current stimulation, and spinal cord stimulation implant. Conclusion: Knee hyperextension, non-sagittal pelvic movements, and reduced ROM at the knee, ankle, and hip represent the most peculiar patterns in HSP, compared to diplegic cerebral palsy and stroke. Botulinum improved comfortable gait velocity after 2 months. Nonetheless, interventions reducing spasticity might result in ineffective functional outcomes unveiling weakness. Intensive active physical therapy and FES might improve gait velocity in the very short term.

Effect of Ankle-Foot Orthoses in Pediatric Patients with Hereditary Motor-Sensory Neuropathy: A Case Series Study.

(1) Aims: to evaluate the effect on gait performance and standing stability of ankle-foot orthoses (AFO) in pediatric patients with hereditary motor-sensory neuropathy (HMSN). (2) Methods: a retrospective case-series study including three adolescents (S1, S2, S3, mean age 14 years) with HMSN. The subjects were evaluated barefoot, with carbon AFO (Botter) and with solid AFO (SAFO) by means of: gait analysis, stabilometry and gait functional tests (10 Meter Walk Test, 2 Minute Walk Test). Finally, the CSD-OPUS questionnaire was administered to the assess satisfaction and impact of the orthoses on life quality. (3) Results: orthoses improved gait and stability performance. Botter allowed greater ankle movement than SAFO and provided greater push-off power. This, combined with the carbon elastic energy return, might explain better performances in the 2MWT, with a larger distance traveled compared to SAFO for both S1 (110 m vs. 72 m) and S2 (170 m vs. 155 m) and, compared to barefoot walking, also for S3 (211 m vs. 160 m), for which SAFO analysis was not available. Both orthoses improved performance at the stabilometric analysis. The CSD-OPUS questionnaire showed a significantly higher level of satisfaction with Botter for the subjects (S1, S2) who completed the comparison. (4) Conclusions: Both orthoses improved gait and standing, though Botter proved to be better tolerated and more effective in improving gait endurance.

Evidence-based management and motor rehabilitation of cerebral palsy children and adolescents: a systematic review.

Background: Evidence regarding the management of several aspects of cerebral palsy improved in recent years. Still, discrepancies are reported in clinical practice. Italian professionals and stakeholders expressed the need of setting up updated, evidenced-based, shared statements, to address clinical practice in cerebral palsy rehabilitation. The objective of the present study was to provide an updated overview of the state of knowledge, regarding the management and motor rehabilitation of children and young people with cerebral palsy, as the framework to develop evidence-based recommendations on this topic. Methods: Guidelines and systematic reviews were searched, relative to evidence-based management and motor treatment, aimed at improving gross motor and manual function and activities, in subjects with cerebral palsy, aged 2-18 years. A systematic search according to the Patients Intervention Control Outcome framework was executed on multiple sites. Independent evaluators provided selection and quality assessment of the studies and extraction of data. Results: Four guidelines, 43 systematic reviews, and three primary studies were included. Agreement among guidelines was reported relative to the general requirements of management and motor treatment. Considering the subject's multidimensional profile, age and developmentally appropriate activities were recommended to set individual goals and interventions. Only a few approaches were supported by high-level evidence (i.e., bimanual therapy and constraint-induced movement therapy to enhance manual performance). Several task-specific active approaches, to improve gross motor function and gait, were reported (mobility and gait training, cycling, backward gait, and treadmill), based on low-level evidence. Increasing daily physical activity and countering sedentary behavior were advised. Based on the available evidence, non-invasive brain stimulation, virtual reality, action-observation therapy, hydrotherapy, and hippotherapy might be complementary to task or goal-oriented physical therapy programs. Conclusion: A multiple-disciplinary family-centered evidence-based management is recommended. All motor rehabilitation approaches to minors affected by cerebral palsy must share the following fundamental characteristics: engaging active involvement of the subject, individualized, age and developmentally appropriate, goal-directed, skill-based, and preferably intensive and time-limited, but suitable for the needs and preferences of the child or young person and their family, and feasible considering the implications for themselves and possible contextual limitations.

Preserving Ambulation in a Gene Therapy-Treated Girl Affected by Metachromatic Leukodystrophy: A Case Report.

(1) Background: Atidarsagene autotemcel is a hematopoietic stem and progenitor cell gene therapy (HSPC-GT) approved to treat early-onset metachromatic leukodystrophy (MLD). The purpose of this case report is to describe the long-term management of residual gait impairment of a child with late infantile MLD treated with HSPC-GT. (2) Methods: Assessment included Gross Motor Function Measure-88, nerve conduction study, body mass index (BMI), Modified Tardieu Scale, passive range of motion, modified Medical Research Council scale, and gait analysis. Interventions included orthoses, a walker, orthopedic surgery, physiotherapy, and botulinum. (3) Results: Orthoses and a walker were fundamental to maintaining ambulation. Orthopedic surgery positively influenced gait by reducing equinovarus. Nonetheless, unilateral recurrence of varo-supination was observed, attributable to spasticity and muscle imbalance. Botulinum improved foot alignment but induced transient overall weakness. A significant increase in BMI occurred. Finally, a shift to bilateral valgopronation was observed, more easily managed with orthoses. (4) Conclusions: HSPC-GT preserved survival and locomotor abilities. Rehabilitation was then considered fundamental as a complementary treatment. Muscle imbalance and increased BMI contributed to gait deterioration in the growing phase. Caution is recommended when considering botulinum in similar subjects, as the risk of inducing overall weakness can outweigh the benefits of spasticity reduction.

Identification of bi-allelic LFNG variants in three patients and further clinical and molecular refinement of spondylocostal dysostosis 3.

Spondylocostal dysostosis (SCD), a condition characterized by multiple segmentation defects of the vertebrae and rib malformations, is caused by bi-allelic variants in one of the genes involved in the Notch signaling pathway that tunes the "segmentation clock" of somitogenesis: DLL3, HES7, LFNG, MESP2, RIPPLY2, and TBX6. To date, seven individuals with LFNG variants have been reported in the literature. In this study we describe two newborns and one fetus with SCD, who were found by trio-based exome sequencing (trio-ES) to carry homozygous (c.822-5C>T) or compound heterozygous (c.[863dup];[1063G>A]) and (c.[521G>T];[890T>G]) variants in LFNG. Notably, the c.822-5C>T change, affecting the polypyrimidine tract of intron 5, is the first non-coding variant reported in LFNG. This study further refines the clinical and molecular features of spondylocostal dysostosis 3 and adds to the numerous investigations supporting the usefulness of trio-ES approach in prenatal and neonatal settings.

Prevalence and determinants of hip pain in non-ambulatory cerebral palsy children: a retrospective cohort study.

BACKGROUND: Hip pain is common in cerebral palsy children, particularly at Gross-Motor Function Classification System level IV-V. It is associated to hip displacement and relates to the migration percentage. Recent literature suggested early reconstructive bone surgery, as the best approach to prevent hip luxation, then hip pain. Still, high rates of hip pain are reported. AIM: To investigate prevalence and determinants of hip pain in an Italian cerebral palsy sample. DESIGN: Single-center retrospective cohort study. SETTING: Inpatient and outpatient. POPULATION: Patients with spastic or dyskinetic cerebral palsy, Gross-Motor Function Classification System level IV or V, age 0-18. METHODS: A chart review was implemented to report hip pain, as a dichotomous variable (pain/no pain), age, sex, cerebral palsy subtype, Gross-Motor Function level, lumbar scoliosis, migration percentage, previous orthopedic surgery, or botulinum injections, oral or intrathecal baclofen, drug-resistant epilepsy, assistive devices for standing or walking. Descriptive statistics and a multivariate logistic stepwise regression were performed. RESULTS: A total of 504 subjects were included: 302 level V, 209 females, 432 spastics. The mean length of follow-up was 6 years. The overall prevalence of hip pain was 8.9% (6.3% were at level V) and of hip dislocation was 19% (15.9% were at level V). Just 39% of dislocated hips were painful. Children at spastic subtype and level V were predominantly affected. Botulinum and soft tissue surgery related to lower rates of hip pain, without statistical significance. Age (OR 1.19, 95%CI 1.14-1.25, P value 0.000), sex (OR 1.72, 95%CI 1.18-2.52, P value 0.005), migration percentage (OR 1.02, 95%CI 1.02-1.03, P value 0.000) and lumbar scoliosis (OR 1.32, 95%CI 0.86-2.01, P value 0.200) resulted significant independent determinants of hip pain. CONCLUSIONS: Hip pain relates with the migration percentage, but not all dislocated hips become painful. Hip pain may be transient and requires a targeted and individualized approach. Children at spastic subtype and level V were predominantly affected. Age and sex are confirmed as determinants. Specific validated measures are to be implemented to assess hip pain. CLINICAL REHABILITATION IMPACT: Considering severe non-ambulatory cerebral palsy patients, pain and quality of life should be considered as outcomes, in the management of hip luxation.

Gait Alterations in Two Young Siblings with Progressive Pseudorheumatoid Dysplasia.

Progressive pseudorheumatoid dysplasia (PPRD) is an autosomal recessive inherited skeletal dysplasia characterized by progressive non-inflammatory arthropathy affecting primarily the articular cartilage. Currently, little is known about the functional musculoskeletal aspects of these patients. In particular, an abnormal gait pattern has been described, without a clear hypothesis of the underlying causes in terms of muscular activity. This study presents the case of two siblings, 4 and 9 years old, a boy and a girl, respectively, suffering from PPRD at different stages of the disease. In addition to the clinical assessment, an instrumental gait analysis was performed. Swelling of the interphalangeal finger joints and fatigue were present in both cases. Gait abnormalities consisted of a relevant reduction in the ankle plantarflexion in the terminal phase of the gait cycle, associated with reduced gastrocnemius EMG activity and increased activity of the tibialis anterior, resulting in overloading at the initial peak of ground reaction forces. Gait anomalies observed were similar in both siblings with PPRD, although at different ages, and confirm walking patterns previously described in the literature. The calf muscle strength deficit and reduced activity during the stance phase of gait present in these two siblings indicate the typical absence of the propulsive phase. A stomping gait pattern, with the foot striking the ground hard on each step, was originally described. Further neurophysiological investigations are required to determine the origin of muscle weakness.

Hip subluxation in Italian cerebral palsy children and its determinants: a retrospective cohort study.

The study's aim was two-fold: to describe the trend of hip subluxation in the largest sample of Italian nonambulatory cerebral palsy (CP) children ever published; to investigate its determinants. This single-centre retrospective cohort study included patients with spastic or dyskinetic CP, Gross Motor Function Classification System (GMFCS) level IV or V, age 0-18 years, having been referred to our unit before March 2020. The hip subluxation was measured by means of the migration percentage (MP). Other data were gathered such as sex, CP subtype, GMFCS level, presence of drug-resistant epilepsy, age, use of walkers with weight relief or standing devices, previous botulinum injection or hip surgery, oral or intrathecal baclofen and hip pain. Multiple linear stepwise regression was performed and descriptive statistics are provided. Spastic CP had MP maximum increase in early ages, with GMFCS level V values persistently higher than level IV. The dyskinetic subtype showed a slower increase of the MP, with GMFCS level IV presenting similar or higher values, compared to level V. Age, CP severity and spastic subtype are the main determinants. The stepwise multiple regression analysis demonstrated that weight relief walking and standing assistive devices, combined with botulinum contributed to reduce the MP progression. Dyskinetic CP showed overall lower MP values and a more variable behaviour relative to age and GMFCS level, compared to the spastic subtype. Standing and walking assistive devices, with partial or total weight relief, combined with individually targeted botulinum injections, should be considered in the management of bilateral nonambulatory CP patients, to prevent hip subluxation or its recurrence after surgery.

A retrospective cohort study about hip luxation in non-ambulatory cerebral palsy patients: The point of no return.

Purpose: The migration percentage is a widely used criterion for surgery in displaced hips. Literature suggests that no hip can spontaneously improve if the migration percentage exceeds 45%, in a mixed population of cerebral palsy children. The aim of the present article was to identify the point of no return of the migration percentage in a selected sample of non-ambulatory cerebral palsy children, being the most exposed to hip luxation. Methods: This single-center retrospective cohort study included patients with spastic or dyskinetic cerebral palsy, Gross Motor Function Classification System level IV or V, age 0-18, having at least three pelvic radiographies, excluding radiographies relative to hips having previously undergone surgery. The following information was collected: sex, cerebral palsy subtype, Gross Motor Function Classification System level, presence of drug-resistant epilepsy, migration percentage, age at assessment, use of walking or standing assistive devices, previous botulinum injection, oral or intrathecal baclofen, and hip pain. Data were analyzed at the level of the individual hips. Descriptive statistics were presented. Receiver operating characteristic curve analysis was conducted to investigate which value of the migration percentage could be adopted as the "point of no return": that is, the cutoff value beyond which no migration percentage reduction, by more than 5%, could be expected. Results: The optimal cutoff value was identified as migration percentage ≥50%, with a sensitivity of 84.5% and a specificity of 100% (p-value <0.001). Conclusion: Based on the present study, migration percentage ≥50% is the "point of no return" for Gross Motor Function Classification System IV-V cerebral palsy patients, representing the cutoff value beyond which no spontaneous cerebral palsy reduction may be expected, unless addressing surgery. Level of evidence: level II-retrospective study.

Adducted Thumb and Peripheral Polyneuropathy: Diagnostic Supports in Suspecting White-Sutton Syndrome: Case Report and Review of the Literature.

One of the recently described syndromes emerging from the massive study of cohorts of undiagnosed patients with autism spectrum disorders (ASD) and syndromic intellectual disability (ID) is White-Sutton syndrome (WHSUS) (MIM #616364), caused by variants in the POGZ gene (MIM *614787), located on the long arm of chromosome 1 (1q21.3). So far, more than 50 individuals have been reported worldwide, although phenotypic features and natural history have not been exhaustively characterized yet. The phenotypic spectrum of the WHSUS is broad and includes moderate to severe ID, microcephaly, variable cerebral malformations, short stature, brachydactyly, visual abnormalities, sensorineural hearing loss, hypotonia, sleep difficulties, autistic features, self-injurious behaviour, feeding difficulties, gastroesophageal reflux, and other less frequent features. Here, we report the case of a girl with microcephaly, brain malformations, developmental delay (DD), peripheral polyneuropathy, and adducted thumb-a remarkable clinical feature in the first years of life-and heterozygous for a previously unreported, de novo splicing variant in POGZ. This report contributes to strengthen and expand the knowledge of the clinical spectrum of WHSUS, pointing out the importance of less frequent clinical signs as diagnostic handles in suspecting this condition.

How Did Italian Adolescents with Disability and Parents Deal with the COVID-19 Emergency?

The COVID-19 emergency has imposed distanced education and has interrupted most rehabilitation services. Adolescents with disabilities have been isolated, and the burden on their families has been exacerbated. A cross-sectional survey was administered to adolescents with disability and to parents of disabled children to describe their experience during lockdown and their concerns or expectations about rehabilitation. A sample of 53 adolescents and 239 parents completed the survey. Adolescents were ages 13-18 years old (45.3% female). Most parents were between 35 and 55 years old (84.9% female). While 53.6% of the parents reported no positive effects of the lockdown, 92.5% of the adolescents expressed favorable consequences. The increased time spent with family members was judged positively by 27.2% of parents and by 64.2% of adolescents. Concern for their child's disability was expressed by 47.3% of parents, while 73.6% of adolescents expressed concerns regarding the ban on meeting friends. In both groups, anxiety symptoms were correlated with the fear of contracting COVID-19 and with financial problems. Parents would have liked even more remote support from school and healthcare professionals, which was available for most participants. Thus, socioeconomic support, assistive technology and telerehabilitation strategies might help families with disabilities during a lockdown.

Clinical and Genetic Findings in a Series of Eight Families with Arthrogryposis.

The term "arthrogryposis" is used to indicate multiple congenital contractures affecting two or more areas of the body. Arthrogryposis is the consequence of an impairment of embryofetal neuromuscular function and development. The causes of arthrogryposis are multiple, and in newborns, it is difficult to predict the molecular defect as well as the clinical evolution just based on clinical findings. We studied a consecutive series of 13 participants who had amyoplasia, distal arthrogryposis (DA), or syndromic forms of arthrogryposis with normal intellectual development and other motor abilities. The underlying pathogenic variants were identified in 11 out of 13 participants. Correlating the genotype with the clinical features indicated that prenatal findings were specific for DA; this was helpful to identify familial cases, but features were non-specific for the involved gene. Perinatal clinical findings were similar among the participants, except for amyoplasia. Dilatation of the aortic root led to the diagnosis of Loeys-Dietz syndrome (LDS) in one case. The phenotype of DA type 5D (DA5D) and Escobar syndrome became more characteristic at later ages due to more pronounced pterygia. Follow-up indicated that DA type 1 (DA1)/DA type 2B (DA2B) spectrum and LDS had a more favorable course than the other forms. Hand clenching and talipes equinovarus/rocker bottom foot showed an improvement in all participants, and adducted thumb resolved in all forms except in amyoplasia. The combination of clinical evaluation with Next Generation Sequencing (NGS) analysis in the newborn may allow for an early diagnosis and, particularly in the DAs, suggests a favorable prognosis.

Severe Peripheral Joint Laxity is a Distinctive Clinical Feature of Spondylodysplastic-Ehlers-Danlos Syndrome (EDS)-B4GALT7 and Spondylodysplastic-EDS-B3GALT6.

Variations in genes encoding for the enzymes responsible for synthesizing the linker region of proteoglycans may result in recessive conditions known as "linkeropathies". The two phenotypes related to mutations in genes B4GALT7 and B3GALT6 (encoding for galactosyltransferase I and II respectively) are similar, characterized by short stature, hypotonia, joint hypermobility, skeletal features and a suggestive face with prominent forehead, thin soft tissue and prominent eyes. The most outstanding feature of these disorders is the combination of severe connective tissue involvement, often manifesting in newborns and infants, and skeletal dysplasia that becomes apparent during childhood. Here, we intend to more accurately define some of the clinical features of B4GALT7 and B3GALT6-related conditions and underline the extreme hypermobility of distal joints and the soft, doughy skin on the hands and feet as features that may be useful as the first clues for a correct diagnosis.

Eventos adversos relacionados à profilaxia anti-retroviral em acidentes ocupacionais / Adverse events relating to antiretroviral prophylaxis for occupational accidents

O objetivo do estudo foi descrever os eventos adversos clínicos e laboratoriais secundários ao uso dos agentes anti-retrovirais em indivíduos submetidos à quimioprofilaxia. Foram avaliados 37 funcionários de um hospital universitário submetidos à quimioprofilaxia com quatro esquemas de medicação anti-retroviral após exposição ocupacional a fluidos de pacientes contaminados com infecção pelo vírus da imunodeficiência humana. Trinta e dois (86,5 por cento) desenvolveram eventos adversos clínicos ou laboratoriais. A profilaxia teve que ser suspensa em dois profissionais (5,4 por cento) em virtude das reações ocorridas. Os eventos adversos relacionados à quimioprofilaxia para infecção por HIV em funcionários de saúde, vítimas de acidente ocupacional foram freqüentes. Porém, raramente foi necessário retirar a medicação anti-retroviral.

The objective of the study was to describe adverse events detected clinically or in the laboratory that were secondary to the use of antiretroviral agents among individuals undergoing antiretroviral prophylaxis. Evaluations were performed on 37 teaching hospital employees who underwent prophylaxis using four regimens of antiretroviral medication following occupational exposition to contaminated fluids from patients with human immunodeficiency virus infection. Thirty-two (86.5 percent) developed adverse events detected clinically or in the laboratory. The prophylaxis administered to two professionals (5.4 percent) had to be suspended because of the reactions that occurred. Adverse events relating to prophylaxis for HIV infection in health care workers who were victims of occupational accidents were frequent. However, it was rarely necessary to withdraw the antiretroviral medication.

[Adverse events relating to antiretroviral prophylaxis for occupational accidents]. / Eventos adversos relacionados à profilaxia anti-retroviral em acidentes ocupacionais.

The objective of the study was to describe adverse events detected clinically or in the laboratory that were secondary to the use of antiretroviral agents among individuals undergoing antiretroviral prophylaxis. Evaluations were performed on 37 teaching hospital employees who underwent prophylaxis using four regimens of antiretroviral medication following occupational exposition to contaminated fluids from patients with human immunodeficiency virus infection. Thirty-two (86.5%) developed adverse events detected clinically or in the laboratory. The prophylaxis administered to two professionals (5.4%) had to be suspended because of the reactions that occurred. Adverse events relating to prophylaxis for HIV infection in health care workers who were victims of occupational accidents were frequent. However, it was rarely necessary to withdraw the antiretroviral medication.