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Background: Spinal amyotrophy is a rare, neurodegenerative disease, with progressive evolution, disabling until death in severe forms, but for which 3 disease-modifying drugs have recently been approved (in the last 8 years). In this context, it became necessary to find predictive factors for the evolution of patients and for the effectiveness of the treatment applied to personalize the therapy to obtain the best results according to the particularities of each patient. Objective: The objective of this retrospective study is to analyze the evolution of different clinical (motor functional scales) and paraclinical biomarkers (level of pNF-H neurofilaments in serum and cerebrospinal fluid and of serum creatinine) under treatment with nusinersen in various types of spinal muscular atrophy (SMA). Methods: We analyzed the biomarkers values for a group of 69 pediatric patients diagnosed with SMA in different stages of treatment over three years, depending on the type of SMA, the number of copies of the SMN2 gene, and the age at initiation of therapy. Results: We observed significant increases in the levels of pNF-H neurofilaments in both cerebrospinal fluid (CSF) and serum, with correlations to the age of symptom onset in patients and an inverse relationship to the number of copies of the SMN2 gene. These levels decreased during treatment with nusinersen, coinciding with increased serum creatinine values and improved motor functional assessment scores. The most pronounced effects were noted in patients with severe forms of the disease, such as SMA type 1, mainly when treatment was initiated at a younger age. Conclusion: The evolution of patients under disease-modifying treatments should be analyzed both for the evolution on specific motor functional scales, as well as against the biomarkers of neuronal degradation: pNF-H, present in CSF and serum, and serum creatinine, a marker of muscle activity. Administering the disease-modifying treatment promptly after diagnostic confirmation halts neural degradation and enhances the patient's motor function.

Background and aim: The early identification of the former premature neonates at risk of neurologic sequelae could lead to early intervention and a better prognosis. This pilot study aimed to investigate whether the General Movement patterns observed at term-equivalent age in former premature infants could serve as predictors for guiding early intervention and improving prognosis. Materials and methods: In a population of 44 premature neonates (mean gestational age 33.59 weeks (+2.43 weeks)) examined at term-equivalent age, 10 neonates with a cramped–synchronized General Movements motor pattern were identified. These neonates were included in an early intervention program consisting of physiotherapy executed both by the therapist and by the parents at home. They were again examined at a corrected age of 12 weeks. The presence or absence of fidgety movements and the MOS-R (motor optimality score revised) was noted. The examinations were performed by certified specialists. Results: Normal fidgety movements and a MOS-R of 20–24 were presented in 9/10 of the former premature infants, with normal foot to foot contact present in 7/10, and normal hand to hand contact present in 5/10. The atypical patterns noted were side to side movements of the head in 5/10, a non-centered head in 9/10, asymmetric tonic neck reflex in 9/10 and jerky movements in 10/10. One patient presented with no fidgety movements and a MOS-R score of 9. Conclusion: Early intervention in our group of patients allowed for an improvement in the neurologic status, demonstrated by the presence of fidgety movements. We suggest that early intervention should be indicated in all premature infants that present with a cramped–synchronized GM pattern during examination at term-equivalent age. However, due to the small sample size, the absence of statistical analysis and a control group, and the limited follow-up period, the conclusions must be approached with caution.

Neurofilaments are crucial in neuronal cytoskeleton formation, influencing axonal growth and impulse modulation. This study focuses on understanding the dynamics of the phosphorylated neurofilament heavy subunit (pNFH) in pediatric spinal muscular atrophy (SMA) patients un-dergoing Nusinersen treatment. The presence of five neurofilament types, particularly pNFH, is explored as a potential biomarker. SMA, an autosomal recessive disease impacting motor neu-rons, is characterized by disease severity linked to the number of SMN2 gene copies. Approved drugs, including Nusinersen, have demonstrated efficacy in enhancing motor activity. Methods: A retrospective analysis was conducted on 18 pediatric SMA patients treated with Nusinersen from October 2018 to July 2023. Cerebrospinal fluid (CSF) samples were utilized to assess pNFH levels. Motor scales were employed to evaluate performance, focusing on patients with varying SMN2 gene copies. Results: Following the initiation of Nusinersen treatment, a substantial de-crease in pNFH levels was observed in CSF samples. Motor scales indicated improved perfor-mance, particularly in patients with more SMN2 copies. However, the correlation between pNFH levels and motor improvement was not strongly evident, suggesting a limited role as a prognostic indicator within this timeframe. Conclusion: Nusinersen effectively reduced pNFH levels in pediatric SMA patients, showcasing promising outcomes in motor function. However, the predictive value of pNFH remains inconclusive, emphasizing the need for further research. Study limitations, including the rarity of SMA, the absence of a control group, and the disease's dynamic nature over time, should be considered when interpreting these findings

Background: Cerebral palsy is a non-progressive neurodevelopmental condition that re-sults in varied degrees of disability, with upper limb functioning affected in over 80% of cases. The objective of this study was to investigate the impact of passive movement train-ing of the hand (PMT) with robot-assisted therapy (RAT) compared to PMT with function-al electrical stimulation (FES). Methods: Fifty-eight patients diagnosed with CP, aged be-tween 7 and 14 years, participated in a two-week rehabilitation program involving physi-cal therapy (PT) combined with either RAT or FES. Post-rehabilitation, we assessed the evolution of cylinder grip, finger extension, pinch grips, lateral grip, and three-point grip in each therapy group to determine the more effective passive movement training. Results: Both the RAT group (p < 0.001) and the FES group (p < 0.01) demonstrated a statistically significant improvement in all parameters. Patients who received PT and FES exhibited more significant improvement in each movement, except for the pinch index grip, where the RAT group showed superior results. Conclusions: Our findings indicate the positive effects of both PMTs on hand function rehabilitation. We recommend incorporating both therapies into rehabilitation programs for enhanced outcomes.

Posture, hyper-kyphosis or “the postural round back”, and balance are topics that have been extensively studied, although with some conflicting findings. Body position is representative of physical and mental health. Bad posture can lead to spinal complications (affects the muscular system, deforms the skeletal bone, and causes abnormal development) and the same can be said the other way around. As the standard of living increases, there is an increase in consumerism for technological devices, especially among teenagers. Identified as a public health problem, postural changes among children and adolescents have a high prevalence, emphasizing the need for prevention, diagnosis, and early initiation of treatment, especially from the growth and development phase of the body, because during this period teenagers are most vulnerable to live changes. Taking these elements into consideration, we conducted an extensive literature review of the subject, considering adolescence a key element for early diagnosticating and the institution of a complex rehabilitation program, with full functional restoration. Efforts to reduce the prevalence of bad posture will improve not only body posture but will also reduce the prevalence and the severity of spine deformities.

Joubert syndrome is a genetic disease with an autosomal-recessive or X-linked inheritance pattern caused by pathogenic variants in at least 35 genes, all encoding structures of the primary cilium involved in signaling pathways that coordinate the normal development of the kidneys, retina, brain, liver and skeletal system. The symptoms can consist in cystic renal disease and renal dystrophy, oculomotor apraxia, global developmental delay, hypotonia evolving into ataxia, skeletal and endocrine abnormalities, abnormal breathing patterns and congenital hepatic fibrosis, with the neurologic and ophthalmologic manifestations appearing early in life. The diagnostic hallmark is “the molar tooth sign”, a malformation of the brainstem and cerebellum easily identifiable using brain imaging techniques. As Joubert syndrome is a highly heterogeneous disease with a large type of phenotypes, it is oftentimes underdiagnosed. This article presents a case of Joubert syndrome type 17, a rare syndrome with many features overlapping orofaciodigital syndrome type VI. Adding to the rarity of this disease, our patient is homozygous and heterozygous for two pathogenic variants in C5orf42, with one located upstream of the other, thus manifesting the phenotype of a compound heterozygous in this gene. We believe that the presentation of this rare syndrome is useful to the pediatric practice by facilitating a fast diagnosis of these patients, which helps provide genetic counselling to the patients and their families.

Aim and Objectives: The objective of our retrospective study was to investigate the changes in pNFH levels in cerebrospinal fluid, which is a reliable marker of neuronal damage, after the loading dose of nusinersen in different types of spinal muscular atrophy. Materials and Methods: We analyzed the spinal muscular atrophy types, the number of copies of the SMN2 gene, and the progression of the motor status using specific motor function scales in a group of 38 patients with spinal muscular atrophy types 1, 2, and 3. Results: We found a significant inverse correlation between pNFH levels and patient age, progress on functional motor scales, and nusinersen administration. Our results also revealed that the neurofilament levels in the cerebrospinal fluid were higher in patients with 2 SMN2 copies than those with more than 2 copies, although the association was not statistically significant due to the abnormal distribution of the values. Conclusions: We identified several predictors of favorable evolution under nusinersen treatment, including spinal muscular atrophy type 1, children aged ≤ 30 months, and the presence of only 2 copies of SMN2. Our study provides important insights into the use of pNFH as a biomarker to monitor disease progression and responses to treatment in patients with spinal muscular atrophy.

Spinal muscular atrophy is a neuromuscular degenerative disorder characterized by progressive apoptosis of motor neurons, with severe weakness and bulbar dysfunction. The aim of the study was to analyze the correlations between the moment of initiation of treatment (nusinersen) and clinical evolution, and also the change of electrophysiological parameters and motor scales, fol-lowed up for 2 years. This study was carried out between 2018 and 2022 on 60 SMA children (29 girls, 31 boys), (29 type 1 and 31 type 2; 29 with 2 copies of SMN2, 29 with 3 copies, and 2 with 4 copies), aged between 3 weeks and 196 months, divided into 2 groups according type of SMA. For both types of SMA, statistically significant negative correlations were found between the elapsed interval from the onset of the disease to the initiation of treatment and upper motor acquisitions (type 1: p < 0.0001, r = -0.713, type 2: p

Spinal muscular atrophy is a congenital neuromuscular disease characterized by the deterioration of the motor neurons located mainly in the anterior horns of the spinal cord, leading to progressive muscle weakness and atrophy. Globally, SMA is, after cystic fibrosis, the second cause of death due to a a genetic disease in the pediatric population. Over 95% of the total cases of SMA are represented by 5q SMA, caused by biallelic mutations in the SMN1 gene (5q13.2), the rest of the SMA types being called, generically, non-5q SMA. Currently, a few genetic targeted therapies are available for 5q SMA, while other innovative therapies are still in clinical trials. Early diagnosis and treatment of 5q SMA have an essential role in preventing the onset and evolution of symptoms and can save the life of the patient and prevent debilitating sequelae. This article aims to briefly describe the cause and symptomatology of 5q SMA as well as to make a short review of the genetic therapies available for this disease.

Cystic fibrosis, also named mucoviscidosis, is the most frequent hereditary pulmonary disease and is produced by mutations in the CFTR gene, encoding an anionic channel for chloride and bicarbonate involved in the regulation of salt and bicarbonate metabolisms. Currently, about half of the patients with cystic fibrosis can benefit personalized therapy consisting in modulators, drugs which restore or improve the functionality and stability of CFTR. Moreover, presently, other therapies, such as gene therapy using the CRISP/CAS-9, modified antisense oligonucleotides or the insertion of the wild-type gene using nanolipidic particles or viral vectors, are being developed. This article aims to take stock of the principal types of cystic fibrosis therapies which have been approved or are in clinical trials.

1q44 microdeletion syndrome (1q44 monosomy) is a newly described genetic syndrome characterized by the haploinsufficiency of a 6 Mb locus on the long arm of chromosome 1. The main features are global developmental delay, seizures, hypotonia and craniofacial dysmorphism. With a prevalence below one in a million cases, this syndrome is very rare and, hence, often passes undiagnosed. We present the case of a one year old girl admitted to our hospital with global developmental delay and several congenital abnormalities suggesting a plurimalformative syndrome. Microarray analysis detected a 967 kb deletion in the 1q44 region as well as a a 530 kb microduplication in the 14q31.1q31.2 region, the latter having unknown clinical significance as it contains no currently known OMIM genes. The patient’s phenotype was in accordance to 1q44 microdeletion syndrome. Furthermore, after studying the 1q44 microdeletion syndrome cases reported so far in the literature, we have noticed that our patient presented previously undescribed features of this syndrome, namely prenatal hydronephrosis, bifid hallux and grey matter heterotopy. Based on the cerebral, renal and skeletal involvement in 1q44 microdeletion syndrome, we suspect these might be additional, previously unreported features of 1q44 microdeletion syndrome.

Fibroza chistică, numită și mucoviscidoză, este cea mai frecventă boală pulmonară ereditară și este produsă de mutații în gena CFTR, ce codifică un canal anionic pentru clor și bicarbonat cu rol în reglarea metabolismului bicar-bonatului și sării.În momentul de față, aproximativ jumătate din totalul pacienților cu fibroză chistică pot beneficia de terapie perso-nalizată cu ajutorul modulatorilor, substanțe care restaurează sau îmbunătățesc funcționalitatea și stabilitatea CFTR. Mai mult, la ora actuală se află în stadiul de studiu clinic și alte tipuri de terapii, ca de exemplu terapia geni-că utilizând sistemul CRISP/CAS-9, oligonucleotide antisens modificate sau inserția genei sălbatice utilizând parti-cule nanolipidice sau vectori virali. Acest articol își propune să treacă în revistă principalele tipuri de terapii aproba-te sau aflate în stadiul de studiu clinic pentru tratamentul fibrozei chistice.

Introduction. Ehlers Danlos syndrome is a group of hereditary diseases of the connective tissue with a combined prevalence of 1 in 5,000 cases which have in common articular hyperlaxity and skin abnormalities. In some types, rapid diagnosis can mean saving the life of the patient. Case presentation. We will present the case of a two year old girl which was brought for genetic consult with the suspicion of Ehlers Danlos syndrome. The patient had joint and skin hyperextensibility, velvety skin with a tendency of bruising, congenital hip luxation with a failed surgical intervention, talus varus and severe motor development retardation. Genetic testing revealed the substitution c.1780C>T, p.(Arg594*) in the COL5A1 gene which leads to the apparition of a premature stop codon, the mutation being class 2 (potentially pathogenic). Conclusions. Up until now, this variant has been reported in the literature in only two patients, ours being the third. All three cases correspond to the classic type Ehlers Danlos syndrome.

In the new therapeutic era, disease-modifying treatment (nusinersen) has changed the natural evolution of spinal muscular atrophy (SMA), creating new phenotypes. The main purpose of the retrospective observational study was to explore changes in clinical evolution and electrophysiological data after 2 years of nusinersen treatment. We assessed distal compound motor action potential (CMAP) on the ulnar nerve and motor abilities in 34 SMA patients, aged between 1 and 16 years old, under nusinersen treatment, using specific motor scales for types 1, 2 and 3. The evaluations were performed at treatment initiation and 26 months later. There were registered increased values for CMAP amplitudes after 2 years of nusinersen, significantly correlated with motor function evolution in SMA type 1 patients (p < 0.005, r = 0.667). In total, 45% of non-sitters became sitters and 25% of sitters became walkers. For SMA types 1 and 2, the age at the treatment initialization is highly significant (p < 0.0001) and correlated with treatment yield. A strong negative correlation (r = −0.633) was observed for SMA type 1 and a very strong negative correlation (r = −0.813) for SMA type 2. In treated SMA cases, the distal amplitude of the CMAP and motor functional scales are important prognostic factors, and early diagnosis and treatment are essential for a better outcome.

Introduction: Spinal muscular atrophy (SMA) is a progressive neurological disease with autosomal recessive transmission that affects motor neurons, causing their loss and resulting in muscle waste and motor deficiency. Nusinersen, the first SMN2 pre-mRNA targeted therapy approved by the Food and Drug Administration and the European Medicines Agency, has demonstrated high efficacy in improving motor function, as well as respiratory and nutritional statuses. Materials and Methods: We observed 55 patients (children/adolescents) diagnosed with spinal muscular atrophy (SMA), who received nusinersen therapy. To investigate the benefits of physical therapy on rehabilitation outcomes, we compared the motor evolution of patients who received nusinersen and performed daily physical therapy (study group) to those of the control group, who received only nusinersen therapy. Results: Motor skill improvements were statistically significantly (p < 0.001) higher in the study group, being almost four times better (12.66%), effect size, in comparison to the control group (3.18%). Conclusions: Physical therapy has provided superior results for those who receive it on a regular basis. These results include the correction of posture, reduction in stiffness, expansion of the range of motion and strengthening of muscles, thus allowing patients to do more movements and boosting their ability to perform everyday tasks.

Aim: This research aims to determine whether the time of injury (congenital or acquired) affects the quality of life (QOL) in families having a child or adolescent with neurological impairment. Design: Comparative, cross-sectional study. Material and methods: To find out if there are differences in the quality of life domains between these two groups, 66 subjects (31 mothers of patients with congenital disorders and 35 mothers of patients with acquired disorders) completed the PedsQL-Family Impact Module (PedsQL-FIM), the World Health Organization Quality of Life Instrument—Short Form (WHOQOL-BRIEF), and the Cognitive Emotion Regulation Questionnaire (CERQ). Results: Analyzing the PedsQL-FIM dimensions, we found significant differences between groups in terms of emotional functioning, communication, and worry, which favor the congenital group. There are no statistically significant differences between social functioning, cognitive functioning, and daily activities groups. No significant differences between groups when evaluating the WHOQOL-BRIEF’s domains (physical health, psychological health, social relationships, environment) have been found. According to CERQ results, adaptive strategies had higher mean scores in the congenital than in the acquired group. The mean score for maladaptive strategies in the congenital group is higher than that in the acquired one, except for catastrophizing, which is higher for acquired. Conclusion: Our findings show that the mothers of patients with acquired neuropathology have a lower quality of life in the emotional functioning, communication, and worry domains.

This paper overviews the state-of-the-art in upper limb robot-supported approaches, focusing on advancements in the related mechatronic devices for the patients' rehabilitation and/or assistance. Dedicated to the technical, comprehensively methodological and global effectiveness and improvement in this inter-disciplinary field of research, it includes information beyond the therapy administrated in clinical settings-but with no diminished safety requirements. Our systematic review, based on PRISMA guidelines, searched articles published between January 2001 and November 2017 from the following databases: Cochrane, Medline/PubMed, PMC, Elsevier, PEDro, and ISI Web of Knowledge/Science. Then we have applied a new innovative PEDro-inspired technique to classify the relevant articles. The article focuses on the main indications, current technologies, categories of intervention and outcome assessment modalities. It includes also, in tabular form, the main characteristics of the most relevant mobile (wearable and/or portable) mechatronic/robotic orthoses/exoskeletons prototype devices used to assist-rehabilitate neuromotor impairments in the upper limb.