Euterpe music therapy method for children with cerebral palsy.

Introduction: The main purpose of our study was to evaluate whether involvement in a personalized music therapy program (Euterpe method), could improve the condition of children with cerebral palsy and their parents, compared to a control group. It investigated whether it could positively affect children's sleep quality, temperament and quality of life, quality of family life, and parental stress. Methods: A prospective single-center experimental study was conducted at "Bambino Gesù" Children's Hospital (Rome, Italy). All subjects involved attended an intensive rehabilitation program in the Neurorehabilitation Unit. In a group of patients (n = 25), a music therapy treatment was applied to evaluate the effect before and after the intervention. This group was also compared with a control group (n = 10) undergoing a standard protocol without music therapy. Results: In the experimental group, the analysis shows statistically significant effects in the Disorders of initiating and maintaining sleep (p = 0.050) and the Sleep wake transition disorders (p = 0.026) factors, and the total score (p = 0.031) of Sleep Disturbances Scale for Children; the Positive emotionality scale (p = 0.013) of Italian Questionnaires of Temperament (QUIT); the Emotional Functioning (p = 0.029), Social Functioning (p = 0.012), Worry (p = 0.032), Daily Activities (p = 0.032), Total Score (p = 0.039) and Parent HRQL Summary Score (p = 0.035) dimensions of Pediatric Quality of Life for family. While in the control group, only the Attention scale of QUIT (p = 0.003) reaches statistical significance. Discussion: Our study suggests that music therapy with the Euterpe Method has beneficial effects on fundamental aspects of the child's and his parents' lives, such as sleep, emotion control, and quality of family life.

Intranasal human-recombinant NGF administration improves outcome in children with post-traumatic unresponsive wakefulness syndrome.

BACKGROUND: Severe traumatic brain injury (TBI) is one of the most dramatic events in pediatric age and, despite advanced neuro-intensive care, the survival rate of these patients remains low. Children suffering from severe TBI show long-term sequelae, more pronounced in behavioral, neurological and neuropsychological functions leading to, in the most severe cases, an unresponsive wakefulness syndrome (UWS). Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. In experimental animal models, human- recombinant Nerve Growth Factor (hr-NGF) promotes neural recovery supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated processes. Only a few studies reported the efficacy of intranasal hr-NGF administration in children with post- traumatic UWS. METHODS: Children with the diagnosis of post-traumatic UWS were enrolled. These patients underwent a treatment with intranasal hr-NGF administration, at a total dose of 50 gamma/kg, three times a day for 7 consecutive days. The treatment schedule was performed for 4 cycles, at one month distance each. Neuroradiogical evaluation by Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG), and Power Spectral Density (PSD) was determined before the treatment and one month after the end. Neurological assessment was also deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. RESULTS: Three children with post-traumatic UWS were treated. hr-NGF administration improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary movements, facial mimicry, attention and verbal comprehension, ability to cry, cough reflex, oral motility, and feeding capacity, with a significant improvement of their neurological scores. No side effects were reported. CONCLUSION: These promising results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from severe TBI and in patients with better baseline neurological conditions, to explore more thoroughly the benefits of this new approach on neuronal function recovery after traumatic brain damage.

Combined treatment of nerve growth factor and transcranical direct current stimulations to improve outcome in children with vegetative state after out-of-hospital cardiac arrest.

BACKGROUND: Out-of-hospital cardiac arrest (OHCA) is one of the most dramatic events in pediatric age and, despite advanced neurointensive care, the survival rate remains low. Currently, no effective treatments can restore neuronal loss or produce significant improvement in these patients. Nerve Growth Factor (NGF) is a neurotrophin potentially able to counteract many of the deleterious effects triggered by OHCA. Transcranial Direct Current Stimulation (tDCS) has been reported to be neuroprotective in many neurological diseases, such as motor deficit and cognitive impairment. Children with the diagnosis of chronic vegetative state after OHCA were enrolled. These patients underwent a combined treatment of intranasal administration of human recombinant NGF (hr-NGF), at a total dose of 50 gamma/kg, and tDCS, in which current intensity was increased from zero to 2 mA from the first 5 s of stimulation and maintained constant for 20 min. The treatment schedule was performed twice, at one month distance each. Neuroradiogical evaluation with Positron Emission Tomography scan (PET), Single Photon Emission Computed Tomography (SPECT), Electroencephalography (EEG) and Power Spectral Density of the brain (PSD) was determined before the treatment and one month after the end. Neurological assessment was deepened by using modified Ashworth Scale, Gross Motor Function Measure, and Disability Rating Scale. RESULTS: Three children with a chronic vegetative state secondary to OHCA were treated. The combined treatment with hr-NGF and tDCS improved functional (PET and SPECT) and electrophysiological (EEG and PSD) assessment. Also clinical conditions improved, mainly for the reduction of spasticity and with the acquisition of voluntary finger movements, improved facial mimicry and reaction to painful stimuli. No side effects were reported. CONCLUSIONS: These promising preliminary results and the ease of administration of this treatment make it worthwhile to be investigated further, mainly in the early stages from OHCA and in patients with better baseline neurological conditions, in order to explore more thoroughly the benefits of this new approach on neuronal function recovery after OHCA.

Neurological impairment and malnutrition in children: The role of home enteral nutrition in real life.

Objective: Recent decades have brought an increased survival of children with Neurologic Impairment (NI) but malnutrition and digestive comorbidity remain important challenges to face. We designed the present study to assess the course of nutritional status following standardized Home Enteral Nutrition (HEN) program and to evaluate impact of changing mode of feeding, as a part of overall multidisciplinary management, on digestive co-morbidity as Gastro-Esophageal Reflux Disease (GERD), Oropharyngeal Dysphagia (OPD), constipation and airway aspiration. Methods: We performed a retrospective analysis on NI children entered into Institutional HEN program due to NI disorders between January 2011 and 2019. Demographic, anthropometric characteristics (BMI z-score and weight for age z-score) and symptoms (GERD, OPD constipation and airway aspiration) were collected at the enrolment and during the follow up. Results: We enrolled 402 patients (median age: 39 months); overall survival was 97%. Nutritional status was significantly improved by HEN; in particular growth profile significantly changed within the first 2 years following HEN beginning; GERD and airways aspirations decreased after HEN beginning. Constipation and OPD remained unchanged over time. Conclusions: Malnutrition and digestive complaints are distinctive features of NI children. Nutritional status improve after 2 years from the beginning of standardized nutritional interventions. Overall multidisciplinary care, including standardized HEN protocols, seems to also impact on GERD and airway aspirations, which can decrease over time. It is possible that constipation and OPD, unchanged over time, are more dependent on underlying diseases than on overall treatments.

Home-based music therapy for children with developmental disorders during the COVID-19 pandemic.

INTRODUCTION: During the COVID-19 pandemic, children with neurodevelopmental disabilities could not attend their usual rehabilitation therapies, with a consequent reduced support of developmental process and risk of worsening of their clinical conditions. METHODS: We prospectively enrolled 14 children with developmental delay, who had already tried a personalised music therapy (Euterpe method). We included them in a 12-day programme of home-based music therapy. The children and their parents were investigated using the Sleep Disturbance Scale for Children and the Parent Stress Index-Short Form. RESULTS: Fourteen children started the intervention, while only 12 children completed all the planned home sessions and assessments. We observed a significant improvement in children's sleep quality and a reduction of parental distress. DISCUSSION: The significant improvements in parental distress and sleep quality must be considered important achievements for the quality of life of a child and their family. Home-based music therapy can provide a feasible approach to improving sleep and parent's stress for children with developmental disorders.

Fighting autoinflammation in FIRES: The role of interleukins and early immunomodulation.

Febrile infection-related epilepsy syndrome (FIRES) is a challenging condition with unfavorable outcome in most cases. Preliminary evidence suggests that some interleukins, in particular IL-1 Receptor Antagonist (IL-1RA), could be elevated due to a functional deficiency of anti-inflammatory pathways. Therefore, treatment strategies acting on innate immunity could represent a targeted treatment. We describe the case of an 11-year-old child with super-refractory status epilepticus (SE), lasting more than two months. After being treated aggressively with antiseizure medications, anesthetics and empiric treatment for autoimmune encephalitis without success, she responded to anakinra and ketogenic diet. Escalation of the therapy was supported by the finding of a very high serum level of IL-1RA. This immunomodulatory approach allowed to discharge the child from intensive care 48 days after the SE onset. After more than one year follow-up the patient has moderate intellectual disability but with good language skills; she is seizure free and without motor deficits. This case suggests that serum IL-1RA serum levels may help to support treatment escalation. Moreover, anakinra and ketogenic diet represent encouraging immunomodulatory strategies which deserve further studies and could potentially have a synergistic effect. Finally, structured neuropsychological testing is an important outcome measure that will help to define the effectiveness of different treatment strategies.

Glycopyrrolate for drooling in children with medical complexity under three years of age.

BACKGROUND: The aim of the study is to determine that Glycopirrolate is safe and effective in decreasing drooling in children with medical complexity under 3 years of age. Medical treatment is based on anticholinergic drugs as transdermal scopolamine, benzotropine and GLY. GLY (Glycopyrronium bromide) is a synthetic quaternary ammonium anticholinergic agent with poor blood-brain barrier penetration and consequently has limited central effects. Actually, the oral GLY formulation was approved by the United States Food and Drug Administration (FDA) to treat drooling in children aged 3-16 years. Five studies reported on GLY use for the treatment of drooling in children with cerebral palsy and other conditions with neurological impairment; four are prospective studies while one a retrospective review. METHODS: this is a case report of eighteen children (sex ratio 11/8, median age 17 months, range 2-36 months) under three years of age, followed by a multidisciplinary team at the Bambino Gesù Children Hospital. The median follow-up was of 31.5 months (range 1-69 months). Response to treatment was assessed according to the Drooling Impact Scale administered at time 0 and after 1 month. All patients have an important neurological impairment: nine patients have a cerebral palsy (Gross Motor Function Classification System class V) and nine a genetic/malformative syndrome. Twelve patients have a tracheostomy and two need mechanical ventilation. Gastrostomy is present in 16 out of 18 patients. All patients received Glycopirrolate. The median starting daily dose was 0.065 mg/kg/die (range 0.02-0.21 mg/kg/die) three times a day. The drooling impact scale was administered at time O and after 1 month. RESULTS: Four out 18 patients stopped treatment for adverse event, lack of efficacy or parental decision. The mean Drooling Impact Scale at time 0 was 89 (range 81-100) and after 1 month 61(range 43-78); the difference was statistically significant (P < 0.001). The overall response to treatment was 94%. CONCLUSIONS: This is the first study to determine the safety and effectiveness of Glycopyrrolate in decreasing drooling in a specific subset of patients. No major side effects were observed. Further comparative studies are needed to confirm our results.

Early visual and neuro-development in preterm infants with and without retinopathy.

BACKGROUND: Retinopathy of prematurity (ROP) is often associated with visual impairment and multiple developmental disabilities. AIMS: As most of the previous studies include infants with brain lesions, that can determine visual impairment per se, a cohort of low neurological risk preterm infants without ROP and with various degree of severity of ROP was assessed in order to establish visual and neurodevelopmental outcome. STUDY DESIGN: Preterm infants born at <31 weeks gestation, without major brain lesions, underwent visual function assessment at 1 year corrected age and neurodevelopmental assessment at 2 years corrected age. SUBJECTS: One hundred and five infants were included in the study: 42 infants did not develop ROP, 7 reached stage 1 in zone 2 ROP, 37 reached prethreshold (untreated) type 2 ROP. The remaining 19 infants were classified as type 1 ROP. OUTCOME MEASURES: Visual function (including fixing, tracking, visual acuity, visual field, attention at distance and nystagmus) were assessed at 12 months corrected age and Griffiths Scales at 2 years corrected age. RESULTS: The severity of ROP was strongly correlated (p < 0.001) with both visual function at 1 year and neurodevelopment at 2 years. Similarly, the presence of nystagmus was also strongly correlated with visual and neurodevelopmental sequelae. CONCLUSIONS: Infants with no or milder retinopathy showed normal visual function at 1 year and neurodevelopment at 2 years. Infants who underwent treatment more frequently showed abnormal results on several aspects of visual function. Presence of nystagmus appeared to increase the risk for abnormal visual function and neurodevelopmental outcome.

Intranasal nerve growth factor administration improves neurological outcome after GBS meningitis.

Nerve growth factor (NGF) is a neurotrophin that promotes neural recovery and plasticity after experimental brain injury, supporting neuronal growth, differentiation, and survival of brain cells. Only a few studies reported NGF administration in pediatric patients with impaired brain functions after traumatic injuries, ischemic or infectious diseases, such as meningitis. We described the beneficial therapeutic effects of human-recombinant nerve growth factor (hr-NGF) treatment in an infant with persistent unresponsive wakefulness syndrome (UWS), due to late-onset group B Streptococcus meningitis. The infant received five monthly cycles of intranasal hr-NGF (0.1 mg/kg, 3 times daily for 7 consecutive days) through a mucosal atomizer device (MAD). NGF administration improved functional [positron emission tomography/computed tomography (PET/CT), single-photon emission/computed tomography (SPECT/CT), and magnetic resonance imaging (MRI)] assessments, electrophysiological [Electroencephalogram (EEG)] studies, as well as main cognitive processes and clinical and neurological functions. After hr-NGF treatment, significant improvements in facial mimicry, attention, motor reactions, oral motility, and feeding capacity were observed. She also recovered some hypothalamic functions and her cough reflex was restored. No side effects were reported during and after the treatment. For the first time ever, hr-NGF has been successfully utilized in an infant with UWS and severe neurologic outcome due to a bacterial meningitis. Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal hr-NGF administration appears to be a promising and save rescuing strategy treatment in infants with severe neurological impairment after brain damage.

Intranasal Nerve Growth Factor administration improves cerebral functions in a child with severe traumatic brain injury: A case report.

BACKGROUND: Nerve growth factor (NGF) promotes neural recovery after experimental traumatic brain injury (TBI) supporting neuronal growth, differentiation and survival of brain cells and up-regulating the neurogenesis-associated protein Doublecortin (DCX). Only a few studies reported NGF administration in paediatric patients with severe TBI. METHODS: A four-year-old boy in a persistent unresponsive wakefulness syndrome (UWS) was treated with intranasal murine NGF administration 6 months after severe TBI. The patient received four cycles of intranasal NGF (0.1 mg/kg, twice a day for 10 consecutive days). RESULTS: NGF administration improved functional [Positron Emission Tomography/Computed Tomography (PET/CT); Single photon emission/Computed Tomography (SPECT/CT) and Magnetic Resonance Imaging (MRI)] assessment, electrophysiological [Electroencephalogram (EEG) and Visual Evoked Potential (VEP)] studies and clinical conditions. He showed improvements in voluntary movements, facial mimicry, phonation, attention and verbal comprehension, ability to cry, cough reflex, oral motility, feeding capacity, and bowel and urinary functions. After NGF administration, raised levels of both NGF and DCX were found in the cerebrospinal fluid of the patient. No side effects were reported. CONCLUSIONS: Although further studies are needed for better understanding the neuroprotective role of this neurotrophin, intranasal NGF administration appears to be a promising and safe rescuing strategy treatment in children with neurological impairment after TBI.

Totally implantable venous access devices in children with medical complexity: preliminary data from a tertiary care hospital.

INTRODUCTION: Children with special health-care needs are an emerging and consistent population. In a subset of children with medical complexity (CMC) a continuous access to the central vascular system is advisable to eliminate unnecessary pain and stress and to improve home management and palliative care. METHODS: The surgical registry of a tertiary hospital was checked in order to identify CMC who underwent totally implantable venous access device (VAD) placement. Medical records were reviewed. RESULTS: From October 2009 to August 2014, a totally implantable VAD was placed in 10 children. Seven out of 10 patients were affected by cerebral palsy while 3 presented a genetic syndrome. The median duration of the indwelling catheter was 31 months (range 5 to 77 months). Six catheters are still in place since the first placement. Infectious complications were observed in two patients, respectively, a Candida albicans and a Staphylococcus aureus colonization; in both cases the VAD was removed. In another two cases, removal was planned for reservoir dislodgment within the subcutaneous tissue. No other major complications were observed during the procedure and the follow-up period. Emergency admissions decreased from a median value of 0.4/month (range 0-1.5/month) to 0.2/month (range 0-0.6/month) after the VAD placement. CONCLUSIONS: A totally implanted VAD in CMC is safe and manageable. As expected, infection seems to be the major complication with no infection-related death. Malnutrition and musculoskeletal deformities, which are frequent comorbidities in CMC, should be considered to reduce the risk of dislodgment/migration.

Wernicke encephalopathy in pediatric neuro-oncology: presentation of 2 cases and review of literature.

Wernicke encephalopathy represents a well-known entity characterized by a set of cognitive and neurologic alterations. Wernicke encephalopathy is rare and under-recognized in childhood and may be fatal. Few cases have been documented in pediatric oncology. We report on 2 Wernicke encephalopathy cases that occurred in children having a brain tumor. The diagnosis of Wernicke encephalopathy was suggested by clinical manifestations associated with the typical radiologic findings and a laboratory evidence of thiamine deficiency. No large series have been published to support the evidence that pediatric malignancies represent a demonstrated factor of increased risk to develop a Wernicke encephalopathy. Moreover, the diagnosis may be even more difficult in brain tumors, considering the overlapping symptoms and the risk of encephalopathy related to both the disease and the treatment. Wernicke encephalopathy should be considered in all children with cancer presenting a neurologic deterioration, mainly in brain tumors. An early diagnosis is imperative for a prompt therapy that might prevent or minimize the irreversible brain damage related to this condition.

Cortical visual function in preterm infants in the first year.

OBJECTIVE: To assess visual function in low-risk preterm infants at 3, 5, and 12 months corrected age to determine whether the maturation of visual function in the first year is similar to that reported in term-born infants. STUDY DESIGN: Seventy-five low-risk infants (25.0-30.9 weeks gestation) underwent ophthalmological examinations and a battery of tests (fix and follow, visual fields, acuity, attention at distance, and fixation shift) designed to assess various aspects of visual function at 3, 5, and 12 months corrected age. RESULTS: The results were comparable with normative data from term-born infants in all tests but fixation shift, suggesting that maturation of most aspects of visual function is not significantly affected by preterm birth. In contrast, >25% of preterm infants failed the fixation shift test at 3 months, with a higher percentage of failing at 5 and 12 months. CONCLUSIONS: There is a specific profile of early visual behavior in low-risk preterm infants, with a high percentage of infants failing a test that specifically assesses visual attention and provides a measure of cortical processing.

Outpatient assessment of neurovisual functions in children with Cerebral Palsy.

This study examined the feasibility of the Atkinson Battery for Child Development for Examining Functional Vision (Atkinson, Anker, Rae, et al., 2002) to evaluate neurovisual functions of children with neurodevelopmental disorders in outpatient setting. A total of 90 patients underwent a comprehensive evaluation. Among these, a group of 33 children with Cerebral Palsy (CP), mean age 6 years, with different types of CP (26% diplegic, 37% hemiplegic and 37% tetraplegic) were selected to constitute the cohort of the study. Visual sensory measures as well as higher level visual functions were considered. Overall, 73% patients had impairments at the assessment protocol, the majority of which presenting difficulties on both visuoperceptual and visuospatial tasks (79%). Subgroups of participants presented similar profiles of impairments with spared basic visuocognitive abilities and limitations in visuoperceptual and visuospatial domains. The Atkinson's battery proved to be valuable for evaluation in outpatient setting and follow-up testing. Some limitations emerged. For the definition of personalized and detailed rehabilitation programs a breakdown of the different components of vision and subsequent in-depth evaluation are needed.

Daily salbutamol in young patients with SMA type II.

The aim of this open pilot study was to establish the profile of tolerability and clinical response of salbutamol (albuterol) in a cohort of young children affected by type II spinal muscular atrophy (SMA). Twenty-three children between 30 months and 6 years of age were treated with salbutamol (2 mg three times a day) for 1 year. All children were longitudinally assessed using the Hammersmith motor functional scale 6 months before treatment started (T0), at baseline (T1) and 6 and 12 months later. There was no significant change in function between T0 and T1 assessments, but the functional scores recorded after 6 and 12 months of treatment were significantly higher than those recorded at baseline (p=0.006). Our results suggest that salbutamol may be beneficial to SMA patients without producing any major side effect. Larger prospective randomized, double-blind, placebo controlled trials are needed to confirm these preliminary findings.