BACKGROUND: Cystinosis is a lysosomal storage disease resulting from impaired transport of cystine due to variants in CTNS gene. Cystine accumulation leads to renal, corneal, and endocrine involvements. Patients typicall...BACKGROUND: Cystinosis is a lysosomal storage disease resulting from impaired transport of cystine due to variants in CTNS gene. Cystine accumulation leads to renal, corneal, and endocrine involvements. Patients typically present with growth retardation, polyuria/polydipsia, rickets. However, neurological manifestations are rare and become more pronounced with increasing age. METHODS: Fifty-one patients with cystinosis were evaluated using cerebral magnetic resonance imaging, electroneuromyography, audiological and psychometric tests. RESULTS: The mean age of the patients was 164.8 ± 112.4 months. The common symptoms were failure to thrive (56.9 %), polyuria/polydipsia (45.1 %), and short stature (37.3 %). Renal, endocrine, ocular, and neurological involvement was present in 100 %, 78.4 %, 76.5 %, and 49 % of patients, respectively. Abnormal magnetic resonance imaging findings were observed in three patients. Psychometric tests were performed in 20 patients. Four patients had borderline intelligence, two had mild, four had moderate, and two had severe intellectual disability. Eight patients had delays in personal-social, fine/gross motor, and language development. Two of 29 patients who underwent audiological evaluation were found to have hearing loss. Three patients had neuropathy, one had myopathy. One patient had epilepsy. There was no significant difference in cystine levels between the patients with and without neurological involvement. DISCUSSION: Compared to literature, our study appears to be a case series in which mental affect was reported the most. This effect may be due to frequent hospitalization, lack of stimulation, sociocultural status of the family and cortical atrophy in patients with chronic renal disease. Hearing loss was first reported in our study, regardless of audiotoxic drug usage.
Lysosomal storage disorders are a group of multisystem monogenic conditions caused mostly by enzyme deficiencies which disrupt lysosomal functioning. Those which result in neuronal dysfunction are considered 'neuronopath...Lysosomal storage disorders are a group of multisystem monogenic conditions caused mostly by enzyme deficiencies which disrupt lysosomal functioning. Those which result in neuronal dysfunction are considered 'neuronopathic'. These neurodegenerative conditions, while individually rare, are collectively not uncommon, and are attractive targets for gene and cell-based therapies. In this review we describe the current landscape of such therapies in this group of disorders, where the more severe phenotypes manifest in children. We describe the conditions, the principles of cell therapy and gene therapy, and compare AAV and lentiviral approaches. This is a rapidly evolving area of medicine, and we highlight progress made, and the challenges that are ahead in bringing these therapies to all patients. Throughout, we offer real-world insight into delivering these therapies and suggest a way forward for the future; utilising combined therapies to bridge the obligate delays and increasing collaborative working practices in therapeutic development between clinicians, academics and industry.
Duchenne muscular dystrophy (DMD) is a progressive X-linked recessive neuromuscular disorder caused by pathogenic variants in the DMD gene manifesting in early childhood with progressive muscle weakness. First symptoms o...Duchenne muscular dystrophy (DMD) is a progressive X-linked recessive neuromuscular disorder caused by pathogenic variants in the DMD gene manifesting in early childhood with progressive muscle weakness. First symptoms of muscle weakness usually appear around age of three, however, other signs of the disease like muscle hypertrophy, poor motor skills and social, language and motor delay can be detected earlier. Significant delays in the diagnostic process for DMD have been reported in many countries, with the diagnosis generally being made around five years. A collaborative historical cohort study was conducted to identify the age at diagnosis of DMD in five neuromuscular centers in Brazil, covering cases diagnosed between January 2019 and March 2024. In addition to data from the centers, data on age at diagnosis were obtained from The Brazilian National Network for Rare Diseases (RARAS). The final analytic cohort included 173 DMD individuals. The mean age at which patients were diagnosed with probable DMD based on clinical suspicion was 5.7 (±2.7) years, with diagnostic confirmation by genetic testing/muscle biopsy at 6.9 (±4.0) years, with medians of 6.0 and 6.8 years, respectively. The mean age at which parents noticed symptoms was 3.4 (±1.9) years with a median of 3.0 years. The most frequently observed initial symptoms by parents included frequent falls (35.5 %), gait abnormalities (31.4 %), difficulties in stair climbing (17.2 %), developmental delay (13.6 %), and difficulties in rising from the floor (8.9 %). The presence of co-occurring neurocognitive conditions was associated with a delay of 1.12 years (p = 0.008) in the median age at suspected diagnosis and 1.0 years in the median age at diagnosis confirmation (p = 0,022). These results suggest that while there have been improvements in the age of diagnosis of DMD in Brazil in recent decades, diagnosis still occurs later than ideal and then what has been achieved in high-income countries.
Panagi M, Blaschek A, Selek A
… +24 more, Baumann M, Cleaveland R, Panzer A, Conrad C, Della Marina A, Egler K, Finsterwalder J, Geis T, Hartmann H, Häusler M, Hofstetter P, Karenfort M, Kluger G, Leiz S, Merkenschlager A, Nosadini M, Sartori S, Salandin M, Schimmel M, Kornek B, Wendel EM, Reindl M, Rostasy K, BIOMARKER Study Group
BACKGROUND: Acute disseminated encephalomyelitis (ADEM) without myelin oligodendrocyte glycoprotein (MOG) antibodies (abs) presents a diagnostic challenge. OBJECTIVE: To investigate whether the diagnosis of MOG-negative...BACKGROUND: Acute disseminated encephalomyelitis (ADEM) without myelin oligodendrocyte glycoprotein (MOG) antibodies (abs) presents a diagnostic challenge. OBJECTIVE: To investigate whether the diagnosis of MOG-negative (neg) ADEM was confirmed over time and to highlight the clinical and neuroradiological characteristics distinguishing monophasic MOG-neg ADEM from alternative diagnoses. MATERIAL AND METHODS: Children diagnosed with a first clinical episode of MOG-neg ADEM and a dataset including clinical presentation, MRI, CSF studies and at least 3-month follow-up were included. RESULTS: 47 children with MOG-neg ADEM were identified (m:f = 27:20 , median age 8.0 years. 38 (79.2 %) children maintained the initial diagnosis after a median follow-up of 34.2 months. In 9 (19.1 %) children an alternative diagnosis was assigned after a median follow-up of 4.2 months including multiple sclerosis (MS) n = 2; glioblastoma (GBM) n = 2; hemophagocytic lymphohistiocytosis (HLH) n = 2; CNS vasculitis n = 1; ADEM followed by optic neuritis (ADEMON) n = 2. Cerebral white matter lesions were identified in 84.2 % of MOG-neg ADEM children. Gadolinium enhancement was noted in 11.4 % of MOG-neg ADEM children. Of 38 MOG-neg ADEM children, 9 (23.7 %) had only one atypical MRI finding, whereas 23 (60.5 %) showed multiple atypical MRI features. All children with alternative diagnoses exhibited more than one atypical MRI feature. The outcome was favorable (mRS </ = 2) in 36/38 (94.7 %) children with MOG-neg ADEM CONCLUSION: A substantial number of children initially diagnosed with MOG-neg ADEM will have another diagnosis. Children with MOG-neg ADEM showed white matter lesions but also atypical MRI findings. Monophasic MOG-neg ADEM was associated with a favorable outcome.
OBJECTIVES: This study aims to investigate the incidence, risk factors, and long-term outcomes of acute symptomatic seizures and post-stroke epilepsy in a cohort of children and adolescents who suffered from arterial isc...OBJECTIVES: This study aims to investigate the incidence, risk factors, and long-term outcomes of acute symptomatic seizures and post-stroke epilepsy in a cohort of children and adolescents who suffered from arterial ischemic stroke (AIS-C). METHODS: Children and adolescents (aged 29 days to 16 years) with AIS-C were prospectively enrolled in the population-based Swiss Neuropediatric Stroke Registry (SNPRS) between 2000 and 2020. Demographic data, clinical presentation, and seizure characteristics were documented. Follow-up evaluations were performed at six- and 24-months post-stroke to assess the development of epilepsy. Risk factors for acute seizures and post-stroke epilepsy were analysed using univariate regression models. Of 315 patients with AIS, 201 children were male (63.5 %), with a median age of 6.1 years (IQR: 2.1-11.4). Acute seizures were observed in 75 (23.8 %) children, being the initial symptom in 44/75 (58.7 %). Status epilepticus occurred in 12/75 (16.0 %). Acute symptomatic seizures were associated with younger age (median 1.1 years [IQR 0.4-6.0] vs 7.2 years [IQR 3.8-12.2]; p < 0.001) and cortical involvement (OR 3.3; 95 % CI 1.8-6.0; p < 0.001). At the 6-month follow-up, 12 patients (4.5 %) had developed active epilepsy and 12 patients (5.4 %) at 24 months. The presence of acute symptomatic seizures did not increase the risk for epilepsy at 6 months (OR 1.5; 95 % CI 0.5 to 5.1; p = 0.47) but was associated with a higher risk at 24 months (OR 3.2; 95 % CI 1.0 to 10.7; p = 0.047). The most common stroke aetiologies, classified using the Childhood AIS Standardized Classification and Diagnostic Evaluation (CASCADE) criteria, were cardioembolic (32.0 % in patients with acute seizures vs 18.4 % in those without) and unilateral focal cerebral arteriopathy (22.7 % vs 26.4 %). Stroke aetiology remained undetermined in 20.0 % vs 31.8 %. Drug-resistant epilepsy was reported in seven children (2.2 %) with severe comorbid conditions, such as congenital heart disease and sepsis. Children with post-stroke epilepsy experienced significantly worse neurological outcomes, as measured by the Pediatric Stroke Outcome Measure (PSOM), compared to children without post-stroke epilepsy (median PSOM score 3.0 vs. 0.5, p < 0.001). CONCLUSIONS: Acute symptomatic seizures are a common complication of paediatric ischemic stroke and are strongly associated with younger age and cortical involvement. Although these seizures do not predict early epilepsy development at 6 months, they are a risk factor for post-stroke epilepsy at 24 months. Children with post-stroke epilepsy show poorer neurological outcomes and those with severe underlying conditions are at an increased risk of drug-resistant epilepsy. These findings highlight the need for careful monitoring and early intervention in children with high-risk profiles.
OBJECTIVE: To identify factors associated with the neurological outcome of HSVE in children. MATERIALS AND METHODS: In this retrospective multicentric observational study, clinical, paraclinical data at onset and neurolo...OBJECTIVE: To identify factors associated with the neurological outcome of HSVE in children. MATERIALS AND METHODS: In this retrospective multicentric observational study, clinical, paraclinical data at onset and neurological outcomes at last follow-up of children (≥28 days and <18 years old) with HSVE, were studied. Univariate and multivariate analyses were performed to identify factors associated with neurological outcome. RESULTS: 49 children (mean age of 4.9 ± 5.5 years) were included. At last follow-up of 5.9 ± 3,13 years, 2 children died (4 %) and 37 (76 %) children presented with poor neurological outcome with epilepsy (57 %), intellectual disability (51 %) and language disorders (47 %). Rehabilitation was necessary for 76 % and 59 % had abnormal academic performances. At onset, younger age and seizures were significantly associated to language disorders (p < 0.01), motor disabilities (p = 0.01), and intellectual disabilities (p = 0.01) in univariate analysis. Abnormal MRIs were more frequent in children with neurological sequalae (p = 0.01). Multivariate analyses identified that: (1) epilepsy occurred more frequently in females (p = 0.03), with insular lesions (p = 0.048); (2) language disorders were more common in children who had seizures at onset (p 0.02); (3) motor disorders were more frequent in younger children (p = 0.03) with thalamic lesions (p = 0.04). CONCLUSION: Our findings indicate that despite decrease in mortality rates, neurological disabilities in children with HSVE still persist at high levels. This underscores the need to enhance HSVE management strategies. Moreover, the identified risk factors associated with poor neurological outcomes can aid in identifying high-risk children, facilitating the implementation of alternative treatment approaches such as immunotherapy or intensive rehabilitation.
BACKGROUND: Spinal muscular atrophy (SMA) in children is a hereditary neuromuscular disorder characterized by motor neuron degeneration, which leads to progressive muscle weakness and impaired movement. Ultrasound imagin...BACKGROUND: Spinal muscular atrophy (SMA) in children is a hereditary neuromuscular disorder characterized by motor neuron degeneration, which leads to progressive muscle weakness and impaired movement. Ultrasound imaging, owing to its non-invasive, radiation-free, and cost-effective nature, provides an invaluable tool for visualizing muscle morphology. This technique offers a significant advantage in the clinical evaluation of SMA. The aim of this study was to quantitatively assess muscle abnormalities in children with SMA using both conventional ultrasound and shear wave elastography (SWE), and to explore the potential of these imaging modalities in the assessment of the disease. METHODS: A total of 20 patients with type II or III SMA, who had not received any prior disease-modifying treatment (DMT), were included in the SMA group. These patients were enrolled between May 2022 and January 2024. The control group comprised 20 healthy children matched for age and gender. Muscle thickness (MT) and shear wave velocity (SWV) of the biceps brachii (BB) and quadriceps femoris (QF) were measured using B-mode ultrasound and SWE. Ultrasound parameters were compared between children with SMA and healthy controls. Additionally, motor function in the SMA group was assessed using the Hammersmith Functional Motor Scale Expanded (HFMSE), and the correlation between ultrasound parameters and HFMSE scores was analyzed. RESULTS: The BB-MT, BB-SWV, QF-MT and QF-SWV in the SMA group, were significantly lower than those in the control group (p = 0.030, 0.000, 0.004, and 0.001, respectively). Correlation analysis revealed a significant positive correlation between QF-MT and QF-SWV in the SMA group and the HFMSE score (r = 0.802, p = 0.000; r = 0.56, p = 0.000, respectively). CONCLUSIONS: Ultrasound imaging is an effective modality for detecting and quantifying muscle atrophy and structural changes in children with SMA. Moreover, it demonstrates a significant correlation with motor function, providing valuable insights into the clinical assessment of SMA.
RATIONALE: There is limited data comparing quality of life (QOL) in young adolescents with epilepsy with young adolescents without epilepsy. This study aimed to compare self and caregiver rated child quality of life in y...RATIONALE: There is limited data comparing quality of life (QOL) in young adolescents with epilepsy with young adolescents without epilepsy. This study aimed to compare self and caregiver rated child quality of life in young adolescents with epilepsy and a matched control group without epilepsy, and to explore factors associated with quality of life in young adolescents with epilepsy. METHOD: Young adolescents with epilepsy (aged between 11 and 15 years) (n = 60; 25/35 boys/girls), a group of matched controls (n = 49 25/24; boys/girls), and their primary caregivers completed a measure of the child's quality of life (Pediatric Quality of Life Inventory; PedsQL). Comparisons between the epilepsy and control group were undertaken using chi-square analysis and independent t-tests. Linear regression was used to explore factors associated with quality of life in the adolescents with epilepsy. An alpha level of p < 0.05 was used. RESULTS: Adolescents with epilepsy had significantly lower scores on all QoL domains, summary scores and total score of the self-rated PedsQL (all p < 0.001 with exception of physical functioning (p = 0.003)). Adolescents with epilepsy also had significantly lower caregiver rated total QOL with lower scores on all of the PedsQL domains, summary scores, and on the total score (all p < 0.001). Increased adolescent mental health difficulties, increased adolescent motor coordination difficulties, and having had seizures in the week prior to the assessment were associated with reduced quality of life scores on both adolescents and caregiver rated quality of life in the adolescents with epilepsy. CONCLUSION: Young adolescents with epilepsy have lower QOL on both self- and caregiver report compared to peers without epilepsy. The association with mental health and motor coordination difficulties highlights the need for identification and management of these co-occurring conditions. It is important that resources for identification and management of these difficulties are available in epilepsy clinics to optimise QoL for these adolescents.
Quality of life in Duchenne muscular dystrophy has been reported to be negatively affected by the lack of qualifying education and the lack of opportunities for participation in leisure activities. Two thirds of patients...Quality of life in Duchenne muscular dystrophy has been reported to be negatively affected by the lack of qualifying education and the lack of opportunities for participation in leisure activities. Two thirds of patients with Duchenne muscular dystrophy have cognitive and/or psychiatric problems. Thus, we conducted a survey study on mobility, school problems, executive functions, social participation and quality of life in young patients in Switzerland. We contacted 60 male patients with Duchenne muscular dystrophy aged 8-18 years through the Swiss Registry for Neuromuscular Disorders. Mobility, school problems and social participation in leisure activities were assessed with a self-constructed questionnaire. Quality of life and executive function were assessed using KIDSCREEN-10 and BRIEF scores, respectively. Out of 60 dispatched surveys, 67 % were filled out and included. Approximately half of the participants went to a special needs school, and 83 % rated their overall quality of life as good. We did not find a correlation between mobility and quality of life, whereas more social participation was correlated with higher quality of life. Furthermore, patients with more difficulties in executive functions showed less participation and lower quality of life. These results underline the need for neuropsychological and adapted assistance in patients with Duchenne muscular dystrophy to facilitate education and social participation.
We studied a retrospective cohort of children with developmental and epileptic encephalopathy (DEE), a group of neurological conditions characterized by early onset epilepsy and severe developmental delay. Cases were rec...We studied a retrospective cohort of children with developmental and epileptic encephalopathy (DEE), a group of neurological conditions characterized by early onset epilepsy and severe developmental delay. Cases were recruited from three university hospitals based on clinical criteria, after a blinded cross-validation process, and most were subject to both array-CGH and exome-based gene panel analyses. 155 subjects were included. A genetic diagnosis was identified in 105 (68 %). A majority of patients (71 %) had onset of symptoms before the age of one year. In this age group a disease-causing variant was identified in 73 % of children, the highest proportion of cases reported so far. Genetic heterogeneity was high, involving 40 different genes. The most prevalent gene was SCN1A. Eight genes were identified in multiple patients and accounted for 50 % of all diagnoses. The remaining genes represented ultra-rare disorders. In many cases, molecular diagnosis leads to treatment adaptation and allows for genetic counseling. Those results highlight the growing importance of genetic investigations especially in children with symptoms onset before the age of 1. Finally, we evaluated the disease-causing variants in an intention-to-treat approach and found that almost half would theoretically be amenable to personalized therapy using antisense oligonucleotides (ASOs).
Newborn screening (NBS) is a successful program of secondary prevention for rare diseases, such as neuro-metabolic diseases, enabling early identification of affected individuals and pre-symptomatic treatment. Driven by...Newborn screening (NBS) is a successful program of secondary prevention for rare diseases, such as neuro-metabolic diseases, enabling early identification of affected individuals and pre-symptomatic treatment. Driven by innovations in high-throughput sequencing technologies, NBS panels have continued to grow and will probably be extended further in the future. However, implementing NBS for a disease is subject to various preconditions to maximize the benefit for the affected children, while avoiding harm to the screened healthy cohort, their families and the society. Ideally, data on clinical long-term benefit of NBS and early treatment is collected prior to NBS implementation through long-term observational studies and registries. In addition, NBS should be implemented as an iteratively evaluated public health program and the data collection should be accompanied by intra-operable long-term observational studies, ideally extended in international cooperations. In this review, the current expertise in NBS, the screening strategies and possible long-term clinical benefits are presented and discussed for several neuro-metabolic diseases, including propionic acidemia and isolated methylmalonic acidemias, homocystinurias, remethylation defects, acquired cobalamin (vitamin B) deficiency, urea cycle disorders, tetrahydrobiopterin (BH) and primary neurotransmitter disorders, as well as lysosomal storage disorders. Given these prerequisites, several of the neuro-metabolic diseases discussed here might be part of future NBS programs worldwide.
The development of the fetal central nervous system (CNS) is a complex process influenced by genetic, environmental, and physiological factors. The absence of identifiable genetic variants and low risk of recurrence in f...The development of the fetal central nervous system (CNS) is a complex process influenced by genetic, environmental, and physiological factors. The absence of identifiable genetic variants and low risk of recurrence in families with certain brain malformations has led to the hypothesis that disruptive events may play a critical role in the development of brain malformations. These events include disruption of blood flow, ischemia, hemorrhage, placental insufficiency, prenatal drug exposure (e.g cocaine), and infections (e.g CMV). Likely disruptive anomalies include polymicrogyria (PMG), cerebellar hypoplasia, septo-optic dysplasia (SOD), absent septum pellucidum, and Dandy-Walker malformation (DWM). The timing of these disruptions is expected to reflect the stages of fetal brain development. Understanding the mechanisms behind disruptive-developmental anomalies of the fetal CNS is crucial for improving prenatal screening, counseling strategies, and potential interventions.
OBJECTIVE: This study aimed to analyze the demographic, clinical, and therapeutic profiles of pediatric patients diagnosed with tremor at a tertiary neurology outpatient clinic and to identify the most frequently employe...OBJECTIVE: This study aimed to analyze the demographic, clinical, and therapeutic profiles of pediatric patients diagnosed with tremor at a tertiary neurology outpatient clinic and to identify the most frequently employed therapeutic modalities. METHODS: A retrospective analysis was conducted between November 1, 2022, and April 1, 2024. Patients were categorized into etiological groups, including essential tremor, metabolic causes (e.g., vitamin deficiencies and thyroid dysfunction), functional tremor, and other etiologies. Patients diagnosed with essential tremor were further divided based on whether they were prescribed anti-tremor medications, and the groups were compared regarding daily functional abilities. RESULTS: A total of 192 patients were included, of whom 81 (42.1 %) were male. The mean age was 170 months, and the mean tremor duration was 19 months. Essential tremor accounted for 125 cases (65.1 %), while 38 patients (19.7 %) had a metabolic etiology. First-line anti-tremor medication (propranolol) was administered to 58 out of 125 patients (46.4 %), and four patients required second-line therapy (primidone). Between the medicated and non-medicated groups no significant gender differences or difficulty in bringing food to the mouth accurately were observed. However, significant statistical differences were noted in difficulties with drinking water, using a spoon, and handwriting impairments. CONCLUSION: Childhood tremor is a common clinical condition with diverse etiologies, where treatable causes, especially vitamin deficiencies, play a significant role. Functional impairments, such as difficulty in drinking water, using a spoon, and writing, may serve as key predictors for initiating first-line anti-tremor therapy. Propranolol remains an effective therapeutic option for essential tremor in children.
BACKGROUND: New-onset super-refractory status epilepticus (NOSRSE) leads to functional deficits and residual epilepsy. This study aimed to describe pediatric NOSRSE cohort to gain clinical insights of their features. MET...BACKGROUND: New-onset super-refractory status epilepticus (NOSRSE) leads to functional deficits and residual epilepsy. This study aimed to describe pediatric NOSRSE cohort to gain clinical insights of their features. METHODS: A retrospective review of children with NOSRSE in 2013-2024 was conducted at two tertiary hospitals. Patient clinical data, including MRI, CSF profile, EEG, and treatments, were collected and reviewed. The primary outcome measure was the modified Rankin scale score (mRS) at 3-month post-seizure. RESULTS: Twenty-three patients with NOSRSE, with a median age of 7.9 years, were included. Twenty-one (91 %) had febrile infection-related epilepsy syndrome (FIRES). The initial cerebrospinal fluid (CSF) profile was normal in five (23 %), pleocytosis was present in nine (39 %), and CSF protein was elevated in 15 (68 %) patients. Initial Brain MRI was normal in 14 (61 %) patients. First- and second-line immunotherapy was delivered to 21 (91 %) and 15 (68 %) patients, respectively. The etiology was viral infection in two (9 %) patients, and presumed cryptogenic in the remaining. The primary outcome was poor (mRS ≥4) in 14 (61 %) patients and all had residual epilepsy. Elevated initial CSF protein levels were associated with poor outcomes. Mental status before treatment, time to immunotherapy, intubation of >2 weeks or tracheostomy, and the duration of anesthetics were also associated with the primary outcome. CONCLUSION: Most pediatric NOSRSE patients presented as cryptogenic FIRES, with poor long-term outcomes. None of the patients with NOSRSE tested positive for autoimmune antibodies. Many showed permanent MRI changes but did not correlate with outcome. The initial CSF profile may serve as an objective disease severity marker in NOSRSE.
INTRODUCTION: Pontocerebellar hypoplasia type 2A (PCH2A) is a rare neurogenetic disease characterized by severe cognitive and motor impairment. This study reports on brain morphometry and psychomotor development of affec...INTRODUCTION: Pontocerebellar hypoplasia type 2A (PCH2A) is a rare neurogenetic disease characterized by severe cognitive and motor impairment. This study reports on brain morphometry and psychomotor development of affected children. MATERIALS AND METHODS: We analyzed 78 cerebral MRI datasets of 57 patients with genetically confirmed PCH2A. Volumetric and in-plane measurements were conducted in cerebellum, neocortex and pons. Supratentorial width and width of the anterior horns of the lateral ventricles was used to calculate the Evans index. Caregivers of 65 patients (aged 7 months to 33 years) filled in a survey assessing motor and cognitive development. Developmental status was compared to MRI measurements. RESULTS: In children with PCH2A, cerebellar volume was markedly smaller than in healthy children at birth, with slower increase and stagnation at around 12 months. No cerebellar growth was observed in the cranio-caudal axis. Longitudinal data did not reveal a decrease in cerebellar volume or in-plane measurements. Supratentorial measurements showed progressive microcephaly and a continuous increase of the Evans index, reflecting progressive cerebral atrophy. Patients demonstrated severe cognitive and motor impairments, with developmental regression reported in only a minority. No statistical relationship between brain measurements and cognitive or motor development was observed. CONCLUSION: MRI in PCH2A patients shows limited cerebellar growth during infancy, especially restricted along the cranio-caudal axis. After infancy, cerebellar volume remains relatively stable. Supratentorial measurements indicate slowly progressive atrophy. Psychomotor development is significantly impaired, but regression is rare.
AIM: Germinal-matrix-intraventricular hemorrhage (GM-IVH) is a leading cause of seizures in preterm infants. This study aimed to analyze risk factors associated with seizures and to evaluate neurodevelopmental outcomes i...AIM: Germinal-matrix-intraventricular hemorrhage (GM-IVH) is a leading cause of seizures in preterm infants. This study aimed to analyze risk factors associated with seizures and to evaluate neurodevelopmental outcomes in preterm infants with GM-IVH and seizures. METHODS: We conducted a retrospective study from 2011 to 2019, identifying preterm infants with GM-IVH grades 2-4 through an electronic patient file system. Seizures were diagnosed based on clinical manifestations and abnormal EEG findings. Infants were grouped by the presence or absence of seizures, and associated comorbidities were compared. Neurodevelopmental follow-up was assessed at two years of age using the Mental Bayley Scales of Infant Development II (BSID-II). Outcomes of infants with seizures were compared to all tested preterm infants with birth weight <1500 g born between 2011 and 2019 (n = 195). RESULTS: A total of 34 preterm infants with GM-IVH grades 2-4 were included. Seizures occurred in 52.9 % of cases. Their occurrence was significantly associated with lower gestational age (mean 28.1 vs. 30 weeks, p = 0.04) and pneumonia (p = 0.003). Infants with seizures had significantly lower BSID-II Mental scores (n = 15) compared to those without seizures (86.3 ± 18.3 vs. 104.9 ± 8.5, p = 0.03). However, as these infants had a lower gestational age, we could not distinguish if they had a poorer outcome because of seizures or because of immaturity. CONCLUSION: Seizures in preterm infants with GM-IVH were significantly associated with lower gestational age and pneumonia. Infections and inflammation may contribute to seizure development. Larger studies with continuous EEG monitoring are needed to validate these findings.
OBJECTIVE: We aimed to assess medium-to long-term neurological outcomes in children with severe acute brain injury (ABI) and to identify cardiovascular predictors associated with unfavorable outcomes, such as heart rate...OBJECTIVE: We aimed to assess medium-to long-term neurological outcomes in children with severe acute brain injury (ABI) and to identify cardiovascular predictors associated with unfavorable outcomes, such as heart rate (HR), blood pressure (BP), and heart rate variability (HRV). HRV refers to the oscillations in the intervals between consecutive heartbeats, reflecting the dynamic interplay between sympathetic and parasympathetic impulses to the heart. It provides a non-invasive indicator of autonomic nervous system (ANS) activity. DESIGN: Prospective observational cohort. SETTING: Tertiary academic pediatric intensive care unit (PICU). PATIENTS: Children >27 days and <18 years old admitted to the PICU after severe ABI who survived to PICU discharge. Children suspected of being brain dead at PICU admission or with cardiac arrythmias were excluded. INTERVENTIONS: None. MEASURE: ments: Physiological variables, neurological data, chemistry and hematologic tests and medication were collected within the initial 12 h following admission to the PICU. Linear and nonlinear indices of HRV obtained from electrocardiogram (ECG) Holter recordings, computerized tomography (CT) and PICU scores, as well as survival rates within the PICU, were evaluated. The primary outcome measure was global functional outcome as measured by the Pediatrics Glasgow Outcome Scale Extended (GOSE-Peds) at 3 and 12 months after injury. These data were taken by reviewing the medical records. The outcome was dichotomized into favorable and unfavorable based on predefined cutoffs. None to mild disability (GOSE-E PEDS category ≤2) was categorized as favorable outcome, whereas moderate to severe disability was categorized as unfavorable (GOSE-E PEDS category ≥3). MAIN RESULTS: Thirty-one children with ABI were eligible for the study. Twenty-four were male (77.4 %) and they had the median age of 11.3 years old (IQR 5.6-14.3). Twenty-two (71.0 %) patients had traumatic brain injury (TBI) and five (16.1 %) cerebral hemorrhage. Sixteen children (51.6 %) had a favorable outcome at 3 months and twenty-one (67.7 %) at 12 months. The presence of tachycardia or bradycardia was not related to the prognosis. Patients with systolic arterial blood pressure (SBP) above the 95th percentile in the first 12 h after admission to the PICU exhibited a significantly better neurological outcome [15 (68.2 %) vs. 9 (31.8 %), p = 0.006] at 3 months, and [20 (83.3 %) vs. 4 (16.7 %), p = 0.002] at 12 months. Calculated HRV values were higher, both on admission and 12 h after admission, in patients with a favorable prognosis at 3 and 12 months. However, these results were statistically significant only for RMSSD, LF, TP, and Poincaré SD1 and SD2 at 12 h after admission and for outcomes at 3 months. Patients with LF > 70.0 ms at 12 h after admission had a significantly better outcome at 12 months [11.0 (91.7 %) vs 1.0 (8.3 %), p = 0.046]. 87.5 % of patients with SDNN >35.0 ms and 70.5 % of patients with RMSSD >3.2 ms, at 12 h after admission, showed a statistically significative better outcome at 3 months. Patients who had a more unfavorable prognosis spent significantly more time on mechanical ventilation and had a longer length of stay (LOS) in the PICU. CONCLUSIONS: This study suggests that elevated early SBP and HRV indices-particularly LF power measured 12 h after PICU admission-may serve as independent, non-invasive predictors of long-term neurological outcomes in children with severe ABI. These findings support the role of early autonomic activation as a marker of favorable prognosis and underscore the potential value of incorporating cardiovascular and autonomic monitoring into prognostic models and individualized neuroprotective strategies in pediatric neurocritical care.