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Calmodulin‐binding transcriptional activator 1 (CAMTA1) is highly expressed in the brain and plays a role in cell cycle regulation, cell differentiation, regulation of long‐term memory, and initial development, maturation, and survival of cerebellar neurons. The existence of human neurological phenotypes, including cerebellar dysfunction with variable cognitive and behavioral abnormalities (CECBA), associated with CAMTA1 variants, has further supported its role in brain functions. In this study, we phenotypically and molecularly characterize the largest cohort of individuals (n = 26) with 23 novel CAMTA1 variants (frameshift‐7, nonsense‐6, splicing‐1, initiation codon‐1, missense‐5, and intragenic deletions‐3) and compare the findings with all previously reported cases (total = 53). We show that the most notable phenotypic findings are developmental delay/intellectual disability, unsteady or uncoordinated gait, hypotonia, behavioral problems, and eye abnormalities. In addition, there is a high incidence of dysarthria, dysgraphia, microcephaly, gastrointestinal abnormalities, sleep difficulties, and nonspecific brain MRI findings; a few of which have been under‐reported. More than one third of the variants in this cohort were inherited from an asymptomatic or mildly affected parent suggesting reduced penetrance and variable expressivity. Our cohort provides a comprehensive characterization of the spectrum of phenotypes and genotypes among individuals with CECBA and the large data will facilitate counseling and formulating management plans and surveillance recommendations for these individuals. [ABSTRACT FROM AUTHOR]

We report the case of a Syrian female refugee with late diagnosis of glutaric aciduria type 1 characterised by massive axial hypotonia and quadriplegia who only started adequate diet upon arrival in Switzerland at the age of 4 years, after a strenuous migration journey. Soon after arrival, she died from an unexpected severe upper cervical myelopathy, heralded by acute respiratory distress after a viral infection. This was likely due to repeated strains on her hypotonic neck and precipitated by an orthotopic os odontoideum who led to atlanto‐axial subluxation. This case reminds us not to omit handling patients with insufficient postural control and hypotonia with great care to avoid progressive cervical myelopathy. [ABSTRACT FROM AUTHOR]

Purpose: Malignant stroke is a life-threatening emergency, with a high mortality rate (1–3). Despite strong evidence showing decreased morbidity and mortality in the adult population, decompressive hemicraniectomy (DCH) has been scarcely reported in the pediatric stroke population, and its indication remains controversial, while it could be a potential lifesaving option. Methods and results: We performed an extensive literature review on pediatric malignant arterial ischemic stroke (pmAIS) and selected 26 articles reporting 97 cases. Gathering the data together, a 67% mortality rate is observed without decompressive therapy, contrasting with a 95.4% survival rate with it. The median modified Rankin score (mRS) is 2.1 after surgery with a mean follow-up of 31.8 months. For the 33% of children who survived without surgery, the mRS is 3 at a mean follow-up of 19 months. As an illustrative case, we report on a 2-year-old girl who presented a cardioembolic right middle cerebral artery stroke with subsequent malignant edema and ongoing cerebral transtentorial herniation in the course of a severe myocarditis requiring ECMO support. A DCH was done 32 h after symptom onset. At the age of 5 years, she exhibits an mRS of 3. Conclusion: Pediatric stroke with malignant edema is a severe condition with high mortality rate if left untreated and often long-lasting consequences. DCH might minimize the vicious circle of cerebral swelling, increasing intracranial pressure and brain ischemia. Our literature review underscores DCH as an efficient therapeutic measure management of pmAIS even when performed after a significant delay; however, long-lasting morbidities remain high. [ABSTRACT FROM AUTHOR]

Background: Mutations in the TTN gene, encoding the muscle filament titin, are a major cause of inherited dilated cardiomyopathy. Early‐onset skeletal muscle disorders due to recessive TTN mutations have recently been described, sometimes associated with cardiomyopathies. Case Description: We report the case of a boy with congenital core myopathy due to compound heterozygosity for TTN variants. He presented in infancy with rapidly evolving restrictive cardiomyopathy, requiring heart transplantation at the age of 5 years with favorable long‐term cardiac and neuromuscular outcome. Conclusion: Heart transplantation may have a role in selected patients with TTN‐related congenital myopathy with disproportionally severe cardiac presentation compared to skeletal and respiratory muscle involvement. [ABSTRACT FROM AUTHOR]

This document is a reply to a letter commenting on a previous study about a pediatric patient with a cerebellar peduncle pilocytic astrocytoma. The authors of the reply discuss the complex relationship between tumor location, trigeminal nerve involvement, and clinical manifestations in the management of trigeminal neuralgia. They highlight the importance of recognizing and addressing trigeminal nerve involvement in these cases, as it can lead to significant sensory and motor deficits. The authors also mention a recent condylar fracture in their patient, which they hypothesize may be related to secondary masticatory muscle atrophy. They emphasize the need for comprehensive multidisciplinary management strategies and long-term follow-up in these cases. The document concludes by suggesting that more research is needed to explore the long-term outcomes of managing pediatric pilocytic astrocytoma in the posterior fossa. [Extracted from the article]

Background and purpose: HIBCH and ECHS1 genes encode two enzymes implicated in the critical steps of valine catabolism, 3‐hydroxyisobutyryl‐coenzyme A (CoA) hydrolase (HIBCH) and short‐chainenoyl‐CoA hydratase (ECHS1), respectively. HIBCH deficiency (HIBCHD) and ECHS1 deficiency (ECHS1D) generate rare metabolic dysfunctions, often revealed by neurological symptoms. The aim of this study was to describe movement disorders spectrum in patients with pathogenic variants in ECHS1 and HIBC. Methods: We reviewed a series of 18 patients (HIBCHD: 5; ECHS1D: 13) as well as 105 patients from the literature. We analysed the detailed phenotype of HIBCHD (38 patients) and ECHS1D (85 patients), focusing on MDs. Results: The two diseases have a very similar neurological phenotype, with an early onset before 10 years of age for three clinical presentations: neonatal onset, Leigh‐like syndrome (progressive onset or acute neurological decompensation), and isolated paroxysmal dyskinesia. Permanent or paroxysmal MDs were recorded in 61% of HIBCHD patients and 72% of ECHS1D patients. Patients had a variable combination of either isolated or combined MD, and dystonia was the main MD. These continuous MDs included dystonia, chorea, parkinsonism, athetosis, myoclonus, tremors, and abnormal eye movements. Patients with paroxysmal dyskinesia (HIBCHD: 4; ECHS1D: 9) usually had pure paroxysmal dystonia with normal clinical examination and no major impairment in psychomotor development. No correlation could be identified between clinical pattern (especially MD) and genetic pathogenic variants. Conclusions: Movement disorders, including abnormal ocular movements, are a hallmark of HIBCHD and ECHS1D. MDs are not uniform; dystonia is the most frequent, and various types of MD are combined in single patient. [ABSTRACT FROM AUTHOR]

Background Joubert syndrome (JS) is a recessively inherited ciliopathy characterised by congenital ocular motor apraxia (COMA), developmental delay (DD), intellectual disability, ataxia, multiorgan involvement, and a unique cerebellar and brainstem malformation. Over 40 JS-associated genes are known with a diagnostic yield of 60%–75%. In 2018, we reported homozygous hypomorphic missense variants of the SUFU gene in two families with mild JS. Recently, heterozygous truncating SUFU variants were identified in families with dominantly inherited COMA, occasionally associated with mild DD and subtle cerebellar anomalies. Methods We reanalysed next generation sequencing (NGS) data in two cohorts comprising 1097 probands referred for genetic testing of JS genes. Results Heterozygous truncating and splice-site SUFU variants were detected in 22 patients from 17 families (1.5%) with strong male prevalence (86%), and in 8 asymptomatic parents. Patients presented with COMA, hypotonia, ataxia and mild DD, and only a third manifested intellectual disability of variable severity. Brain MRI showed consistent findings characterised by vermis hypoplasia, superior cerebellar dysplasia and subtle-to-mild abnormalities of the superior cerebellar peduncles. The same pattern was observed in two out of three tested asymptomatic parents. Conclusion Heterozygous truncating or splice-site SUFU variants cause a novel neurodevelopmental syndrome encompassing COMA and mild JS, which likely represent overlapping entities. Variants can arise de novo or be inherited from a healthy parent, representing the first cause of JS with dominant inheritance and reduced penetrance. Awareness of this condition will increase the diagnostic yield of JS genetic testing, and allow appropriate counselling about prognosis, medical monitoring and recurrence risk. [ABSTRACT FROM AUTHOR]

Aim: The aim of this cross-sectional study was to measure the effect of dual tasks on gait stability in ambulant children with cerebral palsy (CP) compared to typically developing (TD) children. Methods: The children of the CP (n = 20) and TD groups (n = 20) walked first without a dual task, then while counting forward and finally while alternatively naming fruits and animals (DTf/a). They then completed the same cognitive exercises while sitting comfortably. We calculated the distance between the foot placement estimator (FPE) and the real foot placement in the anterior direction (DFPEAP) and in the mediolateral direction (DFPEML) as a measure of gait stability, in a gait laboratory using an optoelectronic system. Cognitive scores were computed. Comparisons within and between groups were analysed with linear mixed models. Results: The dual task had a significant effect on the CP group in DFPEAP and DFPEML. The CP group was more affected than the TD group during dual task in the DFPEML. Children in both groups showed significant changes in gait stability during dual tasks. Interpretation: The impact of dual task on gait stability is possibly due to the sharing of attention between gait and the cognitive task. All children favoured a 'posture second' strategy during the dual task of alternatively naming animals and fruits. Children with CP increased their mediolateral stability during dual task. [ABSTRACT FROM AUTHOR]

Ataxia-telangiectasia (A-T) is a neurodegenerative and primary immunodeficiency disorder (PID) characterized by cerebellar ataxia, oculocutaneous telangiectasia, immunodeficiency, progressive respiratory failure, and an increased risk of malignancies. It demands specialized care tailored to the individual patient's needs. Besides the classical ataxia-telangiectasia (classical A-T) phenotype, a variant phenotype (variant A-T) exists with partly overlapping but some distinctive disease characteristics. Here we present a case series of 6 patients with classical A-T and variant A-T, which illustrates the phenotypic variability of A-T that can present in childhood with prominent extrapyramidal features, with or without cerebellar ataxia. We report the clinical data, together with a detailed genotype description, immunological analyses, and related expression of the ATM protein. We show that the presence of some residual ATM kinase activity leads to the clinical phenotype variant A-T that differs from the classical A-T. Our data illustrate that the diagnosis of the variant form of A-T can be delayed and difficult, while early recognition of the variant form as well as the classical A-T is a prerequisite for providing a correct prognosis and appropriate rehabilitation and support, including the avoidance of diagnostic X-ray procedures, given the increased risk of malignancies and the higher risk for side effects of subsequent cancer treatment. [ABSTRACT FROM AUTHOR]

Aim: To assess the gait and cognitive performances of children with cerebral palsy (CP) during dual tasks (DT) in comparison to typically developing (TD) children.Method: This prospective, observational, case-control study included 18 children with CP (7 girls, 11 boys; median age 12 [10:13] years and 19 controls (9 girls, 10 boys; median age 12 [10:13y6mo] years). Performances were recorded during a simple walking task, 5 DT (walking + cognitive tasks with increasing cognitive load), and 5 simple cognitive tasks (while sitting). Gait parameters were computed using an optoelectronic system during walking tasks. Six parameters were selected for analysis by a principal component analysis. Cognitive performance was measured for each cognitive task. The dual-task cost (DTC) was calculated for each DT.Results: Gait performance decreased in both groups as DT cognitive load increased (e.g., walking speed normalized by leg length, in simple task: 1.25 [1.15:1.46] s-1 for CP, 1.53 [1.38:1.62] s-1 for TD; DT with highest load: 0.64 [0.53:0.80] s-1 for CP, 0.95 [0.75:1.08] s-1 for TD). The CP group performed significantly worse than TD group in every task (including the simple task), but DTC were similar in both groups. A task effect was found for the majority of the gait parameters.Interpretation: The reduced gait performance induced by DT may generate underestimated difficulties for children with CP in daily-life situations, where DT are common. This should be considered in clinical assessments. [ABSTRACT FROM AUTHOR]

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Both hand and finger sensory perception and motor abilities are essential for the development of skilled gestures and efficient bimanual coordination. While finger dexterity and finger sensory perception can be impaired in children with cerebral palsy (CP), the relationship between these two functions in this population is not clearly established. The common assumption that CP children with better sensory function also demonstrate better motor outcomes has been recently challenged. To study these questions further, we assessed both finger dexterity and finger gnosia, the ability to perceive one's own fingers by touch, in groups of 11 children with unilateral (i.e., hemiplegic CP) and 11 children with bilateral spastic CP (i.e., diplegic CP) and compared them with typical children. In our sample, children with hemiplegia exhibited finger dexterity deficit in both hands and finger gnosia deficit only in their paretic hand. In contrast, children with diplegia exhibited finger gnosia deficits in both hands and finger dexterity deficit only in their dominant hand. Thus, our results indicated that children with spastic hemiplegia and diplegia present different sensory and motor profiles and suggest that these two subgroups of CP should be considered separately in future experimental and clinical research. We discuss the implications of our results for rehabilitation. [ABSTRACT FROM AUTHOR]

Objective: Intravenous thrombolysis and endovascular therapy (IVT/EVT) are evidence-based treatments for adults with arterial ischemic stroke (AIS). However, randomized controlled trials in pediatric patients are lacking. This study aimed to describe feasibility, safety, and outcome of IVT/EVT in children with AIS.Methods: This retrospective study (01/2000-12/2015) included a multicenter, population-based consecutive cohort of patients aged 1 month to 16 years, diagnosed with AIS and presenting with pediatric National Institutes of Health Stroke Scale (pedNIHSS) ≥ 4. Clinical and radiological data of patients receiving IVT/EVT were compared to those receiving standard care (SC) using linear regression to adjust for potential confounders. EVT included intra-arterial thrombolysis and/or mechanical thrombectomy. Outcome was assessed 6 months after stroke using the pediatric stroke outcome measure (PSOM).Results: Overall, 150 patients (age 7.1 ± 4.9 years, 55 [37%] females) presented with pedNIHSS ≥ 4. Recanalization treatment was performed in 16 (11%), of whom 5 (3%) were treated with IVT and 11 (7%) with EVT. Patients receiving recanalization treatment were older (mean age = 11.0 vs 6.9 years, p = 0.01) and more severely affected (median pedNIHSS = 13.5 vs 8.0, p < 0.001). Death and bleeding complications did not differ between the 2 groups. Median (interquartile range) PSOM 6 months after AIS was 2.5 (1-4.3) and 1 (0-2) in the IVT/EVT and SC groups, respectively (p = 0.014). However, after multiple linear regression analysis, only higher baseline pedNIHSS remained associated with an unfavorable outcome (p < 0.001).Interpretation: Recanalization treatment is feasible and seems to be safe in severely affected pediatric AIS patients. The assessment of efficacy of IVT/EVT in pediatric stroke patients requires larger studies. Ann Neurol 2018;83:1125-1132. [ABSTRACT FROM AUTHOR]

Background: Neonatal thalamic hemorrhagic stroke is related to cerebral sinus venous thrombosis and associated with neurological sequelae. Predicting factors are however lacking. Methods: Clinical and radiological findings at onset and on follow-up of 5 neonates with thalamic hemorrhage stroke are described. Results: All neonates presented with abrupt lethargy, ophistotonos, irritability and/or seizures. The thalamic hemorrhagic stroke was most often unilateral (4/5), involving the posterior/entire thalamus in 3 cases and the anterior thalamus in 2. Cerebral venous thrombosis was identified in a single patient. At follow-up, children with unilateral anterior thalamic hemorrhagic stroke demonstrated thalamic atrophy without neurological symptoms, whereas children whose thalamus lesion was extensive exhibit a porencephalic cavity and presented with late-onset epilepsy. Discussion: Although deep cerebral venous thrombosis is probably the cause of neonatal thalamic hemorrhagic stroke, its radiological evidence is challenging. Outcome seems dependent of the size and location of thalamic hemorrhagic stroke. Epilepsy is a frequent morbidity after thalamic hemorrhagic stroke. [ABSTRACT FROM AUTHOR]

This study aimed to know how frontline physicians in France, Belgium, and Switzerland implement guidelines regarding the secondary prevention of childhood arterial ischemic stroke and to introduce physicians' point of view on a clinical trial assessing the efficacy of aspirin as a preventive strategy. The authors conducted an online survey directed at specialists throughout dedicated networks and used a mixed method for data analysis. Overall, 63 physicians responded, and 88% prescribe aspirin when sickle cell disease, cardio-embolic stroke, and dissection of cervical arteries are excluded. Prescribing habits vary among respondents with respect to their specialty. A majority would choose placebo or a treatment given to historical controls to compare with an aspirin arm in a trial. In studied countries, there seems to be good adherence to guidelines regarding the secondary prevention of childhood stroke. A trial assessing the efficacy of aspirin could be well accepted if several factors regarding study design were taken into account. [ABSTRACT FROM AUTHOR]

Aim: To determine the efficacy of mirror therapy in children with hemiparesis.Method: The design was an observer-blinded parallel-group randomized controlled trial (International Standard Randomised Controlled Trial Number 48748291). Randomization was computer-generated, 1:1 allocation to mirror therapy or comparison groups. The settings were home-based intervention and tertiary centre assessments. Participants were 90 children with hemiparesis aged 7 to 17 years. Intervention was 15 minutes per day of simultaneous arm training, 5 days a week, for 5 weeks. The mirror therapy group used a mirror; those in the comparison group looked at their paretic limb. Assessments comprised measures of upper limb strength, function (Melbourne Assessment 2), daily performance (ABILHAND-Kids), and sensory function at weeks 0 (T0 ), 5 (T1 ), and 10 (T2 ).Results: There were no significant differences in outcomes and their progression over time between the mirror therapy and comparison groups. Post-hoc intention-to-treat analyses showed significant improvements in both groups for grasp strength (T0 -T1 +12.6%), pinch strength (T0 -T2 +9.1%), upper limb function in terms of accuracy (T0 -T2 +2.7%) and fluency (T0 -T2 +5.0%), as well as daily performance (T0 -T2 +16.6%). Per protocol analyses showed additional improvements in dexterity (T0 -T2 +4.0%).Interpretation: The use of the mirror illusion during therapy had no significant effect on treatment outcomes. However, 5 weeks of daily simultaneous arm training significantly improved paretic upper limb strength, function, and daily use. [ABSTRACT FROM AUTHOR]

Background The aetiology of perinatal arterial ischemic stroke remains speculative. It is however widely accepted that the aetiology is multifactorial, involving various maternal, placental, foetal and neonatal risk factors. A resulting thromboembolic process is hypothesized and the placenta identified as the most plausible source. An arteriopathy, as observed in a significant proportion of childhood ischemic stroke, is thought to be rare. Methods We report here five cases of perinatal stroke that differ from the vast majority by documented carotid occlusion, and add eleven other similar cases from the literature. Results In the majority, an intraluminal thrombus of placental origin is the most probable hypothesis, while in the remaining ones, one can reasonably presume a direct vessel wall injury related to a traumatic delivery, yet generally unproven by imaging. Conclusion We hypothesize that most of these cases share similar pathophysiology with the more common perinatal arterial ischemic stroke but differ by a persistent identified thrombus in the carotid artery at the time of first imaging, leading to a more severe and extended ischemic damage responsible for an adverse neurological outcome. [ABSTRACT FROM AUTHOR]

Background: Herpes simplex virus (HSV) is the most common identified cause of focal encephalitis worldwide. However, postoperative HSV encephalitis (HSVE) is a rare complication of neurosurgical procedures and a significant clinical challenge Method: We describe 3 cases of postoperative HSVE and review all published reports. A total of 23 cases were identified. Discussion: Clinical heterogeneity represents a diagnostic challenge in the postoperative setting. Cerebral magnetic resonance imaging showed typical findings in a minority of patients only, whereas HSV-specific polymerase chain reaction on the cerebrospinal fluid proved to be a valuable test. The postoperative viral pathophysiology remains a subject of debate. The rate of adverse outcome is high and early antiviral treatment seems to be a strong predictor of clinical outcome. Conclusion: We recommend early empirical treatment for any patient presenting with post-neurosurgical lymphocytic meningo-encephalitis, and prophylactic antiviral treatment for patients with a history of previous HSVE who will undergo a neurosurgical procedure. [ABSTRACT FROM AUTHOR]

Stroke-like presentation in Lyme neuroborreliosis is rare in the pediatric age group. We report a previously healthy 12-year-old boy who presented with acute left hemiparesis and meningeal signs. Neuroimaging failed to reveal any cerebral infarction but demonstrated a multifocal cerebral vasculitis involving small, medium and large-sized vessels affecting both the anterior and posterior circulation. Concentric contrast enhancement of the basilar artery was also observed. Further investigations and laboratory findings were consistent with Lyme neuroborreliosis. A rapidly favorable clinical outcome was obtained with appropriate antibiotic treatment along with antiaggregants and steroids. Lyme neuroborreliosis should be considered in the diagnostic differential, not only in adults but also among children, especially in the context of an unexplained cerebral vasculitis. [ABSTRACT FROM AUTHOR]