Magnetic Resonance Imaging in Preterm Infant: A Systematic Review on Clinical Procedure Safety.

BACKGROUND: Currently, there is no evidence that MRI produces harmful effects on premature newborns, as well as short-term and long-term safety issues regarding radiofrequency fields and loud acoustic environment, while the examination that is being performed has not been clearly investigated. MRI of the brain conducted on preterm infants should be part of the diagnostic workup, when necessary. This article is intended to evaluate the short-term safety of MRI performed in preterm infants, when required, by analyzing all vital parameters available before, during, and after the MRI procedures. METHODS: We conducted a systematic review of the literature on electronic medical databases (PubMed and ClinicalTrials.gov) following the Preferred Reported Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. We included all preterm infants who underwent MRI whose clinical, hemodynamic, and respiratory parameters were reported. The quality of the included articles was assessed using QUADAS-2 (Quality Assessment of Diagnostic Accuracy Studies) tool. RESULTS: Six studies were included with a total of 311 preterm infants. No severe adverse event, such as death, occurred during MRI procedures. Vital signs remained stable in about two-thirds of all patients. CONCLUSIONS: Given the general clinical safety of MRI, we suggest it as a tool to be used in preterm infants in Neonatal Intensive Care Units, when necessary. We further suggest the development of standard protocols to guide the use of MRI in preterm infants to maximize the clinical safety of the procedure.

Drug resistant epilepsies: A multicentre case series of steroid therapy.

PURPOSE: Our study aimed to evaluate the effectiveness of corticosteroids on seizure control in drug-resistant epilepsies (DREs). Our primary goal was to assess the response to steroids for various underlying etiologies, interictal electroencephalographic (EEG) patterns and electroclinical seizure descriptions. Our second goal was to compare steroid responsiveness to different treatment protocols. METHODS: This is a retrospective multicentre cohort study conducted according to the STROBE guidelines (Strengthening the Reporting of Observational Studies in Epidemiology). The following data were collected for each patient: epilepsy etiology, interictal EEG pattern, seizure types and type of steroid treatment protocol administered. RESULTS: Thirty patients with DRE were included in the study. After 6 months of therapy, 62.7 % of patients experienced reduced seizure frequency by 50 %, and 6.6 % of patients experienced complete seizure cessation. Findings associated with favourable response to steroids included structural/lesional etiology of epilepsy, immune/infectious etiology and focal interictal abnormalities on EEG. Comparing four different steroid treatment protocols, the most effective for seizure control was treatment with methylprednisolone at the dose of 30 mg/kg/day administered for 3 days, leading to greater than 50 % seizure reduction at 6 months in 85.7 % of patients. Treatment with dexamethasone 6 mg/day for 5 days decreased seizure frequency in 71.4 % of patients. Hydrocortisone 10 mg/kg administered for 3 months showed a good response to treatment in 71 %. CONCLUSIONS: In our study, two-thirds of patients with DRE experienced a significant seizure reduction following treatment with steroids. We suggest considering steroids as a potential therapeutic option in children with epilepsy not responding to conventional antiseizure medicines (ASM).

Tracheostomy and long-term invasive ventilation decision-making in children: A scoping review.

An increasing number of children are surviving critical illnesses requiring tracheostomy/long-term ventilation (LTV). This scoping review seeks to collate the available evidence on decision-making for tracheostomy/LTV in children. Systematic searches of electronic databases and websites were conducted for articles and reports. Inclusion criteria included: (1) children 0-18 years old; (2) described use of tracheostomy or tracheostomy/LTV; and (3) information on recommendations for tracheostomy decision-making or decision-making experiences of family-caregivers or health care providers. Articles not written in English were excluded. Of the 4463 records identified through database search and other methods, a total of 84 articles, 2 dissertations, 1 book chapter, 3 consensus statement/society guidelines, and 8 pieces of grey literature were included. Main thematic domains identified were: (1) legal and moral standards for decision-making; (2) decision-making models, roles of decision-makers, and decisional aids towards a shared decision-making model; (3) experiences and perspectives of decision-makers; (4) health system and society considerations; and (5) conflict resolution and legal considerations. A high degree of uncertainty and complexity is involved in tracheostomy/LTV decision-making. There is a need for a standardized decision-support process that is consistent with a child's best interests and shared decision-making. Strategies for optimizing communication and mechanism for managing disputes are needed.

Pediatric Moyamoya Revascularization Perioperative Care: A Modified Delphi Study.

BACKGROUND: Surgical revascularization decreases the long-term risk of stroke in children with moyamoya arteriopathy but can be associated with an increased risk of stroke during the perioperative period. Evidence-based approaches to optimize perioperative management are limited and practice varies widely. Using a modified Delphi process, we sought to establish expert consensus on key components of the perioperative care of children with moyamoya undergoing indirect revascularization surgery and identify areas of equipoise to define future research priorities. METHODS: Thirty neurologists, neurosurgeons, and intensivists practicing in North America with expertise in the management of pediatric moyamoya were invited to participate in a three-round, modified Delphi process consisting of a 138-item practice patterns survey, anonymous electronic evaluation of 88 consensus statements on a 5-point Likert scale, and a virtual group meeting during which statements were discussed, revised, and reassessed. Consensus was defined as ≥ 80% agreement or disagreement. RESULTS: Thirty-nine statements regarding perioperative pediatric moyamoya care for indirect revascularization surgery reached consensus. Salient areas of consensus included the following: (1) children at a high risk for stroke and those with sickle cell disease should be preadmitted prior to indirect revascularization; (2) intravenous isotonic fluids should be administered in all patients for at least 4 h before and 24 h after surgery; (3) aspirin should not be discontinued in the immediate preoperative and postoperative periods; (4) arterial lines for blood pressure monitoring should be continued for at least 24 h after surgery and until active interventions to achieve blood pressure goals are not needed; (5) postoperative care should include hourly vital signs for at least 24 h, hourly neurologic assessments for at least 12 h, adequate pain control, maintaining normoxia and normothermia, and avoiding hypotension; and (6) intravenous fluid bolus administration should be considered the first-line intervention for new focal neurologic deficits following indirect revascularization surgery. CONCLUSIONS: In the absence of data supporting specific care practices before and after indirect revascularization surgery in children with moyamoya, this Delphi process defined areas of consensus among neurosurgeons, neurologists, and intensivists with moyamoya expertise. Research priorities identified include determining the role of continuous electroencephalography in postoperative moyamoya care, optimal perioperative blood pressure and hemoglobin targets, and the role of supplemental oxygen for treatment of suspected postoperative ischemia.

Phenotype expansion and neurological manifestations of neurobehavioural disease caused by a variant in RFX7.

The RFX7 gene is one of eight genes within the regulatory factor X family. RFX7 is highly expressed in the brain and plays an important role in cell maturation and differentiation. It has only recently been implicated in disease in humans. Reports from 15 individuals have described RFX-associated phenotype as a neurobehavioural disease, manifesting primarily with global developmental delay and intellectual disability. Autism spectrum disorder and attention deficit hyperactivity disorder have also been described in some children. Here we report a case of a 19-month-old with a de novo missense variant in RFX7 resulting in severe global developmental delay including significant speech delay, microcephaly, dyskinetic movements, and failure to thrive. This is the first association between variants in RFX7 and failure to thrive, expanding the phenotype of this newly described gene. In this report we will also show RFX7 associated progressive central nervous system involvement through serial brain imaging.

Startle Seizures and Diffuse Leukoencephalopathy After Resolution of Herpes Simplex Virus 1 Encephalitis in a Child.

We describe a unique clinical presentation of a child after the acute phase of herpes simplex virus 1 (HSV1) encephalitis. A 17-month-old boy first presented with HSV1 encephalitis and was promptly treated with antiviral medication. Seven months later, he was re-admitted for startle seizures. Magnetic Resonance Imaging of the brain showed diffuse confluent leukoencephalopathy. This constellation of symptoms has not been previously reported in HSV1 encephalitis. In conclusion, we showed that brain injury due to HSV1 encephalitis can be associated with the development of startle seizures and diffuse white matter injury in the post-acute phase.

aEEG vs cEEG's sensivity for seizure detection in the setting of neonatal intensive care units: A systematic review and meta-analysis.

AIM: Amplitude-integrated electroencephalography (aEEG)'s accuracy compared to conventional electroencephalography (cEEG) has not been fully established. The aim of our study was to conduct a systematic review on the sensitivity of the aEEG for neonatal seizure detection. METHODS: Studies from PubMed and Google Scholar databases comparing recordings of cEEG and aEEG in newborns were included according to the PRISMA method. A quality assessment using the QUADAS-2 tool was provided. A random-effect model was used to account for different sources of variations among studies. Publication biases were represented by a funnel plot, and funnel plot symmetry was assessed. RESULTS: Fourteen studies were reported; sensitivity of each diagnostic tool used (single-channel aEEG, two-channel aEEG, two-channel aEEG plus raw trace EEG) was compared to that of the gold-standard cEEG and to those of the other methods used. Overall sensitivity of the aEEG ranged from 31.25% to 90%. CONCLUSION: Our study provides evidence that sensitivity of aEEG varies significantly and that seizure detection rate is lower than that of cEEG. The two-channel aEEG with raw trace EEG shows a high sensitivity and might represent a valid alternative to the cEEG in the setting of neonatal intensive care units (NICUs).

Management of seizures in neonates with neonatal encephalopathy treated with hypothermia.

Neonatal encephalopathy (NE) is the most common etiology of acute neonatal seizures - about half of neonates treated with therapeutic hypothermia for NE have EEG-confirmed seizures. These seizures are best identified with continuous EEG monitoring, as clinical diagnosis leads to under-diagnosis of subclinical seizures and over-treatment of events that are not seizures. High seizure burden, especially status epilepticus, is thought to augment brain injury. Treatment, therefore, is aimed at minimizing seizure burden. Phenobarbital remains the mainstay of treatment, as it is more effective than levetiracetam and easier to administer than fosphenytoin. Emerging evidence suggests that, for many neonates, it is safe to discontinue the phenobarbital after acute seizures resolve and prior to hospital discharge.

Monogenic Syndromes with Congenital Heart Diseases in Newborns (Diagnostic Clues for Neonatologists): A Critical Analysis with Systematic Literature Review.

Congenital heart disease (CHD), the most common major congenital anomaly, is associated with a genetic syndrome (chromosomal anomalies, genomic disorders, or monogenic disease) in 30% of patients. The aim of this systematic review was to evaluate if, in the neonatal setting, clinical clues that orient the diagnostic path can be identified. For this purpose, we revised the most frequent dysmorphic features described in newborns with CHD, comparing those associated with monogenic syndromes (MSG) with the ones reported in newborns with genomic disorders. For this systematic review according to PRISMA statement, we used PubMed, Medline, Google Scholar, Scopus database, and search terms related to CHD and syndrome. We found a wide range of dysmorphisms (ocular region, ears, mouth, and/or palate and phalangeal anomalies) detected in more than half of MSGs were found to be associated with CHDs, but those anomalies are also described in genomic rearrangements syndromes with equal prevalence. These findings confirmed that etiological diagnosis in newborns is challenging, and only the prompt and expert recognition of features suggestive of genetic conditions can improve the selection of appropriate, cost-effective diagnostic tests. However, in general practice, it is crucial to recognize clues that can suggest the presence of a genetic syndrome, and neonatologists often have the unique opportunity to be the first to identify abnormalities in the neonate.

Neuroimaging in pediatric temporal lobe epilepsy: Does neuroimaging accurately predict pathology and surgical outcome?

Temporal lobe epilepsy (TLE) in children is considered different from that in adults. As such, characterizing the structural lesions present in pediatric patients with TLE and their association with long-term seizure control is important. Here, we aimed to assess the concordance between preoperative imaging and postoperative histopathological diagnoses and their associations with seizure outcomes in pediatric patients with TLE undergoing temporal lobe surgery. We retrospectively reviewed the charts of pediatric patients with TLE who underwent surgical treatment between 1988 and 2020 as a part of the Comprehensive Epilepsy Program at the University of Alberta. Demographic, age at seizure onset, age at surgery, preoperative electroencephalography (EEG), long-term video EEG, imaging (magnetic resonance imaging [MRI] and computed tomography), neuropathology, and long-term seizure outcome data were acquired and analyzed. One hundred and seventeen patients underwent surgery for refractory TLE; the preoperative MRI diagnosis was concordant with the histopathological diagnosis in 76 % of cases. Tumors were identified with high accuracy (91 %). Mesial temporal sclerosis (MTS) was strongly associated with an excellent outcome after surgery (94 %). Patients with normal imaging results or non-specific pathologies were more likely to experience poor seizure outcomes after surgery (50 %). The radiological identification of lesions was associated with good long-term seizure outcomes, whereas normal MRI results were associated with significantly poorer long-term seizure outcomes. An accurate preoperative MRI is essential to epilepsy surgery since it impacts all stages of management; these results will thereafter help inform practitioners' efforts to predict seizure outcome.

Ocular Motor Paroxysmal Events in Neonates and Infants: A Review of the Literature.

BACKGROUND: Ocular paroxysmal events can accompany a variety of neurological disorders. Particularly in infants, ocular paroxysmal events often represent a diagnostic challenge. Distinguishing between epileptic and nonepileptic events or between physiological and pathologic paroxysmal events can be challenging at this age because the clinical evaluation and physical examination are often limited. Continuous polygraphic video-electroencephalography (EEG) monitoring can be helpful in these situations. METHODS: We review ocular paroxysmal events in newborns and infants. The aim is to improve clinical recognition of ocular paroxysmal events and provide a guide to further management. Using the PubMed database, we identified studies focused on all ocular motor paroxysmal events in neonates and infants. RESULTS: Fifty-eight articles were selected on the topic. We summarized and divided these studies into those describing nonepileptic and epileptic ocular paroxysmal events. CONCLUSIONS: The diagnosis of ocular paroxysmal events can be difficult, but their recognition is important because of the variety of underlying etiologies. The distinction between epileptic versus nonepileptic ocular paroxysmal events often often requires polygraphic video-EEG to identify the epileptic events. For nonepileptic events, further testing can characterize pathologic ocular movements. To determine the etiology and prognosis of ocular paroxysmal events, a multimodal approach is required, including a thorough full history and clinical examination, polygraphic video-EEG monitoring, neuroimaging, and a careful follow-up plan.

Pediatric Hyperacute Arterial Ischemic Stroke Pathways at Canadian Tertiary Care Hospitals.

BACKGROUND: Childhood acute arterial ischemic stroke (AIS) is diagnosed at a median of 23 hours post-symptom onset, delaying treatment. Pediatric stroke pathways can expedite diagnosis. Our goal was to understand the similarities and differences between Canadian pediatric stroke protocols with the aim of optimizing AIS management. METHODS: We contacted neurologists at all 16 Canadian pediatric hospitals regarding AIS management. Established protocols were analyzed for similarities and differences in eight domains. RESULTS: Response rate was 100%. Seven (44%) centers have an established AIS protocol and two (13%) have a protocol under development. Seven centers do not have a protocol; two redirect patients to adult neurology, five rely on a case-by-case approach for management. Analysis of the seven protocols revealed differences in: 1) IV-tPA dosage: age-dependent 0.75-0.9 mg/kg (N = 1) versus age-independent 0.9 mg/kg (N = 6), with maximum doses of 75 mg (N = 1) or 90 mg (N = 6); 2) IV-tPA lower age cut-off: 2 years (N = 5) versus 3 or 10 years (each N = 1); 3) IV-tPA exclusion criteria: PedNIHSS score <4 (N = 3), <5 (N = 1), <6 (N = 3); 4) first choice of pre-treatment neuroimaging: computed tomography (CT) (N = 3), magnetic resonance imaging (MRI) (N = 2) or either (N = 2); 5) intra-arterial tPA use (N = 3) and; 6) mechanical thrombectomy timeframe: <6 hour (N = 3), <24 hour (N = 2), unspecified (N = 2). CONCLUSIONS: Although 44% of Canadian pediatric hospitals have established AIS management pathways, several differences remain among centers. Some criteria (dosage, imaging) reflect adult AIS literature. Canadian expert consensus regarding IV-tPA and endovascular treatment should be established to standardize and implement AIS protocols across Canada.

Improved care and management of paediatric neurological patients evaluated at a paediatric Rapid Access Neurology clinic: A pilot study.

AIM: Referral wait times for paediatric neurological patients are increasing, leading to an increased burden on the emergency department (ED). The paediatric Rapid Access Neurology (pRAN) clinic was created for paediatric patients who are clinically stable, but require an urgent paediatric neurology consultation. The objectives were to evaluate the pathways of referral, accuracy of referring diagnoses, adherence to clinic appointments, impact of clinic visitation on ED visits and patient satisfaction. METHODS: Data were collected from the pRAN clinic from March 2018 until April 2019. Information was obtained from patient charts including the referring and final diagnosis, management plan and the number of visits made to the ED before and after visiting the pRAN clinic. RESULTS: Of the 256 referred patients, 91 met inclusion criteria. The most frequent referral diagnosis was a seizure. Referring physicians and pRAN clinic neurologists differed significantly in the level of diagnostic agreement for patients <2 years of age (P = 0.03; 95% confidence interval (CI) -0.294, 0.373). There was a significant reduction in visits to the ED made by patients 3 months after the pRAN appointment compared with before the visit (P < 0.001; 95% CI -0.9070, -0.4088). The majority of patients felt that the clinic had high value and were satisfied with their follow-up plan. CONCLUSION: This pilot study showed that a pRAN clinic can improve the accuracy of neurological diagnoses and management, especially for children <2 years of age. In addition, pRAN clinic patients make fewer subsequent visits to the ED and express high satisfaction with their care.

Graph theory in paediatric epilepsy: A systematic review.

Graph theoretical studies have been designed to investigate network topologies during life. Network science and graph theory methods may contribute to a better understanding of brain function, both normal and abnormal, throughout developmental stages. The degree to which childhood epilepsies exert a significant effect on brain network organisation and cognition remains unclear. The hypothesis suggests that the formation of abnormal networks associated with epileptogenesis early in life causes a disruption in normal brain network development and cognition, reflecting abnormalities in later life. Neurological diseases with onset during critical stages of brain maturation, including childhood epilepsy, may threaten this orderly neurodevelopmental process. According to the hypothesis that the formation of abnormal networks associated with epileptogenesis in early life causes a disruption in normal brain network development, it is then mandatory to perform a proper examination of children with new-onset epilepsy early in the disease course and a deep study of their brain network organisation over time. In regards, graph theoretical analysis could add more information. In order to facilitate further development of graph theory in childhood, we performed a systematic review to describe its application in functional dynamic connectivity using electroencephalographic (EEG) analysis, focussing on paediatric epilepsy.

Early onset retinal dystrophies: clinical clues to diagnosis for pediatricians.

INTRODUCTION: Inherited retinal dystrophies are major cause of severe progressive vision loss in children. Early recognition and diagnosis are essential for timely visual rehabilitation during the appropriate stages of the visual development, as well as for genetic diagnosis and possible gene therapy. The aim of this study is to characterize a pattern of the initial visual symptoms, which could help the pediatricians and the primary care providers to suspect an inherited retinal disorder in its early stage. METHODS: We analyzed the initial clinical symptoms, based on parental report during the first visit to specialist, in 50 children diagnosed with retinal dystrophy confirmed by full-field electroretinography. The analysis included the age of symptoms onset and the type of visual symptoms, both in the total population and in the following diagnostic subgroups: rod-cone dystrophy (n.17), cone-rod dystrophy (n.12), achromatopsia (n.13), congenital stationary night blindness (n.6) and Leber's congenital amaurosis (n.2). RESULTS: The majority of children (80%) had the onset of clinical symptoms before one year of age. The most frequent visual complaints reported by parents were nystagmus (76%), visual loss (28%) and photophobia (8%). Nystagmus was the first symptom reported by parents if the disease onset was before the age of six months, while the onset after the six months of age was more likely associated with the complain of vision loss. CONCLUSIONS: Low vision and nystagmus observed by parents, particularly in the first year of life, may represent a red flag, prompting an appropriate ophthalmological workup for inherited retinal dystrophy.

Developmental EEG hallmark or biological artifact? Glossokinetic artifact mimicking anterior slow dysrhythmia in two full term newborns.

The aim of this paper is to describe an uncommon physiological EEG artifact in newborns caused by tongue movements (TM), mimicking anterior slow dysrhythmia (ASD). The subjects are two full-term newborns (39 weeks gestational age (GA)), admitted to the Neonatal Intensive Care Unit for respiratory distress. Both underwent polygraphic video-EEG recording in order to better characterize tremor-like movements of all four limbs that appeared 48 hours after birth. Multichannel video-EEG polygraphy was performed using the 10-20 electrode montage modified for neonates. Ninety minutes of EEG was recorded for each subject, capturing different behavioral states. Background EEG activity was normal for both subjects. During active sleep (AS), synchronous and symmetric slow activity was recorded over bifrontal head regions. For subject 1, bursts of monomorphic 2Hz delta waves, with an amplitude between 50-100µV lasting two seconds, were recorded and identified as anterior slow dysrhythmia. For subject 2, polymorphic 1-2Hz delta waves, 50-100µV in amplitude and lasting for 20 seconds, were recorded only during suction. After thorough analysis of simultaneous digital video recording synchronized with the EEG trace, this activity was thought to be compatible with glossokinetic artifact. Interpretation of neonatal EEG can be challenging; the background activity is frequently intermixed with physiological artifacts, such as ocular, muscle and movement artifacts, complicating the interpretation. Even continuous video-recording might not make the diagnosis immediately obvious. Therefore, when a rhythmic monomorphic pattern without evolution in amplitude or frequency is seen, we suggest that tongue movement artifact should be considered.

Breaking the cycle: A comparison between intravenous immunoglobulins and high dosage prednisone in the treatment of medically intractable epilepsy in children.

PURPOSE: Because immune mediated mechanisms are suspected in epileptogenesis, IVIg and corticosteroids have been used as alternatives to treat refractory seizures. We present our experience treating intractable epileptic children with IVIg and prednisone. METHODS: Children with intractable epilepsy treated with prednisone or IVIg between 2005-2016 were reviewed retrospectively. Children with infantile spasms and autoimmune epilepsy were excluded. Data analyzed include epilepsy type and etiology, duration of epilepsy prior to treatment, seizure outcome, time to best seizure outcome, and adverse effects. RESULTS: Fifty-one patients were included: 26 received IVIg; 25 received prednisone. Etiologies were similar between cohorts: genetic (13 IVIg; 10 prednisone), lesional (8 IVIg; 7 prednisone), and unknown (5 IVIg; 8 prednisone). In the prednisone cohort, 92.0% had generalized epilepsy compared to 61.5% for IVIg. Among the IVIg treated, 84.6% responded (10 genetic, 4 unknown, and 8 lesional) with mean seizure reduction of 77.3% and mean time to best response of 9.8 weeks. With prednisone, 24.0% responded (2 genetic, 3 unknown, and 1 lesional) with a mean seizure reduction of 95.0% and mean time to best response of 2.7 weeks. Adverse effects occurred in 2 and 16 patients treated with IVIg and prednisone, respectively. The difference in responders and seizure reduction was statistically significant (p<0.0001 and p=0.001, respectively). CONCLUSION: IVIg had greater responders and lower adverse effects and honeymoon effect. This response was independent of epilepsy type, etiology, and duration suggesting different mechanisms of action between prednisone and IVIg and a common, reversible, immune-mediated pathway to intractability.