Cerebral venous thrombosis and deep medullary vein thrombosis: Padua experience over the last two decades.

BACKGROUND: Cerebral venous thrombosis (CVT) is a cerebrovascular disorder that accounts for 20% of perinatal strokes. CVT incidence ranges from 0.67 to 1.12 per 100,000 newborns, while the incidence of "deep medullary vein thrombosis" (DMVT), a subtype of CVT, cannot be accurately estimated. This study aims to analyze the case history of CVT in the neonatal period, with a specific focus on DMVT. MATERIALS AND METHODS: Newborns diagnosed with CVT, with or without DMVT, between January 2002 and April 2023, were collected using the Italian Registry of Infantile Thrombosis (RITI). Cerebral MRIs were reviewed by an expert neuroradiologist following a standardized protocol. RESULTS: Forty-two newborns with CVT were identified, of which 27/42 (64%) had CVT, and the remaining 15/42 (36%) had DMVT (isolated DMVT in 9/15). Symptom onset occurred in the first week of life (median 8 days, IQR 4-14) with a male prevalence of 59%. The most common risk factors for CVT were complicated delivery (38%), prematurity (40%), congenital heart diseases (48%), and infections (40%). Seizures were the predominant presenting symptom in 52% of all cases. Hemorrhagic infarction was higher in cases with isolated DMVT (77%) compared to patients with CVT without DMVT (p = 0.013). Antithrombotic treatment was initiated in 36% of patients. Neurological impairment was observed in 48% of cases at discharge, while 18 out of 31 infants (58%) presented one or more neurological deficits at long term follow up.     Conclusion: DMVT occurs in over a third of neonates with CVT. Multicentric studies are essential to establish standardized protocols for therapy, neuroimaging, and follow-up in these patients.

Corrigendum: The new Italian registry of infantile thrombosis (RITI): a reflection on its journey, challenges and pitfalls.

[This corrects the article DOI: 10.3389/fped.2023.1094246.].

Hemiplegic Migraine in Children and Adolescents.

BACKGROUND: Only a few studies have focused on hemiplegic migraine (HM) in children despite its early age of onset. The aim of this review is to describe the peculiar characteristics of pediatric HM. METHODS: This is a narrative review based on 14 studies on pediatric HM selected from 262 papers. RESULTS: Different from HM in adults, pediatric HM affects both genders equally. Early transient neurological symptoms (prolonged aphasia during a febrile episode, isolated seizures, transient hemiparesis, and prolonged clumsiness after minor head trauma) can precede HM long before its onset. The prevalence of non-motor auras among children is lower than it is in adults. Pediatric sporadic HM patients have longer and more severe attacks compared to familial cases, especially during the initial years after disease onset, while familial HM cases tend to have the disease for longer. During follow-up, the frequency, intensity, and duration of HM attacks often decrease. The outcome is favorable in most patients; however, neurological conditions and comorbidities can be associated. CONCLUSION: Further studies are needed to better define the clinical phenotype and the natural history of pediatric HM and to refine genotype-phenotype correlations in order to improve the knowledge on HM physiopathology, diagnosis, and outcome.

Efficacy and safety of ketamine for neonatal refractory status epilepticus: case report and systematic review.

Background: Evidence-based data on treatment of neonatal status epilepticus (SE) are scarce. We aimed to collect data on the efficacy and safety of ketamine for the treatment of neonatal SE and to assess its possible role in the treatment of neonatal SE. Methods: We described a novel case and conducted a systematic literature review on neonatal SE treated with ketamine. The search was carried out in Pubmed, Cochrane, Clinical Trial Gov, Scopus and Web of Science. Results: Seven published cases of neonatal SE treated with ketamine were identified and analyzed together with our novel case. Seizures typically presented during the first 24 h of life (6/8). Seizures were resistant to a mean of five antiseizure medications. Ketamine, a NMDA receptor antagonist, appeared to be safe and effective in all neonates treated. Neurologic sequelae including hypotonia and spasticity were reported for 4/5 of the surviving children (5/8). 3/5 of them were seizure free at 1-17 months of life. Discussion: Neonatal brain is more susceptible to seizures due to a shift towards increased excitation because of a paradoxical excitatory effect of GABA, a greater density of NMDA receptors and higher extracellular concentrations of glutamate. Status epilepticus and neonatal encephalopathy could further enhance these mechanisms, providing a rationale for the use of ketamine in this setting. Conclusions: Ketamine in the treatment of neonatal SE showed a promising efficacy and safety profile. However, further in-depth studies and clinical trials on larger populations are needed.

Deep Medullary Vein Thrombosis in Newborns: A Systematic Literature Review.

BACKGROUND: Deep medullary vein (DMV) thrombosis is a rare cause of brain damage in both preterm and full-term neonates. In this study, we aimed to collect data on clinical and radiological presentation, treatment, and outcome of neonatal DMV thrombosis. METHODS: Systematic literature review on neonatal DMV thrombosis was carried out in PubMed, ClinicalTrial.gov, Scopus, and Web of Science up to December 2022. RESULTS: Seventy-five published cases of DMV thrombosis were identified and analysed (preterm newborns were 46%). Neonatal distress, respiratory resuscitation, or need for inotropes were present in 34/75 (45%) of patients. Signs and symptoms at presentation included seizures (38/75, 48%), apnoea (27/75, 36%), lethargy or irritability (26/75, 35%). At magnetic resonance imaging (MRI), fan-shaped linear T2 hypointense lesions were documented in all cases. All had ischaemic injuries, most often involving the frontal (62/74, 84%) and parietal lobes (56/74, 76%). Signs of haemorrhagic infarction were present in 53/54 (98%). Antithrombotic treatment was not mentioned in any of the studies included. Although mortality was low (2/75, 2.6%), a large proportion of patients developed neurological sequelae (intellectual disability in 19/51 [37%] and epilepsy in 9/51 [18%] cases). CONCLUSIONS: DMV thrombosis is rarely identified in the literature, even if it is possibly under-recognized or under-reported. Presentation in neonatal age is with seizures and non-specific systemic signs/symptoms that often cause diagnostic delay, despite the pathognomonic MRI picture. The high rate of morbidity, which determines significant social and health costs, requires further in-depth studies aimed at earlier diagnosis and evidence-based prevention and therapeutic strategies.

The new Italian registry of infantile thrombosis (RITI): A reflection on its journey, challenges and pitfalls.

Introduction: Thrombotic events in neonates and children represent a rare although severe occurrence in view of the associated risk of mortality and sequelae. Quality evidence is limited in this field, and registry studies provide an essential base for research. The aim of this paper is to present the new Italian Registry of Infantile Thrombosis (RITI), set it into the scene of international thrombosis and stroke registries, and provide some insight on the challenges associated with registry management. Methods: We present the detailed structure and content of the new RITI registry, a brief overview of its main data, and a reflection on its features, pitfalls and the main challenges related to its management. Results: The RITI, initially started in 2007 and officially re-launched in 2017 after structural modifications, is a non-interventional retrospective and prospective registry study collecting data on neonatal and pediatric patients (0-18 years) who experienced a systemic or cerebral thrombotic event in Italy. The RITI is managed by a multidisciplinary team with expertise in pediatric thrombosis, and participation is open to all Italian physicians, on a voluntary basis. The overall aim of the registry is to acquire new evidence to better characterize the population of children with thrombotic events and improve their management and outcome. 48 Italian pediatric and intensive care units are actively involved in the RITI, including 85 medical doctors from 16 Italian regions. A total of 1,001 neonates and children affected by cerebral or systemic thrombosis have been enrolled. Discussion: The RITI is one of the largest available European registries of neonatal and pediatric thrombosis. National registries like the RITI represent a model for the study of rare conditions based on multidisciplinary and multicenter collaboration, aimed at overcoming the limitations due to small populations of patients, and creating a network of experts for patient referral and continuous education. Moreover, registry studies have a pivotal role in the research on pediatric thrombosis, due to the limited feasibility of high-quality studies. In our experience, the main critical stages, pitfalls and challenges in registry management include adequate registry designing, diffusion, data completeness and quality control.

Neonatal Arterial Ischemic Stroke Secondary to Carotid Artery Dissection: A Case Report and Systematic Literature Review.

BACKGROUND: Carotid artery (CA) dissection is a rare etiology of neonatal arterial ischemic stroke (NAIS). METHODS: We describe one novel case and conduct a systematic literature review on NAIS attributed to CA dissection, to collect data on its clinical-radiological presentation, treatment, and outcome. RESULTS: Eight published cases of NAIS attributed to CA dissection were identified and analyzed with our case. All patients (nine of nine) were born at term, and eight of nine experienced instrumental/traumatic delivery or urgent Caesarean section. None had fetal problems during pregnancy or thrombophilia. Signs and symptoms at presentation (between days of life 0 and 6) included seizures (eight of nine), respiratory distress or irregular breathing (five of nine), hyporeactivity, decreased consciousness or irritability (four of nine), and focal neurological signs (two of nine). At magnetic resonance imaging (MRI), stroke was unilateral in seven of nine and extensive in five of nine. CA dissection was documented by neuroimaging or at postmortem studies (seven of nine), and hypothesized by the treating physicians based on delivery and neuroradiology characteristics (in the remaining two of nine). Antithrombotic treatment was used in two of nine. According to available follow-up, one of eight died at age seven days, seven of eight had neurological/epileptic sequelae, and CA recanalization occurred in three of four. CONCLUSIONS: NAIS attributed to CA dissection is rarely identified in the literature, often preceded by traumatic/instrumental delivery, presenting with seizures and systemic signs/symptoms, and often characterized by extensive MRI lesions and neurological sequelae. Definite evidence and recommendations on antithrombotic treatment are lacking.