Procedural sedation and analgesia in pediatric diagnostic and interventional radiology: An expert DELPHI consensus document developed by the ITALIAN scientific society of anesthesia, analgesia, resuscitation and intensive care (SIAARTI).

BACKGROUND: Children undergoing diagnostic and interventional radiology procedures often require sedation to achieve immobility and analgesia if the procedure is painful. In the past decades, leading scientific organizations have developed evidence-based guidelines for procedural sedation and analgesia in children outside of the operating room. Their recommendations are being applied to procedural sedation in radiology. However, some questions remain open regarding specific aspects contextualized to the radiology setting, such as elective prone sedation, the urgency of the procedure, when venous access or airway protection is required, and others. AIMS: To address the unresolved issues of procedural sedation and analgesia in pediatric diagnostic and interventional radiology. METHODS: An expert panel of pediatricians, pediatric anesthesiologists, intensivists, and neuroradiologists selected topics representative of current controversies and formulated research questions. Statements were developed by reviewing the literature for new evidence, comparing expertise and experience, and expressing opinions. Panelists' agreement with the statements was collected anonymously using the DELPHI method. RESULTS: Twelve evidence-based or expert opinion incorporate are presented, considering risks, benefits, and applicability. CONCLUSIONS: This consensus document, developed by a multidisciplinary panel of experts involved in the field, provides statements to improve the quality of decision-making practice in procedural sedation and analgesia in pediatric radiology.

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.

Electroclinical Features in Two Novel STRADA Patients and a Functional Yeast Assay for the Validation of Missense STRADA Mutations.

Loss of function of the STRADA gene, an upstream mTOR inhibitor, causes a rare neurodevelopmental disorder characterized by polyhydramnios, megalencephaly, and symptomatic epilepsy (PMSE syndrome). Patients display a homogeneous phenotype including early-onset drug-resistant epilepsy, severe psychomotor delay, multisystemic comorbidities, and increased risk of premature death. The administration of sirolimus, an mTOR inhibitor, is helpful in controlling seizures in this syndrome. We report the electroclinical phenotype of two novel patients and the development of a yeast model to validate the pathogenicity of missense variants. Patient 1 harbored a missense STRADA variant and had a peculiar electroclinical phenotype with a relatively mild epilepsy course. Patient 2 harbored a truncating STRADA variant and showed a typical PMSE phenotype and a favorable response to early treatment with sirolimus. When we modeled the p.(Ser264Arg) STRADA change in its yeast homolog SPS1, it impaired SPS1 function. The results underlie the importance of a timely molecular diagnosis in these patients and show that yeast is a simple yet effective model to validate the pathogenicity of missense variants.

Onset of Chiari type 1 malformation: insights from a small series of intrauterine MR imaging cases.

PURPOSE: Morphometric studies on idiopathic Chiari malformation type 1 (CM1) pathogenesis have been mainly based on post-natal neuroimaging. Prenatal clues related to CM1 development are lacking. We present pre- and post-natal imaging time course in idiopathic CM1 and assess fetal skull and brain biometry to establish if clues about CM1 development are present at fetal age. METHODS: Multicenter databases were screened to retrieve intrauterine magnetic resonance (iuMR) of children presenting CM1 features at post-natal scan. Syndromes interfering with skull-brain growth were excluded. Twenty-two morphometric parameters were measured at fetal (average 24.4 weeks; range 21 to 32) and post-natal (average 15.4 months; range 1 to 45) age; matched controls were included. RESULTS: Among 7000 iuMR cases, post-natal scans were available for 925, with postnatal CM1 features reported in seven. None of the fetuses presented CM1 features. Tonsillar descent was clear at a later post-natal scan in all seven cases. Six fetal parameters resulted to be statistically different between CM1 and controls: basal angle (p = 0.006), clivo-supraoccipital angle (p = 0.044), clivus' length (p = 0.043), posterior cranial fossa (PCF) width (p = 0.009), PCF height (p = 0.045), and PCFw/BPDb (p = 0.013). Postnatally, only the clivus' length was significant between CM1 cases and controls. CONCLUSION: Pre- and post-natal CM1 cases did not share striking common features, making qualitative prenatal assessment not predictive; however, our preliminary results support the view that some of the pathogenetic basis of CM1 may be embedded to some extent already in intrauterine life.

Neurosteroid pathway derangement in asphyctic infants treated with hypothermia: an untargeted metabolomic approach.

BACKGROUND: The pathobiological mechanisms associated with perinatal asphyxia and hypoxic-ischemic encephalopathy are complex and poorly understood. The metabolic effects of therapeutic hypothermia have been partially explored. METHODS: We conducted a single-center longitudinal study to investigate the metabolic effects of perinatal asphyxia and hypoxic-ischemic encephalopathy on the urinary metabolome of a group of 12 asphyctic infants over time compared to 22 matched healthy newborns, using untargeted metabolomics based on mass spectrometry. FINDINGS: Over-representation pathway analysis identified the steroidogenesis pathway as being significantly disrupted, with reduced steroid levels in the first three days of life despite treatment with hypothermia. Comparison with matched healthy newborns showed that the urinary steroid content was lower in asphyctic infants before hypothermia. The lysine degradation and carnitine synthesis pathways were also significantly affected. INTERPRETATION: Steroidogenesis is significantly disrupted in asphyctic infants compared to healthy newborns. Given how neurosteroids are involved in neuromodulation and neuroprotection, translational research is warranted on the potential role of neurosteroid-based intervention in asphyctic infants. FUNDING: None.

Complete agenesis of corpus callosum and unilateral cortical formation anomalies detected on fetal MR imaging: a phenotype strongly associated with the male fetuses.

INTRODUCTION: In a previous study of classifying fetuses with cortical formation abnormalities (CFA) with fetal MR, we noticed a cluster of cases with unilateral CFA and complete agenesis of the corpus callosum (ACC). In this study, we provide a detailed morphological analysis of such fetuses using fetal MR to determine if there are indicators (such as the gender of the fetus) that could be used to delineate a genetic substrate of the phenotype in order to inform future studies. METHODS: We have studied 45 fetuses with the unilateral CFA/ACC phenotype and analysed through an expert consensus panel the location and fine detail of the CFA and the associated findings such as associated anomalies, head size, and sex of the fetus. RESULTS: The frontal lobe was significantly more frequently involved by CFA when compared with other lobes (p < 0.001) but no preference for the left or right hemisphere. CFA most often consisted of excessive/dysmorphic sulcation. The CFA/ACC phenotype was overwhelmingly more frequent in male fetuses (M:F 4.5:1-p < 0.0001). The most frequent associated findings were: ventriculomegaly (16/45 fetuses) and interhemispheric cysts (12/45 cases). CONCLUSIONS: This report highlights the specific phenotype of unilateral CFA/ACC that is much more common in male fetuses. This finding provides a starting point to study possible sex-linked genetic abnormalities that underpin the unilateral CFA/ACC phenotype. KEY POINTS: • We collected fetuses with unilateral cortical formation abnormality and callosal agenesis. • That distinctive neuroimaging phenotype has a strong male gender prevalence (over 80%). • This observation forms the basis of studies about outcomes and genetic substrates.

Preoperative Devascularization of Choroid Plexus Tumors: Specific Issues about Anatomy and Embolization Technique.

(1) Background: Surgical treatment of choroid plexus tumors is challenging, burdened by a notable risk of bleeding. Neoadjuvant chemotherapy and preoperative embolization have been attempted, with encouraging results; however, the consensus on these procedures is lacking. (2) Methods: We present a case of a 10-month-old girl who underwent preoperative embolization of a hemorrhagic choroid plexus carcinoma of the lateral ventricle via the anterior choroidal artery, followed by total resection. (3) Results: The endovascular procedure was successfully completed, despite the rectification of the anterior choroidal artery associated with the absence of flow proximal to the plexal point. Minimal bleeding was observed during resection and the patient remained neurologically intact. (4) Conclusions: The time from entrance to exit in the anterior choroidal artery should be monitored and regarded as a potential 'occlusion time' in this specific group of patients. Nevertheless, our case supports the feasibility and effectiveness of preoperative embolization of a choroid plexus carcinoma of the lateral ventricle via the anterior choroidal artery, without complications. Furthermore, we suggest the use of a fast-embolic agent, such as N-butyl cyanoacrylate glue, as the preferred agent for this specific pathology and patient population.

A case of Wernicke encephalopathy combined with disulfiram intoxication.

There have been several reports of disulfiram intoxication, but little evidence of neurologic conditions resulting from disulfiram-induced brain damage combined with Wernicke encephalopathy-associated lesions. We report a rare patient with both Wernicke encephalopathy and disulfiram intoxication. This 50-year-old woman, who was taking disulfiram for chronic alcohol abuse, presented with an acute confusional state, dysarthria, nystagmus, supranuclear ophthalmoplegia, and paraparesis. Biochemical serum and cerebrospinal fluid analyses were normal. An electromyogram detected a motor polyneuropathy. Cognitive assessment revealed severe impairment of memory, attention, and logical and executive abilities. Magnetic resonance imaging with gadolinium enhancement showed brain lesions consistent with Wernicke encephalopathy, but also symmetric hyperintensities on T2-weighted images in the globus pallidus. Stopping the disulfiram and treating with hydration, high-dose thiamine supplements, and benzodiazepines significantly improved the patient's consciousness and oculomotor function. A magnetic resonance imaging scan after 1 month of treatment showed complete disappearance of the brain lesions and the hyperintensities in the globus pallidus. After a further month of intensive neurorehabilitation, the patient was able to interact with the medical staff, and her neuropsychological tests showed only mild memory impairment. Patients with alcoholism who present at emergency departments are at high risk for misdiagnosis, especially because there is no specific routine laboratory test for detecting asymptomatic disulfiram intoxication. Although uncommon, the combination of Wernicke encephalopathy and disulfiram intoxication should be suspected in patients with alcoholism. The disorder can be detected through a careful history and prompt clinical evaluation, together with characteristic magnetic resonance imaging findings.