Expansion of the prenatal phenotype of Baraitser-Winter syndrome: Presentation of two cases of multiple congenital anomaly syndrome.

Baraitser-Winter cerebrofrontofacial syndrome (BWCFF) is a variable multiple congenital anomaly condition, typically presenting postnatally with neurocognitive delays, distinctive facial features, cortical brain malformations, and in some, a variety of additional congenital malformations. However, only a few cases have reported the prenatal presentation of this syndrome. Here, we report two cases of BWCFF and their associated prenatal findings. One case presented with non-immune hydrops fetalis and a horseshoe kidney and was found to have a de novo heterozygous variant in ACTB (c.158A>G). The second case presented with gastroschisis, bilateral cleft lip and palate, and oligohydramnios, and was found to harbor a different de novo variant in ACTB (c.826G>A). Limited reports exist describing prenatally identified anomalies that include fetal growth restriction, increased nuchal fold, bilateral hydronephrosis, rocker bottom foot, talipes, cystic hygroma, omphalocele, and hydrops fetalis. In addition, only three of these cases have included detailed prenatal imaging findings. The two prenatal cases presented here demonstrate an expansion of the prenatal phenotype of BWCFF to include gastroschisis, lymphatic involvement, and oligohydramnios, which should each warrant consideration of this diagnosis in the setting of additional anomalies.

Fetal Cerebral Ventriculomegaly: A Narrative Review and Practical Recommendations for Pediatric Neurologists.

Fetal cerebral ventriculomegaly is one of the most common fetal neurological disorders identified prenatally by neuroimaging. The challenges in the evolving landscape of conditions like fetal cerebral ventriculomegaly involve accurate diagnosis and how best to provide prenatal counseling regarding prognosis as well as postnatal management and care of the infant. The purpose of this narrative review is to discuss the literature on fetal ventriculomegaly, including postnatal management and neurodevelopmental outcome, and to provide practice recommendations for pediatric neurologists.

Aerosol drug therapy in critically ill patients (Aero-in-ICU study): A multicentre prospective observational cohort study.

BACKGROUND: In recent years, a significant understanding of delivering optimal aerosol therapy and the availability of various drugs and devices have led to an increase in its use in clinical practice. There are only a few studies available regarding their use in critically ill patients from a few parts of the world. We aimed to study the practice pattern of aerosol therapy in critically ill patients from Indian intensive care units (ICUs). METHODS: After ethical approval, this multi-centric prospective observational study was performed over a study period of four weeks. Newly admitted adult patients considered who had an artificial airway and/or ventilation (including non-invasive). Patients were followed up for the next 14 days or until ICU discharge/death (whichever came first) for details of each aerosol therapy, including ongoing respiratory support, drug type, and aerosol-generating device. RESULTS: From the nine participating centers across India, 218 patients were enrolled. Of 218 enrolled patients, 72.48% received 4884 aerosols with 30.91 ± 27.15 (95%CI: 26.6-35.1) aerosols per patient over 1108 patient days. Approximately 62.7% during IMV, 30.2% during NIV, 2.3% in spontaneously breathing patients with an artificial airway during weaning, and 4.7% were given without an artificial airway after weaning or decannulation. In 59%, a single drug was used, and bronchodilators were the most frequent. The jet nebulizer was the most common, followed by the ultrasonic and vibrating mesh aerosol generator. The ventilator setting was changed in only 6.6% of the aerosol sessions with IMV and none with NIV. CONCLUSION: Aerosol therapy is frequently used with a wide variation in practices; bronchodilators are the most commonly used drugs, and jet nebulizers are the most widely used.

Interdisciplinary fetal neurology care: Current practice, challenges, and future directions.

As the field of fetal-neonatal neurology has expanded over the past 2 decades with increasingly complex diagnoses, multidisciplinary collaboration with many subspecialties including genetics, neonatology, obstetrics, maternal fetal medicine, surgical sub-specialties, cardiology, radiology, palliative care, and ethics has needed to evolve to strive to offer optimal patient care. While comprehensive care delivery with an inter-disciplinary approach is preferred, there are often barriers based on numerous health disparities especially in resource limited settings. Even in the context of comprehensive care, diagnostic and prognostic uncertainty lead to challenges for providers during fetal neurology consultations. We present a case that highlights advantages of a comprehensive multi-disciplinary team in caring for the medical and social challenges of patients faced with a fetal neurologic diagnosis. Inter-disciplinary training focusing on maternal, fetal, neonatal, and childhood neurodevelopmental course and collaboration among the numerous stakeholders that contribute to fetal neurology practice is needed to provide optimal counseling and care for families faced with a fetal neurological diagnosis.

Clinical decisions in fetal-neonatal neurology I. reproductive and pregnancy health influence the neural exposome over multiple generations.

Interdisciplinary fetal neonatal neurology (FNN) training requires integration of reproductive health factors into evaluations of the maternal-placental-fetal (MPF) triad, neonate, and child over the first 1000 days. Serial events that occur before one or multiple pregnancies impact successive generations. A maternal-child dyad history highlights this continuity of health risk, beginning with a maternal grandmother's pregnancy. Her daughter was born preterm and later experienced polycystic ovarian syndrome further complicated by cognitive and mental health disorders. Medical problems during her pregnancy contributed to MPF triad diseases that resulted in her son's extreme prematurity. Postpartum maternal death from the complications of diabetic ketoacidosis and her child's severe global neurodevelopmental delay were adverse mother-child outcomes. A horizontal/vertical diagnostic approach to reach shared clinical decisions during FNN training requires perspectives of a dynamic neural exposome. Career-long learning is then strengthened by continued interactions from al stakeholders. Developmental origins theory applied to neuroplasticity principles help interpret phenotypic expressions as dynamic gene-environment interactions across a person's lifetime. Debiasing strategies applied to the cognitive process reduce bias to preserve therapeutic and prognostic accuracy. Social determinants of health are essential components of this strategy to be initiated during FNN training. Reduction of the global burden of neurologic disorders requires applying the positive effects from reproductive and pregnancy exposomes that will benefit the neural exposome across the lifespan.

Clinical decisions in fetal-neonatal neurology II: Gene-environment expression over the first 1000 days presenting as "four great neurological syndromes".

Interdisciplinary fetal-neonatal neurology (FNN) training considers a woman's reproductive and pregnancy health histories when assessing the "four great neonatal neurological syndromes". This maternal-child dyad exemplifies the symptomatic neonatal minority, compared with the silent majority of healthy children who experience preclinical diseases with variable expressions over the first 1000 days. Healthy maternal reports with reassuring fetal surveillance testing preceded signs of fetal distress during parturition. An encephalopathic neonate with seizures later exhibited childhood autistic spectrum behaviors and intractable epilepsy correlated with identified genetic biomarkers. A systems biology approach to etiopathogenesis guides the diagnostic process to interpret phenotypic form and function. Evolving gene-environment interactions expressed by changing phenotypes reflect a dynamic neural exposome influenced by reproductive and pregnancy health. This strategy considers critical/sensitive periods of neuroplasticity beyond two years of life to encompass childhood and adolescence. Career-long FNN experiences reenforce earlier training to strengthen the cognitive process and minimize cognitive biases when assessing children or adults. Prioritizing social determinants of healthcare for persons with neurologic disorders will help mitigate the global burden of brain diseases for all women and children.

Advancing the Field of Fetal Neurology: A Call for Global Collaborations.

Fetal Neurology continues to grow as a distinct subspecialty informed by evolving precision diagnosis with advancements in prenatal neuroimaging, genetic and infectious testing. While there are inherent limitations and challenges in prenatal diagnostic testing and prognostic counseling, the interdisciplinary approach allows comprehensive guidance for perinatal and postnatal management of neurological disorders detected early in development. The current practice of fetal neurology is heterogenous and variable across centers. In low- and middle-income countries (LMICs), fetal neurology practice is under the umbrella of neonatal and perinatal medicine. Since infrastructure and capacity for prenatal diagnostic and prognostic counseling may be variable, the practice approach may have to be modified regionally based on resources, education, and setting. There is a need for collaborative development of educational opportunities, training, guidelines, and research exploring short- and long-term outcome of prenatally identified neurological conditions. Interdisciplinary collaborations and global professional networks are crucial to advance this unique subspecialty.

Fetal Neurology Practice Survey: Current Practice and the Future Directions.

BACKGROUND: Fetal neurology is a rapidly evolving field. Consultations aim to diagnose, prognosticate, and coordinate prenatal and perinatal management along with other specialists and counsel expectant parents. Practice parameters and guidelines are limited. METHODS: A 48-question online survey was administered to child neurologists. Questions targeted current care practices and perceived priorities for the field. RESULTS: Representatives from 43 institutions in the United States responded; 83% had prenatal diagnosis centers, and the majority performed on-site neuroimaging. The earliest gestational age for fetal magnetic resonance imaging was variable. Annual consultations ranged from <20 to >100 patients. Fewer than half (n = 17.40%) were subspecialty trained. Most respondents (n = 39.91%) were interested in participating in a collaborative registry and educational initiatives. CONCLUSIONS: The survey highlights heterogeneity in clinical practice. Large multisite and multidisciplinary collaborations are essential to gather data that inform outcomes for fetuses evaluated across institutions through registries as well as creation of guidelines and educational material.

Frontonasal Dysplasia: A Diagnostic Challenge with Fetal MRI in Twin Pregnancy.

Callosal agenesis is a complex condition with disruption in the steps such as cellular proliferation, migration, axonal growth, guidance, or glial patterning at the midline. Agenesis of the corpus callosum (AgCC) is associated with diverse midline craniofacial malformations affecting the frontal-cranial and midface skeleton. Diagnosing midline abnormalities prenatally can be challenging, especially in twin pregnancies, due to poor resolution of skull base structures on fetal MRI, basal cephalocele could be mistaken for fluid in the nasopharynx, motion limitation, and fetal positioning. Our case highlights the importance of evaluation for other associated midline anomalies when there is callosal agenesis.

Prenatal Neurological Diagnosis: Challenges in Neuroimaging, Prognostic Counseling, and Prediction of Neurodevelopmental Outcomes.

Prenatal diagnosis of fetal brain abnormalities is rapidly evolving with the advancement of neuroimaging techniques, thus adding value to prognostic counseling and perinatal management. However, challenges and uncertainties persist in prenatal counseling due to limitations of prenatal imaging, continued development and maturation of the brain structure, and the heterogeneity and paucity of outcome studies. This topical review of fetal neurological consultations highlights prenatally diagnosed brain abnormalities that challenged prognostic counseling and perinatal management. Representative cases across multiple centers that highlighted diagnostic challenges were selected. Charts were reviewed for neuroimaging, genetic evaluation, prenatal prognostic discussion, postnatal imaging and testing, and infant outcome. We present case studies with prenatal and postnatal information discussing prenatal testing, fetal MRI interpretation, and complexities in the prognostic counseling process. Advocating for large-scale multicenter studies and a national collaborative fetal neurological registry to help guide the ever-expanding world of prenatal diagnostics and prognostic counseling is critical to this field. Study of large-scale outcomes data from such a registry can better guide fetal neurological consultations and facilitate comprehensive multidisciplinary planning and program development for educational curriculum for fetal-neonatal neurology.

Prolonged neurologic deficits with brain MRI changes following ECT in an adolescent with a CACNA1a-related disorder; a case report.

BACKGROUND: Electroconvulsive therapy is used to treat depression and schizophrenia with infrequent use in pediatric patients. We report a case of an adolescent with autism spectrum disorder and acute catatonia that presented with status epilepticus (SE) and prolonged neurologic deficits with unilateral left cerebral edema on imaging following unilateral electroconvulsive therapy (ECT) on the right side, subsequently found to have a CACNA1a pathogenic variant. This case highlights a potential adverse effect of ECT in patients with CACNA1a related disorders. CASE: The patient received unilateral ECT to the right side and subsequently had an episode of SE with right-sided hemiplegia for 72 h prior to regaining some function with persistent mild right-hand weakness that persisted for at least 1-2 weeks. A brain MRI 2 days after ECT was unremarkable, but a repeat MRI on day four of admission showed left hemisphere cortical diffusion restriction, increased perfusion and T2 prolongation suggestive of cortical edema. They had whole exome genetic testing sent after discharge that showed a known pathogenic CACNA1a variant (p.I1709T). CACNA1a encodes the P/Q type calcium channels and deleterious variants in this gene result in a channelopathy associated with a spectrum of neurodevelopmental disorders that include autism spectrum disorder, hemiplegic migraine with unilateral cerebral edema, epileptic encephalopathies, or episodic ataxia syndromes. CONCLUSION: A literature review of ECT and neurologic deficits showed that most neurologic deficits resolve within 30 min of ECT. Case reports of prolonged deficits are rare and there are no prior reports of acute MRI changes related to ECT. Thus, the acute deterioration and MRI findings in this patient are likely related to the underlying CACNA1a channelopathy disorder with ECT as a precipitating event. This case report suggests care should be taken when using ECT in patients with pathogenic variants in CACNA1a. Furthermore, it reinforces the utility and importance of expanded genetic testing in patients with neurodevelopmental disorders as findings can provide valuable information that can guide treatment decisions.

Fetal-neonatal neurology program development: Continuum of care during the first 1000 days.

Global estimates show that 10-20% of persons express developmental disability. During critical and sensitive periods of developmental neuroplasticity over the first 1000 days, adverse gene-environment interactions are likely to contribute to permanent life-long disabilities and early mortality. This article describes fetal-neonatal neurology (FNN) program development that integrates vertical and horizontal diagnostic perspectives. Trimester-specific conditions to the maternal-placental-fetal triad begin at conception, followed by pediatric patient care over the first two years of life to address changing phenotypic form and function. While fetal and neonatal neurology trainees prepare to offer person-centric healthcare, population-based considerations address obstacles to optimal health relevant to resource-rich and poor nations. Maternal and pediatric care practices over the first 1000 days underscore equitable health policy. Global initiatives apply geographic distance, biosocial dynamics, and cultural differences to developmental origins and life-course theories, to more effectively reduce disease burden over the life continuum.

The Guiding Star: The Journey of an International Physician From Maternal Fetal Medicine to Fetal Neonatal Neurology.

My path to the American dream took me from maternal fetal medicine in India to fetal and neonatal neurology in the United States, a journey spanning 2 continents, 3 countries, 3 healthcare systems, 4 rounds of the residency match process, 2 residency trainings and 4 fellowships. Through it all I had the good fortune to be guided by a wonderful support system of mentors, family, and friends. This is my story of how and why.