A case of treatable encephalopathy, developmental regression, and proximal tremor.

Tyrosine hydroxylase (TH) deficiency is an autosomal recessive condition first described as a progressive, early-onset hypokinetic-rigid and dystonic syndrome that was responsive to levodopa. Here we present a child with developmental regression, proximal tremor, and encephalopathy found to have tyrosine hydroxylase deficiency in whom treatment resulted in acquisition of developmental milestones.

Why the Maternal Medication List Matters: Neonatal Toxicity From Combined Serotonergic Exposures.

Serotonergic medications are used for the prevention and treatment of depression during pregnancy. Selective serotonin reuptake inhibitors and serotonin-norepinephrine reuptake inhibitors (SNRIs) can cause poor neonatal adaptation, which has been attributed to withdrawal versus toxicity. Bupropion, a norepinephrine-dopamine reuptake inhibitor, is often used as an adjunctive agent to selective serotonin reuptake inhibitors or SNRIs for refractory depression. Quetiapine, an atypical antipsychotic, may also be used in more complex cases. When combined with serotonergic drugs, bupropion and quetiapine are associated with increased risk of serotonin syndrome in adults. We describe a neonate exposed to venlafaxine (an SNRI), bupropion, and quetiapine in utero who presented nearly immediately after birth with encephalopathy and abnormal movements. The severity and rapidity of symptoms may be attributable to potentiation of venlafaxine's serotonergic effects by bupropion and quetiapine. Neonatal providers should be aware of maternal medications and prepare for possible adverse effects, particularly from common psychotropic exposures.

Síndrome de encefalopatía posterior reversible en el postparto. Estudio de caso / Posterior reversible encephalopathy syndrome in postpartum. Case study

El objetivo del presente ensayo es evaluar el síndrome de encefalopatía posterior reversible en el posparto en una paciente de 22 años, sin antecedentes patológicos personales, antecedentes ginecoobstetricos G(1), C(1), A(0), P(0). Antecedente quirúrgico, cesárea segmentaria de 39 semanas de gestación que es referida por presentar cuadro clínico de 24 horas posteriores a la cesárea segmentaria con dolor abdominal, vómitos y distensión abdominal por lo que es intervenida quirúrgicamente donde realizan re-lapartomias para control de daños. Es ingresada a la Unidad de terapia intensiva con apoyo ventilatorio y sin apoyo vasopresor. Se le realiza Angioresonancia evidenciándose, en secuencia s3DI MC, se identifican las arterias cerebrales anteriores, arterias cerebrales medias, arterias comunicantes posteriores, arteria comunicante anterior y el segmento P1, P2 de la arteria cerebral posterior bilateral con diámetros trayectos conservados. Sin embargo, llama la atención la disminución del diámetro de las arterias corticales de las arterias cerebrales posteriores segmento P3 bilateral. Se concluye que el conocimiento del PRES debe ser extenso y de amplia difusión, de modo que todos los actores relacionados con el cuidado de la salud materna identifiquen de forma precoz y oportuna la condición, reducir la morbimortalidad materna y las secuelas neurológicas a largo plazo(AU)

The objective of this trial is to evaluate the posterior reversible encephalopathy syndrome in the postpartum in a 22-yearold patient, with no personal medical history, G (1), C (1), A (0), P (0). Surgical history, segmental cesarean section of 39 weeks of gestation that is referred for presenting a clinical picture 24 hours after segmental cesarean section with abdominal pain, vomiting and abdominal distension, for which she undergoes surgery where re-lapartomies are performed for damage control. She admitted to the intensive care unit with ventilator support and without vasopressor support. Angioresonance performed, showing, in s3DI MC sequence, the anterior cerebral arteries, middle cerebral arteries, posterior communicating arteries, anterior communicating artery and segment P1, P2 of the bilateral posterior cerebral artery with preserved trajectory diameters identified. However, the reduction in the diameter of the cortical arteries of the bilateral posterior cerebral arteries segment P3 is striking. It concluded that the knowledge of PRES should be extensive and widely disseminated, so that all actors related to maternal health care identify the condition early and in a timely manner, reduce maternal morbidity and mortality and longterm neurological sequelae(AU)

Prognostic Accuracy of Fetal MRI in Predicting Postnatal Neurodevelopmental Outcome.

BACKGROUND AND PURPOSE: The superior diagnostic accuracy of fetal MR imaging in detecting fetal brain abnormalities has been previously demonstrated; however, the ability of fetal MR imaging to prognosticate postnatal outcome is not well-studied. We performed a retrospective analysis to determine the prognostic accuracy of fetal MR imaging in predicting postnatal neurodevelopmental outcome. MATERIALS AND METHODS: We identified all fetal MR imaging performed at the Children's Hospital of Eastern Ontario during a 10-year period and assessed agreement between prenatal prognosis and postnatal outcome. Prenatal prognosis was determined by a pediatric neurologist who reviewed the fetal MR imaging report and categorized each pregnancy as having a favorable, indeterminate, or poor prognosis. Assessment of postnatal neurodevelopmental outcome was made solely on the basis of the child's Gross Motor Function Classification System score and whether the child developed epilepsy. Postnatal outcome was categorized as favorable, intermediate, or poor. We also assessed the diagnostic accuracy of fetal MR imaging by comparing prenatal and postnatal imaging diagnoses. RESULTS: We reviewed 145 fetal MR images: 114 were included in the assessment of diagnostic accuracy, and 104 were included in the assessment of prognostic accuracy. There was 93.0% agreement between prenatal and postnatal imaging diagnoses. Prognosis was favorable in 44.2%, indeterminate in 50.0%, and poor in 5.8% of pregnancies. There was 93.5% agreement between a favorable prenatal prognosis and a favorable postnatal outcome. CONCLUSIONS: A favorable prenatal prognosis is highly predictive of a favorable postnatal outcome. Further studies are required to better understand the role of fetal MR imaging in prognosticating postnatal development, particularly in pregnancies with indeterminate and poor prognoses.

Neonatal encephalopathy and hypoxic-ischemic encephalopathy.

Acute hypoxic-ischemic encephalopathy around the time of birth remains a major cause of death and life-long disability. The key insight that led to the modern revival of studies of neuroprotection was that, after profound asphyxia, many brain cells show initial recovery from the insult during a short "latent" phase, typically lasting approximately 6h, only to die hours to days later after a "secondary" deterioration characterized by seizures, cytotoxic edema, and progressive failure of cerebral oxidative metabolism. Studies designed around this framework showed that mild hypothermia initiated as early as possible before the onset of secondary deterioration and continued for a sufficient duration to allow the secondary deterioration to resolve is associated with potent, long-lasting neuroprotection. There is now compelling evidence from randomized controlled trials that mild to moderate induced hypothermia significantly improves survival and neurodevelopmental outcomes in infancy and mid-childhood.

Neuroprotection of the preterm brain.

Despite notable advances in the care and survival of preterm infants, a significant proportion of preterm neonates will have life-long cognitive, behavioral, and motor deficits, and robustly effective neuroprotective strategies are still missing. These therapies must target the pathophysiologic mechanisms observed in contemporaneous infants and rely on modern epidemiology, imaging, and experimental models and assessment techniques. Two drugs, magnesium sulfate and caffeine, are already in use in several units, and although their targets are apnea of prematurity and myometrial contractility (respectively), they do offer improved odds of positive outcomes. Nevertheless, these drugs have limited efficacy, and NICU-to-NICU administration varies greatly. As such, there is an obvious need for additional specific neurotherapeutic strategies to further enhance the outcome of this very fragile population of neonates. The chapter reviews these issues, highlights bottlenecks that need to be solved for meaningful progress in the field, and proposes future innovative avenues for intervention, including delayed interventions.

Diagnosis of seizures and encephalopathy using conventional EEG and amplitude integrated EEG.

Seizures are more common in the neonatal period than at any other time of life, partly due to the relative hyperexcitability of the neonatal brain. Brain monitoring of sick neonates in the NICU using either conventional electroencephalography or amplitude integrated EEG is essential to accurately detect seizures. Treatment of seizures is important, as evidence increasingly indicates that seizures damage the brain in addition to that caused by the underlying etiology. Prompt treatment has been shown to reduce seizure burden with the potential to ameliorate seizure-mediated damage. Neonatal encephalopathy most commonly caused by a hypoxia-ischemia results in an alteration of mental status and problems such as seizures, hypotonia, apnea, and feeding difficulties. Confirmation of encephalopathy with EEG monitoring can act as an important adjunct to other investigations and the clinical examination, particularly when considering treatment strategies such as therapeutic hypothermia. Brain monitoring also provides useful early prognostic indicators to clinicians. Recent use of machine learning in algorithms to continuously monitor the neonatal EEG, detect seizures, and grade encephalopathy offers the exciting prospect of real-time decision support in the NICU in the very near future.

Isolated periventricular pseudocysts do not affect white matter microstructure development in neonatal stage: A retrospective case-control diffusion tensor imaging study.

BACKGROUND AND PURPOSE: Periventricular pseudocysts (PVPCs) are cystic cavities originating from the germinal matrix. The effects of PVPCs on the development of white matter (WM) in neonates remain unclear. This study aimed to characterise WM microstructural variations in neonates with PVPCs with and without additional abnormities on MRI. MATERIALS AND METHODS: Neonates with PVPCs and controls with no MRI abnormalities were retrospectively enrolled. Test subjects were divided into groups 1 (isolated PVPCs) and 2 (PVPCs with additional MRI abnormalities). The PVPC MRI features collected included lateralisation, locularity, anatomic location, and the maximum anteroposterior diameter. Diffusion tensor imaging (DTI)-derived fractional anisotropy (FA), radial diffusivity (RD), and axial diffusivity (AD) were compared between the PVPC and control groups using tract-based spatial statistics. RESULTS: Thirty-eight neonates with PVPCs and 60 controls were enrolled. Groups 1 and 2 contained 15 and 23 subjects, respectively. The additional MRI findings in group 2 included intracranial haemorrhage, punctate WM lesions, hypoxic-ischaemic encephalopathy, and acute cerebral infarction. No significant differences were found in PVPC MRI features between the 2 test groups. Compared to controls, no significant changes in DTI metrics were observed in group 1 neonates; whereas extensive WM regions with decreased FA, increased RD, and unchanged/increased AD were found in group 2. CONCLUSIONS: Isolated PVPCs are not independently correlated with WM microstructural variations in neonates. This result provides further evidence for supporting the benign outcome of fetuses with isolated PVPCs.

Neu Laxova syndrome.

NeuLaxova syndrome (NLS) is a rare congenital abnormality involving multiple systems. Until date, only 60 cases of this syndrome have been reported in the literature. A stillborn fetus from a 23-year-old female with bad obstetrics history and consanguinity marriage, presented at 41 weeks gestation and not appreciating fetal movements for the past 3 days. Ultrasound examination revealed the absence of fetal cardiac activity and features of growth retardation. The fetus was sent for pathological examination. At autopsy, fetus had ichthyosis over the scalp and face, depressed nasal bridge, low set ears, microcephaly, slopping forehead, wide interdigital spaces, edema of hands and feet, hypoplastic penis, right leg showed congenital talipes equinovarus and left leg showed rocker bottom foot. On dissection, all organs were in situ. Both lungs were hypoplastic, brain was atrophied, and heart showed right ventricle hypertrophied. A diagnosis of NLS was made. Genetic counseling and early serial ultrasound examination should be performed at high-risk families because of its autosomal recessive mode of inheritance. Early diagnosis of the disease may offer termination of the pregnancy as an option. The prognosis is poor, and the affected newborns are either stillborn or die immediately after birth.

Body Temperature, Heart Rate, and Short-Term Outcome of Cooled Infants.

Therapeutic hypothermia following neonatal encephalopathy is neuroprotective. However, approximately one in two cooled infants still die or develop permanent neurological impairments. Further understanding of variables associated with the effectiveness of cooling is important to improve the therapeutic regimen. To identify clinical factors associated with short-term outcomes of cooled infants, clinical data of 509 cooled infants registered to the Baby Cooling Registry of Japan between 2012 and 2014 were evaluated. Independent variables of death during the initial hospitalization and survival discharge from the cooling hospital at ≤28 days of life were assessed. Death was associated with higher Thompson scores at admission (p < 0.001); higher heart rates after 3-72 hours of cooling (p < 0.001); and higher body temperature after 24 hours of cooling (p = 0.002). Survival discharge was associated with higher 10 minutes Apgar scores (p < 0.001); higher blood pH and base excess (both p < 0.001); lower Thompson scores (at admission and after 24 hours of cooling; both p < 0.001); lower heart rates at initiating cooling (p = 0.003) and after 24 hours of cooling (p < 0.001) and lower average values after 3-72 hours of cooling (p < 0.001); higher body temperature at admission (p < 0.001); and lower body temperature after 24 hours and lower mean values after 3-72 hours of cooling (both p < 0.001). Survival discharge was best explained by higher blood pH (p < 0.05), higher body temperature at admission (p < 0.01), and lower body temperature and heart rate after 24 hours of cooling (p < 0.01 and <0.001, respectively). Lower heart rate, higher body temperature at admission, and lower body temperature during cooling were associated with favorable short-term outcomes.

Multiple subependymal pseudocysts in neonates play a role in later attention deficit hyperactivity and autistic spectrum disorder.

BACKGROUND/PURPOSE: To assess the long-term neurodevelopmental outcome of normal-term neonates who were accidentally found to exhibit subependymal pseudocysts (SEPCs), frontal horn cysts, or choroid plexus cysts through cranial ultrasound (CUS) examination in a neonatal health examination. METHODS: In total, 5569 neonates received CUS examination as an item in a health examination during the first week of birth between 2002 and 2012. Among them, 5147 infants fulfilled the inclusion criteria. The participants were aged between 5 and 15 years at the time when the data were collected. We retrospectively collected these data and interpreted their statistical significance by using one-way analysis of variance, Chi-square test with Yate's correction and odds ratios. RESULTS: The presence of SEPCs was significantly correlated with developmental delay and developmental disability, particularly with attention deficit hyperactivity disorder (ADHD) and autistic spectrum disorder (ASD). The risk of ADHD or ASD was significantly higher in participants with multiple SEPCs, among whom the odds ratios for ADHD and ASD were 6.50 (95% confidence interval [CI] = 2.27-18.64) and 28.54 (95% CI = 5.98-136.36), respectively, higher than those for the total study population. CONCLUSION: Our data revealed multiple SEPCs in normal-term neonates as a risk factor for neurobehavioral outcome, particularly in ADHD and ASD. Simultaneously, the utility of CUS examination as a health examination item for neonates was confirmed.

Dyke-Davidoff-Masson syndrome and chiari type ii malformation / Síndrome de Dyke-Davidoff-Masson e malformação de chiari tipo II

Dyke-Davidoff-Masson Syndrome is a syndrome associated with refractory epilepsy. The Chiari II malformation is a complex congenital malformation of the brain. The authors report a case of a 15 years-old adolescent presenting Dyke-Davidoff-Masson syndrome and Chiari type II malformation association. This case demonstrates an unusual association in neuroimaging tests that indicates the need to evaluate associated diseases, such as myelomeningocele, corpus callosum dysgenesis and syringohydromyelia.

A Síndrome de Dyke-Davidoff-Masson é uma síndrome associada à epilepsia refratária. A malformação de Chiari II é uma malformação congênita complexa do cérebro. Os autores relatam um caso de uma adolescente de 15 anos apresentando a síndrome de Dyke-Davidoff-Masson associada à malformação de Chiari tipo II. Este caso demonstra uma associação incomum nos exames de neuroimagem que indica a necessidade de avaliar doenças associadas, como mielomeningocele, disgenesia do corpo caloso e a siringohidromielia.

Twenty-Five Diagnoses on Midline Images of the Brain: From Fetus to Child to Adult.

Midsagittal images of the brain provide a wealth of anatomic information and may show abnormalities that are pathognomonic for particular diagnoses. Using an anatomy-based approach, the authors identify pertinent anatomic structures to serve as a checklist when evaluating these structures. Subregions evaluated include the corpus callosum, pituitary gland and sellar region, pineal gland and pineal region, brainstem, and cerebellum. The authors present 25 conditions with characteristic identifiable abnormalities at midsagittal imaging. Midsagittal views from multiple imaging modalities are shown, including computed tomography, ultrasonography, and magnetic resonance (MR) imaging. Standard MR imaging sequences are shown, as well as fetal MR and sagittal diffusion-weighted images. To demonstrate these conditions, fetal, neonatal, childhood, adolescent, and young adulthood images are reviewed. The differentiation of normal variants is guided by the understanding of anatomy and pathology. When a specific diagnosis is not possible, the authors present information to evaluate differential considerations and discuss when follow-up imaging may be indicated. The authors hope each case will clarify a pertinent differential diagnosis, appropriately guide patient management, and improve understanding of normal anatomy and identification of pathologic entities. It is in these hopes that the authors have presented a checklist of pertinent anatomy and pathologic entities that can build on existing search patterns. Improved confidence and accuracy in the evaluation of midsagittal images will benefit physicians and patients. ©RSNA, 2018.

Proteomics in the Diagnosis of Inborn Encephalopathies of Unknown Origin: A Myth or Reality.

Synaptopathy underlies a great variety of neurological or neurodevelopmental disorders, including neurodegenerative diseases and the highly complex neuropsychiatric syndromes. Standard diagnostic assays in the majority of synaptopathies are insufficient to make an appropriate and fast diagnosis, which has spurred a search for more accurate diagnostic methods using recent technological advances. As synaptopathy phenotypes strictly depend on genetics and environmental factors, the best way to approach these diseases is the investigation of entire sets of protein characteristics. Thus, proteomics has emerged as a mainstay in the studies on synaptopathies, with mass spectrometry as a technology of choice. This review is an update on the proteomic methods and achievements in the understanding, diagnostics, and novel biomarkers of synaptopathies. The article also provides a critical point of view and future perspectives on the application of neuroproteomics in clinical practice.

Fetal MRI, lower acceptance by women in research vs. clinical setting.

AIM: To determine acceptance of pregnant women to undergo fetal magnetic resonance imaging (MRI) examination in research and clinical setting. METHODS: A prospective study included a research group [part of a study comparing brain ultrasound (US) to MRI in fetuses at risk for acquired brain damage] and a clinical group [fetuses with suspected (brain) anomalies after structural US examination] from 2011 to 2014. All women were advised to use sedatives. MRI declinations, use of sedation, MRI duration and imaging quality were compared between both groups. RESULTS: Study participation was accepted in 57/104 (55%) research cases. Fetal MRI was performed in 34/104 (33%) research and 43/44 (98%) clinical cases. Reasons to decline study participation were MRI related in 41%, and participation was too burdensome in 46%. Acceptance was highest for indication infection and lowest in alloimmune thrombocytopenia and monochorionic twin pregnancy. Sedatives were used in 14/34 research and 43/43 clinical cases. Scan duration and quality were comparable (21 and 20 min in research and clinical cases, respectively, moderate/good quality in both groups). CONCLUSIONS: Pregnant women consider MRI more burdensome than professionals realize. Two-third of women at risk for fetal brain damage decline MRI examination. Future studies should evaluate which information about fetal MRI is supportive.