Congenital aqueduct stenosis: Progressive brain findings in utero to birth in the presence of severe hydrocephalus.

PURPOSE: To evaluate the effects of progressive hydrocephalus on the developing brain in a cohort of fetuses diagnosed with congenital aqueduct stenosis by comparing prenatal magnetic resonance imaging and postnatal imaging. METHODS: This IRB approved single center retrospective review of prenatally diagnosed children with congenital aqueduct stenosis interrogated changes in the brain between prenatal and postnatal imaging and analyzed statistics using SAS software package version 9.3. RESULTS: Thirty fetuses imaged at a mean gestational age of 26 weeks had aqueduct obstruction confirmed by postnatal imaging. Progressive hydrocephalus required shunting in all but one patient (97%). Those patients with increasing hydrocephalus showed increase in ventricular rupture (60%), loss of septal leaflets (47%), and reduction in white matter and corpus callosum volume (43%). Cerebellar ectopia developed in 27% with 6% meeting the criteria for Chiari I malformation. CONCLUSION: Hydrocephalus in the fetus results in enlarging ventricular rupture, loss of the septum pellucidum leaflets, volume reduction of brain parenchyma including corpus callosum, and risk for Chiari I anomaly. Given advances in fetal surgery and imaging in the last 3 decades, there may be cause to revisit the idea of in utero cerebral spinal fluid diversion as a means to potentially ameliorate progressive loss of the developing brain.

Prenatal aqueduct stenosis: Association with rhombencephalosynapsis and neonatal outcome.

BACKGROUND AND PURPOSE: To examine prenatal MRI and postnatal imaging in fetuses with congenital aqueductal stenosis (CAS) to determine the frequency of association of rhombencephalosynapsis (RES) and how it may affect neonatal intensive care unit (NICU) course. MATERIALS AND METHODS: A single center IRB-approved retrospective study of children with CAS was performed. Prenatal MRI, postnatal images, and clinical data were reviewed. Statistical analysis was performed with SAS statistical software package version 9.3. RESULTS: Aqueduct obstruction was confirmed for all 30 participants. Hydrocephalus required shunting in all but one (97%). Fifteen neonates had CAS with rhomboencephalosynapsis (RES) (50%). Although neonatal course between the two groups was comparable, 53% of CAS with RES neonates required feeding assistance versus 20% in CAS only (P = 0.128). Shunting in the CAS with RES group occurred at average of 6 days of life versus CAS group at 55 days (P = 0.196). Biometry measurements showed a statistically significant decrease in pons antero-posterior diameter in both groups (CAS only P = 0.0049 and CAS with RES P = 0.0003) when compared with norms for gestational age. CONCLUSION: CAS has a high association with RES. Feeding assistance in the NICU and earlier neurosurgical intervention may be required in patients with CAS who also have RES.

Compound Heterozygous Variants of GOSR2 Associated With Congenital Muscular Dystrophy and Progressive Myoclonus Epilepsy: A Case Report.

Objectives: The GOSR2 gene is a Golgi vesicle transport gene that encodes for the Golgi SNAP receptor complex member 2 protein. This protein mediates transport between the medial and trans-Golgi compartments. The homozygous missense variant in the GOSR2 gene, c.430G>T, has been associated with progressive myoclonus epilepsy (PME). There have been reports suggesting that compound heterozygous GOSR2 variants are associated with the congenital muscular dystrophy (CMD) phenotype. Methods: In this article, we report a pediatric case with congenital hypotonia, motor delay, elevated creatine kinase, and abnormal muscle biopsy consistent with CMD who subsequently developed PME. Whole-exome sequencing identified pathogenic compound heterozygous variants in the GOSR2 gene, one of which was the previously described PME-related c.430G>T(p.Gly144Trp), and a novel variant, c.22dup(p.Thr8fs). Result: To our knowledge, this is a novel case of compound heterozygous variants in GOSR2 associated with both CMD and PME phenotypes. Discussion: This case adds to the expanding clinical phenotype of GOSR2-related neurologic diseases.

Coats plus in prematurity.

BACKGROUND: Coats plus syndrome or cerebroretinal microangiopathy with calcifications and cysts (CMCC) is an exceedingly rare autosomal recessive disorder that predominantly affects the microvasculature in the retina, brain, bones, and gastrointestinal system. Unlike Coats disease, CMCC is bilateral and affects multiple organ systems. MATERIALS AND METHODS: Case report. RESULTS: We report the case of two brothers with Coats Plus syndrome who presented with variable phenotypic expression. One sibling (Patient 1) was thought to have atypical retinopathy of prematurity and was only diagnosed with Coats plus after his older brother (Patient 2) presented with a seizure and a left upper extremity tremor at 4 years of age. The CTC1 mutation was confirmed in both patients. Aggressive treatment with laser photocoagulation and intravitreal bevacizumab dramatically improved the retinal vascular and exudative changes. CONCLUSION: Coats Plus syndrome can have a variable phenotypic presentation, including retinal vascular findings. This rare genetic disease should be in the differential diagnosis in patients who present with atypical retinal pathology, including Retinopathy of Prematurity, Familial Exudative Vitreoretinopathy, or Coats disease associated with non-specific multiorgan abnormalities.

Fetal brain MRI findings and neonatal outcome of common diagnosis at a tertiary care center.

Fetal Magnetic Resonance Imaging (MRI) is increasingly used in prenatal evaluations. OBJECTIVE: Identify common brain malformations on fetal MRI and evaluate perinatal course. METHODS: Fetal consultations from 10/2016 to 12/2017 reviewed. RESULTS: Hundred consultations were requested; 94 were completed. Findings included: posterior fossa malformations (19%), agenesis/dysgenesis of corpus callosum (15%), congenital aqueductal stenosis (CAS) (14%), ventriculomegaly (11%), isolated cortical malformations (8.5%), and holoprosencephaly (6%). Posterior fossa malformations were more likely to be associated with genetic conditions and cardiac malformations. Patients with CAS all required intensive care unit admission. Overall, few patients with congenital brain malformations required feeding or respiratory support at discharge. None had seizures as neonates except two with early epileptic encephalopathy syndromes. CONCLUSIONS: Even though long term neurological prognosis is poor for many conditions including high lifetime risk of epilepsy, most are discharged with no feeding or respiratory support. Seizures are rarely seen in the neonatal period.

Acute Management of Symptomatic Subependymal Giant Cell Astrocytoma With Everolimus.

BACKGROUND: Subependymal giant cell astrocytomas (SEGA) are slow-growing tumors, which can cause obstructive hydrocephalus in patients with tuberous sclerosis complex (TSC). These tumors require routine surveillance with magnetic resonance imaging. Current consensus guidelines recommend treatment of asymptomatic SEGAs with an mechanistic target of rapamycin (mTOR) inhibitor because these medications have demonstrated efficacy and safety in multiple prospective clinical trials. For symptomatic SEGAs, standard therapy typically involves surgical resection of the tumor to relieve mass effect and resolve hydrocephalus. However, resection can be associated with significant perioperative morbidity and complications. There are anecdotal reports of using mTOR inhibitors to reduce tumor size in preparation for surgery, but prospective studies comparing sole mTOR inhibitor therapy with surgical management have not been completed. METHODS: Here, we present a seven-year-old boy with a large, symptomatic SEGA which was treated acutely with everolimus. RESULTS: Everolimus treatment resulted in rapid reduction in tumor size, symptomatic improvement, and decrease in cerebrospinal fluid protein. CONCLUSIONS: Everolimus can effectively reduce tumor size, decrease cerebrospinal fluid protein, and allow successful ventriculoperitoneal shunt placement without the need for surgical resection of a symptomatic SEGA.

Individuals with agenesis of the corpus callosum show sensory processing differences as measured by the sensory profile.

OBJECTIVE: Given reports of high pain thresholds and reduced auditory response in individuals with agenesis of the corpus callosum (AgCC), this study investigated whether affected participants report atypical experiences and behaviors on a well-established sensory processing measure. METHODS: Fourteen participants with AgCC (ages 11-59) completed the Adolescent/Adult Sensory Profile (Brown & Dunn, 2001). Sensory profile scales were classified as "Atypical" if they were more than 1 standard deviation from the mean. RESULTS: Fifty-seven percent of participants with AgCC reported reduced sensory registration as compared to an expected 16% of the normative sample. Similarly, 50% of the AgCC participants reported atypically increased auditory processing difficulties. CONCLUSIONS: Using a well-established sensory processing questionnaire, participants with AgCC reported measurable differences in multiple aspects of sensory processing. The most notable difference was in the quadrant of low sensory registration, suggesting that individuals with AgCC may require sensory information to be presented more slowly or at a higher intensity for adequate processing. The sensory modality that was most affected was the auditory system, which is consistent with increased rates of language disorders and autism spectrum disorders in this population. Understanding sensory processing in individuals with AgCC can both elucidate the role of interhemispheric transfer in the development of intact sensory processing as well as contribute to our knowledge of the role of the corpus callosum in a range of disorders in which sensory processes are impacted. (PsycINFO Database Record

Children with autism show reduced somatosensory response: an MEG study.

The neural underpinnings of sensory processing differences in autism remain poorly understood. This prospective magnetoencephalography (MEG) study investigates whether children with autism show atypical cortical activity in the primary somatosensory cortex (S1) in comparison with matched controls. Tactile stimuli were clearly detectable, and painless taps were applied to the distal phalanx of the second (D2) and third (D3) fingers of the right and left hands. Three tactile paradigms were administered: an oddball paradigm (standard taps to D3 at an interstimulus interval (ISI) of 0.33 and deviant taps to D2 with ISI ranging from 1.32 s to 1.64 s); a slow-rate paradigm (D2) with an ISI matching the deviant taps in the oddball paradigm; and a fast-rate paradigm (D2) with an ISI matching the standard taps in the oddball. Study subjects were boys (age 7-11 years) with and without autism disorder. Sensory behavior was quantified using the Sensory Profile questionnaire. Boys with autism exhibited smaller amplitude left hemisphere S1 response to slow and deviant stimuli during the right-hand paradigms. In post-hoc analysis, tactile behavior directly correlated with the amplitude of cortical response. Consequently, the children were re-categorized by degree of parent-report tactile sensitivity. This regrouping created a more robust distinction between the groups with amplitude diminution in the left and right hemispheres and latency prolongation in the right hemisphere in the deviant and slow-rate paradigms for the affected children. This study suggests that children with autism have early differences in somatosensory processing, which likely influence later stages of cortical activity from integration to motor response.