Erin S. Schwartz

Reversal of Hindbrain Herniation after Maternal-fetal Surgery for Myelomeningocele Subsequently Impacts on Brain Stem Function

The aim of our study was to delineate whether the reversal of hindbrain herniation (HH) following fetal myelomeningocele (fMMC) closure subsequently reduces the incidence and severity of HH-associated brainstem dysfunction (BSD). Prior to the NIH-sponsored Management of Myelomeningocele Study (MOMS) trial, 54 children underwent fMMC closure at our institution. Forty-eight (89%) families participated in a structured survey focusing on HH-associated BSD (e.g., apnea, neurogenic dysphagia [ND], gastro-esophageal reflux disease [GERD], neuro-ophthalmologic disturbances [NOD]). Median age at follow-up was 72 months (range: 46-98). Fifty-percent required shunting. HH-related symptoms were completely absent in 15 (63%) non-shunted and 10 (42%) shunted children (P=0.15). No HH-related death occurred and none developed severe persistent cyanotic apnea. ND was reported in 2 (8%) non-shunted and 9 (38%) shunted infants (P=0.03). Mild GERD (medically managed) developed in 2 (8%) without and 6 (25%) with shunt placement (P=0.24). NOD was found in 6 (25%) and 13 (54%) of non-shunted and shunted children, respectively (P=0.07). The majority of fMMC children developed no or only mild BSD at follow-up. Our data support the hypothesis that neurodevelopmental deficits associated with MMC are at least partially acquired and that reversal of HH following fMMC surgery may help to reduce the incidence and severity of BSD.

Principles and implementation of diffusion-weighted and diffusion tensor imaging

We review the physiological basis of diffusion-weighted imaging and discuss the implementation of diffusion-weighted imaging pulse sequences and the subsequent postprocessing to yield quantitative estimations of diffusion parameters. We also introduce the concept of directionality of “apparent” diffusion in vivo and the means of assessing such anisotropy quantitatively. This in turn leads to the methodological application of diffusion tensor imaging and the subsequent postprocessing, known as tractography. The following articles deal with the clinical applications enabled by such methodologies.

Magnetoencephalography for Pediatric Epilepsy: How We Do It

SUMMARY: Magnetoencephalography (MEG) is increasingly being used in the preoperative evaluation of pediatric patients with epilepsy. The ability to noninvasively localize ictal onset zones (IOZ) and their relationships to eloquent functional cortex allows the pediatric epilepsy team to more accurately assess the likelihood of postoperative seizure freedom, while more precisely prognosticating the potential functional deficits that may be expected from resective surgery. Confirmation of clinically suggested multifocality may result in a recommendation against resective surgery because the probability of seizure freedom will be low. Current paradigms for motor and somatosensory testing are robust. Paradigms allowing localization of those regions necessary for competent language function, though promising, are under continuous optimization. MR imaging white matter trajectory data, created from diffusion tensor imaging obtained in the same setting as the localization brain MR imaging, provide ancillary information regarding connectivity of the IOZ to sites of rapid secondary spread and the spatial relationship of the IOZ to functionally important white matter bundles, such as the corticospinal tracts. A collaborative effort between neuroradiology, neurology, neurosurgery, neuropsychology, technology, and physics ensures successful implementation of MEG within a pediatric epilepsy program.

Thickening and enhancement of multiple cranial nerves in conjunction with cystic white matter lesions in early infantile Krabbe disease

We present serial MR findings in a child ultimately diagnosed with the early infantile form of Krabbe disease. MR showed typical features of Krabbe disease including cerebellar and brainstem hyperintensity, periventricular and deep white matter hyperintensity, and cerebral atrophy. In addition, the combination of both enlargement and enhancement of multiple cranial nerves in conjunction with unusual cystic lesions adjacent to the frontal horns of the lateral ventricles was previously unreported and expands the spectrum of imaging findings in early Krabbe disease.

The Relationship of Seizure Activity and Chronic Epilepsy in Early Infancy and Short-Term Neurodevelopmental Outcome Following Fetal Myelomeningocele Closure

We explored the relationship between seizure activity (SA) and/or chronic epilepsy (CE) and short-term neurodevelopmental outcomes following fetal myelomeningocele (fMMC) surgery. Retrospective databases and a parental questionnaire focusing on common complications of hindbrain herniation associated with MMC were used to determine the incidence of seizures following fMMC surgery. The Bayley Scales of Infant Development II was used to evaluate the neurocognitive outcomes. The available 3-year outcome data were used for analysis. 54 children underwent fMMC closure at our institution between 1998 and 2003. 48 (89%) families participated. The shunt rate was 50% (n=24). Seizures developed in 8/48 (17%) children, 2 (8%) non-shunted and 6 (25%) shunted (P=0.07). Of those six, 3 developed CE. Neurodevelopmental scores in the average range were found in both non-shunted and 3 shunted fMMC children. The remaining 3 shunted toddlers had CE and significant neurodevelopmental delays. Of those, 2 had severe intracranial hemorrhage and one developed frequent apneic spells in combination with epilepsy. The incidence of seizures in fMMC children was similar to previously reported data of postnatally repaired MMC patients. SA alone without CE was not associated with a worse neurocognitive outcome. The occurrence of severe acquired intracranial injury and CE, however, appeared to be correlated with adverse neurocognitive outcome following fMMC surgery.

Diagnostic Features of Myelomeningocele: The Role of Ultrafast Fetal MRI

Fetal magnetic resonance imaging (MRI) is a useful adjunct to ultrasound in the evaluation of neural tube defects. The development of ultrafast imaging techniques has contributed to the increasing clinical use of fetal MRI. This review summarizes the utility, safety and technical aspects of fetal MRI and the role it plays in the evaluation of myelomeningocele. Emphasis is placed on the benefit of fetal MRI as it pertains to presurgical planning and perinatal management.

18-month outcomes of heterologous bilateral hand transplantation in a child: a case report

BACKGROUND Although heterologous vascular composite allotransplantation has become a burgeoning treatment option for adult amputees, there have been no successful cases previously reported in children. Here, we describe the surgical, immunological, and neurorehabilitation details with functional outcomes 18 months after heterologous bilateral hand and forearm transplantation in an 8-year-old child with quadrimembral amputations and a previous kidney transplant. METHODS 2 years of extensive preparation by medical and surgical teams preceded the hand-forearm transplantation of this child. The initial immunosuppressive protocol included thymoglobulin, tacrolimus, prednisone, and mycophenolate mofetil. In July, 2015, our vascularised composite allotransplantation team did the first bilateral hand and forearm transplantation in a child, an 8-year-old boy with previous living-related kidney transplantation. The surgery included four teams working simultaneously on the donor and recipient limbs, aided by customised cutting guides that aimed to reduce ischaemia time. Following an extended length of time in hospital, skin biopsies and close monitoring of renal function and drug concentrations occurred weekly for the first 3 months and were slowly tapered to monthly, and then quarterly. Skin biopsies were also done when tissue rejection was suspected. Paediatric-specific rehabilitation techniques were applied to promote patient engagement during rehabilitation. Progress was assessed by monthly sensory and motor function tests during routine clinic visits and with serial functional brain imaging studies, including structural brain MRI, magnetoencephalography and transcranial magnetic stimulation. FINDINGS The surgery lasted 10 h and 40 min. Vascular revision of the ulnar artery was required a few hours postoperatively. There were no further immediate postsurgical complications. Rejection episodes occurred throughout the first year but were reversed. An increase in serum creatinine led to the addition of sirolimus at 3 months after transplantation with concomitant reduction in tacrolimus targets. Sensibility to light touch was present by 6 months after transplantation. Intrinsic hand muscle innervation was present by 7-10 months after transplantation. At 18 months, the child had exceeded his previous adapted abilities. As of 18 months after transplantation surgery he is able to write and feed, toilet, and dress himself more independently and efficiently than he could do before transplantation. He remains on four immunosuppressive medications and functional neuroimaging studies have shown motor and somatosensory cortical reorganisation. INTERPRETATION Hand transplantation in a child can be surgically, medically, and functionally successful under carefully considered circumstances. Long-term data on the functional trajectory, neurological recovery, psychological sequelae, and the potential late effect of immunosuppression are still needed to support broader implementation of paediatric vascular composite allotransplantation. FUNDING The Childrens Hospital of Philadelphia.

Correlation of Prenatal and Postnatal MRI Findings in Schizencephaly

BACKGROUND AND PURPOSE: Schizencephaly is a rare malformation of the brain characterized by a gray matter–lined defect extending from the pial surface to the lateral ventricles. The purpose of this study was to correlate imaging findings of schizencephaly and associated anomalies on fetal and postnatal MR imaging and assess possible changes that may occur from the prenatal-to-postnatal state. MATERIALS AND METHODS: A retrospective review of subjects with schizencephaly who had both pre- and postnatal MR imaging was performed. Subject age, cleft type, number, location, and features of the defects and associated anomalies were recorded. Normalized dimensions of the defect and ipsilateral ventricle were measured and correlated to changes in the clefts between pre- and postnatal imaging. RESULTS: Ten subjects with 18 clefts (8 bilateral) were included. Most defects (83%) were open on prenatal MR imaging, but 47% of those were found to have subsequently closed on postnatal imaging. Evidence of prior hemorrhage was seen in 83%. Prenatal MR imaging detected all cases of an absent septum pellucidum but detected a fraction of gross polymicrogyria and missed all cases of optic nerve hypoplasia. The normalized ipsilateral ventricular and inner and middle width dimensions of the defects were significantly decreased at postnatal imaging (P < .05). The widths of the defects, ventricular width, and presence of hemorrhage were not predictors of closure of prenatally diagnosed open defects (P > .05). CONCLUSIONS: In our series, nearly half of prenatally open schizencephaly defects had closed on postnatal imaging. Prenatal MR imaging was only able to demonstrate some of the associated anomalies.

Cerebral Diffusion Tensor MR Tractography in Tuberous Sclerosis Complex: Correlation with Neurologic Severity and Tract-Based Spatial Statistical Analysis

BACKGROUND AND PURPOSE: The neurologic significance of residual cerebral white matter tracts, identified on diffusion tensor tractography, has not been well studied in tuberous sclerosis complex. We aimed to correlate the quantity of reconstructed white matter tracts with the degree of neurologic impairment of subjects with the use of DTI and determined differences in white matter integrity between patients with tuberous sclerosis complex and controls with the use of voxelwise analysis. MATERIALS AND METHODS: In this case-control study, 16 patients with tuberous sclerosis complex and 12 control subjects underwent DTI. Major white matter tracts, comprising bilateral PF and CF, were reconstructed and assessed for quantity, represented by NOP and NOF. A neurologic severity score, based on the presence of developmental disability, seizure, autism, and other neuropsychiatric disorders, was calculated for each subject. We then correlated this score with white matter quantity. Voxelwise tract-based spatial statistics was used to determine differences in FA, axial, and radial diffusivity values between the tuberous sclerosis complex group and the control subjects. RESULTS: NOP and NOF of CF, bilateral PF, and MWT in the tuberous sclerosis complex group were all significantly lower than those in the control subjects (P < .05). The neurologic severity score was moderately negatively correlated with NOF and NOP regarding CF (r = −.70; r = −.75), bilateral PF (r = −.66; r = −.68), and MWT (r = −.71; r = −.74). Tract-based spatial statistics revealed that patients with tuberous sclerosis complex showed a widespread reduction (P < .05) in FA and axial diffusivity in most cerebral white matter regions. CONCLUSIONS: Patients with tuberous sclerosis complex with reduced residual white matter were neurologically more severely affected. Tract-based spatial statistics revealed decreased FA and axial diffusivity of the cerebral white matter in the tuberous sclerosis complex group, suggesting reduced axonal integrity.

Atypical Syncope in a Child Due to a Colloid Cyst of the Third Ventricle

A 10-year-old girl presented to an emergency room with acute-onset, brief, repetitive episodes of loss of consciousness. Computed tomography indicated a 0.6 cm colloid cyst of the anterior third ventricle, adjacent to the foramen of Monro. This finding was confirmed by magnetic resonance imaging. The patient underwent transcallosal surgical resection of the cyst without major complications or neurologic sequelae, and remains symptom-free after more than 18 months. Syncope is quite common in children. In contrast, colloid cysts are relatively uncommon in children, with only 100 cases reported in the literature. Colloid cysts are a known cause of sudden death. The possibility of colloid cyst should be considered in the differential diagnosis of syncope that presents in an atypical fashion, and such cases warrant emergent evaluation via neuroimaging.