Assessment of Ventricular Size and Neurocognitive Outcomes in Children with Postnatal Closure of Myelomeningocele.

OBJECTIVE: To assess if ventricular size before shunting is correlated with neurodevelopmental outcomes in children with postnatal myelomeningocele closure. STUDY DESIGN: This retrospective review included children with postnatal surgical closure of myelomeningocele and neuropsychological testing between 2018 and 2023 at the University of California, San Francisco. Frontal-occipital horn ratio (FOHR) was measured immediately before shunt placement or on the first study that reported ventricular stability for nonshunted patients. The primary outcome was full scale IQ (FSIQ) on the Weschler Intelligence Scale. Secondary outcomes included indices of the Weschler scale, the Global Executive Composite from the Behavior Rating Inventory of Executive Function, and the general adaptive composite from the Adaptive Behavior Assessment Scale. Univariable and multivariable regression was used to determine if FOHR was correlated with neuropsychological scores. RESULTS: Forty patients met the inclusion criteria; 26 (65%) had shunted hydrocephalus. Age at neuropsychological testing was 10.9 ± 0.6 years. FOHR was greater in the shunted group (0.64 vs 0.51; P < .001). There were no differences in neuropsychological results between shunted and nonshunted groups. On univariable analysis, greater FOHR was associated with lower FSIQ (P = .025) and lower Visual Spatial Index scores (P = .013), which remained significant on multivariable analysis after adjusting for gestational age at birth, lesion level, shunt status, and shunt revision status (P = .049 and P = .006, respectively). Separate analyses by shunt status revealed that these effects were driven by the shunted group. CONCLUSIONS: Greater FOHR before shunting was correlated with lower FSIQ and the Visual Spatial Index scores on the Weschler Intelligence Scales. Larger studies are needed to explore further the relationship between ventricle size, hydrocephalus, and neurodevelopmental outcomes.

The intersection of cerebral fat embolism syndrome and traumatic brain injury: a literature review and case series.

OBJECTIVE: To review the historical, clinical, radiographic, and outcome characteristics of individuals diagnosed with an acquired brain injury (ABI) due to cerebral fat embolism syndrome (CFES) with and without features of traumatic brain injury (TBI). METHODS: A retrospective chart review of individuals with the diagnosis of CFES admitted to an ABI rehabilitation program. Cases were divided into two cohorts 1) individuals with evidence of classic features of CFES alone, and 2) individuals with evidence of CFES in conjunction with features of TBI. RESULTS: 14 individuals were identified, seven individuals with diagnosis of CFES alone, and seven with CFES and TBI. Median initial GCS was 15 for the isolated CFES cohort and 8 for the dual diagnosis cohort (p =.006). There were clear qualitative differences in MRI findings with characteristic patterns between the two groups. CONCLUSION: The diagnosis of CFES is an important consideration for individuals who have new neurologic impairment following a trauma, especially in cases where initial GCS was high. MRI has an important role in differentiating lesions of CFES from TBI and should be utilized for prognostication and management decisions. Individuals with neurologic injury secondary to CFES had good functional recovery outcomes as measured by Glasgow Outcome Scale.

Mechanisms of neuroprotection by hemopexin: modeling the control of heme and iron homeostasis in brain neurons in inflammatory states.

Hemopexin provides neuroprotection in mouse models of stroke and intracerebral hemorrhage and protects neurons in vitro against heme or reactive oxygen species (ROS) toxicity via heme oxygenase-1 (HO1) activity. To model human brain neurons experiencing hemorrhages and inflammation, we used human neuroblastoma cells, heme-hemopexin complexes, and physiologically relevant ROS, for example, H(2)O(2) and HOCl, to provide novel insights into the underlying mechanism whereby hemopexin safely maintains heme and iron homeostasis. Human amyloid precursor protein (hAPP), needed for iron export from neurons, is induced ~twofold after heme-hemopexin endocytosis by iron from heme catabolism via the iron-regulatory element of hAPP mRNA. Heme-hemopexin is relatively resistant to damage by ROS and retains its ability to induce the cytoprotective HO1 after exposure to tert-butylhydroperoxide, although induction is impaired, but not eliminated, by exposure to high concentrations of H(2)O(2) in vitro. Apo-hemopexin, which predominates in non-hemolytic states, resists damage by H(2)O(2) and HOCl, except for the highest concentrations likely in vivo. Heme-albumin and albumin are preferential targets for ROS; thus, albumin protects hemopexin in biological fluids like CSF and plasma where it is abundant. These observations provide strong evidence that hemopexin will be neuroprotective after traumatic brain injury, with heme release in the CNS, and during the ensuing inflammation. Hemopexin sequesters heme, thus preventing unregulated heme uptake that leads to toxicity; it safely delivers heme to neuronal cells; and it activates the induction of proteins including HO1 and hAPP that keep heme and iron at safe levels in neurons.

Interdisciplinary care of children with diffuse midline glioma.

Diffuse Midline Glioma (DMG) which includes Diffuse Intrinsic Pontine Glioma (DIPG) is an infiltrative tumor of the midline structures of the central nervous system that demonstrates an aggressive pattern of growth and has no known curative treatment. As these tumors progress, children experience ongoing neurological decline including inability to ambulate, swallow and communicate effectively. We propose that optimal care for patients with DMG should involve a specialized team experienced in caring for the multifaceted needs of these patients and their families. Herein we review the roles and evidence to support early involvement of a specialized interdisciplinary team and outline our views on best practices for these challenging tumors.

Botulinum toxin injection, dilution confusion: The impact of toxin diffusion on clinical practice.

Botulinum toxins (BoNT) are a standard of care for spasticity management of children with a variety of neuromuscular (NM) conditions. BoNT relaxes skeletal muscles by inhibiting the release of acetylcholine from the neuromuscular junction (NMJ). As part of their training physiatrist become proficient in the targeted injections of BoNT into affected skeletal musculature. While the pharmacology and pharmacokinetics of BoNT are well characterized, there is limited literature on the clinical impact that varying the volume of diluent that a toxin is reconstituted within. In theory, injection of a larger volume of dilute BoNT would allow for a larger spread affect reaching more distant NMJs; the reverse is also be true. Dilution volume of BoNT injections in children produces some unique situations due to their low weight, smaller muscle bulk, an increased relative risk of spread to surrounding structures, and novel differences in concentration of NMJ in immature muscle. Some of these factors may act as guiding principles that providers can use when adjusting from their standard BoNT dilutional practices. Although, there are recommended dosing strategies available each child's spasticity pattern represents a unique situation and providers must be allowed flexibility to think creatively about dilution strategies for BoNT injections.