Helmet Therapy for the Management of Deformational Plagiocephaly in Pediatric Patients with Shunted Hydrocephalus.

OBJECTIVE: To evaluate the safety and efficacy of helmet therapy for deformational plagiocephaly in patients with shunted hydrocephalus. DESIGN: Retrospective chart review. SETTING: Institutional, tertiary-care hospital. PATIENTS: All patients at St. Louis Children's Hospital between 2014 and 2021 with shunted hydrocephalus who underwent helmet therapy for deformational plagiocephaly. INTERVENTIONS: Helmet therapy. MAIN OUTCOME MEASURES: Cranial vault asymmetry (CVA), cranial vault asymmetry index (CVAI), and cephalic index (CI) were measured before and after completion of helmet therapy. RESULTS: There were 37 patients with shunted hydrocephalus and documented deformational plagiocephaly. Twelve were managed with helmet therapy. Average age at helmeting initiation and time between shunt placement and helmeting initiation was 5.8 and 4.6 months, respectively. Average CVA, CVAI, and CI at helmeting initiation and termination was 11.6, 7.98, and 85.2, and 6.95, 4.49, and 83.7, respectively. Average duration of helmeting was 3.7 months. CVA and CVAI were significantly lower after helmeting (P = .0028 and .0021) and 11/12 patients had overall improvement in plagiocephaly. CONCLUSIONS: Helmet therapy appears to be a safe and efficacious management strategy for deformational plagiocephaly in patients with shunted hydrocephalus. Despite the occasional need for additional fittings and surveillance beyond the normal schedule, in all cases appropriately fitting helmets were achieved and no major adverse events occurred. This cohort represents a proof of principle for the safety and efficacy of helmet therapy in patients with shunted hydrocephalus. Further work in larger prospective cohorts is needed to confirm these initial findings.

Responsive Neurostimulation for People With Drug-Resistant Epilepsy and Autism Spectrum Disorder.

PURPOSE: Individuals with autism spectrum disorder (ASD) have comorbid epilepsy at much higher rates than the general population, and about 30% will be refractory to medication. Patients with drug-resistant epilepsy (DRE) should be referred for surgical evaluation, yet many with ASD and DRE are not resective surgical candidates. The aim of this study was to examine the response of this population to the responsive neurostimulator (RNS) System. METHODS: This multicenter study evaluated patients with ASD and DRE who underwent RNS System placement. Patients were included if they had the RNS System placed for 1 year or more. Seizure reduction and behavioral outcomes were reported. Descriptive statistics were used for analysis. RESULTS: Nineteen patients with ASD and DRE had the RNS System placed at 5 centers. Patients were between the ages of 11 and 29 (median 20) years. Fourteen patients were male, whereas five were female. The device was implanted from 1 to 5 years. Sixty-three percent of all patients experienced a >50% seizure reduction, with 21% of those patients being classified as super responders (seizure reduction >90%). For the super responders, two of the four patients had the device implanted for >2 years. The response rate was 70% for those in whom the device was implanted for >2 years. Improvements in behaviors as measured by the Clinical Global Impression Scale-Improvement scale were noted in 79%. No complications from the surgery were reported. CONCLUSIONS: Based on the authors' experience in this small cohort of patients, the RNS System seems to be a promising surgical option in people with ASD-DRE.

Decreased but diverse activity of cortical and thalamic neurons in consciousness-impairing rodent absence seizures.

Absence seizures are brief episodes of impaired consciousness, behavioral arrest, and unresponsiveness, with yet-unknown neuronal mechanisms. Here we report that an awake female rat model recapitulates the behavioral, electroencephalographic, and cortical functional magnetic resonance imaging characteristics of human absence seizures. Neuronally, seizures feature overall decreased but rhythmic firing of neurons in cortex and thalamus. Individual cortical and thalamic neurons express one of four distinct patterns of seizure-associated activity, one of which causes a transient initial peak in overall firing at seizure onset, and another which drives sustained decreases in overall firing. 40-60 s before seizure onset there begins a decline in low frequency electroencephalographic activity, neuronal firing, and behavior, but an increase in higher frequency electroencephalography and rhythmicity of neuronal firing. Our findings demonstrate that prolonged brain state changes precede consciousness-impairing seizures, and that during seizures distinct functional groups of cortical and thalamic neurons produce an overall transient firing increase followed by a sustained firing decrease, and increased rhythmicity.

Preoperative functional connectivity by magnetic resonance imaging for refractory neocortical epilepsy.

Objective: Patients with refractory epilepsy experience extensive and invasive clinical testing for seizure onset zones treatable by surgical resection. However, surgical resection can fail to provide therapeutic benefit, and patients with neocortical epilepsy have the poorest therapeutic outcomes. This case series studied patients with neocortical epilepsy who were referred for surgical treatment. Prior to surgery, patients volunteered for resting-state functional magnetic resonance imaging (rs-fMRI) in addition to imaging for the clinical standard of care. This work examined the variability of functional connectivity in patients, estimated from rs-fMRI, for associations with surgical outcomes. Methods: This work examined pre-operative structural imaging, pre-operative rs-fMRI, and post-operative structural imaging from seven epilepsy patients. Review of the clinical record provided Engel classifications for surgical outcomes. A novel method assessed pre-operative rs-fMRI from patients using comparative rs-fMRI from a large cohort of healthy control subjects and estimated Gibbs distributions for functional connectivity in patients compared to healthy controls. Results: Three patients had Engel classification Ia, one patient had Engel classification IIa, and three patients had Engel classification IV. Metrics for variability of functional connectivity, including absolute differences of the functional connectivity of each patient from healthy control averages and probabilistic scores for absolute differences, were higher for patients classified as Engel IV, for whom epilepsy surgery provided no meaningful improvement. Significance: This work continues on-going efforts to use rs-fMRI to characterize abnormal functional connectivity in the brain. Preliminary evidence indicates that the topography of variant functional connectivity in epilepsy patients may be clinically relevant for identifying patients unlikely to have favorable outcomes after epilepsy surgery. Widespread topographic variations of functional connectivity also support the hypothesis that epilepsy is a disease of brain resting-state networks.

Characterization of Ag-Ion Releasing Zeolite Filled 3D Printed Resins.

There has been profound growth in the use of 3D printed materials in dentistry in general, including orthodontics. The opportunity to impart antimicrobial properties to 3D printed parts from existing resins requires the capability of forming a stable colloid incorporating antimicrobial fillers. The objective of this research was to characterize a colloid consisting of a 3D printable resin mixed with Ag-ion releasing zeolites and fumed silica to create 3D printed parts with antiviral properties. The final composite was tested for antiviral properties against SARS-CoV-2 and HIV-1. Antiviral activity was measured in terms of the half-life of SARS-CoV-2 and HIV-1 on the composite surface. The inclusion of the zeolite did not interfere with the kinetics measured on the surface of the ATR crystal. While the depth of cure, measured following ISO4049 guidelines, was reduced from 3.8 mm to 1.4 mm in 5 s, this greatly exceeded the resolution required for 3D printing. The colloid was stable for at least 6 months and the rheological behavior was dependent upon the fumed silica loading. The inclusion of zeolites and fumed silica significantly increased the flexural strength of the composite as measured by a 3 point bend test. The composite released approximately 2500 µg/L of silver ion per gram of composite as determined by potentiometry. There was a significant reduction of the average half-life of SARS-CoV-2 (1.9 fold) and HIV-1 (2.7 fold) on the surface of the composite. The inclusion of Ag-ion releasing zeolites into 3D-printable resin can result in stable colloids that generate composites with improved mechanical properties and antiviral properties.

Brain-Responsive Neurostimulation for the treatment of adults with epilepsy in tuberous sclerosis complex: A case series.

OBJECTIVE: Tuberous sclerosis complex (TSC) is a genetic disorder primarily characterized by the development of multisystem benign tumors. Epilepsy is the most common neurologic manifestation, affecting 80%-90% of TSC patients. The diffuse structural brain abnormalities and the multifocal nature of epilepsy in TSC pose diagnostic challenges when evaluating patients for epilepsy surgery. METHODS: We retrospectively reviewed the safety experience and efficacy outcomes of five adult TSC patients who were treated with direct brain-responsive neurostimulation (RNS System, NeuroPace, Inc). RESULTS: The average follow-up duration was 20 months. All five patients were responders (≥50% disabling seizure reduction) at last follow-up. The median reduction in disabling seizures was 58% at 1 year and 88% at last follow-up. Three of the five patients experienced some period of seizure freedom ranging from 3 months to over 1 year. SIGNIFICANCE: In this small case series, we report the first safety experience and efficacy outcomes in patients with TSC-associated drug-resistant focal epilepsy treated with direct brain-responsive neurostimulation.

Real-world experience with direct brain-responsive neurostimulation for focal onset seizures.

OBJECTIVE: The RNS System is a direct brain-responsive neurostimulation system that is US Food and Drug Administration-approved for adults with medically intractable focal onset seizures based on safety and effectiveness data from controlled clinical trials. The purpose of this study was to retrospectively evaluate the real-world safety and effectiveness of the RNS System. METHODS: Eight comprehensive epilepsy centers conducted a chart review of patients treated with the RNS System for at least 1 year, in accordance with the indication for use. Data included device-related serious adverse events and the median percent change in disabling seizure frequency from baseline at years 1, 2, and 3 of treatment and at the most recent follow-up. RESULTS: One hundred fifty patients met the criteria for analysis. The median reduction in seizures was 67% (interquartile range [IQR] = 33%-93%, n = 149) at 1 year, 75% (IQR = 50%-94%, n = 93) at 2 years, 82% (IQR = 50%-96%, n = 38) at ≥3 years, and 74% (IQR = 50%-96%, n = 150) at last follow-up (mean = 2.3 years). Thirty-five percent of patients had a ≥90% seizure frequency reduction, and 18% of patients reported being clinically seizure-free at last follow-up. Seizure frequency reductions were similar regardless of patient age, age at epilepsy onset, duration of epilepsy, seizure onset in mesial temporal or neocortical foci, magnetic resonance imaging findings, prior intracranial monitoring, prior epilepsy surgery, or prior vagus nerve stimulation treatment. The infection rate per procedure was 2.9% (6/150 patients); five of the six patients had an implant site infection, and one had osteomyelitis. Lead revisions were required in 2.7% (4/150), and 2.0% (3/150) of patients had a subdural hemorrhage, none of which had long-lasting neurological consequences. SIGNIFICANCE: In this real-world experience, safety was similar and clinical seizure outcomes exceeded those of the prospective clinical trials, corroborating effectiveness of this therapy and suggesting that clinical experience has informed more effective programming.

Association of Serum Phosphate Levels and Anemia in Critically Ill Surgical Patients.

BACKGROUND: Deranged serum phosphate (Phos) levels are associated with anemia in hospitalized patients, but their relevance to critical illness is unclear. Therefore, our goal was to investigate whether abnormal Phos on admission to the surgical intensive care unit (ICU) is associated with anemia. MATERIALS AND METHODS: We performed a retrospective analysis of data from an ongoing study of nutrition in critical illness. Serum Phos and hemoglobin levels were obtained at ICU admission. Normal Phos was defined as 2.5-4.0 mg/dL. To investigate the association between Phos and anemia, we performed logistic regression analyses, while controlling for age, sex, race, body mass index, Nutrition Risk Screening score, Deyo-Charlson Comorbidity Index, creatinine, mean corpuscular volume, and serum albumin. RESULTS: In total, 510 patients comprised the analytic cohort; 62% were anemic, 30% had Phos >4.0 mg/dL, and 14% had levels <2.5 mg/dL. Logistic regression analysis demonstrated each unit increment in Phos was associated with a 25% higher likelihood of anemia (odds ratio [OR], 1.25; 95% confidence interval [CI], 1.04-1.50). Moreover, patients with Phos >4.0 mg/dL had a 68% higher likelihood of anemia compared with those with normal levels (OR, 1.68; 95% CI, 1.02-2.80). Patients with Phos <2.5 mg/dL were not more likely to be anemic compared with those with normal levels. CONCLUSION: Surgical ICU patients with admission Phos >4.0 mg/dL are more likely to be anemic compared with those with normal levels. Our findings support the need for studies to determine whether globally maintaining optimal Phos reduces the likelihood of anemia and whether ideal Phos during acute care hospitalization influences clinical outcomes.

Hypophosphatemia in Enterally Fed Patients in the Surgical Intensive Care Unit.

INTRODUCTION: Hypophosphatemia has been associated with refeeding malnourished patients, but its clinical significance is unclear. We investigated the incidence of refeeding hypophosphatemia (RH) in the surgical intensive care unit (SICU) and its association with early enteral nutrition (EN) administration and clinical outcomes. METHODS: We performed a retrospective review of a 2-year database of patients receiving EN in the SICU. RH was defined as a post-EN phosphorus (PHOS) level decrement of >0.5 mg/dL to a nadir <2.0 mg/dL within 8 days from EN initiation. We investigated the risk factors for RH and examined its association with clinical outcomes using multivariable regression analyses. RESULTS: In total, 213 patients comprised our analytic cohort. Eighty-three of 213 (39%) individuals experienced RH and 43 of 130 (33%) of the remaining patients experienced non-RH hypophosphatemia (nadir PHOS level <2.0 mg/dL). Overall, there was a total 59% incidence of hypophosphatemia of any cause (N = 126). Nutrition parameters did not differ between groups; most patients were initiated on EN within 48 hours of SICU admission, and timing of EN initiation was not a significant predictor for the development of RH. The median hospital length of stay (LOS) was 21 and 24 days for those with and without RH, respectively ( P = .79); RH remained a nonsignificant predictor for hospital LOS in the multivariable analysis. CONCLUSIONS: RH is common in the SICU but is not related to timing or amount of EN. Hypophosphatemia is also common in the critically ill, but regardless of etiology, it was not found to be a predictor of worse clinical outcomes.

Hypophosphatemia in Enterally Fed Patients in the Surgical Intensive Care Unit: Common but Unrelated to Timing of Initiation or Aggressiveness of Nutrition Delivery.

INTRODUCTION: Hypophosphatemia has been associated with refeeding malnourished patients, but its clinical significance is unclear. We investigated the incidence of refeeding hypophosphatemia (RH) in the surgical intensive care unit (SICU) and its association with early enteral nutrition (EN) administration and clinical outcomes. METHODS: We performed a retrospective review of a 2-year database of patients receiving EN in the SICU. RH was defined as a post-EN phosphorus (PHOS) level decrement of >0.5 mg/dL to a nadir <2.0 mg/dL within 8 days from EN initiation. We investigated the risk factors for RH and examined its association with clinical outcomes using multivariable regression analyses. RESULTS: In total, 213 patients comprised our analytic cohort. Eighty-three of 213 (39%) individuals experienced RH and 43 of 130 (33%) of the remaining patients experienced non-RH hypophosphatemia (nadir PHOS level <2.0 mg/dL). Overall, there was a total 59% incidence of hypophosphatemia of any cause (N = 126). Nutrition parameters did not differ between groups; most patients were initiated on EN within 48 hours of SICU admission, and timing of EN initiation was not a significant predictor for the development of RH. The median hospital length of stay (LOS) was 21 and 24 days for those with and without RH, respectively (P = .79); RH remained a nonsignificant predictor for hospital LOS in the multivariable analysis. CONCLUSIONS: RH is common in the SICU but is not related to timing or amount of EN. Hypophosphatemia is also common in the critically ill, but regardless of etiology, it was not found to be a predictor of worse clinical outcomes.

Fat metabolism and acute resistance exercise in trained men.

The purpose of this study was to investigate the effect of acute resistance exercise (RE) on lipolysis within adipose tissue and subsequent substrate oxidation to better understand how RE may contribute to improvements in body composition. Lipolysis and blood flow were measured in abdominal subcutaneous adipose tissue via microdialysis before, during, and for 5 h following whole body RE as well as on a nonexercise control day (C) in eight young (24 +/- 0.7 yr), active (>3 RE session/wk for at least 2 yr) male participants. Fat oxidation was measured immediately before and after RE via indirect calorimetry for 45 min. Dialysate glycerol concentration (an index of lipolysis) was higher during (RE: 200.4 +/- 38.6 vs. C: 112.4 +/- 13.1 micromol/l, 78% difference; P = 0.02) and immediately following RE (RE: 184 +/- 41 vs. C: 105 + 14.6 micromol/l, 75% difference; P = 0.03) compared with the same time period on the C day. Energy expenditure was elevated in the 45 min after RE compared with the same time period on the C day (RE: 104.4 +/- 6.0 vs. C: 94.5 +/- 4.0 kcal/h, 10.5% difference; P = 0.03). Respiratory exchange ratio was lower (RE: 0.71 +/- 0.004 vs. C: 0.85 +/- .03, 16.5% difference; P = 0.004) and fat oxidation was higher (RE: 10.2 +/- 0.8 vs. C: 5.0 +/- 1.0 g/h, 105% difference; P = 0.004) following RE compared with the same time period on the C day. Therefore, the mechanism behind RE contributing to improved body composition is in part due to enhanced abdominal subcutaneous adipose tissue lipolysis and improved whole body fat oxidation and energy expenditure in response to RE.

Gene discovery in the apicomplexa as revealed by EST sequencing and assembly of a comparative gene database.

Large-scale EST sequencing projects for several important parasites within the phylum Apicomplexa were undertaken for the purpose of gene discovery. Included were several parasites of medical importance (Plasmodium falciparum, Toxoplasma gondii) and others of veterinary importance (Eimeria tenella, Sarcocystis neurona, and Neospora caninum). A total of 55192 ESTs, deposited into dbEST/GenBank, were included in the analyses. The resulting sequences have been clustered into nonredundant gene assemblies and deposited into a relational database that supports a variety of sequence and text searches. This database has been used to compare the gene assemblies using BLAST similarity comparisons to the public protein databases to identify putative genes. Of these new entries, approximately 15%-20% represent putative homologs with a conservative cutoff of p < 10(-9), thus identifying many conserved genes that are likely to share common functions with other well-studied organisms. Gene assemblies were also used to identify strain polymorphisms, examine stage-specific expression, and identify gene families. An interesting class of genes that are confined to members of this phylum and not shared by plants, animals, or fungi, was identified. These genes likely mediate the novel biological features of members of the Apicomplexa and hence offer great potential for biological investigation and as possible therapeutic targets.