Carpentieri, David

Neurodevelopmental disorders are associated with metabolic pathway imbalances; however, most metabolic measurements are made peripherally, leaving central metabolic disturbances under-investigated. Cerebrospinal fluid obtained intraoperatively from children with autism spectrum disorder (ASD, n = 34), developmental delays (DD, n = 20), and those without known DD/ASD (n = 34) was analyzed using large-scale targeted mass spectrometry. Eighteen also had epilepsy (EPI). Metabolites significantly related to ASD, DD and EPI were identified by linear models and entered into metabolite–metabolite network pathway analysis. Common disrupted pathways were analyzed for each group of interest. Central metabolites most involved in metabolic pathways were L-cysteine, adenine, and dodecanoic acid for ASD; nicotinamide adenine dinucleotide phosphate, L-aspartic acid, and glycine for EPI; and adenosine triphosphate, L-glutamine, ornithine, L-arginine, L-lysine, citrulline, and L-homoserine for DD. Amino acid and energy metabolism pathways were most disrupted in all disorders, but the source of the disruption was different for each disorder. Disruption in vitamin and one-carbon metabolism was associated with DD and EPI, lipid pathway disruption was associated with EPI and redox metabolism disruption was related to ASD. Two microbiome metabolites were also detected in the CSF: shikimic and cis-cis-muconic acid. Overall, this study provides increased insight into unique metabolic disruptions in distinct but overlapping neurodevelopmental disorders.

Millions of patients seek medical attention for diarrhea, vomiting, nausea, and abdominal pain. In the current environment, it is important to recognize that these symptoms may be the only manifestation or may precede more serious systemic complications of COVID-19. Herein, we describe the first case of ischemic colitis (IC) in a young adult who presented with diarrhea and highlight the laboratory pitfalls for patients with COVID-19 presenting with gastrointestinal (GI) symptoms.

Dry blood spots (DBS) offer many advantages over other blood banking protocols due to the reduction of time and equipment needed for collection and the ease of processing, storage, and shipment. In addition, the sample size makes it a very attractive method when considering the banking of small pediatric samples. On that note, the Centers for Disease Control and Prevention (CDC) preanalytical standards for DBS are commonly used in the worldwide mass spectrometry-based inborn errors of metabolism screening programs. However, these guidelines may not apply for analytes and protocols not included in these programs. In fact, the availability of leftover samples and the ongoing interest in protocols outside this scenario are providing us with new DBS biobanking insights. Herein, we review the literature for indicators that should be considered in the design of prospective fit for purpose DBS biobanks, especially for those focused mostly on pediatric and OMIC platforms.

Objective: To present an unusual case of a temporal bone meningioma with intrafascicular spread throughout the temporal facial nerve from cerebellopontine angle (CPA) to stylomastoid foramen. Patient: Four-year-old female with progressive facial weakness and normal hearing. Main Outcome Measure: Clinical, radiological, and histopathological findings of temporal bone meningiomas. Results: A patient presented with progressive facial weakness and normal hearing. Imaging demonstrated a mass within the left internal auditory canal radiologically consistent with a schwannoma. Asymmetric enlargement with enhancement of the left facial nerve from CPA to the stylomastoid foramen suggested facial schwannoma. At surgery, gross tumor was noted in the internal auditory canal, the fallopian canal seemed expanded and the facial nerve was enlarged and had an irregular contour. Resection of the facial nerve from the CPA to just proximal to its exit at the stylomastoid foramen was necessary to achieve negative margins. Cable grafting was performed. The histopathologic diagnosis was transitional meningioma with intraneural growth throughout the length of the resected facial nerve segment. Conclusion: Meningiomas involving the temporal bone are exceedingly rare. We report a rare case of a child presenting with progressive facial weakness due to a presumed facial schwannoma spreading along the facial nerve throughout its intratemporal course that at surgery was found to be an intrafascicular CN VII meningioma.

AbstractWe report the case of a 2.5‐year‐old girl with linear morphea initially diagnosed as an acquired port‐wine stain (PWS). She underwent three treatments to the right face using the pulsed dye laser (PDL) before sclerotic changes were observed and the correct diagnosis was confirmed with histopathology. Treatment using the PDL reduced the skin erythema but did not prevent subsequent sclerosis. The sclerosis became most prominent superior to the patient's right ear in an area not treated using the laser. A review of the English‐language medical literature identified no cases of morphea triggered using a PDL, but there were several reports of early morphea misdiagnosed as an acquired PWS. Briefly, we review those cases, as well as morphea subtypes, and comment on how the pathophysiology of morphea may lend itself to an early underrecognized inflammatory presentation, delaying diagnosis.

Abstract Malignant gliomas are the most common primary brain tumors. Despite intensive clinical investigation and significant technical advances in surgical and radiation treatment, the impact on clinical outcome for patients with malignant gliomas is disappointing. We have previously shown that tumor necrosis factor–like weak inducer of apoptosis (TWEAK), a member of the tumor necrosis factor superfamily, can stimulate glioma cell survival via binding to the Fn14 receptor, activation of the NF-κB pathway, and upregulation of BCL-XL gene expression. Here, we show that TWEAK treatment of glioma cells leads to phosphorylation of Akt and BAD. TWEAK stimulation results in the phosphorylation of both Akt1 and Akt2. However, small interfering RNA (siRNA)–mediated depletion of either Akt1 or Akt2 showed that BAD serine 136 phosphorylation is dependent specifically on Akt2 function. Depletion of Akt2 expression by siRNA also abrogates TWEAK-stimulated glioma cell survival, whereas no effect on glioma cell survival was observed after siRNA-mediated depletion of Akt1 expression. Surprisingly, although siRNA-mediated depletion of BAD in glioma cells abrogates cytotoxic- and chemotherapy-induced apoptosis, TWEAK still displays a strong protective effect, suggesting that BAD serine 136 phosphorylation plays a minor role in TWEAK-Akt2–induced glioma cell survival. We also report here that AKT2 gene expression levels increased with glioma grade and inversely correlate with patient survival. Additionally, immunohistochemical analysis showed that Akt2 expression positively correlates with Fn14 expression in glioblastoma multiforme specimens. We hypothesize that the TWEAK-Fn14 signaling axis functions, in part, to enhance glioblastoma cell survival by activation of the Akt2 serine/threonine protein kinase. (Mol Cancer Res 2009;7(11):1871–81)