OBJECTIVEPatients with neurofibromatosis type 1 (NF1) are predisposed to visceral neurofibromas, some of which can progress to premalignant atypical neurofibromas (ANFs) and malignant peripheral nerve sheath tumors (MPNSTs). Though subtotal resection of ANF may prevent malignant transformation and thus deaths with no neural complications, local recurrences require reoperation. The aim of this study was to assess the surgical morbidity associated with marginal resection of targeted ANF nodules identified via preoperative serial volumetric MRI and 18F-FDG-PET imaging.METHODSThe authors analyzed clinical outcomes of 16 NF resections of 21 tumors in 11 NF1 patients treated at the NIH Clinical Center between 2008 and 2018. Preoperative volumetric growth rates and 18F-FDG-PET SUVMax (maximum standardized uptake value within the tumor) of the target lesions and any electromyographic or nerve conduction velocity abnormalities of the parent nerves were measured and assessed in tandem with postoperative complications, histopathological classification of the resected tumors, and surgical margins through Dunnett’s multiple comparisons test and t-test. The surgical approach for safe marginal resection of ANF was also described.RESULTSEleven consecutive NF1 patients (4 male, 7 female; median age 18.5 years) underwent 16 surgical procedures for marginal resections of 21 tumors. Preoperatively, 13 of the 14 (93%) sets of serial MRI studies and 10 of the 11 (91%) 18F-FDG-PET scans showed rapid growth (≥ 20% increase in volume per year) and avidity (SUVMax ≥ 3.5) of the identified tumor, respectively (median tumor size 48.7 cm3; median growth rate 92% per year; median SUVMax 6.45). Most surgeries (n = 14, 88%) resulted in no persistent postoperative parent nerve–related complications, and to date, none of the resected tumors have recurred. The median length of postoperative follow-up has been 2.45 years (range 0.00–10.39 years). Histopathological analysis confirmed significantly greater SUVMax among the ANFs (6.51 ± 0.83, p = 0.0042) and low-grade MPNSTs (13.8, p = 0.0001) than in benign neurofibromas (1.9).CONCLUSIONSThis report evaluates the utility of serial imaging (MRI and 18F-FDG-PET SUVMax) to successfully detect ANF and demonstrates that safe, fascicle-sparing gross-total, extracapsular resection of ANF is possible with the use of intraoperative nerve stimulation and microdissection of nerve fascicles.

NEPVs for cortisol and ACTH predicted nonremission after TSS for CD.

The failure of recent trials of immune therapies in glioblastoma underscores the need to appropriately measure response in the treated tissue. This trial may provide insight on indicators of which patients will respond to immune therapy.

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Background GNE myopathy is a rare genetic disease characterized by progressive muscle atrophy and weakness. It is caused by biallelic mutations in the GNE gene that encodes for the bifunctional enzyme, uridine diphosphate (UDP)‐N‐acetylglucosamine (GlcNAc) 2‐epimerase/N‐acetylmannosamine (ManNAc) kinase. Typical characteristics of GNE myopathy include progressive myopathy, first involving anterior tibialis muscle and sparing the quadriceps, and rimmed vacuoles on muscle biopsy. Identifying biallelic mutations by sequencing of the GNE gene confirms the diagnosis of GNE myopathy. In a subset of patients, diagnostic confirmation is challenged by the identification of mutations in only one allele, suggesting mutations in deep intronic regions or regulatory regions.MethodsWe performed targeted sequencing and copy number variant (CNV) analysis of GNE in two siblings who clinically presented with GNE myopathy. Further molecular and biochemical studies were done to characterize the effect of a previously uncharacterized GNE mutation.ResultsWe report two siblings of Indian descent with characteristic features of GNE myopathy, including progressive skeletal muscle weakness initially involving the anterior tibialis, and rimmed vacuoles on muscle biopsy, in which a heterozygous mutation, p.Val727Met, was identified in both affected siblings, but no other deleterious variants in either coding region or exon–intron boundaries of the gene. Subsequent insertion/deletion analysis identified a novel 11.3‐kb deletion (Chr9 [GRCh37]: g.36257583_36268910del) encompassing the GNE promoter region, with breakpoints residing in Alu repeats. Gene expression analysis revealed reduced GNE mRNA and protein levels, confirming decreased expression of the deleted allele harboring the deletion.ConclusionsWe have identified GNE as one of the genes susceptible to Alu‐mediated recombination. Our findings suggest that the deletion may encompass the promoter or another region necessary for GNE expression. In patients with typical manifestations of GNE myopathy and a single GNE variant identified, copy number variant (CNV) analysis may be useful in arriving at the diagnosis.

Low-pressure hydrocephalus (LPH) is a rare clinical diagnosis, characterized by neurologic decline and ventriculomegaly that persists despite normal to low intracranial pressure. LPH is typically managed by negative-pressure drainage via ventriculostomy, followed by low-resistance shunt insertion. We present the case of a middle-aged man with a history of hemangioblastomatosis who had spontaneous subarachnoid hemorrhage. He was treated with a ventriculoperitoneal shunt and then underwent resection of a Meckel's cave hemangioblastoma and whole brain irradiation. One month later, he presented to us with worsening symptoms and hydrocephalus despite shunt interrogations and revisions revealing no malfunction. Ventriculostomy drainage at negative-pressure was required for resolution of symptoms and ventriculomegaly, leading us to a diagnosis of LPH. This was successfully treated using an improvised ultra-low pressure valveless ventriculoperitoneal shunt, with maintained resolution of LPH for over one year. The system was created by ligating the distal slit valve end of a peritoneal catheter to prevent reflux and allow sub-zero pressure drainage by siphoning.

Structured Abstract Context Early prediction of hypothalamic-pituitary-adrenal (HPA) axis function following transsphenoidal surgery (TSS) can improve patient safety and reduce costs. Objective Systematic measurement of adrenocorticotropin (ACTH) and cortisol at extubation following anesthesia to predict remission from Cushing’s disease (CD), and HPA axis preservation following non-CD surgery. Design Retrospective analysis of clinical data between August 2015 and May 2022. Setting Referral center. Patients Consecutive patients (n = 129) undergoing TSS who had peri-operative ACTH and cortisol measurements. Interventions ACTH and cortisol measurement at extubation. Further serial 6-hourly measurements in CD patients. Main outcome measures Prediction of future HPA axis status based on ACTH/cortisol at extubation. Results ACTH and cortisol increased sharply in all patients at extubation. CD patients (n=101) had lower ACTH values than non-CD patients (110.1 vs 293.1 pg/mL; P <0.01). In non-CD patients, lower plasma ACTH at extubation predicted the need for eventual corticosteroid replacement (105.8 vs. 449.1 pg/mL, P < 0.01). In CD patients, the peak post-extubation cortisol at 6 hours was a robust predictor for non-remission (60.7 vs. 219.2 µg/dL, p = 0.03). However, normalized early post-operative value (NEPV, the post-extubation values minus the peak preoperative CRH or DDAVP test values) of cortisol reliably distinguished non-remission earlier, at the time of extubation (-6.1 versus 5.9, P = 0.01) and later. Conclusions We found that at extubation following TSS, ACTH can predict the need for eventual steroid replacement in non-Cushing’s patients. In patients with CD, we found a robust prediction of non-remission with NEPV cortisol at extubation and later.

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