Molecular Evidence for Olfactory Neuroblastoma as a Tumor of Malignant Globose Basal Cells.

Olfactory neuroblastoma (ONB, esthesioneuroblastoma) is a sinonasal cancer with an underdeveloped diagnostic toolkit, and is the subject of many incidents of tumor misclassification throughout the literature. Despite its name, connections between the cancer and normal cells of the olfactory epithelium have not been systematically explored and markers of olfactory epithelial cell types are not deployed in clinical practice. Here, we utilize an integrated human-mouse single-cell atlas of the nasal mucosa, including the olfactory epithelium, to identify transcriptomic programs that link ONB to a specific population of stem/progenitor cells known as olfactory epithelial globose basal cells (GBCs). Expression of a GBC transcription factor NEUROD1 distinguishes both low- and high-grade ONB from sinonasal undifferentiated carcinoma, a potential histologic mimic with a distinctly unfavorable prognosis. Furthermore, we identify a reproducible subpopulation of highly proliferative ONB cells expressing the GBC stemness marker EZH2, suggesting that EZH2 inhibition may play a role in the targeted treatment of ONB. Finally, we study the cellular states comprising ONB parenchyma using single-cell transcriptomics and identify evidence of a conserved GBC transcriptional regulatory circuit that governs divergent neuronal-versus-sustentacular differentiation. These results link ONB to a specific cell type for the first time and identify conserved developmental pathways within ONB that inform diagnostic, prognostic, and mechanistic investigation.

Intravascular fasciitis of the scalp as a complication of ICP monitor placement: a case report and review of the literature.

BACKGROUND/IMPORTANCE: There are only 56 documented cases of intravascular fasciitis, a rare variant of nodular fasciitis. Of these cases, only 2 involved the scalp. This lesion is amenable to surgical resection, making it important to differentiate it from soft tissue malignancies of the scalp. CLINICAL PRESENTATION: We report an unusual case of intravascular fasciitis involving the scalp at the site of an intracranial pressure (ICP) monitor of a 13-year-old male patient. The lesion was surgically excised with no recurrence upon 1-month follow-up. CONCLUSION: Intravascular fasciitis is a benign, reactive proliferation of soft tissue that may arise at sites of prior trauma. It appears as a soft, painless, mobile lesion, and immunohistochemical studies are required to differentiate it from malignant lesions. The standard of care is surgical resection of the lesion.

Fatty filum terminale and low-lying conus medullaris in Gollop-Wolfgang complex: a case report and review of literature.

BACKGROUND/IMPORTANCE: Gollop-Wolfgang complex is a rare skeletal dysplasia with only 200 cases reported in the literature. This disorder is usually associated with several extraosseous anomalies. This report describes the first case of a fatty filum terminale and a low-lying conus medullaris in a patient with this complex. A review of the current literature of the Gollop-Wolfgang complex accompanies this case, highlighting the documented extraosseous anomalies seen in this complex. CLINICAL PRESENTATION: We report a case of an 18-month-old patient with Gollop-Wolfgang complex who underwent cord untethering with release of the filum terminale after extensive workup showed the presence of a dyssynergic bladder and radiological evaluation revealed a fatty filum terminale and low-lying conus medullaris. CONCLUSION: Gollop-Wolfgang complex is a skeletal dysplasia usually associated with several extra skeletal anomalies. Our report describes the first case of a fatty filum terminale and low-lying conus medullaris in this complex, as well as provides an overview of the documented anomalies seen in this disorder. A multidisciplinary approach is recommended when treating these infants in order to ensure that occult manifestations of the complex are not missed.

Effect of cerebrospinal fluid drainage on clinical outcomes following aneurysmal subarachnoid hemorrhage.

OBJECTIVES: We study the relationship between external ventricular drainage (EVD) of cerebrospinal fluid output and functional outcomes in patients with aneurysmal subarachnoid hemorrhage (aSAH). METHODS: A retrospective chart review of patients presenting to a single center with aSAH was performed. The primary outcome was good functional outcomes assessed by a composite of the modified Rankin scale (mRS 0-2) at last follow-up. Secondary outcomes were clinical and radiographic vasospasm. For data analysis, multivariable generalized estimating equations adjusting for potential confounders were used. RESULTS: A total of 119 patients were included; 91 (75.6%) presented with a modified Fisher grade 4 and 76 (63.9%) had hydrocephalus. The median EVD duration was 13 days. On average, most EVDs were set at 15 cmH2O (50, 42%). Follow-up was available in 109 patients; median time was 10.7 months; 69 (63.3%) had good outcomes. Multivariable analysis showed that EVDs set at 10 cmH2O had increased odds of good outcomes for every ml increase in the EVD output (OR = 1.02; 95% CI 1.01-1.03; p = 0.001). Post estimation analyses show that EVDs at 10 cmH2O with output close to 200 ml predicted a 50% probability of good outcomes. CONCLUSIONS: Increased EVD outputs were associated with favorable outcomes at the last follow-up.

A Novel Case of Tethered Cord in a Five-Month-Old Male With Pallister-Killian Syndrome.

A five-month-old male presented with an incidentally found low-lying conus medullaris on ultrasound and subsequent MRI demonstrating its position at L4. Pre-operative examination findings included mild, global hypotonia and a coccygeal dimple without bladder or bowel abnormalities or spasticity. The patient underwent spinal cord untethering with a section of filum terminale and was discharged without complication following his procedure. Follow-up at one year revealed continued baseline hypotonia without further neurosurgical needs. This is the first reported case of tethered cord syndrome described in a patient with Pallister-Killian syndrome managed successfully with neurosurgical intervention.

Relationship between external ventricular drain clamp trials and ventriculoperitoneal shunt insertion following nontraumatic subarachnoid hemorrhage: a single-center study.

OBJECTIVE: Currently, there is no established standard regarding the ideal number of external ventricular drain (EVD) clamp trials performed before ventriculoperitoneal (VP) shunt insertion following nontraumatic subarachnoid hemorrhage (SAH). In this study, the authors aimed to evaluate this relationship. METHODS: A retrospective review of all patients presenting with SAH between July 2007 and December 2016 was performed. Patients with SAH who had received an EVD within the first 24 hours of hospital admission and had undergone at least 1 clamp trial prior to EVD removal were eligible for inclusion in the study. Patient demographics, clinical presentations, SAH etiologies and grades, clamp trial data, hospital lengths of stay, and functional outcomes were recorded. RESULTS: One hundred fourteen patients with nontraumatic SAH complicated by posthemorrhagic hydrocephalus were included in the study. The median patient age was 57 years (range 28-90 years), with a male/female ratio of 1:1.7. A ruptured aneurysm was the underlying etiology of SAH in 79.8% of patients. A majority of patients (69.4%) had a Hunt and Hess grade III-V on admission. The median number of clamp trials performed was 2 (range 1-6). A VP shunt was required in 40.4% of patients. In those who underwent 2 and 3 clamp trials, 60% and 38.9%, respectively, did not require subsequent VP shunt placement. CONCLUSIONS: Surgical placement of a VP shunt is associated with complications. Clamp trials are routinely performed before making the decision to insert a shunt. In the present study, the authors found that a significant percentage of patients passed their second and third clamp trials without requiring subsequent shunt insertion. These data support performing multiple clamp trials prior to shunt placement.

Non-classical amine recognition evolved in a large clade of olfactory receptors.

Biogenic amines are important signaling molecules, and the structural basis for their recognition by G Protein-Coupled Receptors (GPCRs) is well understood. Amines are also potent odors, with some activating olfactory trace amine-associated receptors (TAARs). Here, we report that teleost TAARs evolved a new way to recognize amines in a non-classical orientation. Chemical screens de-orphaned eleven zebrafish TAARs, with agonists including serotonin, histamine, tryptamine, 2-phenylethylamine, putrescine, and agmatine. Receptors from different clades contact ligands through aspartates on transmembrane α-helices III (canonical Asp(3.32)) or V (non-canonical Asp(5.42)), and diamine receptors contain both aspartates. Non-classical monoamine recognition evolved in two steps: an ancestral TAAR acquired Asp(5.42), gaining diamine sensitivity, and subsequently lost Asp(3.32). Through this transformation, the fish olfactory system dramatically expanded its capacity to detect amines, ecologically significant aquatic odors. The evolution of a second, alternative solution for amine detection by olfactory receptors highlights the tremendous structural versatility intrinsic to GPCRs.