A Rare and Unusual Presentation of Neurofibromatosis Type 1: Using Available Tools To Distinguish Neurofibromas From Mimicking Pathologies on CT Scan and MRI.

Neurofibromatosis type 1 (NF-1) is the most common neurocutaneous syndrome. Despite its more common appearance relative to other phakomatoses, it has a large variety of disease manifestations that can, at times, make swift diagnosis more challenging if not readily recognized, especially when presenting in an atypical manner. Our case reveals an unusual presentation of NF-1. After initially presenting with a bug bite on the lip with progressive swelling and surrounding inflammatory changes despite treatment with oral antibiotics, a CT scan was performed and demonstrated inflammatory changes surrounding the lip with an adjacent inflammatory mass lesion. Due to hypoattenuating lesions within the retropharyngeal space and misinterpretation by the otorhinolaryngologist, aspiration was attempted but unsuccessful, and the patient's condition worsened. Subsequent MRI was able to confirm the presence of numerous neurofibromas. The patient gradually improved on an extended course of antibiotics and was discharged in stable condition. Familiarizing oneself with the more specific imaging characteristics of this relatively common neurocutaneous disorder can help prevent incorrect or delayed diagnosis and ensure proper management. Furthermore, identifying these features on CT scan and MRI can differentiate them from other mimicking pathologies on each modality. Recognition of a scarcely reported infected neurofibroma as an established diagnostic entity could be important to include in the differential of similar cases in the future and subsequently aid in proper diagnosis and management.

Herpes Simplex Virus Esophagitis as a Presentation of Febrile Neutropenia: A Case Report.

Herpes Simplex Virus esophagitis typically manifests as mucocutaneous lesions in immunocompromised patients, most frequently in organ and bone marrow transplant recipients. However, it has not been appropriately reported as a cause of febrile neutropenia despite being a relatively common opportunistic infection in this patient population.  A 58-year-old man recently diagnosed with Ewing Sarcoma for which he was receiving chemotherapy presented with febrile neutropenia. Following a prolonged hospital course characterized by persistent fevers, an endoscopic evaluation was performed and diagnosis of Herpes Simplex Virus esophagitis was confirmed via histopathology. Prompt administration of acyclovir resulted in the complete resolution of the patient's symptoms.  Recognition of Herpes Simplex Virus esophagitis as an etiology of febrile neutropenia can ensure more prompt diagnosis and allow for appropriate management of these patients. In addition, this case report emphasizes a need for further research into additional diagnostic markers in the workup of these patients and the incorporation of antiviral therapy in febrile neutropenia algorithms.

An autism-associated mutation in GluN2B prevents NMDA receptor trafficking and interferes with dendrite growth.

Autism spectrum disorders (ASDs) are neurodevelopmental disorders with multiple genetic associations. Analysis of de novo mutations identified GRIN2B, which encodes the GluN2B subunit of NMDA receptors, as a gene linked to ASDs with high probability. However, the mechanisms by which GRIN2B mutations contribute to ASD pathophysiology are not understood. Here, we investigated the cellular phenotypes induced by a human mutation that is predicted to truncate GluN2B within the extracellular loop. This mutation abolished NMDA-dependent Ca2+ influx. Mutant GluN2B co-assembled with GluN1 but was not trafficked to the cell surface or dendrites. When mutant GluN2B was expressed in developing cortical neurons, dendrites appeared underdeveloped, with shorter and fewer branches, while spine density was unaffected. Mutant dendritic arbors were often dysmorphic, displaying abnormal filopodial-like structures. Interestingly, dendrite maldevelopment appeared when mutant GluN2B was expressed on a wild-type background, reflecting the disease given that individuals are heterozygous for GRIN2B mutations. Restoring the fourth transmembrane domain and cytoplasmic tail did not rescue the phenotypes. Finally, abnormal development was not accompanied by reduced mTOR signaling. These data suggest that mutations in GluN2B contribute to ASD pathogenesis by disrupting dendrite development.

Presynaptic NMDA receptors - dynamics and distribution in developing axons in vitro and in vivo.

During cortical development, N-methyl-D-aspartate (NMDA) receptors (NMDARs) facilitate presynaptic terminal formation, enhance neurotransmitter release and are required in presynaptic neurons for spike-timing-dependent long-term depression (tLTD). However, the extent to which NMDARs are found within cortical presynaptic terminals has remained controversial, and the sub-synaptic localization and dynamics of axonal NMDARs are unknown. Here, using live confocal imaging and biochemical purification of presynaptic membranes, we provide strong evidence that NMDARs localize to presynaptic terminals in vitro and in vivo in a developmentally regulated manner. The NR1 and NR2B subunits (also known as GRIN1 and GRIN2B, respectively) were found within the active zone membrane, where they could respond to synaptic glutamate release. Surprisingly, NR1 also appeared in glutamatergic and GABAergic synaptic vesicles. During synaptogenesis, NR1 was mobile throughout axons - including growth cones and filopodia, structures that are involved in synaptogenesis. Upon synaptogenic contact, NMDA receptors were quickly recruited to terminals by neuroligin-1 signaling. Unlike dendrites, the trafficking and distribution of axonal NR1 were insensitive to activity changes, including NMDA exposure, local glutamate uncaging or action potential blockade. These results support the idea that presynaptic NMDARs play an early role in presynaptic development.