Rejected

Atypical wounds account for approximately 5% to 20% of chronic ulcerations. Typically, clinical suspicion of an uncommon etiology is warranted for wounds that do not show signs of healing with conventional care, that are associated with pain out of proportion to the clinical presentation, or that are atypical in appearance. This review provides a general overview of various atypical wound etiologies, clinical presentations and appearance, and current treatment protocols. The clinical presentation, pathophysiologic etiology, and current literature on each etiology are presented. The etiologies discussed are pyoderma gangrenosum, calciphylaxis, lichen planus, necrobiosis lipoidica, infectious ulcers, hidradenitis suppurativa, artefactual ulcers, hydroxyurea-induced ulcers, vasculopathies, and neoplastic ulcers. Patients with atypical wounds experience a poorer prognosis and slower healing rate compared with patients with typical wound etiologies (eg, vascular and diabetic wounds). Biopsy is often vital in wound care to identify and differentiate wound etiologies. It is important to note that multiple characteristics or histologic features can overlap in a biopsy with atypical wounds. Therefore, a biopsy will still require an understanding of the presentation of these different wounds and should only be used when appropriate. The proper diagnosis for an atypical wound can greatly hasten wound closure, decrease the cost for the patient and the health care system, and improve the patient's quality of life. Because of the limited availability of patient populations with atypical wound etiologies, literature concerning specific pathologies is limited. More research on each pathology is needed, as is a universally accepted treatment protocol for atypical wounds.

Autoeczematization, the dissemination of a local eczematous reaction to a distal site, is closely associated with lower extremity edema. Our patient is a 50-year-old man with a past medical history of drug-induced lupus to hydralazine and recent bilateral cellulitis in his lower extremities. He was presented with complaints of vesicles on his palms and soles and a scaling rash that had spread over his torso, arms, and trunk. Laboratory studies found no evidence of an active rheumatological condition with complement C3 and C4 levels being normal and no anti-dsDNA, anti-histone, anti-Smith, anti-ribonucleoprotein (anti-RNP), anti-centromere, anti-neutrophil cytoplasmic antibodies (ANCA), anti-Ro, or anti-La antibodies present. Moreover, syphilis, HIV, gonorrhea, chlamydia, rickettsia antibody, and antibody testing was negative suggesting a non-infectious etiology of the rash. Hypothesizing a dermatologic origin of the rash, a skin biopsy was performed that revealed intermittent foci of moderate hyperparakeratosis and mild hypergranulosis indicative of eczematous dermatitis. Unfortunately, treatment of the disseminated rash with 10 mg of daily oral prednisone and topical triamcinolone acetonide 0.1% ointment proved inefficient, and methotrexate therapy was advised. We posit that cellulitis, a soft tissue infection under the skin, is a potential cause of disruption of the skin barrier that leads to activation of autosensitized T cells. These activated T cells circulate to distal areas of the skin and may lead to autoeczematization. The treatment of these id reactions with corticosteroids – both topical and oral – may be insufficient at reducing dermatitis and require the application of systemic methotrexate or cyclosporine. Through this case, we demonstrate the importance of treating id reactions by stepping up the intensity of treatment due to the severity of autosensitization-driven eczema.

Atypical choroid plexus papilloma (aCPP) is very rarely seen in adults. Here, we present the case of a 47-year-old male with several months of headache, nausea, dizziness, and imbalance who was found to have an enhancing mass of the fourth ventricle with imaging findings suggestive of likely ependymoma. The patient underwent suboccipital craniotomy with C1 laminectomy and telovelar approach for gross-total resection of the lesion, with final pathology demonstrating WHO grade II aCPP. Subsequent genomic analysis showed a biologically relevant TERT mutation, as well as several variants of unknown significance. We conclude that aCPP is a rare, benign entity diagnosed by tissue sample that is potentially curative with surgical resection and may harbor targetable genetic mutations.

Pediatric patients often experience severe pain after thoracic surgery, especially in the early postoperative period. Recently, the focus has been on regional analgesia with the introduction of ultrasound-guided erector spinae plane blocks. We assumed that preoperative erector spinae plane block (ESPB) in children undergoing video-assisted thoracoscopic surgery (VATS) would reduce the consumption of perioperative opioids.

Meningioma is the second most common primary brain tumor. There are approximately 5.6 cases of meningioma per 100,000 pregnant women. Foramen magnum meningioma is rare, and the diagnosis, treatment, and prognosis are complex in pregnant women.

Thumb injuries are common in baseball players and can sometimes be challenging to effectively manage. A subset of patients experience failed nonoperative management yet do not have a clear indication for surgery. Cryoneurolysis or cryoanalgesia is a form of neuromodulation for pain that has been approved by the US Food and Drug Administration; it has been used safely and effectively on a variety of peripheral nerves. The mechanism of action involves percutaneous introduction of a small probe under local anesthetic to nerve tissue using ultrasound guidance. The probe is then cooled to -88°C using nitrous oxide, which results in secondary Wallerian degeneration. Axonal and myelin regeneration occurs completely in 3 to 6 months.

Migraineurs often experience severe headache attacks and their quality of life is inhibited. Most migraineurs treat their headaches with acute treatment, but preventive treatment is often not chosen appropriately. Because migraine attack frequency and medication overuse are risk factors for headache progression (chronification) and medication-overuse headache, it is possible that preventive medication may also reduce risk progression. Therefore, it is necessary to select preventive medication if required.

Glioblastoma is the most common malignant central nervous system (CNS) tumor in adults. Acute common clinical symptoms include headache, seizure, behavior changes, focal neurological deficits, and signs of increased intracranial pressure. The classic MRI finding of glioblastoma is an irregularly shaped, rim-enhancing or ring-enhancing lesion with a central dark area of necrosis. This constellation of features correlates with microscopic findings of tumor necrosis and microvascular proliferation. Besides these common features, several well-recognized histological subtypes include giant cell glioblastoma, granular cell glioblastoma, gliosarcoma, glioblastoma with a primitive neuronal component, small cell glioblastoma, and epithelioid glioblastoma. While glioblastoma was historically classified as isocitrate dehydrogenase (IDH)-wildtype and IDH-mutant groups, the Consortium to Inform Molecular and Practical Approaches to CNS Tumor Taxonomy (cIMPACT-NOW) and the fifth edition of the WHO Classification of Tumors of the Central Nervous System clearly updated the nomenclature to reflect glioblastoma to be compatible with wildtype IDH status only. Therefore, glioblastoma is now defined as "a diffuse, astrocytic glioma that is IDH-wildtype and H3-wildtype and has one or more of the following histological or genetic features: microvascular proliferation, necrosis, Telomerase reverse transcriptase promoter mutation, Epidermal growth factor receptor gene amplification, +7/-10 chromosome copy-number changes (CNS WHO grade 4)."

Neurons in the trigeminal ganglion relay sensory information from the face and oral cavity to the brain. The trigeminal ganglion is unique in its complexity, containing a mixed population of modality-specific (i.e., touch, pain) neurons derived from both neural crest and placodal precursors. The identity of trigeminal ganglion neurons is associated with the expression of Trk neurotrophin receptors, which are required for long-term neuronal function and survival. Within sensory ganglia, nociceptive neurons that detect pain or temperature generally express TrkA, while mechanoreceptors responding to touch express TrkB or TrkC. However, the processes that guide the emergence and maintenance of distinct neuronal subpopulations in the trigeminal ganglion are poorly understood. We recently uncovered a role for Elongator complex protein 1 (Elp1) in the maintenance of TrkA-expressing trigeminal ganglion nociceptors. Mutation of ELP1 causes Familial Dysautonomia (FD), a fatal neuropathy characterized, in part, by trigeminal sensory deficits, including impaired facial nociception. In a mouse model of FD, where Elp1 is deleted from neural crest derivatives (Elp1 CKO), we found that Elp1 is required for proper trigeminal nerve morphology. Moreover, loss of Elp1 reduces TrkA levels and enhances death of TrkA neurons during embryogenesis, explaining the facial sensory impairments experienced by FD patients. Given the targeted effects on TrkA neurons in Elp1 CKO, we hypothesized that most TrkA neurons in the trigeminal ganglion arise from the neural crest, while TrkB and TrkC neurons originate from placode cells. To address this, we first examined whether individual Trk receptors are co-expressed with the transcription factor Six1, which has previously been used to identify placodal neurons in the trigeminal ganglion. We discovered that Six1 is expressed in waves, marking newly differentiated trigeminal ganglion neurons regardless of presumptive placode or neural crest origin. Without bona fide immunohistochemical lineage markers, a Wnt1-Cre reporter mouse was used to identify neural crest (Wnt1-Cre recombined) versus placode (not recombined) derivatives. In support of our hypothesis, we observed a majority of TrkA neurons in the trigeminal ganglion had previously undergone Cre recombination, indicating trigeminal ganglion nociceptors are largely neural crest-derived. In contrast, most TrkB and TrkC neurons were not targeted for recombination, confirming trigeminal ganglion mechanoreceptors generally arise from placodes. Lastly, the majority of Six1-expressing cells were, indeed, Wnt1-Cre recombined once neural crest neuronal differentiation commenced in the trigeminal ganglion, confirming that Six1 is not exclusively expressed by placodal neurons at later stages. Future studies will expand upon this work by crossing the Wnt1-Cre reporter with Elp1 CKO to evaluate how Elp1 regulates the development and interactions of neural crest versus placodal derivatives within the trigeminal ganglion. Together, these findings provide novel insight into the origin and maintenance of trigeminal ganglion neurons and enhance our understanding of the pathogenesis of FD and other sensory nerve disorders.

Myofascial pain syndrome (MPS) is described as the muscle, sensory, motor, and autonomic nervous system symptoms caused by stimulation of myofascial trigger points (MTP), but the participation of fascia in this syndrome has often been neglected. This presentation will explore the important contribution of structural and functional alterations of the deep fascia to the pathophysiology and clinical manifestation of MPS. The interaction of the three dimensional fascial system, with the dynamic nature of sensitization, will be presented in the context of the pathophysiology of MTP and the expression of quantitative, reproducible physical findings in the clinical manifestation of chronic myofascial pain. Emphasis will be given to recent developments in the biology of fascia, and in particular, its hyaluronan (HA)-rich matrix content that provide a viscoelastic property possible cause of MPS. The presentation will translate these findings to highlight novel clinical directions in the diagnosis and non-pharmaceutical management of MPS.