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Facial synkinesis is one of the most distressing consequences of facial paralysis. Synkinesis refers to the abnormal involuntary facial movement that occurs with voluntary movement of a different facial muscle group. The pathophysiologic basis of facial synkinesis is likely multifactorial although the predominant mechanism appears to be aberrant regeneration of facial nerve fibers to the facial muscle groups after facial nerve injury. Patients experience hypertonic contractures and synkinetic movements such as eye closure with volitional movement of the mouth or midfacial movement during volitional or reflexive eye closure. Synkinesis can cause functional limitation with activities such as eating, drinking, smiling, and may even lead to social isolation. Evaluation of synkinesis is primarily subjective with facial grading scales such as the Sunnybrook scale. Objective measures of synkinesis using computerized video analysis show promise although no objective techniques are currently widely used. The most common therapeutic modalities for the treatment of facial synkinesis include (1) botulinum toxin type A (BTX-A) injections for selective chemodenervation of affected muscle groups and (2) facial neuromuscular retraining. Biofeedback using mirrors or electromyography has been used both for the treatment and prevention of facial synkinesis. Other treatment options include surgical therapies, such as selective neurolysis or myectomy, although these have been rendered nearly obsolete with the advent of BTX-A.

Type 2 innate lymphoid cells (ILC2s) have recently been identified in human nasal polyps, but whether numbers of ILC2s differ by polyp endotype or are influenced by corticosteroid use is unknown. Here, we show that eosinophilic nasal polyps contained double the number of ILC2s vs. non-eosinophilic polyps. Polyp ILC2s were also reduced by 50% in patients treated with systemic corticosteroids. Further, using a fungal allergen challenge mouse model, we detected greatly reduced Th2 cytokine-producing and Ki-67+ proliferating lung ILC2s in mice receiving dexamethasone. Finally, ILC2 Annexin V staining revealed extensive apoptosis after corticosteroid treatment in vivo and in vitro. Thus, ILC2s are elevated in the eosinophilic nasal polyp endotype and systemic corticosteroid treatment correlated with reduced polyp ILC2s. Finally, allergen-challenged mice showed reduced ILC2s and increased ILC2 apoptosis after corticosteroid treatment suggesting that ILC2 may be responsive to corticosteroids in eosinophilic respiratory disease.

The Cdc25 phosphatases play key roles in cell-cycle progression by activating cyclin-dependent kinases. The latter are absent from neurons that are terminally differentiated in adult brain. However, accumulation of mitotic phosphoepitopes, and re-expression and activation of the M phase regulator, Cdc2/cyclin B, have been described in neurons undergoing degeneration in Alzheimer's disease (AD). To explain this atypical mitotic activation in neurons we investigated the Cdc2-activating Cdc25A phosphatase in human brain. The structural hallmarks of AD neurodegeneration, neurofibrillary tangles and neuritic plaques, were prominently immunolabeled with Cdc25A antibodies. In addition numerous neurons without visible structural alterations were also intensely stained, whereas control brain was very weakly positive. After immunoprecipitation from control and AD tissue, we found that the tyrosine dephosphorylating activity of Cdc25A against exogenous Cdc2 substrate was elevated in AD. Accordingly, Cdc25A from AD tissue displayed increased immunoreactivity with the mitotic phosphoepitope-specific antibody, MPM-2, and co-localized with MPM-2 immunoreactivity in AD neurons. These data suggest that Cdc25A participates in mitotic activation during neurodegeneration. The involvement of Cdc25A in cellular transformation, modulation of the DNA damage checkpoint, and linkage of mitogenic signaling to cell cycle machinery, also implicates one of these cell-cycle pathways in AD pathogenesis.

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Therapies for the protection and regeneration of auditory hair cells are of great interest given the significant monetary and lifestyle impact of hearing loss. The past decade has seen tremendous advances in the use of adenoviral vectors to achieve these aims. Preliminary data demonstrated the functional capacity of this technique as adenoviral-induced expression of neurotrophic and growth factors protected hair cells and spiral ganglion neurons from ototoxic insults. Subsequent efforts confirmed the feasibility of adenoviral transfection of cells in the auditory neuroepithelium via cochleostomy into the scala media. Most recently, efforts have focused on regeneration of depleted hair cells. Mammalian hearing loss is generally considered a permanent insult as the auditory epithelium lacks a basal layer capable of producing new hair cells. Recently, the transcription factor Atoh1 has been found to play a critical role in hair cell differentiation. Adenoviral-mediated overexpression of Atoh1 in culture and in vivo have shown the ability to regenerate auditory and vestibular hair cells by causing transdifferentiation of neighboring epithelial-supporting cells. Functional recovery of both the auditory and vestibular systems has been documented following adenoviral induced Atoh1 overexpression.

Objective/Hypothesis?Superior semicircular canal (Sup SC) dehiscence syndrome is a rare condition, causing a variety of auditory and vestibular symptoms. The traditional surgical management is a middle cranial fossa, extradural approach to resurface the Sup SC. Recently, a transmastoid approach for plugging of the Sup SC has been developed. We present further data supporting the use of the transmastoid approach in preference to the middle fossa approach. Design?This is a retrospective multi-institutional case series. Method?We included 10 patients in this case series from two tertiary otology institutions. Sup SC dehiscence was confirmed by correlation of clinical symptoms with positive audiometric, vestibular evoked myogenic potential, and computed tomography findings. A transmastoid approach was used for plugging of the Sup SC. Either a single fenestration was created at the site of dehiscence or separate fenestrations sited ampullopetal and ampullofugal to the dehiscence. Results?All patients who underwent this procedure had good symptom control and hearing preservation postoperatively. Conclusion?In patients with adequate temporal bone pneumatization, the transmastoid approach provides a safe and effective alternative to the middle cranial fossa approach. This series has demonstrated excellent symptom control and preservation of hearing with the transmastoid approach.

BackgroundTumor necrosis factor (TNFA) is the canonical member of the TNF superfamily, which plays a major role in both inflammation and apoptosis. To evaluate the role of TNFs in otitis media (OM), the most common disease of childhood, we evaluated middle ear (ME) expression of genes encoding the TNF and TNF receptor superfamilies during bacterial OM in the mouse, characterized OM in TNFA-deficient mice, and assessed apoptosis during OM in normal versus TNF-deficient MEs.ResultsTNFs and TNF receptors were broadly regulated during OM, with TNFA showing the highest level of up-regulation. TNF deficient mice exhibited mucosal hyperplasia even in the absence of infection and exuberant growth of the mucosa during OM, including the formation of mucosal polyps. Mucosal recovery during OM was also delayed, in parallel with a delay in mucosal apoptosis and reduced caspase gene expression.ConclusionsThe TNF and TNF receptor superfamilies mediate both inflammation and apoptosis during OM. TNF appears to be critical for the maintenance of mucosal architecture in both the normal and infected ME, since excessive accumulation of mucosal tissue is seen in TNFA-/- MEs both before and after bacterial inoculation of the ME. TNFA is also required for appropriate regulation of caspase genes.