Otologic Manifestations of Langerhans Cell Histiocytosis: A Systematic Review.

OBJECTIVE: To perform a systematic review to investigate common otologic manifestations of Langerhans cell histiocytosis, the incidence of these findings, methods for diagnosis, as well as medical and surgical management. DATA SOURCES: PubMed/MEDLINE, Embase, and Cochrane Library. REVIEW METHODS: A search of PubMed/MEDLINE, Embase, and Cochrane Library for all articles published between 1963 to 2020 was performed with variations and combinations of the following search terms: Langerhans cell histiocytosis, eosinophilic granuloma, Letterer-Siwe, Hand-Schüller-Christian, otitis, otologic, ear. A review of the references of all included articles was also conducted. RESULTS: Sixty-two articles encompassing 631 patients met inclusion criteria. Otologic symptoms at presentation were found in 246 (39%) patients in the reported studies with 48% reporting bilaterality. The mean age was 14.8 years with a male predominance (64%). The most common otologic presenting symptom was otorrhea (46%). A majority had the multisystem variant (52%). The most common treatment modalities were chemotherapy (52%), followed by surgery (50%), systemic steroids (45%), and radiotherapy (31%). Surgery was performed in 75.8% with unisystem involvement and in 50.6% with multisystem involvement. The most effective treatments included radiotherapy (56% success rate, 17% of treated patients), systemic steroids (44% success, 20% treated), chemotherapy (41% success, 21% treated), and surgical modalities (36% success, 19% treated). CONCLUSIONS: Otologic manifestations that occur with the multisystem variant or are at high risk for central nervous system involvement necessitate systemic treatment. For unifocal lesions, surgery is recommended. Lastly, radiotherapy should be reserved for extensive lesions involving vital structures or presenting in older patients.

Implications of Transcranial Magnetic Stimulation as a Treatment Modality for Tinnitus.

Repetitive transcranial magnetic stimulation (rTMS) is a non-invasive, neuromodulating technique for brain hyperexcitability disorders. The objective of this paper is to discuss the mechanism of action of rTMS as well as to investigate the literature involving the application of rTMS in the treatment of tinnitus. The reviewed aspects of the protocols included baseline evaluation, the total number of sessions, frequency and the total number of stimuli, the location of treatment, and the outcome measures. Even with heterogeneous protocols, most studies utilized validated tinnitus questionnaires as baseline and outcome measures. Low frequency (1 Hz) stimulation throughout 10 consecutive sessions was the most widely used frequency and treatment duration; however, there was no consensus on the total number of stimuli necessary to achieve significant results. The auditory cortex (AC) was the most targeted location, with most studies supporting changes in neural activity with multi-site stimulation to areas in the frontal cortex (FC), particularly the dorsolateral prefrontal cortex (DLPFC). The overall efficacy across most of the reviewed trials reveals positive statistically significant results. Though rTMS has proven to impact neuroplasticity at the microscopic and clinical level, further studies are warranted to demonstrate and support the clinical use of rTMS in tinnitus treatment with a standardized protocol.

Advancements in Stem Cell Technology and Organoids for the Restoration of Sensorineural Hearing Loss.

BACKGROUND: Sensorineural hearing loss (SNHL) is a significant cause of morbidity worldwide and currently has no curative treatment. Technological advancements in stem cell therapy have led to numerous studies that examine the generation of otic sensory cells from progenitors to restore inner ear function. Recently, organoids have emerged as a promising technique to further advance the process of creating functional replacement cells after irreversible hearing loss. Organoids are the three-dimensional generation of stem cells in culture to model the tissue organization and cellular components of the inner ear. Organoids have emerged as a promising technique to create functioning cochlear structures in vitro and may provide crucial information for the utilization of stem cells to restore SNHL. PURPOSE: The purpose of this review is to discuss the recent advancements in stem cell-based regenerative therapy for SNHL. RESULTS: Recent studies have improved our understanding about the developmental pathways involved in the generation of hair cells and spiral ganglion neurons. However, significant challenges remain in elucidating the molecular interactions and interplay required for stem cells to differentiate and function as otic sensory cells. A few of the challenges encountered with traditional stem cell therapy may be addressed with organoids. CONCLUSION: Stem cell-based regenerative therapy holds a great potential for developing novel treatment modalities for SNHL. Further advancements are needed in addressing the challenges associated with stem cell-based regenerative therapy and promote their translation from bench to bedside.

Diagnosis and management of eosinophilic otitis media: a systematic review.

BACKGROUND: Eosinophilic Otitis Media (EOM) is a relatively newly defined entity of recurrent and resistant otitis media. OBJECTIVE: To perform a systematic review of otologic manifestations, diagnosis and management of eosinophilic otitis media (EOM). METHODS: 393 patients diagnosed with EOM of 26 studies met inclusion criteria and were assessed for demographics, otologic manifestations, diagnostic criteria fulfilled, and medical and surgical treatments. RESULTS: Most common otologic manifestations were hearing loss (65%), otitis media with effusion (16%), tympanic membrane perforation (13%), and otorrhea (13%). 93% had a predominantly eosinophilic middle ear effusion, 95% had asthma, 85% had a highly viscous middle ear effusion, 71% had nasal polyposis, and 58% had resistance to conventional treatment. For treatment, 39% received intratympanic steroid injections, 33% received systemic steroids, 17% received steroid ear drops and 13% received a biological agent. 39% of patients underwent a surgical intervention with 26% receiving functional endoscopic sinus surgery and 18% receiving myringotomy with tube insertion. Success rates were highest with use of intratympanic steroids (45%), systemic steroids (26%), and biological agents (58%). CONCLUSION: Intratympanic steroids show the most efficacy in treating EOM, and aggressive optimization of asthma may be beneficial in resolving otologic symptoms. Surgery should be reserved for refractory cases and complications.

Otologic Manifestations of Eosinophilic Granulomatosis With Polyangiitis: A Systematic Review.

OBJECTIVE: To perform a systematic review of the diagnosis, treatment, and management of patients with otologic manifestations of eosinophilic granulomatosis with polyangiitis. DATABASES REVIEWED: PubMed, Embase, Cochrane. METHODS: A systematic search for relevant published literature in PubMed, Cochrane Library, and EMBASE databases was done. Data was collected on demographics, otologic manifestations, specific diagnostic criteria fulfilled, common clinical, and imaging findings as well as medical and surgical treatments received. RESULTS: Fifteen articles encompassing 219 patients met inclusion criteria including 8 case reports and 7 case series. The mean age was 52.8 (range of 24-70). The most common otologic presenting symptoms were hearing loss (76%), otitis media with effusion (44%), vertigo (22%), tinnitus (21%), and chronic otitis media (20%). The most common diagnostic criteria observed in these patients were paranasal sinus abnormalities (75%), asthma (66%), and eosinophilia >10% (44%). The most common treatment was systemic steroids (66%), followed by surgery (52%), with myringotomy with tube insertion (M&T) (32%) and endoscopic sinus surgery (21%) being the most prevalent. Thirty-four percent of patients received an immunosuppressive agent. Successful treatments included systemic steroids (23%), surgical modalities (13%) with M&T being the most common (7%), topical nasal steroids (12%), and cyclophosphamide (10%). CONCLUSION: Hearing loss and a middle ear effusion are the most common presenting otologic manifestations of eosinophilic granulomatosis with polyangiitis. Sinonasal disease was more prevalent in patients with otologic manifestations. Primary treatment consists of systemic steroids and immunomodulation. M&T, endoscopic sinus surgery, and local steroid administration can be adjunctive measures to alleviate local disease.Level of Evidence: Level 1.