Elias Michaelides

Cell-type Phylogenetics and the Origin of Endometrial Stromal Cells

A challenge of genome annotation is the identification of genes performing specific biological functions. Here, we propose a phylogenetic approach that utilizes RNA-seq data to infer the historical relationships among cell types and to trace the pattern of gene-expression changes on the tree. The hypothesis is that gene-expression changes coincidental with the origin of a cell type will be important for the function of the derived cell type. We apply this approach to the endometrial stromal cells (ESCs), which are critical for the initiation and maintenance of pregnancy. Our approach identified well-known regulators of ESCs, PGR and FOXO1, as well as genes not yet implicated in female fertility, including GATA2 and TFAP2C. Knockdown analysis confirmed that they are essential for ESC differentiation. We conclude that phylogenetic analysis of cell transcriptomes is a powerful tool for discovery of genes performing cell-type-specific functions.

Contemporary management of pediatric lateral sinus thrombosis: a twenty year review.

OBJECTIVES A case of pediatric otogenic lateral sinus thrombosis is reported, followed by a substantive literature review. DESIGN 104 patients were reviewed, culled from published case reports from 1993 to 2011 on the PubMed database. METHODS All full text case reports on the PubMed database from 1993 to 2011 with patients less than or equal to 16 years of age that outlined specific treatments were included. RESULTS 73% of patients were male and average age of presentation was 7.7 years. The most common symptoms were fever, headache, and otalgia, while the most common signs included otorrhea and neck stiffness. CT scans had a sensitivity of 87% and MR studies had a sensitivity of 100%. Single bacterial organisms were isolated in 46% of cases, with beta hemolytic streptococcus, streptococcus pneumoniae, and staphylococcus aureus being most common. Management included broad spectrum antibiotics (100%), mastoidectomy (94%), manipulation of the thrombosed sinus (50%), and anticoagulation (57%). The mortality rate was one in 104 patients. Morbidities occurred in 10% of patients and included cranial nerve palsy, sensorineural hearing loss, stroke, and septic hip joint. CONCLUSION Lateral sinus thrombosis is a rare but treatable complication of otologic disease in the pediatric population, warranting a high index of suspicion. Management should include broad spectrum antibiotics and surgical removal of all perisinus infection. Anticoagulation is not definitively associated with improved outcomes and warrants further investigation.

Hemifacial Spasm and Neurovascular Compression

Hemifacial spasm (HFS) is characterized by involuntary unilateral contractions of the muscles innervated by the ipsilateral facial nerve, usually starting around the eyes before progressing inferiorly to the cheek, mouth, and neck. Its prevalence is 9.8 per 100,000 persons with an average age of onset of 44 years. The accepted pathophysiology of HFS suggests that it is a disease process of the nerve root entry zone of the facial nerve. HFS can be divided into two types: primary and secondary. Primary HFS is triggered by vascular compression whereas secondary HFS comprises all other causes of facial nerve damage. Clinical examination and imaging modalities such as electromyography (EMG) and magnetic resonance imaging (MRI) are useful to differentiate HFS from other facial movement disorders and for intraoperative planning. The standard medical management for HFS is botulinum neurotoxin (BoNT) injections, which provides low-risk but limited symptomatic relief. The only curative treatment for HFS is microvascular decompression (MVD), a surgical intervention that provides lasting symptomatic relief by reducing compression of the facial nerve root. With a low rate of complications such as hearing loss, MVD remains the treatment of choice for HFS patients as intraoperative technique and monitoring continue to improve.

The correlation between the vestibulo-ocular reflex and multi-focal ocular correction: implications for vestibular compensation.

PURPOSE An accurate vestibulo-ocular reflex is important for gaze stability, and is adaptable through modification, based on stable and repeated vestibular and visual feedback. The optical power of eye glasses changes the ocular rotation needed to view an object due to the prismatic effect. Depending on the diopter of a lens, eyes have to rotate through fewer or more degrees to correct for refractive change. We aim to determine how multifocal lenses, such as progressives, affect needed ocular rotation and ocular gain based on location of the lens in which an object is viewed. Differing ocular gains within the same field of vision will create non-stable visual feedback possibly delaying vestibular recovery. METHODS AND MATERIALS Needed ocular rotation, and ocular gain to view an object 30° lateral to midline were calculated across different points in the vertical axis of a representative progressive lens. RESULTS In a progressive lens with superior correction of +1 D and inferior correction of +5.5 D, needed ocular rotation to view an object 30° lateral to midline would differ by 4.015°, with difference in ocular gain of 0.1336, indicating a 13.027% change in ocular gain, based on superior verse inferior viewing. CONCLUSIONS Progressive lenses have variable areas of VOR gain. This lack of consistent vestibulo-visual feedback may lead to prolonged compensation time in patients with vestibular injury.

Use of middle ear immittance testing in the evaluation of patulous eustachian tube.

BACKGROUND Patulous Eustachian tube is the uncommon condition of a persistently open Eustachian tube, which causes the disturbing symptoms of autophony and respiratory-synchronous tinnitus. We review this condition and propose a specific evaluation protocol that can be performed quickly and easily using standard audiologic test equipment. We have used this protocol in the evaluation of a number of patients and will discuss our findings. PURPOSE To establish a standardized protocol for the audiologic evaluation of patulous Eustachian tube using a standard clinical tympanometer and to establish norms with respect to tympanic membrane movement during breathing tasks. RESEARCH DESIGN Quantitative analysis of test results obtained during clinical evaluation of patients referred for suspected patulous Eustachian tube during 2008 and 2009. STUDY SAMPLE The cohort was 35 individuals including 25 patients referred for suspected patulous Eustachian tube and 10 control (normal) patients. Of the total group, 25 individuals were female, 10 were male, and the overall age range was 8 yr to 82 yr. DATA COLLECTION AND ANALYSIS Patients underwent audiologic and otologic testing including quantitative measurement of middle ear compliance during breathing and nasal endoscopy. Two tympanometers were used to assess middle ear compliance: the Grason-Stadler Instruments Model 33 and Tympstar. Endoscopy was performed using either a Storz Endoskope Xenon Nova 175 or a Pentax EPM 1000. Results of middle ear immittance tests performed during breathing tasks were compared with results of endoscopy as well as the impressions of the examining physician. Magnitude of middle ear compliance was examined for mean and standard deviation, and the control/normal group results were compared with those of individuals complaining of symptoms suggestive of patulous Eustachian tube. RESULTS We found that slightly greater than 75% of individual ears with patulous Eustachian tube exhibited middle ear compliance greater than 0.07 ml during breathing tasks. All ears with patulous Eustachian tube exhibited a respiratory-synchronous compliance pattern during breathing tasks. Of individual ears without patulous Eustachian tube, 97% exhibited middle ear compliance during breathing of less than 0.07 ml with no respiratory-synchronous pattern. CONCLUSIONS Measurement of middle ear compliance during breathing appears to be a sensitive and specific tool in the examination of patulous Eustachian tube, particularly when both the magnitude of compliance and the pattern of compliance are considered.

Impairment of Caloric Function After Cochlear Implantation

PURPOSE This article seeks to review current literature on caloric function following cochlear implantation while analyzing any correlations of caloric function changes with vestibular symptoms. METHOD This article is a systematic review of evidence-based literature. English language articles published between 1980 and 2014 that presented some form of caloric data from cochlear implant (CI) patients and that did not solely analyze overlapping data from a previous study were reviewed. Twenty-five articles met these criteria. RESULTS Of the 439 individuals tested, 37% of patients demonstrated reduced maximum slow-phase velocity, and 34% had onset of caloric asymmetry post-CI. CONCLUSIONS This review article found that cochlear implantation can affect caloric responses but is variable. When counseling patients preoperatively, possible effects of CI on labyrinthine function should be discussed.

High rate of bilaterality in internal auditory canal metastases

PURPOSE Presentation of three cases of metastatic carcinoma to the internal auditory canal bilaterally, as well as a systematic review of the literature regarding the characteristics of these lesions. MATERIALS AND METHODS Using a MEDLINE Ovid search (1946-2015), we identified and reviewed 102 cases of metastatic carcinoma to the internal auditory canal. Metrics recorded include: patient age, sex, tumor type, laterality, past oncologic history, co-occurring metastatic sites, clinical findings, radiographic findings, therapy received, and outcome. Cases of unilateral versus bilateral IAC were compared. RESULTS Remarkably, 52.9% reported cases of internal auditory canal metastases have bilateral occurrence. The most common primary tumor sites for internal auditory canal metastases were lung (21.2%), skin (18.6%), and breast (16.7%), with lung and skin cancers having the highest rates of bilateral metastasis. Meningeal metastasis occurred at a much higher rate in bilateral cases (47.2%) versus unilateral cases (8.5%). Brain parenchymal metastasis also occurred at a higher rate in bilateral cases (38.2%) versus unilateral cases (19.2%). Outcomes for cases of internal auditory canal metastases are generally poor, with 56.3% of unilateral cases and 86.1% of bilateral cases reporting patient death within 5 years from diagnosis. CONCLUSIONS In cases of internal auditory canal metastasis, clinicians should carefully assess for not only contralateral disease but also additional metastatic disease of the central nervous system. Rapid-onset hearing loss, tinnitus, vertigo, or facial palsy should raise suspicion for internal auditory canal metastasis, particularly in patients with a known oncologic history.

Langerhans Cell Histiocytosis of the Temporal Bone with Otic Capsule Involvement

IntroductionThis study is conducted to demonstrate that destructive lesions of the otic capsule by Langerhans cell histiocytosis (LCH) causing both radiographic and audiologic findings can be completely reversed with adequate treatment. Retrospective case review and analysis of clinical and imaging data were obtained as part of the diagnosis and treatment of patients with LCH of the temporal bone.MethodsWith Institutional Review Board (IRB) approval, cases of LCH involving the temporal bone were searched for within the institutional databases. Criteria for inclusion was histologic diagnosis of LCH and pretreatment computed tomography (CT) demonstrating temporal bone and/or otic capsule involvement and posttreatment follow-up CT/magnetic resonance imaging (MRI) scans obtained at least 6 months after starting treatment.ResultsWe report eight cases of LCH of the temporal bone with three demonstrating otic capsule involvement radiographically and/or clinically. Review of posttreatment imaging revealed all three patients had complete restoration of the bony labyrinthine architecture and near or complete restoration of their hearing.ConclusionsThough LCH of the temporal bone is a common site within the spectrum of the disease, involvement of the otic capsule remains rare. Here, we report the largest series of otic capsule involvement by LCH and investigate whether both architecture and hearing are recovered with appropriate treatment. Lastly, restoration of the bony architecture of the labyrinth suggests the mechanism of LCH is demineralization and not ablative.

Bilateral osteomas and exostoses of the internal auditory canal

Osteomas and exostoses are benign tumors of the bone that occur in the head and neck region but are rarely found within the internal auditory canal (IAC). In this report, we review the literature on bony lesions of the IAC and present two cases: one case of bilateral compressive osteomas and one case of bilateral compressive exostoses of the IAC.

Medical management of tinnitus: role of the physician.

Tinnitus is a common auditory complaint that can be caused by many auditory as well as nonauditory systems diseases. Comorbidities including insomnia, anxiety, and depression are common in severe tinnitus. Other factors such as personality characteristics and socioeconomic difficulties can also contribute to tinnitus distress. Management of tinnitus therefore requires diagnosis and treatment expertise by physicians to adequately address existing etiologies and comorbidities, as well as relevant expertise by nonphysician specialists such as audiologists and psychologists. In assessing the efficacy of tinnitus treatments, nonspecific effects such as placebo effects must be taken into consideration. Management of complex tinnitus cases often requires a multidisciplinary team approach. Physicians and nonphysician specialists need to promptly refer patients to relevant specialist colleagues for adequate evaluation and treatment when such needs are present.