Risk stratification in endoscopic type I. tympanoplasty.

PURPOSE: Several risk factors were studied in endoscopic type I. tympanoplasty, however, an easy-to-use risk stratification model is still missing. METHODS: Retrospective chart review, focusing on individual risk factors and middle ear risk index (MERI). Patients who underwent endoscopic type I. tympanoplasty were included. RESULTS: Closed tympanic cavity was succesfully created in 88.1% of the 42 cases, the overall 21,5 dB air-bone gap (ABG) was reduced by 9,8 dB. The average MERI score of the patients was 2.1 ± 1.5. 78.6% of the patients were categorised into the mild, while 21.4% into the moderate risk group. The perforation was considered small in 81.0% of the cases, while large in 19.0%. The size of the perforation and the preoperative ABG, but not the MERI status were the only single predictors of success. Using a risk stratification model that is based on the size of the perforation, the preoperative ABG and MERI status, patients could be referred into two distinct groups of risk: the majority expecting excellent outcomes with maximum one risk factor present, and patients with deteriorated rate of success when having two or three risk factors. CONCLUSIONS: Endoscopic type I. tympanoplasty with underlay perichondrium graft can be performed with good chance of success. However, if more than one risk factors are present, the chance of residual perforation becomes great. In addition to the established risk factors, our results point out that despite its strong correlation with perforation size, ABG may have a predictive role.

Limitations of non-echo planar diffusion weighted magnetic resonance imaging (non-EPI MRI) in cholesteatoma surveillance after ossicular chain reconstruction. A prospective study.

OBJECTIVE: Non-echo planar diffusion weighted magnetic resonance imaging is a reliable surveillance tool of residual cholesteatoma nowadays. It is not known whether the material of the ossicular chain prosthesis modifies the sensitivity and specificity of MRI in these cases. The aim of the study was to compare the sensitivity, specificity and a localization-specific accuracy of non-EPI DW MRI sequences for residual cholesteatoma in the following 3 subgroups: patients with titanium ossicular prosthesis (group T), with autologous cortical bone columella (group A) or without any reconstruction (group WR) of hearing bones. METHODS: This prospective study covered 28 cases with cholesteatoma of the middle ear undergone second-look surgery, who had preoperative PROPELLER DW-MRI. Surgical findings were compared to the results of the DWI-MRI. RESULTS: The overall sensitivity, specificity, positive predictive value (PPV) and negative predictive value (NPV) were: 0.76-0.8-0.76-0.8. Group T, group A and group WR sensitivity was 0.83-0.6-1, specificity: 0.75-0.75-0.85, PPV: 0.83-0.75-0.66, NPV: 0.75-0.6-1. Overall accuracy was 0.78. Size of missed cholesteatoma was 2-4 mm (mean: 2.66±1.15). CONCLUSIONS: Various materials are suitable for ossicular chain reconstruction. The poor detectability of residual or recurrent cholesteatoma in the middle ears reconstructed with autologous bony prosthesis may still claim second-look surgery instead of the usage of non- EPI DWI sequences independently in these patients.

Mal de débarquement syndrome ­ "sickness of disembarkment" / [Mal de débarquement szindróma - "partraszállási betegség"]

Mal de débarquement syndrome is an uncommon vestibular disorder characterized by a constant sensation of swaying or motion after one disembarks from a vehicle such as a ship or plane, however, spontaneous onset also appears. These symptoms temporarily subside when the patient is subjected again to passive motion like driving a car. Chronic fatigue, anxiety, and depression are frequently associated with primary symptoms. The diagnosis is challenging, and often made by the patients themselves. The underlying pathophysiology and definitive therapy are unknown. Exposure to optokinetic stimulations and transcranial magnetic stimulations open therapeutic perspectives. We report a case series of 5 patients who presented with constant rocking, bobbing sensation that had been ongoing for several months. We found normal inner-ear function, non-related abnormalities and normal brain imaging. By presenting our patients' histories, we discuss the different diagnostic issues that help to diagnose this condition. We aimed to report the most recent findings on aetiology and treatment methods and to share our experiences with different therapeutic attempts. Mal de débarquement syndrome is a diagnosis of exclusion and often unrecognized. A thorough clinical history, negative or non-specific clinical findings with a high degree of suspicion are needed for recognizing this disorder. Increasing awareness can lead to early diagnosis and prevent multiple physician visits and unnecessary diagnostic testing. Frequent diagnostic failure has a negative impact on the quality of life, associated with anxiety and depression. Orv Hetil. 2020; 161(20): 846-851.

[Otosclerosis. 2nd part. Diagnosis]. / Otosclerosis. 2. rész. Diagnózis.

Otosclerosis is a bone remodeling disorder affecting exclusively the human temporal bone which causes small bony lesions in the otic capsule. The symptoms depend on the location and the extent of the otosclerotic foci. Hence, clinically the most relevant sign is the conductive hearing loss due to the stapedial otosclerosis with fixation of the stapes footplate. In many cases, the specific anamnestic features, the age of presentation and usually the absence of tympanic membrane pathology can provide a strong clinical suspicion for otosclerosis. Although audiometric and imaging examinations and VEMP testing can confirm our preoperative diagnosis, the histolopathologic examination of the removed stapes footplate is the most accurate way to determine the diagnosis. Orv Hetil. 2019; 160(51): 2007-2011.

Does The Type of Ossicular Chain Lesion Affect Outcomes in Chronic Suppurative Otitis Media Without Cholesteatoma?

OBJECTIVES: We evaluated the pattern of ossicular chain (OC) lesion in chronic suppurative otitis media (CSOM) without cholesteatoma and its impact on outcomes in primary and revision surgeries. MATERIALS AND METHODS: This was a retrospective chart review. Patients who underwent tympanoplasty due to CSOM with OC defect between 2010 and 2015 were included in the study. RESULTS: OC lesions were found during 40 of 147 tympanoplasties performed due to CSOM. The preoperative air-bone gap (ABG) was greater in both discontinuity and fixation cases than in cases with CSOM with an intact OC (p<0.001). Twenty-nine patients were followed up postoperatively, after excluding four patients with stapes footplate fixation, in whom stapedotomy was not performed simultaneously. Among the 29 patients, the audiological results were similar in cases of discontinuity and fixation regarding gap change, residual ABG, and the rate of successful ossiculoplasty. Primary tympanoplasties provided better results according to postoperative ABG and the rate of successful ossiculoplasty than revision surgeries (p<0.05); however, similar patterns of OC lesions were found during primary and revision surgeries. CONCLUSION: Both OC discontinuity and fixation occur in CSOM in a similar distribution in primary tympanoplasties and revision surgeries. The type of OC lesion does not affect outcomes. Primary surgeries provide better results, but that is not due to a difference in the character of the OC lesion.

A unique manifestation of Langerhans cell histiocytosis: Diagnostic and therapeutic considerations of atypical cases.

Langerhans cell histiocytosis (LCH) is regarded as a clonal disease, usually carrying the activating BRAF mutation V600E. Although LCH theoretically may affect all types of human tissue and typically appears during childhood, temporal bone involvement in adult patients is exceedingly rare. We report an atypical case of a 56-year-old man as one of the oldest patients diagnosed with temporal bone involvement of a BRAF-negative LCH, which caused painless otorrhea and hearing loss. Cutaneous manifestation (multifocal multisystem LCH, also known as Letterer-Siwe disease) was later recognized incidentally. Administration of ifosfamide plus doxorubicin and mesna with supplementary irradiation resulted in a temporary remission followed by slow but constant tumor progression, which after 2.5 years became resistant to treatment with cytarabine and dasatinib. Attempts at therapy (cladribine) to achieve cure are ongoing.

Comparative analysis of preoperative diagnostic values of HRCT and CBCT in patients with histologically diagnosed otosclerotic stapes footplates.

This prospective case review was performed with the aim to compare and asses the diagnostic values of cone-beam computed tomography (CBCT) and high-resolution computed tomography (HRCT) in the preoperative evaluation of otosclerosis. A total of 43 patients with histologically confirmed stapedial otosclerosis, who underwent unilateral stapedectomies were analyzed. Preoperative temporal bone CBCT and HRCT scans were performed in all cases. Both CBCT and HRCT imaging were characterized by a slice thickness of 0.4-0.625 mm and multiplanar image reconstruction. Histopathologic examination of the removed stapes footplates was performed in all cases. Findings of CBCT and HRCT were categorized according to the modified Marshall's grading system (fenestral or retrofenestral lesions). Histopathologic results were correlated with multiplanar reconstructed CBCT and HRCT scans, respectively. Negative control groups for CBCT (n = 36) and HRCT (n = 27) examinations consisted of patients, who underwent CBCT imaging due to various dental disorders or HRCT analysis due to idiopathic sudden sensorineural hearing loss. Histologically active foci of otosclerosis (n = 31, 72 %) were identified by both CBCT and HRCT in all cases with a sensitivity of 100 %. However, CBCT could not detect histologically inactive otosclerosis (n = 12, 23 %; sensitivity 0 %). In contrast, HRCT showed inactive otosclerosis with a sensitivity of 59.3 %. According to CBCT results, no retrofenestral lesions were found and the overall sensitivity for hypodense lesions was 61.37 %. In conclusion, CBCT is a robust imaging method in the detection of histologically active fenestral hypodense foci of otosclerosis with high sensitivity and radiologic specificity. In the light of these results, HRCT still remains the basic imaging method in the preoperative diagnosis of otosclerosis, since it has much greater sensitivity and specificity in the detection of retrofenestral hypodense lesions and histologically inactive otosclerotic foci in the oval window niche.

Severe neck infections that require wide external drainage: clinical analysis of 17 consecutive cases.

Infections in the neck layers and spaces are potentially life-threatening diseases causing further complications, like mediastinitis, airway obstruction, or sepsis. Despite of the need for a conservative approach, they still regularly require surgical intervention. Records of 17 patients with severe neck infections that were treated by wide external incision and open wound management were retrospectively analyzed. The aim of the study was to clinically characterize these most serious neck infections. The most common presenting symptoms were neck pain and tense neck mass (94-94%) regularly with fever (65%), always accompanied by a marked elevation of C reactive protein level (average 192 uG/l). These findings were constant and very similar among both the deep neck infection and necrotizing fasciitis cases. More than half of the patients (53%) had at least one systemic co-morbidity. The parapharyngeal space was most commonly affected (83%), but extended disease involving more than two major neck regions was found in 13 cases (76%). Dental (29%) was the most common primary infection, followed by peritonsillar abscess (23%), Microbiological results showed a wide variety of corresponding bacteria. Mediastinitis was developed in three cases (18%), and airway obstruction requiring tracheostomy in two cases (12%). All the patients survived. Severe neck infections are a heterogenous group of diseases regarding to the primary site of infection, microbiology, localisation and host reaction. However, rapidly developed, painful, tense neck mass with a highly elevated CRP level should always alert for an extended or phlegmonous process in the layers or spaces of the neck.

Primary tuberculosis of the middle ear cleft: diagnostic and therapeutic considerations.

Tuberculosis remains one of the most challenging infectious diseases, which rarely manifests in the middle ear cleft exclusively. Typical symptoms of tuberculosis have become more and more confusing due to the genetic evolution of different Mycobacterium species. In the diagnosis of tuberculous otitis media (TOM), clinical suspicion plays a fundamental role, when topical and/or systemic antibiotic treatment cannot lead to improvement in ear discharge and inflammation. If there is no other reason of persisting otorrhea, microbiological sampling and culturing are the subsequent steps of diagnosis. These investigations, however, have low sensitivity; therefore a canal wall-up mastoidectomy is recommended, which includes the removal of necrotic bone and multiple histological sampling from various locations. Currently, histopathological analysis is the most robust and reliable method in the diagnosis of TOM. Tuberculin skin test, Mycobacterium-specific PCR and interferon-gamma release assay cannot distinguish between active, inactive or post-infective conditions. According to these considerations, these methods may serve as supplementary assays for the final diagnosis. Having the appropriate diagnosis after surgical intervention and laboratory analysis, medical management should be continued by anti-tuberculosis chemotherapy. Hereby, we demonstrate two cases with primary TOM and provide an overview of the literature in the light of diagnostic and therapeutic guidelines in the management of TOM.

Expression of bone morphogenetic protein 2, 4, 5, and 7 correlates with histological activity of otosclerotic foci.

CONCLUSION: This study is the first to establish that bone morphogenetic protein 5 (BMP5) plays a role in the pathogenesis of otosclerosis. These results confirm that elevated expression levels of BMPs, members of the transforming growth factor (TGF)-ß superfamily, contribute to the pathologically increased bone turnover in early, active stages of otosclerosis. OBJECTIVES: Otosclerosis is a complex bone remodeling disorder of the otic capsule, which might be characterized by increased expression of different types of BMPs. TGF-ß and BMP are both members of the TGF-ß superfamily and play a critical role in bone resorption and new bone formation. It has been suggested that BMP and its receptors may be involved in the pathologically increased bone turnover observed in otosclerosis. METHODS: Fifty-one otosclerotic and 16 non-otosclerotic ankylotic stapes footplates were histologically analyzed: conventional hematoxylin-eosin staining and BMP2, 4, 5, and 7specific immunofluorescent assays were performed. Cortical bone fragments (n = 35) and incus specimens (n = 6) were used as negative controls. RESULTS: Active otosclerosis (n = 39) was characterized by increased expression of BMP2, 4, 5, and 7. Inactive cases of otosclerosis (n = 12) were characterized by negative immunoreaction for BMPs. Non-otosclerotic stapes specimens (n = 16) and negative controls (n = 41) showed negligible BMP expression. The BMP expression pattern showed a strong correlation with the histological activity of otosclerosis.

No evidence for disturbed COL1A1 and A2 expression in otosclerosis.

Otosclerosis is a complex bone remodeling disorder of the human otic capsule that might be associated with various mutations of A1 and A2 alleles of type-I collagen. The study herein presented, investigates the possibilty of the genetic involvement of type-I collagen in the pathogenesis of histologically confirmed otosclerosis. A total of 55 ankylotic stapes footplates were analyzed. Cortical bone fragments (n = 30), incus (n = 3) and malleus (n = 2) specimens were employed as negative controls. Specimens were divided into two groups. The first group was processed using conventional H.E. hematoxylin-eosin (H.E.) staining and type-I collagen-specific immunofluorescent assay (IFA), while the second group was examined by COL1A1 and A2-specific RT-PCR. Otosclerotic- (n = 31) and non-otosclerotic stapes footplates (n = 9) as well as cortical bones (n = 20), incus (n = 2) and malleus specimens (n = 1) showed normal and quite similar A1 and A2 allele expression confirmed by IFA. RT-PCR analysis revealed normal and consistent mRNA expression of both alleles in each specimen. Expression levels and patterns of COL1A1/A2 alleles did not show significant correlation with the histological diagnosis of otosclerosis. Type-I collagen is a highly conserved structure protein, which plays a fundamental role in the integritiy of various connective tissues. Mutations of A1 and A2 alleles result in serious systemic disorders of the skeleton, tendons and skin. Since otosclerosis is an organ-specific disease, it is difficult to explain its genetic association with type-I collagen. In conclusion, we found no evidence supporting the putative link of COL1A1 and COL1A2 alleles with otosclerosis.

Otosclerosis: disturbed balance between cell survival and apoptosis.

HYPOTHESIS: Otosclerosis is an inflammatory bone remodeling disorder of the human otic capsule, which might be characterized by a disturbed balance between cell survival and apoptosis due to an increased expression of inflammatory cytokines, mainly tumor necrosis factor-[alpha] (TNF-[alpha]). BACKGROUND: Histologic features of otosclerosis have been well described; however, different histopathologic and clinical stages have not been attributed precisely to the molecular biology of the pathologically increased metabolism of bone-forming and bone-resorbing cells. METHODS: Forty ankylotic stapes footplates (n = 40, males = 17, females = 23) removed by stapedectomy were histologically analyzed by conventional hematoxylin-eosin staining, and hCIAP1/2 (inhibitors of apoptosis) and granzyme-[beta] (apoptosis inducer) specific immunofluorescent assays were performed. Four normal stapes footplates obtained from cadavers with negative otologic history were used as negative controls. RESULTS: Active otosclerosis (n = 19) was featured by robust expression of apoptosis inhibitor proteins hCIAP1/2 and negligible expression of granzyme-[beta]. Inactive cases of otosclerosis (n = 8) were characterized by inverse reaction: granzyme-[beta] was highly expressed; however, hCIAP1/2 specific immunoreactions were absent. Nonotosclerotic and normal stapes specimens showed no considerable little granzyme-[beta] expression and moderate hCIAP1/2-specific immunoreactions. Expression pattern of apoptosis-associated proteins showed strong correlation with the histologic diagnosis and activity of otosclerosis (Yates-corrected [chi]2 test, p < 0.001). CONCLUSION: Detection of the inversely expressed apoptosis inhibitor and inducer proteins in active and inactive stages of otosclerosis demonstrates pathologic regulation of cell survival and apoptosis. These results may suggest active otosclerosis inactivation by TNF-[alpha] induced apoptosis. Anti-TNF-[alpha] biologics may serve as an option in the medical treatment of active otosclerosis.

Histopathology of nonotosclerotic stapes fixations.

HYPOTHESIS: Different diseases without exact histopathologic classification can cause stapes ankylosis. BACKGROUND: Otosclerosis is a complex bone remodeling disorder of the otic capsule due to persisting measles virus infection and consecutive inflammatory reaction. In fact, clinical and demographic features of otosclerosis have reference to stapes ankylosis. In the clinical practice, otosclerosis and stapes ankylosis are incorrect synonyms. METHODS: Nonotosclerotic stapes footplates (n = 284) removed during stapedectomy were analyzed histologically. Otosclerosis was excluded during the histologic preselection (n = 437). Total RNA was extracted, and measles virus-specific reverse-transcriptase-polymerase chain reaction was performed. RESULTS: Nonotosclerotic stapes ankylosis was associated with total absence of measles virus RNA. Six main types of nonotosclerotic stapes fixations could be distinguished histologically: annular calcification (n = 152; 53.5%), globular fibrosis (n = 49; 17.25%), lymphocytic infiltration (n = 31; 10.9%), hemosiderosis (n = 22; 7.75%), granulomas (n = 17; 6%) and amyloidosis (n = 13; 4.6%). Fragmentation of nonotosclerotic stapes footplates was infrequent (7%) during stapes surgery. Only 1 floating footplate (0.35%) was reported. CONCLUSION: Two thirds of nonotosclerotic stapes footplates represented complete pathologic bone remodeling. Unlike otosclerosis, nonotosclerotic stapes fixations were characterized by basic histopathologic findings without organ specificity that can also be identified in case of different diseases. Prevalence of nonotosclerotic stapes ankylosis is approximately 30 to 40% among stapes fixation cases. The long-term prognosis and surgical considerations theoretically differ from those of otosclerosis.

Dual effect of pyruvate in isolated nerve terminals: generation of reactive oxygen species and protection of aconitase.

Generation of reactive oxygen species (ROS) in synaptosomes was investigated in the presence of different substrates. When pyruvate was used as a substrate an increased rate of hydrogen peroxide formation was detected by the Amplex Red fluorescent assay, but aconitase, which is known to be a highly sensitive enzyme to ROS was not inhibited. In contrast, pyruvate exerted a partial protection on aconitase against a time-dependent inactivation that occurred when synaptosomes were incubated in the absence of substrates. Disruption of synaptosomal membranes with Triton X-100 prevented the protective effect of pyruvate. It is suggested that citrate and/or isocitrate formed in the metabolism of pyruvate could be responsible for a partial protection of aconitase. Therefore while pyruvate could have a prooxidant effect it could also exert a protective effect on the aconitase.