Massimo Ralli

Behçet's disease: New insights into pathophysiology, clinical features and treatment options

Behçets disease (BD) is a rare systemic vasculitis characterized by oral aphthous ulcers, genital ulcers, ocular lesions and other systemic manifestations. BD occurs most frequently in Eurasian populations along the ancient trading route known as the Silk Road which extends from eastern Asia to the Mediterranean basin. The causes of BD are unknown: it is believed to be due to an autoimmune process triggered by an infectious or environmental agent in genetically predisposed individuals. HLA-B51 allele located in the MHC locus, on chromosome 6p, has been the most strongly associated risk factor for BD in areas along the Old Silk Route. Herpes simplex virus-1 and Streptococcus have been postulated as possible environmental triggers of BD. T cell homeostasis perturbation, especially Th1 and Th17 expansion and decreased regulation by Tregs are now supposed to be the cornerstone of BD pathogenesis. The histology shows vasculitis that involves both arteries and veins, and vessels of any size. BD is a systemic vasculitis with significant neutrophil infiltration, endothelial cell swelling, and fibrinoid necrosis. The diagnosis of BD is only supported by clinical criteria and requires the exclusion of other diagnoses based on clinical presentation. There are no pathognomonic laboratorial findings of BD. This rare disease often leads to blindness and fatal systemic involvement. Main causes of death include major vessel disease and central nervous system involvement. Corticosteroids are commonly used to treat clinical manifestations of BD in combination with immunosuppressant drugs. Tumor necrosis factor (TNF)-blocking agents such as Infliximab, Etanercept, and Adalimumab have been reported to have success in patients with BD.

Hearing loss in autoimmune disorders: Prevalence and therapeutic options

The objective of this study was to review our current knowledge relative to the correlation between sensorineural hearing loss (SNHL) and autoimmune diseases, focusing on the prevalence of hearing loss in different pathologies and possible therapeutic approaches. A review of the literature on hearing loss in different forms of autoimmune disease has been carried out, with emphasis on incidence and prevalence of SNHL. Therapeutic protocols have been assessed including both conservative medical and rehabilitative methods. Cochlear implant outcomes have been investigated. The prevalence of hearing loss in autoimmune and immune-mediated inner ear diseases, as referred by case reports or single-center statistics, is widely variable. More difficult is the evaluation of severe/profound SNHL, usually reported in relation to cochlear implantation. Though these patients represent ideal candidates for cochlear implantation, as they become deaf after years of hearing; the associated systemic disease, the specific damage on inner ear structures and the medication taken may influence the result of cochlear implantation. The main problem is the cochlear fibrosis or ossification that has been found to affect 50% of implanted ears in patients suffering from autoimmune and immune-mediated SNHL. Hence, in the presence of severe/profound SNHL earlier implantation may be indicated before post-inflammatory obliterative changes to the cochlea.

Diagnosis and management of neuromyelitis optica spectrum disorders - An update

Neuromyelitis optica (NMO) and Neuromyelitis optica spectrum disorders (NMOSD) are a group of autoimmune conditions characterized by inflammatory involvement of the optic nerve, spinal cord and central nervous system. Novel evidence showed a key role of autoantibodies against aquaporin-4 immunoglobulin G (AQP4 IgG) in the pathogenesis of NMOSD and, recently, new classification and diagnostic criteria have been adopted to facilitate an earlier identification and improve the management of these conditions. Diagnosis of NMOSD is currently based on clinical, neuroimaging and laboratory features. Standard treatment is based on the use of steroids and immunosuppressive drugs and aims to control the severity of acute attacks and to prevent relapses of the disease. This review gives an update of latest knowledge of NMOSD and NMO, emphasizing the novel diagnostic criteria and both current and future therapeutic approaches.

Does focal mechanical stimulation of the lower limb muscles improve postural control and sit to stand movement in elderly

BackgroundsImbalance in elderly is a common problem strictly related to fall.AimsThis study investigates the possibility that a new protocol based on the focal mechanical muscle vibration may improve balance and stability in elderly.MethodsPre-post non-randomized clinical trial has been used. Patients referring postural disequilibrium with negative vestibular bed-side examinations have been treated with focal muscle vibration applied to quadriceps muscles and evaluated before and immediately after therapy and after 1xa0week and after 1xa0month with postural stabilometric examination and with an inertial measurement units during the time up and go test.ResultsStabilometric analysis showed statistically significant differences in both the area (pu2009=u20090.01) and sway (pu2009<u20090.01) of the center of pressure during the close eyes tests. Moreover, the global time of the time up and go test was reduced (pu2009<u20090.05) and the rotation velocity was increased (pu2009<u20090.01).ConclusionsThe findings confirm the beneficial role of focal muscle vibration in elderly patients improve postural stability and mobility.

Development of progressive hearing loss and tinnitus in a patient with myasthenia gravis: an overlooked comorbidity?

Abstract Purpose: There is evidence of progressive antibody-mediated loss of acetylcholine receptors on outer hair cells in the inner ear that underlies hearing dysfunction in myasthenia gravis patients. In this paper, we present the case of a 35-year-old patient with adult-onset myasthenia gravis and thymoma who experienced progressive hearing loss and bilateral high-pitched tone tinnitus worsening over time. Materials and methods: Patient underwent pure tone audiometry, acoustic immittance test, decay test, transient-evoked and distortion product otoacustic emissions with and without contralateral acoustic stimulation, somatosensory tinnitus screening maneuvers and self-assessment questionnaires for tinnitus, hearing loss and hyperacusis, in addition to anamnestic interview and complete ENT visit. Questionnaires for psychiatric comorbidities (SCL90R – Symptom Checklist 90 Revisited) were also administered to the patient. The patient was studied in baseline conditions and 1u2009h after administration of the acetylcholinesterase inhibitor pyridostigmine bromide, a drug that has been reported to have a temporary effect on outer hair cell electromotility in myasthenia gravis patients. Results: Pure-tone audiometry showed a progressive hearing loss for high frequencies. Consistently, transient-evoked and distortion product otoacoustic emission amplitudes were significantly reduced for mid and, especially, high frequencies; after drug administration, a significant otoacoustic emission amplitude increase was recorded. Conclusions: Our findings documented a chronic dysfunction of outer hair cells consistent with acetylcholine receptor loss; these alterations could represent a basis for development of hearing loss and tinnitus.

Electrochemotherapy in head and neck cancer: A review of an emerging cancer treatment (Review)

Patients affected by aggressive neoplasms with a high propensity to metastasize to the skin, including some types of head and neck cancer, may benefit from electrochemotherapy, a modality that combines the electroporation of cell membranes and chemotherapy to facilitate the transport of non-permeant molecules into cells; the host immune response consequently participates in achieving the abolition of tumors. Electrochemotherapy can be successfully used for skin metastases of head and neck tumors and, with some limitations, for primary and relapsing neoplasms; it can also be applied on an outpatient basis with a favorable cost-benefit ratio and it is a repeatable treatment that, if necessary, can be followed by traditional antineoplastic therapies. Although still a palliative treatment, the good level of tolerability and the high success rates of electrochemotherapy make it worth consideration among treatment options in selected patients.

Nasopharyngeal angiofibroma in an elderly female patient: A rare case report

Juvenile nasopharyngeal angiofibroma, which accounts for <1% of all head and neck neoplasms, occurs predominantly in males between 10 and 18 years of age. The small number of patients older than 30 years confirms that presentation after this age is exceptional. Only rare cases of nasopharyngeal angiofibroma in female patients have been documented to date, and some authors believe that sex chromosome studies are indicated in such cases. The pathogenesis of nasopharyngeal angiofibroma remains unknown, but it has been hypothesized that it is a testosterone-dependent tumor. We herein report a particularly rare case of a 68-year-old woman diagnosed with nasopharyngeal angiofibroma and describe the diagnostic and therapeutic workup. This case describes, to the best of our knowledge, the oldest patient reported in the literature.

Universal newborn hearing screening in the Lazio region, Italy

BackgroundThe introduction of Universal Newborn Hearing Screening (UNHS) programs has drastically contributed to the early diagnosis of hearing loss in children, allowing prompt intervention with significant results on speech and language development in affected children. UNHS in the Lazio region has been initially deliberated in 2012; however, the program has been performed on a universal basis only from 2015. The aim of this retrospective study is to present and discuss the preliminary results of the UNHS program in the Lazio region for the year 2016, highlighting the strengths and weaknesses of the program.MethodsData from screening facilities in the Lazio region for year 2016 were retrospectively analyzed. Data for Level I centers were supplied by the Lazio regional offices; data for Level II and III centers were provided by units that participated to the study.ResultsDuring 2016, a total of 44,805 babies were born in the Lazio region. First stage screening was performed on 41,821 children in 37 different birth centers, with a coverage rate of 93.3%. Of these, 38.977 (93.2%) obtained a “pass” response; children with a “refer” result in at least one ear were 2844 (6.8%). Data from Level II facilities are incomplete due to missing reporting, one of the key issues in Lazio UNHS. Third stage evaluation was performed on 365 children in thexa0three level III centersxa0of the region, allowing identification of 70 children with unilateral (40%) or bilateral (60%) hearing loss, with a prevalence of 1.6/1000.ConclusionsThe analysis of 2016 UNHS in the Lazio region allowed identification of several strengths and weaknesses of the initial phase of the program. The strengths include a correct spread and monitoring of UNHS among Level I facilities, with an adequate coverage rate, and the proper execution of audiological monitoring and diagnosis among Level III facilities. Weakness, instead, mainly consisted in lack of an efficient and automated central process for collecting, monitoring and reporting of data and information.

Hidden age-related hearing loss and hearing disorders: current knowledge and future directions

Abstract Age-related hearing loss, which affects roughly 35% of those over the age of 70, is the second most common disorder among the elderly. The severity of age-related hearing loss may actually be worse if assessments are made under more realistic conditions, such as communicating in noise. Emerging data from humans and animal models suggest that damage to the inner hair cells and/or type I neurons that relay sound information to the brain may contribute to hearing deficits in a noisy background. Data obtained from carboplatin-treated chinchillas suggest that tone-in-noise thresholds are a sensitive and frequency dependent method of detecting damage to the IHC/type I system. Therefore, tone detection thresholds measured in broadband noise may provide an efficient method of detecting the deficits in specific frequency regions. Preliminary data obtained in elderly subject with normal thresholds in quiet compared to young subjects illustrate the importance of repeating these measurements in broadband noise because thresholds in noise were worse for our elderly subjects than young subjects, even though both groups had similar hearing thresholds in quiet. N-acetyl cysteine supplementation which protects against inner hair cell loss in animal models may represent a viable therapy for protecting the inner hair cell/type I neurons.

Audiovestibular Symptoms in Systemic Autoimmune Diseases

Immune-mediated inner ear disease can be primary, when the autoimmune response is against the inner ear, or secondary. The latter is characterized by the involvement of the ear in the presence of systemic autoimmune conditions. Sensorineural hearing loss is the most common audiovestibular symptom associated with systemic autoimmune diseases, although conductive hearing impairment may also be present. Hearing loss may present in a sudden, slowly, rapidly progressive or fluctuating form, and is mostly bilateral and asymmetric. Hearing loss shows a good response to corticosteroid therapy that may lead to near-complete hearing restoration. Vestibular symptoms, tinnitus, and aural fullness can be found in patients with systemic autoimmune diseases; they often mimic primary inner ear disorders such as Menières disease and mainly affect both ears simultaneously. Awareness of inner ear involvement in systemic autoimmune diseases is essential for the good response shown to appropriate treatment. However, it is often misdiagnosed due to variable clinical presentation, limited knowledge, sparse evidence, and lack of specific diagnostic tests. The aim of this review is to analyse available evidence, often only reported in the form of case reports due to the rarity of some of these conditions, of the different clinical presentations of audiological and vestibular symptoms in systemic autoimmune diseases.