Hearing and Ageing.

Age-related hearing loss (ARHL), or presbycusis, occurs in most mammals, humans included, with a different age of onset and magnitude of loss. It is associated with two major symptoms: loss of sensitivity to sound, especially for high pitches, and a reduced ability to understand speech in background noise. This phenomenon involves both the peripheral structures of the inner ear and the central acoustic pathways. Several mechanisms have been identified as pro-ageing in the human cochlea. The main one is the oxidative stress. The inner ear physiological degeneration can be affected by both intrinsic conditions, such as genetic predisposition, and extrinsic ones, such as noise exposure. The magnitude of neuronal loss precedes and exceeds that of inner hair cell loss, which is also less important than the loss of outer hair cells. Patients with HL often develop atrophy of the temporal lobe (auditory cortex) and brain gliosis can contribute to the development of a central hearing loss. The presence of white matter hyperintensities (WMHs) on the MRI, which is radiologic representation of brain gliosis, can justify a central HL due to demyelination in the superior auditory pathways. Recently, the presence of WMHs has been correlated with the inability to correctly understand words in elderly with normal auditory thresholds.

Global and local brain connectivity changes associated with sudden unilateral sensorineural hearing loss.

Recent studies suggest that even moderate sudden sensorineural hearing loss (SSNHL) causes reduction of gray matter volume in the primary auditory cortex, diminishing its ability to react to sound stimulation, as well as reorganization of functional brain networks. We employed resting-state functional MRI (rs-fMRI), in conjunction with graph-theoretical analysis and a newly developed functional "disruption index," to study whole-brain as well as local functional changes in patients with unilateral SSNHL. We also assessed the potential of graph-theoretical measures as biomarkers of disease, in terms of their relationship to clinically relevant audiological parameters. Eight patients with moderate or severe unilateral SSNHL and 15 healthy controls were included in this prospective pilot study. All patients underwent rs-fMRI to study potential changes in brain connectivity. From rs-fMRI data, global and local graph-theoretical measures, disruption index, and audiological examinations were estimated. Mann-Whitney U tests were used to study the differences between SSNHL patients and healthy controls. Associations between brain metrics and clinical variables were studied using multiple linear regressions, and the presence or absence of brain network hubs was assessed using Fisher's exact test. No statistically significant differences between SSNHL patients and healthy controls were found in global or local network measures. However, when analyzing brain networks through the disruption index, we found a brain-wide functional network reorganization (p < 0.001 as compared with controls), whose extent was associated with clinical impairment (p < 0.05). We also observed several functional hubs in SSNHL patients that were not present in healthy controls and vice versa. Our results demonstrate a brain involvement in SSNHL patients, not detectable using conventional graph-theoretical analysis, which may yield subtle disease clues and possibly aid in monitoring disease progression in clinical trials.

Cochlear Dysfunction Is a Frequent Feature of Facioscapulohumeral Muscular Dystrophy Type 1 (FSHD1).

INTRODUCTION: Facioscapulohumeral muscular dystrophy type 1 (FSHD) represents one of the most common forms of muscular hereditary diseases and it is characterized by a great clinical variability with the typical muscular symptoms and other clinical features, including hearing impairment. However, etiopathogenetic mechanisms of auditory dysfunction are still not completely understood and it has been suggested that it could be assigned to a cochlear alteration that is present even in those subjects with a normal pure tonal audiometry (PTA) examination. METHODS: We found out the cochlear function in 26 patients with molecular diagnosis of FSHD1 and in healthy controls. All patients underwent complete neurological and audiological examinations, including FSHD clinical score, pure-tone audiometry (PTA), and otoacoustic emissions (OAEs), in particular transient evoked otoacoustic emissions (TEOAEs) and distortion product evoked otoacoustic emissions (DPOAEs). RESULTS: All FSHD1 patients showed significantly reduced DPOAEs and TEOAEs, bilaterally and at all frequencies, even when considering only subjects with a normal PTA or a mild muscular involvement (FSHD score ≤ 2). No correlation between OAEs and FSHD clinical score was found. DISCUSSION: Cochlear echoes represent a sensitive tool in detecting subclinical cochlear dysfunction in FSHD1 even in subjects with normal hearing and/or subtle muscle involvement. Our study is focused on the importance of evaluating the cochlear alteration through OAEs and, in particular, by performing TEOAEs and DPOAEs sequentially, to evaluate more frequent specificities of cochlear dysfunction with a wider spectrum of analysis.

Global and local reorganization of brain network connectivity in sudden sensorineural hearing loss.

Recent reports suggested that even moderate sudden sensorineural hearing loss (SSNHL) can be partly responsible for a loss of gray matter volume in the primary auditory cortex, hence reducing the capacity of the auditory cortical areas to react to sound stimulation. There is also evidence for a plastic reorganization of brain functional networks visible as enhanced local functional connectivity. The aim of this study was to use rs-fMRI, in conjunction with graph- theoretical analysis and a newly developed functional "disruption index" to study whole-brain as well as local functional changes in patients with acute and unilateral sensorineural hearing loss. No statistically significant differences in global or local network measures we found between SSNHL patients and healthy controls. However, when analyzing local metrics through the disruption index k, we found negative values for k which were statistically different from zero both in single subject analysis. Additionally, we found several associations between graph-theoretical metrics and clinical parameters.

HPV infection and clinical profiles in laryngeal diseases. A preliminary study.

PURPOSE: The study analysed the presence of HPV in samples tissue from laryngeal chronic hyperplastic inflammation, with and without pre-neoplastic potential, and from squamous cell carcinoma of the larynx. The aim of this analysis was to evaluate the presence/absence of different types of HPV and their relationship to the clinical profile of the patients studied (habit of smoking and drinking). METHODS: Sixty cases were randomly selected from patients undergoing surgical treatment of the larynx for inflammatory/ neoplastic lesions and of neck nodes. Patients underwent standard clinical workup, comprising medical history and physical examination, panendoscopy, whole-body CT scan (in cancer patients), diagnostic or therapeutic microlaryngoscopy with laryngeal biopsy, and HPV evaluation. RESULTS: The HPV analysis showed an increased risk for heavy smokers of HPV positivity, as well as precancer lesions and cancer. Type 6 and 16 seem to be prevalent in all types of laryngeal mucosa disease, but pre-neoplastic conditions versus cancer seem to show a wider variety of HPV infections while cancer patients are invariably affected by types 6 and 66. Heavy smoking is related to HPV infection likewise alcohol in association with smoking. Advanced T is more associated with HPV positivity. CONCLUSIONS: These data impose a closer follow-up of smokers and pre-neoplastic cases and the utility of the broadspectrum polymerase chain reaction assay in laryngeal dysplastic and cancer lesions. This study may allow to develop biomarkers for early detection or recurrence surveillance, to identify therapeutic targets, and to begin individualization of treatment based on the biology of these tumours. KEY WORDS: HPV infection, Larynx, Laryngeal chronic hyperplastic inflammation, Squamous cell carcinoma.

Subclinical cochlear dysfunction in newly diagnosed relapsing-remitting multiple sclerosis.

BACKGROUND: Hearing impairment in multiple sclerosis has long been considered a process mainly related to the central auditory system. However, increasing evidence also suggests a peripheral involvement of the inner ear. The objective of this study was to investigate subclinical cochlear dysfunction and possible correlation with disease severity in untreated newly diagnosed multiple sclerosis patients using transient-evoked and distortion-product otoacoustic emissions. METHODS: Forty patients with newly diagnosed relapsing-remitting multiple sclerosis, clinically normal hearing and no brainstem lesions (study group) and forty matched controls (control group) were included in the study. All subjects had a routine audiological evaluation including history and clinical examination, pure tone audiometry, acoustic immittance test, auditory brainstem response and otoacoustic emissions recording. Self-administered questionnaires were used to evaluate self-perception of hearing disability. RESULTS: Auditory brainstem response and pure tone audiometry thresholds resulted within normal range in all patients. The amplitudes of transient-evoked and distortion-product otoacoustic emissions responses were significantly reduced at 1000, 1500, 2000 and 3000 Hz in the study group compared to the control group. CONCLUSIONS: This study shows decreased otoacoustic emission amplitudes in untreated multiple sclerosis patients with clinically normal hearing and no brainstem demyelinating plaques, suggesting a subclinical cochlear impairment. This alteration may represent an early sign of peripheral hearing damage, suggesting a role for otoacoustic emissions in the early diagnosis of cochlear dysfunction in multiple sclerosis patients. However, given that otoacoustic emissions primarily reflects cochlear function, and that the wave I of the auditory brainstem responses was spared, the evidence supporting a peripheral involvement of acoustic pathways due to multiple sclerosis can only be hypothetically attributed to an early subclinical involvement of outer hair cells.

Pisa Syndrome in Parkinson's Disease: Evidence for Bilateral Vestibulospinal Dysfunction.

INTRODUCTION: Pisa syndrome (PS) is a postural complication of Parkinson's disease (PD). Yet, its pathophysiology remains unclear, although a multifactorial component is probable. Cervical vestibular evoked myogenic potentials (cVEMPs) explore vestibulospinal pathway, but they have not been measured yet in PD patients with PS (PDPS) to assess a potential vestibular impairment. MATERIALS AND METHODS: We enrolled 15 PD patients, 15 PDPS patients, and 30 healthy controls (HCs). They underwent neurological examination and were examined with Unified Parkinson's Disease Rating Scale II-III (UPDRSII-III), audiovestibular workup, and cVEMP recordings. Data were analysed with Chi-square, one-way ANOVA, multinomial regression, nonparametric, and Spearman's tests. RESULTS: cVEMPs were significantly impaired in both PD and PDPS compared with HCs. PDPS exhibited more severe cVEMP abnormalities with prevalent bilateral loss of potentials, compared with the PD group, in which a prevalent unilateral loss was instead observed. No clinical-neurophysiological correlations emerged. CONCLUSIONS: Differently from HC, cVEMPs are altered in PD. Severity of cVEMPs alterations increases from PD without PS to PDPS, suggesting an involvement of vestibulospinal pathway in the pathophysiology of PS. Our results provide evidence for a significant impairment of cVEMPs in PDPS patients and encourage further studies to test validity of cVEMPs as diagnostic and prognostic biomarkers of PD progression.

The role of intraoperative stroke volume variation on bleeding during functional endoscopic sinus surgery.

BACKGROUND: Functional endoscopic sinus surgery (FESS) is a minimally-invasive surgical technique for patients with paranasal sinus pathology. Surgical bleeding reduces operative field visibility and increases the incidence of serious complications. Epinephrine injection into the nasal mucosa and controlled hypotension are used to minimize bleeding. Hypotension carries risks and sometimes does not reduce surgical bleeding. The goal of this study is to discover which hemodynamic parameter better correlates with surgical bleeding. METHODS: We enrolled 55 patients undergoing FESS. Inclusion criteria: male or female with chronic rhinosinusitis (CRS), older than 18 years, ASA I to III and primary surgery. Exclusion criteria: ASA>III, cerebrovascular and cardiac disorders, supraventricular tachycardia, renal or hepatic diseases, non-treated arterial hypertension, beta-blocking agent therapy, platelet-inhibiting agent or anticoagulant therapy, coagulopathy, pregnancy, clotting disorders, presence of neoplastic lesions and history of cranio-facial surgery. We used standard ASA plus ClearSight to assess hemodynamic parameters. Surgical procedures were performed by one surgeon and divided in ten surgical times (from T0 to T9). Intraoperative bleeding was assessed using the Fromme-Boezaart Scale. RESULTS: Analysis between all the hemodynamic parameters registered and the Fromme-Boezaart Score showed a negative correlation between surgical bleeding and stroke volume variation (SVV) only. When dichotomizing according to Fromme-Boezaart Score (above or below 2), SVV was the only parameter which showed significant differences between groups. A cut-off of 12.5% in SVV is optimal to distinguish the group with the better surgical visibility from the group with the worst one. CONCLUSIONS: Targeting SVV larger than 12% achieves a possible reduction of the intraoperative bleeding in patients undergoing FESS.

An investigation of hearing impairment in de-novo Parkinson's disease patients: A preliminary study.

OBJECTIVE: To investigate the peripheral auditory pathway in Parkinson's disease (PD) by using objective, quantitative and non-invasive audiological techniques, transient-evoked (TEOAE) and distortion product (DPOAE) otoacoustic emissions, in order to detect subclinical alterations of cochlear functioning and possible changes after dopaminergic stimulation. METHODS: We enrolled 11 untreated de-novo PD patients and 11 age and sex-matched healthy controls. Subjects underwent a routine audiological evaluation and otoacoustic emission recordings. The patients were then slowly-titrated to a stable dose of 100 mg levodopa four times in a day. A post-treatment assessment was made in order to detect significant changes in audiological responses. Finally, possible associations between clinical data and hearing results were also evaluated. RESULTS: At pure-tone audiometry, higher auditory threshold levels were observed in PD when compared to the controls. Moreover, DPOAE responses in PD patients were found low at almost all tested frequencies, suggesting subclinical cochlear damage. Interestingly, after dopaminergic treatment, a significant increase in DPOAE responses was detected. Notably, DPOAE dysfunction correlated with clinical severity, whereas high hearing thresholds appeared positively related with more prolonged disease duration. CONCLUSIONS: Our findings demonstrate that otoacoustic emission recording and pure-tone audiometry reveal levodopa-sensitive cochlear dysfunction and hearing loss in PD. A parallel improvement in subjective motor symptoms and DPOAE objective responses could help clinicians in monitoring therapeutic responses and dynamic changes during the course of the disease.

A survey of the nature of trauma of post-traumatic benign paroxysmal positional vertigo.

OBJECTIVE: A clinical description of post-traumatic benign paroxysmal positional vertigo (t-BPPV) in a large cohort is reported, sometimes caused by apparently insignificant minor head traumas. The aim of the study was to carefully assess the prevalence of t-BPPV and the main outcomes belonging to specific traumatic events. DESIGN: Retrospective analysis of medical records of t-BPPV cases among patients suffering from BPPV. STUDY SAMPLE: Among 3060 patients with a clinical diagnosis of BPPV, we reviewed 716 clinical cases in which a clear association to a traumatic event was present. RESULTS: A traumatic event was identified in 23.4% of total enrolled BPPV patients. Some minor head traumas could be more prone to determine BPPV in females. We confirmed that t-BPPV appeared significantly more difficult to treat than idiopathic form. Posterior canal t-BPPV cases required more treatment sessions before obtaining therapeutic success, while horizontal ones recovered at most after two repositioning maneuvers. CONCLUSION: Post-traumatic BPPV is considered one of the most common known etiologies. An accurate understanding of trauma mechanism, gender prevalence, and therapeutic success rates of each event, could be useful in adequately treating and planning follow-up examinations.

Great auricular nerve preservation in parotid surgery: rationale and long-term results insights.

Great auricular nerve (GAN) is frequently sacrificed during parotid surgery. GAN preservation during parotidectomy is advised to avoid complications such as sensitive disorders, but debate still exists. In this study, our experience is reported on the matter. From a cohort of 173 parotidectomies carried out in the period 2005-2010, we studied 60 patients: 20 patients in which we preserved only the posterior branch of GAN (group A), 20 patients in which we preserved also the lobular branch (group B) and 20 patients in which the main trunk of GAN was sectioned (group C); we evaluated tactile sensitivity in all the skin supplied by GAN at 1 week, 1 month, 6 months and 1 year after surgery. Group B is the best in terms of loss and recovery of sensitivity after 1-year post-surgery, followed closely by group A, on the contrary group C confirmed to be the worst. Results suggest that saving as many branches of the GAN as possible during parotid surgery could be useful for reducing hypo-dysesthesia. Preserving posterior and lobular branches of the GAN, when possible, improves the sensitivity of the preauricular area with better quality of life for the patient.

Surgical management of rhinosinusitis in onco-hematological patients.

OBJECTIVES: In onco-hematological diseases, the incidence of paranasal sinuses infection dramatically increase and requires a combination of medical and surgical therapy. Balloon dilatation surgery (DS) is a minimally invasive, tissue preserving procedure. The study evaluates the results of DS for rhinosinusitis in immunocompromised patients. METHODS: A retrospective chart review was conducted in 110 hematologic patients with rhinosinusitis. Twenty-five patients were treated with DS technique and 85 patients with endoscopic sinus surgery (ESS). We considered the type of anesthesia and the extent of intra- and postoperative bleeding. Patients underwent Sino-Nasal Outcome Test (SNOT-20) to evaluate changes in subjective symptoms and global patient assessment (GPA) questionnaire to value patient satisfaction. RESULTS: Local anesthesia was employed in 8 cases of DS and in 15 of ESS. In 50 ESS patients, an anterior nasal packing was placed and in 12 cases a repacking was necessary. In the DS group, nasal packing was required in 8 cases and in 2 cases a repacking was placed (P=0.019 and P=0.422, respectively). The SNOT-20 change score showed significant improvement of health status in both groups. However the DS group showed a major improvement in 3 voices: need to blow nose, runny nose, and facial pain/pressure. The 3-month follow-up GPA questionnaire showed an higher satisfaction of DS group. CONCLUSION: Balloon DS represents a potentially low aggressive treatment and appears to be relatively safe and effective in onco-hematologic patients. All these remarks may lead the surgeon to consider a larger number of candidates for surgical procedure.

Unusual postrhinoplasty complication: nasal dorsum cyst.

AMONG ALL THE POSSIBLE COMPLICATIONS OF AESTHETIC RHINOPLASTY, A RARE ONE IS THE DEVELOPMENT OF CYSTIC MASSES ON THE NASAL DORSUM: several theories suggest that cysts develop commonly by entrapment of nasal mucosa in the subcutaneous space, but they can also originate from foreign body reactions. This report deals with two cases of nasal dorsum cysts with different pathogenesis: both patients had undergone aesthetic rhinoplasty in the past (26 years ago and 14 years ago, resp.). Both cystic masses were removed via a direct open approach and nasal reconstruction was performed successfully with autologous vomer bone. The pathologic investigations showed a foreign body inclusion cyst associated with latex rubber in the first case and a sequestration of a mucosal-lined nasal bone was not removed at the time of primary rhinoplasty in the second case. A brief review of the literature focuses on the pathophysiology and treatment options for nasal dorsal cysts following aesthetic rhinoplasty.

Robotic image-guided stereotactic radiotherapy, for isolated recurrent primary, lymph node or metastatic prostate cancer.

PURPOSE: To evaluate the outcome of robotic CyberKnife (Accuray, Sunnyvale, CA)-based stereotactic radiotherapy (CBK-SRT) for isolated recurrent primary, lymph node, or metastatic prostate cancer. METHODS AND MATERIALS: Between May 2007 and December 2009, 34 consecutive patients/38 lesions were treated (15 patients reirradiated for local recurrence [P], 4 patients reirradiated for anastomosis recurrence [A], 16 patients treated for single lymph node recurrence [LN], and 3 patients treated for single metastasis [M]). In all but 4 patients, [(11)C]choline positron emission tomography/computed tomography was performed. CBK-SRT consisted of reirradiation and first radiotherapy in 27 and 11 lesions, respectively. The median CBK-SRT dose was 30 Gy in 4.5 fractions (P, 30 Gy in 5 fractions; A, 30 Gy in 5 fractions; LN, 33 Gy in 3 fractions; and M, 36 Gy in 3 fractions). In 18 patients (21 lesions) androgen deprivation was added to CBK-SRT (median duration, 16.6 months). RESULTS: The median follow-up was 16.9 months. Acute toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event). Late toxicity included urinary events (3 Grade 1, 2 Grade 2, and 2 Grade 3 events) and rectal events (1 Grade 1 event and 1 Grade 2 event). Biochemical response was observed in 32 of 38 evaluable lesions. Prostate-specific antigen stabilization was seen for 4 lesions, and in 2 cases prostate-specific antigen progression was reported. The 30-month progression-free survival rate was 42.6%. Disease progression was observed for 14 lesions (5, 2, 5, and 2 in Groups P, A, LN, and M respectively). In only 3 cases, in-field progression was seen. At the time of analysis (May 2010), 19 patients are alive with no evidence of disease and 15 are alive with disease. CONCLUSIONS: CyberKnife-based stereotactic radiotherapy is a feasible approach for isolated recurrent primary, lymph node, or metastatic prostate cancer, offering excellent in-field tumor control and a low toxicity profile. Further investigation is warranted to identify the patients who benefit most from this treatment modality. The optimal combination with androgen deprivation should also be defined.

3D-conformal hypofractionated radiotherapy for prostate cancer with daily transabdominal ultrasonography prostate localization: toxicity and outcome of a pilot study.

AIMS AND BACKGROUND: To evaluate the feasibility, toxicity and patient outcome of hypofractionated 3-dimensional conformal radiotherapy for low- and intermediate-risk prostate cancer, using daily an ultrasound targeting system (BAT). METHODS: Between May 2005 and October 2006, 25 patients (cT1-T2, GS < or = 7, mean initial PSA = 7.06 ng/ml) received a dose of 72 Gy in 30 fractions. Only the prostate was included in the clinical target volume. Immediately before each radiotherapy session, BATTM ultrasound alignment was performed. Acute and late toxicity was evaluated according to the Radiation Therapy Oncology Group criteria; the Phoenix definition (PSA = nadir + 2 ng/ml) was applied to define biochemical failure. BAT localization data were provided for 300 out of 750 procedures. RESULTS: No interruptions in 3-dimensional conformal radiotherapy due to toxicity were registered. There was no acute rectal toxicity in 52% of patients; 28% had G1, 16% had G2, and 1 patient had a G3 event. No acute urinary toxicity was observed in 28% of the patients. G1 toxicity occurred in 40%, G2 in 28%, and G3 in 1 patient; no G4 event was observed. With an average follow-up of 45 months, one biochemical relapse was observed; late toxicity showed an excellent profile: 78% of the patients had no rectal toxicity, 16% had G1, and 1 patient had G2 toxicity. Most of the patients (68%) had no late urinary complications, whereas 32% had G1 toxicity. Localization data showed systematic and random errors in relation to some procedure biases. CONCLUSIONS: Promising tumor control and toxicity profile were observed with this mildly hypofractionated BAT-based 3-dimensional conformal radiotherapy.