Pharmacological Treatment of Acute Unilateral Vestibulopathy: A Review.

There have been few investigations on the epidemiology, etiology, and medical management of acute unilateral vestibulopathy (AUV). Short-term pharmaceutical resolutions include vestibular symptomatic suppressants, anti-emetics, and some cause-based therapies. Anticholinergics, phenothiazines, antihistamines, antidopaminergics, benzodiazepines, and calcium channel antagonists are examples of vestibular suppressants. Some of these medications may show their effects through multiple mechanisms. In contrast, N-acetyl-L-leucine, Ginkgo biloba, and betahistine improve central vestibular compensation. Currently, AUV pathophysiology is poorly understood. Diverse hypotheses have previously been identified which have brought about some causal treatments presently used. According to some publications, acute administration of anti-inflammatory medications may have a deleterious impact on both post-lesional functional recovery and endogenous adaptive plasticity processes. Thus, some authors do not recommend the use of corticosteroids in AUV. Antivirals are even more contentious in the context of AUV treatment. Although vascular theories have been presented, no verified investigations employing anti-clotting or vasodilator medications have been conducted. There are no standardized treatment protocols for AUV to date, and the pharmacological treatment of AUV is still questionable. This review addresses the most current developments and controversies in AUV medical treatment.

Multisystemic RFC1-Related Disorder: Expanding the Phenotype Beyond Cerebellar Ataxia, Neuropathy, and Vestibular Areflexia Syndrome.

Background and Objectives: The RFC1 spectrum has become considerably expanded as multisystemic features beyond the triad of cerebellar ataxia, neuropathy, and vestibular areflexia syndrome (CANVAS) have started to be unveiled, although many still require clinical replication. Here, we aimed to clinically characterize a cohort of RFC1-positive patients by addressing both classic and multisystemic features. In a second part of this study, we prospectively assessed small nerve fibers (SNF) and autonomic function in a subset of these RFC1-related patients. Methods: We retrospectively enrolled 67 RFC1-positive patients from multiple neurologic centers in Portugal. All patients underwent full neurologic and vestibular evaluation, as well as neuroimaging and neurophysiologic studies. For SNF and autonomic testing (n = 15), we performed skin biopsies, quantitative sensory testing, sudoscan, sympathetic skin response, heart rate deep breathing, and tilt test. Results: Multisystemic features beyond CANVAS were present in 82% of the patients, mainly chronic cough (66%) and dysautonomia (43%). Other features included motor neuron (MN) affection and motor neuropathy (18%), hyperkinetic movement disorders (16%), sleep apnea (6%), REM and non-REM sleep disorders (5%), and cranial neuropathy (5%). Ten patients reported an inverse association between cough and ataxia severity. A very severe epidermal denervation was found in skin biopsies of all patients. Autonomic dysfunction comprised cardiovascular (67%), cardiovagal (54%), and/or sudomotor (50%) systems. Discussion: The presence of MN involvement, motor neuropathy, small fiber neuropathy, or extrapyramidal signs should not preclude RFC1 testing in cases of sensory neuronopathy. Indeed, the RFC1 spectrum can overlap not only with multiple system atrophy but also with hereditary motor and sensory neuropathy, hereditary sensory and autonomic neuropathy, and feeding dystonia phenotypes. Some clinical-paraclinical dissociations can pose diagnostic challenges, namely large and small fiber neuropathy and sudomotor dysfunction which are usually subclinical.

Changes in Coagulation Study and Risk of Developing Cholesteatoma: Is There a Link?

BACKGROUND AND OBJECTIVES: The etiopathogenesis of acquired pediatric cholesteatoma has not yet been fully clarified. Recent studies and modern technologies have led researchers to look for explanations at a molecular level. This study aims to understand if the origins of cholesteatoma could be related to dysfunctions in coagulation factors, thereby emphasizing its role in angiogenesis. Subjects and. METHODS: This was a retrospective case-control study carried out at a tertiary hospital center between January 2010 and December 2020. The study included 92 children. The variables of the summary coagulation study (partial thromboplastin time, prothrombin time, and international normalized ratio) were compared among children with and without development of chronic otitis media with cholesteatoma. RESULTS: The cases and controls were comparable in terms of age, type, and number of times that ventilation tubes were placed. Partial thromboplastin times tended to be higher in children who developed cholesteatoma, with a statistically significant difference between the two groups in terms of normal and abnormal partial thromboplastin times (p=0.029). CONCLUSIONS: The results of this case control study indicate that slight extension of partial thromboplastin times in the coagulation study may not meet the criteria for diagnosis of certain hematological pathologies or clinical significance, but at a molecular level may already have implications for activation of angiogenesis and other growth factors involved in the onset, growth, and expansion of acquired pediatric cholesteatoma.

Let Us Not Forget About Bleeding: A Case Report and Brief Literature Review on Hemorrhagic Vestibular Schwannoma.

Hemorrhagic vestibular schwannoma (HVS) consisting of acute intratumoral and subarachnoid hemorrhage is a rare phenomenon. We present the case of a 31-year-old woman who attended the Otorhinolaryngology department with right-sided intense tinnitus, dizziness, imbalance, and headache. Brain computed tomography revealed a spontaneous hyperdensity in the posterior fossa with marked deformation of the brainstem, middle cerebral peduncle, and cerebellum, with the near collapse of the fourth ventricle. Ophthalmology evaluation confirmed bilateral papilledema. Brain magnetic resonance imaging confirmed a voluminous 33 x 28 x 29 mm extra-axial lesion centered on the right pontine-cerebellar angle cistern, extending from the plane of the trigeminal nerve/tent of the cerebellum. The acoustic pore was enlarged. The patient underwent retrosigmoid craniotomy and microscopic tumor resection showing significant improvement in the follow-up. Pathological findings confirmed HVS. Delayed treatment of HVS can increase morbidity or even be fatal. The objective of this work is to describe and revise HVS, in order to bring awareness to this uncommon entity.

Hyperacusis and stapes surgery: An observation in fifty patients after stapedotomy.

OBJECTIVE: To assess hyperacusis after stapedotomy and its possible influencing factors. STUDY DESIGN: Prospective, interventional, and longitudinal study. SETTING: A tertiary referral center. PATIENTS: Fifty consecutive patients (35 females, mean age = 46.8 years). INTERVENTION: All patients underwent stapedotomy. The validated Portuguese version of the "Hyperacusis Questionnaire" (HQ) was administered before and two weeks and one month after surgery. RESULTS: No hyperacusis was reported by any patient before surgery. At two weeks after surgery, all patients experienced hyperacusis, with a mean HQ at 16.88 ± 6.54 (range 4-25). One month after surgery, hyperacusis had already resolved in most patients. Gender, preoperative presentation or surgeon had no influence on HQ scores (p > 0.05). Patients with previous contralateral stapedotomy showed lower HQ scores (p = 0.001). Audiological parameters improvement measured at one month after surgery (PTA, SRT and contralateral SRT) were associated with HQ higher scores. CONCLUSION: This study confirms that hyperacusis is a common complaint after stapedotomy that usually resolves in one month after surgery. The HQ highest scores were registered among patients with the highest audiological gain after surgery. This suggests that hyperacusis may be a positive prognostic factor for audiological success after stapedotomy.

Long term outcomes of balloon sinuplasty for the treatment of chronic rhinosinusitis with and without nasal polyps.

OBJECTIVES: The aim of this study was to evaluate the 4-year outcomes and effectiveness of balloon sinuplasty in the treatment of chronic rhinosinusitis (CRS). MATERIAL AND METHODS: We evaluated the long-term outcomes in terms of symptoms, nasal endoscopy and computed tomography of 110 patients with CRS submitted to balloon sinuplasty in Centro Hospitalar do Funchal retrospectively. Sinus symptoms were determined by the Sino-Nasal Outcome Test (SNOT-22), endoscopic examination determined by Modified Lund Kennedy score (MLK) and computerized tomography scan of paranasal sinuses (CT-PNS) was evaluated through Lund Mackay scores (LM). Data was collected from 82 patients with chronic rhinosinusitis without nasal polyps (CRSsNP) and from 28 patients with nasal polyps (CRSwNP). RESULTS: Local anesthesia procedures were performed in 45.5% of the patients. First follow up was obtained at 2 years (median 22.45 ± 13.6 months) and at 4 years (median 44.45 ± 14 months) after balloon sinuplasty. The mean baseline SNOT-22 score was of 50.26 ± 15.33 for patients with CRSsNP and 52.25 ± 18.06 in CRSsNP patients. Both scores were reduced to 7.00 ± 13.5 and 10.00 ± 22.50 at 4 years follow-up respectively. Baseline MLK score was 4.90 ± 2.12 for patients in CRSsNP group and 10.00 ± 2.00 in the CRSwNP group Both scores were reduced to 1.65 ± 1.67 and 4.86 ± 2.16. The overall mean average LM CT-PNS score was 8.71 ± 4.728 preoperatively for the CRSsNP and 16.18 ± 3.9 in patients with CRSwNP and were reduced to 1.00 ± 1.75 and 8.69 ± 4.6 after BSP. SNOT 22, MLK and LM scores showed consistent improvement over baseline at all time points until the end of the study (median 44.45 ± 14 months). Significant improvements were recorded at all time points in the patient's symptom score, nasal endoscopy scores and imaging scores (P < 0.0001). CONCLUSION: Balloon sinuplasty appears to be safe and effective for the treatment of CRS with great long-term outcomes.

The cardiovascular aspects of a Ménière's disease population - A pilot study.

INTRODUCTION: MD is considered a rare disease. An adequate model that explains MD's pathophysiology is not well established. Recently, the vascular theory of the disease has been revived. OBJECTIVES: To characterize a MD population according to its cardiovascular risk and correlate it to the MD clinical course. METHODS: In this retrospective chart study the data of 31 MD patients observed between January 2017 and April 2018 in a tertiary university hospital were reviewed. Patients included in the study were diagnosed according to the Bárány Society criteria. Lost follow-ups, patients with autoimmune disease, atopy or allergy, major psychiatric disease and migraine were excluded. Age, gender, cardiovascular risk factors, audiometric and vestibular parameters, occurrence of MD attacks in the previous 6 months, vestibular medication in course and time course of MD were recorded and compared between groups (with and without cardiovascular risk factors). RESULTS: 31 patients (61.3% females) mean aged 60.3 years (±9.7) were studied. 74% of the population had at least one risk factor and 51.6% of patients had attacks in the last 6 months. There was a statistically significant difference in the occurrence of MD attacks in the last 6 months (p = 0.014) between MD patients with and without risk factors. Mean PTA thresholds were higher and speech discrimination was lower in individuals with more cardiovascular risk factors. CONCLUSIONS: Treatment of MD focusing on vascular risk factors may allow a better control of symptoms and result in a decreased need for ablative procedures in this disorder.

Spare roof technique in reduction rhinoplasty: Prospective study of the first one hundred patients.

OBJECTIVE: Assess the aesthetic and functional outcomes of the first 100 patients who underwent reduction rhinoplasty with the spare roof technique (SRT). METHODS: Prospective, interventional, and longitudinal study performed on consecutive patients undergoing primary rhinoplasty by SRT. All the surgical procedures were performed by the surgeon who first described this technique. The validated Portuguese version of the Utrecht Questionnaire for Outcome Assessment in Aesthetic Rhinoplasty was used. Patients completed the questionnaire presurgery and again 3 and 12 months postsurgery. In addition, a visual analogue scale (VAS) was used to score nasal patency for both sides. RESULTS: The study population included 100 Caucasian Mediterranean patients (33 males; 67 females). Mean age at surgery was 32.8 years. Analysis of the preoperative and postoperative mean aesthetic VAS scores showed a significant improvement from 3.67 to 8.1 (P < 0.001) and 8.44 (P < 0.001), respectively, 3 and 12 months postsurgery. Analysis of the five aesthetic Likert scale questions all showed a highly significant improvement after rhinoplasty. The mean preoperative aesthetic sum score was 13.9, which improved to 8.26 and 7.08, respectively, 3 and 12 months postsurgery (P < 0.001), indicating a significant improvement of subjective body image in relation to nasal appearance. Analysis of the preoperative and postoperative mean functional VAS score showed a significant improvement on both sides. CONCLUSION: This prospective statistical study confirms that SRT significantly improved patient quality of life regarding nose function and appearance. It is a reliable technique that can help deliver consistently good results in reduction rhinoplasty in Caucasian patients with dorsal hump seeking rhinoplasty. LEVEL OF EVIDENCE: 2 Laryngoscope, 129:2702-2706, 2019.

DOOR syndrome: A case report and its embryological basis.

DOOR syndrome is an extremely rare genetic disorder. "DOOR″ is an acronym to describe the combination of: deafness, onychodystrophy, osteodystrophy and mental retardation. We present a patient, with all of the above-mentioned main symptoms, that was rehabilitated with convencional hearing aids. The presented case suggested that every case of deafness and abnormal nails and phalanges in the hands and feet should have a clinical diagnosis of possible DOOR syndrome. Based on embryological process, congenital abnormal nails or phalanges highlights the importance for detailed hearing screening.

Behavioral Profile of Children With Vocal Fold Nodules-A Case-control Study.

OBJECTIVES: The aim of this case-control study was to evaluate the overall behavior of children with vocal fold nodules (VNs). METHODS: The study group included children with VNs between 4 and 15 years old diagnosed using fiberoptic video laryngoscopy with stroboscopy in a tertiary university hospital. As a control group, children between 4 and 13 years old without VNs, routinely followed up in a primary care facility, were included in the study. Parents of the participants completed the parent-proxy strengths and difficulties questionnaire (SDQ), a brief behavioral screening questionnaire designed for children. The SDQ evaluates emotional, conduct, and peer problems, and also focuses on hyperactivity and prosocial behavior. Children are classified into "normal," "borderline," or "abnormal" according to the total SDQ score. RESULTS: Twenty-seven children (24 boys and 3 girls) with VNs and 41 controls (33 boys and 8 girls) were enrolled in the study. The two groups did not differ significantly in age or gender (P > 0.05). Statistical analysis revealed that 52% individuals of the VNs group presents borderline or abnormal overall behavioral, which is statistically different from the general population (P < 0.001). Total, hyperactivity, and prosocial SDQ subscales were statistically different between study groups (P < 0.05). CONCLUSIONS: Our findings suggest association between VNs and hyperactivity and also with poorer prosocial behaviors in children for the first time. We propose that every child with VNs must be evaluated from a behavioral point of view to detect and to treat potential underlying psychological conditions that may interfere with VNs treatment and prognosis.

A novel PLEC nonsense homozygous mutation (c.7159G > T; p.Glu2387*) causes epidermolysis bullosa simplex with muscular dystrophy and diffuse alopecia: a case report.

BACKGROUND: Epidermolysis bullosa simplex with muscular dystrophy (EBS-MD; OMIM #226670) is an autosomal recessive disease, characterized mainly by skin blistering at birth or shortly thereafter, progressive muscle weakness, and rarely by alopecia. EBS-MD is caused by mutations in the PLEC gene (OMIM *601282), which encodes plectin, a structural protein expressed in several tissues, including epithelia and muscle. We describe a patient affected with EBS-MD and diffuse alopecia in which we identified a novel pathogenic mutation by PCR amplification of all coding exons and exon-intron boundaries of PLEC gene, followed by bidirectional Sanger sequencing. CASE PRESENTATION: The patient, a 28-year-old female and only child of consanguineous healthy parents, was born after uneventful pregnancy. At 2 days of age, she developed skin and oral mucosal blistering, accompanied by voice hoarseness. On physical examination as an adult, we observed diffuse non-scarring alopecia on the scalp, onychodystrophy (pachyonychia) in all 20 nails, dental decay, mild dysphonia, and severe muscle atrophy mainly affecting the extremities. Neurological examination showed profoundly diminished reflexes. Mutation analysis revealed the patient to be homozygous for the novel PLEC nonsense mutation - c.7159G > T (p.Glu2387*) - located in exon 31. Thismutation predicts the lack of expression of the full-length plectin isoform. CONCLUSION: The present case appears to be the second association of EBS-MD with diffuse alopecia, both cases having different mutations involving PLEC exon 31. It remains to be elucidated whether diffuse alopecia results from PLEC mutations and/or from environmental factors.

Monophosphoryl Lipid-A: A Promising Tool for Alzheimer's Disease Toll.

Neuroinflammation is a two-edged sword in Alzheimer's disease (AD). A certain degree of neuroinflammation is instrumental in the clearance of amyloid-ß (Aß) peptides by activated microglia, although a sustained neuroinflammation might accelerate Aß deposition, thus fostering the neurodegenerative process and functional decline in AD. There is an increasing body of evidence suggesting that the innate immune system via Toll-like receptor 4 (TLR4) finely orchestrates the highly regulated inflammatory cascade that takes place in AD pathology. Herein we critically review pre-clinical (in vitro and in vivo approaches) and clinical studies showing that monophosphoryl lipid A (MPL), a partial TLR4 agonist, may have beneficial effect on AD physiopathology. The in vivo data elegantly showed that MPL enhanced Aß plaque phagocytosis thus decreasing the number and the size of Aß deposits and soluble Aß in brain from APPswe/PS1 mice. Furthermore, MPL also improved their cognition. The mechanism underlying this MPL effect was proposed to be microglial activation by recruiting TLR4. Additionally, it was demonstrated that MPL increased the Aß antibody titer and showed a safe profile in mice and primates, when used as a vaccine adjuvant. Clinical studies using MPL as an adjuvant in Aß immunotherapy are currently ongoing. Overall, we argue that the TLR4 partial agonist MPL is a potentially safe and effective new pharmacological tool in AD.