Efficacy and Safety of AM-111 in the Treatment of Acute Unilateral Sudden Deafness-A Double-blind, Randomized, Placebo-controlled Phase 3 Study.

OBJECTIVE: To confirm the efficacy and safety of AM-111 (brimapitide), a cell-penetrating c-Jun N-terminal Kinase (JNK) inhibitor, in patients suffering from severe to profound acute unilateral idiopathic sudden sensorineural hearing loss (ISSNHL). STUDY DESIGN: Prospective, double-blind, randomized, placebo-controlled phase 3 study with follow-up visits on Days 3, 7, 28, and 91. SETTING: Fifty-one European and Asian sites (tertiary referral centers, private ENT practices). PATIENTS: Two hundred fifty-six patients aged 18 to 65 years presenting within 72 hours following ISSNHL onset with mean hearing loss ≥ 40 dB and mean threshold ≥ 60 dB at the 3 worst affected contiguous test frequencies. INTERVENTIONS: Single-dose intratympanic injection of AM-111 (0.4 or 0.8 mg/ml) or placebo; oral prednisolone as reserve therapy if hearing improvement < 10 dB at Day 7. MAIN OUTCOME MEASURES: Hearing improvement to Day 28 was the primary efficacy endpoint; complete hearing recovery, frequency of reserve therapy used, complete tinnitus remission, improvement in word recognition were secondary endpoints. Safety was evaluated by the frequency of clinically relevant hearing deterioration and adverse events. RESULTS: While the primary efficacy endpoint was not met in the overall study population, post-hoc analysis showed a clinically relevant and nominally significant treatment effect for AM-111 0.4 mg/ml in patients with profound ISSNHL. The study drug and the administration procedure were well tolerated. CONCLUSIONS: AM-111 provides effective otoprotection in case of profound ISSNHL. Activation of the JNK stress kinase, AM-111's pharmacologic target, seems to set in only following pronounced acute cochlear injury associated with large hearing threshold shifts.

[Perilymphatic fistula: diagnosis and treatment]. / Przetoka perylimfatyczna jako problem diagnostyczny i leczniczy.

INTRODUCTION: Diagnosis and management of perilymphatic fistula (PLF) is a controversial topic in the international neurotologic literature. An illustrative case of post traumatic PLF with clear surgical indications is presented. This manuscript also reviews the various clinical presentations, pathogenesis, diagnostic examinations, and management options of PLF. MATERIALS AND METHODS: Case report and literature review. RESULTS: A 40 y/o female presented with paroxysmal vertigo, imbalance and severe sensorineural hearing loss (SNHL) following minor occipital head trauma from a fall six months prior to presentation. Laboratory examination included intermittently positive fistula sign on video-nystagmography. Patient failed to respond to trials of pharmacologic treatment and bedrest and ultimately underwent surgical exploration and repair. Patient had earlobe fat placed in the round and oval windows. Postoperatively, she had prompt resolution of vestibulopathy and ultimate full return of sensorineural function. CONCLUSIONS: Patients with appropriate antecedent history demonstrating fluctuating SNHL and vestibulopathy, failing to respond to conservative medical treatments, should be considered for exploratory tympanotomy. In the absence of any other violations of labyrinthine integrity, connective tissue grafting of the round and oval windows should be performed even if no obvious flow of fluid is observed. This management protocol is safe and effective in properly selected patients.

[Benign paroxysmal positional vertigo in the own material]. / Lagodne napadowe polozeniowe zawroty glowy w materiale wlasnym.

INTRODUCTION: The complaint of dizziness can be caused by a variety of disorders affecting central or peripheral vestibular system. Benign paroxysmal positional vertigo BPPV is the most common cause of vertigo. It is a syndrom characterized by short-lasted episodes of true vertigo, induced by a rapid head position change and associated with a positional, transient nystagmus. It is classically identified by the Dix-Hallpike test. Vestibular and audiology function tests are usually normal. Patient is succesfully treated with physical maneuvres (Canalith Repositioning Procedure CRP). MATERIAL AND METHODS: This raport presents eight patients (four are described in details) suffered from BPPV-PSC, hospitalized in the Department of Phoniatric and Audiology, Poznan University of Medical Sciences. Methods include laryngologic examination, audiology and vestibular tests, Dix-Hallpike'a maneuver. RESULTS: All patients presented characteristic history and results of performed diagnostic tests. The efficacy of physical maneuvers were confirmed. CONCLUSIONS: BPPV is usually easy to diagnose and physical maneuvers are very effective.