Efficacy of Intratympanic OTO-104 for the Treatment of Ménière's Disease: The Outcome of Three Randomized, Double-Blind, Placebo-Controlled Studies.

OBJECTIVE: To determine the efficacy of intratympanic OTO-104 for the treatment of Ménière's disease. STUDY DESIGNS: Three randomized, double-blind, placebo-controlled, multicenter studies of OTO-104 in patients with Ménière's disease. SETTING: The United States and throughout Europe. PATIENTS: Individuals with Ménière's disease aged 18 to 85 years. INTERVENTIONS: All three studies were conducted according to a similar protocol, whereby after a 1-month lead-in period, eligible patients received a single intratympanic injection of either 12 mg OTO-104 (otic formulation of dexamethasone in thermosensitive poloxamer) or placebo (1:1) and were observed for 3 months. MAIN OUTCOME MEASURES: The primary efficacy endpoint was measured by the number of definitive vertigo days (DVDs) at month 3. Secondary objective was OTO-104 safety and tolerability including adverse events, audiometry, tympanometry, and otoscopic examinations. RESULTS: Although OTO-104 demonstrated numerically greater reductions in DVD compared with placebo across all three studies, statistical significance versus placebo (primary efficacy endpoint) was only achieved in one study, the AVERTS-2 study (n = 174, p = 0.029). Secondary vertigo efficacy endpoints were statistically significant at month 3 in that study including vertigo severity, the effect of vertigo on daily activity (days at home sick or bedridden), and vertigo frequency. In the AVERTS-1 study, which did not meet the primary endpoint, a subgroup analysis of the 115 patients (69.7% of study population) who did not previously receive intratympanic steroid injections demonstrated that OTO-104 patients had significantly lower mean DVD at month 3 than patients receiving placebo (1.9 for OTO-104 versus 3.0 for placebo; p = 0.045). Importantly, a significant placebo response was observed across studies in Ménière's disease patients. OTO-104 and the intratympanic injection procedure were well tolerated. CONCLUSIONS: In all three high-quality, randomized, double-blind, placebo-controlled, multicenter studies, a single intratympanic injection of 12 mg OTO-104 demonstrated numerically greater reductions in vertigo versus placebo in patients with Ménière's disease, but statistical separation from placebo was demonstrated in only one of the studies. OTO-104 was safe and well tolerated.(Otonomy, Inc. funded; NCT02717442, NCT02612337, NCT03664674).

Intratympanic corticosteroids for sudden sensorineural hearing loss.

BACKGROUND: Idiopathic sudden sensorineural hearing loss (ISSNHL) is common, and defined as a sudden decrease in sensorineural hearing sensitivity of unknown aetiology. Systemic corticosteroids are widely used, however their value remains unclear. Intratympanic injections of corticosteroids have become increasingly common in the treatment of ISSNHL. OBJECTIVES: To assess the effects of intratympanic corticosteroids in people with ISSNHL. SEARCH METHODS: The Cochrane ENT Information Specialist searched the Cochrane ENT Trials Register; CENTRAL (2021, Issue 9); PubMed; Ovid Embase; CINAHL; Web of Science; ClinicalTrials.gov; ICTRP and additional sources for published and unpublished trials (search date 23 September 2021). SELECTION CRITERIA: We included randomised controlled trials (RCTs) involving people with ISSNHL and follow-up of over a week. Intratympanic corticosteroids were given as primary or secondary treatment (after failure of systemic therapy). DATA COLLECTION AND ANALYSIS: We used standard Cochrane methods, including GRADE to assess the certainty of the evidence. Our primary outcome was change in hearing threshold with pure tone audiometry. Secondary outcomes included the proportion of people whose hearing improved, final hearing threshold, speech audiometry, frequency-specific hearing changes and adverse effects. MAIN RESULTS: We included 30 studies, comprising 2133 analysed participants. Some studies had more than two treatment arms and were therefore relevant to several comparisons. Studies investigated intratympanic corticosteroids as either primary (initial) therapy or secondary (rescue) therapy after failure of initial treatment. 1. Intratympanic corticosteroids versus systemic corticosteroids as primary therapy We identified 16 studies (1108 participants). Intratympanic therapy may result in little to no improvement in the change in hearing threshold (mean difference (MD) -5.93 dB better, 95% confidence interval (CI) -7.61 to -4.26; 10 studies; 701 participants; low-certainty). We found little to no difference in the proportion of participants whose hearing was improved (risk ratio (RR) 1.04, 95% CI 0.97 to 1.12; 14 studies; 972 participants; moderate-certainty). Intratympanic therapy may result in little to no difference in the final hearing threshold (MD -3.31 dB, 95% CI -6.16 to -0.47; 7 studies; 516 participants; low-certainty). Intratympanic therapy may increase the number of people who experience vertigo or dizziness (RR 2.53, 95% CI 1.41 to 4.54; 1 study; 250 participants; low-certainty) and probably increases the number of people with ear pain (RR 15.68, 95% CI 6.22 to 39.49; 2 studies; 289 participants; moderate-certainty). It also resulted in persistent tympanic membrane perforation (range 0% to 3.9%; 3 studies; 359 participants; very low-certainty), vertigo/dizziness at the time of injection (1% to 21%, 3 studies; 197 participants; very low-certainty) and ear pain at the time of injection (10.5% to 27.1%; 2 studies; 289 participants; low-certainty). 2. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as primary therapy We identified 10 studies (788 participants). Combined therapy may have a small effect on the change in hearing threshold (MD -8.55 dB better, 95% CI -12.48 to -4.61; 6 studies; 435 participants; low-certainty). The evidence is very uncertain as to whether combined therapy changes the proportion of participants whose hearing is improved (RR 1.27, 95% CI 1.15 to 1.41; 10 studies; 788 participants; very low-certainty). Combined therapy may result in slightly lower (more favourable) final hearing thresholds but the evidence is very uncertain, and it is not clear whether the change would be important to patients (MD -9.11 dB, 95% CI -16.56 to -1.67; 3 studies; 194 participants; very low-certainty). Some adverse effects only occurred in those who received combined therapy. These included persistent tympanic membrane perforation (range 0% to 5.5%; 5 studies; 474 participants; very low-certainty), vertigo or dizziness at the time of injection (range 0% to 8.1%; 4 studies; 341 participants; very low-certainty) and ear pain at the time of injection (13.5%; 1 study; 73 participants; very low-certainty).  3. Intratympanic corticosteroids versus no treatment or placebo as secondary therapy We identified seven studies (279 participants). Intratympanic therapy may have a small effect on the change in hearing threshold (MD -9.07 dB better, 95% CI -11.47 to -6.66; 7 studies; 280 participants; low-certainty). Intratympanic therapy may result in a much higher proportion of participants whose hearing is improved (RR 5.55, 95% CI 2.89 to 10.68; 6 studies; 232 participants; low-certainty). Intratympanic therapy may result in lower (more favourable) final hearing thresholds (MD -11.09 dB, 95% CI -17.46 to -4.72; 5 studies; 203 participants; low-certainty). Some adverse effects only occurred in those who received intratympanic injection. These included persistent tympanic membrane perforation (range 0% to 4.2%; 5 studies; 185 participants; very low-certainty), vertigo or dizziness at the time of injection (range 6.7% to 33%; 3 studies; 128 participants; very low-certainty) and ear pain at the time of injection (0%; 1 study; 44 participants; very low-certainty).  4. Intratympanic plus systemic corticosteroids (combined therapy) versus systemic corticosteroids alone as secondary therapy We identified one study with 76 participants. Change in hearing threshold was not reported. Combined therapy may result in a higher proportion with hearing improvement, but the evidence is very uncertain (RR 2.24, 95% CI 1.10 to 4.55; very low-certainty). Adverse effects were poorly reported with only data for persistent tympanic membrane perforation (rate 8.1%, very low-certainty). AUTHORS' CONCLUSIONS: Most of the evidence in this review is low- or very low-certainty, therefore it is likely that further studies may change our conclusions.   For primary therapy, intratympanic corticosteroids may have little or no effect compared with systemic corticosteroids. There may be a slight benefit from combined treatment when compared with systemic treatment alone, but the evidence is uncertain. For secondary therapy, there is low-certainty evidence that intratympanic corticosteroids, when compared to no treatment or placebo, may result in a much higher proportion of participants whose hearing is improved, but may only have a small effect on the change in hearing threshold. It is very uncertain whether there is additional benefit from combined treatment over systemic steroids alone. Although adverse effects were poorly reported, the different risk profiles of intratympanic treatment (including tympanic membrane perforation, pain and dizziness/vertigo) and systemic treatment (for example, blood glucose problems) should be considered when selecting appropriate treatment.

Stereotactic radiotherapy in three weekly fractions for the management of vestibular schwannomas.

PURPOSE: This study evaluates the rates of tumor control, hearing preservation and cranial nerve toxicity with the use of CyberKnife stereotactic radiotherapy consisting of 2100 cGy to the 80% isodose line delivered in three weekly fractions to treat vestibular schwannomas. MATERIALS AND METHODS: Retrospective chart review of vestibular schwannoma patients treated with CyberKnife stereotactic radiotherapy or undergoing watchful waiting between 2006 and 2017 was performed. For inclusion, patients receiving CyberKnife stereotactic radiotherapy must have had pretreatment magnetic resonance imaging and audiography, and 2 follow-up magnetic resonance imaging and audiograms. Watchful waiting patients must have had a minimum of 2 magnetic resonance imaging and 2 audiograms. RESULTS: Forty patients met inclusion criteria. Twenty-two underwent CyberKnife stereotactic radiotherapy. Eighteen remain in watchful waiting. Crude tumor control was 86.4% at mean radiographic follow-up of 52.3 months. Kaplan-Meier progression-free survival was 76.9% at 5 years. Kaplan-Meier survival from radiographic growth was 61.5% at 5 years. Kaplan-Meier hearing preservation was 17.5% at 5 years. All patients undergoing watchful waiting presenting with serviceable hearing maintained serviceable hearing. Serviceable hearing among CyberKnife stereotactic radiotherapy patients was 42.9% prior to treatment and 14.2% through mean follow-up of 53.7 months. One patient experienced trigeminal nerve toxicity 45 months after SRT. 95.5% of CyberKnife stereotactic radiotherapy patients were complication-free. CONCLUSIONS: Our fractionation regimen provides tumor control consistent with current literature. Hearing outcomes, however, should be discussed with patients prior to CyberKnife stereotactic radiotherapy.

Butterfly cartilage tympanoplasty outcomes: A single-institution experience and literature review.

PURPOSE: In 1998, Dr. Eavey described the trans-canal inlay butterfly cartilage tympanoplasty technique, also known as cartilage button tympanoplasty. Many retrospective studies have since demonstrated its efficacy and decreased operative time when compared to underlay and overlay tympanoplasty techniques. The butterfly cartilage tympanoplasty approach uses only a cartilage graft to repair tympanic membrane perforations. The aim of this study was to review the literature for studies that examined butterfly cartilage tympanoplasty success rates and outcomes and compare them to outcomes from our cohort. MATERIALS AND METHODS: Butterfly cartilage tympanoplasties were performed in 23 pediatric patients and 7 adult patients. We evaluated the tympanic membrane perforation closure rate and hearing results measured by closure of the air-bone gap. RESULTS: The reviewed studies evaluating butterfly cartilage tympanoplasties demonstrated perforation closure rates between 71%-100%. The hearing outcomes in the reviewed literature varied, although the majority reported improved hearing. In our cohort, 21 of the 32 repaired tympanic membrane perforations demonstrated complete perforation closure. The mean follow-up length was 13.4 months. The mean air-bone gap decreased from 13.4 dB to 6.9 dB. CONCLUSIONS: The butterfly cartilage/cartilage button technique is effective in closing tympanic membrane perforations and decreasing the air-bone gap in both adults and children.

Total caloric eye speed in patients with vestibular migraine.

PURPOSE: Vestibular migraine is a common cause of dizziness that lacks a known objective test. This study examined total eye speed on caloric testing as a diagnostic marker for vestibular migraine. MATERIALS AND METHODS: Retrospective chart review of patients seen in a tertiary otologic practice between 2004 and 2016 who had undergone caloric testing with water irrigation and had a diagnosis of vestibular migraine (n=34). A group of patients with benign paroxysmal positional vertigo (n=10) were used as a control group. Patients were grouped into quartiles based on total eye speed. RESULTS: Only patients in the lowest quartile (total eye speed<79) had a diagnosis of vestibular migraine. All other quartiles included a mix of control and vestibular migraine patients. CONCLUSION: Low total eye speed may be suggestive of a diagnosis of vestibular migraine, but most patients with vestibular migraine do not have low total eye speed.

Intratympanic Triamcinolone and Dexamethasone in the Treatment of Ménière's Syndrome.

OBJECTIVE: To describe the safety and potential efficacy of intratympanic administration of triamcinolone (40 mg/mL) in the treatment of unilateral Ménière's syndrome. STUDY DESIGN: Single-institution retrospective analysis. SETTING: Tertiary referral neurotology clinic. PATIENTS: Eighteen patients diagnosed with unilateral Ménière's syndrome with vertigo refractory to medical management. INTERVENTION(S): Intratympanic injection of triamcinolone or dexamethasone. OUTCOME MEASURE(S): Kaplan-Meier analysis was implemented to determine the rate of successful vertigo control. Responders were defined as patients who achieved sufficient vertigo control to decline ablative therapy. Nonresponders were defined as those who did not achieve satisfactory vertigo control and required ablative or surgical therapy. Pre- and posttreatment audiogram data was used to evaluate changes in hearing. Patient follow-up data was assessed for complications potentially resulting from intratympanic therapy. RESULTS: No patient experienced profound hearing loss or other serious adverse events as a result of intratympanic triamcinolone therapy. Tympanic membrane perforation occurred in three (18%) patients, all of whom had received three or more previous intratympanic injections. Satisfactory vertigo control with intratympanic triamcinolone therapy was achieved in 14 (78%) of 18 subjects. CONCLUSION: Our results suggest that intratympanic triamcinolone therapy on an as-needed basis is a safe and potentially effective procedure for vertigo control in patients with Ménière's syndrome. These findings warrant the implementation of prospective, controlled trials to investigate its safety and efficacy further.

Intratympanic Sustained-Exposure Dexamethasone Thermosensitive Gel for Symptoms of Ménière's Disease: Randomized Phase 2b Safety and Efficacy Trial.

OBJECTIVE: To evaluate safety and efficacy of a single intratympanic injection of OTO-104, sustained-exposure dexamethasone, in patients with unilateral Ménière's disease. STUDY DESIGN: Randomized, double-blind, placebo-controlled, Phase 2b study over 5 months. SETTING: Fifty-two academic and community otolaryngology centers. PATIENTS: One hundred fifty four patients (77 per group) aged 18 to 85 years inclusive. INTERVENTION: Single intratympanic injection of OTO-104 (12 mg dexamethasone) or placebo. MAIN OUTCOME MEASURES: Efficacy (vertigo) and safety (adverse events, otoscopy, audiometry, tympanometry). RESULTS: Primary endpoint (change from baseline in vertigo rate at Month 3) was not statistically significant (placebo [-43%], OTO-104 [-61%], P = 0.067). Improvements with OTO-104 were observed in prospectively defined secondary endpoints number of days with definitive vertigo, (Month 2 [P = 0.035], Month 3 [P = 0.030]), vertigo severity (Months 2-3, P = 0.046) and daily vertigo counts (Month 2, P = 0.042), and in some Short Form-36 (SF-36) subscales (Month 2 bodily pain P = 0.039, vitality P = 0.045, social functioning P = 0.025). No difference in tinnitus loudness or tinnitus handicap inventory (THI-25) was observed. OTO-104 was well tolerated; no negative impact on safety compared with placebo. Persistent tympanic membrane perforation was observed in two OTO-104 treated patients at study end. CONCLUSION: OTO-104 was well-tolerated, did not significantly affect change from baseline in vertigo rate, but did reduce number definitive vertigo days, vertigo severity, and average daily vertigo count compared with placebo during Month 3. Results provide insight into analyzing for a vertigo treatment effect and support advancing OTO-104 into Phase 3 clinical trials for the treatment of Ménière's disease symptoms.

Multifocal melanocytoma of the posterior fossa and subcutaneous scalp in the absence of neurocutaneous melanosis.

BACKGROUND: Primary leptomeningeal melanocytic neoplasms of the central nervous system are rare. Multifocal lesions typically occur in the setting of cutaneous melanosis. We present the first report of a posterior fossa melanocytoma and subcutaneous melanocytoma of intermediate grade in the absence of cutaneous melanosis. CASE DESCRIPTION: We present the case of a 22-year-old male with decreased hearing on the right side, ataxia, nausea, vomiting and a scalp mass. Magnetic resonance imaging (MRI) demonstrated occipital and cerebellopontine (CP) angle masses. The patient underwent gross total resection of the scalp mass and subtotal resection of the CP angle mass. Pathologic examination revealed melanocytoma with intermediate grade. The patient underwent stereotactic radiosurgery to the residual CP angle tumor. This case represents, to the author's knowledge, the first report associating a posterior fossa melanocytoma with a subcutaneous melanocytoma of intermediate grade in the absence of cutaneous melanosis. CONCLUSION: This case introduces the first report of a new variant of multifocal melanocytoma which is not confined to the central nervous system.

Short-term Peripheral Auditory Effects of Cranial Irradiation: A Mouse Model.

OBJECTIVES: Assess postcranial irradiation: (1) short-term threshold shift, (2) short-term peripheral auditory histopathology, and (3) the mouse as an experimental model. METHODS: Adult mice were exposed to single-dose radiation of 10 to 60 Gy. Pre- and post-irradiation (baseline, 2-8 days) audiometric brainstem response data were recorded with analysis of cochlear ultrastructure. RESULTS: Significant threshold shift occurred at all test frequencies in mice exposed to ≥20 Gy at 4 to 6 days post-irradiation. Ultrastructurally in Rosenthal's canal and the spiral lamina, neuronal density and extracellular matrix decreased dramatically. There was overall preservation of hair cells, stria vascularis, and vasculature. No difference within Gy group was noted in the frequency or severity of pathology along the length of the cochlea. CONCLUSIONS: The initial impact of radiation in the first week post-exposure focuses on spiral ganglion cell bodies and peripheral projections, resulting in significant threshold shift for irradiation dosages≥20 Gy. This study demonstrates that the mouse is a viable model for study of short-term peripheral auditory effects using single-dose cranial irradiation. Additionally, with access to a precise animal irradiator, the mouse may be used as an experimental model for a fractionated irradiation dosage of 10 Gy, simulating stereotactic therapeutic cranial irradiation.

Quantification of hearing loss in patients with posterior semicircular canal dehiscence.

CONCLUSION: Patients with posterior semicircular canal dehiscence (PSCD) have low frequency conductive hearing loss similar to patients with superior semicircular canal dehiscence (SSCD) secondary to a pathologic third window. OBJECTIVES: PSCD can result in conductive hearing loss, but the magnitude of this hearing loss remains to be quantified. Patients with SSCD have been shown to have low frequency conductive hearing loss. The underlying pathophysiology of hearing loss from PSCD and SSCD is similar and related to a pathologic third window. METHOD: A PubMed search was completed for a meta-analysis of patients with PSCD. Articles with quality audiograms were obtained. Air conduction thresholds for ears with posterior semicircular canal dehiscence were compared to the opposite ear as well as normal control data. RESULTS: Eight articles with 21 patients with PSCD and quality audiograms were included. Two patients had bilateral PSCD and one of those was excluded because hearing thresholds were at the limit of the audiometer. Patients with posterior semicircular canal dehiscence have statistically significant lower air conduction thresholds in frequencies at and below 2000 Hz.

Intratympanic steroid therapy for treatment of idiopathic sudden sensorineural hearing loss.

Idiopathic sudden sensorineural hearing loss (ISSHL) is the sudden loss of unilateral hearing of unknown etiology. The standard treatment consist of a high dose oral steroid taper. This article serves to review the current literature on intratympanic steroid injections for ISSHL. Current literature suggested intratympanic steroids are equivalent to oral steroid therapy, primary combined therapy is superior to either alone and intratympanic steroids should be offered for salvage therapy in ISSHL.

Acceptance of neurotology board certification among leaders in the field.

INTRODUCTION: Neurotology board certification was born a decade ago and is available to otolaryngologists who specialize in clinical neurotology. The degree of participation in this voluntary program among leaders in the field has not been previously assessed. METHODS: The Web sites of ACGME accredited otolaryngology programs were used to identify chairpersons who self-identified as neurotologists. Past presidents of the American Neurotology Society (ANS) since 1997 were also evaluated. The participation of both groups in neurotology board certification (NC) was ascertained using the search tool available on the American Board of Otolaryngology Web site (aboto.org). RESULTS: Of the 26 chairmen (all were men) identified as neurotologists, 18 (69%) participated in NC. Ten of 13 past presidents (77%) of the ANS participated in NC. Combining the 2 groups, 28 (72%) of 39 leaders in neurotology in the United States participated in NC. CONCLUSION: Adoption of the NC process among leaders in the field of neurotology in the United States has been robust, despite the significant costs entailed in participation.

Enlarged vestibular aqueduct syndrome mimicking otosclerosis in adults.

INTRODUCTION: An enlarged vestibular aqueduct (EVA) results in hearing loss which is often progressive and heterogenous, the long-term natural history of which is not well understood. Patients born before the era of newborn hearing screening can present as adults with previously undiagnosed EVA. METHODS: A retrospective chart review of patients seen at a tertiary adult academic otologic clinic from 2004 to 2012 were reviewed and cases of EVA were identified. RESULTS: Adult EVA was found to present with a mixed progressive hearing loss with absent stapedial reflexes. CONCLUSION: Enlarged vestibular aqueduct abnormality can present in adulthood and mimic other more common pathology such as otosclerosis.

Autoimmune inner ear disease preliminary case report: audiometric findings following steroid treatments.

PURPOSE: This study examined the audiometric findings following steroid treatment for autoimmune inner ear disease (AIED), which is characterized by bilateral subacute hearing loss, using oral and intratympanic treatment. METHOD: The charts of 9 patients with AIED who had been seen in the Saint Louis University School of Medicine's clinic between 2004 and 2011 were reviewed, with special focus on audiometric results. RESULTS: The majority of patients benefited from treatment for AIED. Four patients (6 ears) received intratympanic therapy as part of their treatment. CONCLUSION: Patients with AIED appeared to benefit from a clinical pathway using a prolonged course of oral steroids, followed by a trial of intratympanic steroids and/or immunosuppresants for refractory cases.

A humble task: restoring virtue in an age of conflicted interests.

Virtues define how we behave when no one else is watching; accordingly, they serve as a bedrock for professional self-regulation, particularly at the level of the individual physician. From the time of William Osler through the end of the 20th century, physician virtue was viewed as an important safeguard for patients and research participants. However, the Institute of Medicine, Association of American Medical Colleges, and other policy groups-relying on social science data indicating that ethical decisions often result from unconscious and biased processes, particularly in the face of financial conflicts of interest-have increasingly rejected physician virtue as an important safeguard for patients.The authors argue that virtue is still needed in medicine-at least as a supplement to regulatory solutions (such as mandatory disclosures). For example, although rarely treated as a reportable conflict of interest, standard fee-for-service medicine can present motives to prioritize self-interest or institutional interests over patient interests. Because conflicts of interest broadly construed are ubiquitous, physician self-regulation (or professional virtue) is still needed. Therefore, the authors explore three strategies that physicians can adopt to minimize the influence of self-serving biases when making medical business ethics decisions. They further argue that humility must serve as a crowning virtue-not a meek humility but, rather, a courageous willingness to recognize one's own limitations and one's need to use "compensating strategies," such as time-outs and consultation with more objective others, when making decisions in the face of conflicting interests.

Quantification of hearing loss associated with superior semi-circular canal dehiscence.

INTRODUCTION: Superior semi-circular canal dehiscence (SSCD) is a known cause of hearing loss. This study quantifies hearing loss in SSCD ears in a frequency-specific fashion. METHODS: A meta-analysis of English language literature pertaining to SSCD was performed, with extraction and evaluation of available human audiometric data. Our own institution's case series of SSCD patients was also similarly analysed. Hearing loss in SSCD ears was compared to same patient control ears and to age-matched normative audiometric data. RESULTS: Ears with SSCD had statistically significant worse hearing as compared to both normative data and to own normal ear controls at 2000 Hz and below. The effect appears to diminish with increasing frequency. DISCUSSION: The presence of statistically significant conductive hearing loss in the low frequencies was confirmed for SSCD ears. SSCD may also predispose ears to high frequency sensorineural hearing loss.

Evaluation of the efficacy of caffeine cessation, nortriptyline, and topiramate therapy in vestibular migraine and complex dizziness of unknown etiology.

OBJECTIVE: The aim of this study was to evaluate the efficacy of a therapeutic pathway for vestibular migraine (VM) and complex dizziness of undetermined etiology (CDUE) with caffeine cessation and pharmacotherapy. STUDY DESIGN: This study is a retrospective chart review. INTERVENTION(S): Patients were recommended to stop intake of caffeine and other putative migraine-triggering agents. Pharmacotherapy was initiated with nortriptyline or topiramate if symptoms persisted despite diet modification. MAIN OUTCOME MEASURE: Self-reported dizziness is the main outcome measure. RESULTS: Vestibular migraine and CDUE were considered contributing factors to dizziness in 34 and 10, respectively, of 156 patients. Fourteen percent of patients reported improvement in symptoms upon caffeine cessation, whereas 46% of patients reported a reduction in dizziness after nortriptyline therapy (P = .007). Topiramate reduced symptoms in 25% of patients. In total, 75% of VM patients and 56% of patients with CDUE received sufficient benefit from this therapeutic pathway to not progress to other treatments. CONCLUSIONS: Vestibular migraine and CDUE can be treated effectively with a therapeutic pathway consisting of caffeine cessation followed by pharmacotherapy.