A hypothetical proposal for association between migraine and Meniere's disease.

Meniere's disease (MD) is a chronic condition affecting the inner ear whose precise etiology is currently unknown. We propose the hypothesis that MD is a migraine-related phenomenon which may have implications for future treatment options for both diseases. The association between MD and migraine is both an epidemiological and a mechanistic one, with up to 51% of individuals with MD experiencing migraine compared to 12% in the general population. The presence of endolymphatic hydrops in those with MD may be the factor that unites the two conditions, as hydropic inner ears have an impaired ability to maintain homeostasis. Migraine headaches are theorized to cause aura and symptoms via spreading cortical depression that ultimately results in substance P release, alterations in blood flow, and neurogenic inflammation. Chronically hydropic inner ears are less able to auto-regulate against the changes induced by active migraine attacks and may ultimately manifest as MD. This same vulnerability to derangements in homeostasis may also explain the common triggering factors of both MD attacks and migraine headaches, including stress, weather, and diet. Similarly, it may explain the efficacy of common treatments for both diseases: current migraine treatments such as anti-hypertensives and anti-convulsants have shown promise in managing MD. Though the etiology of both MD and migraine is likely multifactorial, further exploration of the association between the two conditions may illuminate how to best manage them in the future. MD is likely a manifestation of cochleovestibular migraine, which occurs as a result of migraine related changes in both the cochlea and vestibule

Adjuvant Migraine Medications in the Treatment of Sudden Sensorineural Hearing Loss.

Objectives/hypothesisTo examine the hearing outcomes of patients with sudden sensorineural hearing loss (SSNHL) treated with oral and intratympanic (IT) steroid only or a combination of steroid and migraine treatment. Our hypothesis was that adjuvant migraine medications may improve outcomes in SSNHL.MethodsA retrospective chart review at a tertiary otology center was conducted to identify patients with SSNHL who received oral steroid and IT dexamethasone injection(s) with or without migraine medications (a combination of nortriptyline and topiramate).ResultsA total of 47 patients received oral steroid and IT dexamethasone injection(s) only, and 46 patients received oral steroid and IT dexamethasone injection(s) as well as migraine lifestyle changes plus a combination of nortriptyline and topiramate. There were no significant differences in demographics and baseline audiometric data between the two groups. Both groups demonstrated improvements in pure tone average (PTA) and hearing thresholds at 250 Hz and 8000 Hz posttreatment. However, compared to steroid-only group, the adjuvant migraine medications group had significantly greater improvements in hearing thresholds at the lower frequencies (250 Hz, 500 Hz, 1000 Hz). Patients in the latter cohort also had greater improvement in PTA (P = .01) and received fewer IT injections (P = .04) PTA improvement of ≥ 10 dB was observed in 36 patients (78%) in the adjuvant migraine medications group and 22 patients (46%) in the control group (P < .001).ConclusionIn multimodal treatment of SSNHL, supplementing oral and IT steroid with migraine medications may result in greater improvements in lower frequency hearing thresholds and PTA. Furthermore, adjuvant migraine treatment can lead to decrease in number of IT injections, thus reducing procedure-related risks and complications.Level of evidence3 Laryngoscope, 131:E283-E288, 2021

Rings Reconcile Genotypic and Phenotypic Evolution within the Proteobacteria.

Although prokaryotes are usually classified using molecular phylogenies instead of phenotypes after the advent of gene sequencing, neither of these methods is satisfactory because the phenotypes cannot explain the molecular trees and the trees do not fit the phenotypes. This scientific crisis still exists and the profound disconnection between these two pillars of evolutionary biology--genotypes and phenotypes--grows larger. We use rings and a genomic form of goods thinking to resolve this conundrum (McInerney JO, Cummins C, Haggerty L. 2011. Goods thinking vs. tree thinking. Mobile Genet Elements. 1:304-308; Nelson-Sathi S, et al. 2015. Origins of major archaeal clades correspond to gene acquisitions from bacteria. Nature 517:77-80). The Proteobacteria is the most speciose prokaryotic phylum known. It is an ideal phylogenetic model for reconstructing Earth's evolutionary history. It contains diverse free living, pathogenic, photosynthetic, sulfur metabolizing, and symbiotic species. Due to its large number of species (Whitman WB, Coleman DC, Wiebe WJ. 1998. Prokaryotes: the unseen majority. Proc Nat Acad Sci U S A. 95:6578-6583) it was initially expected to provide strong phylogenetic support for a proteobacterial tree of life. But despite its many species, sequence-based tree analyses are unable to resolve its topology. Here we develop new rooted ring analyses and study proteobacterial evolution. Using protein family data and new genome-based outgroup rooting procedures, we reconstruct the complex evolutionary history of the proteobacterial rings (combinations of tree-like divergences and endosymbiotic-like convergences). We identify and map the origins of major gene flows within the rooted proteobacterial rings (P < 3.6 × 10(-6)) and find that the evolution of the "Alpha-," "Beta-," and "Gammaproteobacteria" is represented by a unique set of rings. Using new techniques presented here we also root these rings using outgroups. We also map the independent flows of genes involved in DNA-, RNA-, ATP-, and membrane- related processes within the Proteobacteria and thereby demonstrate that these large gene flows are consistent with endosymbioses (P < 3.6 × 10(-9)). Our analyses illustrate what it means to find that a gene is present, or absent, within a gene flow, and thereby clarify the origin of the apparent conflicts between genotypes and phenotypes. Here we identify the gene flows that introduced photosynthesis into the Alpha-, Beta-, and Gammaproteobacteria from the common ancestor of the Actinobacteria and the Firmicutes. Our results also explain why rooted rings, unlike trees, are consistent with the observed genotypic and phenotypic relationships observed among the various proteobacterial classes. We find that ring phylogenies can explain the genotypes and the phenotypes of biological processes within large and complex groups like the Proteobacteria

Proposal for a new diagnosis for U.S. diplomats in Havana, Cuba, experiencing vestibular and neurological symptoms.

Between 2016 and 2017, several U.S. Diplomats in Havana, Cuba, experienced perplexing vestibular and neurological symptoms attributed to an unknown source. They presented with significant vestibular and headache symptoms similar to individuals who experience vestibular migraine (VM). As such, we hypothesize that VM may be a possible explanation for the Havana cohorts presenting symptoms. To evaluate this hypothesis, we compared symptoms reported by the affected individuals in Havana, Cuba, to symptoms reported by corresponding patients from a tertiary academic neurotology clinic with a chief complaint of vertigo or disequilibrium, who met the International Classification of Headache Disorders criteria for VM. The prevalence of the Havana subjects experiencing various symptomatic domains was compared with the VM cohort, leading to 26 unique domains and statistical comparisons between the cohorts. Of the 26 domains compared between the two cohorts, 18 were not significantly different. This included the two most important components of meeting criteria for VM, namely the co-existence of headache and vestibular symptoms. On regression analysis, the only feature which kept its significant difference between the two cohorts was acute intense head pressure (P = 0.007). The domains with similar occurrence ratios included dizziness, headache, light sensitivity, hearing reduction, and tinnitus. In other words, multiple headache and vestibular symptoms, consistent with VM criteria, were similar between the two cohorts. The considerable similarities across various domains between VM patients and Havana subjects could be due to migraine as a possible common etiology for both groups. We propose VM as a potential etiology for the symptomatology in the U.S. diplomats in Cuba

Proposal for a new diagnosis for U.S. diplomats in Havana, Cuba, experiencing vestibular and neurological symptoms.

Between 2016 and 2017, several U.S. Diplomats in Havana, Cuba, experienced perplexing vestibular and neurological symptoms attributed to an unknown source. They presented with significant vestibular and headache symptoms similar to individuals who experience vestibular migraine (VM). As such, we hypothesize that VM may be a possible explanation for the Havana cohort's presenting symptoms. To evaluate this hypothesis, we compared symptoms reported by the affected individuals in Havana, Cuba, to symptoms reported by corresponding patients from a tertiary academic neurotology clinic with a chief complaint of vertigo or disequilibrium, who met the International Classification of Headache Disorders criteria for VM. The prevalence of the Havana subjects experiencing various symptomatic domains was compared with the VM cohort, leading to 26 unique domains and statistical comparisons between the cohorts. Of the 26 domains compared between the two cohorts, 18 were not significantly different. This included the two most important components of meeting criteria for VM, namely the co-existence of headache and vestibular symptoms. On regression analysis, the only feature which kept its significant difference between the two cohorts was acute intense head pressure (P = 0.007). The domains with similar occurrence ratios included dizziness, headache, light sensitivity, hearing reduction, and tinnitus. In other words, multiple headache and vestibular symptoms, consistent with VM criteria, were similar between the two cohorts. The considerable similarities across various domains between VM patients and Havana subjects could be due to migraine as a possible common etiology for both groups. We propose VM as a potential etiology for the symptomatology in the U.S. diplomats in Cuba

Perilymphatic Fistula: A Review of Classification, Etiology, Diagnosis, and Treatment.

A perilymphatic fistula (PLF) is an abnormal communication between the perilymph-filled inner ear and the middle ear cavity, mastoid, or intracranial cavity. A PLF most commonly forms when the integrity of the oval or round window is compromised, and it may be trauma-induced or may occur with no known cause (idiopathic). Controversy regarding the diagnosis of idiopathic PLF has persisted for decades, and the presenting symptoms may be vague. However, potential exists for this condition to be one of the few etiologies of dizziness, tinnitus, and hearing loss that can be treated surgically. The aim of this review is to provide an update on classification, diagnosis, and treatment of PLF. Particular attention will be paid to idiopathic PLF and conditions that may have a similar presentation, with subsequent information on how best to distinguish them. Novel diagnostic criteria for PLF and management strategy for PLF and PLF-like symptoms is presented

Perilymphatic Fistula: A Review of Classification, Etiology, Diagnosis, and Treatment.

A perilymphatic fistula (PLF) is an abnormal communication between the perilymph-filled inner ear and the middle ear cavity, mastoid, or intracranial cavity. A PLF most commonly forms when the integrity of the oval or round window is compromised, and it may be trauma-induced or may occur with no known cause (idiopathic). Controversy regarding the diagnosis of idiopathic PLF has persisted for decades, and the presenting symptoms may be vague. However, potential exists for this condition to be one of the few etiologies of dizziness, tinnitus, and hearing loss that can be treated surgically. The aim of this review is to provide an update on classification, diagnosis, and treatment of PLF. Particular attention will be paid to idiopathic PLF and conditions that may have a similar presentation, with subsequent information on how best to distinguish them. Novel diagnostic criteria for PLF and management strategy for PLF and PLF-like symptoms is presented