Cisplatin is a potent antineoplastic agent widely used for a variety of cancer types. Unfortunately, its use leads to dose limiting side effects such as ototoxicity. Up to 93% of patients receiving ...cisplatin chemotherapy will develop progressive and irreversible sensorineural hearing loss which leads to a decreased quality of life in cancer survivors. No treatment is currently available for cisplatin-induced ototoxicity. It appears that cisplatin causes apoptosis by binding DNA, activating the inflammatory cascade as well as generating oxidative stress in the cell. Various studies have aimed to assess the potential protective effects of compounds such as antioxidants, anti-inflammatories, caspase inhibitors, anti-apoptotic agents and calcium channel blockers against the toxicity caused by cisplatin in the inner ear with variable degrees of protection. Nevertheless, the pathophysiology of cisplatin-induced ototoxicity remains unclear. This review summarizes all of the known transporters that could play a role in cisplatin influx, leading to cisplatin-induced ototoxicity. The following were evaluated: copper transporters, organic cation transporters, the transient receptor potential channel family, calcium channels, multidrug resistance associated proteins, mechanotransduction channels and chloride channels.
► Increase in ctr1 and decrease in ctr2 causes an increase in intracellular cisplatin. ► Organic cation transporter OCT2 is an important transporter for cisplatin, not OCT1. ► TRPA1 and TRPV1 expression is increased when cells are exposed to cisplatin. ► Roles of TRPA1 and TRPV1 in cisplatin toxicity are poorly understood. ► There is no evidence to suggest cisplatin may enter cells through calcium channels.
Advances in vestibular testing have now allowed us to test each semicircular canal as well as the utricle and saccule, independently. This has led to the discovery of new patterns of vestibular ...dysfunction that were once impossible to evaluate. This report describes the case of a 20-year-old woman with a 2-month history of recurrent dizziness. She had a complete audiovestibular assessment. The only abnormality observed was the absence of a cervical vestibular-evoked myogenic potential response for the right side, hence an isolated saccular dysfunction. In conclusion, isolated otolithic dysfunction is probably an overlooked and neglected clinical presentation. Its true incidence is unknown, and further research is needed to understand this clinical entity.
Vestibular assessment tests such as the video head impulse test (vHIT) for the horizontal semicircular canal, and caloric test (Cal), both evaluate horizontal canal function. One would assume that ...the outcomes for these tests should lead to concordant results, yet several studies have suggested that dissociation can occur in certain pathological conditions. As this topic remains inconclusive, this review aims to analyze the scientific evidence regarding the patterns of hypofunction observed in vHIT and Cal in different otoneurological diseases. A comprehensive review of the literature regarding dissociation between these tests in common neurotological diseases was carried out. Articles were analyzed when data for vHIT and Cal were described in a way that it was possible to calculate discordance rates; both retrospective and prospective studies were analyzed. In this review, the discordance rates were as follows: 56% in Ménière’s disease, 51.5% in vestibular migraine, 37.2% in vestibular schwannoma, and 20.8% in vestibular neuritis. These results highlight the benefit of using both Cal and vHIT, and that they are complementary tests.
Cisplatin is a known ototoxic chemotherapy drug, causing irreversible hearing loss. Evidence has shown that cisplatin causes inner ear damage as a result of adduct formation, a proinflammatory ...environment and the generation of reactive oxygen species within the inner ear. The main cochlear targets for cisplatin are commonly known to be the outer hair cells, the stria vascularis and the spiral ganglion neurons. Further evidence has shown that certain transporters can mediate cisplatin influx into the inner ear cells including organic cation transporter 2 (OCT2) and the copper transporter Ctr1. However, the expression profiles for these transporters within inner ear cells are not consistent in the literature, and expression of OCT2 and Ctr1 has also been observed in supporting cells. Organ of Corti supporting cells are essential for hair cell activity and survival. Special interest has been devoted to gap junction expression by these cells as certain mutations have been linked to hearing loss. Interestingly, cisplatin appears to affect connexin expression in the inner ear. While investigations regarding cisplatin-induced hearing loss have been focused mainly on the known targets previously mentioned, the role of supporting cells for cisplatin-induced ototoxicity has been overlooked. In this mini review, we discuss the implications of supporting cells expressing OCT2 and Ctr1 as well as the potential role of gap junctions in cisplatin-induced cytotoxicity.
Background
Cisplatin (CDDP) chemotherapy can cause serious side effects including irreversible and progressive hearing loss. Studies have aimed to assess potential protective strategies; however, ...systemic treatments have presented variable results, and potential interactions with CDDP have limited clinical trials.
Methods
A review of the literature was performed in order to evaluate clinical trials that have studied a transtympanic approach as an otoprotectant strategy.
Results
Six clinical trials were included. While a transtympanic approach can limit side effects and avoid interactions with CDDP, recurrent issues have been expressed including which otoprotectant to test, time delays between CDDP treatment and transtympanic injections, side effects such as pain and dizziness, concentrations, and number of injections. Clinical trials have used sodium thiosulfate,
N
-acetylcysteine and dexamethasone.
Conclusions
While a transtympanic approach seems like an attractive strategy, further research is needed to clarify which is the optimal otoprotectant, its dosage, and the number of injections.
Introduction
We are now able to detect abnormalities for any semicircular canal with the use of the video head impulse test (vHIT). Prior to the vHIT, the gold standard for unilateral canal paresis ...of the lateral canal was considered the caloric test. Clinical cases where the caloric test and vHIT are discordant are not uncommon.
Methods
Retrospective study. All consecutive cases of dizziness seen from 11/2020 to 12/2021 for which the patient underwent both caloric and vHIT tests performed within 10 days, were reviewed. Patients with discordant results were included. We evaluated the caloric response, vHIT gains for all canals and saccades, with and without gain abnormalities.
Results
We included 74 cases of dizziness with dissociated results. The most common finding was a normal caloric response with abnormal vHIT results (60.8%); the main abnormal finding on vHIT was the presence of saccades. In this group, 37.7% of patients had normal gains and refixation saccades. In addition, the most found low gain was for the posterior canal. The main diagnosis in this group was vestibular migraine. For the group with unilateral caloric paresis and normal vHIT gain in the lateral canal, the main diagnosis was Ménière's disease.
Discussion
The most common disorders with discordant results were Ménière's disease and vestibular migraine. The caloric test and vHIT are complementary and combining both tests provide greater clinical information. Further research is needed to understand refixation saccades with normal gains.
Lindsay-Hemenway syndrome was first described as an acute unilateral peripheral vestibulopathy followed by positional vertigo. A vascular etiology was proposed. An association between cardiovascular ...risk factors and benign paroxysmal positional vertigo secondary to acute unilateral peripheral vestibulopathy has been described with contradictory evidence. The study aimed to evaluate the prevalence of cardiovascular risk factors in patients with benign paroxysmal positional vertigo secondary to acute unilateral peripheral vestibulopathy and analyze differences in prior history of benign paroxysmal positional vertigo, affected semicircular canals, and response to repositioning maneuvers between patients with idiopathic benign paroxysmal positional vertigo and secondary to acute unilateral peripheral vestibulopathy.
We performed a retrospective, descriptive study of all cases of benign paroxysmal positional vertigo between January/2017 and June/2020, with or without a history of acute unilateral peripheral vestibulopathy within the previous year. Cases secondary to trauma or otoneurological causes and acute unilateral peripheral vestibulopathy without confirmatory tests and cases with auditory symptoms were excluded.
In total, 242 cases were obtained; 158 idiopathic benign paroxysmal positional vertigo and 84 secondary to acute unilateral peripheral vestibulopathy. No statistically significant differences were found in relation to age: 61.2 ± 14.6 versus 62.4 ± 16.2 years (P=.55), sex: female 78.5% versus 73.8% (P=.41), presence of cardiovascular risk factors: 52.5% versus 54.8% (P=.67), prior history of benign paroxysmal positional vertigo: 22.2% versus 27.7% (P=.43), affected semicircular canals (P=.16) or number of repositioning maneuvers (P=.57).
Associations between age, cardiovascular risk factors, and benign paroxysmal positional vertigo secondary to acute unilateral peripheral vestibulopathy have been described with conflicting evidence. This is the first study to evaluate cardiovascular risk factors specifically for Lindsay-Hemenway syndrome, and we did not observe any differences between idiopathic benign paroxysmal positional vertigo cases and those secondary to acute unilateral peripheral vestibulopathy.
Background: Vestibular migraine (VM) is the most frequent etiology of recurrent spontaneous episodic vertigo. Vestibular and oculomotor abnormalities have been described in VM; however, the diagnosis ...is currently based on symptoms. The objective of this study was to determine the most frequent abnormalities in videonystagmography (VNG), caloric testing (Cal) and video head impulse test (vHIT) in patients with VM. Methods: A retrospective cohort study was conducted, including all VM and probable VM patients seen from January 2021 to July 2022. Demographics, auditory symptoms and results via VNG, Cal and vHIT were evaluated. VNG results were compared with a control group. Results: Sixty patients, 81.7% with VM and 18.3% with probable vestibular migraine, were included. VNG revealed the following abnormalities: 21.7% spontaneous nystagmus; 33.3% positional nystagmus, mostly central; 26.7% optokinetic nystagmus; 56.7% smooth pursuit abnormalities and 70% saccade test abnormalities, mostly velocity and latency. An abnormal unilateral caloric response was seen in 22.9%, while vHIT revealed a low gain in at least one canal in 21.7%, and saccades were seen in at least one canal with normal gains in 18.3%. Concordant results between Cal and lateral vHIT were seen in 77.1% of cases. Conclusions: Although VM is a clinical diagnosis, vestibular and oculomotor abnormalities are commonly seen. The most frequent oculomotor findings were an abnormal saccade test, abnormal smooth pursuit and central positional nystagmus.
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