Sensorineural hearing loss is mainly acquired and affects an estimated 1.3 billion humans worldwide. It is related to aging, noise, infection, ototoxic drugs, and genetic defects. It is essential to identify reversible and preventable causes to be able to reduce the burden of this disease. Inflammation is involved in most causes and leads to tissue injury through vasospasm-associated ischemia. Vasospasm is reversible. This review summarized evidence linking inflammation-induced vasospasm to several forms of acquired sensorineural hearing loss. The link between vasospasm and sensorineural hearing loss is directly evident in subarachnoid haemorrhage, which involves the release of vasoconstriction-inducing cytokines like interleukin-1, endothelin-1, and tumour necrosis factor. These proinflammatory cytokines can also be released in response to infection, autoimmune disease, and acute or chronically increased inflammation in the ageing organism as in presbyacusis or in noise-induced cochlear injury. Evidence of vasospasm and hearing loss has also been discovered in bacterial meningitis and brain injury. Resolution of inflammation-induced vasospasm has been associated with improvement of hearing in autoimmune diseases involving overproduction of interleukin-1 from inflammasomes. There is mainly indirect evidence for vasospasm-associated sensorineural hearing loss in most forms of systemic or injury- or infection-induced local vascular inflammation. This opens up avenues in prevention and treatment of vascular and systemic inflammation as well as vasospasm itself as a way to prevent and treat most forms of acquired sensorineural hearing loss. Future research needs to investigate interventions antagonising vasospasm and vasospasm-inducing proinflammatory cytokines and their production in randomised controlled trials of prevention and treatment of acquired sensorineural hearing loss. Prime candidates for interventions are hereby inflammasome inhibitors and vasospasm-reducing drugs like nitric oxide donors, rho-kinase inhibitors, and magnesium which have the potential to reduce sensorineural hearing loss in meningitis, exposure to noise, brain injury, arteriosclerosis, and advanced age-related and autoimmune disease-related inflammation.
Vasospasm is a consistent feature of all forms of cerebral inflammation including forms caused by infections like bacterial meningitis, cerebral malaria, and sterile vascular inflammation as detectable in diabetic ketoacidosis and brain injury [
Included were the following studies: Reports providing evidence relating to conditions associated with inflammation and SNHL and/or a focus on a potential association between inflammation-induced vasospasm and SNHL. As indicator of vasospasm was in the interpretation hereby taken that a proportion of people affected by a condition associated with SNHL showed laterality/ and or reversibility of the SNHL. Both animal and human studies. All studies reporting randomised controlled trials of anti-inflammatory or vasospasm-relieving drugs in prevention and/or treatment of SNHL. Studies which reported on the pathophysiology of cytokine-induced hearing loss or vasospasm.
Excluded were the following studies: Studies in which patients with conductive hearing loss were investigated. Studies not reported in English language. Case reports on effect of treatment modalities on SNHL. Nonrandomised studies with regard to treatment trials in humans. Studies on compromise of vascular supply by arterial wall thickening, e.g., in vasculitis and endoluminal stenosis like in subendothelial atherosclerotic proliferation or in obstruction of the vascular lumen by embolism.
Searches using the following keywords were carried out in September 2019: (i) “hearing loss” and “vasospasm” in the PubMed database and (ii) “sensorineural hearing loss” in the Cochrane Library database.
References of relevant articles were searched and incorporated where indicated. For flow chart of literature search, see Figure
Flow chart of literature search.
In the descending order of strength of a potential causal association of inflammation-induced vasospasm and SNHL, conditions were categorized into 3 categories: “Direct evidence” for inflammation-associated vasospasm causing SNHL studies where there was evidence of vasospasm on in vivo dynamic imaging like Doppler flow studies in patients with conditions with SNHL more than in patients without the same conditions. Evidence regarding vasoconstrictors and treatment with ant-inflammatory agents and vasodilators was similarly labelled if based on a model with direct evidence. “Features consistent with inflammation-associated vasospasm-induced SNHL” and the associated treatment addressing and/or leading to a change in those features. “Conditions associated with increased risk of inflammation associated with vasospasm-induced SNHL.” All forms of inflammation involving vasoconstriction causing cytokines were regarded as putting the cochlear perfusion at risk of vasospasm-induced compromise.
Direct evidence for a vasospasm as etiological factor in acquired SNHL is the analysis of data from children with sudden SNHL where influence of noise exposure, medication and drugs including illicit substances, and exposure to chemicals at the work place which could cause temporary hair cell dysfunction is much less likely. A pooled analysis of 226 cases (ears) of sudden SNHL in children from two centres in China demonstrated 85% of children had unilateral hearing loss, of which the largest proportion was profound (51%). The hearing loss was reversible to a variable extent (including any form of recovery) in 48.6% [
The hearing loss found associated with autoimmune-induced inflammation has features consistent with inflammation-associated vasospasm-induced sensorineural hearing loss. The hearing loss in autoimmune-induced inflammation is potentially reversible, and anti-inflammatory treatment can prevent and treat SNHL [
Autoimmune diseases like systemic lupus erythematosus and Crohn’s disease which induce overproduction of tumor necrosis factor (TNF) and rarer diseases like the cryopyrin-associated periodic syndromes with inflammasome activation and subsequent overproduction of interleukin-1(IL-1) like CINCA syndrome and Muckle–Wells disease have been associated with SNHL [
In bacterial meningitis, severe inflammation of the meninges is observed which should, if there was a link between inflammation and SNHL lead to SNHL. Hearing loss is indeed observed in all forms of bacterial meningitis [
In a prospective study of 236 children with meningitis using brainstem auditory evoked responses, 38 were detected with hearing loss in the acute (early) phase of meningitis; among these, 32 were available for follow-up, and within the latter group, 22 recovered normal hearing, i.e., reversibility was seen in 68.7% of the cases available for documentation. The hearing loss was unilateral in 21 of the 38 children with hearing loss detected in the acute meningitis phase (= 55.3%). The 21 unilateral HL cases among 236 children with bacterial meningitis amounted therefore to 9% [
An analysis of risk factors for SNHL in patients with bacterial meningitis identified focal neurological signs, as found in localized vasospasm, as an associated feature but not general severity of sepsis (see Table
Clinical manifestations, indicators of disease severity, and SNHL in bacterial meningitis (data from [
Cases with SNHL after bacterial meningitis ( |
Controls without SNHL after bacterial meningitis ( |
|
Odds ratio (95% CI) | |
---|---|---|---|---|
Signs of shock on admission | 13 | 48 | 0.65 | 0.78 (0.35–1.76) |
Mechanical ventilation | 2 | 16 | 0.24 | 0.36 (0.05–1.76) |
Seizures | 10 | 29 | 0.96 | 1.11 (0.45–2.71) |
Focal neurological signs | 16 | 9 | <0.001 | 9.0(3.11–27.7) |
A prospective investigation of adults with bacterial meningitis by transcranial Doppler sonography related the degree of arterial narrowing to outcome including focal cerebral ischemic deficits, which were more frequent in patients with cerebral blood flow velocity >210 cm/s compatible with vasospasm [
Other investigations confirmed features of cerebral vasospasm in bacterial meningitis. Patients with features of vasospasm had significantly increased concentrations of IL-1 and IL-6 in the CSF. Underlying mechanisms have been explored in a rat model, where cerebral blood flow as measured by injection and recovery of microspheres from the brain tissue was found to be reduced in pneumococcal meningitis. The cerebral blood flow could be restored by the endothelin-1 antagonist bosentan with a reduction in cortical cerebral injury. Strong evidence of a protective role of the vasodilator nitric oxide against vasospasm in bacterial meningitis was derived from an animal model of neonatal meningitis where inhibition of NO synthase worsened outcome in some models of bacterial meningitis, leading to local cerebral ischemia [
All these lines of evidence revealed features consistent with inflammation-associated vasospasm-induced SNHL but no direct evidence for a link between the hearing loss observed and vasospasm of blood supply of the cochlea.
A recent systematic review of 13 studies encompassing 773 patients found that the studies with the highest level of evidence reported a transient or chronic hearing loss of at least 10–15 dB across a range of frequencies in as many as 58% of patients with traumatic brain injury without bone fracture [
Vasospasm has hereby previously been associated with brain injury and was more severe in patients with associated features of a systemic inflammatory response [
In subarachnoid haemorrhage, vasospasm has been directly linked to hearing loss [
A retrospective case control study of neonatal brain injury including 58 infants with SNHL and comparing them with 116 controls without hearing loss established that cerebral infarction was significantly increased in infants with SNHL compared to normal hearing controls [
The labyrinthine artery is known to constrict during and after noise overstimulation [
Age-related inflammatory diseases like type II diabetes and cardiovascular disease have been associated with SNHL [
The theoretic possibility of vasospasm related to arteriosclerotic inflammation is raised by the transient audiovestibular dysfunction with transient hearing loss found as prodromal symptom of stroke affecting the supply area of the anterior inferior cerebellar artery in vertebrobasilar ischemic stroke affecting 8 to 31% of prospectively observed patients including patients with normal diffusion-weighted MRI after the attack [
Overall, the findings in presbyacusis justify the conjecture of an increased risk of inflammation-associated vasospasm-induced sensorineural hearing loss as a contributory underlying mechanism.
The pain of migraine-associated headaches has been linked to the activation of nociceptors by the vasoconstriction-inducing cytokines TNF and IL-1 [
Inflammatory mediator action could explain the role of vasospasm in the pathogenesis of SNHL in all the aforementioned conditions. For many years, the cochlea was considered an “immune-privileged” organ because of the presence of a tight junction-based blood-labyrinth barrier. A number of more recent studies, however, showed that resident macrophages are always present in the cochlear lateral wall as well as in the spiral limbus and the scala tympani side of the basilar membrane, and they are activated by various types of insults, including noise exposure, ischemia, mitochondrial damage, and surgical stress leading to cytokine release including tumour necrosis factor [
TNF-alpha was shown to be effective in decreasing cochlear blood flow at a dose of 5.0 ng/mL. Lower concentrations or placebo treatment did not lead to significant changes. After pretreatment with etanercept, a recombinant human TNF receptor p75 Fc fusion protein, which blocks TNF action, TNF-alpha at a dose of 5.0 ng/mL, no longer led to a change in cochlear blood flow [
In a prospective clinical trial in Mongolian gerbils, tumor necrosis factor-alpha administered via continuous 8-day intrathecal flow induced SNHL across all frequencies compared to phosphate-buffered saline delivered intrathecally in controls and tumor necrosis factor-alpha antibody injected intraperitoneally reduced SNHL in the pneumococcal meningitis model [
In a prospective observational study, tumor necrosis factor-alpha levels in peripheral venous blood were compared between patients with autoimmune inner ear disease and sudden SNHL compared to controls and steroid responders compared with steroid nonresponders. TNF levels were significantly higher in patients with sudden SNHL, and a high baseline plasma TNF of greater than 18.8 pg/ml had a positive predictive value higher than 97% for a sudden change in hearing threshold [
The mechanism by which tumor necrosis factor causes a reduction in cochlear blood flow has been identified and involved contraction of cochlear pericytes which has in the guinea pig model been found to cause a reduction of capillary diameter by 3.6 ± 4.3%, which was reversible by anti-TNF therapy with ethanercept [
The effect of TNF on vasoconstriction may be mediated by sphingosine-1-phosphate (S1P) [
S1P has been demonstrated to lead to vasoconstriction in cerebral and basilar arteries in vivo in animal models. This effect was shown to be mediated by elevation of intracellular calcium levels by mobilisation from intracellular stores in smooth muscle cells. Ca2+ sensitization of the contractile filaments, which frequently involves a rho-kinase, is also an effect of S1P and has been observed in human coronary smooth muscle cells. Inhibition of the rho A/rho-kinase pathway has hereby been shown to inhibit vasoconstriction [
The question is whether the chronic inflammation leading up to presbyacusis leads to SNHL via cytokine-induced apoptosis of hair cells of the inner ear or recurrent vasospasm in the labyrinthine artery. In addition to causing vasospasm, TNF could trigger programmed cell death (apoptosis) in hair cells of the inner ear and thus cause SNHL. The extrinsic pathway to apoptosis includes TNF alpha, which via TNF receptor-associated death domain activates cysteine-aspartic proteases (caspases)-8 and -10. Caspase-8 then can activate tBid to recruit the help of the intrinsic pathway and can activate caspases-3, -6, and -7. These caspases lead to the execution phase of cell death induction through their protein-cutting activity. Caspase-3 can hereby cause DNA and chromatin damage, rearrange the cytoskeleton, and disrupt intracellular transport [
An investigation in patients with SAH showed that levels of IL-1 beta but not TNF-alpha were increased and correlated with the later development of vasospasm. IL-1 acts through G-protein-coupled receptors in three ways which cause contraction of vascular smooth muscle [ Activation of phospholipase C-generated phosphatidylinositol trisphosphate causes calcium release which leads to myosin light chain kinase activation leading to myosin light chain activation and calcium-dependent vasospasm. Phosphorylation of myosin light chain (MLC) by MLC kinase is one of the most important steps for vascular smooth muscle contraction. Activation of protein kinase C (PKC) through phospholipase C-generated diacylglycerol (from phosphatidylinositol (4,5) bisphosphate) can act through phosphorylation, hence activating the myosin light chain kinase. Prolonged contraction in cerebral vasospasm for up to two weeks can be mediated by this mechanism. PKC activation regulates MLC phosphorylation through activation of rho-kinase and the myosin-binding subunit (MBS) of MLC phosphatase (MLCPh).
A secondary pathway for vascular smooth muscle contraction that is not directly dependent on Ca2+ concentration, but rather mediating Ca2+ sensitization, is the rho A/rho-kinase pathway. In cultured human coronary vascular smooth muscle cells, inflammatory stimuli, such as IL-1 beta, increase rho-kinase expression (at both mRNA and protein levels) and function [
Both endothelial NO production and NO-mediated signaling in vascular smooth muscle cells (VSMC) are targets and effectors of the rho A/rho-kinase pathway. In endothelial cells (ECs), the rho A/rho-kinase pathway negatively regulates NO production [
Mechanism of action of interleukin-1 (IL-1) via G-protein coupled receptors (GPCR) on reduction of nitric oxide (NO) production by reducing nitric oxide synthase (NOS) activity in the vascular endothelial cell (EC) and by activation of the enzyme Rho kinase via RhoA in the vascular smooth muscle cell to activate by phosphorylation through protein kinase C (PKC) myosine phosphatase targeting subunit-1 (MYPT1), protein kinase C-potentiated phosphatase inhibitor-17 (CPI-17 and myosine binding subunit (MBS)), which all three inhibit the myosine light chain phosphatase (MLCP) which dephosphorylates the myosine light chain, a process, which is necessary for smooth muscle relaxation. This process thus causes vasoconstriction.
Endothelin-1 is one way of action of both TNF and IL-1 on vasospasm-induced hearing loss. Only ET-1 is produced in cerebral endothelium and mediates cerebral vasoconstriction via endothelin-A (ETA) receptors. ETA is localized in vascular smooth muscle cells, and stimulation leads to increase in intracellular calcium concentrations leading to vasoconstriction. ET-1 expression is enhanced by IL-1 and TNF and can be inhibited by NO, nitric oxide donor drugs, and dilator prostanoids via an increase in cellular cGMP. NO can produce relaxation of some blood vessels from some species via activation of potassium channels [
Should cytokines have a role in SNHL one would expect that cytokine gene polymorphisms which are associated with differences in cytokine production differ between patients prone to hearing loss and those who are not. This is in fact the case.
A significant difference in carriage of both the IL-1
Genetic linkage studies have investigated the association of polymorphisms of the TNF-alpha and TNF-beta genes with sudden SNHL comparing 97 SSNHL patients and 587 controls and found that the TNF-beta +252 A− ⟶ G polymorphism which is associated with increase in production of this cytokine was significantly increased in patients with SSNHL [
Blockade of L-type voltage-gated Ca2+ channels protected against NIHL in mice and in guinea pigs, and blockade of T-type voltage-gated Ca2+ channels was effective in mice. Also consistent with a contribution of calcium-mediated events in hair cell damage, application of the calcineurin inhibitor FK506 attenuated NIHL in guinea pigs [
In addition to the well-characterized effects on vasodilation, biochemical effects of magnesium include modulation of calcium channel permeability, influx of calcium into cochlear hair cells, and glutamate release [
The first evidence for the importance of magnesium in prevention of SNHL was gained in observational studies of magnesium deficiency in rats and guinea pigs exposed to noise. Magnesium deficiency increased susceptibility to NIHL in rats [
The results of magnesium in animal experiments have have been confirmed in 3 randomised controlled trials [
Evidence for effectiveness of magnesium in prevention of noise-induced SNHL from randomised controlled trials in humans.
Design | Number of participants | Age of participants | Intervention | Outcome | Critical appraisal | Reference |
---|---|---|---|---|---|---|
Placebo-controlled double blind | 28 participants in total, number per group unknown | 22 to 75 years of age, mean 53 years | 6.7 mmol of magnesium aspartate orally once a day | Improvement of sudden SNHL excluding noise, mumps, Meniere’s disease, and traumatic SNHL: more patients with improved hearing and a greater improvement in those with SSNHL were noted in the magnesium treated group across all frequencies assessed | The investigation did not report method of randomisation, number randomised into each group, and number of patients with improved hearing for each frequency | [ |
|
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Placebo-controlled double blind | 150 participants in each group | 17.7 to 18.5 years old | 6.7 mmol of magnesium aspartate orally once a day | Noise-induced permanent hearing threshold shifts in 11.2% in the magnesium group versus 21.5% in the placebo group ( |
The method of randomisation was unclear, and the duration of prophylactic treatment and timing of measurement were not specified | [ |
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Placebo-controlled double blind | 215 participants, 105 in the magnesium group, and 110 in the placebo group | 18-year-old men | 6.7 mmol of magnesium aspartate orally once a day | There was a noise-induced pure tone audiometry threshold shift (>25 dB at 3 to 8 kHz) in 11.2% (both ears) of the magnesium group and 21.5% in the left ear and 28.5% in the right ear in the placebo group | The method of randomisation was unclear, and the duration of prophylactic treatment and timing of sampling were not specified | [ |
Meta-analyses of randomised controlled trials in humans to treat SNHL with steroids.
Design | Number of participants/number of randomised controlled trials | Age of participants | Intervention | Outcome | Critical appraisal | Reference |
---|---|---|---|---|---|---|
Systematic review with meta-analysis of randomised controlled trials | 1394/14 | Unknown | Combined intratympanic and systemic use of steroids as a first-line treatment for sudden SNHL | The proportion of patients with hearing improvement as the outcome measure was observed in 13 studies, which resulted in an odds ratio (OR) of 2.50 (95% confidence interval (CI): 1.95–2.1) | The differences in treatment regimes or unclear treatment invalidate the pooling of results | [ |
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Systematic review and meta-analysis of randomised controlled trials | 416/8 | Mean age 47 to 60 years | Isolated intratympanic dexamethasone for sudden SNHL | Pure-tone audiogram improvement criterion did not reach statistical significance (OR 5 0.39, CrI 5 0.11–1.27) | Large heterogeneity was noted among these studies | [ |
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Systematic review and meta-analysis of randomised, controlled trials | 203 /5 | Unknown overall age distribution | Intratympanic steroid therapy as a salvage treatment for sudden SNHL after failure of conventional therapy | The meta-analysis data were derived from 5RCTs of 102 patients in the ITS group and 101 control subjects; the mean difference and 95% CI of the PTA improvement (indB) were 7.43 and 4.25–10.60, respectively | The authors suspected that the small number of trials (5) available for their meta-analysis was due to publication bias with studies reporting nonsignificant results under represented | [ |
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Systematic review and meta-analysis of randomised, controlled trials | 1166/15 | Unknown | Treatment of sudden SNHL | Three articles (181 subjects), steroid versus placebo analysis: OR = 1.52 (95% confidence interval (CI): 0.83–2.77); six articles (702 subjects) in systemic versus intratympanic steroids analysis (OR 1.14 (95% CI: 0.82–1.59)); six articles (283 subjects): salvage treatment analysis (OR: 6.04 (95% CI: 3.26–11.2)) | Numbers are small in the subgroup analyses shown; a clinically significant effect may have been missed | [ |
This result confirmed a previous study: The Blue Mountains Hearing Study is a population-based survey of age-related hearing loss which aimed to assess associations between dietary intake of fats (saturated and monounsaturated fats and cholesterol) and certain food groups (butter, margarine, and nuts) with the prevalence, incidence, and progression of age-related hearing loss. It also investigated the link between serum lipids and cholesterol-lowering medication (statins) and hearing loss. Among persons self-reporting statin use (
On the other hand, a population-based study in Taiwan showed a slight but significant association of previous statin use and SNHL (27% with versus 21% without previous statin use, OR 1.36 (95% CI: 1.18 to 1.57)) [
The only randomised double-blind clinical trial in this area was geared to investigate the impact of statins on presbyacusis. It was very small with a total of 50 patients. Pure-tone audiometry and tinnitus evaluation at enrolment and after 7 and 13 months of atorvastatin did not show any impact on hearing thresholds or tinnitus [
It is therefore not surprising that oral curcumin in a highly bioavailable preparation has been shown to reduce noise-induced SNHL in a murine model in a dose-dependent fashion [
One mechanism may be its capacity for reduction of TNF expression [
Increasing intracellular cGMP, which inhibits calcium entry into the cell, and decreasing intracellular calcium concentrations Activating K+ channels, which leads to hyperpolarization and relaxation Stimulating a cGMP-dependent protein kinase that activates myosin light chain phosphatase, the enzyme that dephosphorylates myosin light chains, which leads to smooth muscle relaxation
Because of the central role of cGMP in NO-mediated vasodilation, drugs that inhibit the breakdown of cGMP (cGMP-dependent phosphodiesterase inhibitors) are used to enhance NO-mediated vasodilation.
Experiments in the mouse model of noise-induced SNHL demonstrated that Pde5 inhibition protected against NIHL [
There have been concerns about an association of phosphodiesterase-5 inhibitor use and SNHL but this can be attributed to a confounding association of erectile dysfunction and hearing loss. Erectile dysfunction is the most common indication for phosphodiesterase-5 inhibition. Erectile dysfunction is liked to SNHL because both can be due to vascular dysfunction or vasospasm in the supplying artery in arteriosclerosis [
Inflammation is a normal adaptive response aimed at restoring tissue functionality and homeostasis after infection and tissue injury, and suppressing it could have unintended negative consequences. Previous authors recognized the potentially important role of inflammation in causing age, noise, and drug-induced acquired SNHL but merely proposed to reduce the inflammatory response as a strategy to reduce SNHL [
The evidence for a link between inflammation-induced vasospasm and acquired SNHL revealed in this review can be categorized as indicating a risk, as showing features or directness for the conditions identified above (see Table
Directness of evidence for a role of inflammation-induced vasospasm in conditions associated with acquired SNHL.
Condition associated with SNHL | Evidence for vasospasm | Evidence of link of SNHL to vasoconstrictors | Evidence for response to anti-inflammatory treatment | Evidence for treatment response to vasodilators |
---|---|---|---|---|
Autoimmune | Features | Features | Features | Not investigated |
Bacterial meningitis | Features | Features | Features | Features |
Phonic injury | Direct | Direct | Direct | Not investigated |
Subarachnoid haemorrhage | Features | Features | Features | Not investigated |
Brain trauma | Increased risk | No evidence | No evidence | Not investigated |
Presbyacusis | No evidence | No evidence | No evidence | Not investigated |
Migraine | Features | Not investigated | Not investigated | Not investigated |
Sudden SNHL | Direct | Not investigated | Direct | Direct |
In conditions like bacterial meningitis, there is some hearing loss and there is some indirect evidence that there is vasospasm in bacterial meningitis. Further research needs to link vasospasm with hearing loss in prospective observational studies focussing on cochlear blood supply.
Similarly in traumatic brain injury, there is hearing loss in brain injury and there is vasospasm in brain injury, but the association between brain injury and vasospasm-mediated SNHL is only inferred from these two separate sets of findings, without being actually proven in any study.
Inhibition of rho-associated kinases by agents like fasudil needs to be explored in all patients at risk of vasospasm associated hearing loss or with established acquired SNHL [
Future studies need to explore substances known to increase cochlear blood flow in ex vivo experiments, and these include herbal drugs used by traditional herbal medicine to treat hearing loss like
Tinnitus has been associated with vasospasm in subarachnoid haemorrhage [
Vascular inflammation may not just be reduced in the labyrinthine artery by the modes of treatment explored in this review but other vascular beds as well, and future randomised controlled trials should incorporate other vestibular disorders including vertigo and tinnitus and vascular headaches as secondary outcomes as well as heart disease, stroke, vascular dementia, peripheral vascular disease, and their incidence could be monitored during long term follow-up of patients enrolled.
There is mainly indirect evidence for vasospasm-associated SNHL in most forms of systemic or injury- or infection-induced local vascular inflammation. This opens up avenues in prevention and treatment of vascular and systemic inflammation as well as vasospasm itself as a way to prevent and treat most forms of acquired SNHL. Future research needs to investigate interventions antagonising vasospasm and vasospasm-inducing proinflammatory cytokines and their production in randomised controlled trials of prevention and treatment of acquired SNHL. Prime candidates for interventions are hereby inflammasome inhibitors and vasospasm-reducing drugs like nitric oxide donors, rho-kinase inhibitors and magnesium which have the potential to reduce SNHL in meningitis, exposure to noise, brain injury, arteriosclerosis, and advanced age-related and autoimmune disease-related inflammation.
Anterior inferior cerebellar artery
G-protein coupled receptors
Capillary density
Protein kinase C-potentiated phosphatase inhibitor-17
Farnesylpyrophosphate
Geranylgeranylpyrophosphate
Hearing loss
Interleukin-1
Myosine-binding subunit
Myosine light chain
Myosine light chain phosphatase
Myosine phosphatase targeting subunit-1
Noise-induced hearing loss
Nitric oxide
Nitric oxide synthase
Protein kinase C
Postocclusive reactive hyperaemia
Sphingosine-1-phosphate
Sensorineural hearing loss
Tumor necrosis factor.
The author declares that there are no conflicts of interest involved in the publication of this article.