Vestibular disease
Vestibulotoxicity
This information is intended as a general introduction to this topic. As everyone is affected differently by balance and dizziness problems, you should speak to your doctor for individual advice.
For reasons of better readability, the generic masculine is used and the simultaneous use of the language forms male, female and diverse (m/f/d) is dispensed with. Unless otherwise indicated, the personal designations used in this patient information refer to all genders.
What is vestibulotoxicity?
The term "vestibulotoxicity" describes damage to the vestibular system caused by toxic (poisonous) drugs and chemicals. Vestibulotoxicity can damage the structures of balance in the inner ear (semicircular canals and macular organs), the vestibular nerve (8th cranial nerve) and/or neurons in the parts of the brain that control balance. The damage can be temporary or permanent. Although it is not a life-threatening condition, the effects of vestibulotoxicity can have a significant impact on quality of life.
The use of vestibulotoxic drugs is common, especially in patients with potentially life-threatening conditions such as malignant tumors and severe infections. Sometimes there are no alternative drugs. In these cases, the risk of not taking the medication may be much greater than the risk of potential damage to the vestibular system.
One or more side effects of thousands of medications can affect balance. Some of these drugs suppress the information processing of the vestibular system and can cause dizziness and unsteadiness of gait. Others lower blood pressure, which can cause 'blackness before the eyes' (presyncope) when sitting up, standing up or standing for long periods of time. This type of dizziness is also known as orthostatic dizziness. The two examples of medication mentioned above cause temporary symptoms and do not fall under vestibulotoxicity.
Some drugs and chemicals that damage the vestibular system also damage the cochlea. This can result in hearing loss and tinnitus. However, some toxic substances are highly selective and only damage structures of the auditory or vestibular system.
Vestibulotoxicity has not yet been comprehensively investigated. It is likely that the number of people affected is underestimated. If patients have balance problems or dizziness but no hearing loss after exposure to a toxic substance, their gait unsteadiness or dizziness may be due to other causes. This is especially true for very ill or frail patients. If they are bedridden, they may not even notice their unsteady gait. Only when they are able to walk again do they notice their balance problems. By this time, the damage may already be severe and permanent.
Damage to the vestibular system caused by toxic substances is rare. Although they affect all age groups, the total number of people affected is unknown. Unborn babies, babies, young children and people over 65 are most at risk.
Risk factors
The frequency and severity of damage to the vestibular system depends on the dose and properties of the toxic substance itself. Increased risk factors can be:
- The duration of the medication
- The medication dosage
- How the substance enters the body (orally, drops in the ear, intramuscular injection, intravenously, via the skin or inhalation)
- Interactions with other medications or substances
- Simultaneous exposure to more than one vestibular toxin
- Multiple exposure
- Existing vestibular disorder
- General physical condition
- Other medical conditions such as heart failure, pancreatic insufficiency, diabetic retinopathy and peripheral neuropathy, kidney failure, liver cirrhosis and high blood pressure (hypertension)
- Reduced ability to excrete the substance due to poor kidney function
- Genetic susceptibility or allergic reaction
- Simultaneous exposure to noise and toxic substances
Older people are particularly at risk. They often take several medications and tend to metabolize them more slowly. As a result, the medication often remains in the body for longer.
Drugs that are toxic to the vestibular system should not be prescribed to:
- Pregnant women
- Hearing-impaired and/or elderly people, if there is a non-toxic alternative
Summary
- Temporary or permanent damage to the vestibular organ caused by certain medications and chemicals. Fortunately only occurs rarely.
- Unborn babies, very young children, the hearing impaired and the elderly are most at risk.
- Vestibulotoxicity is caused by aminoglycoside antibiotics, platinum-based chemotherapeutics, mefloquine, solvents, organophosphates and heavy metals.
- Exposure may be unavoidable in the treatment of potentially life-threatening diseases such as malignant tumors and serious infections.
- In other cases, equally effective - but non-toxic - alternatives can prevent damage.
- Some toxic substances damage both the structures for balance and for hearing.
- Others only damage structures for balance or hearing.
- The damage that occurs is irreversible. Early diagnosis can therefore prevent permanent damage.
- Vestibular rehabilitation is the most effective treatment for balance disorders.
- Hearing aids or a cochlear implant can help with hearing loss.
What causes vestibulotoxicity?
Drugs and other substances known to cause significant vestibulotoxicity include:
Medication
Aminoglycoside antibiotics
Aminoglycoside antibiotics (AGA) have been used since the 1940s to treat some serious bacterial infections. Of all drugs, they are the most toxic to the vestibular organ. AGAs work by preventing bacteria from making proteins they need to survive. They are usually administered intravenously. However, they can also be taken orally or as ear drops. Studies suggest that no dose is safe, regardless of the route of administration.
Up to 15 % of patients suffer damage to the vestibular organ when taking AGA. They are used in around 3% of patients admitted to hospital. Patients with cystic fibrosis, immune disorders and certain chronic infectious diseases are more likely to be treated with AGA. Some people have mitochondrial DNA mutations that make them more susceptible to AGA toxicity.
AGA can cause both temporary (reversible) and permanent (irreversible) damage to the structures in the inner ear. The hair cells in the semicircular canals are damaged first, followed later by the sacculus and the utriculus. An early sign of poisoning can be positional nystagmus (uncontrollable rapid eye movements). The vestibulocochlear nerve is only rarely damaged. The toxic effect builds up gradually over several weeks and is slowly broken down. There may be a delay in vestibular disorders. In some patients treated with AGA for longer than 10 days, the damage to the vestibular organ may not become noticeable until 1 - 10 days after the end of treatment. It is important to monitor patients for vestibulotoxic effects for up to 6 months after the end of AGA treatment.
Severe AGA toxicity usually causes symmetrical bilateral vestibulopathy. In some cases, the hair cells in the macular organs (utriculus and sacculus) may remain undamaged in either one or both ears.
The likelihood of AGA toxicity increases with the use of several commonly used medications, including:
- Vancomycin (an antibiotic used to treat some serious bacterial infections)
- Loop diuretics such as bumetanide, ethacyrnic acid, furosemide and torsemide (which are used to treat high blood pressure)
- Cisplatin (a cytostatic drug used to treat many different types of cancer such as testicular, ovarian, urinary bladder, squamous cell and small cell lung cancer)
- Metronidazole (an antibiotic used to treat certain bacterial and parasitic infections)
Of the approved AGA, two are highly toxic to the vestibular organ:
- Streptomycin - in one study, 15% of patients treated for tuberculosis with 1 g streptomycin daily developed vestibulotoxicity.
- Gentamicin toxicity is responsible for 15-50% of people with bilateral vestibulopathy.
Gentamicin tends to be more toxic in combination with vancomycin and/or with concomitant noise exposure. Injecting gentamicin into the middle ear is an effective treatment for some people with Ménière's disease. It can completely eliminate the vertigo. One disadvantage is that around 20% of those affected suffer additional hearing loss after treatment.
Gentamicin in the form of ear drops appears to be toxic to the vestibular system when administered over a prolonged period of time. In the case of perforated eardrums, the drug can enter the inner ear, where it is absorbed into the inner ear fluid and damages both hearing and balance. Particular caution is therefore required in this case.
Platinum-based chemotherapeutic (antineoplastic) drugs
These drugs inhibit or prevent the growth and spread of tumors and cancer. A number of studies show a link between platinum-based chemotherapy (especially cisplatin) and vestibulotoxicity. Research suggests that patients with pre-existing vestibular dysfunction are more likely to experience vestibulotoxicity after cisplatin treatment. The toxicity of cisplastin varies considerably from patient to patient. Studies suggest that this is partly related to genetic variations.
Chemicals
Solvents
Solvents are routinely used in industry. Solvents have a toxic effect on the parts of the brain that process information about balance, but not on the structures in the inner ear. Solvents affect the areas of the brain that control eye movements in response to head movements. The effects of solvents on the vestibular system are not as well documented, nor are their effects on hearing. Combined exposure to noise and solvents is worse than exposure to solvents alone. The following commonly used solvents are known to be vestibulotoxic:
- Toluene diisocyanates (TDI)
The occupational groups most exposed include machine operators in plastics processing, followed by workers in rubber and plastics manufacturing, automotive technicians, assemblers and inspectors of plastic products, and automotive mechanics. - Styrene
Exposure is mainly through inhalation. The main occupational groups exposed to styrene include automotive technicians, machine operators in plastics processing, carpenters and upholsterers. - Trichloroethylene (TCE)
Exposure is mainly through inhalation and skin contact. The main occupational groups exposed are machine operators in metalworking, operators of coating and metal spraying equipment and workers in metal processing.
Mefloquine
Mefloquine belongs to the class of quinolones and is used for the prevention (prophylaxis) and treatment of malaria. Mefloquine can cause permanent dizziness, spinning dizziness, tinnitus and balance disorders in some people. Serious side effects not related to balance problems and dizziness include anxiety, paranoia, depression, hallucinations, psychotic behavior and suicidal thoughts.
Phosphoric acid esters
Phosphoric acid esters are the most commonly used insecticides. They are used in agriculture, in the home and garden and in veterinary medicine. Very limited data indicate that phosphoric acid esters can damage the vestibular system.
Heavy metals
Research results indicate that there could be a connection between lead and cadmium in the blood and disorders of the vestibular organ.
Symptoms vary from person to person, depending on the type of exposure, whether one or both sides are affected, and how severe the damage is.
- Impaired balance, especially in situations where vision is restricted (e.g. with eyes closed or at night) or when walking on uneven ground.
- Oscillopsia (blurred, shaky vision when moving the head): This symptom is caused by the loss of vestibular input on both sides (bilaterally) to the eye muscles. For example, when you move your head while walking, you have the feeling that your surroundings are wobbling up and down. If you turn your head to one side, you feel that your surroundings are swirling around. Severe oscillopsia can make it impossible to see clearly even with the slightest movement of the head. This makes it difficult to participate in the activities of daily life.
- Ataxia (impaired coordination of voluntary muscle movements.
Rotational vertigo and nystagmus do not usually occur if both inner ears are damaged at the same time, e.g. if the exposure to a vestibular toxin is systemic (affecting the whole body).
- Increased swaying of the posture
- Lagenystagmus
If the toxic substance has also damaged the cochlea, hearing loss and tinnitus can occur.
Diagnosis of vestibulotoxicity
If you suspect that you have suffered vestibulotoxicity, speak to a doctor as soon as possible. Early diagnosis can prevent permanent damage.
The diagnosis of vestibulotoxicity is usually a diagnosis of exclusion. The doctor will take a detailed history of your past and current complaints. You will be asked about previous and current medication use, including ear drops.
If bilateral vestibulopathy is suspected, the vestibulo-ocular reflex (VOR) can be examined using the so-called head impulse test, among other things. Depending on your symptoms, you may be referred to an ENT specialist, neurologist or neuro-otologist.
Treatment of vestibulotoxicity
Therapy option
The focus is on avoiding and limiting damage caused by vestibulotoxic substances. The strategies include:
- Avoid exposure to vestibular toxins. In many cases, a good non-toxic alternative can be used.
- Use the lowest therapeutic dose of a vestibulotoxic drug when medically necessary and there is no alternative.
- Avoid simultaneous exposure to several vestibulotoxic substances and noise to reduce damage.
- Exposure to toxic chemicals in some industrial processes may be unavoidable. Replace chemicals with safer alternatives where possible.
- Minimize potential exposure to toxic chemicals by changing work procedures, ventilation or protective measures (wearing hearing protection, protective clothing and masks).
- Reduction of the noise level.
Therapy option
Unfortunately, once the balance function has been lost, it cannot be restored. The brain must learn to compensate for this deficit with the help of the eyes and proprioception (skin, muscles and joints). In patients with partial damage, symptoms may improve spontaneously.
The most effective treatment is vestibular rehabilitation therapy. This is an exercise therapy that aims to teach the brain to maintain balance and respond to signals from the vestibular and visual systems. A certified IVRT® Dizziness and Vestibular Therapist can help you create a suitable program for you and define training goals. The results depend mainly on:
- the severity of the damage
- the state of health of the other parts of the vestibular system (visual and proprioceptive)
- whether one or both sides are affected
- whether the damage is peripheral (inner ear) or central (brain)
For most people with unilateral vestibular loss, overall balance function improves significantly. For people with bilateral loss, vestibular rehabilitation therapy aimed at adaptation and substitution can help.
A hearing aid or cochlear implant can help people with hearing loss.
What happens next?
What you can expect in the future.
Damage to the vestibular organ can worsen for months after exposure to a vestibulotoxic substance has ceased. As a rule, the damage is completed 6 months after the end of exposure.
Most people with unilateral damage to the vestibular organ recover within a few weeks. About 20% develop chronic gait instability and oscillopsia. These symptoms may improve with spontaneous compensation or vestibular rehabilitation therapy.
A bilateral loss of the vestibular organ is usually permanent. Unfortunately, the hair cells in the inner ear do not grow back. People with bilateral loss are prone to falls. It is unlikely that they will be able to return to their previous physical activities and their ability to work independently will be significantly impaired.
Strategies and treatment methods that could help patients in the future are being researched further. These include:
- The identification of genetic variations to better predict the severity of vestibulotoxic effects.
- The identification of drugs with protective effects that can be used in conjunction with known vestibulotoxic drugs to reduce the adverse effects of treatment.
- Vestibular implants are a promising technical solution for restoring balance for people with bilateral vestibular loss.
