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The inner ear can be affected by diseases of different origin, which are generally poorly understood. Inner ear damage results in impaired hearing and/or balance, depending on whether the damage is located in the cochlea and/or the vestibule (or labyrinth).
Sudden SensoriNeural Hearing Loss (SSNHL)
SSNHL is also known as sudden deafness and belongs to the group of rare conditions that affect the inner ear. Hearing loss is rapid (instant or in <72 hours) and typically unilateral. The loss is >30 decibels (or a 1000-fold reduction of sound perception). It is often accompanied by tinnitus and vertigo and a significant increase in risk of falling.
SSNHL most commonly affects people over 45 years of age.
SSNHL occurs with the damage or loss of sensory hair cells (sound detectors), the sensory neurons (conducting auditory information to the brain), or their connections.
While the cause of most cases is unknown (idiopathic in 71% of cases), other possible causes include:
infectious (12.8%) or otologic (4.7%) diseases
traumatic injury including noise (4.2%), vascular/hematologic issues (2.8%), neoplasia (2.3%), or other (2.2%)
Ototoxicity and Cisplatin-induced ototoxicity
Ototoxicity is the toxic effect of substances, such as solvents, foods and pharmaceuticals, on the inner ear. Some pharmacologic therapies can affect cochlear or vestibular tissue depending on their sensitivity. When administered orally, intravenously or intramuscularly, drugs spread throughout the body and reach the inner ear, entering the labyrinth liquids, vestibular and cochlear tissues. Substances can then damage the membranes and intracellular organelles of the hair cells. Such damage can lead to symptoms of vertigo, tinnitus and hearing loss, which may even progress to complete deafness.
A wide range of drugs can cause this damage including:
Antibiotics belonging to the aminoglycoside class
Aspirin and some non-steroidal anti-inflammatory drugs
Quinine antimalarial drugs
Platinum salts, including cisplatin, used in chemotherapy
The damage is typically bilateral and is a limiting factor for the chemotherapy, requiring dose-adjustment and occasionally a change in chemotherapy protocol.
Platinum-based agents such as cisplatin, carboplatin and oxaliplatin, alone or in combination, are often used to treat a wide variety of cancers. However, ototoxicity leading to hearing loss and tinnitus is one of the common and often severe adverse effects.
Cisplatin is used in 25% of primary chemotherapeutic treatment of various cancers. Hearing loss with cisplatin is seen in more than 30% of adults and observed to varying degrees in >70% of treated children. The hearing loss is also progressive with each successive chemotherapy cycle and irreversible.
Otoferlin Deficiency
• Otoferlin deficiency is a rare genetic disorder caused by mutations of the OTOF gene. It’s one of the more frequent forms of congenital deafness. Affected babies typically have a bilateral severe to profound hearing loss.
• The Otoferlin protein is the major calcium sensor for synaptic exocytosis in cochlear sensory cells (Inner Hair Cells, IHCs). Thus, it’s essential for transmitting sound information at the auditory sensory cell synapses.
Usher Syndrome Type 1
• Usher Syndrome Type 1 is the most severe expression of Usher Syndrome. It’s caused by various mutations on USH1C, MYO7A, CDH23, PCDH15, USH1G and CIB2 genes. It is characterized by congenital profound deafness and balance defects. Affected patients subsequently undergo sight loss during childhood, leading to blindness.
• Inner hair cells lacking the scaffold protein called Sans, encoded by the USH1G gene, cannot develop, maintain and have a functional hair bundle.
