Tinnitus and Sound predictability

Tinnitus, often described as ringing or buzzing in the ears, is a complex condition that affects millions worldwide. It is primarily diagnosed based on self-reported symptoms. However, it can also be a diagnosis of exclusion, as it may sometimes be caused by an underlying condition. In many cases, the exact cause remains elusive.

A comprehensive hearing (audiological) exam is crucial in assessing tinnitus. This typically includes Pure Tone Audiometry that evaluates hearing thresholds and identifies any hearing loss associated with tinnitus. It also helps describe the characteristics of tinnitus, such as loudness and pitch.

Different types of tinnitus sounds can provide clues about potential causes:

Clicking: May indicate muscle contractions in or around the ears

Pulsing, rushing, or humming: Could stem from vascular causes, such as high blood pressure

Low-pitched ringing: Might suggest ear canal blockages, Menière's disease, or otosclerosis

High-pitched ringing: Often associated with loud noise exposure, hearing loss, or certain medications

Continuous, high-pitched ringing in one ear: Could indicate acoustic neuroma

Additional diagnostic tools may include Lab tests - to check for anemia, thyroid problems, heart disease, or vitamin deficiencies and Imaging - CT scans or MRIs to identify structural abnormalities in the ear

A recent study from the Netherlands explored how tinnitus affects auditory processing, specifically focusing on sensory gating (SG) and predictability in sound perception.

Imaging: CT scans or MRIs of the ear can identify structural abnormalities.

Study Design:

Participants: 52 age-, education-, and sex-matched individuals with and without tinnitus

Task: Listening to paired-tone oddball sequences varying in pitch (standard vs. deviant) and timing (isochronous vs. random)

Measurement: 128-channel EEG recording

Analysis: Temporal spatial principal component analysis (tsPCA)

Both groups demonstrated sensory gating, suppressing responses to the second tone in a pair.

Deviant tones elicited larger amplitudes than standard tones in both groups.

Only participants without tinnitus showed an enhanced N100-like deviance response in the isochronous (predictable) timing condition compared to the random timing condition.

The study suggests that individuals with tinnitus may not benefit from temporal predictability in sound processing to the same extent as those without tinnitus. This indicates a potential deficit in temporal sensitivity in auditory processing for people with tinnitus.

Understanding tinnitus involves exploring its various manifestations, potential causes, and the underlying differences in auditory processing. While diagnosis primarily relies on self-reported symptoms, comprehensive audiological exams and additional tests can provide valuable insights. Recent research highlights the complex nature of tinnitus and its impact on sound perception, opening avenues for future studies and potential therapeutic approaches.

REFERENCE

Brinkmann P, Devos JVP, van der Eerden JHM, Smit JV, Janssen MLF, Kotz SA, Schwartze M. Parallel EEG assessment of different sound predictability levels in tinnitus. Hear Res. 2024 Jul 6;450:109073. doi: 10.1016/j.heares.2024.109073. Epub ahead of print. PMID: 38996530.

Genomic Therapy Restores Hearing in Children

Imagine a world where children born deaf can hear for the first time. This once far-fetched dream is becoming a reality thanks to a recent breakthrough in genomic therapy. A new study published in Nature Medicine reports promising results from an innovative gene therapy designed to treat autosomal recessive deafness 9 (DFNB9). 

DFNB9 is a genetic condition that leads to severe-to-complete hearing loss from birth or early childhood. It's caused by mutations in the OTOF gene, which encodes a crucial protein called otoferlin necessary for hearing. Without functional otoferlin, sound signals cannot be properly transmitted to the brain, resulting in deafness.

Researchers have been exploring gene therapy as a way to treat genetic disorders like DFNB9. In this approach, a healthy copy of the defective gene is delivered to the patient's cells using a viral vector. In previous studies, a single injection of an adeno-associated virus (AAV) carrying the human OTOF gene showed safety and some hearing improvement in one ear.

Building on this success, the researchers expanded their trial to test the therapy in both ears (binaural therapy) in children with DFNB9. Their latest paper presents interim results from this ongoing study.

Five children with DFNB9 who never received cochlear implants participated in the trial. Each received the gene therapy in both ears. The primary goals were to evaluate safety and to observe any improvements in hearing. Here’s what they found:

Safety: No serious adverse events or dose-limiting toxicities were reported. Out of 36 minor adverse events, the most common were increased lymphocyte counts and cholesterol levels, both manageable.

Efficacy: Remarkably, all five children showed significant improvement in hearing. Before therapy, their average auditory brainstem response thresholds were greater than 95 dB, indicating profound hearing loss. After therapy, these thresholds improved dramatically. For example:

Patient 1: Improved to 58 dB and 63 dB in the right and left ears, respectively.

Patient 2: Improved to 75 dB and 85 dB.

Patients 3, 4, and 5 showed similar improvements.

Beyond these quantitative measures, qualitative improvements were equally striking. All five children gained the ability to perceive speech and locate sounds. Here are some inspiring individual stories:

Patient 1: An 11-year-old girl, deaf since birth, began responding to her name and recognizing sounds within weeks. By 13 weeks, she could speak simple syllables like "ba" (father) and "ma" (mother).

Patient 2: This child, who couldn’t hear at all initially, could turn to his grandparents' calls within six weeks and started saying words like "ayi" (aunt) and "bai" (bye) by 26 weeks.

Patient 3: Similarly, this patient began responding to his name within three weeks and could dance to music and say words like "baba" (father) and "yeye" (grandfather) by 26 weeks.

This study offers a glimmer of hope for the 430 million people worldwide who suffer from disabling hearing loss, including 34 million children. Approximately 26 million people have congenital hearing loss, with 60% of these cases due to genetic factors like DFNB9.

While these interim results are promising, the trial is ongoing, and longer follow-up is needed to confirm the therapy's long-term safety and efficacy. If successful, this gene therapy could revolutionize the treatment of genetic hearing loss, offering a new lease on life for countless individuals.

For more details, you can check the trial registration at the Chinese Clinical Trial Registry: ChiCTR2200063181.

REFERENCE

Wang, H., Chen, Y., Lv, J. et al. Bilateral gene therapy in children with autosomal recessive deafness 9: single-arm trial results. Nat Med (2024). https://doi.org/10.1038/s41591-024-03023-5

SARS-CoV-2 Lurking in the Middle Ear

From the common rhinovirus to infamous coronavirus, respiratory viruses can trigger a cascade of ear complications, including acute otitis media (AOM). This roster includes syncytial virus, rhinovirus, adenovirus, coronavirus, bocavirus, influenza virus, parainfluenza virus, enterovirus, human metapneumovirus and SARS-Cov2. Moreover, Otitis media can often manifest as the initial sign of COVID-19 and be associated with hearing loss. Otitis media secretory is one of the most common ear complications after infection with the Omicron strain of SARS-CoV-2 virus, and the significantly higher incidence is associated with middle ear viral infection. Middle ear effusion SARS-CoV-2 virus antigen test detected the virus, which survived longer in the middle ear effusion than in the nasal cavity. The middle ear effusion test can detect SARS-CoV-2 virus antigen and determine whether the organism contains virus residue. 

Recent findings have unveiled a potentially alarming revelation - individuals diagnosed with otitis media with effusion (OME) post-COVID-19 may harbor traces of the virus within their middle ear. In this study, a striking 12.0% of middle ear effusion samples tested positive for SARS-CoV-2, hinting at the possibility of viral persistence and recurrence.

The study examined 23 patients, ranging from 32 to 84 years of age, who presented with OME following Omicron infection. 91.3% of these patients showcased unilateral symptoms, with fluid accumulation observed in 88.0% of ears. The median duration from infection to middle ear effusion sampling was 21 days, showcasing the potential for prolonged viral presence in this concealed reservoir.

Adding to the intrigue is the elusive nature of OME itself. Characterized by fluid accumulation in the middle ear sans acute infection, OME has long puzzled experts in otolaryngology and audiology. While bacterial infections and immunological responses have been implicated, the precise mechanisms remain veiled in mystery.

REFERENCES

Chengzhou Han, Huifang Wang, Ying Wang, Chao Hang, Yangyang Wang, Xiangming Meng, The silent reservoir? SARS-CoV-2 detection in the middle ear effusion of patients with Otitis media with effusion after omicron infection, American Journal of Otolaryngology, 2024, 104229, ISSN 0196-0709, https://doi.org/10.1016/j.amjoto.2024.104229. 

Zhang Y, Liu J, Yang F, He Y, Yan S, Bai Y, Zhang Z, Luan F. COVID-19-related secretory otitis media in the omicron era: a case series. Eur Arch Otorhinolaryngol. 2023 Oct;280(10):4697-4700. doi: 10.1007/s00405-023-08075-w. Epub 2023 Jun 21. PMID: 37341758.

Fan Y, Gao R, Shang Y, Tian X, Zhao Y, Chen X. Presence of SARS-CoV-2 in middle ear fluid and characterization of otitis media with effusion in patients with COVID-19. International Journal of Infectious Diseases. 2023 Nov 1;136:44-8.

Karimi-Galougahi M, Raad N, Ghorbani J, Mikaniki N, Haseli S. Otitis Media in COVID-19: A Case Series. Authorea Preprints. 2020 Jul 7.

Gene Therapy Rescues Childhood Deafness

Gene therapy, a revolutionary medical technique first conceptualized in the 1980s, has steadily advanced, offering new hope in treating various genetic disorders. This approach involves altering a person’s genetic makeup to combat diseases, representing a significant shift from traditional methods like drugs or surgery. 

Gene therapy faces challenges, including immune reactions, targeting errors, and the risk of new mutations. But in many cases benefits outweigh the risks.

A recent milestone in gene therapy has been its application in treating inherited hearing loss. The focus is on DFNB9, a form of deafness caused by mutations in the OTOF gene, responsible for producing otoferlin, a crucial protein in sound signal transmission. This leads to nonsyndromic Hearing Loss - a hearing loss that occurs with no other symptoms. A collaborative clinical trial between Chinese researchers and Mass Eye and Ear investigators has yielded remarkable results.

The trial involved six children with autosomal recessive deafness (DFNB9), all between one and seven years old. The gene therapy entailed injecting a functional OTOF gene using viral carriers into the inner ear. This process enabled the cells to produce otoferlin, thereby restoring hearing capabilities.

Over 26 weeks, five of the six children showed significant hearing improvements, with abilities ranging from understanding speech to verbalizing words, even holding phone conversations. 

This success paves the way for addressing other genetic forms of deafness involving genes like GJB2, MYO15A, TMC1, or SLC26A4. These genes play various roles in the inner ear's development and function, and researchers are diligently working to develop targeted gene therapies for these conditions.

Gene therapy, once a concept, is now transforming lives. As research continues, it holds the promise of curing not just deafness but a spectrum of genetic disorders, marking a new era in medical science.

REFERENCE

Qi J, Tan F, Zhang L, Lu L, Zhang S, Zhai Y, Lu Y, Qian X, Dong W, Zhou Y, Zhang Z, Yang X, Jiang L, Yu C, Liu J, Chen T, Wu L, Tan C, Sun S, Song H, Shu Y, Xu L, Gao X, Li H, Chai R. AAV‐Mediated Gene Therapy Restores Hearing in Patients with DFNB9 Deafness. Adv Sci (Weinh). 2024 Jan 8:e2306788. doi: 10.1002/advs.202306788. Epub ahead of print. PMID: 38189623.