by Barry Keate
The International Tinnitus Forum (ITF) held its 25th annual meeting on September 15, 2007 at the Renaissance Washington, DC Hotel. The focus of the meeting was Nuclear Medicine Imaging. We were in attendance once again as well as for the 2007 American Academy of Otolaryngology Annual Meeting, September 16-19 being held at the DC Convention Center.
Nuclear Medicine Imaging as it applies to tinnitus refers to varying technologies of brain scanning that produce detailed images showing areas of the brain that are affected. The technologies include Positron Emission Tomography (PET), Electroencephalography (EEG) and other techniques that use radiation to produce the images.
This is basic research into the causes of and treatments for tinnitus. The goal is to find an objective method of determining exactly where tinnitus is located in the brain and the degree of neuronal damage. If this technique can be perfected it will give scientists a powerful new tool to objectively determine the severity of tinnitus and the effects of new treatments.
The subject is way over the head of this lay person and after viewing literally hundreds of brain scans; my eyes were glazing over. Also, I am more interested in possible new treatments than in how to measure the results. Fortunately, there were many other subjects discussed and papers presented that show the breadth of new thinking about this sometimes debilitation condition. Following are synopses of some of the papers presented. Please read through these; the last two are very important.
1 – Martin Lenhardt, PhD, AuD. Dr Lenhardt presented a hypothesis that the insular cortex is part of the final common pathway for tinnitus. The insular cortex, or insula, is connected to the limbic system which is responsible for emotion, motivation, and emotional memory. It also plays a large role in sexual pleasure, addiction and the “fight-or-flight” chemicals that are produced during times of extreme stress.
Dr. Lenhardt states that the insula also connects to the auditory cortex and wondered if, in some emotional sense, people become addicted to tinnitus.
2 – Claus Claussen, MD. Dr. Claussen presented a paper on the slow brain syndrome in elderly tinnitus patients. In this condition there is a reduction in central nervous system (CNS) activity and these patients typically have hazy tinnitus and some vertigo. Equilibrium and hearing are closely related and intermingled in the CNS.
There are 50-60 neurotransmitters in the CNS. Gamma-aminobutyric acid (GABA) plays a large role in reducing hyperactivity. In those with slow brain syndrome, GABA is overly predominant and needs to be reduced. Dr. Claussen treats these patients with a homeopathic preparation of hemlock, a deadly poison in large doses. Hemlock was used to execute Socrates in 399 BC. It contains cicutoxin, a potent GABA antagonist.
3 – Erik Viire, MD. Dr. Viire presented one of the papers on Electroencephalogram (EEG) imaging and tinnitus. He stated that chronic disabling tinnitus is the result of a “failure of neuroplasticity” in the auditory cortex. Neuroplasticity refers to the brain’s ability to change the organization of neuronal pathways in the brain, essentially rewiring neuronal connections. This happens when new experiences or changes in the environment occur which change the way we think. Without neuroplasticity, we would be unable to learn from our experiences.
EEG and PET imaging can localize where tinnitus occurs in the cortex. New data and better modeling will lead to a better understanding of system failures and methods to correct them.
He also discussed people who have normal hearing but still have tinnitus. In this case, masking around the tinnitus frequency, not the same frequency, is effective in reducing the perception of the tinnitus sound.
4 – Abraham Shulman, MD. Dr. Shulman’s subject was neurodegenerative disease (NDD) and tinnitus. Severe, disabling tinnitus is a “soft” sign of NDD but is not related to Alzheimer’s disease. It leads to progressive damage or death of neurons. NDD is most often caused by inflammation and/or ischemia, a reduction of blood supply leading to lack of oxygen.
Hypertension and cerebrovascular disease are highly correlated with severe, disabling tinnitus. Of 18 patients studied, 10 had hypertension and 15 had cerebrovascular disease.
He discussed evolving imaging techniques and showed many brain images using MRI, SPECT and EEG.
5 – Alfred Stracher, PhD. Dr. Stracher discussed calpain inhibitors as magic bullets for treatment of NDD and tinnitus. Calpains are protein enzymes that can lead to hyperactivity and death of neurons. They are associated with neurological and muscular degeneration. Head trauma, ischemia and noise exposure lead to elevated glutamate which in turn creates excess calpain and neuronal damage.
Leupeptin is a powerful calpain inhibitor and has been shown in animal studies to protect against ototoxicity and muscle degeneration. It can eliminate MS if treated early and can protect against noise damage if infused into the inner ear prior to exposure. It has tremendous potential in the fight against NDD. Leupeptin can intervene in all forms of NDD but will not reverse them.
Researchers have applied to the FDA for approval to conduct human studies. So far all studies have been conducted on animals.
6 – Arnold Strashun, MD. Dr. Strashun presented a paper on nuclear imaging and discussed new advances in higher resolution. He showed many images of brain scans.
One study using Iomazenil, a radioisotope, which binds with brain receptors showed GABA activation reduced tinnitus. The function of the GABA receptor is to inhibit central nervous system synapse activity. Impairment of GABA function has been considered to lead to convulsions, which provides clinical support for the concept that tinnitus is an epileptic-like auditory phenomenon. Hyperactivity in the auditory cortex is universal in tinnitus patients. This has been evident for some time and GABA activating medications, such as Neurontin, are known to be helpful.
Dr. Strashun mentioned that hyperinsulinemia leads to NDD and tinnitus. Hyperinsulinemia is a condition where the body becomes less able to utilize insulin and is the first step in Type II diabetes. He stated that the current wave of increased Type II diabetes will lead to increased NDD and Alzheimer’s in the future.
7 – Barbara Goldstein, PhD. Dr. Goldstein presented results of a small study on Clear Tinnitus, a product that is marketed for tinnitus patients. The study was extremely small with only 15 patients. All patients had tinnitus due to Eustachian Tube Dysfunction, not hearing loss. There were no controls in the study and Clear Tinnitus was not compared to decongestants, which also help with this condition.
Three patients had GI problems and dropped out of the study. Seven patients out of the remaining 12 reported improvement. Audiometry showed no improvement in any of the patients, nor did standard tinnitus tests show statistical improvement. However, middle ear pressure did improve.
8 – Michael Hoffer, MD. Dr. Hoffer discussed blast injury, head trauma and tinnitus. He is a Commander in the US Navy and went to Iraq to treat war fighters. Most soldiers were 18-30 years old and had no ear disease before going to Iraq. Urban warfare makes hearing protection difficult because the soldier must be able to hear. Therefore, very few wear hearing protection.
Dr. Hoffer saw 4 types of tinnitus due to warfare: 1 – Noise induced, 2 – Blast induced (pressure), 3 – Tinnitus without hearing loss, 4 – Post traumatic Meniere’s disease.
Blast induced tinnitus is out of proportion to the amount of hearing loss. Tinnitus without hearing loss is poorly understood and seems to accompany cognitive difficulties.
The last two papers were considered by ITF Chair Abraham Shulman, MD, to be the most important presentations because they represent significant developments in the treatment of tinnitus.
9 – John Dornhoffer, MD. Dr. Dornhoffer has been studying repetitive Transcranial Magnetic Stimulation (rTMS) for treating tinnitus. We published an earlier article on rTMS that describes the history and treatment protocol.
rTMS therapy consists of inducing a magnetic field inside the brain by the use of extremely powerful magnets outside the skull. It is completely non-invasive. The induced magnetic field affects cortical neurons and regulates activity of the neurons. Low frequency rTMS is inhibitory and high frequency is excitatory. Since tinnitus is caused by hyperactivity of cortical neurons, low frequency rTMS is used.
rTMS only penetrates 2 cm inside the skull while the auditory cortex can be as deep as 5 cm. It is therefore necessary to pinpoint the area of hyperactivity for the treatment to be effective. The area is selected using neuronavigation techniques and PET scans.
All patients had tinnitus in both ears and were part of a placebo-controlled, crossover study. This kind of study has patients use either the active or sham treatment for a period of one month then cross over to the other treatment. Dr. Dornhoffer had a 70% positive response to the active treatment. Interestingly, many patients had a reduction of tinnitus in the ear opposite the stimulation.
Dr. Dornhoffer will conduct a further study in the near future. It also will be placebo-controlled but will not be a crossover study. He wants to find out if continued treatment for a longer period of time will produce better results.
10 – Michael Seidman, MD / Ilaaf Darrat, MD. Drs. Seidman and Darrat have been conducting experiments using direct electrical stimulation of the auditory cortex for tinnitus. This is a highly invasive procedure during which electrodes are implanted inside the brain. The electrodes are controlled by a pulse generator which is also implanted in the side of the torso. This procedure will only be suitable for people with severe, disabling tinnitus who are willing to undergo hospitalization and surgery.
The work began on noise exposed animals and they were able to reduce cortical hyperactivity. They now have approval to conduct experiments on humans and have implanted electrodes in 4 patients so far with 8 more scheduled. Three of the 4 patients were implanted in the US and one in Belgium. The surgeries have resulted in a significant reduction of sound in 3 of the 4 patients and the patients would recommend the procedure to others.
The remaining 8 patients have already been chosen and the study is now closed. We will publish a complete paper on the experiments so far after they have been published in a peer-reviewed journal.