WO2009029040A1

WO2009029040A1 - Methods and devices for the treatment of tinnitus, anosmia and nerve injury

Info

Publication number: WO2009029040A1
Application number: PCT/SE2008/050976
Authority: WO
Inventors: Tore Persson
Original assignee: Tore Persson
Priority date: 2007-08-31
Filing date: 2008-08-29
Publication date: 2009-03-05

Abstract

The invention refers to methods of generating a vibrational signal for treating tinnitus, anosmia and nerve damage in a mammal subject, whereby the affected tissue is exposed to the vibrational signal, preferably having a frequency in the interval of 39- 41 Hz, and most preferably about 40 Hz. Also, the invention refers to devices for use in such treatments. Further, the invention refers to a method of adapting an audio sample for the treatment of tinnitus.

Description

METHODS AND DEVICES FOR THE TREATMENT OF TINNITUS, ANOSMIA AND NERVE INJURY

Technical field The present invention refers to a method of treatment of tinnitus, anosmia and regeneration of injured neural tissue. The invention also refers to devices for use in the treatment of tinnitus, anosmia and regeneration of injured neural tissue. Further, the invention refers to methods of creating audio recordings for use in the treatment of tinnitus.

Background of the invention

Tinnitus is defined as the aberrant perception of noise or sound without any external stimulation. It may be unilateral or bilateral and has equal prevalence in women and men and is most prevalent between the ages of 40 and 70. Occasionally tinnitus can also occur in children. Periodic bouts of mild, high-pitched tinnitus lasting for several minutes are common in normal-hearing individuals. Severe and persistent tinnitus can interfere with sleep and the ability to concentrate, causing great psychological distress. In extreme cases, patients with severe chronic tinnitus may consider suicide. Tinnitus can be classified into two types: (i) subjective tinnitus and (ii) objective tinnitus (see e.g. http://www.aetna.com/cpb/medical/data).

Subjective tinnitus, which is more common, is audible only to the patient. It may arise from some types of electrophysiological disturbance anywhere in the auditory system - the external ear canal, tympanic membrane, ossicles, cochlea, auditory nerve, brainstem or cerebral cortex. The underlying causes of subjective tinnitus include otological (presbycusis, noise-induced hearing loss, Meniere's disease, or chronic otitis media), metabolic (diabetes, thyroid diseases, hyperlipidemia, or zinc deficiency/vitamin deficiency), pharmacological (aspirin compounds, non-steroidal anti-inflammatory drugs, caffeine, nicotine, aminoglycosides, or antidepressants), neurological (whiplash, skull fracture/closed head trauma, multiple sclerosis, or following meningitis), psychological (depression or anxiety) as well as infectious and neoplastic (syphilis, acoustic neuroma, autoimmune diseases, or acquired immune deficiency syndrome) disorders.

Objective tinnitus, the less common type of tinnitus, usually refers to noises that can be heard by an examiner. The physician must put his/her ear against the patient's ear or use a stethoscope against the patient's external auditory canal. Objective tinnitus usually has a vascular (arteriovenous malformations/shunts, arterial bruits, hypertension, arteriosclerosis, venous hums, or aneurysms) or mechanical (Eutaschian tube dysfunction, temporomandibular joint disease, palatal myoclonus, or idiopathic muscle spasm) origin. The management of patient's with tinnitus often depends on the severity of the condition. If the patient's activities of daily living are not affected by tinnitus, treatment options include counselling, reassurance, and/or behavioural and dietary modifications. Medications also occur for treating or alleviating severe tinnitus.

Other means for treating tinnitus include e.g. electrical stimulation, the use of masking instruments, and tinnitus retraining therapy (a neuroophysiological approach centering on behavioural retraining of the associations induced by the perception of tinnitus). Devices similar to tinnitus maskers are used for retraining therapy. Transcranial magnetic stimulation, transmeatal laser irradiation and hyperbaric oxygen therapy are other approaches for treating or alleviating tinnitus.

Further, Lockwood et al. (N Engl J Med, VoI 347, No 12) discloses a summary of clinical approaches, pathophysiology and therapy of tinnitus that are used today.

Thomas et al. (Ear, Nose and Throat Journal vol. 68 Nov 1989 pp. 810-818) disclose use of vibrational stimulation at 10, 50, 100, 200, 300 or 400 Hz for the treatment of tinnitus. In the short term, five patients reported some improvement. No long-term benefits were reported.

EP-A- 1040847 discloses a method of wave therapy, whereby a low frequency current, an electromagnetic wave and/or an acoustic wave is used for treating various diseases. Especially, the disclosure is focused on an apparatus for use in the treatment. Also, US-A-5788656 discloses an electronic stimulation system for treating tinnitus disorders whereby an electronically actuated probe produces a complex signal to the patient. The complex signal is produced by two oscillators, one working at 600-1000 Hz, and the other working at 200-400 Hz. Moreover, Rossi et al. (Progress in Neurobiology 81 (2007)1-28) discloses regulation of intrinsic neuronal properties for axon growth and regeneration, and the effect of external stimuli on nerve regeneration.

Anosmia is characterised by olfactory disorders and described with associated complaints. Anosmia is the lack of olfaction, or an absence of the ability to smell. It can be either temporary or permanent. A related term, hyposmia, refers to a decrease in the ability to smell, while hyperosmia refers to an increased ability to smell. Some people may be anosmic for one particular odor. This is called "specific anosmia" and may be genetically based. Epidemiological studies show that loss in odour sensitivity is common in both general and clinical populations, whereas dysosmia is less common in general populations but frequent in clinical populations. Possible causes of olfactoctoctory dysfunction can be e.g. nasal polyposis, deviated nasal septum, intranasal tumour, sensory — viral infection, chronic sinusitis, allergic rhinitis, cigarette smoke, toxic chemical exposure, drugs, neural — head injury, Alzheimer's disease, Parkinson's disease, hypothyroidism, intracranial tumour. Sinonasal disease, head injury, and upper respiratory tract infection account for most cases of olfactory dysfunction. Anosmia causes significant lowering in the quality of life of the sufferers and no effective treatments are currently known. A lot of work and effort has, over time, been put at the task to evaluate the potential for improvement in sensory function. Recent data indicate that improvement in olfactory function may occur spontaneously, but the improvement may take several years or not happen at all.

Therefore an unmet need exists for effective treatments for anosmia. With the methods and devices described herein, good results can be achieved within days after minutes of treatment.

Injury to nerves may be a result of multiple causes. Mechanical trauma (such as cutting or crashing injuries, traffic accidents) and neurodegenerative diseases such as Alzheimer's, Parkinson's, multiple sclerosis and amyotrophic lateral sclerosis. Current treatments include surgery and drag therapy. For most nerve injuries, there is need for improved treatments. The present invention discloses new improved methods and devices of treating nerve injury. To summarise, new efficient methods and devices for treating tinnitus, anosmia, nerve injury or similar neurological disorders and/or tissue damages in general, and for regenerating damaged nerve tissue are needed.

As disclosed above, behavioural therapy, hearing aids, acupuncture and antidepressants are some of the means that are used today for reducing the effects of tinnitus. However, to completely revoke the symptoms, and to regenerate the nervous system and/or to cure tissue damage is not yet possible.

Accordingly, it is an object of the present invention to improve current methodologies by providing devices and methods for non-invasively treating tinnitus, anosmia and for treating nerve injury.

Summary of the invention

By increased understanding of the physiological mechanisms behind tinnitus and other similar nervous system disorders, the present inventor has surprisingly discovered that by subjecting a damaged tissue, such as a neurological tissue, and for example a vibrationally injured neurological tissue, with a vibrational influence, the symptoms of the neurological disorder are taken away. Especially, the vibrational influence may be a sound, such as a tune or a tone.

Hereby, means and methods for curing tissue damages, especially of neurological tissue is provided, which means and methods have proven to be effective. Especially, since the inventor has found that vibrational signals in the range of 39-41 Hz, preferably about 40 Hz are especially effective, the principle of the invention can be used for curing many different tissue damages.

In a first aspect, the invention provides a device for treatment of tinnitus in a subject in need thereof, characterized by that it comprises a. means of processing ambient sounds in essentially real time resulting in specific amplification of the sound intensity at the frequency range(s) at which the affected ear exhibits hearing loss; and b. means of exposing at least the ear of the subject which is contralateral in relation to the tinnitus to be treated, to the processed sounds generated by the device in step (a); wherein the device is adapted to operate by playing back the processed ambient sounds in essentially real time into at least the ear of the subject which is contralateral in relation to the tinnitus to be treated. In a second aspect, a method for individual adaptation a device of the first aspect is provided characterized by that it comprises the steps of: a. obtaining information on the audio frequency range(s) where an individual subject suffering from tinnitus exhibits hearing loss;

b. adapting the device of the first aspect to the individual subject's hearing loss comprising adjusting the settings the device such that it increases the intensity of ambient sounds specifically at the frequency range(s) where the individual subject exhibits hearing loss.

In a third aspect, a method of producing an audio recording for the treatment of tinnitus is provided characterized by that it comprises the steps of: a. obtaining information on the audio frequency range(s) where an individual subject suffering from tinnitus exhibits hearing loss; b. adapting a pre-existing audio sample of choice to the individual subject's hearing loss comprising increasing the sound intensity of the recording specifically at the frequency range(s) at which the ear affected by the tinnitus exhibits hearing loss wherein the specific amplification is applied to at least one audio channel intended for playback at least on the contralateral ear in relation to the tinnitus; c. mixing an audio signal in the frequency range 39-41 Hz to at least one audio channel of the recording; and d. preferably, storing the adapted audio recording on a suitable medium, such as a CD-disc, a DVD-disc, a computer or a digital audio player or similar.

In a fourth aspect, a method of treatment for tinnitus is provided comprising subjecting the subject in need thereof to an audio signal in the frequency range 39-41 Hz.

In a fifth aspect , a device for the treatment of anosmia is provided, characterized by means of generating a vibrational signal in the frequency range 39-41 Hz and means of applying the vibrational signal to the olfactory epithelium of the subject to be treated.

In a sixth aspect, a method of treatment for anosmia is provided comprising subjecting the olfactory epithelium of a subject in need thereof to a vibrational signal in the frequency range 39-41 Hz.

In a seventh aspect, a device for curative treatment of a nerve injury is provided, characterized by a. means of generating a vibrational signal in the frequency range 39-41 Hz, preferably about 40 Hz;

b. means of locating the nerve injury, preferably by ultrasonic imaging; and c. means of applying the vibrational signal to the nerve injury of the subject to be treated.

In an eight aspect, a method of curative treatment of a nerve injury is provided, comprising subjecting the nerve injury of a subject in need thereof to a vibrational signal in the frequency range 39-41 Hz, preferably about 40 Hz.

Brief description of the drawings

Figure 1 discloses a profile of a wave motion describing a vibrational signal of the invention.

Figure 2 is an illustration of a device for treatment of anosmia.

Figure 3 is an illustration of a device for curative treatment of wounded neural tissue. Definitions

By a "method for curing a tissue damage" is meant a method alleviating symptoms or folly curing a damage or disorder in a bodily tissue of a mammal subject By a "subject" is meant any mammal such as humans, cats, dogs, cattle, horses, sheep etc. A human subject is preferred.

By "vibrational signal" or "vibrational treatment" is meant a treatment based on subjecting the subject to a signal, such as a sound, e.g. a piece of music, or a vibrational treatment by a vibrating device. E.g., the vibrational treatment can be experienced as a sound, as a result of an elastic wave (or an acoustic wave) propagating through a gas, a liquid or a solid, reaching the ear, where it produces vibrations in the ear's membrane resulting in the sensation called sound.

By "vibrationally wounded" tissue is meant that the tissue damage (or wound) has resulted from overexposure to vibrations. By "in essentially real time" is meant a response (or a stream of continuous responses) that is so rapid that it is experienced as being without any disturbing delay by normal human senses. The delay of a response, from a stimuli to a response, that is in essentially real time, is no more than 500 ms, more preferably less than 100 ms, even more preferably less than 10 ms, and most preferably less than 2 ms. For example, a sound processing device may record a sound with a microphone, process the sound and then play the sound back "in essentially real time" if the delay from the recording to the playback is within the limits set forth above.

By "ambient sounds" are meant any sounds that occur in the surroundings of the recording device that would be audible to a normal human ear. For the purposes of this disclosure, the term "anosmia" is also taken to encompass hyposmia and specific anosmia. Detailed description of the invention

In the study "Anatomical localization of cortical beta rhythms in cat" (Bouyer et al 1987), it was shown that beta electrocorticographic rhythms (40Hz) develop during motionless focused attention in two distinct cortical foci in cats. The cat purr mainly consists of sounds between 5 - 200 Hz, with a focus around 25 - 65 Hz and an even stronger focus between 35 — 45 Hz. The places of origin for the cats purr were previously unknown.

Both foci are located in the right hemisphere of the cat's brain. Their gross cortical localization (precentral) suggested homology with what was former called "beta rhythms" described in the human electrocorticogram (ECoG) (Jasper et al. 1949).

The 40 Hz event-related potential (ERP) or gamma band responses (GBR) in humans have been widely studied ever since Galambos et al. described the phenomena as a 40 Hz auditory steady-state potential (SSP) in 1981.

Historically it has also been closely studied from many other fields; visual (Judd 1987), somatosensory (Galambos 1982) and olfactory (Freeman 1975).

It is today also known and demonstrated that many species of mammals, including cats, dolphins and humans, among many others, produces fast gamma oscillations, often at ~40 Hz from the cortex of the right hemisphere of the brain.

Thus, the background to the technical effect of the present invention is that the present inventor has shown that tissue damages in general, and especially neurological damages such as tinnitus and anosmia, can be cured and/or regenerated by treating the damaged tissue with vibrations within a chosen frequency or frequency interval.

Especially, this has proven effective for treating conditions such as tinnitus and anosmia, as well as for regenerating nervous tissue, such as curing nerve injury. Accordingly, in a first aspect, the invention refers to the use of a device generating a vibrational signal for curing a tissue damage in a mammal subject, whereby the damaged tissue is exposed to the vibrational signal having a frequency in the interval 35-45 Hz, such as 35, 36, 37, 38, 39, 40, 41, 42, 43, 44 or 45 Hz, preferably 39-41 Hz, and most preferably about 40 Hz. In one embodiment, the vibrational signal has a frequency that varies, e.g. between about 20-60 Hz, preferably between about 35-45 Hz, more preferably between about 39-41 Hz

A frequency within these intervals and especially at around 40 Hz has proven to be most effective in curing tissue damages, not the least with regard to nerve regeneration.

In one embodiment, the tissue is a neurological tissue. Preferably, the neurological tissue is a vibrationally injured neurological tissue, such as in the case of tinnitus. In another embodiments, the neurological tissue is the olfactory epithelium, damage to which may result in anosmia. In yet another embodiments, the neurological tissue is a injured nerve, preferably a peripheral nerve or the spinal cord.

Various other states and tissue damages that can be cured by the present invention are e.g. nerve regeneration, mobility of joints, fracture heal, bone growth, increased bone density, oedema, venous insufficiency, leg ulcers, dyspnoea, muscle spasms, asthma, pain, chronic pain, neurogenic pain, neurogenic inflammation, fibromyalgia, migraine, inflammation, stress, neuropathies, Parkinson's disease, Alzheimer's disease, tinnitus, rhinitis, impulse control, schizophrenia, depression, bipolar disorder, heart failure.

The vibrational principle and basis disclosed above can also be used in many other situations and for curing many states, of which some are disclosed in this disclosure. In the case of tinnitus, the symptoms are often experienced by the patient in the same way as a "phantom"-pain, i.e. pain from a non-existing limb. E.g. the nervous tissue having damage that gives rise to tinnitus tries to send a nervous signal (a sound) at a specific frequency, but because of the injury, no response is given. The brain tries to compensate for the non-responding part of the frequency. The brain then increases the strength of the sound, since it expects a sound to come. This is what is experienced as tinnitus. According to the present invention, when the brain is relearned that the sound exists, and that the brain does not need to increase the signal to achieve a response. Such relearning may be achieved by providing a sound for the brain to process where the frequency range(s) where the hearing loss is present are compensated for. It is standard procedure for an audiologist to determine the specific frequency range or ranges where the patient suffering from tinnitus exhibits hearing loss or losses, in an audiological examination. Patients suffering from tinnitus almost invariably exhibit hearing losses. In one aspect, tinnitus is treated by a method comprising subjecting the subject in need thereof to an audio signal in the frequency range 39-41 Hz, preferably about 40 Hz. This signal facilitates tissue regeneration to help heal the injury.

The audio signal in the frequency range 39-41 Hz of the invention may be a continuous signal or a pulsatile signal, continuous being preferred. The signal may be of any wavefoπn, such a sinus, triangle, rectangle or even noise, while an essentially sinus-formed signal is preferred.

Preferably, the subject is also subjected to an audio recording specifically adapted to the subject's hearing loss e.g. by a method of the present invention, by amplifying the intensity of the recording specifically at the frequency range(s) where the subject exhibits hearing loss. The audio recording is preferably played back at a sound intensity of 40-80 dB (10^"8 to 10^"4 W/m²).

In another preferred embodiment the method also comprises that ambient sounds are specifically amplified at the frequency range(s) where the individual user exhibits hearing loss and played back in essentially real time into the user's ears, e.g. by using a device of the present invention.

Subjecting the subject to be treated to the audio signals of the invention may be done using any conventional device suitable for playback of audio signals and/or recordings, such as a cassette player, a radio, a CD-player, a DVD-player, a LP-disc player, a digital audio player such as MP3-player, a computer, a stream via a streaming device connected to the Internet, or any other device capable of playing back recorded audio, or capable of generating audio signals in real time.

In a further preferred embodiment, the method further comprises that the subject wears ear plugs with integrated loudspeakers individually adapted the user's ears to minimize hearing of any external sounds while simultaneously allowing playback of vibrations and sounds generated according to the disclosed invention into the user's ears.

In a further preferred embodiment, the method further comprises that the vibrations and sounds generated according to the above embodiments are applied at least to the ear that is contralateral relative to the tinnitus to be treated.

In a further preferred embodiment, the method further comprises that the audio signal in the frequency range 39-41 Hz, preferably about 40 Hz₅ is applied about 7-20 minutes per occasion.

In a further preferred embodiment, the method further comprises that the audio signal in the frequency range 39-41 Hz, preferably about 40 Hz has an intensity of 40-80 dB (10^"8 to 10^"4 W/m²), preferably 40-50 dB, most preferably about 50 dB (10^"7 W/m²).

In one aspect of the invention, a device for the treatment of tinnitus is provided. Programmable hearing aids are known in the art. A hearing professional programs the hearing aid with a computer and can adjust the parameters of the processed sound on an individual basis. Digital circuitry provides the most flexibility for the hearing professional to make adjustments for the hearing aid, although adaptable analog devices are also known. Digital hearing aids use at least one microphone, receiver, battery, at least one loudspeaker and computer chip. For example, digital hearing aids can be specially programmed with multiple programs for quiet situations, background noise reduction, music listening, and directionality. Many also have powerful feedback-reduction and/or cancellation technology.

Such known programmable hearing aids may be used as a starting point in constructing a device of one aspect the invention for the treatment of tinnitus. The device of the invention is programmed to specifically amplify the sound intensity at the frequency range(s) at which the affected ear of the subject to be treated exhibits hearing loss. An amplification of 10-20 dB is preferred.

The device is also fitted with means of exposing at least the ear of the subject which is contralateral in relation to the tinnitus to be treated, to the processed sounds generated by the device. I.e. the device is adapted so that, for the treatment of tinnitus in the left ear, the ambient sound are processed according to the hearing loss(es) in the left ear, and played back at least in the right ear. Such means of exposing an ear may comprise e.g. in principle any form of earphone or ear plug, widely available in the market and well known within the art. Preferably, the means also prevent any sounds other than those provided by the device from entering the ear as well as possible. Most preferably, the means comprise one or two ear plug(s) with integrated loudspeaker(s) individually adapted to the shape and form of the user's ear(s) to minimize hearing of any external sounds, while simultaneously allowing playback of sounds into the subject's ear(s). The means may also be comprise means to transmit the signals via bone, wax, oil or another liquid, also known in the art.

For the treatment of bilateral tinnitus, two similar devices according to above may be used simultaneously, each one specifically programmed for the hearing loss for each afflicted ear. Alternatively, a single device with capabilities of providing two different processed outputs may be used. The processed sounds, specifically amplified to match the hearing loss of an affected ear are played back in the contralateral ear. I.e. the device is adapted so that the sound processed according to the hearing loss of the right ear are played back into the left ear, and vice versa.

The device for treatment of tinnitus above is preferably used in conjunction with a treatment with an audio signal of 39-41 Hz, preferably 40 Hz as described above. Thus, the device may optionally be provided with controllable means of generating an audio signal in the frequency range 39-41 Hz, and means of exposing an ear of the subject to the generated audio signal.

At its simplest, the device has a programming for generating the signal, which may be activated by a optionally provided switch (accessible to the user). Preferably, an extra means of exposing an ear to an audio signal generated by the device (e.g. an extra earphone) may be provided for the ipsilateral ear, whereby the device is adapted to play back the audio signal in the frequency range 39-41 Hz for both ears. The audio signal in the frequency range 39-41 Hz may also be triggered automatically by the device at a certain time of day or in response to a specific audio cue. In one aspect, the invention also provides a method of programming a device for the treatment of tinnitus, comprising a. obtaining information on the audio frequency range(s) where an individual subject suffering from tinnitus exhibits hearing loss e.g. by audiological examination; b. adapting the device of to the individual subject's hearing loss comprising adjusting the settings the device such that it increases the intensity of ambient sounds specifically at the frequency range(s) where the individual subject exhibits hearing loss. In one aspect, the invention provides a method of adapting an audio recording for the treatment of tinnitus. The first step of the method is obtaining information on the audio frequency range(s) where an individual subject suffering from tinnitus exhibits hearing loss e.g. with a standard audiological examination. This information is used in adapting a pre-existing audio sample of choice to the individual subject's hearing loss comprising increasing the sound intensity of the recording specifically at the frequency range(s) at which the ear affected by the tinnitus exhibits hearing loss. An amplification of 10-20 dB is preferred. The adaptation of the audio sample may be performed by a number of known methods, e.g. computer software, e.g. Sound Forge by Sony Media Software (www.sonycreativesoftware.com). The audio sample may be in principle any sound sample. Preferably, it is one that the intended user knows well and associates with positive emotion. Preferably, the sound sample is a piece of recorded music, even more preferably at least 3 minutes long. The audio sample may be multichannel or single channel. A stereophonic (i.e. having 2 channels, left and right) sample is preferred. The adaptation is performed on at least on one audio channel that is intended for playback on at least the contralateral ear in relation to the tinnitus. E.g. a stereophonic recording is adapted, according to hearing loss(es) in the left ear, in the right channel of the recording, for treatment of tinnitus in the left ear.

In addition to the adaptation to the hearing loss, an audio signal in the frequency range 39-41 Hz, preferably 40 Hz is mixed to at least one audio channel of the audio sample being adapted. Mixing the audio signal in the frequency range 39-41 Hz, preferably 40 Hz to at least one channel intended for each ear is preferred.

Optionally, the adapted audio sample is recorded on a suitable medium, such as a CD- disc, a DVD-disc, a computer or a digital audio player or similar. It is also preferable to perform the adaptation and mixing live, or online through an internet audio streaming.

Preferably, the audio signal in the frequency range 39-41 Hz that is mixed is -40 to 40 dB in relation to the average intensity of the pre-existing audio sample. Preferably, the audio signal in the frequency range 39-41 Hz that is mixed totals 7-20 minutes in length. Also preferably, an audio signal in the frequency range 39-41 Hz is mixed at least to the beginning of the audio sample.

In another embodiment, the invention provides a method of adapting an audio recording for the treatment of bilateral tinnitus. For bilateral tinnitus, the audio recording produced has at least two discrete audio channels, and that the adaptation to specific hearing loss is performed individually for each affected ear; and the audio signal in the frequency range 39-41 Hz is mixed to at least one audio channel intended for playback on each affected ear.

In another aspect, the invention also provides an audio recording for the treatment of tinnitus produced using the method(s) described above for adapting audio recording for the treatment of tinnitus, recorded on a suitable medium, such as a CD-disc, a DVD-disc, a computer or a digital audio player or similar.

In a yet further aspect, an audio recording for the treatment of tinnitus is provided, having to the recording mixed an audio signal of the invention in the frequency range 39-41 Hz is provided. In the case of asthma, the vibrational signal or treatment could be provided by means of e.g. a vibrating air column that is positioned within the subjects throat or the like, to thereby alleviate the symptoms of the asthmatic condition. With regard to curing pain, chronic pain or neurogenic pain, a vibrational treatment according to the invention can e.g be: Circumferential vibration (f) 40 Hz, (I) 30 dB, from a soft mattress, wrapped around the afflicted body part for 20 min.

With regard to curing neuropathies or neurogenic inflammation, a vibrational treatment according to the invention can e.g. be: Combined treatment with circumferential vibration (f) 40 Hz, (I) 0-60 dB, from a soft mattress as well as from ear phones in sessions of 20 min duration.

With regard to curing dyspnoea, asthma or rhinitis, a vibrational treatment according to the invention can e.g. be: Together with a CPAP mask (Continuously Positive Airway Pressure), vibration (f) 40 Hz, (I) 30-60 dB in sessions of 20 min duration.

With regard to curing inflammation, oedema, mobility of joints, fracture heal, bone growth, increased bone density, pathological fracture (oncology), osteoporosis, venous insufficiency, leg ulcers a vibrational treatment according to the invention can e.g. be: Circumferential vibration (f) 40 Hz, (I) 30-60 dB, from a vibrating soft mattress in sessions of 20 min duration.

With regard to curing and/or treatment of symptoms resulting from connections to a prosthesis or a false limb, a vibrational treatment according to the invention can e.g. be: Treatment during night time. Combined treatment with a vibrating mattress wrapped around the afflicted limb, from the prosthesis it self as well as from head phones. Vibration with frequency (f) of 40 Hz, or combined vibrations with frequency of 10-170 Hz, (I) 0-60 dB, Sessions of 7 min every 30 minutes during 8 hours.

Normally, the vibrational signal has a duration within the interval of 1-60 min, preferably in the interval of 7-20 min. That is the signal is preferably applied for at least 7 minutes on occasion, and preferably no longer than 20 minutes on occasion. Shorter applications are less effective and longer signals give limited added benefits due to desensitisation. Especially, a treatment duration of about 7 min repeated every 30 minutes, or a duration of about 20 min, have proven to be effective. Longer intervals between treatments are also useful. In one preferred embodiment, the treatment is applied once daily, even more preferably in the mornings. In another preferred embodiment, the treatment is applied once weekly. In one aspect, the invention provides a method of treatment for anosmia comprising subjecting the olfactory epithelium of a subject in need thereof to a vibrational signal in the frequency range 39-41 Hz, preferably about 40 Hz. Preferably, the vibrational signal has an intensity of 20-80 dB, preferably 40-50 dB. Also preferably, the vibrational signal is applied 7-20 minutes per occasion on a daily basis (preferably in the morning) until improvement is achieved.

In a related aspect of the invention, a device for the treatment for anosmia is provided. The device comprises means of generating a vibrational signal in the frequency range 39-41 Hz, preferably about 40 Hz, and means of applying the vibrational signal to the olfactory epithelium of the subject to be treated. In one embodiment, the means of applying the vibrational signal to the olfactory comprises a tubular conduit. In a preferred embodiment, the device provides a vibrational signal having an intensity of 20-80 dB, preferably 40-50 dB.

In one aspect, the invention provides a method of curative treatment of a nerve injury, comprising subjecting the nerve injury of a subject in need thereof to a vibrational signal in the frequency range 39-41 Hz. Preferably, the vibrational signal is applied 7- 20 minutes per occasion on a daily basis (preferably in the morning) until improvement is achieved.

In a related aspect a device for curative treatment of a nerve injury is provided, having means of generating a vibrational signal in the frequency range 39-41 Hz, means of locating the nerve injury, preferably by ultrasonic imaging; and means of applying the vibrational signal to the nerve injury of the subject to be treated.

Preferably, the subject is a human patient.

In yet another embodiments, the use of the vibrational signal is combined with other therapeutic means, such as chemotherapy, radiation therapy or the like. This is especially preferable in the case tissue damages as a result of a tumor, i.e. within the field of oncology, where the combination of e.g. a vibrational signal with radiation therapy can give a surprisingly strong effect. Especially this is effective for strengthening bone tissue. The details and particulars described above and in the claims and relating to the methods and devices according to the invention apply mutatis mutandis to the other aspects of the invention.

While the invention has been described in relation to certain disclosed embodiments, the skilled person may foresee other embodiments, variations, or combinations which are not specifically mentioned but are nonetheless within the scope of the appended claims.

All references cited herein are hereby incorporated by reference in their entirety.

The expression "comprising" as used herein should be understood to include, but not be limited to, the stated items.

The invention will now be described in relation to the following appended examples, which are only to be seen as illustrations of the invention, thereby not limiting the claimed scope of protection.

Examples

Example 1 - tinnitus

Method

Mapping of the hearing disorder

With the aid of a conventional audiometric laboratory the character and extent of the likely hearing disorder are mapped.

Mapping of tinnitus disorder

With the aid of a joy-stick, tone generator and stereophonic sound reproduction the morphology of the tinnitus disorder is compared and calibrated, with regard to frequency and amplitude, to an existing sound bank. Mapping of possible morphological/mathematical connection between existing hearing disorder and tinnitus disorder.

Treatment The treatment proceeds during 1- 3 months along several parallel lines. Proprimo

The priming of the nervous system proceeds initially via massive stress reduction. The purpose during the entire curing process is to bring the number of stress factors to an absolute minimum level. Depending on the habitus of the patient this is made via diet, exercise, relaxation, meditation etc. Further, cognitive behavioural therapy is used. The purpose is to provide the patient with instrumental psychological skills in order to safely return to the known neuro-acoustic environment.

Pro secundo The patient chooses 1 - 9 favourite pieces of music (3-5 minutes long), that are well known and associated with strongly positive emotions.

Via an electronic multiband modulator (EQ) every area specific for the unique hearing disorder of the patient is circumvented. This is achieved by amplifying every frequency of the sound picture that corresponds to a missing part of the hearing disorder with about 5-25 dB, and hereby compensating for the frequency losses of the hearing disorder.

The favourite music is processed in a conventional sound program and is EQ- modulated in accordance with the specification above, and is presented on a sound file that is unique for the patient. The treatment session is started with an about 7 minutes long orally led relaxation. Thereafter an about 7 minutes long soft bilateral vibration follows; comprising one- second sweeps of about 20-60 Hz (about 5-20 dB). Thereafter one or more of the electronically processed favourite pieces of music are played. The session is ended with an about 7 minutes long relaxing sound file (waves at a beach or a summer meadow or the like).

The return of the processed material to the brain is achieved via conventional headphones via air and via the side of the head that is contra-lateral to the disorder. Other returning principles (via bone, wax, oil or liquid, depending on the tinnitus disorder of the patient) are also conceivable, depending on the specific tinnitus disorders of the respective patient.

Pro tertio When the method is well established with the patient, the running treatment comprising the entire process via a 15-45 minutes long sound file, either presented via compact disc, cellular phone, MP3, iPod or the like, or a stream via a computer connected to Internet, wherever the patient is geographically located.

Taken together the present invention provides an overcoming of the attempts of the central nervous system to restore hearing perceptions, which according to the present invention is the main principle of the brain's/attention's generation of tinnitus.

When the brain/attention has been restored to the normal setting, the curing is accomplished and the tinnitus disorder gone.

At severe, invalidating tinnitus the patient can be provided with a unique bilateral hearing device, through which incoming sounds are processed online, and further are presented contra-laterally (as above).

Example 2 — Preferred tinnitus treatment

Method

1. Mapping of hearing disorder. Via a conventional audiometric lab the subjective character and the objective specification of the actual hearing disorder is characterised.

2. Mapping of the tinnitus.

A tone is generated via a tone-generator, and through a stereophonic (earphones) representation presented to the patient, the tinnitus problem is objectively characterised; regarding frequence, amplitude, and stereotactic morphology. Via a joystick the tinnitus-problem is "described" in detail by the patient: if the joy-stick is moved forward: the problem is louder than the generated tone, if moved backwards: the problem is more silent than the generated tone, if moved to the right: the tone is at higher pitch (20Hz - 2OkHz), and moved to the left: the tone is at lower pitch (20Hz - 2OkHz)).

3. Mapping of the mathematical/morphological relation between the manifest hearing disorder and the tinnitus problem.

Customising an audio sample for the treatment

A piece of the patient's favourite music was chosen by the patient. It was instructed that the chosen music piece should be well known by the patient since a long time, and associated to strong positive memories/feelings.

Via an electronically multiband equaliser (EQ modulator), the recorded music piece of patients choosing was enhanced in respect of every lost frequency, with +10-20 dB; in such a manner that every lost frequency, specified in the mapping of the hearing disorder, was compensated for and enhanced with +10-20 dB, in the final version of the favourite music piece, thus individually tailoring the chosen recorded music piece to the individual patients hearing loss. The music piece was then transformed to a suitable form (i.e. MP3, wav., or any other widely available format, of the patients choice) for the further process.

This resulted in a unique piece of music, where every lost part (frequency) of the hearing system, was compensated for, electronically, with +10-20 dB.

Treatment a) Protocol for unilateral tinnitus:

1. A (priming) bilateral vibration (40Hz sinus signal at 5OdB (10^"7W/m²) sound intensity) was propagated to both sides, via earphones (Right/Left, hereafter R/L) for 3 min.

2. The above described music piece (electronically enhanced in the unique frequencies, according/corresponding to the patients hearing loss) was played to the patient via earphones (R/L) for the duration of the recording (typically approx 3-4 min), at 5OdB (10^"7W/m²) sound intensity, to the afflicted side (i.e. the tinnitus side), and at 60-7OdB (10^"6W/m²) sound intensity, to the un-afflicted (i.e. the non-tinnitus side).

3. A (conserving) bilateral vibration (40Hz sinus signal at 5OdB (10^~7W/m²) sound intensity) was propagated to both sides, via earphones (RfL) for 3 min. 4. The above described music piece (electronically enhanced in the unique frequencies, according/corresponding to the patients hearing loss) was played to both the afflicted side as well as the un-afflicted side, via earphones (R/L) for its own length (approx 3-4 min), at 60-7OdB (10^"6W/m²) sound intensity to both sides.

5. A (closing) bilateral vibration (40Hz sinus signal at 5OdB (10^"7W/m²) sound intensity) was propagated to both sides, via earphones (R/L) for 3 min.

All these five steps were morphed together to one continuous audio recording. b) Protocol for bilateral tinnitus:

1. A (priming) bilateral vibration (40Hz sinus signal at 5OdB (10^'7W/m²) sound intensity) was propagated to both sides, via earphones (R/L) for 3 min. 2. The above described music piece (electronically enhanced in the unique frequencies, according/corresponding to the patients hearing loss) was played via earphones (R/L) for the duration of the recording (approx 3-4 min), at 5OdB (10^" ⁷W/m²) sound intensity, to both sides.

3. A (conserving) bilateral vibration (40Hz sinus signal at 5OdB (10^"7W/m²) sound intensity) was propagated to both sides, via earphones (R/L) for 3 min.

4. The above described music piece (electronically enhanced in the unique frequencies, according/corresponding to the patients hearing loss) was played via earphones (R/L) for the duration of the recording (approx 3-4 min), at 60-7OdB (10^" ⁶W/m²) sound intensity, to both sides. 5. A (closing) bilateral vibration (40Hz sinus signal at 5OdB (10^"7W/m²) sound intensity) was propagated to both sides, via earphones (R/L) for 3 min.

All these five steps were morphed together to one continuous audio recording. Example 3 - Tinnitus case reports

Case 1

Female 38 y, non-smoker, orchestra musician, presents episodic unilateral ringing tinnitus in left ear since > 10 years. The onset was gradual. No associated vertigo or pain. Also presents associated problems with insomnia. Treated as described in example 2, during 2 weeks, with the unilateral protocol, for 20 min at three consecutive occasions, with one week between. Reported significant improvement of symptoms at follow up after 4 weeks. The improvement was persistent at least to the follow up at 3 months after treatment.

Case 2

Male 55 y, smoker, orchestra musician, presents constant unilateral ringing tinnitus in right ear since 5 years. The onset was gradual. No associated vertigo or pain. Also presents associated problems with depression. Treated as described in example 2, during one week, with the unilateral protocol, for 20 min at two consecutive occasions, with one week between. Reported essentially full recovery of symptoms at follow up after 4 weeks. The improvement was persistent at least to the follow up at 3 months after treatment.

Case 3

Male 64 y, smoker, onboard motorship personal, presents constant unilateral buzzing tinnitus in right ear since 12 years. The onset was gradual. No associated vertigo or pain. Also presents associated problems with insomnia. Treated as described in example 2, during 2 weeks, with the unilateral protocol, for 20 min at three consecutive occasions, with one week between. Reported significant improvement of symptoms at follow up after 4 weeks. The improvement was persistent at least to the follow up at 3 months after treatment.

Case 4

Male 32 y, non-smoker, orchestra musician, presents constant unilateral ringing tinnitus in right ear since 2 years. The onset was sudden. No associated vertigo, or pain. Also presents associated problems with episodical anxiety. Treated as described in example 2, with the unilateral protocol, for 20 min at one occasion. Reported essentially full recovery of symptoms at follow up after 4 weeks. The improvement was persistent at least to the follow up at 3 months after treatment.

Several additional patients were treated successfully but are not described in detail.

Example 4: Treatment of anosmia.

Before treatment with the described method begun, all conventionally treatable causes were excluded. Conductive or inflammatory conditions such as nasal polyps or chronic rhinosinusitis were treated with a short course of oral steroids followed by a topical steroid spray.

Patients with sinonasal disease not responding to steroids and those with no obvious cause for altered olfaction were referred to an ear, nose, and throat specialist.

When olfaction loss was concluded potentially irrecoverable, the patients were included and treatment was offered with the method and device of the invention. The treatment as applied using a device illustrated in figure 2. The vibration (40Hz at 20 to 6OdB (10^'10 to 10^"6W/m²)) was delivered from a Model 301 5 MHz Function Generator (6). The signal was amplified through an Amplifier PA25E CE Ser No N593 (5) and led on to a Vibrator V201-M4-CE Ser No 100393/14 (4). The vibration was propagated further on via a Chest Piece (Precordial Stethoscope) (3) and then through two plastic cones (2) to the nostrils via two MAD: Mucosal Atomization Device; Wolfe Tory Medical, Inc. (1). The vibration frequency (f) was 40Hz. During 10 to 30 min the nostrils were vibrated at 20 to 6OdB (10^"10 to 10^'6W/m²).

Example 5: Anosmia case reports

Case 1 Male 60 y, non-smoker, teacher. Episode of severe inflammation in respiratory tract, due to a viral infection. Manifest anosmia after 3 months. Treated with bilateral vibration with the device of example 4, 40Hz at 5OdB (10^"7W/m²), for 20 min daily under 5 days, with essentially full recovery. The effect was persistent after 3 months. Case 2

Male 25 y, non-smoker, unemployed. Lifelong, intermittent inflammation in respiratory tract, due to allergy to cats, horses and dogs. Successive development of anosmia, no effect of corticosteroid treatment. Treated with bilateral vibration with the device of example 4, 40Hz at 4OdB (10^~8W/m²), for 20 min daily under 5 days, with significant improvement. The effect was persistent after 3 months.

Case 3

Female 35 y, smoker, shop-owner. Head trauma due to traffic accident, which led to a classical whiplash syndrome and with a reported anosmia that had been reported stabile for 2 years. Treated with bilateral vibration with the device of example 4, 40Hz at 6OdB (10^"6W/m²), for 20 min daily under 5 days, with essentially full recovery. The effect was persistent after 3 months.

Case 4

Male 47 y, non-smoker, garage employed. Head trauma due to motorcycle accident. After 7 months the patient gradually developed anosmia. Treated with bilateral vibration with the device of example 4, 40Hz at 6OdB (10^"6W/m²), for 20 min daily under 5 days, with essentially full recovery. The effect was persistent after 3 months.

Several additional patients were successfully treated but are not described in detail.

Example 6: Nerve regeneration

As described in "Piezoelectric Vibrating Needle and Catheter for Enhancing Ultrasound-Guided Peripheral Nerve Blocks" by S.M. Klein, M.P. Fronheiser, J. Reach, K.C. Nielsen, S.W. Smith, in Anesth Analg 2007;105:1858-60; an insulated needle with a Teflon-coated steel stylet is to be customised by either adhering in place a piezoelectric actuator or by modifying the Stimuplex operating device, in such a manner as that the operating device will produce the same vibration as would the piezoelectric actuator. This device will then create a 1-8 kHz vibration when coupled to a Function Generator and an Amplifier. When activated, the tip of the needle is to be highlighted in colour when scanned in the short axis using the colour Doppler mode of a two-dimensional ultrasound. An illustration of such a device is shown in Figure 3.

The ultrasound-probe (7) is then used for monitoring (8) and identification of the damaged nerve. A Stimuplex A 50; 0,7 X 50MM 22G X 2"; B. Braun Melsungen AG needle (9) is vibrated at an ultrasonic frequency suitable (1-8 kHz) for imaging, corresponding to position "A" on the modified Stimuplex operating device (10), thus creating a colour doppler image of the needle tip at the damaged nerve.

With the Stimuplex needle in proper position near the damaged nerve, the switch on the modified Stimuplex operating device (10), is turned from position "A" to position "B", thereby vibrating the Stimuplex needle with 40 Hz and thus treating the damaged nerve for 20 min.

In the actual set-up a two-dimensional ultrasound and a 12 MHz L38 probe (MicroMaxx, Sonosite, Bothell, WA) is used. Together with a A Stimuplex A 50; 0,7 X 50MM 22G X 2"; B. Braun Melsungen AG needle, a Model 301 5 MHz Function Generator and a Amplifier PA25E CE Ser No N593.

Cases that are treated are hand/finger knife-wounds, spinal cord injuries, traffic injuries and neurodegenerative diseases (including Alzheimer, Parkinson, MS, ALS).

Claims

1. Device for treatment of tinnitus in a subject in need thereof, characterized by that it comprises a. means of processing ambient sounds in essentially real time resulting in specific amplification of the sound intensity at the frequency range(s) at which the affected ear exhibits hearing loss; and b. means of exposing at least the ear of the subject which is contralateral in relation to the tinnitus to be treated, to the processed sounds generated by the device in step (a); wherein the device is adapted to operate by playing back the processed ambient sounds in essentially real time into at least the ear of the subject which is contralateral in relation to the tinnitus to be treated.

2. Device of claim 1 for the treatment of bilateral tinnitus, wherein the device has bilateral means of performing the processing and ear exposure.

3. Device of claim 1-2, characterized by further comprising controllable means of generating an audio signal in the frequency range 39-41 Hz, and means of exposing at least one ear of the subject, preferably at least the ipsilateral ear, to the generated audio signal.

4. Device according to claims 1-3 wherein the means of exposing the ear(s) of the subject to be treated to sounds generated by the device comprise ear plugs with integrated loudspeaker(s) individually adapted to the shape and form of the user's ear(s) to minimize hearing of any external sounds, while simultaneously allowing playback of sounds into the subjects ear(s).

5. Method for individual adaptation a device of claims 1-4, characterized by that it comprises the steps of: a. obtaining information on the audio frequency range(s) where an individual subject suffering from tinnitus exhibits hearing loss; b. adapting the device of claim 1 to the individual subject's hearing loss comprising adjusting the settings the device such that it increases the intensity of ambient sounds specifically at the frequency range(s) where the individual subject exhibits hearing loss. 6. Method of producing an audio recording for the treatment of tinnitus characterized by that it comprises the steps of: a. obtaining information on the audio frequency range(s) where an individual subject suffering from tinnitus exhibits hearing loss; b. adapting a pre-existing audio sample of choice to the individual subject's hearing loss comprising increasing the sound intensity of the recording specifically at the frequency range(s) at which the ear affected by the tinnitus exhibits hearing loss wherein the specific amplification is applied to at least one audio channel intended for playback at least on the contralateral ear in relation to the tinnitus; c. mixing an audio signal in the frequency range 39-41 Hz to at least one audio channel of the recording; and d. preferably, storing the adapted audio recording on a suitable medium, such as a CD-disc, a DVD-disc, a computer or a digital audio player or similar. 7. Method of claim 6 wherein the audio signal mixed in step (c) is -40 to 40 dB in relation to the average intensity of the pre-existing audio sample.

8. Method of claims 6-7 wherein the audio signal mixed in step (c) totals 7-20 minutes in length.

9. Method of claims 6-8 wherein the audio signal mixed in step (c) is mixed at least to the beginning of the audio sample.

10. Method of claims 6-9 for treatment of bilateral tinnitus wherein a. the audio recording produced has at least two discrete audio channels; b. step (b) of claim 6 is performed individually for each affected ear; and c. audio signal in step (c) of claim 6 is mixed to at least one audio channel intended for playback on each affected ear.

11. Audio recording for the treatment of tinnitus produced using the method of claims 6-10 recorded on a suitable medium, such as a CD-disc, a DVD-disc, a computer or a digital audio player or similar.

12. Audio recording for the treatment of tinnitus, having to the recording mixed an audio signal in the frequency range 39-41 Hz.

13. Method of treatment for tinnitus comprising subjecting the subject in need thereof to an audio signal in the frequency range 39-41 Hz. 14. Method of treatment according to claim 13, further comprising subjecting the subject to an audio recording specifically adapted to the subject's hearing loss by amplifying the intensity of the recording specifically at the frequency range(s) where the subject exhibits hearing loss.

15. Method of treatment according to claim 13, further comprising specifically amplifying ambient sounds at the frequency range(s) where the individual user exhibits hearing loss and playing back the amplified ambient sounds in essentially real time into the user's ears.

16. Method of treatment according to claim 13, further comprising that the subject wears ear plugs with integrated loudspeakers individually adapted the user's ears to minimize hearing of any external sounds while simultaneously allowing playback of vibrations and sounds generated according to claims 13-15 into the user's ears.

17. Method of treatment according claim 13, further comprising that the vibrations and sounds generated according to any of claims 13-15 are applied to the ear that is contralateral relative to the tinnitus to be treated.

18. Method of treatment according claim 13, further comprising that the vibrations and sounds generated according to any of claims 13-15 are applied 7-20 minutes per occasion.

19. Method of treatment according claim 13, further comprising that the vibrations and sounds generated according to any of claims 13-15 have an intensity of 30- 70 dB, preferably 40-50 dB.

20. Device for the treatment of anosmia, characterized by means of generating a vibrational signal in the frequency range 39-41 Hz, preferably about 40 Hz, and means of applying the vibrational signal to the olfactory epithelium of the subject to be treated.

21. Device according to claim 20, wherein the means of applying the vibrational signal to the olfactory comprises a tubular conduit. 22. Device according to claim 20, wherein the vibrational signal has an intensity of

30-70 dB, preferably 40-50 dB.

23. Method of treatment for anosmia comprising subjecting the olfactory epithelium of a subject in need thereof to a vibrational signal in the frequency range 39-41 Hz. 24. Method of treatment according to claim 23, wherein the vibrational signal has an intensity of 30-70 dB, preferably 40-50 dB.

25. Method of treatment according to claim 23, wherein the vibrational signal is applied 7-20 minutes per occasion on a daily basis (preferably in the morning) until improvement is achieved. 26. Device for curative treatment of a nerve injury, characterized by a. means of generating a vibrational signal in the frequency range 39-41 Hz, preferably about 40 Hz; b. means of locating the nerve injury, preferably by ultrasonic imaging; and c. means of applying the vibrational signal to the nerve injury. 27. Method of curative treatment of a nerve injury, comprising subjecting the nerve injury of a subject in need thereof to a vibrational signal in the frequency range 39-41 Hz, preferably about 40 Hz.

8. Method of treatment according to claim 27, wherein the vibrational signal is applied 7-20 minutes per occasion on a daily basis (preferably in the morning) until improvement is achieved.