Meniere's Disease - A New Theory And A Promising Vestibular Prosthesis

According to researchers at University of Colorado School of Medicine there is a strong association between Meniere's disease and conditions involving temporary low blood flow in the brain such as migraine headaches.

Foster explains that these attacks can be caused by a combination of two factors: 1) a malformation of the inner ear, endolymphatic hydrops (the inner ear dilated with fluid) and 2) risk factors for vascular disease in the brain, such as migraine, sleep apnea, smoking and atherosclerosis.

The researchers propose that a fluid buildup in part of the inner ear, which is strongly associated with Meniere's attacks, indicates the presence of a pressure-regulation problem that acts to cause mild, intermittent decreases of blood flow within the ear. When this is combined with vascular diseases that also lower blood flow to the brain and ear, sudden loss of blood flow similar to transient ischemic attacks (or mini strokes) in the brain can be generated in the inner ear sensory tissues. In young people who have hydrops without vascular disorders, no attacks occur because blood flow continues in spite of these fluctuations. However, in people with vascular diseases, these fluctuations are sufficient to rob the ear of blood flow and the nutrients the blood provides. When the tissues that sense hearing and motion are starved of blood, they stop sending signals to the brain, which sets off the vertigo, tinnitus and hearing loss in the disorder.

Restoration of blood flow does not resolve the problem. Scientists believe it triggers a damaging after-effect called the ischemia-reperfusion pathway in the excitable tissues of the ear that silences the ear for several hours, resulting in the prolonged severe vertigo and hearing loss that is characteristic of the disorder. Although most of the tissues recover, each spell results in small areas of damage that over time results in permanent loss of both hearing and balance function in the ear.

Since the first linkage of endolymphatic hydrops and Meniere's disease in 1938, a variety of mechanisms have been proposed to explain the attacks and the progressive deafness, but no answer has explained all aspects of the disorder, and no treatment based on these theories has proven capable of controlling the progression of the disease. This new theory, if proven, would provide many new avenues of treatment for this previously poorly-controlled disorder.

Many disorders of the inner hear which affect both hearing and balance can be hugely debilitating and are currently largely incurable. Cochlear implants have been used for many years to replace lost hearing resulting from inner ear damage. However, to date, there has not been an analogous treatment for balance disorders resulting from inner ear disease. One potential new treatment is an implantable vestibular prosthesis which would directly activate the vestibular nerve by electrical stimulation.

Phillips and his colleagues have developed a vestibular prosthesis which delivers electrical stimulation to the fluid inside the semi-circular canals of the ear. In effect, the stimulation of the fluid makes the brain believe that the body is moving or swaying in a certain direction. This then causes a compensatory postural reflex to stabilize the posture thereby helping to restore balance.

This prosthesis was inserted into the ears of four subjects all suffering from long-term Meniere's disease and differing degrees of hearing loss which was resistant to other management strategies. The researchers found that electrical stimulation of the fluid in the semicircular canals of the affected ear did result in a change in posture, the direction of which was dependent on which ear was stimulated. However, each subject had different sway responses to the stimulation given. The authors believe this could be caused by small differences in the location of the electrode between subjects. Thus fine tuning and individual calibration for each electrode implant would be required for it to be effective. Overall the results illustrate that this type of prosthesis may eventually be a possible treatment for balance issues caused by Meniere's disease.


References:

1. Carol Foster, MD and Robert Breeze, MD. The Meniere attack: An ischemia/reperfusion disorder of inner ear sensory tissues. Medical Hypotheses, December 2013
2. Phillips, C. et al. Postural responses to electrical stimulation of the vestibular end organs in human subjects. Experimental Brain Research, 2013 DOI:10.1007/s00221-013-3604-3

Role Of Multisensory Plasticity In Tinnitus

That area, called the dorsal cochlear nucleus, is the first station for signals arriving in the brain from the ear via the auditory nerve. But it's also a center where "multitasking" neurons integrate other sensory signals, such as touch, together with the hearing information.

In tinnitus, some of the input to the brain from the ear's cochlea is reduced, while signals from the somato-sensory nerves of the face and neck, related to touch, are excessively amplified.  

Susan Shore, Ph.D., the senior author of the paper, explains that her team has confirmed that a process called stimulus-timing dependent multisensory plasticity is altered in animals with tinnitus -- and that this plasticity is "exquisitely sensitive" to the timing of signals coming in to a key area of the brain.  It's as if the signals are compensating for the lost auditory input, but they overcompensate and end up making everything noisy," says Shore.

The new findings illuminate the relationship between tinnitus, hearing loss and sensory input and help explain why many tinnitus sufferers can change the volume and pitch of their tinnitus's sound by clenching their jaw, or moving their head and neck.  But it's not just the combination of loud noise and overactive somatosensory signals that are involved in tinnitus, its the precise timing of these signals in relation to one another that prompt the changes in the nervous system's plasticity mechanisms, which may lead to the symptoms known to tinnitus sufferers. 

In this study, only half of the animals receiving a noise-overexposure developed tinnitus. This is similarly the case with humans -- not everyone with hearing damage ends up with tinnitus. An important finding in the new paper is that animals that did not get tinnitus showed fewer changes in their multisensory plasticity than those with evidence of tinnitus. In other words, their neurons were not hyperactive.

Shore is now working with other students and postdoctoral fellows to develop a device that uses the new knowledge about the importance of signal timing to alleviate tinnitus. The device will combine sound and electrical stimulation of the face and neck in order to return to normal the neural activity in the auditory pathway.

"If we get the timing right, we believe we can decrease the firing rates of neurons at the tinnitus frequency, and target those with hyperactivity," says Shore. She and her colleagues are also working to develop pharmacological manipulations that could enhance stimulus timed plasticity by changing specific molecular targets.

Ref:

1. Seth D. Koehler And Susan E. Shore. Stimulus Timing-Dependent Plasticity in Dorsal Cochlear Nucleus Is Altered in Tinnitus. Journal of Neuroscience, December 2013

ANNUAL OTOLOGY CONFERENCE – ISOCON 2013 BENGALURU

The annual otology conference is one of the best conferences organised by the ENT fraternity in India.  It is a much awaited event and one of the well attended conferences. This  time it was held at Bangalore, Karnataka,  from November 8th 2013 to November 10 2013.  Bangalore being a major hub in  the  south,  attracted well over 800 delegates.  The event was organized at the NIMHANS convention  centre, which was well located, spacious, with comfortable seating and good air conditioning.  The organizers had done a good job.  The entire conference was managed by an  event management company.  Bar coding of delegate badges ensured that nobody gate crashed into the dining area and also for the entertainement events in the  evening.  

The focus of this conference was Transcanal endoscopic approach to the ear.  This approach was showcased by two surgeons from Italy.  Dr.Livio Presutti,  from Modena Italy and his contemporary Dr. Marchioni Daniele, also working in the same hospital.  Dr. Presutti’s presentation “ Physiological basis and principles of the Transcanal endoscopic approach to the ear” was excellent. 

His other lecture “Endoscopic procedures in Otoneurosurgery” was also an eye opener to the way of using angled endoscopes to reach those areas which cannot be reached with an operating microscope.  Dr.  Marchioni Daniele’s talk “Exclusive endoscopic approach to cholesteatoma” was also excellent.  He highlighted the use of angled endoscopes to eradicate cholesteatoma in the sinus tympani and the epitympanic regions.  This was followed the next day by live endoscopic cadaveric dissection, where we had a chance to learn the minute surgical anatomy of the middle ear.  They then performed live endoscopic Myringoplasty, tympanoplasty, and surgery for cholesteatoma.  The images were excellent.  The only drawback to this approach is that only one hand can be used for surgical manipulation since the other hand is used to hold the endoscope.  Hence, the operating field has to be bloodless, since suction cannot be used simultaneously like when operating under the operating microscope.  The cholesteatoma surgery performed by Dr. Marchioni was really outstanding.  He followed the cholesteatoma right back to the mastoid antrum.  The use of cartilage for reconstruction too was done perfectly.  Dr. Presutti also demonstrated great skill in decompressing  the tympanic segment of the facial nerve in a case of temporal bone fracture following trauma.  I think that these surgeons have ushered in the era of Endoscopic Otology in  India. 

Dr. Bethold Langguth, a psychiatrist from the University of Regensburg, Germany is the chairman of the executive board of the tinnitus research initiative.  He is part of the interdisciplinary tinnitus clinic in Regensburg.  He spoke on the Diagnosis and therapeutic management of tinnitus.  It was interesting to note that tinnitus involved even non-auditory brain areas and the relevance of the memory mechanisms in persistent tinnitus with its associated distress.

Of course our Indian colleagues like Dr. Vijendra and Dr. Mahadeviah too demonstrated some very interesting live surgery.  

Like in the American Academy meetings, for the first time, there were instructional courses between 8 and 10 in the mornings.  Dr. P.G. Visvanathan shared his experiences on cartilage tympanoplasty in this forum, which was well attended and which benefited us immensely.

Of course the entertainment in  the evening matched the academic sessions.  The world renowned percussionist Sivamani, entertained us on the first day followed  by live musical show by S.P. Balasubramaniam.

Hats off to Dr. Vijendra and his team for putting up such  a good show.  It was a pleasant experience at Bangalore.  Looking forward to the Chennai conference.  I am  sure that Dr.Ravi and his team will do a fine job there too.

New breakthroughs in pathophysiology and treatment for Noise Induced Hearing Loss (NIHL)

It's easy to say that we should avoid loud noises, but in reality, this is not always possible. Front-line soldiers or first responders do not have time to worry about the long-term effects of loud noise when they are giving their all. If, however, a drug could be developed to minimize the negative effects of loud noises, it would benefit one and all.

Noise-induced hearing loss, with accompanying tinnitus and sound hypersensitivity is a common condition which leads to communication problems and social isolation.

In a research report published in the September 2013 issue of The FASEB Journal, scientists describe exactly what type of damage noise does to the inner ear, and provide insights into a compound that may prevent noise-related damage.

To make this discovery, Shi and colleagues used three groups of 6 - 8 week old mice, which consisted of a control group, a group exposed to broadband noise at 120 decibels for three hours a day for two days, and a third group given single-dose injections of pigment epithelium-derived factor (PEDF) prior to noise exposure. PEDF is a protein found in vertebrates that is currently being researched for the treatment of diseases like heart disease and cancer. The cells that secrete PEDF in control animals showed a characteristic branched morphology, with the cells arranging in a self-avoidance pattern which provided good coverage of the capillary wall. The morphology of the same cells in the animals exposed to wide-band noise, however, showed clear differences -- noise exposure caused changes in melanocytes located in the inner ear.

At the present time, the only treatment strategies for hearing loss are hearing aids and cochlear implants. Drug therapies for noise-induced hearing loss have only recently been proposed and, to date, there are virtually no treatments that can repair the damage to the inner ear and reduce the impact of hearing loss.

Researchers from the University of Auckland, New Zealand, have discovered that a potent new drug restores hearing after noise-induced hearing loss in rats. The landmark discovery found that injection of an agent called 'ADAC', activates adenosine receptors in cochlear tissues, resulting in recovery of hearing function.

Vlajkovic and his team's study investigates the potential of adenosine amine congener (ADAC) -- a selective A1 adenosine receptor agonist -- in the treatment of noise-induced hearing loss. Wistar rats were exposed to narrow-band noise for 2 -- 24 hours in an acoustic chamber to induce cochlear damage and permanent hearing loss. ADAC or placebo control was then administered by injection(s) in the abdomen, either as a single injection at six hours or multiple daily injections. The researchers measured the hearing in the rats before and after the treatments using a technique known as auditory brainstem response (ABR). They also used histological techniques to determine the number of missing cochlear sensory hair cells after noise exposure and the noise-induced production of free radicals.

Their results show that cochlear injury and hearing loss in rats exposed to narrow-band noise can be substantially restored by ADAC administration after noise exposure. Early treatment starting six hours after noise exposure was the most effective and provided greater recovery than late treatment starting 24 hours after noise exposure. The most sustainable treatment strategy was the one involving multiple injections of ADAC for five days after noise exposure. This therapy significantly attenuated noise-induced hearing loss and improved sensory hair cell survival.

Resveratrol, a substance found in red grapes and red wine, may have the potential to protect against hearing and cognitive decline, according to a published laboratory study from Henry Ford Hospital in Detroit.

The study shows that healthy rats are less likely to suffer the long-term effects of noise-induced hearing loss when given resveratrol before being exposed to loud noise for a long period of time. Resveratrol is a very powerful chemical that seems to protect against the body's inflammatory process as it relates to aging, cognition and hearing loss. The latest study focuses on the inflammatory process as it relates to aging, cognition and hearing loss.

It was designed to identify the potential protective mechanism of resveratrol following noise exposure by measuring its effect on cyclooxygenase-2 (or COX-2, key to the inflammatory process) protein expression and formation of reactive oxygen species, which plays an important role in cell signaling and homeostasis.

The study reveals that acoustic over-stimulation causes a time-dependent, up-regulation of COX-2 protein expression, and, resveratrol, significantly reduces reactive oxygen species formation, inhibits COX-2 expression and reduces noise-induced hearing loss following noise exposure in rats. Ultimately, these findings suggest that resveratrol may exert a protective effect from noise-induced hearing loss by the inhibition of COX-2 expression and reactive oxygen species formation, although other mechanism may also be involved.

An epilepsy drug shows promise in an animal model at preventing tinnitus from developing after exposure to loud noise, according to a new study by researchers at the University of Pittsburgh School of Medicine.

The team focused on an area of the brain that is home to an important auditory center called the dorsal cochlear nucleus (DCN). From previous research in a mouse model, they knew that tinnitus is associated with hyperactivity of DCN cells -- they fire impulses even when there is no actual sound to perceive. For the new experiments, they took a close look at the biophysical properties of tiny channels, called KCNQ channels, through which potassium ions travel in and out of the cell.

They found that mice with tinnitus have hyperactive DCN cells because of a reduction in KCNQ potassium channel activity. These KCNQ channels act as effective "brakes" that reduce excitability or activity of neuronal cells.

Tzounopoulos and his team tested whether an FDA-approved epilepsy drug called retigabine, which specifically enhances KCNQ channel activity, could prevent the development of tinnitus. Thirty minutes into the noise exposure and twice daily for the next five days, half of the exposed group was given injections of retigabine. The researchers found that mice that were treated with retigabine immediately after noise exposure did not develop tinnitus.

Such a medication could be a very helpful preventive strategy for soldiers and other people who work in situations where exposure to very loud noise is likely,

Source:

1. Federation of American Societies for Experimental Biology. "Now hear this: Scientists discover compound to prevent noise-related hearing loss." ScienceDaily, 29 Aug. 2013. Web. 29 Sep. 2013. 
2. Srdjan M. Vlajkovic, Kyu-Hyun Lee, Ann Chi Yan Wong, Cindy X. Guo, Rita Gupta, Gary D. Housley, Peter R. Thorne.Adenosine amine congener mitigates noise-induced cochlear injury. Purinergic Signalling, 2010; DOI:10.1007/s11302-010-9188-5
3. M. D. Seidman, W. Tang, V. U. Bai, N. Ahmad, H. Jiang, J. Media, N. Patel, C. J. Rubin, R. T. Standring. Resveratrol Decreases Noise-Induced Cyclooxygenase-2 Expression in the Rat Cochlea. Otolaryngology -- Head and Neck Surgery, 2013; DOI: 10.1177/0194599813475777
4. J. W. Middleton, T. Kiritani, C. Pedersen, J. G. Turner, G. M. G. Shepherd, T. Tzounopoulos. Mice with behavioral evidence of tinnitus exhibit dorsal cochlear nucleus hyperactivity because of decreased GABAergic inhibition. Proceedings of the National Academy of Sciences, 2011; 108 (18): 7601 DOI:10.1073/pnas.1100223108

The Exciting Science Behind Taste

We know that the human tongue can detect five tastes -- sweet, salt, sour, bitter and umami (a taste for identifying protein rich foods).

Taste cells are found in papillae, the little bumps on our tongues. These cells contain the receptors that interact with chemicals in foods to allow us to sense sweet, salty, sour, bitter, and umami. Taste cells are located in clusters called taste buds, which in turn are found in papillae, the raised bumps visible on the tongue's surface.

Two types of taste cells contain chemical receptors that initiate perception of sweet, bitter, umami, salty, and sour taste qualities. A third type appears to serve as a supporting cell.

A remarkable characteristic of these sensory cells is that they regularly regenerate. All three taste cell types undergo frequent turnover, with an average lifespan of 10-16 days. As such, new taste cells must constantly be regenerated to replace cells that have died.

When sweet, bitter and umami molecules reach the tongue, they activate taste receptors in specialized cells called Type II taste cells. 'how do these taste cells tell the brain that they have detected something?' This question has been a longstanding missing link in our understanding of taste perception. The scientists already knew that activation of taste receptors on Type II cells initiates a complex chain of events inside the taste cells. What they found, as reported in the current issue of Nature, is that the final step involves the opening of a pore formed by CALHM1 (calcium-homeostasis-modulator-1) in the taste cell membrane. The open channel allows molecules of the neurotransmitter ATP to leave the taste cell and relay a signal to adjacent nerve cells connected to the brain.

Monell molecular neurobiologist Ichiro Matsumato, PhD, contributed to the work by showing that the gene for CALHM1 is expressed in Type II taste cells, but not in other types of taste tissue. Their findings demonstrate that the CALHM1 pore is localized specifically in cells that detect sweet, bitter and umami taste.

The necessity of CALHM1 for the ability to taste sweet, bitter, and umami was demonstrated in behavioral tests performed by Tordoff. Reasoning that mice lacking the CALMH1 channel would not be able to release ATP to send information about sweet, bitter and umami taste detection to the brain, Tordoff tested the taste preferences of Calhm1 'knockout' mice. Engineered by co-author Philippe Marambaud, PhD, of the Feinstein Institute for Medical Research, the knockout mice lack the gene that codes for CALHM1.

"Like humans, mice with an intact CALHM1 gene avidly drink sucrose and other sweeteners, and avoid bitter compounds such as quinine. However, mice lacking CALHM1 are very unusual," said Tordoff. "These mice treat sweeteners and bitter compounds as if they were water. They behave as if they can't taste them at all."

Responses to salty and sour tastes were not affected by the missing gene because perception of these taste qualities is mediated via a different set of taste cells.

Of the five taste sensations -- sweet, bitter, sour, salty and umami -- sour is arguably the strongest yet the least understood. Sour is the sensation evoked by substances that are acidic, such as lemons and pickles. The more acidic the substance, the more sour the taste.

Acids release protons. How protons activate the taste system had not been understood. The USC team expected to find protons from acids binding to the outside of the cell and opening a pore in the membrane that would allow sodium to enter the cell. Sodium's entry would send an electrical response to the brain, announcing the sensation that we perceive as sour.

Instead, the researchers found that the protons were entering the cell and causing the electrical response directly.

"In order to understand how sour works, we need to understand how the cells that are responsive to sour detect the protons," said senior author Emily Liman, associate professor of neurobiology in the USC College of Letters, Arts and Sciences.

"In the past, it's been difficult to address this question because the taste buds on the tongue are heterogeneous. Among the 50 or so cells in each taste bud there are cells responding to each of the five tastes. But if we want to know how sour works, we need to measure activity specifically in the sour sensitive taste cells and determine what is special about them that allows them to respond to protons."

Liman and her team bred genetically modified mice and marked their sour cells with a yellow florescent protein. Then they recorded the electrical responses from just those cells to protons.

The ability to sense protons with a mechanism that does not rely on sodium has important implications for how different tastes interact, Liman speculates.

"This mechanism is very appropriate for the taste system because we can eat something that has a lot of protons and not much sodium or other ions, and the taste system will still be able to detect sour," she said. "It makes sense that nature would have built a taste cell like this, so as not to confuse salty with sour."



References:

1. Akiyuki Taruno, Valérie Vingtdeux, Makoto Ohmoto, Zhongming Ma, Gennady Dvoryanchikov, Ang Li, Leslie Adrien, Haitian Zhao, Sze Leung, Maria Abernethy, Jeremy Koppel, Peter Davies, Mortimer M. Civan, Nirupa Chaudhari, Ichiro Matsumoto, Göran Hellekant, Michael G. Tordoff, Philippe Marambaud, J. Kevin Foskett. CALHM1 ion channel mediates purinergic neurotransmission of sweet, bitter and umami tastes. Nature, 2013; DOI:10.1038/nature11906
2. Monell Chemical Senses Center. "Scientists help identify a missing link in taste perception."ScienceDaily, 6 Mar. 2013. Web. 8 Mar. 2013.
3. Rui B. Chang, Hang Waters, Emily R. Liman. A proton current drives action potentials in genetically identified sour taste cells. Proceedings of the National Academy of Sciences, 2010; DOI:10.1073/pnas.1013664107
4. University of Southern California (2010, November 25). How people perceive sour flavors: Proton current drives action potentials in taste cells. ScienceDaily. Retrieved March 8, 2013, from http://www.sciencedaily.com­/releases/2010/11/101124114709.htm

Temporary Hearing Deprivation Can Lead to 'Lazy Ear'

Scientists have gained new insight into why a relatively short-term hearing deprivation during childhood may lead to persistent hearing deficits, long after hearing is restored to normal. The research, published by Cell Press in the March 11 issue of the journal Neuron, reveals that, much like the visual cortex, development of the auditory cortex is quite vulnerable if it does not receive appropriate stimulation at just the right time.

It is well established that degraded sensory experience during critical periods of childhood development can have detrimental effects on the brain and behavior. In the classic example, a condition called amblyopia (also known as lazy eye) can arise when balanced visual signals are not transmitted from each eye to the brain during a critical period for visual cortex development.

An analogous problem may exist in the realm of hearing, in that children commonly experience a buildup of viscous fluid in the middle ear cavity, called otitis media with effusion, which can degrade the quality of acoustic signals reaching the brain and has been associated with long-lasting loss of auditory perceptual acuity," explains senior study author, Dr. Daniel Polley from the Massachusetts Eye and Ear Infirmary.

Dr. Polley and his colleague Dr. Maria Popescu from Vanderbilt University implemented a method to reversibly block hearing in one ear in infant, juvenile, and adult rats then looked at how auditory brain areas were impacted by the temporary hearing loss.

They observed that the temporary hearing loss in one ear distorted auditory patterning in the brain, weakened the deprived ear's representation and strengthened the open ear's representation. The scope of reorganization was most striking in the cortex (and not "lower" parts of the auditory pathway) and was more pronounced when hearing deprivation began in infancy than in later life. Therefore, it appears that maladaptive plasticity in the developing auditory cortex might underlie "amblyaudio," in a similar fashion to the contributions of visual cortex plasticity to amblyopia.

"The good news about amblyaudio is that it is unlikely to be a permanent problem for most people," concludes Dr. Polley. "Even if the acoustic signal isn't improved within the critical period, the mature auditory cortex still expresses a remarkable degree of plasticity. We know that properly designed visual training can improve visual acuity in adult amblyopia patients. We are gearing up now to study whether auditory perceptual training may also be a promising approach to accelerate recovery in individuals with unresolved auditory processing deficits stemming from childhood hearing loss."

Journal reference:
Maria V. Popescu, Daniel B. Polley. Monaural Deprivation Disrupts Development of Binaural Selectivity in Auditory Midbrain and Cortex. Neuron, 2010; 65 (5): 718-731 DOI:10.1016/j.neuron.2010.02.019

Health risks for women suffering from Migraine with aura

Women who have migraines with aura, which are often visual disturbances such as flashing lights, may be more likely to have problems with their heart and blood vessels, and those on newer contraceptives may be at higher risk for blood clots,

The first study showed that migraine with aura is a strong contributor to the development of major cardiovascular events such as heart attack and stroke. After high blood pressure, migraine with aura was the second strongest single contributor to risk of heart attacks and strokes, It came ahead of diabetes, current smoking, obesity, and family history of early heart disease. while people with migraine with aura have an increased risk, it does not mean that everyone with migraine with aura will have a heart attack or stroke. People with migraine with aura can reduce their risk in the same ways others can, such as not smoking, keeping blood pressure low and weight down and exercising.

The second study looked at women with migraine who take hormonal contraceptives and the occurrence of blood clots. The study involved women with migraine with and without aura who were taking both newer contraceptives such as the contraceptive patch and ring and older contraceptives. Women with migraine with aura were more likely to have experienced blood clot complications such as deep vein thrombosis with all types of contraceptives than women with migraine without aura. The occurrence of blood clot complications was also higher in women with migraine who took contraceptives than women taking the contraceptives who did not have migraine.

Women who have migraine with aura should be sure to include this information in their medical history and talk to their doctors about the possible higher risks of newer contraceptives

Migraine with aura is associated with a twofold increased risk of stroke, The risk was highest among young women with migraine with aura who smoke and use estrogen containing contraceptives. An international team of researchers analysed the results of nine studies on the association between any migraine (with and without aura) and cardiovascular disease. They show that migraine with aura is associated with a twofold increased risk of ischemic stroke. This risk is further increased by being female, age less than 45 years, smoking, and estrogen containing contraceptive use. In light of these findings, the authors recommend that young women who have migraine with aura should be strongly advised to stop smoking, and methods of birth control other than estrogen containing contraceptives should be considered. They suggest that patients who have migraine with aura should be followed closely and treated aggressively for modifiable cardiovascular risk factors.

Citations:

American Academy of Neurology (AAN). "Migraine with aura may lead to heart attack, blood clots for women." ScienceDaily, 15 Jan. 2013. Web. 3 Mar. 2013.