Being ‘Mindful’ May Help in Managing Essential Tremor

By Dr. Michael Braitsch, PT, DPT
Tribe Wellness, LLC

Photo of Michael Braitsch, Tribe WellnessIf you’re like me, you’ve heard over and over again the value of mindfulness. It’s become quite a popular buzzword in a variety of manners of marketing. As we enter the next frontier of neuroscience and brain health, it seems like you can’t go anywhere without hearing about mindfulness. But what does mindfulness really mean and how can it be useful in daily life or in managing life with a tremor?

As a physical therapist, I have seen time and again the role of increased stress ramping up the severity of a patient’s symptoms (whether it be chronic pain in someone’s lower back, the amplitude or frequency of a tremor, the incidence of freezing gait in someone with Parkinson’s disease – the  list goes on).

I’ve met many people though with an essential tremor who usually say something like, “If I really focus on it, I can kind of calm my tremor down.” This is mindfulness!

The even better news is that practicing mindfulness can have far reaching benefits to improve quality of life with or without a tremor. It makes good sense. When we are calmer, we learn better, we perform better, we are less distracted, and we can even tap into a level of subconscious skill to make life easier.

While this all sounds great, I’m also here to warn you that it takes some effort and consistency; however, we all know that most worthwhile things in life take some effort. The intention of this blog post is to clarify what mindfulness practice is and how it could be helpful.

What is Mindfulness?
Many people consider the practice of mindfulness as simply, being aware of the present moment and the task-at-hand. Merriam-Webster’s dictionary defines mindfulness as:

“1 : the quality or state of being mindful

2 : the practice of maintaining a nonjudgmental state of heightened or complete awareness of one’s thoughts, emotions, or experiences on a moment-to-moment basis “

So “mindfulness” is really a practice. It’s NOT a destination. It has a lot of similarities with meditation or directed thinking which is common in all religious beliefs, to quiet the mind you don’t have to run off to the mountains or join a monastery. Rather, mindfulness provides a method of intentionally directing one’s focus to the task-at-hand, while avoiding judgment (both good and bad).

Let’s break each of these down further.

Focus on the Present
An increased focus on the present moment is a heightened commitment to directing one’s attention to the task-at-hand. Even though the mind may wander, coming back to the present is the key for mindfulness. We are all human beings and have a natural tendency to consciously or unconsciously drift into other thoughts, but coming back to “right now” is the goal of this practice. Oddly enough, in a world where multi-tasking is everywhere, mindfulness practices teach us that we are more effective and more efficient when we slow down and focus on what we are doing.

Be Non-Judgmental
Each day we make thousands of decisions. For the sake of survival of the species, we have an evolutionary drive to constantly judge things as good or bad, helpful or harmful, useful or a waste of time. Using our “fight or flight” response has served us tremendously for thousands of years. This is often the hardest part of mindfulness. Reinforcement of use of the “fight or flight” hardwires us to rush ahead to the next moment. However, when we lose sight of the present and constantly let the mind race, neuroscience tells us that we strengthen our brains’ stress responses to everyday tasks. On an extreme level, a heightened stress-response can have far-reaching negative effects. While it’s helped humanity to survive, we’ve become hardwired to get bogged down by incessant mental chatter. Mindfulness shows us that we can remain focused on the task at hand without judgment, and on a very practical level, rewiring our brains from training a ”stress-response,” to instead, training a “relaxation response.”

As we strive to increase our focus and to quiet the mind, we can find an abundance of benefits from improved awareness. We can even gain insight into why we feel a certain way or perhaps a deeper level of relaxation. This training has a powerful effect on our autonomic nervous system. By choosing presence and mindfulness, a hyperactive brain or a hyperactive nervous system can be slowed down, leading to a wealth of benefits including improved cardiovascular health, improved cognition, and more!

But What About My Tremor?
Managing stress is great for everyone. For someone with a tremor, it can be even more helpful. Most people I’ve met who are dealing with essential tremor say something like, “my tremor gets worse when I’m stressed out.” Stress and depression can even create a negative cycle that increases the tremor currently, and because of embarrassment about worsening of the tremor, causes more stress and depression. While there have not yet been studies on practicing mindfulness as a means of managing essential tremor, there have been many anecdotal reports of it helping. It stands to reason that even if mindfulness did nothing for the tremor itself, the already established far-reaching benefits make it worth the effort until a study can show what so many people have already reported. Why not give yourself a chance to reduce stress and feel good, right?

Can I Practice Mindfulness While Exercising?
Now for my favorite topic. . .there are forms of exercise that harness and foster a mindful approach while also striving to calm the mind and strengthen the body. As a physical therapist, my life’s mission is to help people move better and feel better. The research on the role of exercise in managing stress is abundant to say the least. As a long-time martial artist, I’ve seen first-hand the changes that can occur with dedicated practice of martial arts and the increased sense of well-being that students develop. Tai Chi is easily the most common form of martial art with emphasis on mindful practice because it is low-impact, easy to modify, and because it focuses on breath with movement. Alternatively, yoga has provided an avenue for mindful training for centuries and pilates also employs a mindful approach to movement, capturing the benefits of mindfulness and exercise.

What Else Can I Look at to Learn More?
Mindfulness resources are everywhere! There is no shortage of resources when it comes to mindfulness. The best practice though, like the best exercise, is the one that you can do consistently.

Here are a few to start with:

 

Educating Family Physicians about ET and the IETF

By Patrick McCartney,
IETF Executive Director

One of the pillars of the International Essential Tremor Foundation’s mission statement is “to provide hope to the essential tremor (ET) community worldwide through awareness.”

As we all know one of the biggest challenges we face is raising awareness for ET. This is a daily task for our staff. We use a variety of channels including social media, printed materials, and talking with patients, caregivers, and family members every day on the phone who have questions about this disorder.

Another way we try to raise awareness is by attending national conferences and sharing a variety of information on ET. October 10 through 12 I attended the American Academy of Family Physicians Family Medical Experience in New Orleans, LA. There were more than 5,000 family doctors attending the event. This is the third year we have attended and it’s a great opportunity to share with family doctors the resources the IETF has available for them and their patients.

I shared our Patient Handbook, IETF brochure, ET vs. Parkinson’s fact sheet, medical alert cards, IETF pens, and Tremor Talk magazines with them. The ET vs. Parkinson’s fact sheets were so popular I ran out the second day and had to make more copies at the hotel for the last day of the show.

A couple of takeaways from this conference:

  • Every doctor I talked with had treated ET patients, but not one of them was AAFP Conference 2018aware of the IETF.
  • Several of the doctors I talked with have ET or have family members or friends who have it and were excited to see the resources we have to share.
  • Everyone I spoke with said they would share our information and/or direct their patients, friends, or family members with ET to the IETF either through our website or our toll-free phone number.

I would encourage you, as I encouraged these doctors, to be advocates for ET and the IETF in your community. There are a lot of stereotypes and stigmas associated with ET. Don’t let them prevent you from sharing your story and explaining the daily challenges you face because of ET. And let others with ET know they are not alone.  There are IETF support groups all around the country. You can find a listing of them on our website.  If there is not one in your area consider starting one or join our online support group on Facebook (Essential Tremor Awareness Group).

We appreciate your support and if you have any questions please don’t hesitate to contact the IETF at 1-888-387-3667 or info@essentialtremor.org.

Wrapping Your Mind Around Head Tremor

(This is an article from a past issue of Tremor Talk magazine. It’s just a sampling of the stories we include in each issue. Annual donors to the IETF receive Tremor Talk magazine in the mail three times per year.)

By Arif Dalvi, MD, MBA
Director of the Comprehensive Movement Disorders Program
Palm Beach Neuroscience Institute 

Dr. Arif DalviThe term tremor refers to an involuntary shaking of any part of the body. While tremor in the hands is most common, head tremor can also occur. In patients with essential tremor, head tremor can be an isolated symptom or may occur in combination with hand tremor. Essential tremor is by far the most common cause of head tremor. Another cause is cervical dystonia, also known as spasmodic torticollis. Head tremor may also occur in patients with Parkinson’s disease. Stroke, head injury, and multiple sclerosis are other causes of tremor but are less likely to cause head tremor.

Hyperexcitability and rhythmic activity in the circuits of the brain are believed to be the underlying mechanism for tremor. One such circuit includes three areas deep in the brain called the red nucleus, the inferior olivary nucleus (ION), and the dentate nucleus. This circuit is responsible for fine-tuning voluntary movements. Proper function prevents any undershoot or overshoot of movements. An abnormal response in this circuit, especially within the ION, can lead to tremor.

Approximately 95 percent of patients with essential tremor present with hand tremor. However, about 35 percent of patients have head tremor either by itself or in conjunction with hand tremor. Some patients also have voice tremor. Hand tremor occurs mostly with posture, such as when holding an object away from the body and against gravity. This contrasts with hand tremor in Parkinson’s disease that occurs when the hands are at rest. Muscle rigidity, slowness of movement, change in posture and gait also occur with Parkinson’s disease but are uncommon with essential tremor. A lip or chin tremor may also be seen in patients with Parkinson’s disease.

Cervical dystonia can be another cause of head tremor. Dystonia refers to a state of abnormal muscle tone leading to painful muscle spasms and abnormal posturing of a part of the body. When the muscle spasms and abnormal posture affect the neck it is referred to as cervical dystonia. Sustained abnormal posturing of the head is a hallmark of cervical dystonia. An enlargement of the neck muscles may be observed in cervical dystonia but is unusual in essential tremor.

Other features include an asymmetric elevation of the shoulders, excessive eye blinking or blepharospasm, and spasms of the facial muscles. Like ET, cervical dystonia can spread to one or the other arm, in long-standing cases. However, unlike essential tremor the head tremor from cervical dystonia may be associated with neck pain due to dystonic spasms.

Patients with cervical dystonia may employ sensory tricks to reduce the severity of the tremor. Touching the cheek or chin (a geste antagoniste) is a commonly employed sensory trick. Head tremor with cervical dystonia has a directional component and is usually worse when looking in one direction and reduced when looking in the opposite direction. It may be possible when examining the individual to find a head position where the tremor almost disappears. This position is referred to as a “null point”.

The diagnosis of tremor remains a clinical diagnosis. An MRI or CT scan of the brain is usually ordered to rule out structural lesions such as stroke, multiple sclerosis or a midbrain tumor. In patients where there is a question of whether the problem is essential tremor or parkinsonism, a DaTscan may be ordered. This scan is targeted towards the dopamine transporter (DaT) in the brain which is deficient in parkinsonism but normal in essential tremor. Blood tests to rule out hyperthyroidism and, in younger patients, screening tests for Wilson’s disease may also be considered.

The treatment of tremor is guided by the underlying cause. Propranolol and primidone are the mainstay of treatment for essential tremor. Other medication options that are helpful include gabapentin and topiramate. Cervical dystonia may respond to treatment with benzodiazepines. Clonazepam, which is a long-acting benzodiazepine, may be preferred in comparison to shorter acting drugs such as alprazolam or lorazepam. Baclofen can reduce dystonia by acting on GABAB receptors. Tizanidine is an alternative to baclofen. However, since tizanidine can cause liver damage (in rare cases), monitoring of liver enzymes for the first six months is recommended.

Botulinum toxins can play a role in the treatment of head tremor, particularly in dystonic head tremor. Botulinum toxins block the release of neurotransmitters. This results in decreased transmission of the signal from nerve ending to the muscle, thus reducing the tremor. Repeat injections are required every three to four months.

Deep brain stimulation (DBS) surgery was approved by the FDA in 1997 for the treatment of tremor. However, the target in the brain varies based on the condition being treated. DBS surgery carries an approximately two percent risk of bleeding in the brain, hence it is only offered to patients with advanced tremor that is disabling and not controlled by medications. Head tremor can be more difficult to control than hand tremor and may require DBS surgery to be done on both sides of the brain.

Non-pharmacological methods to reduce head tremor rarely provide sustained benefit. Physical therapy is generally not useful, however, relaxation techniques can help reduce tremor as anxiety is often an exacerbating factor. There is no specific diet that is helpful but reducing caffeine intake can help reduce tremor.

Not every person with ET will be affected by head tremor. But if you are, it is important to talk to your physician so you understand what it is and what treatment options are best for you.

 

 

 

Having a Positive Impact on Those Who Struggle with Lifelong Conditions

Each semester, the International Essential Tremor Foundation presents four scholarships to students with essential tremor. The scholarships represent hope for the future, and provide support to these students during a pivotal time in their lives. As part of the scholarship application process, each applicant is asked to write an essay that answers the question, “How has essential tremor affected my life?” The following essay is from one of our fall 2018 scholarship recipients

 

By Deirdre Maciak,
Student Salem State University
Salem, MA

Essential tremor (ET) has affected me physically and emotionally, and has also played a role in my future career plans. I began noticing ET when I was in middle school, and was officially diagnosed as a sophomore in high school.

Photo of Deirdre Maciak, 2018 scholarship recipientPhysically it has affected me when I work out at the gym, play saxophone in my various school bands, and is worse when I’m tired or stressed out. I have tried a couple of medicines so far to treat it, and am working to determine what the right level of medicine is for me for now.

Emotionally it has affected my confidence level, especially when I realized how noticeable it had become. I sometimes hold off on activities I would like to do because of the ET, but am learning to manage the condition more proactively and look forward to being able to try new treatments in the future.

ET has also impacted my career choice to a degree as well. I am looking to pursue either nursing or biology in college, partly because I want to be able to have a positive impact on others who struggle with lifelong conditions. I also want to have the opportunity to either research new drugs or related treatments that would make the lives of those who deal with these types of conditions better.

I recently learned that a family friend, who is a research scientist, is actually working on a new drug for neurological disorders, which was very exciting. This type of work is intriguing to me.

I am very excited to start my college career this fall. While I know that ET will have some impact on me, I am becoming more confident that it’s a condition that I will be able to manage during these upcoming college years. I hope to both benefit from future ET treatments and, also have the chance to work on them as part of my future career path.

*********

Interested in supporting students with ET during their educational journey? Make a donation to the ET scholarship fund online.

Educating Others About Invisible Disabilities, Including Essential Tremor

Each semester, the International Essential Tremor Foundation presents four scholarships to students with essential tremor. The scholarships represent hope for the future, and provide support to these students during a pivotal time in their lives. As part of the scholarship application process, each applicant is asked to write an essay that answers the question, “How has essential tremor affected my life?” The following essay is from one of our fall 2018 scholarship recipients

 

By Megan Hartley,
Student at Florida Southern College

When I was 15, I was diagnosed with essential tremor. In March 2018, my 15-year-old sister was diagnosed with essential tremor. This letter is for her.

You have heard all the negative experiences that have been a part of my diagnosis: the accusations that I stole my grandmother’s handicap because I couldn’t possibly have one of my own; being bullied because I got extra time on exams that I “didn’t need;” and not being able to walk after a long day. People will be cruel because they do not understand.

What I want you to know is that it isn’t something that has to define you or be completely negative; so many positives have come out of it for me. It has allowed me to better understand what it is truly like to have a diversity that no one understands. It has pushed me to try to educate those who do not understand invisible disabilities in a positive way.

In the spring of 2016, I was allowed the opportunity to be on the cover and to speak out about what it is like to have anxiety and essential tremor for the International Essential Tremor Foundation’s magazine, Tremor Talk.

At Florida Southern alone, in my role as a resident advisor, I have been able to design community-wide programs that encourage students to ask questions and to get knowledge about those diversities they do not understand. The series that went on to win community program of the year included invisible disabilities, culture and identity. I have had the opportunity to present at the Florida Resident Advisor Conference and took home an award for my presentation about invisible disabilities inclusion in the residence halls.

Quote about invisible disabilitiesThis semester, I am partnering with other campus organizations to promote invisible disabilities week on campus in October. I have had the opportunity to do multiple projects and papers about disabilities and their relationship to the world around us. You are able to combat the negativity by allowing it to be an education opportunity for those around you.

Overall, what I want you to understand, is that, for me, the positives outweigh the negatives. I believe that essential tremor has allowed me to be a more compassionate person. Though I cannot speak to every diversity, I feel as though I can understand what it is like to have your identity questioned simply because it is not seen from the outside.

Though some days the tremors make it difficult to stand, I will always stand up for those who need it.

*********

Interested in supporting students with ET during their educational journey? Make a donation to the ET scholarship fund online.

 

 

‘It’s the Man Who Overcomes Adversity that is the True Champion’

Each semester, the International Essential Tremor Foundation presents four scholarships to students with essential tremor. The scholarships represent hope for the future, and provide support to these students during a pivotal time in their lives. As part of the scholarship application process, each applicant is asked to write an essay that answers the question, “How has essential tremor affected my life?” The following essay is from one of our fall 2018 scholarship recipients

 

By Robbie Holder,
Georgia Southern University

I do not remember a time when my hands did not noticeably shake. I was diagnosed with essential tremor (ET) at the early age of 14. While I recognized I was not the only Photo of Robert Holder, 2018 IETF Scholarship Recipientperson to experience tremors of this nature, I didn’t know anyone my age who suffered from this diagnosis. My other has ET and her grandmother suffered from it also; therefore, my diagnosis was not unexpected as it is hereditary. Since that time, I have reconciled myself with the knowledge that ET isn’t curable. I have found peace with the fact that I will always have a tremor. I haven’t used my diagnosis as an excuse to quit or avoid certain tasks, but have chosen to work harder in order to succeed.

My mother is an artist and while having a tremor makes it more difficult for her to create art, she doesn’t let it stop her from doing what she loves. She has to intensely focus on the task at hand. She has made adjustments to accomplish daily tasks. Like my mom, I have learned to adapt in order to accomplish tasks that come easily for others. I struggle to open packets, eat with a spoon, peel shrimp, button clothes, brush my teeth and insert contacts. Utilizing both hands, I have more control of my movements.

ET can be frustrating. I enjoy physical activities and working with my hands. My goal is to study exercise science. ET makes it difficult, but not impossible.

I have not let my ET keep me from doing the things I love. I truly believe it’s the little things in life that make a difference. With my family’s help, I built a Little Pantry for my community during my senior year in high school and I continue to run it today. Those in need obtain food and household items without the stigma of being seen as helpless. Others in the community can make a difference by restocking the pantry. Despite the frustrations I encountered during the pantry’s construction, I feel that I have made a difference and continue to do so.

I have been inspired by a quote that I keep close to my heart. It’s by Jock Ewing:

“Any man can win when things go his way. It’s the man who overcomes adversity that is the true champion.”

The challenges I face daily have made an impact on my life. I have to worker harder, persevere when faced with challenges, and find strength from within. These challenges have made me resilient, hard-working and confident. I choose to be strong. I have a desire to succeed and a strong work ethic. I finish what I start and I don’t let anything get in my way.

I know ET will always be a part of my life, but it will not define who I am. I choose to overcome.

*********

Interested in supporting students with ET during their educational journey? Make a donation to the ET scholarship fund online.

 

 

Essential Tremor Has Strengthened My Resolve

Each semester, the International Essential Tremor Foundation presents four scholarships to students with essential tremor. The scholarships represent hope for the future, and provide support to these students during a pivotal time in their lives. As part of the scholarship application process, each applicant is asked to write an essay that answers the question, “How has essential tremor affected my life?” The following essay is from one of our fall 2018 scholarship recipients.

 

By Graham Gaddis,
University of Tennessee

As the sixth child in a family of 16 children I am sometimes overlooked, but if we met for a personal interview you would learn how capable I am.

Photo of Graham Gaddis, IETF Scholarship RecipientIn the shadows and in the quiet, I have found an identity, and much of this identity has developed from facing head-on the difficulties of living with essential tremor (ET). I realize that having ET has actually strengthened my resolve to tackle life’s challenges and achieve my personal goals.

The process of living with ET has also enabled me to focus on my genuine priorities. I don’t have the time or the energy to be pressured to be someone else or simply please someone else. As a result of ET, I have learned to stand in my own skin and really pursue my own interests. For example, I am the fifth kid to go to college in my immediate family. My father, aunt and uncle are physicians. I have three sisters who are registered nurses and my brother is studying engineering. Therefore, most people thought I would enter college in a STEM field (science, technology, engineering, math). But my future dreams include farming and food production. I have chosen to major in a field that is completely new to my family, but that I am sincerely passionate about. I think this boldness to pursue a degree unfamiliar to my large extended family has developed as I found courage dealing with my essential tremor.

It has not been easy to struggle daily to spread peanut butter on my sandwich bread, assemble a bookcase with 80 screws dropping them over and over again, or have to practice, in private, my penmanship so that it would be legible. I don’t really like that I spill a drink if it is too full. These things are not “fun”, but in the scope of the greater things in life I can still do everything that God has called me to do. I can shower those whom I love with kindness. I can contribute to my community and have a legacy of faithfulness. I can be sympathetic to the trials and difficulties others face and help in their time of need.

I know I can walk through the challenges of having essential tremor and I can still find joy in all of the areas of life that really matter.

*********

Interested in supporting students with ET during their educational journey? Make a donation to the ET scholarship fund online.

 

Clinical Trials Are Vital to Improving Medical Care

Manish Gupta has over 15 years of experience in developing and executing global clinical trials in cardiac and neurological devices (including those developed to manage essential tremor). He shares how clinical trials work and how the IETF partners with Cala Health to recruit participants. 

 

By Manish Gupta
Vice President of Clinical Affairs
Cala Health, Inc.

Photo of Manish Gupta with Cala HealthClinical trials are research studies that explore whether a medical device, drug or treatment is safe and effective for humans. These studies also may show which medical approaches work best for certain illnesses, diseases, disorders or groups of patients. Clinical trials produce the most reliable data available for health care decision making. They follow strict scientific standards to protect patients and help produce dependable study results.

Clinical trials are one of the final stages of a long and careful research process. The process often begins in a laboratory, where scientists/technologists first develop and test new ideas. If an approach seems promising, the next step for higher risk devices may involve animal testing. This shows how the approach affects a living body and assesses its safety. However, an approach that works well in the lab or animals may not always work well in people. Thus, research in humans is needed.

For safety purposes, clinical trials start with small groups of patients to find out whether a new approach causes any harm. In later phases of clinical trials, researchers learn more about the new approach’s risks and benefits in larger groups of patients.

Quote from Manish Gupta for Research Month blogA clinical trial may find that a new device, drug or treatment

1) improves patient outcomes; or
2) offers no benefit; or
3) causes unexpected harm

All of these results are important because they advance medical knowledge and help improve patient care.

Patients participating in research are generally referred to as “subjects.” During a clinical trial, doctors, nurses, social workers, and other health care providers might be part of the subject’s treatment team. They will monitor the subject’s health very closely, conducting more tests and medical exams than standard care.

Taking part in a clinical trial can have many benefits. If a new treatment is proven to work, subjects are among the first to benefit.  Even if subjects don’t directly benefit from the clinical trial, the information gathered can help others and add to scientific knowledge. People who take part in clinical trials are vital to the process of improving medical care. Many subjects volunteer because they also want to help others.

Many government agencies, companies, patient advocacy groups and other organizations sponsor clinical trials. Collaboration between two or more of such groups/organizations is common in clinical research to create patient awareness about the clinical research and the disease. Cala Health’s collaboration with International Essential Tremor Foundation (IETF) is one great example of a partnership that creates patient awareness throughout the United States about essential tremor (ET) clinical trials. Cala Health, Inc. is actively conducting ET clinical trials of its wrist-worn therapy at leading centers in the US.

IETF is an essential partner to Cala Health informing the ET community of the clinical research opportunities to advance medical knowledge and patient care.

* * * * * * * * *

About Cala Health, Inc.
Cala Health is a medical technology company pioneering a new class of electrical medicine. The company is merging innovations in neuroscience and electronics to deliver individualized, prescription neuromodulation therapies. These therapies treat chronic disease non-invasively by stimulating peripheral nerves with body-worn electronics. The company is headquartered in the San Francisco Bay Area and backed by leading investors in both healthcare and technology, including Johnson & Johnson Innovation – JJDC, Inc., Corp, Lux Capital, Lightstone Ventures, GV, dRx Capital and Action Potential Venture Capital.

The IETF funds research grants, advocates for more research on essential tremor, and works with companies like Cala Health to recruit participants for research studies. Your donations to research are the reason the IETF is able to carry out these initiatives and work toward improving the quality of life for every generation living with essential tremor. Help us keep hope alive.

 

 

 

 

 

 

 

 

 

Studying Neuron Signals to Find Relief from Essential Tremor

Dr. Huanghe Yang is the head researcher on the IETF’s 2017 funded study, “Elucidating the Roles of the Ca2+-activated Ion Channels in Essential Tremor.” This blog from him shows how detail-oriented this research study is and his depth of knowledge in this subject area.  

  

Photo of Dr. Huanghe Yang, from Duke University School of MedicineBy Huanghe Yang, PhD
Duke University School of Medicine

The exact pathogenesis mechanism (or manner of development) of essential tremor (ET) is still unclear. We do know, however, abnormal neuronal firing directly causes the ET phenotypes (characteristics or traits). Thus, various means to correct the abnormal neuronal firing in the key brain regions for tremor genesis have been developed to improve the life quality of ET patients.

In order to develop more effective ET therapy, we need to have better understanding on how neuronal firing goes awry in ET. Neurons are ‘excitable’, meaning that they can fire electrical signals called ‘action potentials’. These electrical signals can be rapidly propagated from one end of a neuron to the another end, thereby enabling fast information relay from one neuron to its targeting neurons. When the electrical signals fire at abnormal frequency, serious neurological disease will occur, including but not limited to ET, ataxia and epilepsy.

Neuronal firing is controlled by a group of electrogenic proteins residing on cell surface, called ion channels. Ion channels, like dams of water reservoirs, control charged ions to flux across cell membranes. When open, they quickly allow ions to go down their gradients, resulting in change of membrane voltage, thus generating electric signal. Ion channels, thus, are a class of essential proteins that control a cell’s electrical activities. Thus far, many ion channels have been identified to be associated with various neurological disorders.

Voltage-gated calcium channels (VGCCs) are absolutely required for all neurons. Increase of membrane voltage will open the VGCCs and allow calcium ions to flush into a neuron. This calcium influx will not only further alter membrane voltage, but also quickly increase intracellular calcium concentration. During evolution, calcium has been selected as a universal and master regulator of numerous cellular processes. Therefore, the activities of the VGCCs need to be tightly regulated. Too much or too little activities of the VGCCs will lead to severe diseases such as cardiac arrhythmias, epilepsy, ataxia and migraine.

The exact roles of the VGCCs in human ET pathogenesis have not been clearly dissected. Yet interestingly, the involvement of VGCCs in tremorgenesis in rodent models has long been established. In fact, in a routine rodent ET model, a VGCC in the inferior olivary (IO) nucleus is believed to be the major target of harmaline, a psychoactive alkaloid drug from hallucinogenic plants. Injection of harmaline into rodents quickly and reliably activates the VGCCs in IO neurons, resulting in severe tremor.

We recently discovered that in addition to the VGCCs, IO neurons also express various types of calcium-activated ion channels, including calcium-activated chloride channels (CaCC) and calcium-activated large conductance potassium (BK) channels and calcium-activated small conductance potassium (SK) channels. These calcium-activated ion channels stay in close proximity to the VGCCs and form a highly dynamic and balanced feedback network with the VGCCs. Once calcium influxes through the VGCCs, the calcium-activated channels will quickly respond; and the subsequent chloride and potassium flux through these channels will quickly change membrane voltage and in turn, shut down VGCCs. Indeed, when we genetically deleted the CaCC in IO neurons, the mice had severe defect on learning new motor tasks.

With the generous support from International Essential Tremor Foundation, we have been further exploring the dedicated interactions between the VGCCs and the calcium activated ion channels in the IO, one of the key brain region for ET tremorgenesis. We have discovered that there are multiple types of VGCCs in IO neurons, which have long been believed only express the P/Q type and T type VGCCs. We are currently dissecting the contributions of each type of VGCCs and their downstream calcium-activated ion channels in mouse tremorgenesis. Our findings will help understand the basic mechanism of tremorgenesis.

We aim to translate our findings into novel therapeutic interventions to alleviate tremor symptoms and lessen functional disability associated with ET.

* * * * *

July is a time with the IETF draws awareness to its many research initiatives: funding research grants, advocating for more research on essential tremor,  recruiting for research studies, and more. Your generosity is the reason the IETF is able to carry out these initiatives and work toward improving the quality of life for every generation living with essential tremor. Help us keep hope alive. Donate today.