Ask the Mito Doc – February 2026: Understanding MELAS
All answers today are based on personal experience of the participants. As always, please consult your personal physician prior to taking any action.
Topic: Understanding MELAS and Current Treatments/Therapies
Speaker: Amel Karaa, MD, Massachusetts General Hospital
Q: Are the “stroke like episodes” the same as metabolic strokes in MELAS?
A: Stroke-like episodes can be interchangeably described as metabolic strokes. And what that means is that they don’t follow the typical blood vessel territory within their brain. So someone who has high blood pressure or high cholesterol, when they get a stroke and we look at their brain images, we do see that the stroke is happening around a blood vessel that gets clogged or that gets ruptured, and that’s where the stroke is happening. For MELAS, the reason why we call it a stroke-like lesions, stroke-like episode, is because they can present similarly to a stroke with the same symptoms that I discussed. So you can have seizures, you can have weakness in any part of your body, you can have difficulty with your speech, you can have vision problems. You can look like you’re having any other stroke. But when we look at the brain MRI, the brain images, those strokes are happening in different areas of the brain. Usually, it’s in the back and the sides of the brain, and they don’t follow the blood vessel territory, and so that’s why they are called metabolic stroke, because what’s causing them is not really a blood vessel that gets clogged, blocked or ruptures, but because brain tissue itself is not having enough energy, so it starts exhibiting symptoms of cell death and swelling and all of that. And so, stroke-like episodes can present in any neurological way, most often associated with vision changes, because it happens in the area of the brain that controls the vision. And to be able to call it a real stroke-like episode, you have to have brain images that show that there is a lesion in the brain that does not typically follow a blood vessel territory.
Q: In MELAS does the age of onset of disease manifestations predict disease severity such that earlier age onset typically leads to more severe/progressive disease?
A: At the present time, unfortunately, we don’t have any validated tools that can reliably predict disease severity or the timing of the symptoms onset, or the expected trajectory that each patient is going to have and the progression. In any individual patient we’d like to do that, and a lot of people are working to try to figure out how to do that. But just looking at the heteroplasmy level in different tissue is not going to be that much helpful because of all the variability we observe within the same body, within the same person and within different people. So what we can say is that the brain and the nervous system and the muscles are highly affected by this disease. So these are the two major systems that get affected.
Q: Do stroke like events always show visually in brain imaging and can you see past episodes in imaging? Why and how does Arginine Help?
A: We in the US tend to treat our patients with stroke like episodes by giving them intravenous L arginine. And that came about because a group in Japan many years ago have used L arginine they published that they see a more rapid improvement in the symptoms with L arginine. And if they gave L arginine chronically they were able to prevent maybe some of these strokes to happen. And so in the US we adopted the IV use of L arginine. But the problem is the treatment with arginine does not slow down the progression of the disease or revert the cognitive issues that the patient might have. And so we continue to do it because we don’t have another option. But I can tell you that in Europe and in other parts of the world they don’t at all use IV arginine. And in fact in this last meeting we had in November, it was clearly stated that we still don’t have enough information to understand whether L arginine or L citrine or taurine are really helpful whether in IV form or oral form. Because there has have never been robust clinical trial looking at their effect in a population of MELAS patients who are receiving them versus another population of patients who are not receiving them. And so these remain what we call empirical treatment. We give them because we have high hopes that they work biologically. It makes sense. Arginine improves blood flow to the brain and when you’re having a stroke like episode, having more oxygen in your in your brain can be helpful. But we don’t have robust scientific information to really corroborate that assumption. The other thing to note that all of these studies that were done out of Japan, they really focused on the 3243 mutation.
Q: I was told that Quercetin could be effective in treatment for mitochondrial disease. What are your thoughts?
A: I put that in the same bucket as a lot of other supplements and new compounds that are being trialed in many different diseases and being published in the lay press. There’s a lot of stuff going on out there that claims to improve mitochondrial function and mitochondrial longevity and all of that. The problem is in order for something to be safe and to work in our mitochondrial disease patient, they have to have gone through a very rigorous process of clinical trials that are well regulated. It’s enticing to read about something and to want to try it because patients are desperate and we do understand it’s very frustrating to live with these symptoms and to try to do anything you can, but a mitochondrial disease patient has a disabled body, a disabled metabolism that doesn’t always handle drugs the same way as other people. And a lot of the stuff out there is really marketing marketed for people who are getting older, who want to just to improve and boost their energy level. It’s not intended for patient with a mitochondrial disease metabolism. So I would caution people to really discuss any of these things with their treating physician, to look at the scientific evidence and to look at their individual cases and to make an informed decision as to whether or not these supplements could be helpful in their specific situation or not. And also a lot of the time it depends on what the specific disease is and what the specific mutation is and what it is causing biochemically, because sometimes these supplements can be more detrimental if you take them in your specific disease than could be helpful.
Q: I am 44 years old and I recently learned the story of a woman with MELAS who was my age when she was diagnosed with 38% heteroplasmy. She died from metabolic meltdown 4 years later. I have been diagnosed with MIDD MELAS with 73% heteroplasmy so I can’t help wondering if I am in even more danger than she was based on that. Does heteroplasmy percentage correlate with life expectancy in any ways? Thank you for your work to help us!
A: Heteroplasmy is very tricky. So when we are doing genetic testing, the only heteroplasmy that we can check is the heteroplasmy within the tissue that we are testing. So if we’re testing blood, that’s the blood heteroplasmy that we’re looking at. It doesn’t really tell us what the brain heteroplasmy is, or what the muscle heteroplasmy is. We can sometimes do buccal swab or urine test to look at the heteroplasmy, but again, that doesn’t really tell us about everything else going on in the body. Urine heteroplasmy seems to be the best correlation to what’s going on in the muscle, but we’re not always able to do urine because we don’t have enough clinical labs in the US who do urine testing for the whole mitochondrial DNA genome and so technically, the higher the heteroplasmy, we assume the more severe the disease might be, and maybe the earlier the onset the disease might be. And that is true for specific mitochondrial DNA variant or mutation. But for the 3-2-4-3, the most common variant that causes MELAS, that theory does not hold true, because I can tell you all of us seeing patients, we have patient with 3-2-4-3 mutation that have 90% heteroplasmy. I have those patients, they have more than 90% heteroplasmy, and they don’t have any symptoms, and I have patients with 10 or 12% heteroplasmy and they have MELAS. And so for 3-2-4-3, all the theory goes out of the window and we cannot really correlate the heteroplasmy level with the age of onset, the severity or what the prognosis would look like. We can do that for some other mitochondrial DNA, but not for the 3-2-4-3.