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Dr. Natelson is a rare neurologist interested in ME/CFS.

Dr. Natelson, MD, is nothing if not unusual. For one, he’s a neurologist interested in ME/CFS. (His clinic bio states, “Dr. Benjamin H. Natelson is the only neurologist on the East Coast expert in the diagnosis and care of patients with severe fatigue and/or body-wide pain for which there is no apparent medical explanation.”) Not only is he interested in ME/CFS and similar diseases, but he has been for decades and has written several books on it, including his 2007 book, “Your Symptoms Are Real: What to Do When Your Doctor Says Nothing Is Wrong.“ 

Natelson treats chronic fatigue syndrome (ME/CFS), fibromyalgia (FM), and long-term COVID patients at his Pain and Fatigue Center in Mt. Sinai. In the early 2000s, he ran one of the three NIAID-funded ME/CFS research centers and, in 2013, uncovered a new form of orthostatic intolerance in ME/CFS. He was also one of seven ME/CFS physicians to participate in the Multi-site Clinical Assessment of ME/CFS (MCAM) study produced by the CDC.

He scored his first NIH ME/CFS grant in 1992 and is a rare ME/CFS researcher who has pretty consistently been able to get them. Over time, he’s co-authored over 100 papers on ME/CFS, fibromyalgia, Gulf War Illness and, most recently, long COVID.

Early on, Natelson debunked the somatization hypothesis of ME/CFS by showing a diagnosis of somatization disorder simply depended on whether one’s symptoms were coded as psychiatric or physical. With his research consistently turning up physiological abnormalities, the somatization hypothesis was dropped.

In 2007, Natelson appears to have been the first to uncover hypocapnia (low CO2 levels) in ME/CFS. His 2013 study came to the surprising conclusion that ME/CFS patients without depression had worse neurological test results, more fMRI abnormalities (usually in the frontal lobe), worse physical functioning, more spinal fluid abnormalities (white blood counts/protein concentrations), more reduced blood flows in the brain, and higher brain lactate levels than ME/CFS patients with depression.

Natelson is currently working on a large R01 NIH grant, “A Cardiovascular Analysis of Post-exertional Malaise,” and a smaller one, “Structural and Metabolic Neuroimaging of ME/CFS Occurring with and without COVID-19 Infection,” and he was eager to discuss them.

A Neurologist Gets Hooked on ME/CFS – in 1988

First, though, I wanted to know how he—a neurologist—happened to become interested in ME/CFS several decades ago, when finding a neurologist who believed in ME/CFS was like finding a needle in a haystack.

Serendipity, as it often does, played a role. Overwhelmed by the AIDS epidemic, Jim Molesky, a pediatric immunologist at Rutger University, had to give up his ME/CFS patients in the late 1980s. Dr. Natelson took over, decided “there is something going on with them,” and started collecting blood and doing analyses.

When the NIH announced that it was setting up ME/CFS Centers of Excellence in the early 90s, Natelson applied for one and got it – surprising the ME/CFS community, as he was not well known. He kept the Center until the early 2000s when the NIAID decided that ME/CFS was neither immunological nor infectious and closed the Centers.

In 2000, he moved to Mount Sinai, which he said was, “way better than the Rutgers Medical School because it’s full of people way smarter than me, and I love to be surrounded by smart people”.

Current Projects…Participants Needed!

Dr. Natelson is based in New York City. You’d think in a city of that size that, finding people with ME/CFS to participate in a study would be a cinch, but that’s not always true.

Cardiovascular Study

When he introduced Dr. Donna Mancini to ME/CFS and long COVID, Dr. Natelson brought an experienced exercise cardiologist into the mix. In their second study together ( “A Cardiovascular Analysis of Post-exertional Malaise” ), Drs. Natelson and Mancini will study the effect of two exercise stress tests on breathing patterns, fluid loss, stroke volume, and symptoms activity using a wearable device in 40 severe, 40 non-severe, and 40 matched controls.

They believe that the drop in oxygen consumption at the ventilatory threshold (VO2VT) found in the second exercise test is due to the fluid loss caused by sweating and deep rapid breathing during exercise. They’ll determine if a saline IV taken before the second test can mitigate the fluid loss and help with exercise. This is the first ME/CFS study to assess the effects of exercise on blood volume—a big deal in itself. Why blood volume has received so little attention in this disease is a mystery…

The study will also determine if ME/CFS and long COVID exhibit one of two abnormal breathing patterns during exercise. On the subject of breathing…

He and Julian Stewart were the first to find (and name) “POSH” (Postural Orthostatic Syndrome of Hyperventilation) in ME/CFS. POSH refers to overbreathing, or hyperventilation, that occurs when upright. Dr. Natelson’s 2022 study found that it was more common than any other form of orthostatic intolerance.

Overbreathing/hyperpnea/hyperventilation – whatever you want to call it – produces symptoms such as dizziness or lightheadedness, shortness of breath, abdominal bloating and belching, fatigue, feeling weak, cognitive and sleep problems, numbness and tingling sensations, muscle spasms, chest pain, and palpitations.

• Find out how to do a home (Postural Hypocapnic) hyperventilation test

One is “overbreathing” or hyperventilating, which appears to be caused by metabolic issues. One way to check if you are overbreathing is to stop your ears and see if you can hear yourself breathe. Another symptom of overbreathing is frequent yawning or sighing. Both suggest that you are moving too much air. This is not fast breathing; it’s overly deep breathing, which causes too much CO2 to be removed from the lungs.

Overbreathing, or hyperventilation, can be caused by several things, including lactic acidosis (a drop in pH due to a buildup of lactic acid, due to anaerobic respiration), dysfunctional mitochondria (resulting in increased anaerobic respiration), and an inability of cells to extract and use oxygen efficiently, as well as some others. The overbreathing, then, can easily be explained by findings in ME/CFS; indeed, it would be expected.

Dr. Natelson said the overbreathing can be treated with biofeedback, i.e., the nervous system can be retaught how to breathe properly and avoid the low CO2 levels and the symptoms they cause. He found a device from China that is affordable (Contec Veterinary Use Capnograph $250.) and tells his patients to buy it and give it a shot. (Perhaps its approval for veterinary use is keeping the cost down.)

The first thing to measure is how fast you’re breathing. If you’re breathing more than 15x’s a minute – that’s too fast. Then you just use the machine to adjust your breathing to get your CO2 levels up to normal levels (35x or higher).  He said there are all sorts of tricks to do that. There are also apps that can help with overbreathing.

A Different Cause of POTS?

Dr. Natelson noted his studies indicate that some people with ME/CFS do not overbreathe when they are lying down, but as soon as they sit up, they do. The overbreathing then turns on the heart rate—and you have POTS—but the overbreathing may come first in some cases.

He also believes that the bedrest caused by this disease is also producing dysautonomia in some people. Substantial bed rest reduces blood volume, which causes overbreathing in an attempt to get more oxygen to the tissues when standing. This then turns up the heart rate, i.e. POTS. They haven’t found a low blood volume/POTS connection in everyone, but they do in some patients.

I noted that I probably became deconditioned when I first became ill but that now I get from 7-8,000 steps a day of gentle, slow walking. Dr. Natelson called that “gentle physical conditioning”, recommended it, and suggested that people read the chapter on walking in his book “Your Symptoms Are Real: What to Do When Your Doctor Says Nothing Is Wrong”.

He recommended that everyone try the NASA lean test. He uses oral rehydration solution (Trioral), compression tights (from the ankles all the way to the waist), an abdominal binder to keep the blood from pooling there, and, if necessary, drugs.

• Find out how to do the NASA lean test here.

Breathing Issue #2: Strange Sighing Pattern

The Natelson-Cook exercise study found that some people with ME/CFS have, as he put it, a “funny sighing like breathing pattern” when they exercise. As the intensity of exercise increases, you should be bringing more and more air in, but these people would bring more air in, then dip, bring more air in, and then dip. Why this is happening they don’t know but will explore it in the study.

Participation: It’s not required, but they’re particularly looking for ME/CFS patients who have sedentary relatives to participate in the test. Anyone who lives within 50-60 miles of New York city is eligible and they’ll pay for a hotel stay.

If you are interested in participating in the study, contact The Pain and Fatigue Lab at 212-844-6768 or 212-844-6665 or benjamin.natelson@mountsinai.org.

• Dr. Natelson noted that he’s on the hunt for a junior scientist who knows about breathing to help them understand these breathing patterns.

The Brain Study

The “Structural and Metabolic Neuroimaging of ME/CFS Occurring with and without COVID-19 Infection” study will use advanced 7 Tesla MRI neuroimaging techniques to examine oxygen uptake and glucose utilization in the brain. It will also assess changes in oxygen metabolism in the venous blood of the sagittal sinus and global cerebral blood flows.

The sagittal sinus.

The sagittal sinus is where cerebral spinal fluid and interstitial fluid from the brain drain into the venous blood. As such, it could play a role in several potential problems in ME/CFS and long COVID including toxin accumulations, neuroinflammation, increased intracranial pressure, cerebral spinal fluid leaks, and cognitive issues. Any blockage or dysfunction there can contribute to neurodegenerative diseases.

Given the high rates of intracranial hypertension (high cerebral spinal fluid pressure), it wouldn’t be surprising if some patients had problems in the sagittal sinuses.

• Learn more about intracranial hypertension in ME/CFS

Indeed, a case report found that parts of the sagittal sinuses were narrowed in a woman in “a long and debilitating history of chronic fatigue syndrome“. This woman had borderline increased intracranial pressure, but after some cerebral spinal fluid was removed she “felt exceptionally well—headache free, less tired, and (had) reduced body pains—for 4 days before reverting to her baseline state”. Putting stents in to improve the fluid flows “brought about a life-changing remission of symptoms with no regression in 2 years of follow-up.”

The sagittal sinuses are just one of many areas where blood flows may be being interrupted in some people with these diseases.

The study won’t assess blood flows to the brain but will assess what is happening to the blood in the brain. It will allow them to determine “whether energy failure is present in individuals with ME/CFS and long-COVID.”

(This study may be (?) doing in the brain what David Systrom has been doing with his invasive exercise testing in the body: assessing oxygen levels as they enter and leave the brain to determine how much is being used up. Systrom has found that oxygen is not used up in the normal amounts by the muscles during exercise in some people with ME/CFS – resulting in reduced energy production.)

• Contact xiang.xu@mssm.edu about being in the study

The Other ME/CFS / Long-COVID Brain Study 

Dr. Natelson mentioned that his co-researcher on the study, Dr. Xiang Xu, also just got a major R01 grant, “Structural and Metabolic Neuroimaging of ME/CFS Occurring with and without COVID-19 Infection“, funded by NINDS.

Dr. Xu will assess cerebral energy metabolism in people with ME/CFS, long COVID and healthy controls. Dr. Xu’s preliminary results – increased oxygen extraction in the brains of long-COVID patients – suggested that reduced brain blood flows were causing the brain to gobble up as much oxygen as it could get from the blood it had, and/or that dysfunctional mitochondria were present.

Dr. Xu will measure oxygen extraction fraction (how much oxygen is being taken up), cerebral blood flow (how much blood is present in the brain), and cerebral metabolic rate of oxygen and glucose uptake (the rate at which the brain is consuming oxygen and glucose). The brain uses 20% of the body’s oxygen, and the neurons use glucose for energy. It was great to see Dr. Xu get an ME/CFS group in there!

• Coming up – a talk with Dr. Natelson about his new vagus nerve study.