Thread by @Dysautonomia

An important @NIH study on ME/CFS published today. While there is a lot of helpful information in this study, we have concerns about the autonomic testing and skin biopsy portions of this study, which were missing key elements of standard testing. 1/🧵
nature.com/articles/s4146…

@NIH The authors conclude the abnormal autonomic tone they found is central in nature, but they did not assess parts of the peripheral autonomic nervous system known to be abnormal in prior ME/CFS research. 2/🧵

They did not perform QSART, which measures post-ganglionic sudomotor function. Sudomotor nerves are small fiber autonomic nerves. Abnormal QSART, suggestive of autonomic small fiber neuropathy, has been reported in about half of ME/CFS patients. 3/🧵ncbi.nlm.nih.gov/pmc/articles/P…

The did not look at sudomotor or vasomotor (autonomic small fiber) density on skin biopsy, which is known to be abnormal in some ME/CFS patients. 4/🧵

They did not evaluate the autonomic ganglia, an important part of the peripheral autonomic nervous system, before suggesting the autonomic abnormalities found must be central in nature. To be fair, there is no standardized way to assess autonomic ganglia in living patients. 5/🧵

There are multiple prior autopsy studies documenting ganglionitis in ME/CFS patients. Ganglia pathology has also been identified in related conditions like fibromyalgia, POTS, and in animal models of acute COVID. 6/🧵

They did tilt testing, but didn't screen for nOH or POTS, found in 30-90% of ME/CFS patients in prior studies. "Deep phenotyping" should, at a minimum, include a screening for well known easy to diagnose common comorbidiites. 7/🧵

They only recorded HR & BP in 4 minute increments (4, 8, 12, etc), even though the NIH lab where the tilts were done has a continuous beat-to-beat BP and HR device. nOH requires measuring BP at 3 minutes & POTS requires measuring HR & BP at 10 minutes. They didn't do this. 8/🧵

While we expect others will have additional critique, we do think there were some important findings in this study. Low DOPA, DOPAC, and DHPG suggests a common pathway, possibly low or improperly functioning tyrosine hydroxylase, the precursor to all of them. 9/🧵

Here's a dopamine/norepineprhine synthesis and metabolism diagram showing tyrosine hydroxylase is a shared pathway for DOPA, DOPAC and DHPG, which were all low in ME/CFS patients in the NIH study.
10/🧵 mdpi.com/1422-0067/24/1…

They also only did 2 small fiber skin biopsies, but 3 is the standard. They left out the proximal thigh, which would have been helpful to identify non-length dependent small fiber neuropathies, which are associated with ganglia pathology and immune mediated neuropathies. 11/🧵