1/
Why can multiple sclerosis symptoms worsen with heat exposure, something known as the Uhthoff phenomenon?
This question is especially relevant in the era of record-breaking heat waves and climate change.
#tweetorial #medtwitter
2/
In 1890, Wilhelm Uhthoff noted multiple sclerosis (MS) patients having a “marked deterioration of visual acuity during exercise" or after a hot bath, which ⬆️ body temperature.
1 patient lost vision just by walking vigorously in Uhthoff's clinic.
pubmed.ncbi.nlm.nih.gov/20375511/
3/
The Uhthoff phenomenon is now recognized as exceedingly common in MS.
Up to 80% of patients experience ⬆️ neurological symptoms w/ even small body temp increases. These can include diminished physical (eg gait) and cognitive (eg mental fog) function.
journals.sagepub.com/doi/abs/10.117…
4/
Strikingly, almost any source of increased body heat can trigger the Uhthoff phenomenon:
Fevers and hot weather can do it, but even things like sitting in a hot bath/jacuzzi or using a hair dryer (!).
ncbi.nlm.nih.gov/books/NBK47024…
5/
This 1959 case series vividly demonstrated the Uhthoff phenomenon in 14 MS patients.
9 were heated w/ infrared lamps and 4 were immersed in hot water baths.
Raising core body temps 0.5-2.5 deg F caused neurological symptoms in 13/14.
pubmed.ncbi.nlm.nih.gov/13655099/
6/
So what is the mechanism of the Uhthoff phenomenon?Why would heat worsen MS symptoms?
Let's quickly review MS pathogenesis.
7/
Recall that the hallmark pathology of MS involves autoimmune-mediated demyelination of central nervous system neurons.
This leads to impaired conduction of impulses between the Nodes of Ranvier, and slower overall axonal conduction.
ncbi.nlm.nih.gov/pmc/articles/P…
8/
Eventually a neurodegenerative phase can lead to progressive decline in neurological function.
pubmed.ncbi.nlm.nih.gov/24871874/
9/
Returning to the Uhthoff phenomenon, a 2004 study found that heat exposure led to decreased neuronal conduction in MS patients. This could be "rescued" by cold exposure.
Conduction in normal controls was unaffected by heat.
pubmed.ncbi.nlm.nih.gov/15465437/
10/
In the same study, both the amount of heat-induced neuronal conduction blockage and subjective impairment of neuronal function correlated w/ decreases in walking speed.
In essence, heat-induced impairment of nerve conduction led to objective neurological dysfunction.
11/
So why would heat slow conduction specifically in demyelinated neurons?
Neurons adapt to demyelination by adding additional axonal membrane Na channels, a process called ion channel adaptation, to try to maintain conduction speed...
pubmed.ncbi.nlm.nih.gov/30377640/
12/
But these new Na channels have altered physiologic properties so that they are more heat-sensitive, and CLOSE if the temperature increases even slightly.
This premature closure w/ ⬆️ temperature hyperpolarizes the axon and dramatically ⬇️ conduction.
pubmed.ncbi.nlm.nih.gov/23732530/
13/
Demyelinated axons also have excessive potassium efflux, which further hyperpolarizes the membrane and slows conduction, contributing to a predilection for the emergence of the Uhthoff phenomenon.
14/
In terms of treatment, active cooling re-opens closed Na channels and helps resolve symptoms.
The K channel blocker 4-Aminopyridine (4-AP), used for motor symptoms in MS, also improves axonal conduction by prolonging action potential duration.
pubmed.ncbi.nlm.nih.gov/23732530/
15/SUMMARY
🧠The Uhthoff phenomenon in MS involves worsening neurological symptoms w/ heat exposure
🧠Any source of increased body temperature can provoke
🧠It results from increased density of heat-sensitive Na channels in demyelinated axons, which close w/ increased temperature
Share this Scrolly Tale with your friends.
A Scrolly Tale is a new way to read Twitter threads with a more visually immersive experience.
Discover more beautiful Scrolly Tales like this.