Unraveling the Pathophysiology of Res... - Restless Legs Syn...

Restless Legs Syndrome

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Unraveling the Pathophysiology of Restless Legs Syndrome from Multimodal MRI Techniques: A Systematic Review

MrCrow profile image
13 Replies

link to the paper: sciencedirect.com/science/a...

Notable excerpts:

“patients with primary RLS have structural and metabolite alterations, changes in multiple white matter tract architectures, and disrupted functional connectivity within multiple brain areas.”

”3.3.2. DTI

First, many “association pathways” mediating “intra-hemispheric” cortico-cortical connectivity were found to be affected; these include the (a) uncinate fascicle (UF; frontal and temporal connectivity) [51]; (b) cingulum (CG; cingulate gyrus and entorhinal cortex) [49], [51]; (c) superior longitudinal fasciculus (SLF; occipito-frontal connectivity) [51]; (d) inferior longitudinal fasciculus (ILF, occipito-temporal connectivity) [51] and (e) inferior fronto-occipital fasciculus (IFOF, temporal-frontal connection) [49], [51]. Next, weakened “inter-hemispheric” connectivity was evident from an altered integrity of “commissural pathways”; for example, corpus callosum (CC) [54]. Finally, (a) thalamo-cortical pathways, i.e., anterior and posterior thalamic radiations (ATR and PTR) [49], [50], [51] (b) projection fibers (cortex to the spinal cord), i.e., cortico-spinal tract (CST) [49], [51], internal capsule (IC) [43], and (c) brainstem-cerebellar tracts, i.e., superior cerebellar peduncles (SCP) [50] and corona radiata (CR) [50], also demonstrated integrity alterations (see references in Table 4).”

“3.3.3. fMRI

In addition to alterations in the “default mode network” (DMN) [60], [62], altered connectivity patterns were noted in the salience network [63], sensorimotor network [61], brainstem network [61], sensory thalamic network [56], [57], [59], [61], basal ganglia-thalamic network [61], dorsal and ventral attention networks [61], cingulate network [61], executive network [63], and cerebellar networks [63].”

“3.3.4. Iron-imaging MRI

A lower thalamic iron content in two datasets [66], [67] contrasts with the unchanged values noted by others [70]. The cerebellar dentate demonstrated either low [66] or unaltered levels [67], [70]. An increase [70], a decrease [69], or no alterations [40], [66], [67], [68] in red nucleus iron content were noted. Similar conflicting results were noted with regard to the iron contents of the basal ganglia and its sub-divisions. The majority of studies found an unchanged iron content of the caudate, pallidum, and substantia nigra and decreased/unchanged putaminal iron levels. Others, however, noted that the test results are driven by technical factors [69] (Table 5).”

“3.3.5. MRS

All the datasets analyzed thalamic metabolite alterations and found a significant increase in glutamatergic activity coexisting with unaltered GABA-ergic signaling [36], [71], [72], [75]. An increased level of NAA in the ACC has been noted [71].”

Also read the discussion section. Too long to list the content here.

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MrCrow
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Eryl profile image
Eryl

Not all RLS arises from brain malfunctions, some RLS arises from neuroinflammation in the nerves of other parts of the body. I've eliminated my RLS by driving down the systemic inflammation caused by foods.

WideBody profile image
WideBody

That is excellent find. Thank you. I can't seem to get access to the full study. When I do, I will attempt to read it. Give me about a year... wow.

SueJohnson profile image
SueJohnson in reply toWideBody

My laugh for the day - Give me about a year 🤣🤣🤣

MrCrow profile image
MrCrow in reply toSueJohnson

what do you think? is there hope for the future? by future i mean 10 - 20 years?

SueJohnson profile image
SueJohnson in reply toMrCrow

Haven't read it - too much in your excerpts I have no idea what it means.

MrCrow profile image
MrCrow in reply toSueJohnson

I mean in general. From all that you have read so far. Not just this article. Do you see any hope for better treatments in the future?

SueJohnson profile image
SueJohnson in reply toMrCrow

No idea but there is always hope.

WideBody profile image
WideBody in reply toMrCrow

I do see hope. Dr. Ferre (or something like that) published a lot of work on the Adenosine Hypothesis of RLS. Based on that research I now take Dipyridamole and it helps me tremendously . IIRC Dipyridamole is an ENT1/ENT2 blocker and we really only need an effective ENT2 blocker.

The big news is that Dopamine Agonist drugs can make things so much worse for those that don't have issue with their dopamine receptors.

MrCrow profile image
MrCrow in reply toWideBody

Is there any issue with loss of efficacy with Dipyridamole for RLS?

WideBody profile image
WideBody in reply toMrCrow

Yes, after about 20 months Dipyridamole is about 80% effective, down from 100 percent. Dipyridamole still takes away RLS 95-100%. The involuntary kicks and jerks start to come back, but they are not as strong and are more controllable.

Dipyridamole can be stopped with no side effects and taken on an as needed basis, i.e. Car or plane ride.

It's not perfect, but compared to the other medications I have been given, I wish this was given to me after my infusion, prior to gabapentin an of course DA drugs.

MrCrow profile image
MrCrow in reply toWideBody

Can u further increase the dose for higher efficacy? Maybe dose adjustments are kinda common in the first few months/years for several drugs ig.

WideBody profile image
WideBody in reply toMrCrow

I'm trying to get myself to NOT take it. Or in cycles, maybe off for a couple weeks. It's a crutch right now. Maybe after the holidays.

MrCrow profile image
MrCrow in reply toWideBody

Does going off for a few weeks being back the original efficacy?

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