Restless legs syndrome pathophysiology: Difference between revisions

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Revision as of 18:05, 30 March 2018

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]Associate Editor(s)-in-Chief: Mohamadmostafa Jahansouz M.D.[2]

Overview

Pathophysiology

Pathogenesis

Generally most scientists consider restless legs syndrome(RLS) as a central nervous system (CNS)-related disorder, but no specific lesion has been found to be associated with the syndrome.

It is thought that RLS is the result of central nervous system anatomic lesions.
Findings in imaging of CNS witch suggest the relation between the anatomic lesions in CNS and RLS include:
- Presence of morphologic changes in the somatosensory cortex, motor cortex and thalamic gray matter in MRI
- Abnormal bilateral cerebellar and thalamic activation during the manifestation of sensory symptoms, with additional red nucleus and reticular formation activity during periodic leg movements (PLMS), in functional MRI study.
- Evidences of the role of the limbic and opioid systems in SPECT and PET studies
- Low brain iron concentrations and dysfunction of iron metabolism and intracellular iron
  - The "iron-dopamine model" explains that iron deficiency in the brain causes an abnormality in the dopaminergic system leading to manifestation of RLS.

RLS symptoms seem to depend on abnormal spinal sensorimotor integration at the spinal cord level and abnormal central somatosensory processing
In animal models, studies suggest that the All dopaminergic system and the D3 receptor participates in RLS symptoms

Genetics

Genes involved in the pathogenesis of RLS include: RLS 1: 12q and RLS 2: 14q and RLS 3: 9p and RLS 4: 2q and RLS 5: 20p.
40% of cases of RLS are familial and are inherited in an autosomal dominant fashion with variable penetrance.

Associated Conditions

Restless Legs Syndrome and Acidosis

Another possible explanation of RLS is acidosis, though this claim needs to be explored further. RLS as a result of acidosis/insufficient oxygen being circulated to the legs (which reduces acid build up) would explain why symptoms worsen when the legs are at rest, and why moving them (increasing circulation) offers some relief. The fact that iron offers relief for many can be explained by its vital role in hemoglobin, which is responsible for oxygen dispersion to the tissues. The legs would be more prone to the restless condition since they are furthest from the heart and lungs. Additionally, one may see below that many of the "lifestyle changes and other non-medicinal approaches" are related in some way or form to circulation (e.g. heat, stretching, movement), acid build up (e.g. too much exercise, ketosis from high-fat diets), or the amount of oxygen being dispersed in the blood (e.g. deep breathing, iron levels). It should be noted that this potential causal relationship between RLS and acidosis is purely speculative the time being, as far as the contributing editor is aware. If this causal relationship holds true, then finding the cause of the acidosis would most likely lead to the best treatment.

Some experts believe RLS and periodic limb movement disorder are strongly associated with ADHD in some children. Both conditions are hereditary and dopamine is believed to be involved. Many types of medication for both conditions are affecting the dopamine levels in the brain.^[1]

Gross Pathology

On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].

Microscopic Pathology

The exact neuroanatomical substrate imbalance which causes restless legs syndrome (RLS) is unknown.
Chronic ischemic changes were found in some brain tissue samples of patients whit RLS

References

↑ http://www.umm.edu/patiented/articles/other_disorders_associated_with_attention-deficit_disorder_000030_5.htm

Template:WH Template:WS

[1] ttp://www.umm.edu/patiented/articles/other_disorders_associated_with_attention-deficit_disorder_000030_5.htm

[1]

@@ Line 3: / Line 3: @@
 {{CMG}}{{AE}}{{MMJ}}
 ==Overview==
-The exact pathogenesis of [disease name] is not fully understood.
-OR
+==Pathophysiology==
-It is thought that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
+===Pathogenesis===
+*Generally most scientists consider restless legs syndrome(RLS) as a central nervous system (CNS)-related disorder, but no specific lesion has been found to be associated with the syndrome.
-OR
+* It is thought that RLS is the result of central nervous system anatomic lesions.
+* Findings in imaging of CNS witch suggest the relation between the anatomic lesions in CNS and RLS include:
+** Presence of morphologic changes in the somatosensory cortex, motor cortex and thalamic gray matter in MRI
+** Abnormal bilateral cerebellar and thalamic activation during the manifestation of sensory symptoms, with additional red nucleus and reticular formation activity during periodic leg movements (PLMS), in functional MRI study.
+** Evidences of the role of the limbic and opioid systems in SPECT and PET studies
+** Low brain iron concentrations and dysfunction of iron metabolism and intracellular iron
+*** The "iron-dopamine model" explains that iron deficiency in the brain causes an abnormality in the dopaminergic system leading to manifestation of RLS.
-[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
+* RLS symptoms seem to depend on abnormal spinal sensorimotor integration at the spinal cord level and abnormal central somatosensory processing
+* In animal models, studies suggest that the All dopaminergic system and the D3 receptor participates in RLS symptoms
-OR
+==Genetics==
+*Genes involved in the pathogenesis of RLS include: RLS 1: 12q and  RLS 2: 14q and RLS 3: 9p and RLS 4: 2q and RLS 5: 20p.
+*40% of cases of RLS are familial and are inherited in an [[autosomal dominant]] fashion with [[variable penetrance]].
-Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
+==Associated Conditions==
-OR
+===Restless Legs Syndrome and Acidosis===
+Another possible explanation of RLS is acidosis, though this claim needs to be explored further. RLS as a result of acidosis/insufficient oxygen being circulated to the legs (which reduces acid build up) would explain why symptoms worsen when the legs are at rest, and why moving them (increasing circulation) offers some relief. The fact that iron offers relief for many can be explained by its vital role in hemoglobin, which is responsible for oxygen dispersion to the tissues. The legs would be more prone to the restless condition since they are furthest from the heart and lungs. Additionally, one may see below that many of the "lifestyle changes and other non-medicinal approaches" are related in some way or form to circulation (e.g. heat, stretching, movement), acid build up (e.g. too much exercise, ketosis from high-fat diets), or the amount of oxygen being dispersed in the blood (e.g. deep breathing, iron levels). It should be noted that this potential causal relationship between RLS and acidosis is purely speculative the time being, as far as the contributing editor is aware. If this causal relationship holds true, then finding the cause of the acidosis would most likely lead to the best treatment.
+Some experts believe RLS and periodic limb movement disorder are strongly associated with ADHD in some children. Both conditions are hereditary and dopamine is believed to be involved. Many types of medication for both conditions are affecting the dopamine levels in the brain.<ref>http://www.umm.edu/patiented/articles/other_disorders_associated_with_attention-deficit_disorder_000030_5.htm</ref>
-[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
-OR
-The progression to [disease name] usually involves the [molecular pathway].
-OR
-The pathophysiology of [disease/malignancy] depends on the histological subtype.
-==Pathophysiology==
-===Pathogenesis===
-*The exact pathogenesis of [disease name] is not fully understood.
-OR
-*It is understood that [disease name] is the result of / is mediated by / is produced by / is caused by either [hypothesis 1], [hypothesis 2], or [hypothesis 3].
-*[Pathogen name] is usually transmitted via the [transmission route] route to the human host.
-*Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
-*[Disease or malignancy name] arises from [cell name]s, which are [cell type] cells that are normally involved in [function of cells].
-*The progression to [disease name] usually involves the [molecular pathway].
-*The pathophysiology of [disease/malignancy] depends on the histological subtype.
-==Genetics==
-*[Disease name] is transmitted in [mode of genetic transmission] pattern.
-*Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
-*The development of [disease name] is the result of multiple genetic mutations.
-==Associated Conditions==
 ==Gross Pathology==
@@ Line 53: / Line 35: @@
 ==Microscopic Pathology==
-*On microscopic histopathological analysis, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
+*The exact neuroanatomical substrate imbalance which causes restless legs syndrome (RLS) is unknown.
+*Chronic ischemic changes were found in some brain tissue samples of patients whit RLS
-==Overview==
-As with many diseases with diffuse symptoms, there is controversy among physicians, if RLS is a distinct syndrome. The US National Institute of Neurological Diseases and Stroke publishes an information sheet <ref>[http://www.ninds.nih.gov/disorders/restless_legs/detail_restless_legs.htm Restless Legs Syndrome Fact Sheet]</ref> characterizing the syndrome but acknowledging it is a difficult diagnosis. Some physicians doubt that RLS actually exists as a legitimate clinical entity, but believe it to be a kind of "catch-all" category, perhaps related to a general heightened [[sympathetic nervous system]] (SNS) response that could be caused by any number of physical or emotional factors. Other clinicians associate it with lumbosacral spinal subluxations and life stress.
-==Pathophysiology==
-Restless legs syndrome (RLS), which is also sometimes referred to as [[Jimmy legs|Jimmy Legs]], may be described as uncontrollable urges to move the limbs to stop uncomfortable or odd sensations in the body, most commonly in the legs, but can also be in the arms and torso. Moving the affected body part modulates the sensations, providing temporary relief.
-The sensations – and the need to move – may return immediately after ceasing movement, or at a later time. RLS may start at any age, including early childhood, and is a progressive disease for a certain portion of those afflicted, although the symptoms have disappeared permanently in some sufferers.
-===Genetics===
-% of cases of RLS are familial and are inherited in an [[autosomal dominant]] fashion with [[variable penetrance]].
-No one knows the exact cause of RLS at present.  Research and brain autopsies have implicated both dopaminergic system and iron insufficiency in the [[substantia nigra]] (study published in Neurology, 2003).<ref>{{cite journal | author = Connor J, Boyer P, Menzies S, Dellinger B, Allen R, Ondo W, Earley C | title = Neuropathological examination suggests impaired brain iron acquisition in restless legs syndrome. | journal = Neurology | volume = 61 | issue = 3 | pages = 304-9 | year = 2003 | id = PMID 12913188}}</ref> Iron is an essential cofactor for the formation of L-dopa, the precursor of dopamine.  An Icelandic study in 2005 confirmed the presence of an RLS susceptibility gene also found previously in a smaller French-Canadian population.<ref>{{cite journal | author = Desautels A, Turecki G, Montplaisir J, Sequeira A, Verner A, Rouleau G | title = Identification of a major susceptibility locus for restless legs syndrome on chromosome 12q. | journal = Am J Hum Genet | volume = 69 | issue = 6 | pages = 1266-70 | year = 2001 | id = PMID 11704926}}</ref><ref>{{cite journal | author = Levchenko A, Montplaisir J, Dubé M, Riviere J, St-Onge J, Turecki G, Xiong L, Thibodeau P, Desautels A, Verlaan D, Rouleau G | title = The 14q restless legs syndrome locus in the French Canadian population. | journal = Ann Neurol | volume = 55 | issue = 6 | pages = 887-91 | year = 2004 | id = PMID 15174026}}</ref> Various studies suggest chromosome 12q may indicate susceptibility to RLS.<ref>Christopher J. Earley, M.B., B.Ch., Ph.D., "Restless Legs Syndrome" ''New England J Medicine'' 2003; 348:2103 - 9.</ref>
-===Restless Legs Syndrome and Acidosis===
-Another possible explanation of RLS is acidosis, though this claim needs to be explored further. RLS as a result of acidosis/insufficient oxygen being circulated to the legs (which reduces acid build up) would explain why symptoms worsen when the legs are at rest, and why moving them (increasing circulation) offers some relief. The fact that iron offers relief for many can be explained by its vital role in hemoglobin, which is responsible for oxygen dispersion to the tissues. The legs would be more prone to the restless condition since they are furthest from the heart and lungs. Additionally, one may see below that many of the "lifestyle changes and other non-medicinal approaches" are related in some way or form to circulation (e.g. heat, stretching, movement), acid build up (e.g. too much exercise, ketosis from high-fat diets), or the amount of oxygen being dispersed in the blood (e.g. deep breathing, iron levels). It should be noted that this potential causal relationship between RLS and acidosis is purely speculative the time being, as far as the contributing editor is aware. If this causal relationship holds true, then finding the cause of the acidosis would most likely lead to the best treatment.
-Some experts believe RLS and periodic limb movement disorder are strongly associated with ADHD in some children. Both conditions are hereditary and dopamine is believed to be involved. Many types of medication for both conditions are affecting the dopamine levels in the brain.<ref>http://www.umm.edu/patiented/articles/other_disorders_associated_with_attention-deficit_disorder_000030_5.htm</ref>
 ==References==
 {{reflist|2}}
 [[Category:Sleep disorders]]