Restless legs syndrome pathophysiology: Difference between revisions

Jump to navigation Jump to search
VisualWikitext
No edit summary
m (Bot: Removing from Primary care)
 
(5 intermediate revisions by 2 users not shown)
Line 3: Line 3:
{{CMG}}{{AE}}{{MMJ}}
{{CMG}}{{AE}}{{MMJ}}
==Overview==
==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|central nervous system (CNS)]]-related disorder, but no specific lesion has been found to be associated with the syndrome.<ref name="pmid19514512" />


OR
* It is thought that RLS is the result of [[central nervous system]] anatomic lesions.<ref name="pmid19514512">{{cite journal| author=Miyamoto M, Miyamoto T, Iwanami M, Suzuki K, Hirata K| title=[Pathophysiology of restless legs syndrome]. | journal=Brain Nerve | year= 2009 | volume= 61 | issue= 5 | pages= 523-32 | pmid=19514512 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19514512  }} </ref>
* Findings in imaging of [[CNS]] witch suggest the relation between the anatomic lesions in [[CNS]] and RLS include:<ref name="pmid19514512">{{cite journal| author=Miyamoto M, Miyamoto T, Iwanami M, Suzuki K, Hirata K| title=[Pathophysiology of restless legs syndrome]. | journal=Brain Nerve | year= 2009 | volume= 61 | issue= 5 | pages= 523-32 | pmid=19514512 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19514512  }} </ref><ref name="pmid27544840">{{cite journal| author=Li X, Allen RP, Earley CJ, Liu H, Cruz TE, Edden RAE et al.| title=Brain iron deficiency in idiopathic restless legs syndrome measured by quantitative magnetic susceptibility at 7 tesla. | journal=Sleep Med | year= 2016 | volume= 22 | issue=  | pages= 75-82 | pmid=27544840 | doi=10.1016/j.sleep.2016.05.001 | pmc=4992945 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=27544840  }} </ref><ref name="pmid15670702">{{cite journal| author=Etgen T, Draganski B, Ilg C, Schröder M, Geisler P, Hajak G et al.| title=Bilateral thalamic gray matter changes in patients with restless legs syndrome. | journal=Neuroimage | year= 2005 | volume= 24 | issue= 4 | pages= 1242-7 | pmid=15670702 | doi=10.1016/j.neuroimage.2004.10.021 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15670702  }} </ref><ref name="pmid28626420">{{cite journal| author=Guo S, Huang J, Jiang H, Han C, Li J, Xu X et al.| title=Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management. | journal=Front Aging Neurosci | year= 2017 | volume= 9 | issue=  | pages= 171 | pmid=28626420 | doi=10.3389/fnagi.2017.00171 | pmc=5454050 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28626420  }} </ref>
** Presence of morphologic changes in the [[somatosensory cortex]], [[motor cortex]] and thalamic [[Grey matter|gray matter]] in [[Magnetic resonance imaging|MRI]]
** Abnormal bilateral [[cerebellar]] and [[Thalamus|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 system|limbic]] and [[opioid]] systems in [[Single photon emission computed tomography|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
 
Following transmission/ingestion, the [pathogen] uses the [entry site] to invade the [cell name] cell.
 
OR
 
 
[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==
==Genetics==
*[Disease name] is transmitted in [mode of genetic transmission] pattern.
*[[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.<ref name="pmid19514512">{{cite journal| author=Miyamoto M, Miyamoto T, Iwanami M, Suzuki K, Hirata K| title=[Pathophysiology of restless legs syndrome]. | journal=Brain Nerve | year= 2009 | volume= 61 | issue= 5 | pages= 523-32 | pmid=19514512 | doi= | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=19514512  }} </ref>
*Genes involved in the pathogenesis of [disease name] include [gene1], [gene2], and [gene3].
*40% of cases of RLS are familial and are inherited in an [[autosomal dominant]] fashion with [[variable penetrance]].
*The development of [disease name] is the result of multiple genetic mutations.


==Associated Conditions==
==Associated Conditions==


==Gross Pathology==
Conditions which may be associated with RLS include:<ref name="pmid24747872">{{cite journal| author=Katsi V, Katsimichas T, Kallistratos MS, Tsekoura D, Makris T, Manolis AJ et al.| title=The association of Restless Legs Syndrome with hypertension and cardiovascular disease. | journal=Med Sci Monit | year= 2014 | volume= 20 | issue= | pages= 654-9 | pmid=24747872 | doi=10.12659/MSM.890252 | pmc=3999161 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=24747872  }} </ref><ref name="pmid18360657">{{cite journal| author=Cotter PE, O'Keeffe ST| title=Restless leg syndrome: is it a real problem? | journal=Ther Clin Risk Manag | year= 2006 | volume= 2 | issue= 4 | pages= 465-75 | pmid=18360657 | doi= | pmc=1936366 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=18360657  }} </ref><ref name="pmid26944272">{{cite journal| author=Trenkwalder C, Allen R, Högl B, Paulus W, Winkelmann J| title=Restless legs syndrome associated with major diseases: A systematic review and new concept. | journal=Neurology | year= 2016 | volume= 86 | issue= 14 | pages= 1336-43 | pmid=26944272 | doi=10.1212/WNL.0000000000002542 | pmc=4826337 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26944272  }} </ref>
*On gross pathology, [feature1], [feature2], and [feature3] are characteristic findings of [disease name].
*[[Hypertension]]
*[[Cardiovascular disease|Cardiovascular diseases]]
*[[Anxiety]]
*[[Depression]]
*[[Iron deficiency]]
*[[Anemia]]
*[[Kidney diseases]]
*[[Stroke (patient information)|Stroke]]
*[[Parkinson disease]]
*[[Polyneuropathy]]
*[[Multiple sclerosis]]


==Microscopic Pathology==
==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.<ref name="pmid15197711">{{cite journal| author=Pittock SJ, Parrett T, Adler CH, Parisi JE, Dickson DW, Ahlskog JE| title=Neuropathology of primary restless leg syndrome: absence of specific tau- and alpha-synuclein pathology. | journal=Mov Disord | year= 2004 | volume= 19 | issue= 6 | pages= 695-9 | pmid=15197711 | doi=10.1002/mds.20042 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15197711  }} </ref>
 
*Chronic [[Ischemia|ischemic]] changes were found in some brain tissue samples of patients whit RLS.<ref name="pmid15197711">{{cite journal| author=Pittock SJ, Parrett T, Adler CH, Parisi JE, Dickson DW, Ahlskog JE| title=Neuropathology of primary restless leg syndrome: absence of specific tau- and alpha-synuclein pathology. | journal=Mov Disord | year= 2004 | volume= 19 | issue= 6 | pages= 695-9 | pmid=15197711 | doi=10.1002/mds.20042 | pmc= | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=15197711  }} </ref>
 
 
 
 
==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===
40% 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==
==References==
{{reflist|2}}
{{reflist|2}}
 
{{WH}}
{{WS}}


[[Category:Sleep disorders]]
[[Category:Sleep disorders]]
[[Category:Syndromes]]
[[Category:Syndromes]]
[[Category:Neurology]]
[[Category:Neurology]]
[[Category:Primary care]]
{{WH}}
{{WS}}

Latest revision as of 23:58, 29 July 2020

Restless legs syndrome Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Restless legs syndrome from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X-ray

Echocardiography and Ultrasound

CT scan

MRI

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Restless legs syndrome pathophysiology On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Restless legs syndrome pathophysiology

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Restless legs syndrome pathophysiology

CDC on Restless legs syndrome pathophysiology

Restless legs syndrome pathophysiology in the news

Blogs on Restless legs syndrome pathophysiology

Directions to Hospitals Treating Psoriasis

Risk calculators and risk factors for Restless legs syndrome pathophysiology

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.[1]

Genetics

Associated Conditions

Conditions which may be associated with RLS include:[5][6][7]

Microscopic Pathology

  • The exact neuroanatomical substrate imbalance which causes restless legs syndrome (RLS) is unknown.[8]
  • Chronic ischemic changes were found in some brain tissue samples of patients whit RLS.[8]

References

  1. ↑ 1.0 1.1 1.2 1.3 Miyamoto M, Miyamoto T, Iwanami M, Suzuki K, Hirata K (2009). "[Pathophysiology of restless legs syndrome]". Brain Nerve. 61 (5): 523–32. PMID 19514512.
  2. ↑ Li X, Allen RP, Earley CJ, Liu H, Cruz TE, Edden RAE; et al. (2016). "Brain iron deficiency in idiopathic restless legs syndrome measured by quantitative magnetic susceptibility at 7 tesla". Sleep Med. 22: 75–82. doi:10.1016/j.sleep.2016.05.001. PMC 4992945. PMID 27544840.
  3. ↑ Etgen T, Draganski B, Ilg C, Schröder M, Geisler P, Hajak G; et al. (2005). "Bilateral thalamic gray matter changes in patients with restless legs syndrome". Neuroimage. 24 (4): 1242–7. doi:10.1016/j.neuroimage.2004.10.021. PMID 15670702.
  4. ↑ Guo S, Huang J, Jiang H, Han C, Li J, Xu X; et al. (2017). "Restless Legs Syndrome: From Pathophysiology to Clinical Diagnosis and Management". Front Aging Neurosci. 9: 171. doi:10.3389/fnagi.2017.00171. PMC 5454050. PMID 28626420.
  5. ↑ Katsi V, Katsimichas T, Kallistratos MS, Tsekoura D, Makris T, Manolis AJ; et al. (2014). "The association of Restless Legs Syndrome with hypertension and cardiovascular disease". Med Sci Monit. 20: 654–9. doi:10.12659/MSM.890252. PMC 3999161. PMID 24747872.
  6. ↑ Cotter PE, O'Keeffe ST (2006). "Restless leg syndrome: is it a real problem?". Ther Clin Risk Manag. 2 (4): 465–75. PMC 1936366. PMID 18360657.
  7. ↑ Trenkwalder C, Allen R, Högl B, Paulus W, Winkelmann J (2016). "Restless legs syndrome associated with major diseases: A systematic review and new concept". Neurology. 86 (14): 1336–43. doi:10.1212/WNL.0000000000002542. PMC 4826337. PMID 26944272.
  8. ↑ 8.0 8.1 Pittock SJ, Parrett T, Adler CH, Parisi JE, Dickson DW, Ahlskog JE (2004). "Neuropathology of primary restless leg syndrome: absence of specific tau- and alpha-synuclein pathology". Mov Disord. 19 (6): 695–9. doi:10.1002/mds.20042. PMID 15197711.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Restless_legs_syndrome_pathophysiology&oldid=1642836"