Content deleted Content added
m Open access bot: doi added to citation with #oabot. |
Citation bot (talk | contribs) Add: doi-access. | Use this bot. Report bugs. | Suggested by Abductive | #UCB_webform 1942/3833 |
||
| (11 intermediate revisions by 7 users not shown) | |||
Line 22:
'''Hypokalemic periodic paralysis''' ('''hypoKPP'''), also known as '''familial hypokalemic periodic paralysis''' ('''FHPP'''),<ref>{{Cite book|title=Harrison's principles of internal medicine|others=Jameson, J. Larry; Kasper, Dennis L.; Longo, Dan L. (Dan Louis), 1949-; Fauci, Anthony S., 1940-; Hauser, Stephen L.; Loscalzo, Joseph|date=13 August 2018|isbn=978-1-259-64403-0|edition=20th|location=New York|pages=307|oclc=1029074059}}</ref> is a rare, [[autosomal dominant]] [[channelopathy]] characterized by muscle weakness or paralysis when there is a fall in [[potassium]] levels in the [[blood]]. In individuals with this mutation, attacks sometimes begin in [[adolescence]] and most commonly occur with individual triggers such as rest after strenuous exercise (attacks during exercise are rare), high [[carbohydrate]] meals, meals with high [[sodium]] content, sudden changes in temperature, and even excitement, noise, flashing lights, cold temperatures and stress. Weakness may be mild and limited to certain muscle groups, or more severe full-body paralysis. During an attack, reflexes may be decreased or absent. Attacks may last for a few hours or persist for several days. Recovery is usually sudden when it occurs, due to release of potassium from swollen muscles as they recover. Some patients may fall into an abortive attack or develop chronic muscle weakness later in life.
Some people only develop symptoms of periodic paralysis due to [[hyperthyroidism]] (overactive [[thyroid]]). This entity is distinguished with [[thyroid function test]]s, and the diagnosis is instead called [[thyrotoxic periodic paralysis]].<ref>{{cite journal |author=Kung AW |title=Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge |journal=J. Clin. Endocrinol. Metab. |volume=91 |issue=7 |pages=2490–5 |date=July 2006 |pmid=16608889 |doi=10.1210/jc.2006-0356
== Signs and symptoms ==▼
Hypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Attacks cause severe weakness or paralysis that usually lasts from hours to days. Some people may have episodes almost every day, while others experience them weekly, monthly, or only rarely. Attacks can occur without warning or can be triggered by factors such as rest after exercise, a viral illness, or certain medications. Often, a large, carbohydrate-rich meal or vigorous exercise in the evening can trigger an attack upon waking the following morning. Although affected individuals usually regain their muscle strength between attacks, some develop persistent muscle weakness later in life.<ref>{{cite web |title=Hypokalemic periodic paralysis: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/condition/hypokalemic-periodic-paralysis/ |website=medlineplus.gov |publisher=U.S. National Library of Medicine |
==Genetics==
Line 56 ⟶ 58:
[[Action potential]]s from the central nervous system cause [[end-plate potential]]s at the NMJ which causes sodium [[ion]]s to enter and depolarise the muscle cells. This depolarisation propagates to the T-tubules where it triggers the entry of calcium ions via Ca<sub>v</sub>1.1 as well as from the [[sarcoplasmic reticulum]] through the associated [[ryanodine receptor]] RyR1. This causes contraction (tensing) of the muscle. Depolarisation of the [[motor end plate]] causes potassium ions to leave the muscle cells, repolarising the muscle and closing the calcium channels. Calcium is pumped away from the contractile apparatus and the muscle relaxes.{{citation needed|date=September 2020}}
Mutations altering the usual structure and function of these channels therefore
In patients with mutations in SCN4A or CACNA1S, therefore, the channel has a reduced excitability and signals from the central nervous system are unable to depolarise the muscle. As a result, the muscle cannot contract efficiently (paralysis). The condition is hypokalemic (manifests when potassium is low; not "causing hypokalemia") because a low extracellular potassium ion concentration will cause the muscle to repolarise to the [[resting potential]] more quickly, so even if calcium conductance does occur it cannot be sustained. It becomes more difficult to reach the calcium threshold at which the muscle can contract, and even if this is reached then the muscle is more likely to relax. Because of this, the severity would be reduced if potassium ion concentrations are kept high.<ref>{{cite journal |vauthors=Rüdel R, Lehmann-Horn F, Ricker K, Küther G |title=Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters |journal=Muscle Nerve |volume=7 |issue=2 |pages=110–20 |date=February 1984 |pmid=6325904 |doi=10.1002/mus.880070205 |s2cid=25705002 }}</ref><ref>{{cite journal |vauthors=Jurkat-Rott K, Lehmann-Horn F |title=Muscle channelopathies and critical points in functional and genetic studies |journal=J. Clin. Invest. |volume=115 |issue=8 |pages=2000–9 |date=August 2005 |pmid=16075040 |pmc=1180551 |doi=10.1172/JCI25525 }}</ref><ref>{{cite journal|last=Kim|first=SJ|author2=Lee, YJ |author3=Kim, JB |title=Reduced expression and abnormal localization of the KATP channel subunit SUR2A in patients with familial hypokalemic periodic paralysis|journal=Biochemical and Biophysical Research Communications|date=January 2010|volume=391|issue=1|pages=974–8|doi=10.1016/j.bbrc.2009.11.177|pmid=19962959}}</ref>
Line 64 ⟶ 66:
In contrast, [[hyperkalemic periodic paralysis]] refers to gain-of-function mutations in sodium channels that maintain muscle depolarisation and therefore are aggravated by high potassium ion concentrations.{{citation needed|date=September 2020}}
This condition is inherited in an [[autosomal dominant]] pattern (but with a high proportion of sporadic cases), which means one copy of the altered gene in each cell is sufficient to cause the disorder.{{cn|date=July 2021}}
▲== Signs and symptoms ==
▲Hypokalemic periodic paralysis is a condition that causes episodes of extreme muscle weakness typically beginning in childhood or adolescence. Most often, these episodes involve a temporary inability to move muscles in the arms and legs. Attacks cause severe weakness or paralysis that usually lasts from hours to days. Some people may have episodes almost every day, while others experience them weekly, monthly, or only rarely. Attacks can occur without warning or can be triggered by factors such as rest after exercise, a viral illness, or certain medications. Often, a large, carbohydrate-rich meal or vigorous exercise in the evening can trigger an attack upon waking the following morning. Although affected individuals usually regain their muscle strength between attacks, some develop persistent muscle weakness later in life.<ref>{{cite web |title=Hypokalemic periodic paralysis: MedlinePlus Genetics |url=https://medlineplus.gov/genetics/condition/hypokalemic-periodic-paralysis/ |website=medlineplus.gov |publisher=U.S. National Library of Medicine |accessdate=26 October 2020 |language=en}} {{PD-notice}}</ref>
== Diagnosis ==
Diagnosis can be achieved through a specialized form of electromyographic (EMG) testing called the long exercise test. This test measures the amplitude of a nerve response (called the Compound Muscle Action Potential or CMAP) for 40 to 50 minutes following a few minutes of exercise. In affected patients, there is a progressive fall in the amplitude of the potential. Besides the patient history or a report of serum potassium low normal or low during an attack, the long exercise test is the current standard for medical testing. Genetic diagnosis is often unreliable as only a few of the more common gene locations are tested, but even with more extensive testing 20–37% of people with a clinical diagnosis of hypokalemic periodic paralysis have no known mutation in the two known genes.<ref>[https://www.ncbi.nlm.nih.gov/books/NBK1338/ "Sternberg D et al. (2009) Hypokalemic Periodic Paralysis, in GeneReviews "]</ref> Standard [[Electromyography|EMG]] testing cannot diagnose a patient unless they are in a full blown attack at the time of testing. Provoking an attack with exercise and diet then trying oral potassium can be diagnostic, but also dangerous as this form of PP has an alternate form known as [[hyperkalemic periodic paralysis]]. The symptoms are almost the same, but the treatment is different. The old [[glucose]] [[insulin]] challenge is dangerous and risky to the point of being life-threatening and should never be done when other options are so readily available.{{Citation needed|date=June 2010}} Factors known to trigger episodes are: stress, cold environment or hypothermia, carbohydrate load, infection, glucose infusion, metabolic alkalosis, alcohol, strenuous exercise, and steroids.{{cn|date=July 2021}}
People with hypokalemic periodic paralysis are often misdiagnosed as having a [[conversion disorder]] or hysterical paralysis since the weakness is muscle-based and doesn't correspond to nerve or spinal root distributions. The tendency of people with hypokalemic periodic paralysis to get paralyzed when epinephrine is released in "fight or flight" situations further adds to the temptation to misdiagnose the disorder as psychiatric.<ref>[
== Treatment ==
Line 100 ⟶ 99:
==Sources==
* {{cite journal |author=Levitt JO |title=Practical aspects in the management of hypokalemic periodic paralysis |journal=J Transl Med |volume=6 |pages=18 |year=2008 |pmid=18426576 |pmc=2374768 |doi=10.1186/1479-5876-6-18 |doi-access=free }} by Dr Jacob O Levitt, a dermatologist who has hypokalemic periodic paralysis.
== External links ==
Line 114 ⟶ 113:
| eMedicineSubj =
| eMedicineTopic =
| MeshID = D020514
| GeneReviewsNBK = NBK1338
| GeneReviewsName = Hypokalemic Periodic Paralysis
| |||