Individual differences |
Methods | Statistics | Clinical | Educational | Industrial | Professional items | World psychology |
Hypokalemic periodic paralysis is a rare channelopathy characterized by muscle weakness or paralysis with a matching fall in potassium levels in the blood. In individuals with this mutation, attacks often begin in adolescence and are triggered by strenuous exercise followed by rest, high carbohydrate meals, meals with high sodium content, sudden changes in temperature, and even excitement, noise or flashing lights. Weakness may be mild and limited to certain muscle groups, or more severe full body paralysis. 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 tests, and the diagnosis is instead called thyrotoxic periodic paralysis.
Patients often report years wasted with wrong diagnosis, wrong treatments, deadends and multiple doctors, test and clinics. The CMAP (Compound Muscle Amplitude Potential) test, also called the exercise EMG or X-EMG, is diagnostic in 70-80% of cases when done correctly. Besides the patient history or a report of serum potassium low normal or low during an attack, the CMAP 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. Standard 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.
People with hypokalemic periodic paralysis are aften misdiagnosed as having a conversion disorder or hysterical paralysis since the weakenss 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 dismiss the disorder as psychiatric.
Treatment of hypokalemic periodic paralysis focuses on preventing further attacks and relieving acute symptoms. Avoiding carbohydrate-rich meals, strenuous exercise and other identified triggers, and taking acetazolamide (Diamox) or another carbonic anhydrase inhibitor, may help prevent attacks of weakness. Some patients also take potassium-sparing diuretics such as spironolactone to help maintain potassium levels.
Paralysis attacks can be managed by drinking one of various potassium salts dissolved in water (debate exists over which, if any one in particular, is best used, but potassium chloride and bicarbonate are common). Rapidly absorbed boluses of liquid potassium are generally needed to abort an attack, but some patients also find positive maintenance results with time-released potassium tablets. IV potassium is seldom justified unless the patient is unable to swallow. Daily potassium dosage may need to be much higher than for potassium replacement from simple hypokalemia: 100-150 mEqs of potassium is often needed to manage daily fluctuations in muscle strength and function.
The prognosis for periodic paralysis varies. Overactivity, bad diet or simply an unfortunate gene mutation can lead to a type of chronic, low level weakness called an "abortive attack," or to permanent muscle damage. Abortive attacks often respond to extra potassium, cutting carbohydrates, getting plenty of rest, increasing doses of medication and gentle daily exercise such as short walks. Permanent muscle weakness is just what it sounds like, permanent, irreparable damage to the muscles. Vacuoles and tubular aggregates form and destroy healthy muscle tissue. This type of damage should show on a muscle biopsy. Not even anabolic steroids can bring these damaged muscles back.
Life span is expected to be normal, but attacks can drop potassium to levels low enough to cause life threatening breathing problems or heart rhythm difficulties. Patients often report muscle pain and cognitive problems during attacks. Migraines occur in up to 50% of all hypokalemic periodic paralysis patients and may include less common symptoms like phantom smells, sensitivity to light and sound or loss of words. Medical literatures states that muscle strength is normal between attacks, but patients tell a different story. "Normal" for them is not exactly the same as "normal" for everyone else.
Because there are dozens of possible gene mutations, some drugs and treatments that work fine for one patient will not work for another. For example, most patients do well on acetazolamide, but some don't. Some patients will do well with extra magnesium (the body's natural ion channel blocker) or fish oil, while these same nutrients will make other patients worse. Patients and care givers should take extreme caution with all new drugs and treatment plans.
Mutations in the following genes can cause hypokalemic periodic paralysis:
|HOKPP1||170400||CACNA1S (a voltage-gated calcium channel Cav1.1 found in the transverse tubules of skeletal muscle cells)||1q32|
|HOKPP2||613345||SCN4A (a voltage-gated sodium channel Nav1.4 found at the neuromuscular junction)||17q23.1-q25.3|
Action potentials from the central nervous system cause end-plate potentials at the NMJ which causes sodium ions to enter and depolarise the muscle cells. This depolarisation propagates to the T-tubules where it triggers the entry of calcium ions via Cav1.1 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.
Mutations altering the usual structure and function of these channels therefore disrupts regulation of muscle contraction, leading to episodes of severe muscle weakness or paralysis. Mutations have been identified in arginine residues making up the voltage sensor of Nav1.4. This voltage sensor comprises the S4 alpha helix of each of the four transmembrane domains (I-IV) of the protein, and contains basic residues that only allow entry of the positive sodium ions at appropriate membrane voltages by blocking or opening the channel pore. In Cav1.1, mutations have also been found in domains II and IV. These mutations are loss-of-function, such that the channels cannot open normally.
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 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.
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.
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.
- ↑ Kung AW (July 2006). Clinical review: Thyrotoxic periodic paralysis: a diagnostic challenge. J. Clin. Endocrinol. Metab. 91 (7): 2490–5.
- ↑ "Sternberg D et al. (2009) Hypokalemic Periodic Paralysis, in GeneReviews "
- ↑ "Segal MM, Jurkat-Rott K, Levitt J, Lehmann-Horn F, Hypokalemic periodic paralysis - an owner's manual"
- ↑ (Apr 2007). Genotype-phenotype correlation and therapeutic rationale in hyperkalemic periodic paralysis.. Neurotherapeutics 4 (2): 216–24.
- ↑ OMIM 604433
- ↑ Rüdel R, Lehmann-Horn F, Ricker K, Küther G. Hypokalemic periodic paralysis: in vitro investigation of muscle fiber membrane parameters. Muscle Nerve. 1984 Feb;7(2):110-20.
- ↑ Jurkat-Rott K, Lehmann-Horn F. Muscle channelopathies and critical points in functional and genetic studies. J Clin Invest. 2005 Aug;115(8):2000-9.
- National Library of Medicine. Hypokalemic periodic paralysis
- Practical aspects in the management of hypokalemic periodic paralysis by Dr. Jacob O Levitt, a dermatologist who has hypokalemic periodic paralysis.
-  The Periodic Paralysis Newsdesk
-  The Periodic Paralysis Assoc.
-  Muscular Dystrophy Assoc. page on Periodic Paralysis
- GeneReview/NIH/UW entry on Hypokalemic Periodic Paralysis
Diseases of myoneural junction and muscle / neuromuscular disease (G70–G73, 358–359)
|This page uses Creative Commons Licensed content from Wikipedia (view authors).|
<ref>tags exist, but no
<references/>tag was found