Periodic paralysis
Encyclopedia
Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis (rarely death) from common triggers such as cold, heat, high carbohydrate
meals, not eating, stress or excitement and physical activity of any kind. The underlying mechanism of these diseas es are malfunctions in the ion channel
s in skeletal muscle
cell membrane
s that allow electrically charged ions to leak in or out of the muscle cell, causing the cell to depolarize and become unable to move (a channelopathy
).
The symptoms of periodic paralysis can also be caused by hyperthyroidism
, and are then labeled thyrotoxic periodic paralysis
; however, if this is the underlying condition there are likely to be other characteristic manifestations, enabling a correct diagnosis.
with considerable variation in penetrance
, leading to a spectrum of familial phenotype
s (only one parent needs to carry the gene mutation to affect the children, but not all family members who share the gene are affected to the same degree). Specific diseases include:
Also of note is that potassium levels do not have to range outside of normal limits to cause serious, even life-threatening paralysis. These diseases are not the same as having a very low level of potassium (hypokalemia
) or high potassium (hyperkalemia
) and must not be treated as such. The total body store of potassium is usually normal; it is just in the wrong place.
inhibitors (such as acetazolamide
or dichlorphenamide), taking supplemental oral potassium chloride
and a potassium-sparing diuretic
(for hypos) or avoiding potassium (for hypers), thiazide
diuretics to increase the amount of potassium excreted by the kidneys (for Hypers), and significant lifestyle changes including tightly controlled levels of exercise or activity. However, the exact gene mutation, the ion channel affected, and the amount of genetic change or expression can have significant impact on disability and treatment.
Treatment of Andersen-Tawil syndrome is similar to that for other types of periodic paralysis, with dichlorphenamide the drug of first choice. However, Pacemaker
insertion or an implantable cardioverter-defibrillator
may be required to control cardiac symptoms.
Also having potassium ions administered intravenously. Which will speed up recovery.
Carbohydrate
A carbohydrate is an organic compound with the empirical formula ; that is, consists only of carbon, hydrogen, and oxygen, with a hydrogen:oxygen atom ratio of 2:1 . However, there are exceptions to this. One common example would be deoxyribose, a component of DNA, which has the empirical...
meals, not eating, stress or excitement and physical activity of any kind. The underlying mechanism of these diseas es are malfunctions in the ion channel
Ion channel
Ion channels are pore-forming proteins that help establish and control the small voltage gradient across the plasma membrane of cells by allowing the flow of ions down their electrochemical gradient. They are present in the membranes that surround all biological cells...
s in skeletal muscle
Skeletal muscle
Skeletal muscle is a form of striated muscle tissue existing under control of the somatic nervous system- i.e. it is voluntarily controlled. It is one of three major muscle types, the others being cardiac and smooth muscle...
cell membrane
Cell membrane
The cell membrane or plasma membrane is a biological membrane that separates the interior of all cells from the outside environment. The cell membrane is selectively permeable to ions and organic molecules and controls the movement of substances in and out of cells. It basically protects the cell...
s that allow electrically charged ions to leak in or out of the muscle cell, causing the cell to depolarize and become unable to move (a channelopathy
Channelopathy
Channelopathies are diseases caused by disturbed function of ion channel subunits or the proteins that regulate them. These diseases may be either congenital or acquired .There are a large number of distinct dysfunctions known to be caused by ion channel...
).
The symptoms of periodic paralysis can also be caused by hyperthyroidism
Hyperthyroidism
Hyperthyroidism is the term for overactive tissue within the thyroid gland causing an overproduction of thyroid hormones . Hyperthyroidism is thus a cause of thyrotoxicosis, the clinical condition of increased thyroid hormones in the blood. Hyperthyroidism and thyrotoxicosis are not synonymous...
, and are then labeled thyrotoxic periodic paralysis
Thyrotoxic periodic paralysis
Thyrotoxic periodic paralysis is a condition featuring attacks of muscle weakness in the presence of hyperthyroidism . Hypokalemia is usually present during attacks...
; however, if this is the underlying condition there are likely to be other characteristic manifestations, enabling a correct diagnosis.
Types
Periodic paralysis is an autosomal dominant myopathyMyopathy
In medicine, a myopathy is a muscular disease in which the muscle fibers do not function for any one of many reasons, resulting in muscular weakness. "Myopathy" simply means muscle disease...
with considerable variation in penetrance
Penetrance
Penetrance in genetics is the proportion of individuals carrying a particular variant of a gene that also express an associated trait . In medical genetics, the penetrance of a disease-causing mutation is the proportion of individuals with the mutation who exhibit clinical symptoms...
, leading to a spectrum of familial phenotype
Phenotype
A phenotype is an organism's observable characteristics or traits: such as its morphology, development, biochemical or physiological properties, behavior, and products of behavior...
s (only one parent needs to carry the gene mutation to affect the children, but not all family members who share the gene are affected to the same degree). Specific diseases include:
- Hypokalemic periodic paralysisHypokalemic periodic paralysisHypokalemic periodic paralysis is a rare channelopathy characterized by muscle weakness or paralysis with a matching fall in potassium levels in the blood...
, where potassium leaks into the muscle cells from the bloodstream.
- Hyperkalemic periodic paralysisHyperkalemic periodic paralysisHyperkalemic periodic paralysis is a genetic disorder which occurs in both humans and horses, where it is also known as Impressive Syndrome. It is an inherited autosomal dominant disorder which affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood...
, where potassium leaks out of the cells into the bloodstream.
- Paramyotonia congenitaParamyotonia congenitaParamyotonia Congenita , also known as Paramyotonia congenita of von Eulenburg or Eulenburg disease, is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia...
, a form which often accompanies hyperkalemic periodic paralysis, but may present alone. The primary symptom of paramyotonia congenita is muscle contracture which develops during exercise or activity. Paramyotonia congenita attacks may also be triggered by a low level of potassium in the bloodstream. This means people with both hyperkalemic periodic paralysis and paramyotonia congenita can have attacks with fluctuations of potassium up or down.
- Andersen-Tawil syndromeAndersen-Tawil syndromeAndersen–Tawil syndrome, also called Andersen syndrome and Long QT syndrome 7, is a form of long QT syndrome. It is a rare genetic disorder, and is inherited in an autosomal dominant pattern.- Presentation :...
, a form of periodic paralysis that includes significant heart rhythm problems, fainting and risk of sudden death. Potassium levels may be low, high, or normal during attacks of ATS. Patients with ATS may also have skeletal abnormalities like scoliosisScoliosisScoliosis is a medical condition in which a person's spine is curved from side to side. Although it is a complex three-dimensional deformity, on an X-ray, viewed from the rear, the spine of an individual with scoliosis may look more like an "S" or a "C" than a straight line...
(curvature of the spine), webbing between the second and third toes or fingers (syndactylySyndactylySyndactyly is a condition wherein two or more digits are fused together. It occurs normally in some mammals, such as the siamang and kangaroo, but is an unusual condition in humans.-Classification:...
), crooked fingers (clinodactyly), a small jaw (micrognathia) and low-set ears.
Diagnosis
This disease is unusually difficult to diagnose. Patients often report years of wrong diagnosis and treatments that made them worse instead of better. Part of this may be that migraines are present in up to 50% of patients and can cause a confusing array of symptoms including headaches, speech difficulties and visual, auditory or sensory auras. DNA testing is available for only a half dozen common gene mutations, while dozens of known mutations are possible but are not routinely tested. EMG results will be normal except during attacks. A properly performed Exercise EMG (Compound Muscle Amplitude Potential Test) can provide an accurate diagnosis in better than 80% of cases. The old glucose/insulin provocative testing can cause life-threatening symptoms and should not be used.Also of note is that potassium levels do not have to range outside of normal limits to cause serious, even life-threatening paralysis. These diseases are not the same as having a very low level of potassium (hypokalemia
Hypokalemia
Hypokalemia or hypokalaemia , also hypopotassemia or hypopotassaemia , refers to the condition in which the concentration of potassium in the blood is low...
) or high potassium (hyperkalemia
Hyperkalemia
Hyperkalemia refers to the condition in which the concentration of the electrolyte potassium in the blood is elevated...
) and must not be treated as such. The total body store of potassium is usually normal; it is just in the wrong place.
Treatment
Treatment of the periodic paralyses usually includes carbonic anhydraseCarbonic anhydrase
The carbonic anhydrases form a family of enzymes that catalyze the rapid interconversion of carbon dioxide and water to bicarbonate and protons , a reversible reaction that occurs rather slowly in the absence of a catalyst...
inhibitors (such as acetazolamide
Acetazolamide
Acetazolamide, sold under the trade name Diamox, is a carbonic anhydrase inhibitor that is used to treat glaucoma, epileptic seizures, Idiopathic intracranial hypertension , altitude sickness, cystinuria, and dural ectasia...
or dichlorphenamide), taking supplemental oral potassium chloride
Potassium chloride
The chemical compound potassium chloride is a metal halide salt composed of potassium and chlorine. In its pure state, it is odorless and has a white or colorless vitreous crystal appearance, with a crystal structure that cleaves easily in three directions. Potassium chloride crystals are...
and a potassium-sparing diuretic
Potassium-sparing diuretic
Potassium-sparing diuretics are diuretic drugs that do not promote the secretion of potassium into the urine.They are used as adjunctive therapy, together with other drugs, in the treatment of hypertension and management of congestive heart failure....
(for hypos) or avoiding potassium (for hypers), thiazide
Thiazide
Thiazide is a term used to describe a type of molecule and a class of diuretics often used to treat hypertension and edema ....
diuretics to increase the amount of potassium excreted by the kidneys (for Hypers), and significant lifestyle changes including tightly controlled levels of exercise or activity. However, the exact gene mutation, the ion channel affected, and the amount of genetic change or expression can have significant impact on disability and treatment.
Treatment of Andersen-Tawil syndrome is similar to that for other types of periodic paralysis, with dichlorphenamide the drug of first choice. However, Pacemaker
Artificial pacemaker
A pacemaker is a medical device that uses electrical impulses, delivered by electrodes contacting the heart muscles, to regulate the beating of the heart...
insertion or an implantable cardioverter-defibrillator
Implantable cardioverter-defibrillator
An implantable cardioverter-defibrillator is a small battery-powered electrical impulse generator which is implanted in patients who are at risk of sudden cardiac death due to ventricular fibrillation and ventricular tachycardia. The device is programmed to detect cardiac arrhythmia and correct it...
may be required to control cardiac symptoms.
Also having potassium ions administered intravenously. Which will speed up recovery.