Periodic paralysis

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Periodic paralysis
Other namesMyoplegia paroxysmalis familiaris
Specialty Neurology   OOjs UI icon edit-ltr-progressive.svg

Periodic paralysis is a group of rare genetic diseases that lead to weakness or paralysis [1] 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 diseases are malfunctions in the ion channels in skeletal muscle cell membranes that allow electrically charged ions to leak in or out of the muscle cell, causing the cell to depolarize and become unable to move. [2]


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.


Periodic paralysis is an autosomal dominant myopathy with considerable variation in penetrance, leading to a spectrum of familial phenotypes (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:[ citation needed ]


One of the most common descriptions of periodic paralysis are episodic attacks of muscle weakness, which are commonly associated with serum potassium levels. Physical activity and diet content (carbohydrates) have been identified as PP triggers. Unlike non-dystrophic myotonias, the periodic paralysis phenotype is triggered after resting following exercise. Voltage-gated sodium channel (Nav1.4) mutations are among the key causes behind periodic paralysis. [3]

Hyper-kalemic PP (hyperPP) is identified with high extracellular potassium levels which are typically greater than 5 mM during attacks; however, HyperPP attacks can also take place without rise in potassium concentrations. HyperPP has a prevalence rate of 1/100,000. Patients become symptomatic around the age of 10. The weakness attacks in hyperPP are relatively short lasting, and range from minutes to hours. The attacks can happen upwards of ten times per month.[ citation needed ]

Hypo-kalemic PP (hypoPP) is associated with low potassium levels. The onset of hypoPP occurs between the ages of 15 and 35. The prevalence of hypoPP is estimated to 1/100,000. HypoPP can be triggered by many external factors such as stress, high-sugar diet, and rest after exercise. During hypoPP attacks, the serum potassium concentrations can drop to less than 3 mM. Furthermore, hypoPP attacks are considerably longer lasting than hyperPP. As exercise is a trigger for periodic paralysis attacks, recently there is more research going into the physiological changes that accompany exercise including changes in blood pH. [3]


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. Electromyography (EMG) findings are not specific but the McManis Protocol, also called the Compound Muscle Amplitude Potential test (CMAP) can be used by a skilled neurologist capable of utilizing the EMG, which can give assistance in diagnosing several of these PP disorders. The old glucose/insulin provocative testing can cause life-threatening symptoms and should not be used.[ citation needed ]

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.[ citation needed ]


Treatment of the periodic paralyses may include carbonic anhydrase inhibitors (such as acetazolamide, methazolamide 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, treatment should be tailored to the particular type of periodic paralysis. [4] [5] [6]

Treatment of periodic paralysis in Andersen-Tawil syndrome is similar to that for other types. However, pacemaker insertion or an implantable cardioverter-defibrillator may be required to control cardiac symptoms. [7]


While the disability can range from minor, occasional weakness to permanent muscle damage, inability to hold a normal job and use of a powerchair, most people function fairly well with drugs and lifestyle changes.[ citation needed ]

Related Research Articles

Myotonia is a symptom of a small handful of certain neuromuscular disorders characterized by delayed relaxation of the skeletal muscles after voluntary contraction or electrical stimulation.

Hyperkalemic periodic paralysis is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability or weakness which, exacerbated by potassium, heat or cold, can lead to uncontrolled shaking followed by paralysis. Onset usually occurs in early childhood, but it still occurs with adults.

Chorea acanthocytosis Rare autosomal recessive genetic condition

Chorea-acanthocytosis, is a rare hereditary disease caused by a mutation in a gene that directs structural proteins in red blood cells. It belongs to a group of four diseases characterized under the name neuroacanthocytosis. When a patient's blood is viewed under a microscope, some of the red blood cells appear thorny. These thorny cells are called acanthocytes.

Andersen–Tawil syndrome Rare autosomal dominant genetic disorder

Andersen–Tawil syndrome, also called Andersen syndrome and long QT syndrome 7, is a rare genetic disorder affecting several parts of the body. The three predominant features of Andersen–Tawil syndrome include disturbances of the electrical function of the heart characterised by an abnormality seen on an electrocardiogram and a tendency to abnormal heart rhythms, physical characteristics including low-set ears and a small lower jaw, and intermittent periods of muscle weakness known as hypokalaemic periodic paralysis.

Channelopathy Diseases caused by disturbed function of ion channel subunits or the proteins that regulate them

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.

Myotonia congenita is a congenital neuromuscular channelopathy that affects skeletal muscles. It is a genetic disorder. The hallmark of the disease is the failure of initiated contraction to terminate, often referred to as delayed relaxation of the muscles (myotonia) and rigidity. Symptoms include delayed relaxation of the muscles after voluntary contraction (myotonia), and may also include stiffness, hypertrophy (enlargement), transient weakness in some forms of the disorder, severe masseter spasm, and cramping. The condition is sometimes referred to as fainting goat syndrome, as it is responsible for the eponymous 'fainting' seen in fainting goats when presented with a sudden stimulus. Of note, myotonia congenita has no association with malignant hyperthermia (MH).

Dyskeratosis congenita Medical condition

Dyskeratosis congenita (DKC),also known as Zinsser-Engman-Cole syndrome, is a rare progressive congenital disorder with a highly variable phenotype. The entity was classically defined by the triad of abnormal skin pigmentation, nail dystrophy, and leukoplakia of the oral mucosa, but these components do not always occur. DKC is characterized by short telomeres. Some of the manifestations resemble premature ageing. The disease initially mainly affects the skin, but a major consequence is progressive bone marrow failure which occurs in over 80%, causing early mortality.

Hypokalemic periodic paralysis Medical condition

Hypokalemic periodic paralysis (hypoKPP), also known as familial hypokalemic periodic paralysis (FHPP), 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, 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.

Paramyotonia congenita Medical condition

Paramyotonia congenita (PC), is a rare congenital autosomal dominant neuromuscular disorder characterized by “paradoxical” myotonia. This type of myotonia has been termed paradoxical because it becomes worse with exercise whereas classical myotonia, as seen in myotonia congenita, is alleviated by exercise. PC is also distinguished as it can be induced by cold temperatures. Although more typical of the periodic paralytic disorders, patients with PC may also have potassium-provoked paralysis. PC typically presents within the first decade of life and has 100% penetrance. Patients with this disorder commonly present with myotonia in the face or upper extremities. The lower extremities are generally less affected. While some other related disorders result in muscle atrophy, this is not normally the case with PC. This disease can also present as hyperkalemic periodic paralysis and there is debate as to whether the two disorders are actually distinct.

Fazio–Londe disease Medical condition

Fazio–Londe disease (FLD), also called progressive bulbar palsy of childhood, is a very rare inherited motor neuron disease of children and young adults and is characterized by progressive paralysis of muscles innervated by cranial nerves.


Sodium channel protein type 4 subunit alpha is a protein that in humans is encoded by the SCN4A gene.

Mevalonate kinase deficiency Medical condition

Mevalonate kinase deficiency (MKD), is an autosomal recessive metabolic disorder that disrupts the biosynthesis of cholesterol and isoprenoids. It is a very rare genetic disease.


Cav1.1 also known as the calcium channel, voltage-dependent, L type, alpha 1S subunit, (CACNA1S), is a protein which in humans is encoded by the CACNA1S gene. It is also known as CACNL1A3 and the dihydropyridine receptor.

Thyrotoxic periodic paralysis Human disease

Thyrotoxic periodic paralysis (TPP) is a condition featuring attacks of muscle weakness in the presence of hyperthyroidism. Hypokalemia is usually present during attacks. The condition may be life-threatening if weakness of the breathing muscles leads to respiratory failure, or if the low potassium levels lead to cardiac arrhythmias. If untreated, it is typically recurrent in nature.

The Kir2.6 also known as inward rectifier potassium channel 18 is a protein that in humans is encoded by the KCNJ18 gene. Kir2.6 is an inward-rectifier potassium ion channel.

Pontocerebellar hypoplasia Medical condition

Pontocerebellar hypoplasia (PCH) is a heterogeneous group of rare neurodegenerative disorders caused by genetic mutations and characterised by progressive atrophy of various parts of the brain such as the cerebellum or brainstem. Where known, these disorders are inherited in an autosomal recessive fashion. There is no known cure for PCH.​

Louis Ptáček is an American neurologist and professor who contributed greatly to the field of genetics and neuroscience. He was also an HHMI investigator from 1997 to 2018. His chief areas of research include the understanding of inherited Mendelian disorders and circadian rhythm genes. Currently, Ptáček is a neurology professor and a director of the Division of Neurogenetics in University of California, San Francisco, School of Medicine. His current investigations primarily focus on extensive clinical studies in families with hereditary disorders, which include identifying and characterizing the genes responsible for neurological variations.

Hypokalemic sensory overstimulation is characterized by a subjective experience of sensory overload and a relative resistance to lidocaine local anesthesia. The sensory overload is treatable with oral potassium gluconate. Individuals with this condition are sometimes diagnosed as having attention deficit hyperactivity disorder (ADHD), raising the possibility that a subtype of ADHD has a cause that can be understood mechanistically and treated in a novel way.

Hyperkalemic periodic paralysis is a genetic disorder that occurs in horses. It is also known as Impressive syndrome, after an index case in a horse named Impressive. It is an inherited autosomal dominant disorder that affects sodium channels in muscle cells and the ability to regulate potassium levels in the blood. It is characterized by muscle hyperexcitability or weakness which, exacerbated by potassium, heat or cold, can lead to uncontrolled shaking followed by paralysis.

Spinal muscular atrophy with lower extremity predominance 2B Rare genetic disease

Spinal muscular atrophy with lower extremity predominance 2B (SMALED2B) is a rare neuromuscular disorder characterised by generalised muscle weakness.


  1. "Periodic Paralyses: Background, Pathophysiology, Epidemiology". 2017-01-07.Cite journal requires |journal= (help)
  2. "Periodic Paralyses: Background, Pathophysiology, Epidemiology". 2017-01-07.Cite journal requires |journal= (help)
  3. 1 2 Ghovanloo MR, Abdelsayed M, Peters CH, Ruben PC (2018). "A Mixed Periodic Paralysis & Myotonia Mutant, P1158S, Imparts pH-Sensitivity in Skeletal Muscle Voltage-gated Sodium Channels". Scientific Reports. 8 (1): 13. Bibcode:2018NatSR...8.6304G. doi:10.1038/s41598-018-24719-y. PMC   5908869 . PMID   29674667.
  4. Kim, SJ; Lee, YJ; Kim, JB (Jan 2010). "Reduced expression and abnormal localization of the KATP channel subunit SUR2A in patients with familial hypokalemic periodic paralysis". Biochemical and Biophysical Research Communications. 391 (1): 974–8. doi:10.1016/j.bbrc.2009.11.177. PMID   19962959.
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  6. Lee, GM; Kim JB (June 2011). "Hyperkalemic periodic paralysis and paramyotonia congenita caused by a de novo mutation in the SCN4A gene". Neurology Asia. 16 (2): 163–6.
  7. Kim, JB; Chung, KW (Dec 2009). "Novel de novo Mutation in the KCNJ2 gene in a Patient with Andersen-Tawil Syndrome". Pediatric Neurology. 41 (6): 464–466. doi:10.1016/j.pediatrneurol.2009.07.010. PMID   19931173.
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