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Periodic paralyses (PPs) are rare neuromuscular disorders caused by mutations in skeletal muscle sodium, calcium, and potassium channel genes. PPs include hypokalemic paralysis, hyperkalemic paralysis, and Andersen-Tawil syndrome. Common features of PP include autosomal dominant inheritance, onset typically in the first or second decades, episodic attacks of flaccid weakness, which are often triggered by diet or rest after exercise. Diagnosis is based on the characteristic clinic presentation then confirmed by genetic testing. In the absence of an identified genetic mutation, documented low or high potassium levels during attacks or a decrement on long exercise testing support diagnosis. The treatment approach should include both management of acute attacks and prevention of attacks. Treatments include behavioral interventions directed at avoidance of triggers, modification of potassium levels, diuretics, and carbonic anhydrase inhibitors. Muscle Nerve 57: 522-530, 2018., (© 2017 The Authors Muscle & Nerve Published by Wiley Periodicals, Inc.)

Thyrotoxic periodic paralysis (TPP), a disorder most commonly seen in Asian men, is characterized by abrupt onset of hypokalemia and paralysis. The condition primarily affects the lower extremities and is secondary to thyrotoxicosis. Early recognition of TPP is vital to initiating appropriate treatment and to avoiding the risk of rebound hyperkalemia that may occur if high-dose potassium replacement is given. Here we present a case of 31 year old male with thyrotoxic periodic paralysis with diagnostic and therapeutic approach., (© Journal of the Association of Physicians of India 2011.)

Thyrotoxic periodic paralysis is an uncommon thyroid emergency that is associated with electrolyte disturbances and a progressive flaccid paralysis of lower and upper extremities. Although not typically diagnosed within the emergency department setting, advanced practice registered nurses may be key in identifying this unusual condition where rapid and appropriate treatment precipitated by hyperthyroidism, most commonly resulting from Graves' disease can mitigate adverse cardiac, renal, and neurologic sequelae.

A 26-year-old Hispanic woman presented to the emergency department (ED) with myalgia and weakness. There were no prior symptoms and family history was negative for endocrinopathies. She was admitted and started on methimazole 10 mg twice a day for thyroid suppression and given propranolol 10 mg twice a day for anticipated hyperadrenergic adverse effects. The remainder of her hospital stay was uneventful and she was discharged 6 days after admission. Soon after, an outpatient thyroid scan ordered by her primary care physician confirmed that the patient had Graves' disease.

Introduction: We have developed a rare disease center in China., Methods: In this study we analyzed how patients with periodic paralysis accessed centers in China vs. in the USA and UK., Results: A total of 116 patients with periodic paralysis were evaluated in Beijing and Hangzhou (2003-2012). These patients traveled long distances for outpatient specialist care without an appointment or physician referral. In contrast, at the University of Rochester in the USA, >90% of patients were referred from physicians throughout the country by identifying physician expertise or by referrals from a patient advocacy group. In the UK, a single center, supported by the National Health Service, provides assessment/genetic testing for all UK patients., Conclusions: Rare disease centers in China require: (1) establishing a center for clinical characterization of the disease (e.g., periodic paralysis); (2) establishing a genetic diagnostic platform; (3) placing the center at a major city hospital; and (4) facilitating patient access through internet websites., (Copyright © 2013 Wiley Periodicals, Inc.)

A 61-year-old man presented with lower extremity paralysis and severe hypokalemia. His thyroid function test showed thyrotoxicosis. Despite attempts to correct his hypokalemia, he developed pulseless polymorphic ventricular tachycardia two hours later. He was successfully resuscitated after defibrillation. We performed continuous venovenous hemodiafiltration for 10 days due to acute kidney injury and rhabdomyolysis. We observed life-threatening polymorphic ventricular tachycardia requiring urgent defibrillation, as well as rhabdomyolysis requiring dialysis during the transient thyrotoxic phase of painless thyroiditis. Pay attention to the possibility of the development of life-threatening ventricular tachycardia associated with hypokalemia in the setting of thyroiditis and thyrotoxic paralysis.

We report a 53-year-old Turkish female presented with progressive weakness and mild dyspnea. Laboratory results demonstrated severe hypokalemia with hyperchloremic metabolic acidosis. The urinary anion gap was positive in the presence of acidemia, thus she was diagnosed with hypokalemic paralysis from a severe distal renal tubular acidosis (RTA). Immunologic work-up showed a strongly positive ANA of 1:3,200 and positive antibodies to SSA and SSB. Schirmer's test was abnormal. Autoimmune and other tests revealed Sjögren syndrome as the underlying cause of the distal renal tubular acidosis. Renal involvement in Sjogren's syndrome (SS) is not uncommon and may precede sicca complaints. The pathology in most cases is a tubulointerstitial nephritis causing among other things, distal RTA, and, rarely, hypokalemic paralysis. Treatment consists of potassium repletion, alkali therapy, and corticosteroids. Primary SS could be a differential in women with acute weakness and hypokalemia.

11β hydroxylase deficiency (OHD) is one of the main causes of congenital adrenal hyperplasia. There have been only a few reported cases of nonclassic 11β OHD, a milder form of the disease. It is difficult to detect occult nonclassic 11β OHD because patients present with no or mild symptoms. We herein present a case of thyrotoxic periodic paralysis (TPP) with Graves' disease leading to the discovery of a hidden nonclassic 11β OHD. In this case, increased levels of thyroid hormone seem to have induced symptoms of occult nonclassic 11β OHD and aggravated TPP.

We report a rare case of a 38-year-old female who presented with sudden onset flaccid quadriplegia and respiratory arrest with no significant past clinical history. She was later found to have hypokalemia due to distal renal tubular acidosis and further diagnosed as case of Sjogrens Syndrome.

Objective: To report the clinical features and recovery patterns of patients with non-thyrotoxic acquired hypokalemic paralysis., Methods: The clinical and laboratory records of 11 consecutive patients with acquired non-thyrotoxic hypokalemic paralysis were reviewed and compared with those of 3 patients with thyrotoxic periodic paralysis (TPP). The causes of potassium wasting were diarrhea (n=4), alcohol abuse (n=2), pseudoaldosteronism (n=2), primary aldosteronism (n=1), distal renal tubular acidosis associated with Sjögren's syndrome (n=1) and an unknown cause (n=1)., Results: Three of the 11 patients had prominently asymmetric limb weakness, and 2 had predominant upper limb weakness. On admission, mean serum potassium and creatine kinase (CK) levels of patients with acquired hypokalemic paralysis on admission were 1.8 mEq/L and 4,075 U/mL, respectively, and the mean duration between admission and independent walking was 6.8 days (range, 2-31 days). Despite clinical recovery, 10 patients still presented with increased CK levels after several days (mean of maximum levels, 10,519 U/mL). In addition, normalization of serum potassium levels in patients with acquired hypokalemic paralysis patients was much slower compared to that in patients with TPP. One patient with acquired hypokalemic paralysis developed ventricular fibrillation, whereas all 3 patients with TPP had symmetric proximal and lower limb-dominant weakness and exhibited complete recovery from paralysis as well as normalized serum potassium levels within 24h., Conclusions: In patients with acquired non-thyrotoxic hypokalemic paralysis, asymmetric or upper limb-dominant weakness of the extremities is observed. Despite clinical improvement after treatment, normalization of serum potassium and CK levels is often delayed, and therefore, careful monitoring for cardiac and renal complications is required., (Copyright © 2011 Elsevier B.V. All rights reserved.)

Dyskalemic paralyses are characterised by single or periodic episodes with muscle weakness that affect mostly the proximal skeletal muscles. Symptoms may last for a few hours or persist for several days, spontaneous recovery is common. Familial cases can be distinguished from secondary, non-familial forms which are based on other diseases, for example, of the thyroid gland, kidneys or gastrointestinal tract. Familial cases are mostly inherited in an autosomal-dominant pattern and belong to the channelopathies. Both groups are characterised by changed potassium levels in the blood during an episode. A detailed and accurate medical history (plus family history, use of medication and eating habits) often easily leads to the diagnosis. Provoking tests or instrumental and histological investigations can help to solve difficult cases. Treatment focuses on relieving acute symptoms and attacks can be managed by correcting the blood potassium to a normal level. Changing eating and/or exercise habits and also permanent medical treatment helps to prevent further attacks., (© Georg Thieme Verlag KG Stuttgart · New York.)

Hypokalaemic periodic paralysis (hypoPP) is the archetypal skeletal muscle channelopathy caused by dysfunction of one of two sarcolemmal ion channels, either the sodium channel Nav1.4 or the calcium channel Cav1.1. Clinically, hypoPP is characterised by episodes of often severe flaccid muscle paralysis, in which the muscle fibre membrane becomes electrically inexcitable, and which may be precipitated by low serum potassium levels. Initial functional characterisation of hypoPP mutations failed to adequately explain the pathomechanism of the disease. Recently, as more pathogenic mutations involving loss of positive charge have been identified in the S4 segments of either channel, the hypothesis that an abnormal gating pore current may be important has emerged. Such an aberrant gating pore current has been identified in mutant Nav1.4 channels and has prompted potentially significant advances in this area. The carbonic anhydrase inhibitor acetazolamide has been used as a treatment for hypokalaemic periodic paralysis for over 40 years but its precise therapeutic mechanism of action is unclear. In this review we summarise the recent advances in the understanding of the molecular pathophysiology of hypoPP and consider how these may relate to the reported beneficial effects of acetazolamide. We also consider potential areas for future therapeutic development.

Ascariasis is one of the most common helminthic infestations in humans. Massive infestation can give rise to serious complications such as intestinal obstruction. We present a 4-year-old boy, who presented with acute flaccid quadriparesis due to the hypokalemic alkalosis induced by severe vomiting. Severe vomiting was due to intestinal obstruction caused by round worms.

The objective of this study was to present a case series of patients with hypokalemic periodic paralysis. We described all patients with diagnosis of hypokalemic periodic paralysis admitted to the Al Ain Hospital (UAE) during the year 2006. Seventeen patients, all males and mostly Asians, were presented to the Al Ain Hospital over a 12-month period. The majority were admitted during the summer months. Four were thyrotoxic. All of the 17 patients received oral potassium supplements and recovered well without any major complications. In conclusion, clinicians should have a high index of suspicion, especially among Asians presenting with flaccid paralysis and hypokalemia. The main steps in the management include exclusion of other causes of hypokalemia, potassium replacement, hydration and close monitoring of the cardiac rhythm and serum potassium levels. When possible, the underlying cause must be adequately addressed to prevent the persistence or recurrence of paralysis.

The hypokalemic paralysis is a disease characterized by the development of acute muscular weakness, associated to low levels of blood potassium (< 3.5 meq/L). Here we present two cases: in the first one, a 23 years old woman, with 15.5 weeks of gestation has a cuadriplegia associated to blood potassium level of 1.4 meq/L, diagnosed with distal tubular acidosis; she required mechanical ventilation for respiratory paralysis. The medical profile remits with potassium intravenous replacement and the pregnancy ends with a spontaneous abortion. The second case is a 15 years old woman with 26.5 weeks of pregnancy, who suffers a generalized paralysis with blood potassium of 2.7 meq/L, requiring also mechanical ventilation for respiratory paralysis; the final diagnosis was Barterr syndrome, and the medical profile remited after potassium supplement. Her pregnancy got complicated with a severe preeclampsia, enough reason for interrumpting the pregnancy at 29.1 weeks of gestation. In both cases Guilliain-Barre syndrome was ruled out.

This report describes the case of a 29-year-old Chechen refugee with periodic hypokalemic thyreotoxic tetraparesis (PHTP). Besides a partial respiratory insufficiency, the patient was also presented with sinus bradycardia. Medical literature describes several cases of thyreotoxicosis in combination with bradycardia. For the first time, we were able to observe a case of PHTP in combination with sinus bradycardia. PHTP is rarely seen in central Europe. In this case establishing a final diagnosis was difficult because of the concomitant presence of bradycardia and Graves' disease.

Management considerations in hypokalemic periodic paralysis include accurate diagnosis, potassium dosage for acute attacks, choice of diuretic for prophylaxis, identification of triggers, creating a safe physical environment, peri-operative measures, and issues in pregnancy. A positive genetic test in the context of symptoms is the gold standard for diagnosis. Potassium chloride is the favored potassium salt given at 0.5-1.0 mEq/kg for acute attacks. The oral route is favored, but if necessary, a mannitol solvent can be used for intravenous administration. Avoidance of or potassium prophylaxis for common triggers, such as rest after exercise, high carbohydrate meals, and sodium, can prevent attacks. Chronically, acetazolamide, dichlorphenamide, or potassium-sparing diuretics decrease attack frequency and severity but are of little value acutely. Potassium, water, and a telephone should always be at a patient's bedside, regardless of the presence of weakness. Perioperatively, the patient's clinical status should be checked frequently. Firm data on the management of periodic paralysis during pregnancy is lacking. Patient support can be found at http://www.periodicparalysis.org.

Periodic paralyses are rare diseases characterized by severe episodes of muscle weakness concomitant to variations in blood potassium levels. It is thus usual to differentiate hypokalemic, normokalemic, and hyperkalemic periodic paralysis. Except for thyrotoxic hypokalemic periodic paralysis and periodic paralyses secondary to permanent changes of blood potassium levels, all of these diseases are of genetic origin, transmitted with an autosomal-dominant mode of inheritance. Periodic paralyses are channelopathies, that is, diseases caused by mutations in genes encoding ion channels. The culprit genes encode for potassium, calcium, and sodium channels. Mutations of the potassium and calcium channel genes cause periodic paralysis of the same type (Andersen-Tawil syndrome or hypokalemic periodic paralysis). In contrast, distinct mutations in the muscle sodium channel gene are responsible for all different types of periodic paralyses (hyper-, normo-, and hypokalemic). The physiological consequences of the mutations have been studied by patch-clamp techniques and electromyography (EMG). Globally speaking, ion channel mutations modify the cycle of muscle membrane excitability which results in a loss of function (paralysis). Clinical physiological studies using EMG have shown a good correlation between symptoms and EMG parameters, enabling the description of patterns that greatly enhance molecular diagnosis accuracy. The understanding of the genetics and pathophysiology of periodic paralysis has contributed to refine and rationalize therapeutic intervention and will be without doubts the basis of further advances.

Familial hypokalemic periodic paralysis (FHPP) is a rare inherited disease characterized by a dysfunction of the membrane ion channels. Clinical manifestations are attacks of hypokaliemia with flaccid muscle paralysis. Paralysis is sometimes severe but always reversible with symptomatic treatment. Pregnancy and delivery have been reported to exacerbate FHPP. Authors report a case of FHPP during pregnancy with a favourable outcome. Vaginal delivery is usually possible with monitoring and epidural analgesia, avoiding active maternal expulsive efforts (passive descent of the fetus and elective outlet forceps) and other stimulating factors (carbohydrate loads, maternal stress, betamimetics, epinephrine...). Administration of IV potassium supplementation is often necessary.

Context: Thyrotoxic periodic paralysis (TPP) is an unusual presentation of hyperthyroidism in women. The occurrence of this condition in the context of pregnancy is even more uncommon. Impaired glucose tolerance, pregnancy, and TPP impact overall management of thyrotoxicosis. There is little guidance in the literature for management under this constellation of circumstances., Patient and Intervention: This is a case report of a previously healthy 36-year-old Filipino female presenting at 15 weeks gestation with tetraparesis, hypokalemia, and new onset Graves' disease with impaired glucose tolerance. Normal thyroid function was achieved in the mother without further episodes of TPP and a healthy, euthyroid male was delivered at 38 weeks gestation. Acute and long-term management strategies used in this case are described in detail., Conclusions: A synthesis of the available literature allowed development of a practical management strategy applicable to a variety of situations involving TPP in pregnancy.

Rare diseases have attracted little attention in the past from physicians and researchers. The situation has recently changed for several reasons. First, patient associations have successfully advocated their cause to institutions and governments. They were able to argue that, taken together, rare diseases affect approximately 10% of the population in developed countries. Second, almost 80% of rare diseases are of genetic origin. Advances in genetics have enabled the identification of the causative genes. Unprecedented financial support has been dedicated to research on rare diseases, as well as to the development of referral centers aimed at improving the quality of care. This expenditure of resources is justified by the experience in cystic fibrosis, which demonstrated that improved care delivered by specialized referral centers resulted in a dramatic increase of life expectancy. Moreover, clinical referral centers offer the unique possibility of developing high quality clinical research studies, not otherwise possible because of the geographic dispersion of patients. This is the case in France where national referral centers for rare diseases were created, including one for muscle channelopathies. The aim of this center is to develop appropriate care, clinical research, and teaching on periodic paralysis and myotonia. In this review, we plan to demonstrate how research has improved our knowledge of hypokalemic periodic paralysis and the way we evaluate, advise, and treat patients. We also advocate for the establishment of international collaborations, which are mandatory for the follow-up of cohorts and conduct of definitive therapeutic trials in rare diseases.

Thyrotoxic periodic paralysis (TPP) is a disease characterized by recurrent episodes of paralysis and hypokalemia during a thyrotoxic state. The disease primarily affects people of Asian descent, but can affect other ethnic groups. In Asians, the symptoms of thyrotoxicosis are distinct and usually precede the first paralytic episode, whereas in non-Asian populations, paralysis is the presenting symptom. If TPP has not been diagnosed and the patient has a surgical procedure during general or regional anesthesia, symptoms of the disease may be confused with other adverse perioperative events such as delayed recovery from neuromuscular paralysis. No specific anesthetic regimen is superior. Current TTP treatment recommendations involve treating the underlying hyperthyroid state. Other modalities such as beta-blockade and potassium replacement are also important in the acute paralytic state. Future diagnostic and treatment innovations may lie in the genetic and molecular understanding of this disease. We present a case of an Asian male with known TPP undergoing general anesthesia, a brief case series involving 5 patients, and a review of the literature.

Hypokalemic paralysis is a less recognized but reversible disorder in elderly patients. This report describes two elderly Chinese males (age 74 and 78 years) who had progressive muscle weakness and eventually paralysis. Physical examination showed symmetrical flaccid paralysis of extremities. Both had the major biochemical abnormality of profound hypokalemia (1.4 and 1.8 mmol/L) accompanied by high urine K+ excretion and hyperchloremic metabolic acidosis. A positive urine anion gap and alkaline urine pointed to the diagnosis of distal renal tubular acidosis. Large doses of potassium chloride supplementation were required to restore muscle strength. Pertinent investigations, including elevated titers of antinuclear antibody and rheumatoid factor, positive anti-Ro antibody, low serum C3 and C4 levels, and delayed saliva excretion on salivary scintigraphy suggested Sjögren syndrome. Despite the lack of sicca syndrome at the initial presentation, both had development of typical sicca syndrome and positive Schirmer test at the 5-month and 1-year follow-up, respectively. Potassium citrate supplement and prednisolone therapy completely corrected the hypokalemia and metabolic acidosis. Extraglandular involvement with distal renal tubular acidosis preceding the typical sicca syndrome may induce hypokalemic paralysis and unveil Sjögren syndrome in elderly males.

Background: Hypokalemic periodic paralysis as a complication of thyrotoxicosis (THypoKPP) is common in Asians but not well recognized in Western countries or pediatric patients, where most cases are due to the familial variant (FHypoKPP). Ion channel gene mutations may underlie these diseases. We describe the first pediatric and a rare adult Caucasian case of THypoKPP in Finland., Methods: Manifestation and management of two THypoKPP cases. We studied for possible mutations in KCNE3, KCNJ2, SCN4A and CACNA1S genes., Results: A 15-year-old Vietnamese boy presented with sudden-onset paralysis and severe hypokalemia, 1.8 mmol/l. The case was first regarded as FHypoKPP, but thyroid function testing revealed a suppressed TSH and highly elevated FT4. A 37-year-old Caucasian male presented with acute tetraparesis. His plasma potassium was only 1.4 mmol/l. Treatment with carbimazole had been initiated two weeks earlier, but FT4 was still elevated. No mutations in KCNE3, KCNJ2, SCN4A or CACNA1S genes were detected., Conclusions: THypoKPP is a potentially life-threatening condition which bares many similarities with FHypoKPP. THypoKPP is rare in Western countries but should be considered in sudden-onset paralysis, independently of age and especially in males. Mutations in ion channel candidate genes did not underlie the disease in the present cases., (Copyright 2005 S. Karger AG, Basel.)

Hypokalemia with paralysis (HP) is a potentially reversible medical emergency. It is primarily the result of either hypokalemic periodic paralysis (HPP) caused by an enhanced shift of potassium (K(+)) into cells or non-HPP resulting from excessive K(+) loss. Failure to make a distinction between HPP and non-HPP could lead to improper management. The use of spot urine for K(+) excretion rate and evaluation of blood acid-base status could be clinically beneficial in the diagnosis and management. A very low rate of K(+) excretion coupled with the absence of a metabolic acid-base disorder suggests HPP, whereas a high rate of K(+) excretion accompanied by either metabolic alkalosis or metabolic acidosis favors non-HPP. The therapy of HPP requires only small doses of potassium chloride (KCl) to avoid rebound hyperkalemia. In contrast, higher doses of KCl should be administered to replete the large K(+) deficiency in non-HPP.

Modification of K+ currents by exogenous gene expression may lead to therapeutic interventions in skeletal muscle diseases characterized by alterations in electrical excitability. In order to study the specific effects of increasing outward K+ currents, we expressed a modified voltage-dependent K+ channel in primary cultured rat skeletal muscle cells. The rat Kv1.4 channel was expressed as an N-terminal fusion protein containing a bioluminescent marker (green fluorescent protein). Transgene expression was carried out using the helper-dependent herpes simplex 1 amplicon system. Transduced myoballs, identified using fluorescein optics and studied electrophysiologically with single-cell patch clamp, exhibited a greater than two-fold increase in K+ conductance by 20-30 h after infection. This increase in K+ current led to a decrease in membrane resistance and a 10-fold increase in the current threshold for action potential generation. Electrical hyperexcitability induced by the Na+ channel toxin anemone toxin II (1 microM) was effectively counteracted by overexpression of Kv1.4 at 30-32 h after transduction. Thus, virally induced overexpression of a voltage-gated K+ channel in skeletal muscle has a powerful effect in reducing electrical excitability.

Thyrotoxic periodic paralysis is a thyroid-related disorder that is manifested as recurrent episodes of hypokalemia and muscle weakness lasting from hours to days. The periodic paralysis has been associated with thyrotoxicosis from various etiologies. Although the incidence of the disorder is relatively higher among Asians, it has been reported in many other ethnic groups. We review the literature and report the ninth and tenth cases of thyrotoxic periodic paralysis in black patients.

Channelopathy is a term used to describe clinical problems caused by disorders of membrane ion channels. Included in this disease category are certain types of periodic paralyses, ataxia, myotonia, migraine headache, epilepsy, nephrolithiasis, and long QT syndrome. This article briefly summarizes membrane ion channel structure and function and details several relatively common channelopathies. In hyperkalemic periodic paralysis, mutant skeletal muscle sodium channels fail to close completely after an action potential. This evokes two apparently opposite symptoms: myotonia (caused by a small depolarization and repetitive excitation) or paralysis (caused by larger depolarization and inexcitability). In hypokalemic periodic paralysis, mutation affects the closing of skeletal muscle calcium channels, causing transient paresis or paralysis. The task of the advanced practice nurse is to recognize these disorders, institute appropriate prophylactic measures and treatments, monitor symptom progression, and avoid complications. Understanding of channelopathies is advancing rapidly. On the horizon are therapies tailored to counter specific membrane ion channel defects.