Parálisis periódica hipocaliémica: revisión sistemática de casos publicados / Hypokalemic periodic paralysis: a systematic review of published case reports

INTRODUCCIÓN: La parálisis periódica hipocaliémica es una enfermedad neuromuscular hereditaria que se caracteriza por presentar episodios de parálisis flácida o debilidad muscular relacionados con niveles bajos de potasio en sangre. Como consecuencia de su baja prevalencia, todavía hay aspectos clínicos y de manejo por caracterizar. PACIENTES Y MÉTODOS: Se desarrolla una revisión sistemática de los casos clínicos publicados en la última década, analizando las características demográficas y genéticas, las características de los episodios, los tratamientos recibidos y su respuesta, y las diferencias y evolución de los pacientes en función de las mutaciones de los genes más prevalentes: CACNA1S y SCN4A. RESULTADOS: Se incluyeron 33 artículos, que permitieron revisar a 40 sujetos. La edad media del inicio de los síntomas fue de 15,3 ± 9,7 años. El gen alterado con mayor frecuencia fue CACNA1S en 20 (60,5%) casos. Se observó que los sujetos con alteración del gen del canal de calcio CACNA1S presentaron niveles de potasio sérico inferiores, factores desencadenantes propios y una mayor proporción de sujetos con disnea en las crisis. La respuesta al tratamiento oral clásico con acetazolamida sólo alcanzó el 50%. Los diuréticos ahorradores de potasio y los fármacos antiepilépticos emergieron como una alternativa. CONCLUSIONES: La parálisis periódica hipocaliémica tiene una expresión clínica heterogénea con diferencias fenotípicas ligadas a las diferentes mutaciones genéticas. La respuesta al tratamiento preventivo habitual es subóptima. Son necesarios estudios prospectivos para poder discernir la mejor opción terapéutica en función de la carga genética

INTRODUCTION: Hypokalemic periodic paralysis is a neuromuscular disease characterized by a combination of flaccid paralysis episodes (or muscular weakness) that are related to low levels of potassium in blood. As a consequence of its low prevalence, there are still clinical and management aspects to characterize. PATIENTS AND METHODS: A systematic review of the clinical cases published in the last decade has been developed by analyzing demographic and genetic features, the episodes' characteristics, the received treatments, the response to them and also, the differences and evolution of patients depending on the most prevalent genetic alterations: CACNA1S and SCN4A. RESULTS: A total of 33 articles were included, allowing 40 individuals to be reviewed. The average age of onset of symptoms was 15.3 ± 9.7 years. The most frequent altered gene was CACNA1S in 20 (60.5%) cases. It was observed that subjects presenting an alteration of the gene responsible for the calcium channel, CACNA1S, presented lower serum potassium levels, own triggers and a higher proportion of subjects showing dyspnea during the crisis. Only 50% of the subjects respond to classical oral treatment with acetazolamide. Potassium-sparing diuretics and antiepileptics drugs emerge as an alternative. CONCLUSION: Hypokalemic periodic paralysis has an heterogeneous clinical expression with phenotypic differences linked to different genetic mutations. The common preventive treatment response is suboptimal. Prospective studies are needed to discern the best therapeutic option based on genetic load

A rare case of cephalexin-induced acute interstitial nephritis with hypokalemic periodic paralysis.

Drug-induced acute interstitial nephritis (AIN) is often encountered in clinical practice. Cephalexin is a first-generation cephalosporin with antimicrobial sensitivity ranging from Gram-positive to Gram-negative organisms. Cephalexin-induced AIN presenting with hypokalemic periodic paralysis (HPP) has been rarely reported. A 34-year-old female with recent history of oral cephalexin intake presented with acute onset paraplegia with deranged renal parameters and hypokalemia. She was treated conservatively with mechanical ventilator support. HPP could be a rare clinical presentation for cephalexin-induced AIN.

Familial hypokalemic periodic paralysis in pregnancy: A case report.

Familial hypokalemic periodic paralysis (f-hypoPP) is a rare neuromuscular disorder causing intermittent muscle paralysis. Pregnancy can exacerbate f-hypoPP, yet obstetric management is not well documented. We present a case of a nulliparous woman with f-hypoPP, outlining a complete prenatal care plan generalizable to other women with known f-hypoPP. To our knowledge, this is the first obstetric f-hypoPP case to prioritize intrapartum oral potassium over intravenous potassium, as well as to outline the importance of multidisciplinary care. The patient had a spontaneous vaginal delivery at term with an uneventful postpartum period. Muscle weakness and episodes of relative hypokalemia in the second trimester and during labor were effectively treated with oral potassium supplementation. Care was provided by a multidisciplinary team, and caution was taken to avoid known triggers of paralytic episodes.

Review of the Diagnosis and Treatment of Periodic Paralysis.

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.

Thyrotoxic Channelopathies.

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.

Thyrotoxic Periodic Paralysis: A Puzzling Case of Chest Pain and Weakness.

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.

Hyperthyroidism · myalgia · rapidly progressing paralysis · Dx?

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.

Severe hypokalemia and thyrotoxic paralysis from painless thyroiditis complicated by life-threatening polymorphic ventricular tachycardia and rhabdomyolysis.

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.

Rare disease centers for periodic paralysis: China versus the United States and United Kingdom.

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.

Thyrotoxic periodic paralysis with Graves' disease leading to the discovery of a hidden nonclassic 11ß hydroxylase deficiency.

11ß hydroxylase deficiency (OHD) is one of the main causes of congenital adrenal hyperplasia. There have been only a few reported cases of nonclassic 11ß OHD, a milder form of the disease. It is difficult to detect occult nonclassic 11ß 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 11ß OHD. In this case, increased levels of thyroid hormone seem to have induced symptoms of occult nonclassic 11ß OHD and aggravated TPP.

Hypokalemic periodic paralysis in Sjogren's syndrome secondary to distal renal tubular acidosis.

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.

Clinical features and recovery patterns of acquired non-thyrotoxic hypokalemic paralysis.

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.

Sjogren's syndrome presenting with hypokalemic periodic paralysis.

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.

[Pseudo-Conn's syndrome with hypokalemic paralysis due to diuretics and licorice abuse]. / Pseudo-Conn-Syndrom mit hypokaliämischer Lähmung bei Lakritzabusus und Diuretikatherapie.

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.

Parálisis periódica tirotóxica hipopotasémica / Hypokalemic thyrotoxic periodic paralisis

Paciente varón de 29 años, natural y procedente de Lima, mestizo, con historia de dos meses de presentar tres episodios de debilidad y dolor muscular proximal de extremidades, con inicio y predominio en muslos, que llega incluso a presentar cuadriplejia flácida, que afecta severamente las extremidades inferiores a nivel de los músculos proximales. Durante el último episodio, el nivel de potasio sérico fue 2.0 mEq/L, el electrocardiograma evidenció taquicardia leve y discreto aplanamiento de la onda T. La corrección de la hipopotasemia permitió recuperar la fuerza muscular, revertir el dolor y las alteraciones electrocardiográficas.

Male patient of 29 years old, southamerican origin, with history of two months of had presented a flaccid cuadriplejia (he had two previous episodes of less intensity), affecting severely the inferior extremities at the proximal muscle level. During the last acute attack the potassium level was in 2,0 mEq/L, the ECG showed mild tachycardia and T wave flattening. The correction of the hypokalemia allowed to recuperate the muscle strength and reverse the electrocardiographic alterations. Besides, it was shown a thyrotoxic state.

Paralisia periódica hipocalêmica esporádica / Sporadic hypokalemic periodic paralysis

Paralisia periódica hipocalêmica é um distúrbio genético muscular raro que afeta os canais iônicos. É potencialmente fatal se não diagnosticado e tratado adequadamente, e os sintomas inespecíficos dificultam o diagnóstico para médicos não familiarizados com essa condição. Este artigo apresenta um caso de paralisia periódica hipocalêmica primária em um paciente de 25 anos. A apresentação clínica, assim como a laboratorial, foram típicas. Com este relato enfatizamos a importância do conhecimento dessa entidade, porque, se reconhecidos e tratados propriadamente, os pacientes geralmente se recuperam sem sequelas clínicas

Hypokalemic periodic paralysis is a rare genetic disorder that affects muscle ion channels. It is a life-threatening condition if not diagnosed and treated properly, and its nonspecific symptoms make diagnosis difficult for physicians unfamiliar with this condition. This article reports a case of primary hypokalemic periodic paralysis in a 25-year-old patient. The clinical and laboratory parameters were typical. With this report we emphasize the importance of knowing this entity because, if recognized and treated appropriately, patients usually recover without clinical sequelae