A 32-year-old multigravida woman, with known familial hypokalaemic periodic paralysis, underwent spinal anaesthesia for an elective lower segment caesarean section. There are several case reports in the literature discussing the optimal anaesthetic technique. In the past there has not been an emphasis on aggressive and early potassium replacement. A target level to commence replacement of potassium at 4.0 mmol/L or less is proposed. Careful preoperative preparation, frequent perioperative monitoring and early potassium replacement resulted in no perioperative episodes of weakness in this case, in contrast with other case reports where potassium was either not monitored or not replaced early enough, resulting in postoperative attacks. Another factor to consider in hypokalaemic periodic paralysis is the avoidance of triggers, including certain medications. Misoprostol was used in this instance to avoid potential electrolyte derangements from other uterotonics.

The CACNA1S gene encodes the alpha 1 S-subunit of the voltage-gated calcium channel, which is primarily expressed in the skeletal muscle cells. Pathogenic variants of CACNA1S can cause hypokalemic periodic paralysis (HypoPP), malignant hyperthermia susceptibility, and congenital myopathy. We aimed to study the clinical and molecular features of a male child with a CACNA1S variant and depict the molecular sub-regional characteristics of different phenotypes associated with CACNA1S variants.
We presented a case of HypoPP with recurrent muscle weakness and hypokalemia. Genetic analyses of the family members revealed that the proband had a novel c.497 C > A (p.Ala166Asp) variant of CACNA1S, which was inherited from his father. The diagnosis of HypoPP was established in the proband as he met the consensus diagnostic criteria. The patient and his parents were informed to avoid the classical triggers of HypoPP. The attacks of the patient are prevented by lifestyle changes and nutritional counseling. We also showed the molecular sub-regional location of the variants of CACNA1S which was associated with different phenotypes.
Our results identified a new variant of CACNA1S and expanded the spectrum of variants associated with HypoPP. Early genetic diagnosis can help avoid diagnostic delays, perform genetic counseling, provide proper treatment, and reduce morbidity and mortality.

Description Periodic paralysis is a group of muscle diseases that are related to transmembrane ion channels. Dysfunction of these channels causes an increase in sodium-potassium (Na-K) adenosine triphosphatase (ATPase) activity that pushes potassium into the cells that result in serum hypokalemia that manifests as muscle weakness. Beta-adrenergic stimulation and insulin sensitivity might also play a role. Periodic paralysis is divided into hereditary and acquired forms. Thyrotoxic periodic paralysis is an acquired form of periodic paralysis that manifests as muscle weakness, hypokalemia, and hyperthyroidism. The onset of the symptoms is mainly over the age of 20 and can be triggered by intense physical activity, stress, and excessive carbohydrate intake. This review presents the different types of this disease (hypokalemic, hyperkalemic, thyrotoxic, and Andersen-Tawil syndrome) while presenting a unique case of T3 thyrotoxicosis causing periodic paralysis.

Hypokalemic periodic paralysis (HPP) is a rare channelopathy characterized by episodic attacks of acute muscle weakness concomitant with hypokalemia. The etiology of hypokalemia is the shift of potassium into the cells, and the clinical symptoms resolve when potassium starts to leak back to the serum. Most of the time, the underlying ion channel defects are well compensated, and an additional trigger is often required to initiate an attack. Well-known trigger factors include carbohydrate-rich meals, exercise followed by rest, stress, cold weather, and alcohol consumption.
Here, we present the case of a 26-year-old Asian man who suffered from an acute onset of bilateral lower limb weakness with hypokalemia following dexamethasone injection. He was diagnosed with HPP.
We would like to remind physicians to think of steroids as an unusual precipitating factor while managing patients with HPP, per results of this case study.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a rare and most often acquired subtype of hypokalemic periodic paralysis. The association of varying degrees of muscle weakness, hyperthyroidism and hypokalemia characterizes it. The treatment requires potassium supplementation, control of hyperthyroidism and prevention measures. It is a frequent disease in Asian men, but much rare in Caucasian or African populations. This is the first report of TPP associated with lactic metabolic acidosis in an African man.
METHODS: A 23 year-old African man, native from Morocco, with recurrent episodes of tetraparesis for eleven months, and abdominal pain, was referred for evaluation. Biochemical investigations showed severe hypokalemia associated with hyperthyroidism and lactic metabolic acidosis. His EKG showed signs of hypokalemia such as sinus tachycardia and U waves. After potassium supplementation, neurological recuperation was quick and complete. Thyroid ultrasound identified a hypoechogenic and hypervascularized goiter, associated with high levels of thyroid antibodies, in favor of Grave\'s disease. With antithyroid drugs and life-style changes, the patient did not have any other attack.
METHODS: In addition to the case report, this article presents an extended review of literature, from the first large study reporting the diagnosis and incidence of TPP in 1957 to nowadays. Are reported here the latest information concerning epidemiology, clinical manifestations, complementary examinations, management and genetic finding. The lactic acidosis observed initially is exceptional, never described in TPP. TPP is a diagnostic and therapeutic emergency, requiring careful potassium supplementation, in order to avoid the risk of the onset of rebound hyperkalemia, to be maintained until the etiological treatment is effective. Paraclinical assessment with emergency EKG and electromyogram are essential to assess the impact.
CONCLUSIONS: It is essential in the face of any hypokalaemic periodic paralysis, including in non-Asian subjects, to search hyperthyroidism.
CONCLUSIONS: This report demonstrates the importance of thyroid testing in case of acute muscle weakness, even in non-Asian patients in order to diagnose TPP. This is a rare but possible etiology, to be distinguished from the familial form of hypokalemic periodic paralysis. It also questions on the impact of TPP on energetic metabolism, in particular on lactic metabolism.

BACKGROUND: Hypokalemic periodic paralysis is a rare neuromuscular genetic disorder due to defect of ion channels and subsequent function impairment. It belongs to a periodic paralyses group including hyperkalemic periodic paralysis (HEKPP), hypokalemic periodic paralysis (HOKPP) and Andersen-Tawil syndrome (ATS). Clinical presentations are mostly characterized by episodes of flaccid generalized weakness with transient hypo- or hyperkalemia.
METHODS: A teenage boy presented to Emergency Department (ED) for acute weakness and no story of neurological disease, during the anamnestic interview he revealed that he had a carbohydrates-rich meal the previous evening. Through a focused diagnostic work-up the most frequent and dangerous causes of paralysis were excluded, but low serum potassium concentration and positive family history for periodic paralyses raised the diagnostic suspicion of HOKPP. After the acute management in ED, he was admitted to Pediatric Department where a potassium integration was started and the patient was counselled about avoiding daily life triggers. He was discharged in few days. Unfortunately, he presented again because of a new paralytic attack due to a sugar-rich food binge the previous evening. Again, he was admitted and treated by potassium integration. This time he was strongly made aware of the risks he may face in case of poor adherence to therapy or behavioral rules. Currently, after 15 months, the boy is fine and no new flare-ups are reported.
CONCLUSIONS: HOKPP is a rare disease but symptoms can have a remarkable impact on patients\' quality of life and can interfere with employment and educational opportunities. The treatment aims to minimize the paralysis attacks by restoring normal potassium level in order to reduce muscle excitability but it seems clear that a strong education of the patient about identification and avoidance triggering factors is essential to guarantee a benign clinical course. In our work we discuss the typical clinical presentation of these patients focusing on the key points of the diagnosis and on the challenges of therapeutic management especially in adolescence. A brief discussion of the most recent knowledge regarding this clinical condition follows.

Unilateral paralysis is an alarming symptom with broad differential diagnoses, including stroke, Todd\'s paralysis, myelopathy, and peripheral neuropathy. Hypokalemic paralysis (HP), a neuromuscular disorder associated with muscle dysfunction, is caused by hypokalemia and manifests as symmetric proximal extremity muscle weakness. Unilateral paralysis has rarely been reported in the literature. Once hypokalemia is corrected, HP is usually reversible. Delayed diagnosis and treatment may result in fatal consequences. Here, we report an atypical case of unilateral weakness along with a review of the literature on unilateral HP.

Hypokalemic periodic paralysis (hypoPP) is a disorder characterized by episodic, short-lived, and hypo-reflexive skeletal muscle weakness. HypoPP is a rare disease caused by genetic mutations related to expression of sodium or calcium ion channels. Most mutations are associated with autosomal dominant inheritance, but some are found in patients with no relevant family history. A 28-year-old man who visited the emergency room for paralytic attack was assessed in this study. He exhibited motor weakness in four limbs. There was no previous medical history or family history. The initial electrocardiogram showed a flat T wave and QT prolongation. His blood test was delayed, and sudden hypotension and bradycardia were observed. The blood test showed severe hypokalemia. After correcting hypokalemia, his muscle paralysis recovered without any neurological deficits. The patient\'s thyroid function and long exercise test results were normal. However, because of the history of high carbohydrate diet and exercise, hypoPP was suspected. Hence, next-generation sequencing (NGS) was performed, and a mutation of Arg669His was noted in the SCN4A gene. Although hypoPP is a rare disease, it can be suspected in patients with hypokalemic paralysis, and iden tification of this condition is important for preventing further attacks and improving patient outcomes. Diagnosing hypoPP through targeted NGS is a cost-effective and useful method.

BACKGROUND: Skeletal muscle ion channelopathies include non-dystrophic myotonias (NDM), periodic paralyses (PP), congenital myasthenic syndrome, and recently identified congenital myopathies. The treatment of these diseases is mainly symptomatic, aimed at reducing muscle excitability in NDM or modifying triggers of attacks in PP.
OBJECTIVE: This systematic review collected the evidences regarding effects of pharmacological treatment on muscle ion channelopathies, focusing on the possible link between treatments and genetic background.
METHODS: We searched databases for randomized clinical trials (RCT) and other human studies reporting pharmacological treatments. Preclinical studies were considered to gain further information regarding mutation-dependent drug effects. All steps were performed by two independent investigators, while two others critically reviewed the entire process.
RESULTS: For NMD, RCT showed therapeutic benefits of mexiletine and lamotrigine, while other human studies suggest some efficacy of various sodium channel blockers and of the carbonic anhydrase inhibitor (CAI) acetazolamide. Preclinical studies suggest that mutations may alter sensitivity of the channel to sodium channel blockers in vitro, which has been translated to humans in some cases. For hyperkalemic and hypokalemic PP, RCT showed efficacy of the CAI dichlorphenamide in preventing paralysis. However, hypokalemic PP patients carrying sodium channel mutations may have fewer benefits from CAI compared to those carrying calcium channel mutations. Few data are available for treatment of congenital myopathies.
CONCLUSIONS: These studies provided limited information about the response to treatments of individual mutations or groups of mutations. A major effort is needed to perform human studies for designing a mutation-driven precision medicine in muscle ion channelopathies.

BACKGROUND: 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.
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.
CONCLUSIONS: 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.
BACKGROUND: Parálisis periódica hipocaliémica: revisión sistemática de casos publicados.
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.