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.

Thyrotoxic periodic paralysis (TPP) is rarely seen in children and adolescents. Clinical manifestations in children and adolescents may vary. It is important for clinicians to be aware of this rare and life-threatening condition.

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.

Periodic paralyses are a group of disorders characterized by episodes of muscle paralyses. They are mainly divided as primary (hereditary) and secondary (acquired) periodic paralyses. Primary periodic paralyses occur as a result of mutations in genes encoding subunits of muscle membrane channel proteins such as sodium, calcium, and potassium channels, resulting in impairment of their properties. Primary periodic paralyses are further classified on the basis of affected ion channels and other associated complications. Some of these periodic paralyses are hyperkalemic periodic paralysis (Na-channel mutation), hypokalemic periodic paralysis (Na- or Ca-channel mutation), Andersen\'s syndrome (K-channel mutation), etc.

Hypothyroid myopathy is a skeletal muscle disease caused by hypothyroidism. However, patients with hypothyroidism are often misdiagnosed as polymyositis if they do not have a clear history of thyroid gland or obvious hypometabolic symptoms, but with myasthenia and myalgia as the main symptoms or the first symptoms. Moreover, hypothyroid myopathy with periodic paralysis as the first symptom is rare in clinic. In this study, we summarized the clinical data of 1 case of hypothyroid myopathy with periodic paralysis as the first symptom in our clinical diagnosis and treatment. A 27-year-old male patient with recurrent periodic paralysis was found with hypothyroidism during a most recent attack of myasthenia and was diagnosed with hypothyroid myopathy, which was relieved after oral administration of levothyroxine. We also found 13 similar cases reported internationally, and summarized their clinical characteristics, diagnosis, and treatment methods to provide reference for the clinical diagnosis and treatment of such cases. In general, periodic paralysis may be the main symptom or even the first symptom of hypothyroid myopathy, which is easy to be confused with renal tubular acidosis (RTA) or other autoimmune diseases. The diagnosis is mainly based on the detection of thyroid function and thyroid autoantibodies. Timely supplement of thyroxine and correction of electrolyte disorders are the key to treatment.

Thyrotoxic periodic paralysis (TPP) is a rare manifestation of hyperthyroidism. The pathophysiology of hyperthyroidism causing periodic paralysis involves the Na+/K+ ATPase and potassium channels. We present a case of a 30-year-old male who presented to the ED with acute onset of upper and lower limb weakness. The patient was found to have bilateral weakness in the upper and lower limbs, orbital hypertelorism, and mandibular hypoplasia. He was also found to have hypokalemia, low thyroid-stimulating hormone (TSH), elevated thyroid peroxidase antibody, and elevated thyroid-stimulating immunoglobulins. The patient\'s EKG was remarkable for a prolonged QTc interval. The patient regained his muscle strength after potassium replacement in less than 24 hours. He was started on methimazole and potassium supplements. Our case is unique because it shows the possibility of the presence of Andersen-Tawil syndrome (ATS) (long QT syndrome 7), diagnosed by the presence of periodic paralysis, long QT, and dysmorphic facial features with TPP. In conclusion, thyrotoxicosis can trigger ATS; also the two syndromes can co-exist owing to the similarity in their pathophysiology.

We are presenting a case of hypokalemic paralysis in a patient who presented to the emergency department (ED) with a unique clinical picture that did not fully fit with other causes of periodic paralysis (hypokalemic periodic paralysis, thyrotoxic periodic paralysis, hyperkalemic periodic paralysis, and Anderson syndrome). The patient presented to the ED complaining of two days of severe flaccid paralysis in both legs and left arm; his right arm was completely normal. Initially, he was treated as a stroke alert patient and had head and spine computed tomography (CT) scans and both showed no acute pathologic changes. Initial labs showed a potassium level of 1.9 and a magnesium level of 1.8. Electrocardiography (EKG) showed prolonged QTc of 534 ms. The patient was admitted to the ICU and started on intravenous and oral potassium replacement. Over the next 24 hours, he started to regain his muscle power gradually until it came back to his baseline. Repeat EKG also showed QTc back to normal. We compared our patient\'s initial presentation to other published case reports with periodic paralysis and found that his initial presentation was different than other published cases.

BACKGROUND: Thyrotoxic periodic paralysis (TPP) is a rare and potentially lethal complication of hyperthyroidism. It is characterized by sudden onset paralysis associated with hypokalemia. Management includes prompt normalization of potassium, which results in resolution of the paralysis. Definitive treatment of hyperthyroidism resolves TPP completely.
METHODS: A 23-year-old African American male patient presented to the emergency room at the University of Mississippi Medical Center, USA in November 2016 with sudden onset quadriplegia. He also endorsed a history of weight loss, palpitations, heat intolerance and tremors. The patient reported similar episodes of quadriplegia in the past, which were associated with hypokalemia and resolved with normalization of potassium levels. Physical examination was significant for exophthalmos, smooth goiter with bruit consistent with the diagnosis of Graves\' disease. Laboratory assessment showed severe hypokalemia, hypomagnesemia, suppressed thyroid stimulating hormone (TSH) and high free thyroxine (T4). Urine potassium creatinine ratio was less than one, indicating transcellular shift as the cause of hypokalemia. After normalization of potassium and magnesium, the paralysis resolved in 12 hours. He was started on methimazole. On follow up, the patient was clinically and biochemically euthyroid with no further episodes of paralysis.
UNASSIGNED: TPP is a rare and reversible cause of paralysis. Physicians need to be aware of the diagnostic and treatment modalities as delayed recognition in treatment could result in potential harm or unnecessary interventions.

Skeletal muscle sodium channelopathies (SMSCs) including hyperkalemic periodic paralysis (HyperPP), paramyotonia congenita (PC), and sodium channel myotonia are caused by sodium channel gene (SCN4A) mutations, with altered sarcolemal excitability, and can present as episodes of skeletal muscle weakness, paralysis, and myotonia. We report a teenage boy, who presented with features of HyperPP, PC, myotonia congenita, and sodium channel myotonia. His electromyography (EMG) revealed myopathic changes, myotonia, and Fournier EMG pattern I, and posed a diagnostic challenge. Genetic analysis showed Thr704Met mutation in SCN4A gene. While with typical clinical phenotypes, the electromyographic patterns can be used to direct genetic testing, atypical phenotypes may pose diagnostic dilemmas. Clinicians dealing with neuromuscular disorders in children need to be aware of the unusual clinical presentations of SMSC, so that focused genetic testing can be carried out.