Episodic Muscle Disorders.

PURPOSE OF REVIEW: This article reviews the episodic muscle disorders, including benign cramp-fasciculation syndrome, the periodic paralyses, and the nondystrophic myotonias. The core diagnostic criteria for a diagnosis of primary periodic paralysis, including clues to distinguish between the hypokalemic and hyperkalemic forms, and the distinctive elements that characterize Andersen-Tawil syndrome are discussed. Management of patients with these disorders is also discussed. RECENT FINDINGS: Childhood presentations of periodic paralysis have recently been described, including atypical findings. Carbonic anhydrase inhibitors, such as dichlorphenamide, have recently been approved by the US Food and Drug Administration (FDA) for the treatment of both hypokalemic and hyperkalemic forms of periodic paralysis. Muscle MRI may be a useful outcome measure in pharmacologic trials in periodic paralysis. Genetic research continues to identify additional gene mutations responsible for periodic paralysis. SUMMARY: This article will help neurologists diagnose and manage episodic muscle disorders and, in particular, the periodic paralyses and the nondystrophic myotonias.

What the internist should know about hereditary muscle channelopathies.

OBJECTIVES: Non-dystrophic myotonia, periodic paralysis and, to a certain extent, myotonic dystrophies are rare hereditary skeletal muscle channelopathies, charactarized by myotonia or episodic muscle weakness. This review highlights the diagnostic challenges and treatment options. RESULTS: Some of these rare skeletal muscle disorders are associated with a broad range of systemic and nonspecific muscle symptoms. Consequently, patients are often referred to the internist before seeing a neurologist. This article provides clinical clues to better diagnose an tackle these unique disorders. CONCLUSION: A increased knowledge will reduce the diagnostic delay, improve monitoring and treatment, and might even prevent potentially life-threatening conditions as seen in DM.

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.

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: a case report and literature review.

We describe a 37-year-old man with a 4-month history of episodic muscular weakness, involving mainly lower-limbs. Hypokalemia was documented in one episode and managed with intravenous potassium chloride. Hyperthyroidism was diagnosed 4 months after onset of attacks because of mild symptoms. The patient was subsequently diagnosed as having thyrotoxic periodic paralysis associated with Graves' disease. Treatment with propranolol and methimazol was initiated and one year later he remains euthyroid and symptom free. Thyrotoxic periodic paralysis is a rare disorder, especially among Caucasians, but it should always be considered in patients with acute paralysis and hypokalemia, and thyroid function should be evaluated.

Periodic paralysis.

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.

[Periodic paralysis: new pathophysiological aspects]. / Les paralysies périodiques: nouveaux aspects physiopathologiques.

Periodic paralyses are neuromuscular disorders characterized by attacks of muscle weakness coinciding with changes in blood potassium levels. They are thus classified as hypokalaemic, normokalaemic or hyperkalaemic. Most forms are genetic, with autosomal dominant inheritance. These diseases are channelopathies, i.e. caused by mutations in ion channel genes. The culprit genes encode muscle sodium, calcium and potassium channels. Mutations in calcium or potassium channels cause periodic paralyses of the same type (hypokalaemic periodic paralysis or Andersen-Tawil Syndrome). In contrast, distinct mutations in the gene encoding the sodium channel can cause the entire range of periodic paralysis (hypokalaemic, normokalaemic or hyperkalaemic). The physiological consequences of mutations have been studied with patch-clamp techniques and electromyography. Generally speaking, mutations alter the excitability cycle of the muscle membrane, resulting in a loss of function (paralysis). Electromyographic studies have demonstrated a good correlation between symptoms and physiological parameters, giving rise to a classification that can help orient the molecular diagnosis. Work on the genetics and pathophysiology of periodic paralyses has helped to improve the diagnosis and management of these syndromes.

An unrecognized cause of paralysis in ED: thyrotoxic normokalemic periodic paralysis.

Hypokalemic paralysis associated with hyperthyroidism (TPP) is a well-known acute electrolyte and muscle function disorder. Lesser known is normokalemic periodic paralysis associated with hyperthyroidism. We describe two cases of young men with acute muscular paralysis and bilateral impairment of sensation over the lower legs who had normal plasma potassium concentrations. They were initially misdiagnosed as having Guillain-Barré syndrome or hysterical paralysis. However, thyroid function tests showed elevated serum T(3) and T(4) and markedly depressed thyroid-stimulating hormone findings consistent with hyperthyroidism. Control of the hyperthyroidism completely abolished their periodic paralysis. Thyrotoxic normokalemic periodic paralysis (TNPP) should be kept in mind as a cause of acute muscle weakness to avoid missing a treatable and curable condition.

[HYPP: hyperkalemic periodic paralysis in the horse]. / HYPP: hyperkaliëmische periodieke verlamming bij het paard.

Hyperkalaemic periodic paralysis(HYPP) is characterized by intermittent episodes of muscular tremor, weakness, and collapse, and is probably caused by abnormal electrolyte transport in the muscle cell membrane. During an episode of HYPP, most animals are severely hyperkalaemic. HYPP is a hereditary disease and occurs only in American Quarter horses or crossbreds. Because these horses are now being imported into the Netherlands, HYPP should be included in the differential diagnosis of horses showing signs of muscle tremor, paresis, or paralysis. The present article reviews the literature on HYPP and describes a case showing typical signs of the disease.

Thyrotoxic periodic paralysis in a Jamaican male.

Thyrotoxic periodic paralysis is a rare endocrine disorder most prevalent among individuals of Asian descent that presents as proximal muscle weakness, hypokalemia, and signs of hyperthyroidism. We present the case report of a patient with previously undiagnosed hyperthyroidism, protracted muscle weakness with transient exacerbations, and nocturnal onset of periodic paralysis affecting the upper and lower limbs.

Thyrotoxic periodic paralysis in a Jamaican male

Thyrotoxic periodic paralysis is a rare endocrine disorder most prevalent among individuals of Asian descent that presents as proximal muscle weakness, hypokalemia, and signs of hyperthyroidism. We present the case report of a patient with previously undiagnosed hyperthyroidism, protracted muscle weakness with transient exacerbations, and nocturnal onset of periodic paralysis affecting the upper and lower limbs (AU)

Fibromyalgia in hyperkalemic periodic paralysis.

A 43-year-old woman presented at the age of 38 with joint pains and muscle stiffness. Tender points were found fulfilling ACR criteria (1) for fibromyalgia. She had well developed muscles and decreasing muscle power since the age of 35. Muscle pains increased after exercise. Her 10-year-old son had similar symptoms and one paralytic attack. Muscle pain and fatigue increasing with age were found by history in three close relatives. Forearm cold water test produced myotonia in both mother and son. Electromyography was normal and muscle biopsy showed minor unspecific changes. Biochemical investigation of muscle mitochondrial function was normal. Peroral potassium load test produced complete muscle paralysis at a potassium serum level of 5.0 mmol/l. Autosomal dominant hyperkalemic periodic paralysis was diagnosed. Frequent carbohydrate enriched meals, peroral bendroflumethiazide and restriction to submaximal exercise improved muscle and joint pain. Salbutamol peroral spray relieved the periodic weakness.

Parálisis periódica hipokalémica: a propósito de dos casos / Hipokalemic periodic paralysis: apropos of 2 cases

La parálisis periódica hipocalémica es una entidad poco frecuente, con un aparente rasgo genético, que reconoce una variada lista etiológica, dependiendo de las mismas la terapéutica a instaurar. Debido a la gravedad de la presentación clínica y a la restitución ad integrum luego del adecuado tratamiento del desorden electrolítico, es que se presentan los siguientes casos para su discusión.

Parálisis periódica hipokalémica: a propósito de dos casos / Hipokalemic periodic paralysis: apropos of 2 cases

La parálisis periódica hipocalémica es una entidad poco frecuente, con un aparente rasgo genético, que reconoce una variada lista etiológica, dependiendo de las mismas la terapéutica a instaurar. Debido a la gravedad de la presentación clínica y a la restitución ad integrum luego del adecuado tratamiento del desorden electrolítico, es que se presentan los siguientes casos para su discusión. (AU)

[A case of potassium-sensitive periodic paralysis with cardiac dysrhythmia].

The authors reported a case of potassium-sensitive periodic paralysis with cardiac dysrhythmia. The patient was a 21-year-old male and had periodic paralysis and asymptomatic cardiac dysrhythmia since the age of 12. His attacks worsened in frequency and intensity which brought him to our hospital at the age of 21. Physical examination on admission revealed slight dysmorphic features such as hypoplastic mandible and high-arched palate. He had slight proximal muscle atrophy with no myotonia. Electrocardiogram showed multifocal ventricular arrhythmia. The serum potassium levels during his paralytic attacks were normal or slightly decreased (3.6-4.2 mEq/l). Both potassium and glucose tolerance tests provoked paralytic attacks. Glucose tolerance test also aggravated his cardiac dysrhythmia. Acetazoramide administration improved his paralytic attack. Potassium-sensitive periodic paralysis with cardiac dysrhythmia can not be defined by the classification of periodic paralysis based on the serum potassium concentration. Provocative tests should be done to make a definite diagnosis and treatment should be done taking into consideration both paralytic attack and cardiac dysrhythmia.