Pain as a significant symptom in patients with periodic paralysis-A cross-sectional survey.

INTRODUCTION: Periodic paralysis (PP) is thought to be limited to episodes of muscle weakness, but there are reports of fibromyalgia-like pain in PP. We aimed to evaluate pain and comorbid sleep, fatigue, and mood disorders in PP patients. METHODS: We administered a cross-sectional survey to PP patients at the 2019 Periodic Paralysis Conference. The survey consisted of the Brief Pain Inventory, Widespread Pain Index, Pittsburgh Sleep Quality Index, Modified Fatigue Impact Scale, and ten-question Center for Epidemiologic Studies Depression Scale (CESD-10). Descriptive statistics for PP patients were calculated and compared with earlier studies. RESULTS: Forty-four individuals with PP took the survey. Of these patients, 52.3% reported a moderate to severe interference of pain on their lives, and 45.5% met the study criteria for fibromyalgia. Patients with SCN4A mutations had higher rates of fibromyalgia than the next most prevalent gene mutation, CACNA1S. In patients with pain, there were increased rates of comorbid fatigue, depression, and poor sleep quality. DISCUSSION: Pain, akin to fibromyalgia, is a significant symptom of PP and can affect quality of life. Pain in PP was more prevalent than in the general population, at a rate comparable with other chronic neuromuscular disease groups. PP patients could benefit from a multidisciplinary approach to assess their pain, sleep, fatigue, and mood.

Pathophysiologic and anesthetic considerations for patients with myotonia congenita or periodic paralyses.

Myotonia congenita and periodic paralyses are hereditary skeletal muscle channelopathies. In these disorders, various channel defects in the sarcolemma lead to a severely disturbed membrane excitability of the affected skeletal muscles. The clinical picture can range from severe myotonic reactions (e.g., masseter spasm, opisthotonus) to attacks of weakness and paralysis. Provided here is a short overview of the pathomechanisms behind such wide-ranging phenotypic presentations in these patients, followed by recommendations concerning the management of anesthesia in such populations.

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.

A sodium channel defect in hyperkalemic periodic paralysis: potassium-induced failure of inactivation.

Hyperkalemic periodic analysis (HPP) is an autosomal dominant disorder characterized by episodic weakness lasting minutes to days in association with a mild elevation in serum K+. In vitro measurements of whole-cell currents in HPP muscle have demonstrated a persistent, tetrodotoxin-sensitive Na+ current, and we have recently shown by linkage analysis that the Na+ channel alpha subunit gene may contain the HPP mutation. In this study, we have made patch-clamp recordings from cultured HPP myotubes and found a defect in the normal voltage-dependent inactivation of Na+ channels. Moderate elevation of extracellular K+ favors an aberrant gating mode in a small fraction of the channels that is characterized by persistent reopenings and prolonged dwell times in the open state. The Na+ current, through noninactivating channels, may cause the skeletal muscle weakness in HPP by depolarizing the cell, thereby inactivating normal Na+ channels, which are then unable to generate an action potential. Thus the dominant expression of HPP is manifest by inactivation of the wild-type Na+ channel through the influence of the mutant gene product on membrane voltage.

Hypokalemic periodic paralysis in Sjögren's syndrome.

A 30-year-old woman had scleroderma, Sjögren's syndrome, deforming polyarthritis, distal renal tubular acidosis, hypokalemic periodic paralysis, and persistent mild myopathy. During a five-year period the patient's otherwise mild course of disease was complicated by the occurrence of five episodes of severe flaccid muscle paralysis involving both proximal and distal muscle groups. Between the paralytic episodes the patient functioned well without replacement therapy, and had normal potassium levels. The sicca component was mild and went unrecognized for several years. There was no family history of muscle disease. The data presented in this report support the view that the paralytic episodes were due to hypokalemia secondary to renal tubular acidosis associated with Sjögren's syndrome. Hypokalemic periodic paralysis may occur as a rare complication of Sjögren's syndrome and renal tubular acidosis.

Familial hyperkalemic periodic paralysis and bipolar disorder: a linkage and treatment study.

Familial hyperkalemic periodic paralysis and bipolar disorder are both hereditary disorders, characterized by episodes of illness separated by periods of remission, and possibly related to abnormalities in cellular ion transport. Recently we discovered a patient who suffered from both illnesses, as did his mother and grandmother. However, a detailed investigation of the pedigree suggested that these two disorders are not linked genetically. Furthermore, a placebo-controlled double-blind trial of lithium carbonate in this patient found lithium ineffective in preventing the attacks of paralysis, in contrast to another recent study which found lithium effective in hypermagnesemic periodic paralysis.

Biphasic periodic paralysis.

A young man with episodes characteristic of familial normokalemic periodic paralysis was restudied after a change in the nature of his attacks. He now has spontaneously occurring and provokable episodes of both hyperkalemic and hypokalemic periodic paralyses that are superimposed on a persistent myopathy. Hypokalemia seems to be associated with facilitated entry of glucose and potassium into muscles, whereas resistance to glucose and potassium entry accompanies hyperkalemia. The possibility that episodes of both hypokalemic and hyperkalemic weaknesses can occur in one person should be considered in pathogenic postulates regarding periodic paralysis.

Progressive myopathy in hyperkalemic periodic paralysis.

A progressive degenerative myopathy has been well described in hypokalemic periodic paralysis but is not as widely recognized in hyperkalemic periodic paralysis. We studied four families with the latter disease in which some members developed a progressive myopathy. Episodes of paralysis were prolonged, lasting for months in some cases, and in one case paralysis was sufficiently severe to require ventilatory support. The progressive myopathy tended to develop at a time when attacks of paralysis were decreasing in frequency. Muscle biopsy specimens showed variability in fiber size, internal nuclei, and fibers with vacuoles. Electron microscopy showed myofibrillary degeneration and tubular aggregates. An abnormal biopsy specimen was more common in older patients. Our experience suggests that a progressive myopathy is as common in hyperkalemic periodic paralysis as it is in the hypokalemic disorder.

Interictal conduction slowing in muscle fibers in hypokalemic periodic paralysis.

Conduction velocity in muscle fibers of the short head of biceps brachii was reduced between attacks in all the affected members of a family suffering from hypokalemic periodic paralysis. This finding represents a further evidence of a primary alteration of sarcolemmal function in this disease. Interictal conduction slowing in muscle fibers is consistent with the prevailing pathophysiologic hypothesis, which considers an increased membrane permeability to sodium ions as the fundamental defect underlying all forms of familial periodic paralysis.

Insulin-mediated hypokalemia and paralysis in familial hypokalemic periodic paralysis.

To elucidate a potential role for insulin-mediated extra-renal potassium disposal in the clinical syndrome of hypokalemic periodic paralysis, an obese affected man was studied using the euglycemic insulin clamp, which, in normal and obese subjects, produces predictable, insulin dose-dependent declines in plasma potassium levels. During a 20 mU/m2/minute euglycemic clamp (insulin level, 88 microU/ml) procedure, while the patient with hypokalemic periodic paralysis demonstrated severe resistance to insulin-mediated glucose uptake (glucose uptake 50 percent of that of normal control subjects, n = 17), his plasma potassium declined to a degree similar to that seen in normal subjects. During a subsequent higher dose, 200 mU/m2/minute insulin infusion (insulin level, 914 microU/ml), plasma potassium declined to 2.5 meq/liter, a value significantly below that seen in normal (n = 19) (3.3 +/- 0.1 meq/liter) and obese (n = 6) (3.2 +/- 0.1 meq/liter) subjects. During this study, paralysis began in the patient's hand and forearm at the potassium nadir and lasted three hours, despite restoration of normokalemia 30 minutes after paralysis began. Glucose disposal rates during this high-dose insulin infusion were one-half that seen in lean control subjects (n = 19) and similar to those in obese control subjects. If these findings are representative of hypokalemic periodic paralysis and can be generalized to larger numbers of patients, they indicate several new features of this syndrome. The ability of insulin to induce hypokalemia is enhanced in this syndrome even in the presence of marked coexistent obesity-related resistance to the action of insulin to promote glucose utilization. Enhanced sensitivity of potassium uptake systems to activation by insulin (and other factors) may be a central feature of this syndrome. Additionally, paralytic hypokalemia can be induced during a euglycemic insulin clamp procedure, which could be utilized as a diagnostic test for this syndrome.

Linkage of malignant hyperthermia and hyperkalemic periodic paralysis to the adult skeletal muscle sodium channel (SCN4A) gene in a large pedigree.

Hyperkalemic periodic paralysis (HPP) is caused by mutations of the adult skeletal muscle sodium channel (SCN4A) gene on chromosome 17. Malignant hyperthermia (MH) is a genetically heterogeneous autosomal-dominant disorder occurring in association with various neuromuscular diseases or without other apparent abnormalities. In some families, MH is associated with mutations of a calcium release channel (RYR1) gene on chromosome 19. In other families, linkage of this disorder to the SCN4A gene on chromosome 17 has been suggested. We report on linkage analysis in a family in which both HPP and MH are inherited as autosomal-dominant traits. Two polymorphisms within the SCN4A locus, an RFLP and a (C-A)n repeat, were typed on multiple family members. The findings were consistent with linkage of the polymorphic markers within the SCN4A gene to both HPP (Zmax = 6.79 at theta = 0.0) and MH (Zmax = 1.76 at theta = 0) in this family. Our data provide further evidence that MH is linked to the SCN4A locus in some families.

Cardiac dysfunction in a patient with familial hypokalemic periodic paralysis.

A 19-year-old white man with familial hypokalemic periodic paralysis developed evidence of cardiac dysfunction during a episode of flaccid paralysis. This consisted of elevated total creatine phosphokinase (CPK), an increased myocardial fraction of CPK (myocardial band), alteration in the lactic dehydrogenase isoenzyme pattern, severe bradycardia, and evidence of left ventricular dysfunction. These findings, in conjunction with selected cases from the literature, suggest the possibility that cardiomyopathy may be a heretofore unrecognized complication of this disorder.

Thyrotoxic hypokalemic periodic paralysis following second-trimester prostaglandin-induced abortion.

BACKGROUND: Hypokalemic periodic paralysis with thyrotoxicosis has never been described in pregnancy or the puerperium. CASE: A 31-year-old Hispanic woman underwent three prostaglandin inductions for a second-trimester missed abortion. Her management was complicated by hyperthermia, nausea, vomiting, and diarrhea. She developed isolated proximal muscle paralysis and sensory loss on the first post-abortion day. Her serum potassium was 1.5 mEq/L. The serum free thyroxine index exceeded 25 and TSH was below 0.03 microIU/mL, leading to a diagnosis of thyrotoxic hypokalemic periodic paralysis. Oral and parenteral potassium repletion restored full neurologic function, and propylthiouracil treatment was initiated until thyroid ablation could be performed. CONCLUSION: Gastrointestinal potassium loss during prostaglandin-induced abortion may unmask previously undiagnosed periodic paralysis.

Rhabdomyolysis in hypokalaemic periodic paralysis: a clue to the mechanism that terminates the paralytic attack?

The changes in serum levels of myoglobin (Mb) and creatine kinase (CK) during a spontaneous attack of hypokalaemic periodic paralysis were studied. During paralysis, serum Mb and CK were normal. A rise in plasma potassium, resulting in clinical recovery, was associated with a simultaneous rise in serum Mb, and followed by a rise in serum CK. It is postulated that hypokalaemia might cause muscle ischaemia, which would result in an accumulation of free fatty acids (FFA) within the muscle cells. High concentrations of FFA may induce molecular changes and increase the permeability of the sarcolemma. This might be the mechanism by which potassium is released from muscle cells into the circulation and muscle membrane excitability is restored.

Hypokalemic periodic paralysis. A single fiber electromyographic study.

The neurophysiological findings obtained with standard electromyography (EMG) and single fiber EMG (SFEMG) in a case of hypokalemic periodic paralysis (HoPP) are reported. During the period between paralytic attacks the only abnormalities consisted of scanty fibrillation potentials and, with SFEMG, a fiber density increase. In the first stage of an induced paralytic attack the most striking feature was decrease in fiber density, slight increase in jitter with several blocks. These results indicate a failure of the membrane surface to propagate an action potential. In some fibers the block is likely to be permanent, thus explaining the decrease in fiber density. The jitter increase is due to a slight abnormality at the synaptic site or to a variation in the propagation velocity of the muscle fiber.

Psychosis in a patient with hyperkalemic periodic paralysis.

Presentation of an unusual case of a hyperkalemic periodic paralysis patient who developed a psychotic illness during the course of treatment is made in a conference format. The differential diagnosis of this psychotic episode together with some information regarding hyperkalemic periodic paralysis are discussed. The case illustrates the benefits of close cooperation between medical and psychiatric teams in the management of the psychotic patient with medical illness.

Familial periodic paralysis with hypokalaemia. Study of a muscle biopsy in the myopathic stage of the disorder.

A 51 year-old male patient was affected by a dominantly inherited periodic paralysis. With large potassium supplements and ageing, the number and severity of attacks became considerably reduced. Increasing weakness and atrophy of the lower extremities were documented by clinical examination and by computer-assisted tomography of the muscles. A biopsy was taken in the vastus lateralis muscle without any attempt to induce a hypokalaemic paralytic attack. Light microscopy showed multiple intra- and extracellular vacuoles, rimmed vacuoles, myonecrosis, fatty degeneration and endomysial fibrosis. The endomysial nerve bundles were normal. Both fiber types were vacuolated. Quantitative studies revealed abnormal variability coefficients and increased atrophy factors for all types. Electron microscopy showed dilatations of the tubular system and of the sarcoplasmic reticulum communicating with large vacuoles limited by a single membrane. Other vacuoles were covered by a basement membrane and could contain collagen fibers or capillaries. Accumulation of myeloid bodies and of 10-13 nm filaments were also noted in the sarcoplasm. Cytoplasmic bodies were present. No tubular aggregates could be found. The nerve bundles were normal. These findings were in part similar to the ones reported by Gérard et al. (1978) in the son's biopsy during an induced paralytic attack. Significant findings in our case are the sequence of events leading to muscle fibre destruction, still detectable at an advanced stage of the disease. Myopathic changes represent a delayed but severe complication of the disorder.

Clinical syndrome and diagnosis of hyperkalaemic periodic paralysis in quarter horses.

Of the 16 horses studied, 14 belonged to a family previously shown to be susceptible to hyperkalaemic periodic paralysis (HPP), and 8 were shown to have HPP. Diagnosis of HPP by electromyographic detection of myotonic discharges or by oral administration of KCl to induce clinical signs and hyperkalaemia had similar reliability and gave the same result in 80% of cases. KCl had to be administered at doses up to 0.2 g/kg bodyweight to produce signs in some horses. KCl challenge testing was more time consuming than EMG and resulted in one fatality. Overall, electromyography and potassium challenge testing together gave the most accurate diagnosis. Horses were more likely to manifest signs of HPP if they were immature. There was no sex predisposition. The most frequent sign of HPP was muscle fasciculation. Other signs were sweating, muscle spasm, and weakness. Respiratory rate increased greatly during some attacks. Attacks of muscle fasciculation without hyperkalaemia were observed in 2 HPP-affected horses. Affected horses had a greater frequency of spontaneous clinical abnormalities, due mainly to trailering problems, traumatic abrasions and episodes of continuous muscle fasciculation. Hyperkalaemia was confirmed in only one of these instances.