A combination of electrophysiological and genetic studies has
resulted in the identification of several skeletal muscle disorders
to be caused by pathologically functioning ion channels
and has led to the term channelopathies. Typical hereditary
muscle channelopa thies are congenital myasthenic syndromes,
non-dystrophic myotonias, periodic paralyses, malignant hyperthermia,
and central core disease. Most muscle channelopathies
are commonly considered to be benign diseases. However, lifethreatening
weakness episodes or progressive permanent weakness
may make these diseases severe, particularly the periodic
paralyses (PP). Even in the typical PP forms characterized by
episodic occurrence of weakness, up to 60% of the patients suffer
from permanent weakness and myopathy with age. In addition,
some PP patients present with a predominant progressive muscle
weakness phenotype. The weakness can be explained by strongly
depolarized fibers that take up sodium and water and that are
electrically inexcitable. Drugs that repolarize the fiber membrane
can restore muscle strength and may prevent progression.
Congenital myasthenic syndromes; non-dystrophic
myotonias; periodic paralyses; susceptibility to malignant hyperthermia; central core disease
Myotonic syndromes and periodic paralyses are rare disorders of skeletal muscle characterized mainly by muscle stiffness or episodic attacks of weakness. Familial forms are caused by mutation in genes coding for skeletal muscle voltage ionic channels. Familial periodic paralysis and nondystrophic myotonias are disorders of skeletal muscle excitability caused by mutations in genes coding for voltage-gated ion channels. These diseases are characterized by episodic failure of motor activity due to muscle weakness (paralysis) or stiffness (myotonia). Clinical studies have identified two forms of periodic paralyses: hypokalemic periodic paralysis (hypoKPP) and hyperkalemic periodic paralysis (hyperKPP), based on changes in serum potassium levels during the attacks, and three distinct forms of myotonias: paramyotonia congenita (PC), potassium-aggravated myotonia (PAM), and myotonia congenita (MC). PC and PAM have been linked to missense mutations in the SCN4A gene, which encodes α subunit of the voltage-gated sodium channel, whereas MC is caused by mutations in the chloride channel gene (CLCN1). Exercise is known to trigger, aggravate, or relieve symptoms. Therefore, exercise can be used as a functional test in electromyography to improve the diagnosis of these muscle disorders. Abnormal changes in the compound muscle action potential can be disclosed using different exercise tests. Five electromyographic (EMG) patterns (I-V) that may be used in clinical practice as guides for molecular diagnosis are discussed.
Channelopathy; electromyographic; ion channel; myotonia; periodic paralysis
Cisplatin is a well-known nephrotoxic antineoplastic drug. Chronic hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria is one of the rare complications associated with its use.
A 42- year-old woman presented with a 20 year-history of hypokalemic metabolic alkalosis with hypomagnesemia and hypocalciuria after cisplatin-based chemotherapy for ovarian cancer. This patient has had chronic muscle aches and fatigue and has had episodic seizure-like activity and periodic paralysis. Only thirteen other patients with similar electrolyte abnormalities have been described in the literature. This case has the longest follow-up.
Cisplatin can cause permanent nephrotoxicity, including Gitelman-like syndrome. This drug should be considered among the possible causes of chronic unexplained electrolyte disorders.
Thyrotoxic periodic paralysis (TPP) attacks are characterized as recurrent, transient episodes of muscle weakness that range from mild weakness to complete flaccid paralysis. Episodes of weakness are accompanied by hypokalemia, which left untreated can lead to life-threatening arrhythmias (6). In this case study, we followed a patient’s potassium levels analyzing how they correlate with electrocardiogram changes seen while treating his hypokalemia and ultimately his paralysis.
According to the Khmer conception, a person suffering ‘weak heart’ (khsaoy beh daung) has episodes of palpitations on slight provocation (e.g. triggered by orthostasis, anger, a noise, worry, an odor or exercise) and runs the risk of dying of heart arrest during these periods of palpitations; too, the sufferer typically has other symptoms attributed to the purported cardiac dysfunction: fatigue, shortness of breath, and orthostatic dizziness. Many Khmer refugees suffer this cultural syndrome, an anxious–dysphoria ontology, most probably of French colonial provenance. The syndrome demonstrates considerable overlap with those Western illness categories that feature panic attacks, in particular post-traumatic stress disorder (PTSD) and panic disorder. In a psychiatric clinic survey, 60 percent (60/100) of those assessed believed themselves to currently suffer ‘weak heart’; 90 percent (54/60) of those considering themselves to suffer from ‘weak heart’ thought that palpitations (e.g., those resulting from a loud noise or orthostasis) might result in death. The article illustrates the profoundly culturally constructed nature of ‘cardiac sensations,’ located in a specific historical trajectory and episteme; too, the article suggests that trauma may result more in panic disorder than ‘PTSD’ when autonomic arousal symptoms (in the present case, palpitations) are considered potentially life-threatening.
Khmer refugees; panic attacks; panic attacks; PTSD; trauma
Thyrotoxic hypokalemic periodic paralysis (THPP) is a rare, potentially life-threatening endocrine emergency. It is characterized by recurrent muscle weakness and hypokalemia. Because many THPP patients do not have obvious symptoms and signs of hyperthyroidism, misdiagnosis may occur. The published studies revealed that definitive therapy for THPP is control of hyperthyroidism by medical therapy, radioactive iodine or surgery, but the long-term post-operative follow-up result was not observed. We reported two cases of medically refractory THPP with recurrent paralysis of extremities and hypokalemia, and both were combined with thyroid nodules. Both patients were treated with total thyroidectomy; the pathology revealed that one is Graves' disease with thyroid papillary carcinoma, and the other is adenomatous goiter with papillary hyperplasia. No episode of periodic paralysis was noted and laboratory evaluation revealed normal potassium level during the post-operative follow up. Our experience suggests that total thyroidectomy by experienced surgeon is an appropriate and definite treatment for medically refractory THPP, especially in cases combined with thyroid nodules.
thyrotoxic hypokalemic periodic paralysis; hypokalemic periodic paralysis; thyrotoxic; thyrotoxic periodic paralysis; thyroidectomy
Acute kidney injury (AKI) caused by hypothyroidism-induced rhabdomyolysis is a rare and potentially life-threatening syndrome. The aim of this study was to investigate the clinical characteristics of such patients.
Materials and Methods
We retrospectively analyzed five patients treated at the Second Affiliated Hospital of Chongqing Medical University with AKI secondary to hypothyroidism-induced rhabdomyolysis from January 2006 to December 2010.
Of the five cases reviewed (4 males, age range of 37 to 62 years), adult primary hypothyroidism was caused by amiodarone (1 case), chronic autoimmune thyroiditis (1 case), and by uncertain etiologies (3 cases). All patients presented with facial and lower extremity edema. Three patients presented with weakness, while two presented with blunted facies and oliguria. Only one patient reported experiencing myalgia and proximal muscle weakness, in addition to fatigue and chills. Creatine kinase, lactate dehydrogenase, and renal function normalized after thyroid hormone replacement, except in two patients who improved through blood purification.
Hypothyroidism should be considered in patients presenting with renal impairment associated with rhabdomyolysis. Moreover, further investigation into the etiology of the hypothyroidism is warranted.
Acute kidney injury; hypothyroidism; rhabdomyolysis
Thyrotoxic periodic paralysis (TPP) is a rare manifestation of hyperthyroidism characterized by muscle weakness and hypokalemia. All ethnicities can be affected, but TPP typically presents in men of Asian descent. The most common cause of TPP in thyrotoxicosis is Graves' disease. However, TPP can occur with any form of thyrotoxicosis. Up to our knowledge, very few cases ever reported the relationship between TPP and painless thyroiditis. We herein report a 25-yr-old Korean man who suffered from flaccid paralysis of the lower extremities and numbness of hands. The patient was subsequently diagnosed as having TPP associated with transient thyrotoxicosis due to painless thyroiditis. The paralytic attack did not recur after improving the thyroid function. Therefore, it is necessary that early diagnosis of TPP due to transient thyrotoxicosis is made to administer definite treatment and prevent recurrent paralysis.
Thyrotoxic Hypokalemic Periodic Paralysis; Painless Thyroiditis; Thyrotoxicosis
Amyotrophic lateral sclerosis (ALS) is a neurodegenerative disorder of motor neurons causing progressive muscle weakness, paralysis, and finally death. ALS patients suffer from asthenia and their progressive weakness negatively impacts quality of life, limiting their daily activities. They have impaired energy balance linked to lower activity of mitochondrial electron transport chain enzymes in ALS spinal cord, suggesting that improving mitochondrial function may present a therapeutic approach for ALS. When fed a ketogenic diet, the G93A ALS mouse shows a significant increase in serum ketones as well as a significantly slower progression of weakness and lower mortality rate. In this study, we treated SOD1-G93A mice with caprylic triglyceride, a medium chain triglyceride that is metabolized into ketone bodies and can serve as an alternate energy substrate for neuronal metabolism. Treatment with caprylic triglyceride attenuated progression of weakness and protected spinal cord motor neuron loss in SOD1-G93A transgenic animals, significantly improving their performance even though there was no significant benefit regarding the survival of the ALS transgenic animals. We found that caprylic triglyceride significantly promoted the mitochondrial oxygen consumption rate in vivo. Our results demonstrated that caprylic triglyceride alleviates ALS-type motor impairment through restoration of energy metabolism in SOD1-G93A ALS mice, especially during the overt stage of the disease. These data indicate the feasibility of using caprylic acid as an easily administered treatment with a high impact on the quality of life of ALS patients.
Hyperthyroidism may be associated with hypokalemic periodic paralysis. Two cases are presented demonstrating intermittent attacks of flaccid paralysis associated with clinical symptoms, signs and laboratory findings of hyperthyroidism. During an attack, one patient had a serum potassium of 2.1 mEq. per litre.
Various factors such as trauma, exposure to cold, excessive carbohydrate ingestion and certain medications have been stated to precipitate an episode of paralysis. Attacks may range from mild weakness to generalized flaccid paralysis with loss of deep tendon reflexes. Several reported patients have died owing to cardiac arrest or respiratory paralysis.
During attacks, the serum potassium is usually in the range of 2.2 to 3.2 mEq. per litre. It is postulated that a metabolic abnormality affecting the muscle-cell membrane can occur in the hyperthyroid state resulting in a shift of potassium to the intracellular position, thus producing a situation of hyperpolarization of the muscle-cell membrane which in turn alters the muscle contractibility.
The importance of recognizing the unusual association of hypokalemic periodic paralysis with hyperthyroidism is stressed because, with successful treatment of the hyperthyroidism, the episodes of paralysis disappear.
OBJECTIVE--To evaluate the use of microvascular decompression (MVD) for the treatment of hemifacial spasm (HFS). METHODS--Eighty three patients with HFS who underwent MVD via a suboccipital craniectomy are presented. RESULTS--Seventy two out of seventy eight patients available for follow up remained free of any spasms at a mean follow up period of eight years. Two patients continued to have minor intermittent muscle twitches and three had recurrence of HFS. One patient's operation was not completed. Twenty had a transient complication and eight were left with permanent postoperative deficits, the commonest being unilateral sensorineural deafness. Seventy one patients declared themselves satisfied with the procedure. A causative vessel was found on the root exit zone of the seventh cranial nerve in 81 patients. CONCLUSION--The procedure seems to provide lasting relief for most patients. The correct operative technique is essential if complications are to be avoided.
Familial hypokalemic periodic paralysis is an autosomal-dominant channelopathy characterized by episodic muscle weakness with hypokalemia. The respiratory and cardiac muscles typically remain unaffected, but we report an atypical case of a family with hypokalemic periodic paralysis in which the affected members presented with frequent respiratory insufficiency during severe attacks. Molecular analysis revealed a heterozygous c.664 C>T transition in the sodium channel gene SCN4A, leading to an Arg222Trp mutation in the channel protein. The patients described here presented unusual clinical characteristics that included a severe respiratory phenotype, an incomplete penetrance in female carriers, and a different response to medications.
Hypokalemic periodic paralysis; Respiratory insufficiency; Sodium channel
Feedback from service users will provide insight into opportunities for improvement so that performance can be optimised. In the context of a formative evaluation referring clinician and patient satisfaction with a teleneurophysiology service was examined during a 20 week pilot period.
Questionnaire surveys of referring clinicians and patients were conducted.
Fifteen (58%) clinicians responded to the first part of a postal survey which examined their satisfaction with traditional clinical neurophysiology services. Nine (35%) responded to a second part which assessed their experience with the teleneurophysiology service. Teleneurophysiology improved satisfaction with waiting times, availability of results and impact on patient management. There was unanimous support from the clinicians for the permanent development of a teleneurophysiology service, although 2 cautioned this could delay establishing a neurology service in their region.
Eighty-two percent (116/142) of patients responded to a survey of their satisfaction with teleneurophysiology. This was compared to a previous report of 322 patients' experience with traditional CN services in Ireland. Waiting times for appointment were shorter for the former group who supported the telemedicine model recognising that it reduced the travel burden and need for overnight journeys. The two groups were equally anxious about the investigation although the teleneurophysiology patients received more prior information.
This study illustrates that teleneurophysiology is an acceptable model of service delivery for its primary customers. Their feedback is important in informing appropriate design and governance of such innovative models of health service provision.
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.
Allelic disorder; myotonia; periodic paralysis; phenotype-genotype protocols; sodium channelopathy
BACKGROUND/PURPOSE: To determine the relation between visual impairment, visual functioning, and the global quality of life in patients with glaucoma. METHODS: Visual impairment, defined with the American Medical Association Guides to the Evaluation of Permanent Impairment; visual functioning, measured with the VF-14 and the Field Test Version of the National Eye Institute-Visual Functioning Questionnaire (NEI-VFQ); and the global quality of life, assessed with the Medical Outcomes Study 36-Item Short Form Health Survey (SF-36), were determined in 147 consecutive patients with glaucoma. RESULTS: None of the SF-36 domains demonstrated more than a weak correlation with visual impairment. The VF-14 scores were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual impairment. Of the twelve NEI-VFQ scales, distance activities and vision specific dependency were moderately correlated with visual field impairment; vision specific social functioning, near activities, vision specific role difficulties, general vision, vision specific mental health, color vision, and driving were modestly correlated; visual pain was weakly correlated; and two were not significantly correlated. Correcting for visual actuity weakened the strength of the correlation coefficients. CONCLUSIONS: The SF-36 is unlikely to be useful in determining visual impairment in patients with glaucoma. Based on the moderate correlation between visual field impairment and the VF-14 score, this questionnaire may be generalizable to patients with glaucoma. Several of the NEI-VFQ scales correlate with visual field impairment scores in patients with a wide range of glaucomatous damage.
Thyrotoxic periodic paralysis is a disease characterized by recurrent episodes of paralysis and hypokalemia during a thyrotoxic state. Thyrotoxic periodic paralysis is a common complication of hyperthyroidism in Asian populations, but can affect other ethnic groups as well. Due to population mobility, Thyrotoxic periodic paralysis is increasingly common in Western countries. Early diagnosis and prompt treatment of the thyrotoxic state and potassium supplementation prevent life-threatening complications associated with hypokalemia and muscle weakness. We present a young Turkish man who developed acute flaccid paralysis after receiving pulse prednisolone therapy for treatment of Pityriasis versicolor. His muscle strength and serum potassium fully recovered after potassium replacement and treatment of the thyrotoxic state which was a consequence of underlying Graves’ disease.
Seven families with familial hypokalaemic periodic paralysis were found in Finland. Nine of the 103 asymptomatic family members studied had abnormal results on a potassium exercise test. The overall prevalence of familial hypokalaemic periodic paralysis in Finland was 0.4/100,000. Carbohydrate intake and hard exercise were the most important triggers of paralytic attacks. Half of the patients reported having attacks at least once a month. Seven patients reported cardiac symptoms (especially bradycardia) during attacks. Permanent muscular weakness was not prominent.
Purpose: Fatigue is one of the most frequent debilitating symptoms reported by people with end-stage renal disease (ESRD) on haemodialysis (HD) therapy. A wide range of underlying abnormalities, including skeletal muscle weakness, have been implicated as causes of this fatigue. Skeletal muscle weakness is well established in this population, and such muscle weakness is amenable to physical therapy treatment. The purpose of this review was to identify morphological, electrophysiological, and metabolic characteristics of skeletal muscles in people with ESRD/HD that may cause skeletal muscle weakness.
Method: Electronic databases were searched for relevant literature from inception to March 2010. Inclusion criteria were English language; adult subjects with ESRD/HD; and the use of muscle biopsy, electromyography, and nuclear magnetic spectroscopy (31P-NMRS) techniques to evaluate muscle characteristics.
Results: In total, 38 studies were included. All studies of morphological characteristics reported type II fibre atrophy. Electrophysiological characteristics included both neuropathic and myopathic skeletal muscle changes. Studies of metabolic characteristics revealed higher cytosolic inorganic phosphate levels and reduced effective muscle mass.
Conclusion: The results indicate an array of changes in the morphological, electrophysiological, and metabolic characteristics of skeletal muscle structure in people with ESRD/HD that may lead to muscle weakness.
electromyography; end-stage renal disease (ESRD); metabolism; muscle weakness; skeletal muscle; électromyographie; faiblesse musculaire; insuffisance rénale chronique au stade ultime (IRSU); métabolisme; muscle squelettique
The skeletal muscle ryanodine receptor plays a crucial role in excitation–contraction (EC) coupling and is implicated in various congenital myopathies. The periodic paralyses are a heterogeneous, dominantly inherited group of conditions mainly associated with mutations in the SCN4A and the CACNA1S genes. The interaction between RyR1 and DHPR proteins underlies depolarization-induced Ca2+ release during EC coupling in skeletal muscle. We report a 35-year-old woman presenting with signs and symptoms of a congenital myopathy at birth and repeated episodes of generalized, atypical normokalaemic paralysis in her late teens. Genetic studies of this patient revealed three heterozygous RYR1 substitutions (p.Arg2241X, p.Asp708Asn and p.Arg2939Lys) associated with marked reduction of the RyR1 protein and abnormal DHPR distribution. We conclude that RYR1 mutations may give rise to both myopathies and atypical periodic paralysis, and RYR1 mutations may underlie other unresolved cases of periodic paralysis with unusual features.
Multi-minicore disease (MmD); Periodic paralysis; Excitation–contraction coupling (ECC); Skeletal muscle ryanodine receptor (RYR1); gene
Familial hypokalemic periodic paralysis (HOPP) is a rare autosomal-dominant disease characterized by reversible attacks of muscle weakness occurring with episodic hypokalemia. Mutations in the skeletal muscle calcium (CACNA1S) and sodium channel (SCN4A) genes have been reported to be responsible for familial HOPP. Fifty-one HOPP patients from 20 Korean families were studied to determine the relative frequency of the known mutations and to specify the clinical features associated with the identified mutations. DNA analysis identified known mutations in 12 families: 9 (75%) were linked to the CACNA1S gene and 3 (25%) to the SCN4A gene. The Arg528His mutation in the CACNA1S gene was found to be predominant in these 12 families. Additionally, we have detected one novel silent exonic mutation (1950C>T) in the SCN4A gene. As for a SCN4A Arg669His mutation, incomplete penetrance in a woman was observed. Characteristic clinical features were observed both in patients with and without mutations. This study presents comprehensive data on the genotype and phenotype of Korean families with HOPP.
Hypokalemic Periodic Paralysis; Calcium Channels; Sodium Channels; Mutation
Twenty-four cases of birth injury to the brachial plexus were seen in 21 infants over 15 years. Obstetric complications were common, and in 11 cases traction was needed to deliver the shoulders. Three out of every four arms fully recovered after exercises. Splints were not needed. Reconstructive procedures were performed on three permanently paralysed arms when the children were aged about 4. There was no way of predicting which patients would recover. The muscles supplied by the suprascapular nerve were paralysed in all patients, and this paralysis persisted in those whose arms failed to recover fully.
Carnitine deficiency occurring in families has been rarely reported and the genetic transmission has not yet been clearly elucidated. Five members of one family showing marked heterogeneity of carnitine deficiency states are presented. In three patients, there was no correlation between measurable carnitine levels in serum and muscle and the clinical findings. The parents, who are remote relatives from an isolated village in Kurdistan (Iraq), had low muscle carnitine levels; however, they were asymptomatic. One son, with systemic carnitine deficiency causing muscle weakness and recurrent episodes of severe hepatic encephalopathy, died at 3 years of age. His brother had mild proximal muscle weakness associated with low muscle carnitine levels. He was successfully treated with L-carnitine and prednisone. A daughter is asymptomatic, but with low serum and muscle levels of carnitine. The marked heterogeneity of carnitine deficiency states within one family, where both parents had low muscle carnitine levels, suggests an autosomal recessive inheritance with variable expression.
Linkage studies were performed in six European families with hyperkalaemic periodic paralysis (PPII) with myotonia, an autosomal dominantly inherited disorder characterised by episodic weakness. The weakness is caused by non-inactivating sodium channels of reduced single channel conductance of the muscle fibre membrane. Recently, portions of the gene coding for the alpha subunit of the sodium channel of the adult human skeletal muscle (h-Na2) have been cloned and localised on chromosome 17q with no recombinants to the human growth hormone locus (GH1). Linkage between these two chromosome 17 markers and the disease was shown in our families (Z = 7.14, 0 = 0.00). These results, combined with the linkage data of a single large American family, suggest that the disease is caused by dominant mutations of the adult sodium channel, and that it is probably a genetically homogeneous disorder. Hyperkalaemic periodic paralysis is the first non-progressive myotonic disorder to be localised on the human genome.
Silent thyroiditis is a rare cause of thyrotoxic periodic paralysis. The objective was to present a case of silent thyroiditis presenting as periodic paralysis. A 23-year-old man presented with recurrent acute flaccid predominantly proximal weakness of all four limbs. He had a similar episode 3 weeks back. On examination he was found to have hypokalemia secondary to thyrotoxicosis. Clinically there were no features of thyrotoxicosis or thyroiditis. He was initially treated with intravenous and later oral potassium supplementation and propranolol. At 8 weeks of follow-up his thyroid profile became normal and his propranolol was stopped. He had no further recurrence of paralysis. He was diagnosed as a case silent thyroiditis presenting as thyrotoxic periodic paralysis. In cases of recurrent or acute flaccid muscle paralysis, it is important to suspect thyrotoxicosis, even if asymptomatic. Definitive treatment of thyrotoxicosis prevents recurrence.
Hypokalemia; oral potassium; periodic paralysis; thyroiditis; thyrotoxicosis
Patients with an upper motor neurone syndrome (CP) suffer from many disabling primary symptoms: spasms, weakness, and loss of dexterity. These primary ‘neurogenic’ symptoms often lead to secondary disabilities, muscle contractures, and tertiary effects, bone deformations. A common symptom of CP is hypertonia, with. the consequence that the involved muscles remain in an excessively shortened length for most of the time. As a normal reaction of the muscle tissue, the number of sarcomeres is reduced and the muscle fibers shorten permanently: a contracture develops. A possible second type of contracture is that normal muscle lengthening along with bone growth is affected. Current treatments for the secondary effects include (1) reduction of muscle force, (2)lengthening of the muscle fibers by serial plaster casts, and (3)surgical lengthening of tendons or aponeurosis. The choice of treatment depends on the cause of the functional deficit. Bone tissue also adapts itself to abnormal forces, especially in the growth period. The hypertonias or contractures of CP so may give rise to bone malformations that interfere with function (e.g. femur endorotation) or may reduce the action of muscles by changing the lever arm (e.g. ankle varus). Although prevention should always be preferred, a timely surgical intervention cannot always be avoided. The differences in treatment for the various groups require and justify an extensive laboratory investigation, including EMG recordings in gait, measurement of passive elastic properties, and long-term observation of the hypertonia.