[Non-inflammatory muscle pain]. / Nichtentzündliche Muskelschmerzen.

Muscle pain as a common symptom in daily practice frequently occurs as a non-specific accompanying symptom in multiple internal and neurological diseases. Primarily inflammatory or autoimmune muscular diseases are causing muscle pain. However, a number of non-inflammatory causes of pain can also be considered for differential diagnosis. These are presented in this article. In principle, a distinction must be made between focal and diffuse muscle pain. As an invasive diagnostic procedure, a muscle biopsy should only be performed as the last step in the diagnostic alogorithm. If diffuse muscle pain is only associated with slight muscle weakness or is completely absent, there is usually a primary rheumatic cause. Statins (HMG-CoA reductase inhibitors) can lead to rhabdomyolysis, muscle fiber atrophy and muscle necrosis by damaging the muscle fiber membrane. Myotonias are autosomal dominant or autosomal recessive inherited disorders of muscle function. The genetic defect leads to pronounced muscle stiffness. The cause of metabolic myopathies can be disorders of the carbohydrate, fat or purine metabolism. Fibromyalgia syndrome (FMS) is a non-inflammatory disease and, according to the current knowledge, recognized as the result of an exposure to physical, biological and psychosocial factors (biopsychological disease model). To help diagnosing FMS, pain regions and core symptoms (fatigue, sleep disturbances) can be detected using questionnaires (Widespread Pain Index [WPI] and Symptom Severity Scale [SSS]).

"Status myotonicus" in Nav1.4-M1592V channelopathy.

Nav1.4 channelopathies due to SCN4A mutations can present with episodic attacks of myotonia triggered by fluctuation in the potassium level (potassium-aggravated myotonia). We report a case of potassium-aggravated myotonia due to Nav1.4-M1592V channelopathy with severe and long-lasting focal attacks of myotonia resembling dystonic posturing with diffuse muscle edema in the affected muscles in magnetic resonance imaging and almost constant presence of myotonic discharges in electromyography that can best be described as focal "status myotonicus".

Patient-reported study of the impact of pediatric-onset myotonic dystrophy.

INTRODUCTION: The prevalence and impact of symptoms affecting individuals with pediatric forms of myotonic dystrophy type-1 (DM1) are not well understood. METHODS: Patients from the United States, Canada, and Sweden completed a survey that investigated 20 themes associated with pediatric-onset DM1. Participants reported the prevalence and importance of each theme affecting their lives. Surveys from participants were matched with surveys from their caregivers for additional analysis. RESULTS: The most prevalent symptomatic themes included problems with hands or fingers (79%) and gastrointestinal issues (75%). Problems with urinary/bowel control and gastrointestinal issues were reported to have the greatest impact on patients' lives. Responses from participants and their caregivers had varying levels of agreement among symptomatic themes. DISCUSSION: Many symptoms have meaningful impact on disease burden. The highest levels of agreement between caregivers and individuals with pediatric forms of myotonic dystrophy were found for physical activity themes.

Sodium Channelopathies of Skeletal Muscle.

The NaV1.4 sodium channel is highly expressed in skeletal muscle, where it carries almost all of the inward Na+ current that generates the action potential, but is not present at significant levels in other tissues. Consequently, mutations of SCN4A encoding NaV1.4 produce pure skeletal muscle phenotypes that now include six allelic disorders: sodium channel myotonia, paramyotonia congenita, hyperkalemic periodic paralysis, hypokalemic periodic paralysis, congenital myasthenia, and congenital myopathy with hypotonia. Mutation-specific alternations of NaV1.4 function explain the mechanistic basis for the diverse phenotypes and identify opportunities for strategic intervention to modify the burden of disease.

Electromyographic findings in 37 patients with adult-onset acid maltase deficiency.

INTRODUCTION: In acid maltase deficiency (AMD), electrical myotonia (EM) may be restricted to paraspinal muscles. A comprehensive description of the electromyographic (EMG) findings in AMD is lacking. The purpose of this study is to describe the EMG features in adult-onset AMD, focusing on the distribution of EM. METHODS: A retrospective chart review of AMD patients diagnosed at Mayo Clinic over age 18 years. RESULTS: Thirty-seven patients were included. Twenty-eight (76%) had EM in at least 1 muscle, and EM was more common in paraspinal and proximal limb muscles. The tensor fasciae latae (TFL) was equally sensitive to the paraspinals for EM. Three of 4 patients had EM identified in the diaphragm. CONCLUSIONS: Approximately three-quarters of adult-onset AMD patients display EM on EMG. The paraspinal muscles and TFL are the most likely to demonstrate EM, and EM can be detected in the diaphragm of adult onset AMD patients.

Phenotypic variability and molecular genetics in proximal myotonic myopathy.

INTRODUCTION: Myotonic dystrophy type 2 (DM2) is an autosomal dominant inherited disorder with (CCTG)n repeat expansion in intron 1 of the CNBP gene. METHODS: We studied the first 16 Greek DM2 patients who had undergone thorough evaluation. RESULTS: The age at diagnosis ranged from 38 to 69 years. The initial symptoms were proximal weakness, myalgias, and myotonia. Clinical myotonia was elicited in 10 patients, whereas electromyographic myotonic discharges were observed in almost all patients. Subcapsular cataract was frequently present, but cardiac arrhythmias were rare. CONCLUSIONS: In this study of Greek DM2 patients, proximal weakness was the most common initial symptom. Myalgias were also reported in a few patients, yet myotonia was not a major complaint. Although DM2 is considered relatively benign, there are patients who may be affected severely. Thus, a high index of suspicion must be maintained to make a timely diagnosis, especially in those of reproductive age.

[Normokalemic periodic paralysis lasting for two weeks: a severe form of sodium channelopathy with M1592V mutation].

A 73-year-old man with recurrent periodic paralytic episodes lasting for two weeks each admitted to our hospital because of the leg weakness and the elevated value of serum creatine kinase. On admission, weakness in the proximal legs and mild eye lid myotonia were noted. Needle electromyography revealed abundant myotonic discharges. The prolonged exercise test showed a continuous reduction of compound muscle action potentials in the abductor digiti minimi muscle. Direct sequencing of SCN4A in the proband showed a G-to-A alteration at position 4774 that results in a change of 1592(nd) methionine to valine (M1592V). Cosegregation regarding the M1592V mutation and paralytic phenotype in this family was confirmed. Two cardinal features in this family were longer paralytic episodes compared to classical hyperkalemic/normokalemic periodic paralysis and the normal potassium value during the paralytic episodes. This study together with antecedent reports indicates that M1592V mutation shares a much greater clinical diversity ranging from congenital paramyotonia to periodic paralysis with a longer duration.

[A genetic systemic disease: clinical description of type 1 myotonic dystrophy in adults]. / Une maladie systémique génétique : description clinique chez l'adulte de la dystrophie myotonique de type 1.

Type 1 myotonic dystrophy is an autosomal dominant inherited disorder related to the expansion of a trinucleotide (CTG) repeat in the exon 15 in the 3'-untranslated region of the myotonic dystrophy protein kinase (DMPK) gene. Mutant transcripts containing an expanded CUG repeat are retained in nuclear foci and cause numerous dysfunctions by interfering with biogenesis of other mRNAs. Prominent clinical features are progressive muscular weakness and myotonia, which affect skeletal muscles but also white muscles leading to digestive, urinary and obstetrical disorders. Functional prognosis correlates with motor handicap and vital prognosis is linked to cardiac rhythm disturbances and conduction defects due to progressive subendocardial fibrosis, and to complex respiratory dysfunctions, which associate restrictive lung disease, involvement of the central inspiratory pathway, and sleep apnea. Other clinical features are lens opacity, glucose intolerance, metabolic syndrome, several endocrine disorders (gonadal deficiency, hyperparathydoidism), or immunoglobulin deficiency due to immunoglobulin G hypercatabolism. Life expectancy is reduced in myotonic dystrophy, and death is mainly caused by respiratory complications, but also by cardiac arrhythmias. Moreover, an abnormal incidence of tumors has been reported. Therefore, myotonic dystrophy does not only concern neurologists but a multidisciplinary approach is necessary, including at least pneumologist, cardiologist, and physiotherapist. General internists should also be implicated, not only in the initial diagnosis step, but also in the diagnosis of complications and their treatments.

Biophysical characterization of M1476I, a sodium channel founder mutation associated with cold-induced myotonia in French Canadians.

M1476I, a French Canadian founder mutation of Na⁺ channel Nav1.4, causes potassium-aggravated myotonia, with cold-induced myotonia as the most distinctive clinical feature. Mexiletine, a class 1B local anaesthetic, relieves the myotonic symptoms of patients carrying the M1476I mutation. We used the patch-clamp method to investigate the functional characteristics of this mutation by heterologous expression in tsA201 cells. The M1476I mutation caused an increased persistent Na⁺ current, a 2- to 3-fold slower fast inactivation, a 6.4 mV depolarizing shift in the midpoint of steady-state inactivation, and an accelerated recovery from fast inactivation compared to the wild-type (WT) channel. Cooling slowed the kinetics of both channel types and increased the amplitude of the persistent current in M1476I channels.Mexiletine suppressed the persistent Na⁺ current generated by the M1476I mutation and blocked both WT and M1476I channels in a use- dependent manner. The inactivation-deficient M1476I channels were less susceptible to mexiletine during repetitive pulses. The decreased use-dependent block of M1476I channels might have resulted from the slower onset of mexiletine block, and/or the faster recovery from mexiletine block, given that the affinity of mexiletine for the inactivated state of the WT and mutant channels was similar. Increased extracellular concentrations of potassium had no effect on either M1476I or WT currents. These results indicated that cooling can augment the disruption of the voltage dependence of fast inactivation by M1476I channels.

[Clinical analysis of paroxysmal motor phenomena in the neonate]. / Diagnostic des mouvements anormaux du nouveau-né

The newborn infant is prone to motor phenomena of various physiological mechanisms and pathological significance whereas they can share close clinical patterns. A detailed clinical analysis, that should be supported by a video EEG recording, is necessary. That may help to distinguish myoclonus, jitteriness or seizures. Some rare phenomenom such as hyperekplexia or myotonia have also to be known. The pregnancy and birth history, the clinical examination and the search for association of various motor phenomena give essential clues for the diagnosis. Misdiagnosing non epileptic phenomona as seizures has to be avoided as it leads to unnecessary anticonvulsivant therapy with potential harmful effects.

Late onset painful cold-aggravated myotonia: three families with SCN4A L1436P mutation.

We describe three Belgian families with a L1436P mutation in the SCN4A gene, causing a sodium channel myotonia with an atypical clinical presentation, characterized by late onset painful cold-aggravated myotonia. These families represent a distinct phenotype within the spectrum of sodium channel myotonia.