[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]).

Classification of Involuntary Movements in Dogs: Myoclonus and Myotonia.

Myoclonus is a sudden brief, involuntary muscle jerk. Of all the movement disorders, myoclonus is the most difficult to encapsulate into any simple framework. On the one hand, a classification system is required that is clinically useful to aid in guiding diagnosis and treatment. On the other hand, there is need for a system that organizes current knowledge regarding biological mechanisms to guide scientific research. These 2 needs are distinct, making it challenging to develop a robust classification system suitable for all purposes. We attempt to classify myoclonus as "epileptic" and "nonepileptic" based on its association with epileptic seizures. Myotonia in people may be divided into 2 clinically and molecularly defined forms: (1) nondystrophic myotonias and (2) myotonic dystrophies. The former are a group of skeletal muscle channelopathies characterized by delayed skeletal muscle relaxation. Many distinct clinical phenotypes are recognized in people, the majority relating to mutations in skeletal muscle voltage-gated chloride (CLCN1) and sodium channel (SCN4A) genes. In dogs, myotonia is associated with mutations in CLCN1. The myotonic dystrophies are considered a multisystem clinical syndrome in people encompassing 2 clinically and molecularly defined forms designated myotonic dystrophy types 1 and 2. No mutation has been linked to veterinary muscular dystrophies. We detail veterinary examples of myotonia and attempt classification according to guidelines used in humans. This more precise categorization of myoclonus and myotonia aims to promote the search for molecular markers contributing to the phenotypic spectrum of disease. Our work aimed to assist recognition for these 2 enigmatic conditions.

Non-dystrophic myotonia: prospective study of objective and patient reported outcomes.

Non-dystrophic myotonias are rare diseases caused by mutations in skeletal muscle chloride and sodium ion channels with considerable phenotypic overlap between diseases. Few prospective studies have evaluated the sensitivity of symptoms and signs of myotonia in a large cohort of patients. We performed a prospective observational study of 95 participants with definite or clinically suspected non-dystrophic myotonia recruited from six sites in the USA, UK and Canada between March 2006 and March 2009. We used the common infrastructure and data elements provided by the NIH-funded Rare Disease Clinical Research Network. Outcomes included a standardized symptom interview and physical exam; the Short Form-36 and the Individualized Neuromuscular Quality of Life instruments; electrophysiological short and prolonged exercise tests; manual muscle testing; and a modified get-up-and-go test. Thirty-two participants had chloride channel mutations, 34 had sodium channel mutations, nine had myotonic dystrophy type 2, one had myotonic dystrophy type 1, and 17 had no identified mutation. Phenotype comparisons were restricted to those with sodium channel mutations, chloride channel mutations, and myotonic dystrophy type 2. Muscle stiffness was the most prominent symptom overall, seen in 66.7% to 100% of participants. In comparison with chloride channel mutations, participants with sodium mutations had an earlier age of onset of stiffness (5 years versus 10 years), frequent eye closure myotonia (73.5% versus 25%), more impairment on the Individualized Neuromuscular Quality of Life summary score (20.0 versus 9.44), and paradoxical eye closure myotonia (50% versus 0%). Handgrip myotonia was seen in three-quarters of participants, with warm up of myotonia in 75% chloride channel mutations, but also 35.3% of sodium channel mutations. The short exercise test showed ≥10% decrement in the compound muscle action potential amplitude in 59.3% of chloride channel participants compared with 27.6% of sodium channel participants, which increased post-cooling to 57.6% in sodium channel mutations. In evaluation of patients with clinical and electrical myotonia, despite considerable phenotypic overlap, the presence of eye closure myotonia, paradoxical myotonia, and an increase in short exercise test sensitivity post-cooling suggest sodium channel mutations. Outcomes designed to measure stiffness or the electrophysiological correlates of stiffness may prove useful for future clinical trials, regardless of underlying mutation, and include patient-reported stiffness, bedside manoeuvres to evaluate myotonia, muscle specific quality of life instruments and short exercise testing.

[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.

[Proximal myotonic myopathy (PROMM). Clinical variability within a family]. / Proximale myotone Myopathie (PROMM). Klinische Variabilität innerhalb einer Familie.

Proximal myotonic myopathy (PROMM) is a newly described autosomal dominant inherited disorder characterized by predominant proximal weakness of the legs, mild clinical myotonia or myotonia on electromyograms (EMG), cataracts and slight elevation of liver enzymes. The trinucleotide (cytosine, thymine, and guanine) repeat size of the myotonic dystrophy (DM) gene is normal. Magnetic resonance imaging of the brain may reveal a peculiar pattern of white matter abnormalities. We describe seven patients in a new family with PROMM. The only symptoms may be subclinical myotonic changes in the EMG or cataracts, but symptoms may also include severe proximal weakness of the legs and painful paraesthesia. PROMM is an important differential diagnosis of myotonic dystrophy; and because of the proximal weakness it is also a differential diagnosis of other muscle diseases such as limb girdle dystrophy, metabolic and endocrine myopathies, and myositis. Because of the variability of the symptoms, for the definite diagnosis of PROMM it may require the examination of other family members.

A newly-described myotonic disorder (proximal myotonic myopathy--PROMM): personal experience and review of the literature.

The aim of this study is to describe the essential characteristics of a family affected by the newly-described proximal myotonic myopathy (PROMM) The clinical, laboratory and genetic findings are described and compared with those reported in the literature, and the clinical spectrum of the manifestations that are similar to but distinct from myotonic dystrophy (MD) is also explored. This has practical implications because the cases so far described suggest that the long-term prognosis with PROMM seems to be more favourable than that of patients with MD.

Channelopathies: the nondystrophic myotonias and periodic paralyses.

The term channelopathy does not indicate a new group of neuromuscular conditions, but a re-orientation of well- and long-known muscular conditions, the congenital myotonias, and the periodic paralyses. Although, in the past, they have overlapped clinically here and there, both groups were classified differently, as myotonias and as metabolic myopathies, respectively. The discovery of mutations in several ion channels has rewritten nosography of these disorders and procured a new term, the channelopathy-clinical, electrophysiological, and molecular genetic details of which are discussed in this chapter.

Sodium channel defects in myotonia and periodic paralysis.

Myotonias and periodic paralyses constitute a diverse group of inherited disorders of muscle in which the primary defect is an alteration in the electrical excitability of the muscle fiber. The ion channel defects underlying these excitability derangements have recently been elucidated at the molecular and functional levels. This review focuses on sodium channel mutations that disrupt inactivation and thereby cause both the enhanced excitability of myotonia (muscle stiffness due to repetitive discharges) and the inexcitability resulting from depolarization during attacks of paralysis.

Myotonic disorders and periodic paralysis.

The myotonias are a diverse set of diseases, variable in presentation, often difficult to diagnose and, until now, treated with only a limited degree of success. Recent genetic advances have pinpointed many of the mutations that underlie these disorders and have demonstrated that there may be different causative genetic mutations underlying the same phenotype. This chapter summarizes the genetic data currently available for these disorders and attempts to link these to their clinical features. In some instances this is conceptually relatively straightforward but in others, particularly DM, the manner in which the mutation leads to the observed phenotype is very unclear and can be used as a paradigm for some of the more puzzling aspects of modern human genetics. Some suggestions are put forward on how the unusual mutation seen in DM can lead to highly variable symptoms between individual patients, and how the mutation can be transmitted unstably through a pedigree.

[Current aspects of the myotonic syndromes]. / Actualité des syndromes myotoniques

On the basis of a clinical and physiological definition of the myotonic syndrome, the author define the scope of their research in two directions: a) the true myotonic syndromes, b) the related syndromes. Amongst the former, two entities are studied from the point of view of the recent discoveries in the field : Thomsen's disease, with some new anatomopathological and genetic considerations; Steinert's disease, concerning which there is much more new evidence in regard to clinical findings (ocular, endocrine, digestive, nervous and, in particular, cardiac symptoms) as well as biological and morphological tests. The genetic aspects are of great interest, for they lead to practical applications in genetic counselling (linkage). A brief therapeutic survey follows. Amongst the related syndromes, the best known is Eulenburg's congenital paramyotonia, the main characteristics of which are briefly described.