Paramyotonia congenita: Successful treatment with tocainide. Clinical and electrophysiologic findings in seven patients

Streib, Erich W.

doi:10.1002/mus.880100209

Cited by 38 publications

(23 citation statements)

References 28 publications

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“…In one study of paramyotonia congenita patients, tocainide was found to improve electrodiagnostic results and muscle stiffness with a maximal benefit felt after only 10 days of use. 39 Some patients during this study experienced light-headedness, headaches, and irritability from this medication. Tocainide has been used at dosages of 400 to 1200 mg a day in patients refractory to mexiletine.…”

Section: Specific Pharmacologic Treatments Of the Nondystrophic Myotomentioning

confidence: 89%

The Nondystrophic Myotonias

Heatwole

Moxley

2007

Neurotherapeutics

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Summary:The nondystrophic myotonias are a heterogeneous set of rare diseases that demonstrate clinical myotonia, electrical myotonia, or both. These disorders are distinguished from myotonic dystrophy type 1 (DM-1), the more recently described proximal myotonic myopathy/myotonic dystrophy type 2 (PROMM/DM-2), and proximal myotonic dystrophy (a variant of DM-2) by characteristic clinical features, lack of abnormal nucleotide repeat expansions in the DM-1 and DM-2 genes, lack of cataracts and endocrine disturbances, and absence of significant histopathology in the muscle biopsy. The present article reviews each of the nondystrophic myotonias by exploring the unique clinical features, electrodiagnostic findings, diagnostic criteria, gene mutations, and response to pharmacologic therapy. These diseases are divided into those with chloride channel dysfunction (the myotonia congenita disorders) and those with sodium channel dysfunction (paramyotonia congenita, potassium-aggravated myotonia, and hyperkalemic periodic paralysis with myotonia). The variants that occur in each of these conditions are commented on. The differentiating features of the nondystrophic myotonias are summarized, and their predominant clinical, electrodiagnostic, and genetic characteristics are tabulated. For a comprehensive review of pertinent research and studies with application to diagnosis and treatment of individuals with nondystrophic myotonic disorders, the present article is best read in the context of other articles in this issue, especially those on ion channel physiology (Cannon) and pharmacology (Conte-Camerino), and on hyperkalemic periodic paralysis (Lehmann-Horn).

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Section: Specific Pharmacologic Treatments Of the Nondystrophic Myotomentioning

confidence: 89%

The Nondystrophic Myotonias

Heatwole

Moxley

2007

Neurotherapeutics

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“…Ricker et al (1978) reported subjective improvement in muscle stiffness and an improved timed walk in one patient with myotonia congenita and a dose dependant improvement in isometric force in another. The lignocaine derivative tocainide gave encouraging results initially (Rudel et al, 1980;Streib, 1987) but was eventually withdrawn from the market due to the risk of potentially fatal agranulocytosis (Volosin et al, 1985). Synthesis of tocainide analogues has been attempted in vitro and it may be of value for future study as anti-myotonic agents if the efficacy and side effect profiles are favourable (Catalano et al, 2008).…”

Section: Treatmentmentioning

confidence: 99%

The non-dystrophic myotonias: molecular pathogenesis, diagnosis and treatment

Matthews

Fialho

Tan

et al. 2009

Brain

196

226

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The non-dystrophic myotonias are an important group of skeletal muscle channelopathies electrophysiologically characterized by altered membrane excitability. Many distinct clinical phenotypes are now recognized and range in severity from severe neonatal myotonia with respiratory compromise through to milder late-onset myotonic muscle stiffness. Specific genetic mutations in the major skeletal muscle voltage gated chloride channel gene and in the voltage gated sodium channel gene are causative in most patients. Recent work has allowed more precise correlations between the genotype and the electrophysiological and clinical phenotype. The majority of patients with myotonia have either a primary or secondary loss of membrane chloride conductance predicted to result in reduction of the resting membrane potential. Causative mutations in the sodium channel gene result in an abnormal gain of sodium channel function that may show marked temperature dependence. Despite significant advances in the clinical, genetic and molecular pathophysiological understanding of these disorders, which we review here, there are important unresolved issues we address: (i) recent work suggests that specialized clinical neurophysiology can identify channel specific patterns and aid genetic diagnosis in many cases however, it is not yet clear if such techniques can be refined to predict the causative gene in all cases or even predict the precise genotype; (ii) although clinical experience indicates these patients can have significant progressive morbidity, the detailed natural history and determinants of morbidity have not been specifically studied in a prospective fashion; (iii) some patients develop myopathy, but its frequency, severity and possible response to treatment remains undetermined, furthermore, the pathophysiogical link between ion channel dysfunction and muscle degeneration is unknown; (iv) there is currently insufficient clinical trial evidence to recommend a standard treatment. Limited data suggest that sodium channel blocking agents have some efficacy. However, establishing the effectiveness of a therapy requires completion of multi-centre randomized controlled trials employing accurate outcome measures including reliable quantitation of myotonia. More specific pharmacological approaches are required and could include those which might preferentially reduce persistent muscle sodium currents or enhance the conductance of mutant chloride channels. Alternative strategies may be directed at preventing premature mutant channel degradation or correcting the mis-targeting of the mutant channels.

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“…Studies of more families from different ethnic backgrounds might help to establish a correlation between genotype and phenotype, Once the precise alteration in the channel is identified, patch-clamp studies might improve our understanding of how this affects channel gating in both normal and diseased muscle, and available drugs such as mexiletine, potassium-sparing agents, carbonic anhydrase inhibitors, etc. might then be more specifically used [14,30] according to the channel involved and the degree of channel gating involvement [27].…”

Section: Discussionmentioning

confidence: 99%