EFNS Review on the Role of Muscle Biopsy in the Investigation of Myalgia

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EFNS Review on the Role of Muscle Biopsy in the Investigation of Myalgia European Journal of Neurology 2013, 20: 997–1005 doi:10.1111/ene.12174 EFNS REVIEW/CME ARTICLE EFNS review on the role of muscle biopsy in the investigation of myalgia T. Kyriakidesa, C. Angelinib, J. Schaeferc, T. Monginid, G. Sicilianoe, S. Sacconif, J. Josephg, J. M. Burgunderh, L. A. Bindoffi, J. Vissingj, M. de Visserk and D. Hilton-Jonesl aClinical Neurosciences, Cyprus Institute of Neurology and Genetics, Nicosia, Cyprus; bIRCCS Fondazione Ospedale San Camillo, Venezia, Italy; cDepartment of Neurology, University of Dresden, Dresden, Germany; dNeuromuscular Center, S.G. Battista Hospital, University of Turin, Turin, Italy; eDepartment of Neuroscience, Neurological Clinic, University of Pisa, Pisa, Italy; fCentre de reference des Maladies nueuromusculaires, CNRS UMR6543, Nice University Hospital, Nice, France; gSt George’s University of London at the University of Nicosia Medical School, Nicosia, Cyprus; hDepartments of Neurology and Clinical Research, University of Bern, Inselspital, Bern, Switzerland; iDepartment of Neurology, Haukeland University Hospital, Bergen, Norway; jNeuromuscular Clinic and Research Unit, Department of Neurology, Rigshospitalet, University of Copenhagen, Copenhagen, Denmark; kDepartment of Neurology, Academic Medical Center, Amsterdam, The Netherlands; and lOxford Neuromuscular Centre, Department of Neurology, John Radcliffe Hospital, Oxford, UK Keywords: Background: Myalgia, defined as any pain perceived in muscle, is very common in biopsy, muscle, myalgia the general population and a frequent cause for referral to neurologists, rheumatol- ogists and internists in general. It is however only rarely due to primary muscle dis- Received 8 February 2013 ease and often referred from ligaments, joints, bones, the peripheral and central Accepted 14 February 2013 nervous system. A muscle biopsy should only be performed if this is likely to be diagnostically useful. At present no ‘guidelines’ exist. Methods: An EFNS panel of muscle specialists was set to review relevant studies from PubMed dating as far back as 1/1/1990. Only Class IV studies were available and therefore the recommendations arrived at are ‘best practice recommendations’ based on information harvested from the literature search and expert opinion. Results: Muscle cramps should be recognized while drugs, infections, metabolic/ endocrinological and rheumatological causes of myalgia should be identified from the history and examination and pertinent laboratory tests. A muscle biopsy is more likely to be diagnostically useful if myalgia is exertional and if one or more of the following apply: i) there is myoglobinuria, (ii) there is a second wind phenomenon, (iii) there is muscle weakness, (iv) there is muscle hypertrophy /atrophy, (v) there is hyperCKemia (>2–39 normal), and (vi) there is a myopathic EMG. Conclusions: Patients presenting with myalgia can be recommended to have a biopsy based on careful history and examination and on simple laboratory screen- ing. pain is frequently referred from elsewhere, including Objective non-muscular tissues such as ligaments, tendons, To provide guidelines on the role of muscle biopsy in joints and bones or the peripheral and even the cen- the elucidation of the cause of myalgia. The guidelines tral nervous system [1–3]. Less commonly, it is due to cover both adult and pediatric populations. a primary problem within the muscle itself and its Myalgia is a common symptom but is only rarely associated connective tissue and blood vessels [1]. due to underlying primary muscle disease. Rather, the Population-based studies estimate the incidence of diffuse persistent muscle pain to be about 10% [4]. Correspondence: T. Kyriakides, 6 International Airport Avenue, PO Elucidating the cause of myalgia, particularly in the Box 23462, 1683 Nicosia, Cyprus (tel.: +35722392758; fax: absence of other associated features, can be a difficult +35722392786; e-mail: [email protected]). task, but an invasive and expensive procedure such as This is a Continuing Medical Education article, and can be found with corresponding questions on the Internet at http://www.efns.org/EFNS a muscle biopsy, be it with a low morbidity, should Continuing-Medical-Education-online.301.0.html. Certificates for cor- be performed only if it is likely to be diagnostically rectly answering the questions will be issued by the EFNS. useful [5,6]. © 2013 The Author(s) European Journal of Neurology © 2013 EFNS 997 998 T. Kyriakides et al. and no relevant guidelines were found. The only avail- Definitions able guidelines identified were those of the German Myalgia may be defined as any pain perceived to be Neurological Society on the ‘Clinical pathway for the in muscle. investigation of myalgias’ [9]. Muscle cramps are one cause of myalgia and consist The Medline database was accessed between 12 of sudden onset, transient, involuntary, painful and February 2012 and 16 July 2012 with the following vigorous muscle contraction. Cramps may occur spon- key terms: myalgia, and one of myopathy, biopsy, taneously at rest or more often during or after exer- weakness, exercise, drugs, dystrophy, EMG and cise, and usually last from seconds to a few minutes. hyperCKemia; muscle and pain, and one of weakness, Such ‘true’ cramps are neurogenic in origin and are biopsy, exercise, drugs, dystrophy, EMG, myopathy associated with high frequency motor unit discharges and hyperCKemia; myalgia and exercise, and one of [7,8]. myopathy, biopsy, weakness, drugs, dystrophy and The word contracture is used in two unrelated EMG. More than 27 000 reports were identified but senses. Transient, electrically silent contractures, there was much redundancy within individual searches which are painful and clinically resemble cramps, are and between searches. Abstracts were reviewed and characteristically present in metabolic myopathies and relevant articles were identified. To evaluate articles, are evoked by exercise. Persistent contractures, which the critical review of EFNS guidelines was followed may be focal or more usually involve the whole mus- [10]. A hand search was also performed by members cle, causing shortening of the muscle and thus limita- of the Task Force. As predicted, only class IV studies tion of passive joint movements, are a common late were identified and therefore this review is a best prac- feature of many myopathies, such as dystrophies. tice guideline based on the review of the literature and They are an early feature in Emery–Dreifuss syn- the Task Force’s expert opinion. A first draft was pre- drome. Such contractures are usually painless. pared and circulated on 3 September 2012. The draft was reviewed at a meeting on 10 September 2012 and recirculated to members until final consensus was Search strategy reached. The Task Force members met on 12 September 2011 and decided on a literature search policy. This Myalgia and exercise included a search for any existing guidelines and arti- cles dealing with the indications for muscle biopsy in Myalgia can occur at rest, during or after exercise. It patients with myalgia. It was decided that the litera- can be focal or generalized. The circumstances in ture search should go as far back as 1 January 1990 which myalgia develops provide helpful clues to the and Medline was chosen as the sole database to be etiology. Myalgia at rest, especially in the absence of searched. It was felt that clinically important studies weakness, is rarely due to a primary myopathy. were unlikely to be left out with this arbitrary decision There are three major patterns of myalgia in rela- and furthermore the Task Force did not expect to tion to exercise [11]: identify any class I–III studies in the literature. The 1 Pain experienced during (exertional) or immedi- lack of robust prior studies may paradoxically make ately following (post-exertional) exercise. Myalgia these guidelines particularly useful, pending evidence- associated with primary myopathies is commonly based knowledge. exertional (see below). Myalgia associated with pri- It was decided to identify and succinctly summarize mary metabolic myopathies may be associated commonly reported, non-neuromuscular causes of with transient contractures. myalgia, including rheumatological diseases, com- 2 Delayed muscle pain (delayed post-exertional) usu- monly used drugs and general medical conditions. The ally occurs 24–48 h after strenuous or eccentric main emphasis of the search, however, was to identify exercise. Soreness is usually accompanied by loss primary myopathies presenting with or associated of strength and elevated levels of serum creatine with myalgia. Special attention was paid to studies in kinase (sCK) activity. It commonly occurs in unfit which clinical features (e.g. the relation of myalgia to individuals undertaking unaccustomed exercise and exercise or weakness) or investigations [e.g. hyperC- is not a hallmark of primary muscle disease. It is Kemia, electromyography (EMG)] were detailed, in thought to be due to microtrauma and local order to be able to identify patients in whom a biopsy inflammation. could be recommended. The Cochrane Library and 3 Muscle cramps per se are of heterogeneous origin the American Academy of Neurology were accessed (Table 1) and may be associated with specific on 17 March 2011 and again on 3 September 2012 neurogenic disorders (Table 2). © 2013 The Author(s) European Journal of Neurology © 2013 EFNS European Journal of Neurology Muscle biopsy in myalgia 999 Table 1 Common causes of muscle cramps Table 4 Infections commonly associated with myalgia
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