1. Course: Myalgia, Neuralgia, and Arthralgia “Myalgia: Muscle Disorders and Pain” 1 W. David Arnold, MD AAPMR 2015

2. Muscle Disorders and Pain –Overview of the problem –Myopathies associated with pain –Non-muscle disorders associated with myalgia –Approach and diagnosis of the patient with myalgia Acknowledgements: I receive funding through the RMST program (NICHD 5K12HD001097-17) John T. Kissel’s expertise and input regarding content

3. Myalgia: the stats.. Common reason for referral in NM clinics Common reason for referral in NM clinics ~50% of referrals (i.e. for muscle biopsy) 90% of myalgia patients have fatigue 90% of myalgia patients have fatigue –95% of patients with chronic fatigue syndrome have myalgia

4. Myalgia: the problem.. Pain is often an isolated symptom Pain is often an isolated symptom –No objective signs of disease (i.e. weakness) –Difficult to assess at bedside Myalgia may arise from many sources Myalgia may arise from many sources –Orthopedic, rheum, endocrine, vascular, psychological –May not be related to muscle disease Many patients are “not diagnosable” Many patients are “not diagnosable”

5. Diagnoses in Myalgia Patients Mills and Edwards, 1983 Diagnosis# Pts. % Enzyme defects1615% Inflammatory myopathy 8 7% Neurogenic disorders 7 6% Endocrine & metabolic 6 6% No diagnosis72 66% Total 109100%

6. Filosto et al, Neurology 2007 240 patients presenting with isolated myalgias –Excluded statin patients; only 2 FM patients Battery of tests done on each biopsy –Histochem, biochem, immunohistochemistry –No genetic testing Correlated findings with CK, EMG, clinical picture

7. Filosto et al, 2007 Five groups of biopsies –20% normal –80% abnormal BUT Only 20% had diagnosis Only 6% had muscle diagnosis (metabolic) Only 2% with normal strength had diagnosis –High CKs (7x normal) –Exercise pain only Neu Mit Nl Myo Met

8. Filosto et al, Neurology 2007 Many myalgia patients DO have biopsy abnormalities, but they are usually non-specific –They usually do NOT lead to a diagnosis (myth 1!) Routine biopsy NOT indicated in patients with isolated myalgia; careful patient selection is needed Important info for referring doctors AND patients!

9. Pain in Hereditary Myopathies and other NMDs

10. Hereditary muscle disorders often associated with pain Image

11. Hereditary muscle disorders associated with pain (cont.) Image

12. Hereditary muscle disorders associated with pain (cont.) Image

13. The Patient with Muscle Pain General Approach Careful history attending to type of pain Careful history attending to type of pain –Consideration of localization/pathogenesis –Analysis of disease possibilities Exam. with attention to strength testing! Exam. with attention to strength testing! –Most common mistake we see (& make)!! Judicious lab tests Judicious lab tests –Routine (e.g. CK and EMG) –Specialized (biopsy, genetic testing)

14. Evaluation of Muscle Pain FM/sfn? Tender points present? pmr,statins Tender points absent? Normal Repeat <5x nl No other abn Biopsy >5x normal, other sx CK elevated FET, Genetic testing Weak, abn EMG, CK MSK & neuro exam with particular attention to strength Labs. CK, CBC, ESR, TFTs, lytes, Edx studies Biopsy

15. Skin biopsy diagnostic efficiency of 88% for small fiber neuropathy Normal skin biopsy Normal innervation with arrows indicating small nerve fibers in epidermis. No small nerve fibers are seen in the epidermis Small fiber neuropathy TAVEE J, ZHOU L 2009 Other testing in myalgia: skin biopsy?

16. Objective evidence that small-fiber polyneuropathy underlies some illnesses currently labeled as fibromyalgia. Oaklander et al. Pain. 154(11):2310-2316, November 2013. Decreased nerve fiber density noted in large percentage of patients with FM Myalgia in non-muscle related disorders

17. Reduced sweat response at foot Normal sweat response at forearm Testing in myalgia (cont.): Quantitative sudomotor axon reflex testing QSART: assesses the integrity of postganglionic sympathetic sudomotor efferents, which are activated via an axon reflex by controlled iontophoretic stimulation with acetylcholine

18. Conclusions Pain is a frequent reason for referral to the neuromuscular specialist Patients with myalgia infrequently have a primary muscle disorder Muscle biopsy is a low-yield evaluation in the absence of weakness or a CK >1000 Non-muscle disorders are more often the cause of myalgia-like symptoms