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

2. Muscle Disorders and Pain
Overview of the problem
Examples of 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 5K12HD )
John T. Kissel’s expertise and input regarding content

3. Myalgia: the stats.. Common reason for referral in NM clinics
~50% of referrals (i.e. for muscle biopsy)
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
No objective signs of disease (i.e. weakness)
Myalgia may arise from many sources
Orthopedic, rheum, endocrine, vascular, psychological
May not be related to muscle disease
Many patients, despite extensive workup are “not diagnosable”

5. Myalgia Terminology Types of Pain
May be useful to classify into types:
Contractures
Stiffness
Cramps
Aching myalgia
(after Layzer, 1985)

6. Types of Muscle Pain Contracture
Least common myalgia, can be excruciating
Forceful, sustained contraction
Localized hard nodule in muscle
Electrically silent by EMG!
Sudden onset with exercise (may be mild)
May persist for hours & result in rhabdo.
Hallmark of glycolytic dx. (eg McArdle’s)
FET useful screen for these disorders
Others: Brody’s disease, hypothyroid

7. Types of “Muscle Pain” Cramps
Idiopathic (normal cramps)
Exertional, post-exertional, nocturnal
Neurogenic cramps
MND, PN, radics, others.
Cramps due to altered neural environment
Pregnancy
Metabolic disorders (renal or liver failure)
Hypothyroidism
Adrenal insufficiency
Electrolyte disturbances/volume depletion
Cramps are related to nerve hyperexcitability, electrically active on EMG

8. Muscle Stiffness Differential Diagnosis
Myotonic disorders
DM 1 & 2
MC and PMC
Hypothyroidism
Hypo PP
Brody’s disease
PMR
Fibromyalgia

9. Myotonic Dystrophy Two characterized types
DM1-more common and usually more severe
DM2
Multisystem disease
Muscle
Eyes (cataracts) GI
Cardiac-mainly arrhythmia (30% mortality)
CNS (cognitive and personality)
Pulmonary (restrictive and hypoventilation)
Autosomal Dominant
Triplet repeat disease associated with anticipation
DM2 has been associated with fibromyalgia in case series and case reports --Auvinen et al. 2008

10. Nondystrophic myotonia
Muscle Channelopathies
Disease/Phenotype
Gene
KCNJ2
Andersen-Tawil syndrome
Hypokalemic PP
Hyperkalemic PP
Sodium Channel myotonia
Paramyotonia congenita
Myotonic congenita
Periodic Paralysis
CACNA1S
Nondystrophic myotonia
SCN4A
CLCN1
Stiffness, +/- pain

11. Treatment: medications and potential triggers
Paramyotonia
Congenita
Myotonia Congenita
Sodium Channel Myotonia
HyperPP
HypoPP
ATS
Acetazolamide
Yes/No No
Yes
Dichlorphenamide
Thiazides
Mexiletine
Triggers
Cold, exercise
Cold, stress, pregnancy
Rest after exertion, K rich foods, cold
Rest after exertion, carbs
Rest after exertion
Meola et al Tawil et al Matthews et al Trip et al 2011.
Barohn et al. Clinical Investigation of Neurological Channelopathies (CINCH)

12. Study of Ranolazine in Myotonia Congenita and Paramyotonia Congenita
Sponsor:
Ohio State University and Gilead Sciences
ClinicalTrials.gov Identifier:
NCT
This study is currently recruiting participants.

13. Types of Muscle Pain Deep Aching - Generalized Differential Diagnosis
With weakness
PM, DM
Hypothyroidism
Mitochondrial dx.
Myotonic dystrophy 2
Infectious myopathies
Other rare myopathies
Without weakness
Infectious myalgia (esp. viral)
Toxic myopathies (eg statin)
PMR
Fibromyalgia

14. Polymyalgia Rheumatica Epidemiology
Technically not muscle disease per se
Common causes of myalgia
/100,000 in patients >age 50
Incidence of ~50/100,000 per year
Mean age of onset 70 (90% > age 60)
Female predominance of 3:1

15. Polymyalgia Rheumatica Treatment
Prednisone (10-40 mg/day) causes immediate and dramatic improvement
Diagnostic and therapeutic
Treat symptoms and ESR
Taper slowly when sxs. under control
Usually requires 1-2 years treatment
10% require treatment for over 10 years!

16. Diffuse Myalgia Inflammatory Muscle Disease*
*Myth: ALL PM/DM pts. have sig. myalgias (only ~25% do!)

17. Examples of Focal Myalgia
Sarcoid Myopathy Diabetic Thigh Infarct

18. Yield of workup: Diagnoses in Myalgia Patients Mills and Edwards, 1983
Diagnosis # Pts %
Enzyme defects %
Inflammatory myopathy %
Neurogenic disorders %
Endocrine & metabolic %
No diagnosis %
Total %

19. Filosto et al, Neurology 2007
240 patients presenting with 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

20. Filosto et al, 2007 Myo Five groups of biopsies 19% normal Mit Nl
81% abnormal
BUT
Only 20% had diagnosis
Only 6% had muscle diagnosis (metabolic)
Only 2% with normal strength had diagnosis!
Mit Nl
Neu
Met

21. 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
Routine biopsy NOT indicated in patients with isolated myalgia; careful patient selection is needed
Important info for referring doctors AND patients!

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

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

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

25. Other testing in myalgia: skin biopsy?
Normal skin biopsy
Small fiber neuropathy
Normal innervation with arrows indicating small nerve fibers in epidermis.
No small nerve fibers are seen in the epidermis
TAVEE J , ZHOU L 2009

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

27. 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