Evaluation of the Patient With Muscle Weakness - American Family Physician

8/2/2019 Evaluation of the Patient With Muscle Weakness - American Family Physician

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Evaluation of the Patient withMuscle WeaknessAARON SAGUIL, CPT (P), MC, USA,Madigan Army Medical Center, Tacoma, WashingtonMuscle weakness is a common complaint among patients presenting to family physicians. Diagnosis begins with a patienthistory distinguishing weakness from fatigue or asthenia, separate conditions with different etiologies that can coexistwith, or be confused for,weakness. The pattern and severity ofweakness, associated symptoms, medication use, and fam-ily history help the physician determine whether the cause of a patient's weakness is infectious, neurologic, endocrine,inflammatory, rheumatologic, genetic, metabolic, electrolyte-induced, or drug-induced. In the physical examination, thephysician should objectively document the patient's loss of strength, conduct a neurologic survey, and search for patternsof weakness and extramuscular involvement. If a specific cause of weakness is suspected, the appropriate laboratory orradiologic studies should be performed. Otherwise, electromyography is indicated to confirm the presence of a myopathyor to evaluate for a neuropathy or a disease of the neuromuscular junction. Ifthe diagnosis remains unclear, the examinershould pursue a tiered progression of laboratory studies. Physicians should begin with blood chemistries and a thy-roid-stimulating hormone assay to evaluate for electrolyte and endocrine causes, then progress to creatine kinase level,erythrocyte sedimentation rate, and antinuclear antibody assays to evaluate for rheumatologic, inflammatory, genetic,and metabolic causes. Finally,many myopathies require a biopsy for diagnosis. Pathologic evaluation of the muscle tissuespecimen focuses on histologic, histochemical, electron microscopic, biochemical, and genetic analyses; advances in tech-nique have made a definitive diagnosis possible for many myopathies. (Am Fam Physician 2005;7l:1327-36. Copyright2005 American Academy of Family Physicians.)

See page 12 45 fors tr en g t h - o f - e v id e n c elabels .T he o nli ne -o nl y v er sio n o fth is a rt ic le , w h ic h o ff er smo r e d e ta il ed i nf ormat io no n a d di ti on a l s el ec te dc au se s o f m u sc le w ea k-n es s, is a va ila ble a t:h ttp :// www . a af p. o rg Iafp/U R L .

Mscleweakness is a common

complaint among patientspresenting to the family phy-sician's office. Although the

cause ofweakness occasionally may be appar-ent, often it is unclear, puzzling the physicianand frustrating the patient. A comprehen-sive evaluation of these patients includes athorough examination and coordination ofappropriate laboratory, radiologic, electro-diagnostic, and pathologic studies.DefinitionsDetermining the cause of muscle weaknessinvolves distinguishing primary weaknessfrom fatigue or asthenia, common condi-tions that differ from, but often overlapwith, muscle weakness.' Fatigue describes theinability to continue performing a task aftermultiple repetitions; in contrast, a patientwith primary weakness is unable to performthe first repetition of the task. Asthenia isa sense of weariness or exhaustion in theabsence of muscle weakness. This condi-tion is common in people who have chronicfatigue syndrome, sleep disorders, depres-sion, or chronic heart, lung, and kidney

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disease.' Because these conditions are preva-lent in the ambulatory population, familyphysicians can expect to encounter patientswith asthenia and fatigue more frequentlythan those with intrinsic muscle weakness.'Selected causes of asthenia and fatigue arelisted in Table 1.!

Unfortunately, the distinction betweenasthenia, fatigue, and primary weaknessoften is unclear. Patients frequently con-fuse the terms, and the medical literaturesometimes uses them interchangeably.' Inaddition, a patient's condition may causeprogression from one syndrome to another;for example, asthenia in a patient withheart failure may progress to true muscleweakness through deconditioning. Further,asthenia and fatigue can coexist with weak-ness, such as in patients with multiple scle-rosis and concomitant depression. Becausedepression is so prevalent, it is essential toconsider it as a possible cause of a patient'ssymptoms; diagnosis can be facilitated byusing one of the several validated screeningtools designed for the outpatient setting.v'This article discusses only intrinsic muscleweakness in adults.

D own lo ad ed f ro m t he A m e ri ca n F a m il y P h y sic ia n We b s ite a t www.aafp .org /a fp . Co p yr ig h t 2 0 05 Ame r ic a n A c ad emy o f F am il y P h y si ci an s . F or t h e p r iv a te , n o nc omme rc ia lu se o f o ne i nd iv id ua l u se r o f t he We b s it e. A l l o th er r ig ht s r es er ve d. C o nt ac t copyr ights@aafp .org f o r c o py r ig h t q u e st io n s a n dl or p e rm i ss io n r e qu e st s .

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Strength of RecommendationsKey clinical recommendation Label ReferencesIt is essential to consider depression as a possible diagnosis; several screening Atools for depression have been val idated for use in outpat ient sett ings.

Primary muscle weakness must be distinguished from the more common Cconditions of fatigue and asthenia.

If the diagnosis is s till inconclusive after the history, physical examination, and C 41laboratory, radiologic, and electromyographic evaluation, a muscle biopsy isrequired for patients who have a suspected myopathy.

3,4

A = consistent, good-quality patient-oriented evidence; B = inconsistent or limited-quality patient-oriented evidence;C = consensus, disease-oriented evidence, usual practice, opinion, or case series. See page 1245 for more information.

Differential DiagnosisConditions that result in intrinsic weaknesscan be divided into several main categories:infectious, neurologic, endocrine, inflam-matory, rheumatologic, genetic, metabolic,electrolyte-induced, or drug-induced.

In adults, medications (Table 25,6), infec-tions, and neurologic disorders are commoncauses of muscle weakness. The use of alco-hol or steroids can cause proximal weaknesswith characteristic physical and laboratoryfindings.V" Infectious agents that are mostcommonly associated with muscle weakness

TABLE 1Causesof Asthenia and FatigueAddison's diseaseAnemiaAnxietyChemotherapyChronic fatigue syndromeChronic painDecond itioni ng/sedenta rylifestyle

Dehydration and electrolytedisorders

DepressionDiabetesFibromyalgia

Heart diseaseHypothyroidismInfections (such as influenza,Epstein-Barr virus, HIV, hepatit is C,tuberculosis)

MedicationsNarcoticsParaneoplastic syndromePregnancy/postpa rtu mPulmonary diseaseRenal diseaseSleep disorders

HIV= human immunodeficiency virus.Adapted with permission from Hinshaw DB, Carnahan JM, Johnson DL. Depression,anxiety, and asthenia in advanced illness.J Am ColiSurg 2002;195:276.

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include influenza and Epstein-Barr virus(Table 36,9-12). Human immunodeficiencyvirus (HIV) is a less common cause ofmuscle weakness but should be consideredin patients with associated risk factors orsymptorns.v? Neurologic conditions that cancause weakness include cerebrovascular dis-ease (i.e., stroke, subdural/epidural hemato-mas), demyelinating disorders (i.e., multiplesclerosis, Guillain -Barre syndrome), andneuromuscular disorders (i.e., myastheniagravis, botulism). Localizing neurologicdeficits can help the physician focus thediagnostic work_up6,10-12 (Table 36,9-12).

Less common myopathies include thosecaused by endocrine, inflammatory, rheu-matologic, and electrolyte syndromes(Tables 45-8,13-26 and 56,8,15,16,18,20,24-38). Ofthe endocrine diseases, thyroid disease iscommon, but thyroid-related myopathy isuncommon; parathyroid-related myopathyshould be suspected in a patient with muscleweakness and chronic renal failure.14,15,32Inflammatory diseases typically affect olderadults and include both proximal (poly-myositis and dermatomyositis) and dis-tal myopathies (inclusion body myositis);the proximal inflammatory myopathiesrespond to steroids.21-23 Rheumatologic dis-orders causing weakness, such as systemiclupus and rheumatoid arthritis, can occurin young and elderly persons.V'" Disordersof potassium balance are among the morecommon electrolyte myopathies and may beprimary (such as in hypokalemic or hyper-

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TABLE 2Medications and Narcoticsthat Can Cause Muscle WeaknessAmiodarone (Cordarone)Antithyroid agents: methimazole (Tapazole);propylthiouracil

Antiretroviral medications: zidovudine(Retrovir); lamivudine (Epivir)

Chemotherapeutic agentsCimetidine (Tagamet)CocaineCorticosteroidsFibric acid derivatives: gemfibrozil (Lopid)InterferonLeuprolide acetate (Lupron)Nonsteroidal anti-inflammatory drugsPenicillinSulfonamidesStatinsInformation from references 5 and 6.

kalemic periodic paralysis) or secondary(such as in renal disease or angiotensin-converting enzyme inhibitor toxicity).Patients in whom these disturbances aresuspected should have electrocardiographyto screen for cardiac sequelaey,27-30

Rare causes of muscle weakness includegenetic (muscular and myotonic dystro-phies), metabolic (glycogenoses, lipidoses,and mitochondrial defects), and sarcoid-and amyloid -associated myopathies24-26,34-38(Tables 45-8,13-26nd 56,8,15,16,18,20,24-38).HistoryOnce muscle weakness has been differenti-ated from asthenia and fatigue, the physi-cian should ask the patient about diseaseonset and progression. Acute onset mayindicate infection or stroke. Subacute onsetmay implicate drugs, electrolytes, or inflam-matory or rheumatologic disease. Chronicprogressive weakness is the classic presenta-tion in genetic and metabolic myopathies.Despite these generalizations, there is con sid-erable variation in the time courses of differ-ent classes of myopathy, and even within theindividual disorders. For instance, althoughApril 1, 2005 Volume 71, Number 7

typically subacute, myasthenia gravis maypresent with rapid, generalized weakness orremain confined to a single muscle group foryears (as in ocular myasthenia)P

Because of this variability, the pattern ofmuscle weakness is crucial in differentiatingthe etiology. The physician should estab-lish whether the loss of strength is global(e.g., bilateral; may be proxi-mal, distal, or both) or focal.Focal processes (those that areunilateral or involve specificnerve distributions or intra-cranial vascular areas) tend tobe neurologic-although notall neurologic processes arefocal-and may require a different approachthan that used with global strength loss.

In patients with diffuse weakness, thephysician should determine whether the lossof function is proximal or distal by notingwhich physical activities muscle weaknesslimits. If the patient has difficulty rising froma chair (hip muscles) or combing his or herhair (shoulder girdle), the weakness is proxi-mal; if the patient has difficulty standingon his or her toes (gastrocnemius/soleus) or

Musc le Weakne ss

The use of alcohol or ste-roids can cause proximalweakness with characteris-t ic physical and laboratoryfindings.

TABLE 3Infectious and Neurologic Causes of Muscle WeaknessInfectiousEpstein-Barr virusHuman immunodeficiencyvirus

InfluenzaLyme diseaseMeningitis (multiple agents)PolioRabiesSyphilisToxoplasmosisNeurologicAmyotrophic lateral sclerosisCerebrovascular diseaseStrokeSubdural/epidural hematomas

Neurologic (continued)Demyelinating disordersGuillain-Barre syndromeMultiple sclerosis

NeoplasmNeuromuscular disordersBotulismLambert-Eaton myasthenic syndromeMyasthenia gravisOrganophosphate intoxication

RadiculopathiesCervical spondylosisDegenerative disc disease

Spinal cord injurySpinal muscle atrophy

Information from references 6 and 9 through 12.

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TABLE 4Selected Causes of Primary Muscle WeaknessCause Weakness Age of onset/diagnosis Systemic symptoms and findingsDrugsAlcohol Proximal (may be distal) Variable Change in mental status; telangiectasia;

peripheral neuropathy

EndocrineAdrenal insufficiency Generalized Variable Hypotension; hypoglycemia;

bronzing of the skinBuffalo hump; striae; osteoporosislucocorticoid excess Proximal Variable

Parathyroid hormone (secondary Proximal, lower extremity Variable, older adult Usually hasassociated comorbiditieshyperparathyroi dism) more than upper extremity (cardiovascular disease, diabetes)

Thyroid hormone Proximal, bulbar 40 to 49 years Weight loss; tachycardia; increased(hyperthyroidism) perspiration; tremorThyroid hormone Proximal 30 to 49 years Menorrhagia; bradycardia; goiter; delayed(hypothyroi dism) relaxation of deep tendon reflexes

InflammatoryDermatomyositis Proximal Variable, increased Gottron papules; heliotrope rash;

incidence with age calcinosis; interstitial lung disease;disordered GI motility

Inclusion body myositis Distal, especially At least 50 years Dysphagia; extramuscular involvementforearm and hand (younger than not as common

50 years: rare)Polymyositis Proximal Variable, increased Interstitial lung disease, disordered GI

incidence with age motility; overlap with rheumatologicdiseasesmore common

RheumatologicRheumatoi d arthritis Focal, periarticular, or diffuse Adult Symmetric joint inflammation (especially

MCP, PIPjoints); dry eyesand mouthSystemic lupus erythematosus Proximal Adult Malar rash; nephritis; arthritis

GeneticBecker muscular Hip; proximal leg and arm Late childhood to Mental retardation; cardiomyopathydystrophy adulthood

Limb-girdle muscular Variable, usually proximal Variable Variable, may have cardiac abnormalitiesdystrophies** limb, pelvic, and shoulder

girdle musclesMyotonic dystrophy Distal greater than proximal; Adolescence to Conduction abnormalities; mentaltype 1 foot drop; temporal and adulthood retardation; cataracts; insulin resistance

masseter wastingMetabolicGlycogen and lipid storage Proximal Variable Variable; exercise intolerance anddiseases; mitochondrial disease cardiomyopathy more common

GGT = gamma-glutamyltransferase; ACTH = adrenocorticotropin hormone; MUAPs =motor unit action potentials; TJ = triiodothyronine; T4= thyroxine;TSH = thyroid-stimulating hormone; GI= gastrointestinal; ANA = antinuclear antibodies; MCP=metacarpophalangeal; PIP= proximal interphalangeal;EMG = electromyogram; FIET= forearm ischemic exercise testing.*-Myopathic changes are nonspecific and include atrophy, degeneration, and regeneration of muscle fibers.t-Myotonic discharges are a type of prolonged burst of activity seen on insertion of the EMG needle.J;-Myopathic MUAPs are shorter in duration, lower in amplitude, and polyphasic when compared to MUAPs from normal muscle.-Secondary hyperparathyroidism usually caused by renal failure.Information from references 5 though 8 and 13 through 26.


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Laboratory abnormalities Creatine kinase Electromyogram Muscle biopsy

Elevated t ransaminase and GGT Normal to elevated Normal Myopathic changes*; selected atrophylevels; anemia; decreased of type II muscle fibersvitamin B '2

Hyponatremia; hyperkalemia; ACTH Normal Myotonic dischargest Diminished glycogen contentassay; ACTH stimulation test

Elevated urine-free cortisol, Normal Myopathic MUAPs:j: Selective atrophy of type II muscledexamethasone suppression, or fiberscorticotropin-releasing hormonestimulation tests

Hypocalcemia; uremia Normal Myopathic MUAPs:j: Atrophy of type II muscle fibers;increased lipofuscin beneath cellmembrane; calcium deposits inmuscle

Elevated T4and T3; TSH Normal or elevated Myopathic MUAPs:j:with or Usually normalvariable, depending on cause without fibrillation potentials]TSH Elevated With or without myopathic Myopathic changes*; glycogen

MUAPs:j:and fibrillation accumulationpotentials]

Elevated myoglobin; ANA positive; Greater than 10 times Myopathic MUAPs:j:with Inflammatory infiltrate with myopathicmyositis autoantibodies may be normal elevations fibrillation potentials] changes* and replacement bypresent adipose and collagen

Elevated myoglobin; positive ANA Elevated Myopathic MUAPs:j:with Inflammatory infiltrate with vacuolesless common; myositis fibrillation potentials] containing eosinophilic inclusionsautoantibodies may be present

Elevated myoglobin; ANA positive; Greater than 10 times Myopathic MUAPs:j:with Inflammatory infiltrate with myopathicmyositis autoantibodies may be normal elevations fibrillation potentials] changes* and replacement bypresent adipose and collagen

Elevated rheumatoid factor Normal or elevated No data Atrophy of type II muscle fibers;may have overlap syndrome withpolymyositis

ANA, anti-DNA antibodies, Normal to elevated No data Type II fiber atrophy; lymphocyticdepressed C3 and C4~ vasculitis; myositis

None Elevated Myopathic MUAPs:j:with Myopathic changes*; decreased andfibrillation potentials] patchy staining of dystrophin

None Variable, normal, or Myopathic MUAPs:j:+/- Myopathic changes*; may demonstrateelevated fibrillation potentials] absence of specific protein on

immunohistochemical stainingNone Normal to minimally Myopathic MUAPs:j:; Lessnecrosis and remodeling than in

elevated myotonic discharqes] muscular dystrophies; atrophy oftype I muscle fibers; ring fibers

Some glycogenoses associatedwith abnormal FIETtt

Variable, may increasewith exercise

Normal or myopathic MUAPs:j:+/- fibrillation potentialsl]

Myopathic changes* with glycogendeposits, lipid deposits, or raggedred fibers (for glycogen, lipid, ormitochondrial disease, respectively)

II-Fibrillation potentials represent spontaneous activity on the part of single muscle fibers (not usually noted with nondiseased muscle).~-C3 and C4 are complement components.**-Including facioscapulohumeral dystrophy.tt-FIET evaluates the rise of ammonia and lactate in the forearm during exertion.


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doing fine work with the hands(intrinsics), the muscle weak-ness is distal. Although manymyopathies are associated withproximal weakness, a smallnumber are associated predom-inantly with distal weakness;these include myotonic dystro-

phy, inclusion body myositis, and the geneticdistal myopathies.Ps" Patients with statin

Focal processes tend to beneurologic and may requirea different approach thanthat used in patients withglobal strength loss.

TABLE 5Additional Selected Causesof Muscle WeaknessElectrolyteHypercalcemiaHyperkalemia/hypokalemiaHypermagnesemia/hypomagnesemiaEndocrineAcromegalyPrimary hyperparathyroidismHypopitu ita rismVitamin D deficiency (osteomalacia)RheumatologicPolymyalgia rheumaticaSystemic sclerosis/sclerodermaGeneticDistal myopathiesOculopharyngeal muscular dystrophyMyotonic dystrophy type 2 (proximal myotonicmyopathy)

MetabolicG IycogenosesAcid maltase deficiencyAldolase A deficiencyBrancher enzyme deficiencyMyophosphorylase deficiencyPhosphofructokinase deficiencyLipidosesCarnitine deficiencyCarnitine palmitoyltransferase II deficiency

Trifunctional protein deficiencyMitochondrial defectsMiscellaneousAmyloidosisSarcoidosisInformation from references 6, S, 15, 16, IS, 20, and24 through 3S.


or alcohol toxicrty can present with eitherproximal or distal weakness.5,7,39

Other areas to address in the patient'shistory are associated symptoms, familyhistory, and pharmaceutical use. Commondrugs associated with muscle weakness arelisted in Table 2.5,6 Associated symptoms arefound in many myopathies and can be espe-cially helpful in narrowing the differentialdiagnosis among endocrine, rheumatologic,and inflammatory disorders. For example,dysphagia may accompany weakness ininclusion body myositis and systemic scle-rosis, whereas menorrhagia may attend theweakness that occurs in hypothyroidism. Afamily history, which almost always is pres-ent in genetic myopathies, may also be pres-ent in other causes of weakness, includinglupus, rheumatoid arthritis, dermatomyo-sitis, polymyositis, and the potassium-relatedparalyses " (Table 65,7-15,17,18,21,24-27,34,36,38).Physical ExaminationThe physical examination begins with anobjective confirmation of the subjectiveseverity and distribution of muscle weak-ness. In addition to individual muscles, thephysician should survey functional activitiessuch as standing and writing to determinewhether the weakness is proximal, distal, orboth.

Next, a thorough neurologic survey shouldaccompany motor testing. The physicianshould note patterns and relations amongdefects and narrow the differential by deter-mining whether the deficits are referable tothe central or peripheral nervous system. Thepattern is important. A neurologic examina-tion that shows deficits in a single nerve orradicular distribution indicates a possiblemononeuritis, entrapment neuropathy, orradiculopathy, and calls for a different work-up than that required for a limb paresis in apatient with cerebrovascular risk factors.

If the neurologic examination is unreveal-ing, a more general physical examination,searching for extramuscular signs, is war-ranted (Table 65,7-15,17,18,21,24-27,34,36,38). Mentalstatus testing may reveal changes suggestiveof a myopathy-inducing electrolyte disorder(calcium or magnesium) or an arrest of



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TABLE 6Diagnostic Clues for Muscle WeaknessFinding Suggested diagnosesHistoryAbdominal pain; excessive urination; renal stonesAcute weakness with neurologic deficit(s)Arthralgia; malaise; myalgia; respiratory symptomsChronic neck or back pain, with or without sharpshooting pains

Distal weakness

Dysphagia; rash around eyelids; shortness ofbreath

Easybruising; emotional labil ity; obesityExercise-provoked weakness

Family history of myopathy

Heat-induced symptoms; multiple neurologicdef ici ts spread over space and t ime

Legal problems; memory loss; repeated trauma;sexual dysfunction

Positive medication history

Sexually transmitted diseasePhysical examinationArthrit is; malar rash; nephrit isCard iomyopathy

Dry eyes and mouth; joint inflammation(especially MCP, PIPjoints)

Facial weakness; fatigable weakness; ptosisNeurologic deficitsFocalCentralPeripheral

DiffuseCentralPeripheral

Orthostatic hypotension; skin bronzing

Hypercalcemia; hyperparathyroidismSpinal cord injury; strokeEpstein-Barr virus; HIV; influenzaCervical spondylosis; degenerative disc diseaseGenetic distal myopathies; inclusion bodymyositis

Dermatomyositis

Glucocorticoid excess; steroid-induced myopathyGlycogen and lipid storage diseases;mitochondrial myopathies; myasthenia gravis

Hyper- or hypokalemic periodic paralysis;inflammatory disease; muscular dystrophies;rheumatologic disease

Multiple sclerosisAlcoholism

Medication-induced myopathy (esp.anti-retrovirals, statins, steroids)

HIV; syphilis

Systemic lupus erythematosusAlcohol; amyloid; glycogen storage disease;inflammatory myopathies; musculardystrophies; sarcoid

Rheumatoid arthritis

Myasthenia gravis

Multiple sclerosis; strokePeripheral neuropathy; radiculopathy

Amyotrophic lateral sclerosisGuillain-Barre syndrome; polyneuropathyHypoadrenalism

HIV = human immunodef iciency vi rus; Mep = metacarpophalangeal; PIP = proximal interphalangeal.Information from references 5,7 through 15, 17, IS, 21, 24 through 27,34,36, and 3S.

mental development as occurs in geneticmyopathies.e=" The cardiovascular assess-ment may elicit changes consistent witha cardiomyopathy-a nonspecific conse-

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quence of many myopathy-inducing disor-ders-or a pericarditis, as occurs with someof the infectious and rheumatologic causesof muscle weakness.5,7,8,9,18,21,24,25,29,36,38

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Pulmonary testing may reveal the cracklesof a restrictive lung defect, found in someinflammatory and rheumatologic myopa-thies.17,21Gastrointestinal examination may

reveal hepatomegaly, associatedwith metabolic storage diseasesand amyloidosis.Pv'" Skin find-ings are possible in multiplecategories of disease (e.g., skinbronzing in adrenal insuffi-ciency; Gottron's papules andheliotrope rash in dermatomyo-sitis; and erythema nodosumin sarcoidosis). The skeletalexamination may reveal the legbowing and pseudofractures of

osteomalacia or the symmetric joint swellingof lupus and rheumatoid arthritis.8,17,18,21,25,35

In a patient whose muscleweakness is suggestiveof neurologic disease,early neuroimaging (forsuspected cerebrovasculardisease) or lumbar puncture(for possible meningitis,encephalitis, or multiplesclerosis) is indicated.

laboratory and Radiologic EvaluationThe sequence and timing of the ancillaryinvestigations varies with the clinical sce-nario. In a patient whose muscle weak-ness is suggestive of neurologic disease, earlyneuroimaging (for suspected cerebrovasculardisease) or lumbar puncture (for possiblemeningitis, encephalitis, or multiple sclero-sis) is indicated. If infectious disease is sus-pected, appropriate titers or cultures shouldbe obtained. When a specific class or type ofmyopathy is suspected, appropriate testingshould be performed.

If the cause of muscle weakness is unclear,serum chemistries (electrolytes, calcium,phosphate, magnesium, glucose) should beobtained, as well as a thyroid-stimulatinghormone assay to evaluate for electrolyteand endocrine myopathies. If an endocri-nopathy is suspected, more specific assayscan be performed based on clinical suspi-

The AuthorAARON SAGUIL, CPT (P), MC, USA, is a faculty development fellow in theDepartment of Family Medicine at the Madigan Army Medical Center, Tacoma,Wash. Dr. Saguil received his medical degree from the University of FloridaCollege of Medicine, Gainesville. He completed a family practice residency atDeWitt Army Community Hospital , Fort Belvoir, Va.Address correspondence to Aaron Saguil, CPT (P), MC, USA, Department ofFamily Medicine, Madigan Army Medical Center, Tacoma, WA 98431 (e-mail:[email protected]). Reprints are not available from the author.


cion (e.g., 24-hour urine cortisol testingto rule out Cushing's disease; oral glucoseload/growth hormone assay to rule outacromegaly; vitamin D assay to rule outosteomalacia).8,13-15,28,29,32

Next, investigations looking for inflam-matory, rheumatologic, or genetic myop-athies can be performed sequentially orconcurrently. Although nonspecific, the cre-atine kinase (CK) level usually is normal inthe electrolyte and endocrine myopathies(notable exceptions are thyroid and potas-sium disorder myopathies).8,16,28,29However,the CK level may be highly elevated (10 to100 times normal) in the inflammatorymyopathies and can be moderately to highlyelevated in the muscular dystrophies.16,23,25Other conditions that can be associated withelevated CK levels include sarcoidosis, infec-tions, alcoholism, and adverse reactions tomedications. Metabolic (storage) myopa-thies tend to be associated with only mild tomoderate elevations in CK levels.e"

In addition to CK, an erythrocyte sedi-mentation rate (ESR) and an antinuclearantibody assay (ANA) may help determineif a rheumatologic myopathy exists. If eitherESR or ANA assay is positive, additionalstudies may be obtained, including rheuma-toid factor (rheumatoid arthritis); anti-double-stranded DNA or antiphospholipidantibodies (lupus); or anticentromere anti-bodies (scleroderrnal.F"? Patients with idio-pathic inflammatory myopathies also tendto have elevated ESR and ANA levels; manyof these same patients have overlap syn-dromes, in which an inflammatory myopa-thy and a rheumatologic disease coexist. Anantisynthetase antibody, when positive, mayhelp confirm the presence of an inflamma-tory myopathy.PElectromyographyIf the presence of myopathy is uncer-tain, electromyography may be indicated.Although changes seen on electromyographyare not pathognomonic for any specific dis-ease process, an abnormal electromyogramcan indicate if a neuropathy or neuromuscu-lar disease is present or can help solidify thediagnosis of a primary myopathy.



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Electromyography assesses several com-ponents of muscle electrical activity: themuscle's spontaneous activity; its responseto the insertion of a probe; the character ofthe muscle's individual motor unit actionpotentials; and the rapidity with which addi-tional motor units are recruited in responseto an electrical signal. Muscle inflammation,atrophy, necrosis, denervation, or neuromus-cular disease can alter these components,giving rise to patterns that may help illu-minate the underlying pathology. Althoughthe procedure can cause minor discomfort,most patients tolerate it well_l6,24,40Muscle BiopsyIf the diagnosis is still inconclusive after thehistory, physical examination, and laboratory,radiologic, and electromyographic evalua-tions, a muscle biopsy is required for patientswho have a suspected myopathy." The tech-nology of this method, especially regardingthe use of genetic markers, is advancing rap-idly, making a definitive diagnosis possiblefor a wider range of myopathies. 24,25

The biopsy site should be an affected mus-cle that is not diseased to the point of necro-sis. Common biopsy sites are the vastuslateralis of the quadriceps for proximalmyopathies and the gastrocnemius for distalmyopathies; in patients without involve-ment of these muscles, an affected group ischosen.f The muscle biopsy can be accom-plished as an outpatient procedure and car-ries the attendant risks of pain, bleeding,infection, and sensory loss. As with elec-tromyography, patients should avoid usinganticoagulants before the procedure, andthe site chosen for biopsy should be free ofoverlying infection.

The pathologic analysis of biopsy spec-imens focuses on the histologic, histo-chemical, electron microscopic, genetic,and biochemical changes that are found inthe affected muscle. Histology may showatrophic, degenerating, and regeneratingmuscle fibers (general findings referredto as myopathic changes), or it may showmore specific findings such as accumula-tions of glycogen (glycogen storage dis-eases), ragged red fibers (mitochondrialApril 1, 2005 Volume 71, Number 7

myopathies), noncaseating granulomas(sarcoidosis), and amyloid deposits (amy-loidosis). Histochemical techniques assayfor specific enzymes and proteins, andmay reveal deficiencies as in disorders ofcarbohydrate or fatty acid metabolismor the muscular dystrophies. Electronmicroscopy and biochemical assays mayhelp to uncover subtle changes not detect-able by other techniques, further aidingin the diagnosis of metabolic and protein-deficiency myopathies.7,18-2o,21,24,25,27,28,35,37The opinions and assertions contained herein are theprivate views of the authors and are not to be construedas official or as reflecting the views of the u . s . ArmyMedical Department or the u . s . Army Serv ice at large.The author does not have any confli cts o f interest.Sources of funding: none reported.

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Evaluation of the Patient With Muscle Weakness - American Family Physician

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