What causes muscle weakness

Muscle weakness is reduced strength in one or more muscles. Muscle weakness is a common complaint among patients presenting to the family physician’s office ¹. Although the cause of muscle weakness occasionally may be apparent, often it is unclear, puzzling the physician and frustrating the patient. A comprehensive evaluation of these patients includes a thorough examination and coordination of appropriate laboratory, radiologic, electrodiagnostic, and pathologic studies.

Determining the cause of muscle weakness involves distinguishing primary weakness from fatigue or asthenia, common conditions that differ from, but often overlap with, muscle weakness ². Fatigue describes the inability to continue performing a task after multiple repetitions; in contrast, a patient with primary weakness is unable to perform the first repetition of the task. Asthenia is a sense of weariness or exhaustion in the absence of muscle weakness. This condition is common in people who have chronic fatigue syndrome, sleep disorders, depression, or chronic heart, lung, and kidney disease ². Because these conditions are prevalent in the general population, family physicians can expect to encounter patients with asthenia and fatigue more frequently than those with intrinsic muscle weakness ².

Unfortunately, the distinction between asthenia, fatigue, and primary weakness often is unclear ¹. Patients frequently confuse the terms, and the medical literature sometimes uses them interchangeably ³. In addition, a patient’s condition may cause progression from one syndrome to another; for example, asthenia in a patient with heart failure may progress to true muscle weakness through deconditioning. Further, asthenia and fatigue can coexist with weakness, such as in patients with multiple sclerosis and concomitant depression. Because depression is so prevalent, it is essential to consider it as a possible cause of a patient’s symptoms; diagnosis can be facilitated by using one of the several validated screening tools designed for the outpatient setting ⁴.

Causes of muscle weakness in adults

Muscle weakness may be all over the body or in only one area. Muscle weakness is more noticeable when it is in one area. Muscle weakness in one area may occur:

• After a stroke
• After injury to a nerve
• During a flare-up of multiple sclerosis (MS)

You may feel weak but have no real loss of strength. This is called subjective weakness. It may be due to an infection such as the flu. Or, you may have a loss of strength that can be noted on a physical exam. This is called objective weakness.

Conditions that result in intrinsic muscle weakness can be divided into several main categories: infectious, neurologic, endocrine, inflammatory, rheumatologic, genetic, metabolic, electrolyte-induced, or drug-induced.

In adults, medications, infections, and neurologic disorders are common causes of muscle weakness. The use of alcohol or steroids can cause proximal weakness with characteristic physical and laboratory findings ⁵. Infectious agents that are most commonly associated with muscle weakness include influenza and Epstein-Barr virus (EBV) ⁶. Human immunodeficiency virus (HIV) is a less common cause of muscle weakness but should be considered in patients with associated risk factors or symptoms ⁵. Neurologic conditions that can cause weakness include cerebrovascular disease (i.e., stroke, subdural/epidural hematomas), demyelinating disorders (i.e., multiple sclerosis, Guillain-Barré syndrome), and neuromuscular disorders (i.e., myasthenia gravis, botulism). Localizing neurologic deficits can help the physician focus the diagnostic work-up.

Less common causes of muscle weakness include those caused by endocrine, inflammatory, rheumatologic, and electrolyte syndromes. Of the endocrine diseases, thyroid disease is common, but thyroid-related muscle weakness is uncommon; parathyroid-related myopathy should be suspected in a patient with muscle weakness and chronic renal failure ⁷. Inflammatory diseases typically affect older adults and include both proximal (polymyositis and dermatomyositis) and distal myopathies (inclusion body myositis); the proximal inflammatory myopathies respond to steroids ⁸. Rheumatologic disorders causing weakness, such as systemic lupus and rheumatoid arthritis, can occur in young and elderly persons ⁹. Disorders of potassium balance are among the more common electrolyte myopathies and may be primary (such as in hypokalemic or hyperkalemic periodic paralysis) or secondary (such as in renal disease or angiotensin-converting enzyme inhibitor toxicity). Patients in whom these disturbances are suspected should have electrocardiography to screen for cardiac complications ¹⁰.

Rare causes of muscle weakness include genetic (muscular and myotonic dystrophies), metabolic (glycogenoses, lipidoses, and mitochondrial defects), and sarcoidand amyloid-associated myopathies ¹¹.

Muscle weakness may be caused by diseases or conditions affecting many different body systems, such as the following:

Neurologic (brain and nervous system)

• Disease of the nerve cells in the brain and spinal cord (amyotrophic lateral sclerosis; ALS)
• Weakness of the muscles of the face (Bell palsy)
• Group of disorders involving brain and nervous system functions (cerebral palsy)
• Nerve inflammation causing muscle weakness (Guillain-Barre syndrome)
• Multiple sclerosis
• Pinched nerve (for example, caused by a slipped disk in the spine)
• Cancer
• Cerebrovascular disease
  • Stroke
  • Subdural/epidural hematomas
• Neuromuscular disorders
  • Botulism
  • Lambert-Eaton myasthenic syndrome
  • Myasthenia gravis
  • Organophosphate intoxication
• Radiculopathies
  • Cervical spondylosis
  • Degenerative disc disease
• Spinal cord injury
• Spinal muscle atrophy

Muscle diseases

• Becker muscular dystrophy
• Dermatomyositis
• Muscular dystrophy (Duchenne)
• Myotonic dystrophy

Poisoning

• Botulism
• Poisoning (insecticides, nerve gas)
• Shellfish poisoning

Infections

• Epstein-Barr virus
• Human immunodeficiency virus (HIV)
• Influenza (flu)
• Lyme disease
• Meningitis (multiple agents)
• Polio (poliomyelitis)
• Rabies
• Syphilis
• Toxoplasmosis

Electrolyte

• Hypercalcemia (high calcium)
• Hyperkalemia (high potassium)/hypokalemia (low potassium)
• Hypermagnesemia (high magnesium)/hypomagnesemia (low magnesium)
• Hyponatremia (low sodium)

Endocrine

• Acromegaly
• Parathyroid glands producing too much parathyroid hormone (hyperparathyroidism)
• Hypopituitarism
• Vitamin D deficiency (osteomalacia)
• Overactive thyroid (thyrotoxicosis or hyperthyroidism)
• Adrenal glands not producing enough hormones (Addison disease)

Rheumatologic

• Polymyalgia rheumatica
• Systemic sclerosis/scleroderma

Genetic

• Distal myopathies
• Oculopharyngeal muscular dystrophy
• Myotonic dystrophy type 2 (proximal myotonic myopathy)

Metabolic

• Glycogenoses
  • Acid maltase deficiency
  • Aldolase A deficiency
  • Brancher enzyme deficiency
  • Myophosphorylase deficiency
  • Phosphofructokinase deficiency
• Lipidoses
  • Carnitine deficiency
  • Carnitine palmitoyltransferase II deficiency
• Trifunctional protein deficiency
• Mitochondrial defects

Other

• Not enough healthy red blood cells (anemia)
• Amyloidosis
• Sarcoidosis

Medications and Narcotics

• Amiodarone (Cordarone)
• Antithyroid agents: methimazole (Tapazole); propylthiouracil
• Antiretroviral medications: zidovudine (Retrovir); lamivudine (Epivir)
• Chemotherapeutic agents
• Cimetidine (Tagamet)
• Cocaine
• Corticosteroids
• Fibric acid derivatives: gemfibrozil (Lopid)
• Interferon
• Leuprolide acetate (Lupron)
• Nonsteroidal anti-inflammatory drugs (NSAIDs)
• Penicillin
• Sulfonamides
• Statins

Table 1. Selected Causes of Primary Muscle Weakness

Abbreviations: GGT = gamma-glutamyltransferase; ACTH = adrenocorticotropin hormone; MUAPs = motor unit action potentials; T3 = triiodothyronine; T4 = thyroxine; TSH = thyroid-stimulating hormone; GI = gastrointestinal; ANA = antinuclear antibodies; MCP = metacarpophalangeal; PIP = proximal interphalangeal; EMG = electromyogram; FIET = forearm ischemic exercise testing.

Footnotes:

*—Myopathic changes are nonspecific and include atrophy, degeneration, and regeneration of muscle fibers.

†—Myotonic discharges are a type of prolonged burst of activity seen on insertion of the EMG needle.

‡—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.

∥—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.

††—FIET evaluates the rise of ammonia and lactate in the forearm during exertion.

Causes muscle weakness and fatigue

Weakness and fatigue are nonspecific symptoms that may be encountered in a bewildering number of medical and psychiatric disorders; they also may be the expected physiologic consequence of normal human activities ¹². Most patients with weakness or fatigue have self-limited conditions and do not seek medical care. Among those who visit a physician, weakness and fatigue are often part of an easily identified symptom complex. The patient who presents with chronic weakness or fatigue as the sole or major complaint may represent a more difficult diagnostic and therapeutic problem.

The bedside examination is of unique value in evaluating these symptoms. The initial history and physical examination usually allow the clinician to characterize the problem as medical, psychiatric, or physiologic in origin. In a specific patient, weakness or fatigue may be due to multiple causes, or the cause may not be initially apparent.

A precise understanding of the patient’s description of weakness or fatigue is imperative. Is there a loss of muscle strength, or is the problem a vague loss of energy, weariness, or lassitude? True weakness usually indicates a medical disorder. Fatigue, in contrast, may result from medical, psychiatric, or physiologic causes. Other symptoms should not be confused with weakness. For example, some patients speak of weakness when they are actually experiencing shortness of breath, generalized malaise, or joint pain and limitation of motion.

Obtain the history by encouraging the patient to “tell the story” of the problem. This unstructured format should be supplemented, as needed, by specific questions about weakness and fatigue:

• The onset and temporal course
• The distribution (localized vs. generalized)
• Exacerbating and relieving factors
• Associated signs and symptoms
• The setting in which the problem developed
• The impact on daily activities

Weakness beginning in childhood may be the result of Duchenne’s muscular dystrophy. The sudden onset of weakness suggests a cerebrovascular accident; this diagnosis should be strongly considered when the weakness is localized and has a neuroanatomic distribution. Progressively more severe weakness and fatigue are seen with metastatic carcinoma. Recurring episodes of weakness should raise the question of periodic paralysis. Weakness exacerbated by effort and relieved by rest is characteristic of myasthenia gravis. Proximal muscle weakness suggests a myopathy, whereas distal muscle weakness is more consistent with a peripheral neuropathy or pyramidal tract disorder. Loss of interest in daily activities and insomnia may indicate a depressive state. Recurring episodes of apprehension, tremulousness, and palpitations are seen with generalized anxiety. The presence of fever may point to an infection, malignancy, or collagen vascular disease. Paroxysmal nocturnal dyspnea is indicative of left ventricular failure. Inflammatory bowel disease should be considered when the patient has chronic diarrhea. Weakness or fatigue that occur only after jogging, fasting, or insufficient sleep are most likely explained by normal physiologic mechanisms. Physically demanding occupations and pregnancy are commonly associated with fatigue. Learn of the impact of these symptoms on the patient’s routine daily activities, such as combing hair, climbing stairs, or speaking. Difficulty with combing hair and climbing stairs suggests weakness of proximal muscles. These data may help localize the problem, shed light on a specific diagnosis, or provide insight into the patient’s coping skills.

Medical, surgical, and psychiatric problems should be considered as possible causes of weakness and fatigue. All prescription and over-the-counter medications should be listed. Frequently used medications such as antihypertensives, sedative-hypnotics, antidepressants, tranquilizers, and antihistamines are common causes of fatigue. The psychosocial history should provide a personal picture of the patient, including data on lifestyle, home life, occupational experiences, habits, and sexual practices. Interpersonal conflicts, recent losses, and threatening situations should be identified. These data are of great importance because clinical surveys of chronic weakness and fatigue cite psychosocial problems as the most common cause of these symptoms. A carefully elicited family history may identify a heritable disorder that could account for the problem. For example, there may be a strong family history of depression. An essential component of the work-up is a complete review of systems. First examine those systems discussed in the present illness; thereafter, explore all remaining systems in depth. Such an approach may lead to an unsuspected problem. For example, polyuria may be the first clue to a diagnosis of diabetes mellitus. A history of dark urine should raise the question of hepatitis. The diagnosis of a somatoform disorder, such as hypochondriasis, must be considered in a patient with multiple physical symptoms and no demonstrable organic findings.

The physical examination may provide essential data that are not obtainable through the interview or laboratory studies. In particular, testing muscle strength, both individual muscles and groups of muscles, is essential to help distinguish true weakness from fatigue. The examiner should perform a detailed neuromuscular examination, checking for muscle atrophy, abnormal muscle tone, abnormal deep tendon reflexes, pathologic reflexes, fasciculations, muscle tenderness, and sensory deficits. In the presence of a neuromuscular problem, analysis of these neurologic findings may allow the clinician to distinguish between cerebral, spinal, peripheral nerve, and myopathic processes. The history should provide focus for the general physical examination, but all systems should be meticulously examined. The general appearance may suggest an endocrine disorder. Measuring the blood pressure in the erect position may document orthostatic hypotension as a cause of the weakness or fatigue. Palpating an enlarged spleen may lead to the diagnosis of infectious mononucleosis. A formal mental status examination is vital. This should include assessment of thought content, orientation, emotional status, memory, constructional ability, and abstract reasoning. Abnormalities may point to the diagnosis of early dementia or an affective disorder presenting as weakness or fatigue.

Because the history and physical examination usually provide a correct diagnosis, laboratory studies often play, primarily, a confirmatory role. When a satisfactory explanation for the weakness or fatigue does not result from the initial clinical examination, the history and physical examination should be repeated. Diagnostic possibilities should be systematically reviewed. For example, the category of endocrine-metabolic causes of weakness and fatigue include diabetes mellitus, hypoglycemia, hypopituitarism, acromegaly, Addison’s disease, Cushing’s syndrome, iatrogenic corticosteroid myopathy, hypothyroidism, and hyperthyroidism; serum electrolyte abnormalities such as hypophosphatemia, hypercalcemia, hypokalemia, and hyperkalemia are also associated with these symptoms and may lead to a specific diagnosis. Clues from the clinical examination may suggest that a specific laboratory test should be performed, such as the ACTH stimulation test for Addison’s disease. A psychiatric diagnosis should be based on the presence of positive findings and not simply on the absence of a medical explanation for the problem. When a diagnosis cannot be made, the patient should not be told that “there is nothing wrong”; instead, the patient should be advised that careful follow-up is necessary in order to collect additional data. Thoughtful management and support of the patient are always important, particularly in instances where a diagnosis is made but no effective therapy is available, such as chronic Epstein–Barr virus infection.

Physiologic Causes of Weakness and Fatigue

• Physical activity, excessive or inadequate
• Rest and sleep, inadequate or excessive
• Diet, excessive or inadequate intake
• Environmental factors (e.g., heat)
• Pregnancy

Medical Causes of Weakness and Fatigue

• Neurologic (e.g., myasthenia gravis)
• Endocrine-metabolic (e.g., hypothyroidism)
• Infectious (e.g., infectious mononucleosis)
• Musculoskeletal (e.g., rheumatoid arthritis)
• Malignant (e.g., pancreatic cancer)
• Hematologic (e.g., iron deficiency anemia)
• Cardiac (e.g., heart failure)
• Pulmonary (e.g., chronic obstructive lung disease)
• Hepatic (e.g., hepatitis)
• Renal (e.g., renal failure)
• Inflammatory (e.g., Crohn’s disease)
• Miscellaneous (e.g., medication, nutritional deficiencies, surgery)

Psychiatric Causes of Weakness and Fatigue

• Anxiety disorder (e.g., generalized anxiety)
• Affective disorder (e.g., depressive episode)
• Adjustment disorder (e.g., grief)
• Substance use disorder (e.g., sedative-hypnotics)
• Personality disorder (e.g., dependent personality)
• Somatoform disorder (e.g., hypochondriasis)
• Organic mental disorder (e.g., dementia)

Causes of Asthenia and Fatigue

• Addison’s disease
• Anemia
• Anxiety
• Chemotherapy
• Chronic fatigue syndrome
• Chronic pain
• Deconditioning/sedentary lifestyle
• Dehydration and electrolyte disorders
• Depression
• Diabetes
• Fibromyalgia
• Heart disease
• Hypothyroidism
• Infections (such as influenza, Epstein-Barr virus, HIV (human immunodeficiency virus), hepatitis C, tuberculosis)
• Medications
• Narcotics
• Paraneoplastic syndrome
• Pregnancy/postpartum
• Pulmonary disease
• Renal disease
• Sleep disorders

Muscle weakness symptoms

Muscle weakness symptom is reduced strength in one or more muscles.

Muscle weakness diagnosis

Once muscle weakness has been differentiated from asthenia and fatigue, your doctor will ask you about your weakness, such as when it began, how long it has lasted, and whether you have it all the time or only at certain times and its progression. You may also be asked about medicines you take or if you have been ill recently. Acute onset may indicate infection or stroke. Subacute onset may implicate drugs, electrolytes, or inflammatory or rheumatologic disease. Chronic progressive weakness is the classic presentation in genetic and metabolic myopathies. Despite these generalizations, there is considerable variation in the time courses of different classes of myopathy, and even within the individual disorders. For instance, although typically subacute, myasthenia gravis may present with rapid, generalized weakness or remain confined to a single muscle group for years (as in ocular myasthenia) ¹³.

Your doctor will do a physical exam. Your doctor will establish whether the loss of strength is global (e.g., bilateral; may be proximal, distal, or both) or focal. Focal processes (those that are unilateral or involve specific nerve distributions or intracranial vascular areas) tend to be neurologic—although not all neurologic processes are focal—and may require a different approach than that used with global strength loss.

In patients with diffuse weakness, your doctor will determine whether the loss of function is proximal or distal by noting which physical activities muscle weakness limits. If you have difficulty rising from a chair (hip muscles) or combing your hair (shoulder girdle), the weakness is proximal; if you have difficulty standing on your toes (gastrocnemius/soleus) or doing fine work with your hands (intrinsics), the muscle weakness is distal. Although many myopathies are associated with proximal weakness, a small number are associated predominantly with distal weakness; these include myotonic dystrophy, inclusion body myositis, and the genetic distal myopathies ⁸. Patients with statin or alcohol toxicity can present with either proximal or distal weakness ¹⁴.

Other areas to address in the patient’s history are associated symptoms, family history, and pharmaceutical use. Common drugs associated with muscle weakness are listed above. Associated symptoms are found in many myopathies and can be especially helpful in narrowing the differential diagnosis among endocrine, rheumatologic, and inflammatory disorders. For example, dysphagia may accompany weakness in inclusion body myositis and systemic sclerosis, whereas menorrhagia may attend the weakness that occurs in hypothyroidism. A family history, which almost always is present in genetic myopathies, may also be present in other causes of weakness, including lupus, rheumatoid arthritis, dermatomyositis, polymyositis, and the potassium-related paralyses ¹⁵.

Table 2. Diagnostic Clues for Muscle Weakness

Abbreviations: HIV = human immunodeficiency virus; MCP = metacarpophalangeal; PIP = proximal interphalangeal.

Physical Examination

The physical examination begins with an objective confirmation of the subjective severity and distribution of muscle weakness. In addition to individual muscles, the physician should survey functional activities such as standing and writing to determine whether the weakness is proximal, distal, or both.

Next, a thorough neurologic survey should accompany motor testing. The physician should note patterns and relations among defects and narrow the differential by determining whether the deficits are referable to the central or peripheral nervous system. The pattern is important. A neurologic examination that shows deficits in a single nerve or radicular distribution indicates a possible mononeuritis, entrapment neuropathy, or radiculopathy, and calls for a different workup than that required for a limb paresis in a patient with cerebrovascular risk factors.

If the neurologic examination is unrevealing, a more general physical examination, searching for extramuscular signs, is warranted. Mental status testing may reveal changes suggestive of a myopathy-inducing electrolyte disorder (calcium or magnesium) or an arrest of mental development as occurs in genetic myopathies ¹⁰. The cardiovascular assessment may elicit changes consistent with a cardiomyopathy—a nonspecific consequence of many myopathy-inducing disorders—or a pericarditis, as occurs with some of the infectious and rheumatologic causes of muscle weakness ⁵.

Pulmonary testing may reveal the crackles of a restrictive lung defect, found in some inflammatory and rheumatologic myopathies ⁹. Gastrointestinal examination may reveal hepatomegaly, associated with metabolic storage diseases and amyloidosis ¹¹. Skin findings are possible in multiple categories of disease (e.g., skin bronzing in adrenal insufficiency; Gottron’s papules and heliotrope rash in dermatomyositis; and erythema nodosum in sarcoidosis). The skeletal examination may reveal the leg bowing and pseudofractures of osteomalacia or the symmetric joint swelling of lupus and rheumatoid arthritis ¹⁶.

Muscle Strength Grading

The function of muscle strength testing is to evaluate the complaint of weakness, often when there is a suspected neurologic disease. It is an integral part of the neurologic exam, especially for patients with stroke, brain injury, spinal cord injury, neuropathy, amyotrophic lateral sclerosis, and a host of other neurologic problems.

The most commonly accepted method of evaluating muscle strength is the Medical Research Council Manual Muscle Testing scale. This method involves testing key muscles from the upper and lower extremities against the examiner’s resistance and grading the patient’s strength on a 0 to 5 scale accordingly ¹⁷:

• 0 No muscle activation
• 1 Trace muscle activation, such as a twitch, without achieving full range of motion
• 2 Muscle activation with gravity eliminated, achieving full range of motion
• 3 Muscle activation against gravity, full range of motion
• 4 Muscle activation against some resistance, full range of motion
• 5 Muscle activation against examiner’s full resistance, full range of motion

Commonly tested muscles include the shoulder abductors, elbow flexors, elbow extensors, wrist extensors, finger flexors, hand intrinsics, hip flexors, knee extensors, dorsiflexors, great toe extensor, and plantar flexors. These muscle groups are commonly chosen, so that important spinal nerve roots are assessed systematically; however, further muscles can be tested to evaluate individual peripheral nerves. For example, testing the strength of the elbow flexors, elbow extensors, wrist extensors, finger flexors, and hand intrinsics allow for a methodical evaluation of the C5 to T1 nerve roots. However, one could more specifically test the thumb abductors to evaluate the median nerve and the abductor digiti minimi to evaluate the ulnar nerve.

Laboratory and Radiologic Evaluation

The sequence and timing of the ancillary investigations varies with the clinical scenario. In a patient whose muscle weakness is suggestive of neurologic disease, early neuroimaging (for suspected cerebrovascular disease) or lumbar puncture (for possible meningitis, encephalitis, or multiple sclerosis) is indicated. If infectious disease is suspected, appropriate titers or cultures should be obtained. When a specific class or type of myopathy is suspected, appropriate testing should be performed.

If the cause of muscle weakness is unclear, serum chemistries (electrolytes, calcium, phosphate, magnesium, glucose) should be obtained, as well as a thyroid-stimulating hormone assay to evaluate for electrolyte and endocrine myopathies. If an endocrinopathy is suspected, more specific assays can be performed based on clinical suspicion (e.g., 24-hour urine cortisol testing to rule out Cushing’s disease; oral glucose load/growth hormone assay to rule out acromegaly; vitamin D assay to rule out osteomalacia) ¹⁶.

Next, investigations looking for inflammatory, rheumatologic, or genetic myopathies can be performed sequentially or concurrently. Although nonspecific, the creatine kinase (CK) level usually is normal in the electrolyte and endocrine myopathies (notable exceptions are thyroid and potassium disorder myopathies) ¹⁶. However, the creatine kinase level may be highly elevated (10 to 100 times normal) in the inflammatory myopathies and can be moderately to highly elevated in the muscular dystrophies ¹⁸. Other conditions that can be associated with elevated creatine kinase levels include sarcoidosis, infections, alcoholism, and adverse reactions to medications. Metabolic (storage) myopathies tend to be associated with only mild to moderate elevations in creatine kinase levels ¹⁴.

In addition to creatine kinase, an erythrocyte sedimentation rate (ESR) and an antinuclear antibody assay (ANA) may help determine if a rheumatologic myopathy exists. If either ESR or antinuclear antibody assay (ANA) assay is positive, additional studies may be obtained, including rheumatoid factor (rheumatoid arthritis); anti–double-stranded DNA or antiphospholipid antibodies (lupus); or anticentromere antibodies (scleroderma) ⁹. Patients with idiopathic inflammatory myopathies also tend to have elevated ESR and antinuclear antibody assay (ANA) levels; many of these same patients have overlap syndromes, in which an inflammatory myopathy and a rheumatologic disease coexist. An antisynthetase antibody, when positive, may help confirm the presence of an inflammatory myopathy ¹⁹.

Electromyography

If the presence of myopathy is uncertain, electromyography may be indicated. Although changes seen on electromyography are not pathognomonic for any specific disease process, an abnormal electromyogram can indicate if a neuropathy or neuromuscular disease is present or can help solidify the diagnosis of a primary myopathy.

Electromyography assesses several components of muscle electrical activity: the muscle’s spontaneous activity; its response to the insertion of a probe; the character of the muscle’s individual motor unit action potentials; and the rapidity with which additional motor units are recruited in response to an electrical signal. Muscle inflammation, atrophy, necrosis, denervation, or neuromuscular disease can alter these components, giving rise to patterns that may help illuminate the underlying pathology. Although the procedure can cause minor discomfort, most patients tolerate it well ¹⁸.

Muscle Biopsy

If the diagnosis is still inconclusive after the history, physical examination, and laboratory, radiologic, and electromyographic evaluations, a muscle biopsy is required for patients who have a suspected myopathy ²⁰. The technology of this method, especially regarding the use of genetic markers, is advancing rapidly, making a definitive diagnosis possible for a wider range of myopathies ²¹.

The biopsy site should be an affected muscle that is not diseased to the point of necrosis. Common biopsy sites are the vastus lateralis of the quadriceps for proximal myopathies and the gastrocnemius for distal myopathies; in patients without involvement of these muscles, an affected group is chosen ¹¹. The muscle biopsy can be accomplished as an outpatient procedure and carries the attendant risks of pain, bleeding, infection, and sensory loss. As with electromyography, patients should avoid using anticoagulants before the procedure, and the site chosen for biopsy should be free of overlying infection.

The pathologic analysis of biopsy specimens focuses on the histologic, histochemical, electron microscopic, genetic, and biochemical changes that are found in the affected muscle. Histology may show atrophic, degenerating, and regenerating muscle fibers (general findings referred to as myopathic changes), or it may show more specific findings such as accumulations of glycogen (glycogen storage diseases), ragged red fibers (mitochondrial myopathies), noncaseating granulomas (sarcoidosis), and amyloid deposits (amyloidosis). Histochemical techniques assay for specific enzymes and proteins, and may reveal deficiencies as in disorders of carbohydrate or fatty acid metabolism or the muscular dystrophies. Electron microscopy and biochemical assays may help to uncover subtle changes not detectable by other techniques, further aiding in the diagnosis of metabolic and protein-deficiency myopathies ¹⁴.

Muscle weakness treatment

Muscle weakness treatment involves treating the underlying cause of the muscle weakness.

1. Evaluation of the Patient with Muscle Weakness. Am Fam Physician. 2005 Apr 1;71(7):1327-1336. https://www.aafp.org/afp/2005/0401/p1327.html
2. Hinshaw DB, Carnahan JM, Johnson DL. Depression, anxiety, and asthenia in advanced illness. J Am Coll Surg. 2002;195:271–7.
3. Griggs RC. Episodic muscle spasms, cramps, and weakness. In: Harrison TR, Fauci AS, eds. Harrison’s Principles of internal medicine. 14th ed. New York: McGraw-Hill, 1998:118–22.
4. Kumar A, Clark S, Boudreaux ED, Camargo CA Jr. A multicenter study of depression among emergency department patients. Acad Emerg Med. 2004;11:1284–9.
5. Muscle weakness. In: Ferri FF, ed. Ferri’s Clinical advisor: instant diagnosis and treatment. St. Louis: Mosby, 2003:1436.
6. Roos, KL. Viral infections. In: Goetz CG, ed. Textbook of clinical neurology. 2d ed. Philadelphia: Saunders, 2003:895–918.
7. Yew KS, DeMieri PJ. Disorders of bone mineral metabolism. Clin Fam Pract. 2002;4:525–65.
8. Yazici Y, Kagen LJ. Clinical presentation of the idiopathic inflammatory myopathies. Rheum Dis Clin North Am. 2002;28:823–32.
9. Brasington RD Jr, Kahl LE, Ranganathan P, Latinis KM, Velazquez C, Atkinson JP. Immunologic rheumatic disorders. J Allergy Clin Immunol. 2003;111(2 suppl):S593–601.
10. Riggs JE. Neurologic manifestations of electrolyte disturbances. Neurol Clin. 2002;20:227–39.
11. Wortmann RL, DiMauro S. Differentiating idiopathic inflammatory myopathies from metabolic myopathies. Rheum Dis Clin North Am. 2002;28:759–78.
12. Holbrook JH. Weakness and Fatigue. In: Walker HK, Hall WD, Hurst JW, editors. Clinical Methods: The History, Physical, and Laboratory Examinations. 3rd edition. Boston: Butterworths; 1990. Chapter 213. Available from: https://www.ncbi.nlm.nih.gov/books/NBK326
13. Vincent A, Palace J, Hilton-Jones D. Myasthenia gravis. Lancet. 2001;357:2122–8.
14. Preedy VR, Adachi J, Ueno Y, Ahmed S, Mantle D, Mullatti N, et al. Alcoholic skeletal muscle myopathy: definitions, features, contribution of neuropathy, impact and diagnosis. Eur J Neurol. 2001;8:677–87.
15. Bradley WG, Taylor R, Rice DR, Hausmanowa-Petruzewicz I, Adelman LS, Jenkison M, et al. . Progressive myopathy in hyperkalemic periodic paralysis. Arch Neurol. 1990;47:1013–7.
16. Alshekhlee A, Kaminski HJ, Ruff RL. Neuromuscular manifestations of endocrine disorders. Neurol Clin. 2002;20:35–58.
17. Naqvi U, Sherman Al. Muscle Strength Grading. [Updated 2018 Oct 27]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2018 Jan-. Available from: https://www.ncbi.nlm.nih.gov/books/NBK436008
18. Lacomis D. Electrodiagnostic approach to the patient with suspected myopathy. Neurol Clin. 2002;20:587–603.
19. Targoff IN. Laboratory testing in the diagnosis and management of idiopathic inflammatory myopathies. Rheum Dis Clin North Am. 2002;28:859–90.
20. Nirmalananthan N, Holton JL, Hanna MG. Is it really myositis? A consideration of the differential diagnosis. Curr Opin Rheumatol. 2004;16:684–91.
21. Wagner KR. Genetic diseases of muscle. Neurol Clin. 2002;20:645–78.