Muscle weakness

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Muscle weakness
Muscle wasting in HIV. Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

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List of terms related to Muscle weakness

Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-In-Chief: M.Umer Tariq [2]

Overview

Muscle weakness (or "lack of strength") is a direct term for the inability to exert force with ones muscles to the degree that would be expected given the individual's general physical fitness. A test of strength is often used during a diagnosis of a muscular disorder before the etiology can be identified. Such etiology depends on the type of muscle weakness, which can be true or perceived as well as variable topically. True weakness is substantial, while perceived rather is a sensation of having to put more effort to do the same task. On the other hand, various topic locations for muscle weakness are central, neural and peripheral. Central muscle weakness is an overall exhaustion of the whole body, while peripheral weakness is an exhaustion of individual muscles. Neural weakness are somewhere between.

Muscle weakness can be a result of vigorous exercise but abnormal fatigue may be caused by barriers to or interference with the different stages of muscle contraction.

In a broader sense, muscle weakness is the physical part of fatigue (medical).

Complete Differential Diagnosis of Causes of Muscle weakness

(In alphabetical order)

3-Methylglutaconic aciduria 3-Quinuclidinyl benzilate Acamprosate Accessory nerve disorder Acitretin Acute intermittent porphyria Acute peripheral neuropathy Acute viral nasopharyngitis (common cold) Addison's disease Adrenal carcinoma Alcoholic polyneuropathy Aluminum Hydroxide Amiloride and Hydrochlorothiazide Amiodarone Oral Amyotrophic lateral sclerosis Anorexia nervosa Arnold-Chiari malformation Arthrogryposis Autism Bassen-Kornzweig syndrome Becker's muscular dystrophy Beclomethasone Oral Inhalation Benztropine Mesylate Oral Bezafibrate Botulism Brachial plexus injury Brompheniramine Budesonide Inhalation Powder Bulimia nervosa Cadmium poisoning Carnitine palmitoyltransferase I deficiency Chloroquine Phosphate Oral Chlorothiazide Chlorpheniramine Chlorthalidone Chronic fatigue syndrome Chronic inflammatory demyelinating polyneuropathy Ciclesonide Nasal Spray Cirrhosis Clofibrate Colistimethate Injection Congenital muscular dystrophy Congenital myasthenic syndrome Congenital myopathy Connective tissue disease Cushing's syndrome Cyanocobalamin Injection Cyproheptadine Cytarabine Daptomycin Decompression sickness Dejerine Sottas syndrome Dermatomyositis Desipramine Devic's disease Dexamethasone Oral Dextroamphetamine and Amphetamine Diabetic amyotrophy Diabetic neuropathy Dicamba Dicyclomine Diphenhydramine Oral Donepezil Dorzolamide and Timolol Ophthalmic Doxazosin Doxylamine Duchenne muscular dystrophy Emery-Dreifuss Muscular Dystrophy Engelmann syndrome Epidural hematoma Exercise intolerance Ezetimibe Facioscapulohumeral muscular dystrophy Fexofenadine and Pseudoephedrine Fludrocortisone Acetate Flunisolide Nasal Inhalation Fluoride poisoning Fluticasone and Salmeterol Oral Inhalation Fluvastatin Frailty syndrome Friedreich's ataxia Galantamine Gemeprost Glucocorticoids Glutaric aciduria type 1 Glycogen storage disease type II GM1 gangliosidoses Graves' Disease Group A streptococcal infection Guanidinoacetate methyltransferase deficiency Guillain-Barre syndrome Hereditary inclusion body myopathy Hereditary spastic paraplegia Herpes zoster Hexane-2,5-dione HIV Hopkins syndrome Hydrochlorothiazide Hydrocortisone Injection Hydrocortisone Oral Hydroxychloroquine Hydroxyzine Hyperaldosteronism Hypercalcemia Hyperkalaemic periodic paralysis

Hyperkalemia Hypermagnesemia Hypermethioninemia Hyperpituitarism Hyperthyroidism Hypoglycemia Hypokalemic periodic paralysis Hypomagnesemia Hypophosphatemia Hypothyroidism Imiquimod Inclusion body myositis Influenza Interferon Beta-1b Injection Juvenile dermatomyositis Juvenile primary lateral sclerosis Kennedy disease Krabbe disease Lambert-Eaton myasthenic syndrome Leflunomide Letrozole Levalbuterol Oral Inhalation Limb-girdle muscular dystrophy Lisinopril and Hydrochlorothiazide Lithium Loprazolam Lormetazepam Lovastatin Low-carbohydrate diet Machado-Joseph disease Marinesco-Sjogren syndrome Mepyramine Metabolic acidosis Metachromatic leukodystrophy Methyclothiazide Methyldopa and Hydrochlorothiazide Methylprednisolone Oral Metolazone Mitochondrial trifunctional protein deficiency Motor neurone disease Multiple sclerosis Myasthenia gravis Nelson's syndrome Nemaline myopathy Nitrazepam Nitrofurantoin Oxcarbazepine Peripheral Arterial Disease Peripheral neuropathy Phosphofructokinase deficiency Poliomyelitis Polymyositis Postherpetic neuralgia Post-polio syndrome Pott's disease Pramipexole Pravastatin Prazosin and polythiazide Prednisone Primary carnitine deficiency Primary hyperparathyroidism Primary lateral sclerosis Procyclidine Pseudoephedrine and triprolidine Pyridostigmine Pyruvate carboxylase deficiency Reserpine, hydralazine, and hydrochlorothiazide Rhabdomyolysis Rhabdomyolysis Rheumatoid Arthritis Rhinovirus Riluzole Rosuvastatin Salmeterol oral inhalation Sandhoff disease Schilder's disease Scleroderma Selegiline Sjogren's Syndrome Small fiber peripheral neuropathy Somatization disorder Spinal cord injury Spinal disc herniation Spinal stenosis Spironolactone Spondylosis Sturge-Weber syndrome Tabes dorsalis Tamoxifen Telbivudine Temik Tension myositis syndrome Teriparatide (rDNA origin) Injection Thyrotoxicosis Tocopherol Topiramate Trastuzumab Triamcinolone Nasal Inhalation Triamterene Trimeprazine Uremia Variegate porphyria Vitamin D deficiency Walker-Warburg syndrome Zoledronic Acid Injection

Complete Differential Diagnosis of the Causes of Muscle weakness

(By organ system)

Cardiovascular	Peripheral Arterial Disease,
Chemical / poisoning	Cadmium poisoning, Dicamba, Fluoride poisoning, Hexane-2,5-dione, Temik,
Dermatologic	No underlying causes
Drug Side Effect	3-Quinuclidinyl benzilate, Acamprosate (patient information), Acitretin (patient information), Aluminum Hydroxide (patient information), Amiloride and Hydrochlorothiazide (patient information), Amiodarone Oral (patient information), Beclomethasone Oral Inhalation (patient information), Benztropine Mesylate Oral (patient information), Bezafibrate (patient information), Brompheniramine (patient information), Budesonide Inhalation Powder (patient information), Chloroquine Phosphate Oral (patient information), Chlorothiazide (patient information), Chlorpheniramine (patient information), Chlorthalidone (patient information), Ciclesonide Nasal Spray (patient information), Clofibrate (patient information), Colistimethate Injection (patient information), Cyanocobalamin Injection (patient information), Cyproheptadine (patient information), Cytarabine (patient information), Daptomycin, Desipramine (patient information), Dexamethasone Oral (patient information), Dextroamphetamine and Amphetamine (patient information), Dicyclomine (patient information), Diphenhydramine Oral (patient information), Donepezil (patient information), Dorzolamide and Timolol Ophthalmic (patient information), Doxazosin (patient information), Doxylamine (patient information), Ezetimibe (patient information), Fexofenadine and Pseudoephedrine (patient information), Fludrocortisone Acetate (patient information), Flunisolide Nasal Inhalation (patient information), Fluticasone and Salmeterol Oral Inhalation (patient information), Fluvastatin (patient information), Galantamine (patient information), Gemeprost, Glucocorticoids, Hydrochlorothiazide (patient information), Hydrocortisone Injection (patient information), Hydrocortisone Oral (patient information), Hydroxychloroquine (patient information), Hydroxyzine (patient information), Imiquimod (patient information), Insulin lispro injection (patient information), Interferon Beta-1b Injection (patient information), Leflunomide (patient information), Letrozole (patient information), Levalbuterol Oral Inhalation (patient information), Lisinopril and Hydrochlorothiazide (patient information), Lithium (patient information), Loprazolam, Lormetazepam, Lovastatin (patient information), Mepyramine, Methyclothiazide (patient information), Methyldopa and Hydrochlorothiazide (patient information), Methylprednisolone Oral (patient information), Metolazone (patient information), Nitrazepam, Nitrofurantoin (patient information), Oxcarbazepine (patient information), Pramipexole (patient information), Pravastatin (patient information), Prazosin and polythiazide (patient information), Prednisone, Procyclidine (patient information), Pseudoephedrine and triprolidine (patient information), Pyridostigmine (patient information), Reserpine, hydralazine, and hydrochlorothiazide (patient information), Riluzole (patient information), Rosuvastatin (patient information), Salmeterol oral inhalation (patient information), Selegiline (patient information), Spironolactone (patient information), Tamoxifen (patient information), Telbivudine (patient information), Teriparatide (rDNA origin) Injection (patient information), Tocopherol, Topiramate, Trastuzumab (patient information), Triamcinolone Nasal Inhalation (patient information), Triamterene (patient information), Trimeprazine (patient information), Zoledronic Acid Injection (patient information),
Ear Nose Throat	Acute viral nasopharyngitis (common cold),
Endocrine	Addison's disease, Cushing's syndrome, Graves' Disease, Hyperaldosteronism, Hyperpituitarism, Hyperthyroidism, Hypothyroidism, Kennedy disease, Thyrotoxicosis,
Environmental	No underlying causes
Gastroenterologic	Cirrhosis,
Genetic	Bassen-Kornzweig syndrome, Becker's muscular dystrophy, Carnitine palmitoyltransferase I deficiency, Dejerine Sottas syndrome, Devic's disease, Engelmann syndrome, Glutaric aciduria type 1, Glycogen storage disease type II, GM1 gangliosidoses, Hereditary inclusion body myopathy, Hereditary spastic paraplegia, Metachromatic leukodystrophy, Nemaline myopathy, Phosphofructokinase deficiency, Primary carnitine deficiency, Pyruvate carboxylase deficiency, Sandhoff disease, Walker-Warburg syndrome,
Hematologic	Acute intermittent porphyria, Variegate porphyria,
Iatrogenic	No underlying causes
Infectious Disease	Botulism, Group A streptococcal infection, HIV, Influenza, Polymyositis, Pott's disease, Rhinovirus,
Musculoskeletal / Ortho	Arthrogryposis, Congenital muscular dystrophy, Congenital myasthenic syndrome, Congenital myopathy, Dermatomyositis, Diabetic amyotrophy, Duchenne muscular dystrophy, Emery-Dreifuss Muscular Dystrophy, Facioscapulohumeral muscular dystrophy, Inclusion body myositis, Rhabdomyolysis, Spondylosis,
Neurologic	Accessory nerve disorder, Acute peripheral neuropathy, Amyotrophic lateral sclerosis, Arnold-Chiari malformation, Chronic inflammatory demyelinating polyneuropathy, Diabetic neuropathy, Epidural hematoma, Friedreich's ataxia, Guillain-Barre syndrome, Juvenile primary lateral sclerosis, Machado-Joseph disease, Marinesco-Sjogren syndrome, Motor neurone disease, Multiple sclerosis, Myasthenia gravis, Peripheral neuropathy, Sturge-Weber syndrome, Tabes dorsalis,
Nutritional / Metabolic	3-Methylglutaconic aciduria, Guanidinoacetate methyltransferase deficiency, Metabolic acidosis, Vitamin D deficiency,
Obstetric/Gynecologic	No underlying causes
Oncologic	Adrenal carcinoma,
Opthalmologic	No underlying causes
Overdose / Toxicity	Benztropine Mesylate Oral (patient information), Fexofenadine and Pseudoephedrine (patient information), Galantamine (patient information), Salmeterol oral inhalation (patient information), Topiramate,
Psychiatric	Anorexia nervosa, Bulimia nervosa, Tension myositis syndrome,
Pulmonary	Hopkins syndrome,
Renal / Electrolyte	Hypercalcemia, Hyperkalaemic periodic paralysis, Hypermagnesemia, Hypermethioninemia, Hypokalemic periodic paralysis, Hypomagnesemia, Hypophosphatemia, Uremia,
Rheum / Immune / Allergy	Congenital myasthenic syndrome, Graves' Disease, Krabbe disease, Lambert-Eaton myasthenic syndrome, Rheumatoid Arthritis, Scleroderma, Sjogren's Syndrome,
Sexual	No underlying causes
Trauma	Brachial plexus injury,
Urologic	No underlying causes
Miscellaneous	Alcoholic polyneuropathy, Chronic fatigue syndrome, Mitochondrial trifunctional protein deficiency, Spinal cord injury, Spinal disc herniation, Spinal stenosis,

True vs. perceived

The term subsumes two other more specific terms, true weakness and perceived weakness.

• True weakness (or "objective weakness") describes a condition where the instantaneous force exerted by the muscles is less than would be expected. For instance, if a patient suffers from amyotrophic lateral sclerosis (ALS), motor neurons are damaged and can no longer stimulate the muscles to exert normal force.

• Perceived weakness (or "subjective weakness") describes a condition where it seems to the patient that more effort than normal is required to exert a given amount of force. For instance, in some people with chronic fatigue syndrome (CFS) who may struggle to climb a set of stairs when feeling especially fatigued, their muscle strength when objectively measured (eg, the maximum weight they can press with their legs) is essentially normal, though this is not true for CFS patients who may be disabled through post-exertional weakness/malaise etc. and in severe cases may not be able to climb a flight of stairs.

In some conditions, such as myasthenia gravis muscle strength is normal when resting, but true weakness occurs after the muscle has been subjected to exercise. This is also true for some cases of CFS, where objective post-exertion muscle weakness with delayed recovery time has been measured and is a feature of some of the published definitions. .

Topically

In addition to true/perceived, muscle weaknes can also be central, neural and peripheral. Central muscle weakness manifests as an overall, bodily or systemic, sense of energy deprivation, and peripheral weakness manifests as a local, muscle-specific incapacity to do work. . Neural weakness can be both central and peripheral.

Central

The central component to muscle fatigue is generally described in terms of a reduction in the neural drive or nerve-based motor command to working muscles that results in a decline in the force output. It has been suggested that the reduced neural drive during exercise may be a protective mechanism to prevent organ failure if the work was continued at the same intensity. The exact mechanisms of central fatigue are unknown although there has been a great deal of interest in the role of serotonergic pathways.

Neural

Nerves are responsible for controlling the contraction of muscles, determining the number, sequence and force of muscular contraction. Most movements require a force far below what a muscle could in potential generate, and barring pathology nervous fatigue is seldom an issue. For extremely powerful contractions that are close to the upper limit of a muscle's ability to generate force, nervous fatigue can be a limiting factor in untrained individuals. In novice strength trainers, the muscle's ability to generate force is most strongly limited by nerve’s ability to sustain a high-frequency signal. After a period of maximum contraction, the nerve’s signal reduces in frequency and the force generated by the contraction diminishes. There is no sensation of pain or discomfort, the muscle appears to simply ‘stop listening’ and gradually cease to move, often going backwards. As there is insufficient stress on the muscles and tendons, there will often be no delayed onset muscle soreness following the workout. Part of the process of strength training is increasing the nerve's ability to generate sustained, high frequency signals which allow a muscle to contract with their greatest force. It is this neural training that causes several weeks worth of rapid gains in strength, which level off once the nerve is generating maximum contractions and the muscle reaches its physiological limit. Past this point, training effects increase muscular strength through myofibrilar or sarcoplasmic hypertrophy and metabolic fatigue becomes the factor limiting contractile force.

Peripheral

Peripheral muscle fatigue during physical work is considered an inability for the body to supply sufficient energy or other metabolites to the contracting muscles to meet the increased energy demand. This is the most common case of physical fatigue--affecting a national average of 72% of adults in the work force in 2002. This causes contractile dysfunction that is manifested in the eventual reduction or lack of ability of a single muscle or local group of muscles to do work. The insufficiency of energy, i.e. sub-optimal aerobic metabolism, generally results in the accumulation of lactic acid and other acidic anaerobic metabolic by-products in the muscle, causing the stereotypical burning sensation of local muscle fatigue.

The fundamental difference between the peripheral and central theories of muscle fatigue is that the peripheral model of muscle fatigue assumes failure at one or more sites in the chain that initiates muscle contraction. Peripheral regulation is therefore dependent on the localised metabolic chemical conditions of the local muscle affected, whereas the central model of muscle fatigue is an integrated mechanism that works to preserve the integrity of the system by initiating muscle fatigue through muscle derecruitment, based on collective feedback from the periphery, before cellular or organ failure occurs. Therefore the feedback that is read by this central regulator could include chemical and mechanical as well as cognitive cues. The significance of each of these factors will depend on the nature of the fatigue-inducing work that is being performed.

Though not universally used, ‘metabolic fatigue’ is a common alternative term for peripheral muscle weakness, because of the reduction in contractile force due to the direct or indirect effects of the reduction of substrates or accumulation of metabolites within the muscle fiber. This can occur through a simple lack of energy to fuel contraction, or interference with the ability of Ca²⁺ to stimulate actin and myosin to contract.

Substrates

Substrates within the muscle generally serve to power muscular contractions. They include molecules such as adenosine triphosphate (ATP), glycogen and creatine phosphate. ATP binds to the myosin head and causes the ‘ratchetting’ that results in contraction according to the sliding filament model. Creatine phosphate stores energy so ATP can be rapidly regenerated within the muscle cells from adenosine diphosphate (ADP) and inorganic phosphate ions, allowing for sustained powerful contractions that last between 5-7 seconds. Glycogen is the intramuscular storage form of glucose, used to generate energy quickly once intramuscular creatine stores are exhausted, producing lactic acid as a metabolic byproduct.

Substrates produce metabolic fatigue by being depleted during exercise, resulting in a lack of intracellular energy sources to fuel contractions. In essence, the muscle stops contracting because it lacks the energy to do so.

Metabolites

Metabolites are the substances (generally waste products) produced as a result of muscular contraction. They include ADP, Mg²⁺, reactive oxygen species and inorganic phosphate. Accumulation of metabolites can directly or indirectly produce metabolic fatigue within muscle fibers through interference with the release of calcium from the sarcoplasmic reticulum or reduction of the sensitivity of contractile molecules actin and myosin to calcium.

Chloride

Intracellular chloride inhibits the contraction of muscles, preventing them from contracting due to "false alarms", small stimuli which may cause them to contract (akin to myoclonus). This natural brake helps muscles respond solely to the conscious control or spinal reflexes but also has the effect of reducing the force of conscious contractions.

Potassium

High concentrations of potassium also causes the muscle cells to decrease in efficiency, causing cramping and fatigue. Potassium builds up in the t-tubule system and around the muscle fiber in general. This has the effect of depolarizing the muscle fiber, preventing the sodium-potassium pump from moving Na⁺ out of the cell. This reduces the amplitude of action potentials, or stops them entirely, resulting in neurological fatigue.

Lactic acid

It was once believed that lactic acid build-up was the cause of muscle fatigue. The assumption was lactic acid had a "pickling" effect on muscles, inhibiting their ability to contract. The impact of lactic acid on performance is now uncertain, it may assist or hinder muscle fatigue.

Produced as a by-product of fermentation, lactic acid can increase intracellular acidity of muscles. This can lower the sensitivity of contractile apparatus to Ca²⁺ but also has the effect of increasing cytoplasmic Ca²⁺ concentration through an inhibition of the chemical pump that actively transports calcium out of the cell. This counters inhibiting effects of K⁺ on muscular action potentials. Lactic acid also has a negating effect on the chloride ions in the muscles, reducing their inhibition of contraction and leaving potassium ions as the only restricting influence on muscle contractions, though the effects of potassium are much less than if there were no lactic acid to remove the chloride ions. Ultimately, it is uncertain if lactic acid reduces fatigue through increased intracellular calcium or increases fatigue through reduced sensitivity of contractile proteins to Ca²⁺.

Associated conditions

Muscle weakness may be due to problems with the nerve supply, neuromuscular disease such as myasthenia gravis) or problems with muscle itself. The latter category includes polymyositis and other muscle disorders

• Amyotrophic lateral sclerosis
• Botulism
• Centronuclear myopathy
• Myotubular myopathy
• Dysautonomia
• Charcot-Marie-Tooth disease
• Hypokalemia
• Motor neurone disease
• Muscular dystrophy
• Myasthenia Gravis
• Progressive muscular atrophy
• Spinal muscular atrophy
• Cerebral palsy
• Infectious mononucleosis
• Herpes Zoster
• Vitamin D deficiency
• Fibromyalgia
• Celiac Disease
• Hypercortisolism (Cushing's syndrome)
• Hypocortisolism (Addison's disease)
• Primary hyperaldosteronism (Conn's syndrome)
• Ehlers-Danlos syndrome

See also

• Asthenia
• Paresis
• Debility
• Malaise
• Cataplexy
• Hypotonia
• Muscle atrophy
• Mononucleosis
• Dystrophy

Diagnostic Findings

Image courtesy of Professor Peter Anderson DVM PhD and published with permission © PEIR, University of Alabama at Birmingham, Department of Pathology

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  Spinal cord ependymoma

References

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