Editing Approach to the patient with muscle weakness

===Introduction===
*There are three steps to examining the patient with complaints of "weakness".
**Distinguish between true muscle weakness and either asthenia and a motor impairment that isn't due to lack of muscle power.
***neurocirculatory asthenia. an obsolete term for a type of anxiety neurosis formerly encountered often among military personnel during times of war, in which cardiorespiratory symptoms, such as palpitation, rapid pulse, and precordial pain, were prominent. (statref)
**Identify the areas of the neuromuscular system that are affected.
**Determine the cause of the lesion.

===RESPIRATORY MUSCLE WEAKNESS===
*Muscle weakness can be secondary to respiratory issues.
*One can test for respiratory insufficiency which is usually indicated by tachypnea (rapid breathing).
*Respiratory muscles may be the cause of ventilation failure.
**Respiratory volume; normally over 15 mL / kg
**Maximum inspiratory force; normally over 20 cmH<sub>2</sub>O
*Oropharyngeal muscles may also cause respiratory issues because of aspiration of fluid.

====Triage====
*When deciding whether or not a patient with complaint of respiratory muscle weakness needs to be admitted to the ICU one looks for the occurrance of any one of the following characteristics as this may indicate that the patient will need mechanical ventilation:
**Vital capacity <20 mL/kg
**Maximum inspiratory pressure <30 cmH2O
**Maximum expiratory pressure <40 cmH2O
**Rapid progression (<7 days) of weakness
**Inability to raise the head against gravity
**Bulbar dysfunction (eg, dysphagia, dysphonia, aspiration)
**Bilateral facial weakness
**Significant autonomic dysfunction (eg, orthostatic hypotension)

===DISTINGUISHING TRUE MUSCLE WEAKNESS FROM ASTHENIA===
*Most patients will not express weakness when objectively tested for strength.
*Using a careful history, one can usually distinguish weakness due to non-neuromuscular problems (asthenia) and true muscle weakness.
**"careful questioning will reveal that the patient is limited by shortness of breath, chest pain, joint pain, fatigue, poor exercise tolerance, paresthesias, or spasticity rather than a true decrease in muscle power."
**Often patients with asthenia (as opposed to true muscle weakness) have chronic medical conditions.
*Pts with true muscle weakness usually describe specific inabilities like climbing stairs and rarely have pain.  This is in direct contrast to the patient with asthenia who will probably present their problem as general weakness as well as some pain.


*The physical exam can give further insight into the cause of reported weakness.
**Muscle weakness can be measured by resistance testing and the following scale:
***Zero — no muscle contraction
***One — flicker or trace of muscle contraction
***Two — Limb or joint movement possible only with gravity eliminated
***Three — Limb or joint movement against gravity only
***Four — power decreased but limb or joint movement possible against resistance
***Five — normal power against resistance
**During the physical exam, one should remember that:
***Cachexia can be in advance stages before muscle weakness occurs.
***Muscle tenderness rarely indicates a muscle weakness; exceptions include
****infectious myopathies such as trichinellosis and viral myositis, 
****certain drug-induced myopathies, 
****thyroid myopathy, 
****and the inherited metabolic myopathies.

===Localizing the site of the lesion===
*Lesions can occur anywhere along the neuromuscular arc:
**motor cortex,
**corticospinal tracts, 
**anterior (ventral) horn cells, 
**spinal nerve roots, 
**peripheral nerves, 
**neuromuscular junction, 
**and muscle.
*The distribution of the weakness can also be used to determine if the lesion is before sided-splits or not and how early in the arc it occurs.
*"Lesions of the central and peripheral nervous systems should be identifiable from a detailed neurologic examination."
*One can confirm the findings of a physical and neurological exam with an electromyogram (EMG).


====Distribution of weakness as guide to localizing the lesion====
*Generalized muscle weakness (that is, global weakening of the body's muscles) can occur in several situations:
**myasthenia gravis, 
**long-standing periodic paralysis, 
**advanced disuse atrophy from prolonged bed rest, 
**muscle wasting from malignancy, or 
**longstanding motor neuron disease.


*Otherwise we can characterize the weakness as symmetric or asymmetric.
**Asymmetric distributions are most likely lesions of the central or peripheral nervous systems.
***Among these areas, each location for potential lesion shows a distinct weakness distribution pattern (motor cortex, spinal cord, spinal nerve root, and peripheral nerve).


*Symmetric distributions should be further divided into distal or proximal distributions.
**Distal symmetric weakness is characteristic for motor neuron disorders or peripheral neuropathies.
***Signs include: "decreased grip strength, weakness of wrist flexion or extension, decreased plantar flexion strength, and foot drop. These patients have difficulty walking on their heels or toes. Foot drop can be detected by opposing the patient's attempt to dorsiflex the ankle."
**Proximial symmetric weakness is characteristic of various myopathies, certain muscular dystrophies, and myasthenia gravis.
***Signs include: 
****Proximal weakness involves the axial muscle groups, deltoids, and hip flexors, 
****Difficulty flexing or extending the neck against resistance (observe the patient sitting up from the supine position, the head will lag behind), 
****Deltoid muscle strength can be assessed by pressing down on the patient's fully abducted arms with the elbows flexed; the examiner should not be able to overcome the patient's resistance if strength is normal.
****The patient with quadriceps weakness: unable to rise from a seated position without the use of the upper extremities; unable to perform a deep knee bend; may suddenly drop into the chair when trying to sit down slowly; may rise from sitting on the floor by "climbing up their legs with their hands" (Gower's sign, characteristic of, but not specific for, Duchenne muscular dystrophy)


*There can also be very specific distributions that indicate very specific neuropathies or muscular dystrophies.
**Examples: facioscapulohumeral dystrophy, scapuloperoneal dystrophy, and scapulohumeral dystrophy.

===Determining the cause of the lesion===
*Once you have found the site of the lesion (based on the distribution), it can be categorized as (TIMING):
**Toxic
**Immunological
**Metabolic
**Infectious
**Neoplastic
**Genetic

====Sites of lesions====

=====Lesions of the upper motor neurons=====
*Causes for disruption of upper motor neuron function include: acute stroke syndromes, space-occupying lesions of the CNS, and lesions of the spinal cord.
**Lesions of the spinal cord may be secondary to trauma, infection, vascular irregularities, tumors, congenital leukodystropies, skeletal impingements, or demyelinating diseases.
*Image studies, as well as CSF examination, are appropriate methods to identify CNS lesions.
**MRI, CT, radiographs, or radionucleotide bone scanning are options depending on the suspected site.

=====Anterior horn cell lesions=====
*This may also be called "lower motor neuron" lesions.
*There are four major reasons for weakness-causing lesions of the anterior horn cells:
**Poliomyelitis (still a problem for unimmunized populations)
**Lead poisoning
**Familial spinal atrophy
**Motor neuron disease
*Other causes of lower motor neuron lesions may include other viral infections including West Nile virus.
*The examination of CSF and a thorough history including time course of the infection, exposure risks, and family history can differentiate between these causes of weakness.

=====Lesions of the peripheral nervous system=====
*Sequela: "A sequela, is a pathological condition resulting from a disease, injury, or other trauma" per wikipedia.
*In peripheral nerve muscle weakness, the first thought should be consideration of diabetes when symmetric polyneuropathy is present as this is a common '''sequela''' of diabetes mellitus.
*Diabetes mellitus and other vasculitis disorders can also cause '''mononeuropathy multiplex''' which is an ''asymmetric'' weakening of muscles innervated by ''multiple'' nerves.
*Simple mononeuropathies may result from nerve compression (think carpal tunnel syndrome).

=====Lesions of the nueromuscular jxn=====
*Disorders affecting the neuromuscular joint can be manifested from antibodies to the ach receptor (as in myasthenia gravis), inhibition of ach esterase by organophosphate poisoning, or dysfunction of pre-synaptic Ca channels in Lamber-Easton syndrome (also autoimmune).

=====Myopathy=====
*There are several major categories of myopathies:
**inflammatory disorders,
**endocrinopathies,
**metabolic disorders of the muscle,
**drugs / toxins,
**infections,
**causes of rhabdomyelitis.
*Guidelines for myopathy diagnosis include:
**Muscular dystrophies are usually suspected based on age of onset and gender of the patient.
**History of exertion-related pigmenturia is usually associated with myogenic metabolic disorders.
**Medications or drug abuse are a hint toward drug-induced myopathy.
**Evidence of auto-immune syndromes like rheumatic diseases, systemic lupus erythromatous may indicate a myositis.
**Endocrinopathies may be indicated by thyroid dysfunction or cushing's disease.

====Clinical investigations====
*Urinalysis:
**Enzymes specific to muscle tissue found in the plasma usually indicates some muscle disease.
***It can also be caused by trauma, intramuscular injections, motor neuron disease, or even strenuous exercise.
**A positive test for blood in the urine without actual RBCs in the sediment is suggestive of myoglobinuria.
*Serology
**Serological tests should be run if inflammatory, immune, or connective tissue diseases are suspected.
**Results should include:
***antinuclear antibodies, 
***antibodies against extractable nuclear antigens (anti-Ro/SSA, anti-La/SSB, anti-Sm, and anti-RNP), and 
***"myositis specific" antigens (eg, anti-histidyl-t-RNA synthase [anti-Jo-1])
**"Anti-neutrophil cytoplasmic antibody (ANCA) titers, hepatitis B and C serologies, and cryoglobulins should be obtained in patients with suspected vasculitis."
*Electrophysiologic studies:
**EMG is used when the suspected site of lesion is in the peripheral nerve, the neuromuscular jxn, or the muscle itself.
**Also, EMG may be useful in determining where to biopsy the tissue.
*MRI
**Can be useful in determining which muscle to biopsy.
***Note that it identifies the muscle contralateral to the muscle that is affected.
**Is better than EMG because MRI can identify the actual affected muscle as opposed to the ''contralateral'' muscle as is identified in EMGs.
*Muscle biopsy
**Light microscope examination of muscle tissue can identify several "itises":
***dermomyositis, vasculitis, polymyositis, inclusion body myositis, and certain drug-induced myositises.
**EM microscopy can be useful for confirming inclusion body myositis.
**Some special stains can indicate protein deficiencies and metabolic enzyme deficiencies.
*Genetic testing
**Genetic tests are useful for confirmging muscular dystrophies and heritable myopathies.

===Summary===
*"A patient who presents with a complaint of muscle weakness is appropriately assessed for respiratory muscle weakness. If ventilatory compromise is suspected (eg, due to the presence of tachypnea) then testing of vital capacity and of maximal inspiratory and expiratory pressures is recommended (see 'Respiratory muscle weakness' above."
*"The medical history and physical examination generally permit the distinction between whose weakness is the result of a non-neuromuscular disorder (eg, those who are easily fatigued due to cardiac or pulmonary disease, limited by joint pain or stiffness, etc) from those with weakness that is due to reduced muscle strength (see 'Distinguishing true muscle weakness from asthenia' above."
*"If formal muscle testing (see 'Physical examination' above) confirms the presence of muscle weakness, a neurologic examination is performed to localize the site of the lesion (ie, to the central nervous system, peripheral nervous system, neuromuscular junction, or muscle). The distribution of muscle weakness (ie, generalized, distal, proximal, or localized) may help to narrow the number of possible causes (see 'Distribution of weakness as a guide to localizing the lesion' above."
*"Laboratory tests that may be useful in the evaluation of weakness include: serum electrolytes, calcium, magnesium, and phosphate; creatine kinase, aldolase, lactate dehydrogenase, serum aminotransferases, and thyroid stimulating hormone. If there are clinical features that suggest a systemic rheumatic or collagen disease then serologic studies are warranted, including: antinuclear antibodies (ANA). A positive urine test for blood in the absence of red cells in the sediment suggests myoglobinuria. (See 'Laboratory studies' above.)"
*"Electrophysiologic nerve and muscle testing (ie, measurement of nerve conduction velocity, sensory action potentials, and electromyography) may be of value in localizing the site of peripheral neuromuscular disorders (see 'Electrophysiologic studies' above."
*"If the evaluation suggests that myopathy is responsible for weakness, and no drug, toxin, metabolic, or endocrine disorder can be identified as the cause, then we recommend a muscle biopsy as the next step in attempting to arrive at a specific diagnosis (see 'Muscle biopsy' above."