Chapter 21: Neuromuscular Disroders

Chapter 21: Neuromuscular disroders
https://www.dartmouth.edu/~dons/part_3/chapter_21.html
DISORDERS OF THE NERVOUS SYSTEM - REEVES & SWENSON

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Anatomical neuromuscular units
The nervous system can be considered a reflex arc designed for
Functional neuromuscular units
analyzing the environment through sensation and then
Nerve anatomy and action
modifying the environment through movement. The
potentials
neuromuscular component of the nervous system is made up of
Diseases
the first and the last components of this reflex. It consists of the
Motor neuron disease
first sensory element and the last motor element. Table 21-1 lists
Peripheral neuropathy
the parts of this peripheral apparatus.

The neuromuscular system has a relatively simple design
Mononeuropathy
Radiculopathy
and physiology. Therefore,the clinical expression of symptoms
Polyneuropathy
following damage are rather straightforward, consisting of loss of
Mononeuritis multiplex
these normal functions. From the type and the distribution of
Neuromuscular junction
symptoms, it is possible to achieve a diagnosis and to do the
disorders
following:
Myastheinia gravis
1. Confirm that such manifestations arise in the

peripheral nervous system (either sensory or motor
components) rather than in the CNS.
2. Determine which part of the system is affected. For
example, is the weakness caused by damage to a nerve
fiber, neuromuscular junction (NMJ), or muscle
fibers.
3. In the case of nerve fiber disease, it is possible to
determine the level of the lesion along the nerves or
roots.
Myasthenic syndrome
Muscle diseases (myopathy)
Muscular Dystrophy
Duchenne Dystrophy
Limb Girdle Dystrophy
Facioscapulohumeral
Dustrophy
Myotonic Dystrophy
References
Questions
4. In disease of the peripheral nerves, the type of injury

either to myelin or axons can be determined.
The specific neuromuscular diagnosis is made by history, examination and supported by
laboratory studies, neurophysiology and, in selected cases, muscle and nerve biopsies and genetic
testing.
What follows is an integrated picture relating normal and abnormal structure, function and
clinical manifestations.
Anatomy and Physiology of Peripheral Nerve Fibers
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There are several components of the peripheral nervous system. These include sensory and motor
nerve fibers (axons) which pass through nerve roots, plexi and the peripheral nerves themselves.
Sensory nerve fibers (axons) have their origin in receptive elements that may be in the skin,
muscles, joints, bones or even the internal organs. They typically have cell bodies located in the
dorsal root ganglia located close to the spinal cord. Somatic motor nerve fibers (axons) arise from
motor neurons in the ventral horn of the spinal cord. These nerve fibers terminate on muscle
fibers at the neuromuscular junction or on muscle spindles (setting the sensitivity to muscle
stretch). Autonomic motor nerve fibers terminate on glands, organs or smooth muscle fibers. The
autonomic motor nerves are unique since there are typically 2 neurons in a sequence (with the
postganglionic neuron located in a ganglion).
The peripheral nerves not only include the nerve fibers but also several layers of connective
tissue (endoneurium, perineurium and epineurium) and blood vessels.
Nerve fibers have a high metabolic demand and little reserve of energy stores. Therefore,
circulation is critical for moment-to-moment supply of oxygen and metabolic substrates.
Peripheral nerves receive collateral arterial branches from adjacent arteries that anastamose with
other arteries entering the nerve, above and below. There is usually sufficient collateral circulation
to survive damage to one of the feeding arteries.
Individual nerve fibers consist of axons that may be myelinated or unmyelinated. Myelin in
the peripheral nervous system derives from Schwann cells, which adhere to nerve cell membranes
and create multiple layers or wrappings of the membrane. These are fused layers of Schwann cell
membrane, comprising an electrically insulating lipid-rich layer around the nerve fibers. In
between these Schwann cells are the nodes of Ranvier, a short segment of the nerve fiber devoid of
myelin. At these nodes there is a high density of voltage-gated sodium ion channels that facilitate
membrane depolarization. The role of myelin is to increase the velocity of nerve conduction, with
speed being proportional to the distances between adjacent nodes of Ranvier. The usual speed of
large myelinated fibers is 40-70 meters/ second. The function of nerve fibers can, to some extent,
be deduced from the velocity of conduction (see Table 21-2). Most somatic motor axons are large,
heavily myelinated fibers. This is also true of the sensory nerve fibers innervating muscle spindle
(stretch) and Golgi tendon organ (tension) receptors. Intermediate size fibers convey touch and
proprioception and joint position sense. Lightly myelinated fibers convey sharp pain sensation
and autonomic preganglionic motor function. Pathologic processes that primarily affect myelin
tend to affect functions mediated by the most heavily myelinated nerve fibers and would also
profoundly affect the speed of nerve conduction in these nerves.
Unmyelinated nerve fibers conduct very slowly by a continuous mode of propagation of
electrical signal (non-saltatory). These fibers convey aching, burning pain and temperature
sensation and also include the sympathetic, postganglionic motor nerves. Their speed is
approximately 1 meter/second.
Nerves are protected from pressure by connective tissue padding, which also protects them
from traction. Nerve roots are less well protected because there is less connective tissue within the
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nerve root.
In order to accurately diagnose disorders affecting peripheral nerves it is important to recall
the anatomical distribution of sensory fibers in the nerve roots (Figure 9-2) and peripheral nerves
(Figure 9-3). Nerve roots have nearly complete overlap, so there is limited sensory loss (usually
distally, where there is less overlap) with damage to a single nerve root. Peripheral nerve injuries
usually produce more sensory loss. It is important to note that there is significant variability in the
precise borders of the peripheral nerve distribution, although the general pattern is quite
consistent. It is also important to understand the motor innervation of certain major nerve roots
and peripheral nerves (Table 10-5). There may be weakness of shoulder abductors and external
rotators with C5 nerve root lesions, weakness of elbow flexors with C6 nerve root lesions, possible
weakness of wrist and finger extension with C7 nerve root lesions and some weakness of intrinsic
hand muscles with C8 and T1 lesions. In the lower extremity, there may be some weakness of knee
extension with L3 or L4 lesions, some difficulty with great toe (and, to a lesser extent, ankle)
extension with L5 lesions and weakness of great toe plantar flexion with S1 nerve root damage.
It is critical for the survival of nerve fibers that they be able to maintain a stable resting
membrane potential by sustaining ion gradients across the axonal membrane. This requires
normal integrity of the membrane constituents (lipid layers, membrane proteins and ion
channels). It also requires energy, which the neuron uses to create the ion gradients and for
transport, moving constituents from the cell body down the axon, and back to the cell body. All of
this requires high blood flow to the nerve. Diminished blood flow (ischemia) is poorly tolerated by
nerves.
Axonal transport is critical to the function of the peripheral nerve. All protein constituents of
the nerve are synthesized in the neuronal cell body. Microtubules within the axon perform the
transport function and may extend over distances that can exceed a meter in the longest nerve
fibers. Therefore, all structural proteins as well as enzymes that function in the nerve terminal
come from the cell body. Even structural components, such as the mitochondria in the nerve
terminal, are transported down the axon. There is a class of protein compounds (trophic factors)
that travel orthodromically to the periphery or antidromically to the cell body. These factors are
critical to the health of the innerved tissues. Additionally, there are trophic factors released by the
peripheral tissues, taken up by nerve terminals and transported in a retrograde manner back to
the nerve cell bodies. Loss of these trophic factors can result in either the death of neurons or
atrophy of peripheral tissues. This is the reason why a muscle whose innervating axon is sectioned
undergoes atrophy much more quickly and severely than one where the axon is intact, as in
demyelination with conduction block... In both cases, there is complete weakness of the muscle,
yet only in the former case are trophic factors lost.
It is important to note that nerves receive innervation by way of the nervi nervorum. Most of
these nerve fibers are either sensory or motor (from the sympathetic nervous system). The density
of this innervation is not uniform and varies with the particular nerve in question as well as with
the location along the nerve. These fibers may be responsible for some pain associated with nerve
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injury.
Motor Units
The motor unit is a physiologic unit. Normally, contraction of striated muscle is only possible
through firing of motor neurons that are activated either via descending pathways or through
reflex connections.
The muscle fibers in a motor unit respond in an all-or-none fashion to excitation by the motor
neuron (both to natural excitation and artificial stimulation, such as electric nerve stimulation).
The nervous impulse reaches all the muscle fibers in a unit almost at the same time. The result is a
brisk twitch. The electric counterpart of this muscle discharge is a motor unit potential. It can be
recorded with a needle electrode inserted into the muscle. It is the composite of the summated
action potentials of many single muscle fibers. Its amplitude roughly expresses the numbers of
muscle fibers activated. Its duration represents the range of terminal conduction times to those
activated muscle fibers (temporal dispersion). Repeated activation of the same motor unit
produces nearly identical motor unit potentials each time because the times for nerve impulse
arrival and neuromuscular transmission are quite constant for any given nerve branch, and
because all muscle fibers in the motor unit respond every time.
At rest there is normally no motor unit activity. What is the behavior of motor units in effort?
With increasing effort, tension increases by, (1) increasing the firing rates of individual units and
by, (2) recruiting more units into the effort. These are recruited such that, with full effort, the
electrical activity of individual motor units can no longer be recognized.
Irritation of motor neurons or motor axons can result in spontaneous discharge of individual
motor axons and contraction of the motor unit. These can be seen on the skin surface as random,
involuntary twitches that are termed fasciculations. While these are often normal (due to
temporary irritation of motor nerve fibers) persistent fasciculations, especially in a muscle that is
showing weakness or atrophy, indicates damage to the anterior horn cell or its axons.
Muscle fibers that have been denervated for days to weeks become hyperirritable (to the point
where they are spontaneously active). The spontaneous contraction of individual muscle fibers is
termed a fibrillation but it is not visible from the skin surface. Needle electromyography can detect
fibrillations, which are fairly reliable signs of damage to motor nerve fibers, but which may also be
seen in muscles diseases (especially those that damage the distal motor axons).
Conditions that damage some motor units (sparing others) usually result in overall weakness
of the muscle but high firing rates of individual motor units that are still intact. This is because of
the decreased number of motor units which must be activated at maximal frequencies in order to
generate any muscle force. Therefore, weakness with a high firing rate indicates a loss of motor
neurons or motor axons. Of course, voluntary motor activity is also driven by descending motor
tracts of the central nervous system that are collectively referred to as "upper motor neurons."
Damage to these "upper motor neurons" makes it impossible to achieve high firing rates of the
motor units during voluntary contraction. This is similar to the finding of low frequency of firing
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of the individual motor units that would be seen with inadequate effort.
Composition of Nerves and Nerve Action Potentials

Most nerves contain a mixture of myelinated and unmyelinated fibers distributed in three
well-defined sizes of populations: large myelinated fibers, small myelinated fibers, and many small
unmyelinated fibers. Normally, the largest-diameter fibers conduct the fastest, and fibers of
similar diameter conduct at similar velocity. Therefore, following simultaneous stimulation of all
fibers in a nerve, the action potentials of individual nerve fibers summate in time, giving rise to
compound nerve action potentials (NAP). In the clinic, NAP's are recorded routinely, but we can
only record the NAP corresponding to large myelinated fibers.
In the clinic we can also measure nerve conduction velocity (see this discussion of
electrodiagnosis for further explanation).
Disease
The following discussion will consider the four basic types of neuromuscular disorders, i.e.,
damage to the anterior horn cells, damage to the peripheral nerves (including myelin), damage to
muscle (myopathy) and damage to the neuromuscular junction.
Motor Neuron Disease - Amyotrophic Lateral Sclerosis

Motor neuron disease is a general terms for conditions that result in degeneration of the anterior
horn cells (lower motor neurons) and the upper motor neurons of the cerebral cortex that give rise
to descending tracts that control movement. These conditions present with weakness
accompanied by lower motor signs (atrophy, fasciculations and decreased reflexes) or upper
motor neuron signs (spasticity, increased reflexes and upgoing toes). Sensation and cognition are
clinically intact, although we have more recently come to understand that there are subtle signs of
damage to other parts of the nervous system. Most patients have clinical signs of both upper and
lower motor neuron disease and are diagnosed with amyotrophic lateral sclerosis - ALS. Some
show signs that are almost exclusively upper or lower motor neuron in nature and these go by
other names.
In addition to these degenerative motor neuron diseases there are two inherited conditions
(Werdnig-Hoffmann disease in infants and Kugelberg-Welander disease in children and young
adults) that are characterized by anterior horn cell degeneration only, and there are even more
rare inherited forms of amyotrophic lateral sclerosis.
Amyotrophic lateral sclerosis affects mainly adults 40-60 years of age. There is evidence of
degeneration not only of the anterior horn cells of the spinal cord, but also some of the cranial
nerve motor nuclei, especially those controlling the tongue, face, pharynx and soft palate, while
sparing eye movements. Because of additional involvement of corticobulbar and corticospinal
tracts, the weakness is of two types and may express quite differently in the arms and in the legs of
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a single patient. For example, the arms may show more lower motor neuron signs (atrophy and
fasciculations) while the legs may show more upper motor neuron signs (spasticity, increased
reflexes and Babinski sign). The disease often starts asymmetrically, but usually within months it
involves many muscle groups on both sides of the body. The average patient survives three to five
years with death resulting from weakness of the bulbar and respiratory musculature and resultant
superimposed infection.
The variant of motor neuron disease that selectively involves the upper motor neurons is
called primary lateral sclerosis. In the great majority of cases there is eventually some evidence of
lower motor neuron involvement. For this reason most neurologists no longer feel this to be
distinct from ALS despite the fact that the clinical course tends to be longer than in the usual
variety of ALS. Some patients survive ten years or longer. There is also a variant that involves only
lower motor neurons (progressive muscular atrophy) and one that selectively involves the cranial
musculature (termed progressive bulbar palsy). Again, with time these variants often show signs
of evolution to a more typical ALS pattern.
Motor neuron disease is a very active field of research. There has been great interest in the
possible contribution of environmental toxins to the condition and of chronic very low level
activation of inflammatory pathways (despite a lack of overt inflammation in pathological
specimens). Most of these lines of investigation have been based on epidemiological identification
of specific risk factors. Examples include a toxin-induced motor neuron disease termed the
ALS-dementia complex of Guam and also the growing evidence of chronic low-level trauma as a
precipitant. The finding of certain families of patients with clearly hereditary ALS has stimulated
research identifying neuronal deficit of an antioxidant (superoxide dismutase) as a cause. This has
lead to research into free-radical destruction of motor neurons. Despite these preliminary
findings, extensive research has yet to lead to any effective therapy, although riluzole does slightly
delay the progression of disease. The mechanism of action is unknown, although it does decrease
glutamate neurotransmission (decreasing release, increasing reuptake and decreasing activation
of glutamate receptors) and also decreases fast sodium channel activation. Needless to say, much
research remains to be done on motor neuron disease.
Peripheral nerve damage (peripheral neuropathy)

Peripheral neuropathy generally appears in one of three patterns that can be distinguished
clinically. These include involvement of one isolated nerve or root (mononeuropathy), several
isolated nerves (mononeuropathy multiplex), or peripheral nerves diffusely (polyneuropathy). In
each of these patterns, the primary disorder in each case may involve the neuron (or its neurite) or
the Schwann cell. The etiologies of the three patterns of presentation are rather distinct and,
therefore, recognition of the pattern is clinically important.
The particular nerve or nerves that are affected can be determined by the symptoms.
Symptoms may be "positive" (including pain and dysesthesia), may be negative (including loss of
sensation, weakness or loss of reflexes), or may be irritative (such as fasciculations or
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paresthesias).
Mononeuropathy
Mononeuropathy and radiculopathy are most often due to trauma of some type. This may be acute
(such as wounds or blows to the nerve) or chronic (by chronic pressure in vulnerable sites). The
neuropathy in these cases is recognized by the distribution of symptoms. Both negative (loss of
sensation, weakness, atrophy) and positive (paresthesia, pain) may be present in
mononeuropathy. Anything that damages peripheral nerves systemically (see the section on
polyneuropathy) promotes local nerve injury by lowering the resistance of the nerve to damage.
An important clinical feature of local nerve damage is that the nerve becomes very mechanically
sensitive at the site of injury. A "Tinel sign" can often be elicited by gentle tapping over the site of
injury. This is an "electrical" type of paresthesia percieved in the distal distribution of the irritated
nerve. For example in carpal tunnel syndrome the Tinel sign is present at the wrist in the great
majority of cases. The distribution of the paresthesias in this case should be in the sensory region
supplied by the distal median nerve.
The most common mononeuropathies are due to entrapment of nerves at anatomically
vulnerable sites. These sites include places where nerves pass through tight canals in the tissues or
where they are surrounded by hard tissues or subject to repeated pressure or motions that stress
the nerve. The most common entrapment neuropathy is carpal tunnel syndrome (CTS), which is
an entrapment neuropathy that produces chronic damage to the median nerve at the wrist.
Anything that compromises the volume of the carpal tunnel (congenitally small carpal tunnel;
thickening of the ligaments; disruption or swelling of the joint; inflammation of the synovium) can
promote CTS. A controversial subject is how much occupational activities (such as typing)
contribute to symptoms. The symptoms of CTS include decreased sensation in the radial digits
(sparing the palm) along with potential dysesthesias provoked by wrist position (including at
night). There may be weakness in thumb abduction and opposition (often with some clumsiness)
and atrophy of the thenar muscles. Pain is common, but is less predictable and the distribution
may be well beyond the distribution of the median nerve, especially in the wrist and up the
forearm to the elbow or even the shoulder.
Other common nerve entrapments in the upper extremity include the ulnar nerve at the
elbow. Damage can be due to bone and joint problems at the elbow, but is also promoted by
chronic pressure on the elbow and full elbow flexion. Weakness and atrophy of the intrinsic hand
muscles is common. There may be sensory loss over the small digits and the ulnar side of the hand
on the palmar and dorsal side. Damage to the ulnar nerve can occur at the wrist, usually due to
chronic pressure (such as hand position in bicycle riding). In this case, any sensory symptoms
would be minimal.
The radial nerve may be damaged by lesions (such as fractures) of the humerus, since the
radial nerve has a course in close proximity to the humeral shaft. It is also somewhat prone to
trauma at the lateral elbow. When the main part of the radial nerve is injured, there is weakness of
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wrist extension (wrist drop) and diminished sensation on the dorsum of the hand (not to the
finger tips). The radial nerve divides into a superficial (cutaneous) branch and a deep (muscular)
branch at the elbow. The superficial branch can be damaged by trauma or direct pressure over the
distal radius (e.g., handcuffs), producing sensory loss and dysesthesia/paresthesia on the dorsum
of the hand. The deep branch can be compressed in the tunnel that it makes through and under
the supinator muscle. This can weaken many of the extensors (such as for the fingers) while
sparing the brachioradialis muscle and the extensors of the radial side of the wrist.
"Thoracic outlet syndrome" (TOS) is actually a heterogeneous group of disorders that all
involve some mechanical compression of structures in the region of the upper thorax. While most
patients who are diagnosed with TOS have compression of the subclavian or axillary artery when
their limb is in certain positions, some patients have compression of the lower brachial plexus in
the region around the first rib and the scalene muscles that attach to it. In this case, the condition
can be called a "neurogenic thoracic outlet syndrome." This compression may be associated with a
cervical rib or band of connective tissue connecting from the cervical spine to the first rib.
Neurogenic TOS produces symptoms in the distribution of the ulnar nerve (which arises from the
lower brachial plexus) and also in the ulnar aspect of the forearm. A full discussion of "vascular
TOS" is beyond the scope of this book (see this site for further information). However, vascular
TOS is defined by compression of the great vessels in the region around the clavicle and/or upper
ribs. Symptoms of ischemia of the limb may be brought on by sustained depression of the
shoulders, abduction and external rotation of the arm or sustained rotation and extension of the
neck. If these maneuvers reproduce the patient's complaints and, at the same time, abolish the
radial pulse, consideration should be given to possible TOS.
In the lower extremity, the most common entrapment neuropathies include damage to the
lateral femoral nerve, the fibular (peroneal) nerve, the posterior tibial nerve and the interdigital
nerves. The lateral femoral cutaneous nerve can be entrapped where it goes under the lateral part
of the inguinal ligament. This can result from weight gain, tight belts or pregnancy, and produces
decreased sensation and dysesthesia in the lateral thigh. Fibular (peroneal) nerve damage usually
occurs at the fibular head due to direct trauma or pressure. This may produce "numbness" on the
dorsum of the foot and weakness of foot and toe dorsiflexion and eversion. Inversion should be
unaffected. Tibial nerve entrapment at the medial aspect of the ankle has been termed "tarsal
tunnel syndrome." This is rare, occurring after severe ankle trauma or with connective tissue
disorders such as rheumatoid arthritis. Interdigital neuromas are common and result from a
pinching of the common digital nerves between metatarsal heads. This results in paresthesia and
dysesthesia on the sides of adjacent toes (particularly after walking).
Radiculopathy
Radiculopathy indicates damage to nerve root(s), and typically occurs as a component of
several spinal diseases. In younger individuals this is usually due to intervertebral disc herniation.
In older individuals, this is more often due to degenerative changes in the disc, bones and joints,
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which result in thickening of the tissues. Thinning of the discs can result in narrowing of
intervertebral foramina, which can also result in nerve compression. These problems tend to occur
in the lower lumbar region and the mid- to lower cervical area (which are the levels of the most
commonly damage nerve roots).
Nerve root entrapment most often occurs in the cervical and lumbar areas, but should be
considered when symptoms follow a well-defined nerve root distribution and whenever distal
symptoms are coupled with pain in the back or neck. The symptoms often include pain projected
along the distribution of the nerve root along with provocation when the nerve root is stretched
(such as by straight leg raising or lateral flexion of the neck) or pinched (such as by arching the
back or compression of the neck). Coughing, sneezing and straining also often worsen symptoms.
There may also be a more constant, deeper, aching pain ("like a toothache") although this is less
specific and can result from many painful processes.
There is usually not much sensory loss because of overlap of nerve roots, although there are a
few areas of the distal limbs (called "autonomous zones") where there is little overlap between
roots (see Table 21-3). Other signs of radiculopathy include weakness (of a "lower motor neuron"
type) and reflex loss. The most common symptoms of radiculopathy are noted in Table 21-3.
Polyneuropathy
Polyneuropathy is a common condition. It is not always easy to determine its cause. In this
condition the longest peripheral nerve fibers are usually first. Peripheral neuropathy can affect
either the axon, or myelin sheaths (demyelinating), or both. This syndrome is usually symmetrical.
Patients with polyneuropathy are also more susceptible to compression neuropathy.
Since the nerves to the lower limbs are the longest, they are the most dependent on a good
supply of metabolic substrates, and also have the greatest exposure to toxins or conditions
damaging myelin. Therefore, symptoms and signs are most prominent in the feet. Loss of
sensation ("numbness") is the most common finding but paresthesias or dysesthesias (prickling,
tingling, burning, etc) are also common. When large-diameter nerve fibers are affected, vibration
and joint position sense are impaired. Many patients with large-fiber damage in the feet complain
about balance trouble (and have Romberg sign). Such patients may have difficulty walking in the
dark or on irregular surfaces because of proprioceptive problems with the feet. Polyneuropathy
may also result in distal weakness and atrophy if there is actual loss of motor axons. Ankle jerk
reflexes are most often lost.
There are a few conditions that damage small nerve fibers early in their course. Such
conditions would be expected to result in decreased sensitivity to pain and temperature. When
patients lose pain sensitivity, they may injure themselves without awareness (which can result in
tissue loss, including amputation).
In around 2/3 of cases, polyneuropathy has an identifiable cause (table 21-4). The most
common single cause is diabetes mellitus, which can damage axons as well as myelin. High alcohol
intake can also result in peripheral nerve damage but this is most likely due to nutritional
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deficiencies, especially the B vitamins. In the United States, the most common single deficiency is
in vitamin B12 (secondary to poor absorption of Vitamin B12). Usually B-12 deficiency causes
more of a myelopathic picture than a polyneuropathy. Paradoxically, excesses of pyridoxine can
also result in a polyneuropathy. Toxins such as heavy metals, certain organic solvents and
industrial exposures (such as carbon disulfide) may result in peripheral neuropathy. Usually, there
is some history of significant exposure, although testing may be necessary. A variety of
medications, especially some chemotherapeutic agents and some drugs used to treat seizures or
HIV infection (HAART therapy), can be neurotoxic. Certain systemic inflammatory conditions
such as systemic lupus erythematosus, Sjogren Syndrome, Wegner granulomatosis, and
polyarteritis nodosa are associated with neuropathy but most of the time it is in the pattern of
mononeuropathy multiplex (see below). Certain chronic infectious conditions such as tertiary
syphilis, Lyme disease and HIV, may result in polyneuropathy and should be evaluated in the
appropriate clinical setting; although, again, the pattern may be a pattern of mononeuropathy
multiplex. Leprosy causes a patchy sensory neuropathy, which can result in mutilation of the
patient's digits. There are some other metabolic conditions that can cause neuropathy, including
severe sprue and porphyria. Abnormal proteins in the blood may result in a polyneuropathy
associated with monoclonal gammopathy or amyloid.
A special note should be made of immune demyelinating conditions that can present either
acutely or chronically. The acute form is termed Guillain-Barre syndrome or AIDP (acute
inflammatory demyelinating polyradiculoneuropathy). It is markedly different from the other
causes of neuropathy in its rapid course and severe weakness, produced by immune attack on
myelin (demyelination). It is critical to recognize this condition since it can progress rapidly to
respiratory paralysis and life-threatening autonomic instability. This is usually recognized by
subacute weakness (sometimes ascending from the legs and sometimes descending, starting with
eye, face or oropharyngeal muscles). There may or may not be sensory loss, but reflexes are
usually lost early (including often in clinically unaffected muscles). Protein is usually elevated in
the CSF, while there is little, if any, elevation in white cells in CSF. It may follow a viral or
diarrheal illness (particularly Campylobacter jejuni) by a week or two. AIDP patients usually
recover quite well with time. However, the clinical course may be shortened by certain immune
modulating treatments (especially intravenous immunoglobulin).
A chronic immune mediated neuropathy (chronic inflammatory demyelinating
polyradiculoneuropathy - CIDP), may result in relapsing or progressive polyneuropathy. This
usually results in an asymmetric weakness and sensory loss. This condition is associated with very
high cerebrospinal fluid protein levels. As with AIDP, reflexes are lost early in CIDP because the
most heavily myelinated nerve fibers are the muscle stretch sensory nerve fibers and these are
affected first. CIDP requires chronic immune modulating therapies.
Finally, there are a large number of peripheral neuropathies that may be familial. Some of
these have very clear pattern of inheritance, such as Charcot-Marie-Tooth Disease or hereditary
motor sensory neuropathy (HMSN). Sometimes, the hereditary peripheral neuropathies may not
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have a clear pattern of inheritance. It is always necessary to examine many of the patient's
relatives in order to make a diagnosis. EMG/NCS are performed to characterize the peripheral
neuropathy in the patient and it may also be performed on relatives to gain more information.
Most familial neuropathies do not have a rapidly progressive course. Weakness is usually
prominent and there may be marked sensory loss. In HMSN, pain was thought to be rare but this
may not be the case. Finally genetic testing may be done to help with confirmation of the
diagnosis. In HMSN type I, which is the demyelinative form, nerve conduction testing is most
useful. It is less helpful in the axonal forms, known as HMSN II.
Many patients (at least 25%, and maybe as high as 40%) with polyneuropathy have no
identifiable cause of their condition. Therefore, it is often somewhat difficult to determine how
much investigation is required. Most patients with idiopathic neuropathy have relatively mild
sensory symptoms and are older. Additionally, their symptoms are generally quite slowly
progressive. Therefore, when a patient is identified with polyneuropathy, initial consideration
must be given to the identifiable causes listed above, recognizing that the findings may be
negative. These patients do require a good history of the timing of symptoms and of possible risk
factors and exposures to medications and toxins. NCS/EMG are routinely done to confirm
diagnosis and to characterize the peripheral neuropathy. If symptoms are acute, then urgent
consideration must be given to inflammatory conditions (such as Guillain-Barre), severe
metabolic abnormalities or to toxic exposures. Most patients with polyneuropathy should have
certain basic metabolic tests performed, including a CBC, glucose level, HgbA1C, TSH, serum
protein electrophoresis, and sedimentation rate. In selected cases, an RPR, HIV, Lyme titer, ANA,
rheumatoid factor, antineutrophil cytoplasmic antibody titer, and screen for heavy metals and
porphyrins may be indicated. If these tests are negative, a follow-up examination after a number
of months (or sooner if symptoms suggest rapid progression) is imperative. In younger patients
and those with acute or subacute progression, specialty referral for more sophisticated testing
such as sural nerve biopsy or skin biopsy looking for unmyelinated fiber loss is necessary. Some
investigators feel that abnormal glucose tolerance in the absence of diabetes can cause a painful
small fiber neuropathy.
There are several important clinical concerns when managing the patient with
polyneuropathy. First of all, any hope of arresting the polyneuropathy requires an identification of
the cause. In some cases, removing the causative agent can actually improve the polyneuropathy.
Patients who have lost sensitivity to pain are at high risk of damaging their feet (resulting in ulcers
or Charcot joints). Therefore, particular attention must be given to proper footwear and foot
mechanics. Significant proprioceptive loss produces instability, especially when walking on
irregular surfaces or when vision is obscured. These individuals will typically have a Romberg sign
that improves dramatically when touching a stationary object with one finger. These patients
improve with use of a cane.
Mononeuritis Multiplex
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"Mononeuritis multiplex" is a relatively rare presentation of certain disorders that damage nerves
primarily by interfering with blood flow to nerves or plexi or by an autoimmune process damaging
either the myelin or axon. This results in unpredictable and patchy nerve damage. If this is
produced by interruption of circulation, the symptoms can occur abruptly.
The most common cause of mononeuritis multiplex is diabetes mellitus. This may occur along
with or independent of diabetic polyneuropathy. Other potential causes of mononeuritis multiplex
include any conditions that result in systemic vasculitis (such as the autoimmune conditions like
systemic lupus erythematosus or polyarteritis nodosa) or infectious vasculitis (such as with Lyme
disease). If the etiology of the condition is not clear, specialty evaluation is necessary since
treatment is critically dependent on identifying the cause.
In diabetes, an inflammatory disorder of the lumbar plexus or, rarely, the brachial plexus can
occur. This usually affects the femoral nerve, with prominent weakness of the quadriceps muscle
and loss of patellar reflex (termed diabetic amyotrophy). The condition is heralded by severe pain
in the hip or shoulder with prominent weakness of the ilipsosas, thigh adductors, and quadriceps
muscles; when the lumbosacral plexus is affected. Usually the patient has poor control of their
diabetes and systemic symptoms such as weight loss and fatigue. The diagnosis is aided by
NCS/EMG. Treatment is focused on control of diabetes and the judicious use of IVIG or IV pulse
steroids (with very careful monitoring of blood glucose levels). The condition typically shows slow
and variable recovery over months.
There are rare, idiopathic cases of mononeurities multiplex that most often affect the brachial
plexus distribution. This is most common in middle-aged men and has been termed neuralgic
amyotrophy (also known as idiopathic brachial neuralgia or Parsonage-Turner syndrome) due to
the fact that it is usually painful at the outset, with subsequent appearance of atrophy and
weakness. The typical course is very slow improvement. In this condition early judicious use of
IVIG and pulse IV steroids may be helpful. There are more minor and quite focal varieties of this
syndrome, which can complicate diagnosis.
End-plate (neuromuscular junction)

With few exceptions each muscle fiber has one (and only one) end-plate; this is the plug for a
nerve terminal branch. Acetylcholine is the neurotransmitter at this synapse that couples motor
nerve activity with response in the muscles.
Much of the early electrophysiological understanding of chemical synapses was gained from
study of the neuromuscular junction. At rest there are normally intermittent discharges at the
end-plate region of fairly constant amplitude and duration (miniature end-plate potentials). These
are not capable of triggering muscle action potentials. Subsequently, electron microscopists
discovered the synaptic vesicles that contain acetylcholine (ACh). It had been known that ACh is
capable of depolarizing the postsynaptic membrane and, in view of the regular size of such
synaptic vesicles and the morphologic evidence that vesicles may open to the synaptic cleft, it
became obvious that each miniature end-plate potential is the result of spontaneous emptying of a
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fairly constant number (quantum) of molecules of ACh from a vesicle. Arrival of a nervous impulse
at the presynaptic terminal causes release of many quanta, and this is normally sufficient to fire an
end-plate potential, which spreads at 4 m/second along the whole muscle fiber membrane as the
muscle fiber action potential. From the membrane, the potential propagates into the depth of the
muscle fiber to trigger calcium entry into the fibers. This calcium, which is normally sequestered
in the sarcoplasmic reticulum, couples excitation to the interaction between myofilaments that
shorten the fiber.
Once ACh is released into the synaptic cleft, its action is terminated by acetylcholinesterase in
the end-plate, which destroys the ACh molecule with recycling of the fragments. Drugs with
anticholinesterase activity facilitate the depolarizing effect of ACh. It is noteworthy that excess
ACh eventually may block neuromuscular transmission (i.e., cholinergic block) by preventing
normal repolarization of the muscle. This is the action of many insecticides and biological warfare
agents. Also, the neuromuscular junction may be blocked by many agents, including those that
prevent release of ACh (such as botulinum toxin) or that block the nicotinic ACh receptor (such as
curare).
Myasthenia gravis.
Myasthenia gravis is the most common disorder affecting neuromuscular transmission. This
condition is autoimmune, with antibodies directed against nicotinic acetylcholine receptors of the
neuromuscular junction. It is not extremely common (about 1:10,000) and incidence is highest in
young adult women. There is another small spike in late middle age men, who may have thymic
tumors. Thymic epithelial cells have surface proteins with epitopes that cross react with
acetylcholine receptors at the neuromuscular junction. Thymic tumor or hyperplasia may be found
in myasthenic patients.
The earliest symptoms of myasthenia gravis are usually seen in the eyes, with ptosis and/or
diplopia ("ocular myasthenia"). The second most commonly affected muscles are in the pharynx
and soft palate ("bulbar myasthenia") with problems speaking and swallowing. "Generalized
myasthenia" involves many muscles of the body, including the diaphragm. Additionally, it can
result in autonomic instability and may be life-threatening. Myasthenia may present in any one of
these patterns and may remain as only ocular involvement or progress to generalized weakness (it
will usually do so within the first two years if it is going to generalize).
In this condition, there is a reduction in the size of the miniature end-plate potentials caused
by a decrease in the number of ACh receptors on the postsynaptic side. The consequence is a
reduced safety factor for neuromuscular transmission. The "safety factor" is defined as the excess
in excitatory transmitter (in this case, acetylcholine) release above that which is necessary to
activate the muscle fiber. When the safety factor is reduced, conduction of a nerve impulse may
not be followed by contraction of the muscle fiber.
There are degrees of neuromuscular block (as there are of nerve conduction block). The
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mildest form consists of only increased N-M delay in some junctions of motor units. In severe
forms, many end-plates are blocked, but the functional state of a given end-plate varies with time
and use. During high-frequency activations (as in exercise) more end-plates fail to activate the
muscle due to insufficient release of acetylcholine. So, in myasthenia gravis motor units contract
without their full number of muscle fibers; sometimes all contract, sometimes a few, and
sometimes none.
The cardinal clinical feature of myasthenia gravis is that repetitive or sustained use of a
muscle contributes to depletion of acetylcholine in the motor nerve terminal, with ultimate failure
of conduction. This explains why weakness fluctuates in connection with exercise and rest, that is,
fatigability. The effects of this can be seen by repetitive electrical nerve stimulation with a
recording of the amplitude of the compound muscle action potential (summation of all muscle
fiber potentials from all excitable motor units in the muscle). Normally, there is little variation in
successive firings. In myasthenia gravis, there may be an abnormal decrement due to N-M block
(or fatigue). This may be followed by post-tetanic facilitation (Figure 21-2).
Acetylcholine or cholinergic substances or anticholinesterases improve this N-M transmission
defect (before leading to cholinergic block). However, myasthenia gravis is more than just a
functional end-plate disorder. It may lead to muscle fiber atrophy and fixed weakness. Indeed,
often there is evidence of neurogenic atrophy of muscle and also selective type II fiber atrophy.
The thymus gland and immune mechanisms (autoimmunity against ACh receptor) have a
great deal to do with myasthenia gravis, although their exact roles are not totally clear. In practice,
thymectomy, corticosteroids, immunosuppressive drugs, human immunoglobulin and removal of
antibodies by plasma exchange may be useful in treatment.
Myasthenic syndrome.
There is another interesting and uncommon disorder of neuromuscular transmission -- the
myasthenic syndrome or Lambert Eaton Syndrome (LEMS). It may be associated with carcinoma.
LEMS may improve after removal of the tumor (usually bronchogenic small-cell carcinoma). The
defect in neuromuscular transmission is caused by reduced numbers of quanta released from
nerve terminals in response to a nerve impulse. This is due to defective calcium channel function
in the presynaptic membrane. It causes weakness that tends to improve with exercise; repetitive
stimulation causes facilitation rather than the fatigue seen with myasthenia gravis (see Figure
21-2). The defect can be demonstrated also in vitro in nerve/muscle biopsies from other patients.
Acetylcholine-releasing agents such as 4-aminopyridine may help correct the transmission defect.
Another well-known and fortunately rare disorder of transmitter-release blockade is
botulism.
Muscle Disease (myopathy)
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There are many things that can go wrong in muscles: failure to propagate a muscle action
potential to invade the T-system; failure of electromechanical coupling; failure in the physical
mechanism of sliding filaments; and failure of the normal energy production mechanisms. In
recent years, there have been an overwhelming number of "new" muscle diseases based on very
specific failures in the system. However, most of these conditions present in a rather stereotyped
manner, and clarification of the precise etiology may require very elaborate procedures. We will
discuss a practical approach to the recognition of muscle disease, while electron microscopic,
metabolic and genetic testing may be required for precise diagnosis. A list of conditions damaging
muscle can be found in Table 21-5.
Recognition of a myopathy usually begins with recognition of a symmetrical, proximal muscle
weakness, although cramping of muscles (particularly with exercise) or, in rare cases,
symmetrical, aching discomfort in muscles may be the initial findings (especially in inflammatory
myopathies). Muscle enzymes (particularly CK levels), may be helpful in clarifying that there is
actual muscle disease and electromyography can establish that the disorder lies in muscle as
opposed to the neuron or nerve fiber. On EMG, examination of the motor unit action potentials
reveal small, brief and polyphasic (myopathic) motor potentials (see Figure 21-1). Muscle biopsy
may help confirm and classify the myopathy but special staining of the muscle biopsy and genetic
testing may be necessary. Unfortunately, few muscle diseases are effectively treated.
The following is a very oversimplified but practical review. Two major groups of muscle
disease can be distinguished. The first group includes disorders of muscle that cause destruction
of muscle fibers, leading to (usually progressive) muscle weakness and wasting. The second main
group includes diseases that cause more of a functional defect than structural fiber degeneration
(little wasting). Most of these are "channelopathies" that cause altered muscle function without a
lot of fiber death. Within each of these groups of conditions, there are subtypes that we will briefly
discuss.
Diseases that actually progressively destroy muscle fibers fall into three main types: the
dystrophies, the metabolic myopathies and the inflammatory myopathies.
1. Muscular dystrophies: These conditions are non-inflammatory degenerative
conditions of muscle that are genetically determined, not effectively curable, and
progressive. The types of muscular dystrophy are usually classified according to
inheritance and distribution of weakness. The earliest (and most devastating) is
Duchenne dystrophy. This is an X-linked disorder due to mutation of the gene for a
normal protein (inappropriately named "dystrophin") that attaches the contractile
elements to the muscle membrane. Early in life, another protein performs this function,
so symptoms usually don't start until after the child is standing and beginning to walk.
The child experiences a progressive decline in muscle strength (wheelchair in late
childhood and usually death from cardiac involvement in the early 20s). A less severe
mutation in the same gene causes a somewhat later onset condition (Becker dystrophy).
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There are other dystrophies (most with onset in late childhood or early adolescence)
including: facioscapulohumoral dystrophy, limb girdle dystrophy and oculopharyngeal
dystrophy. Each of these has its own hereditary pattern. The names describe the
predominant muscle groups involved. Myotonic dystrophy is unique in that it tends to
affect distal muscles and causes noticeable myotonia. It is more severe in children of
affected mothers and the severity of symptoms is based on the number of repeats found
in a specific part of the genome. Clinical characteristics of some of the more common
dystrophies are discussed below.
2. Metabolic myopathies: Within this category are both acquired and genetic
disorders. The prototypical acquired disorder is thyroid disease. Both hyper- and
hypothyroidism can result in myopathy due to interference with the normal metabolic
activity of muscles. Certain medications and toxins can affect the metabolic machinery
of muscles, causing myopathy. Examples of this include myopathy secondary to statins
(lipid-lowering drugs), colchicine, hydroxychloroquine or large amounts of alcohol.
There are genetic disorders that interfere with metabolism of carbohydrates or fats,
resulting in myopathy and, often, accumulation of intracellular inclusions (usually due
to buildup of metabolic products). Some of these conditions result in exercise
intolerance, occasionally with myoglobinuria and some result in exercise-induced
cramping (due to insufficient energy production needed for muscle relaxation). Some,
more poorly defined conditions result in intracellular inclusions seen on electron
microscopy (nemaline myopathy, myotubular myopathy). The mitochondrial
myopathies are a heterogeneous group of muscle diseases associated with excessive
replication of somewhat defective mitochondria that accumulate in cells. Not
surprisingly, muscles are commonly affected (since they are major consumers of
energy), but many other areas (including the brain) are also affected. Extraocular
muscles are often affected in mitochondrial disease due to the tonic activity of these
muscles. Mitochonidrial myopathies may be associated with exercise intolerance and
elevated serum lactate due to problems with aerobic metabolism. Not surprisingly,
these conditions also may target heart muscles (and some affect the brain).
3. Inflammatory myopathy: Inflammatory myopathies may be acquired or
autoimmune. The acquired inflammations include sarcoidosis and certain infectious
conditions (such as HIV/AIDS and trichinosis). The autoimmune myopathies include
polymyositis and dermatomyositis, as well as inclusion body myositis.
Polymyositis usually appears in people 30-60 years old and presents as insidious onset
of symmetrical, proximal muscle weakness, occasionally accompanied by muscle
soreness. The proximal weakness makes it difficult to climb stairs and to lift things
overhead. Occasionally this is associated with another autoimmune condition or cancer
(especially lymphoma, lung or bladder).
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Dermatomyositis also includes insidious weakness of proximal muscles, but there is

also a red/purple rash. This is most characteristic over the eyelids (heliotrope) and
extensor parts of joints, such as the knuckles, elbows, knees, and toes. The rash may
also include the face, chest and elsewhere (particularly over affected muscles). Muscle
soreness is more common than with polymyositis. Dermaotomyositis tends to be seen
in children (5-15 years old) and in later adulthood (50s and 6os) and has a higher
association with underlying autoimmune or neoplastic disease than polymyositis. In
addition to lymphoma and lung cancer, breast and ovarian cancers should be
considered.
Both Polymyositis and dermatomyositis often elevate inflammatory markers (such as
erythrocyte sedimentation rate and C-reactive protein) and markers of muscle damage
(such as muscle CPK). However, a finding of normal ESR and CPK do not rule out these
conditions, especially in milder cases. Muscle biopsy of affected muscles is diagnostic.
They myopathy usually responds to immunosuppresion but both of these conditions
may be triggered by underlying neoplasm.
Inclusion body myositis is a slowly progressive symmetrical myopathy that, in addition
to affecting proximal muscles (often affecting the ability to climb stairs) also affects
flexors of the fingers and wrists. This also generally has elevated CK levels but the
sedimentation rate is variably elevated. This condition is characterized by cytoplasmic
inclusions on muscle biopsy, and there is no effective treatment. Distinct from
dermatomyositis and polymyositis, this generally occurs in late middle aged and older
individuals and is more insidious. Unfortunately, this does not usually respond to
immunosuppression.
The second main group of disorders affecting muscles includes diseases that cause more of a
functional defect than a structural fiber degeneration (little wasting). These conditions are ion
channelopathies.
1. Myotonic disorders: Myotonic disorders: Here we have congenital myotonia and
paramyotonia congenita. In the former condition (due to chloride transport
abnormality) the symptoms improve with exercise, while the latter condition (due to
sodium channelopathy) worsens with exercise and with cold. Needle insertion into
muscles usually easily identifies myotonic potentials.
2. Periodic paralysis: These are thyrotoxic periodic paralysis and familial periodic
paralysis (hypo-, hyper-, or normokalemic and Andersen syndrome). These often
produce generalized and temporary weakness after large meals or exercise. Diagnosis
can be made by provoking the weakness with a glucose load and exercise.
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Myotonias and periodic paralyses are rare and are recognized clinically. Electromyography
may show typical myotonic discharges. Treatment of symptoms and avoidance of precipitating
factors may be helpful in both groups.
Muscular dystrophies
Collectively, these conditions result in non-inflammatory degeneration of muscles
Duchenne muscular dystrophy

This is the most common type and is a sex-linked recessive trait. It affects young boys, in whom
pseudohypertrophy of the calves and weakness of the hip and shoulder girdles progress from early
childhood. Levels of serum muscle enzymes (CPK and aldolase) are extremely high. The children
are usually confined to a wheelchair by the age of 10, and they usually die in the second to third
decade. It is due to a mutation in the gene for an inappropriately-named normal protein named
dystrophin. A less severe mutation in this same gene is responsible for a somewhat later onset
dystrophy, Becker dystrophy. No effective therapy is known, although steroids may slightly
prolong the course.
Limb-girdle muscular dystrophy

This is a heterogeneous group of conditions that usually appear in adolescence or adult life with
proximal limb weakness. The weakness usually progresses slowly, but it may arrest spontaneously.
There are at least 15 different mutations that contribute to this presentation and some are passed
on recessively while others have dominant inheritance.
Facioscapulohumeral muscular dystrophy

This condition also can be recessive or dominant and appears to have at least several different
genetic abnormalities producing this phenotypically distinct pattern of weakness and wasting.
Symptoms usually appear in adolescence or very early adult life with weakness of face muscles and
of muscles attached to the scapula and proximal upper limb. The weakness usually progresses
slowly and life expectancy is normal. Mental retardation is common and there may be
abnormalities of cardiac rhythm.
Myotonic dystrophy
In this disease myotonia (delayed relaxation of muscles) is combined with dystrophy (muscle
atrophy not secondary to peripheral nerve or anterior horn cell involvement). The disease, which
is transmitted as an autosomal dominant condition, usually begins in childhood or young adult life
(possibly infancy with maternal transmission). There are cases where it has been unrecognized
until advanced ages, however. It is due to repeats in the sequence of the myotonic protein kinase
gene. These repeats often get longer in sequential generations, with earlier onset of symptoms.
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Myotonic dystrophy, as opposed to most forms of myopathy, is distal, affecting the muscles of
the hands before more proximal musculature. In addition, facial and neck musculature are
involved early. Evidence points to an abnormality of membranes that is not restricted to muscle.
Numerous non-neurologic problems are found: frontal balding, testicular atrophy, diabetes,
cardiac arrhythmias, and others. It progresses slowly. Many victims succumb to respiratory failure
and superimposed infection by the fifth decade.
References
Brooke, M.H.: A Clinician's View of Neuromuscular Diseases. Baltimore, Williams &
Wilkins Co., 1977.
Dyck, P.J., Thomas, P.K., Lambert, E.H.: Peripheral Neuropathy, Philadelphia, W.B.
Saunders Co., 1975.
Engle, E.J., Banker, B.Q.: Myology. New York, McGraw-Hill, 1986.
Walton J.N.: Disorders of Voluntary Muscle, ed. 4, New York, Churchill Livingston,
1981.
Questions
Define the following terms:
neuropathy, myopathy, neuromuscular junction/myoneural disease, "dying back",

demyelinative, Wallerian degeneration, epineurium, perineurium, endoneurium,
Schwann cells, myelin, entrapment neuropathy, carpal tunnel, lateral femoral cutaneous
neuropathy/meralgia paresthetica, polyneuropathy, Charcot-Marie Tooth,
Lambert-Eaton myasthenic syndrome, paraneoplastic syndrome, myasthenia gravis,
nerve conduction study, electromyography.
21-1. What modalities are conveyed by large, myelinated nerve fibers?

21-2. What do small-diameter sensory nerve fibers convey?
21-3. What is entrapment neuropathy?
21-4. What are symptoms of polyneuropathy?
21-5. What are the causes of polyneuropathy?
21-6. What are the potential causes of myopathy?
21-7. What are the common symptoms of myopathy?
21-8. What effect do myopathies have on reflexes?
21-9. What additional test would point to myopathy as a cause of weakness?
21-10. What is the most common neuromuscular/myoneural junction disease?
21-11. Who is most often affected by myasthenia gravis?
21-12. What are the symptoms of myasthenia gravis?
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21-13. What blood test may be helpful in diagnosis of myasthenia gravis?

21-14. What regions of the body are most commonly affected by myasthenia gravis?
21-15. What is the treatment for myasthenia gravis?
21-16. What is Lambert-Eaton myasthenic syndrome?
21-17. What is the function of nerve conduction studies?
21-18. What does electromyography evaluate?
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Copyright Reeves 2008

Site editor: Rand Swenson, DC, MD, PhD
Contributors:
Jeffrey Cohen, MD
Camilo Fadul, MD
Lawrence Jenkyn, MD
Thomas Ward, MD
Dartmouth Medical School
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Chapter 21: Neuromuscular Disroders

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Chapter 21: Neuromuscular Disroders

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Chapter 21: Neuromuscular disroders

DISORDERS OF THE NERVOUS SYSTEM - REEVES & SWENSON

Chapter 21 - Neuromuscular system disorders

The nervous system can be considered a reflex arc designed for

Functional neuromuscular units

analyzing the environment through sensation and then

Nerve anatomy and action

modifying the environment through movement. The

neuromuscular component of the nervous system is made up of

Motor neuron disease

the parts of this peripheral apparatus.

and physiology. Therefore,the clinical expression of symptoms

following damage are rather straightforward, consisting of loss of

these normal functions. From the type and the distribution of

symptoms, it is possible to achieve a diagnosis and to do the

1. Confirm that such manifestations arise in the

4. In disease of the peripheral nerves, the type of injury

Anatomy and Physiology of Peripheral Nerve Fibers