+++
Acute Arterial
Insufficiency
++
++
The pain of acute arterial insufficiency is characterized by
its sudden onset. Emboli lodge at artery branch points, which are
also more likely to be affected by atherosclerosis. Emboli may occlude more
than one vessel at a branch point and thereby limit collateral flow.
Muscle necrosis and irreversible changes may occur if blood flow
is not reestablished within 4 to 6 hours.1
++
The five cardinal features of arterial insufficiency (the five “Ps”)
consist of pain, pallor, paresthesias, paralysis, and pulselessness.
The pain is well localized to an extremity and severe. It may be attenuated
by good collateral circulation; that is, occlusion of a brachial
artery may not produce as dramatic a clinical picture as occlusion
of a common femoral artery or popliteal artery. Nerve endings and
muscle tissue are extremely sensitive to hypoxia, and acute obstruction
soon leads to anesthesia and paralysis in an affected extremity.2
++
Pulses usually, but not always, are absent distal to the site
of obstruction. Therefore, pain and associated signs and symptoms
of ischemia in the presence of detectable pulses warrant further investigation.2 Conversely,
pulses may be unusually strong proximal to the site of the occlusion.
++
Acute ischemia in an extremity also is accompanied by a change
in the skin temperature distal to the site of occlusion. The extremity
appears pale, and the veins may seem to be empty. Palpation along
the course of the artery may reveal tenderness over the site of
occlusion. The muscles begin to feel hard and inelastic as the ischemia
progresses.2 Muscular fatigue and weakness are
apparent.
+++
Chronic Arterial
Insufficiency
++
Chronic arterial insufficiency can produce a wide variety of
painful symptoms. Affected patients can have numbness, coldness,
tingling, or total paresis. The degree of insufficiency determines the
type of pain in the lower extremity (intermittent claudication or
rest pain). Atherosclerosis is the most common cause of chronic
lower limb ischemia. Hypertension, diabetes mellitus, hypercholesterolemia,
and cigarette smoking increase the incidence and severity of atheroma
formation.3 Thromboangiitis obliterans (Buerger’s
disease), popliteal artery entrapment, and cystic adventitial disease
can also cause lower limb ischemia.
++
Claudication refers to cramping pain that occurs when blood flow
cannot be increased to a muscle mass in response to the increased
metabolic demands of exercise. Blood flow is adequate in the extremity
at rest. Claudication has several diagnostic features: (1) it is
always relieved by rest after exercise, (2) it is produced by a
consistent amount of exercise, and (3) it is always experienced
in a functional muscle group.4
++
Ischemic rest pain occurs when blood flow in the extremity falls
below resting tissue requirements. It is a manifestation of severe
chronic arterial insufficiency. Pain can occur in the toes and metatarsal
joints and is not confined to functional muscle groups. These patients
may experience relief by hanging the affected limb over the side
of the bed. The pain is constant and aggravated by limb elevation
and exposure to cold.5 Differentiating between
intermittent claudication and ischemic rest pain becomes important because
nondiabetic patients with claudication rarely require extremity
amputation, although many patients with ischemic rest pain do.6,7
++
Measurement of systolic blood pressure at the ankle facilitates
the diagnosis of arterial insufficiency of the lower limbs. The
cuff encircles the ankle, and a Doppler probe is placed over the dorsalis
pedis or posterior tibial arteries. The ratio of the ankle to arm
blood pressure is known as the ankle pressure index. Normally, systolic
augmentation occurs, and the ankle pressure should exceed the arm
pressure by 10 to 20 mm Hg,8 which yields an ankle
pressure index of 1.10 to 1.20. An index less than 1.0 suggests
some degree of arterial insufficiency. Angiographic data correlate
with these indices.9–11 Recently, magnetic
resonance angiography has been used to study vascular insufficiency.12
+++
Popliteal Artery
Entrapment
++
Popliteal artery entrapment can result in unilateral claudication
in even young patients.13,14 The popliteal artery,
instead of coursing downward between the two heads of the gastrocnemius muscle,
passes medially to the muscle. Its compression by muscle or fiber
spans results in calf and foot claudication. The symptoms of numbness,
paresthesias, and cramping associated with exercise may mimic chronic
arterial insufficiency. The unilateral nature of the symptoms and
the young age of the patient should suggest the diagnosis. Physical
examination may reveal either present or absent popliteal and dorsalis
pedis pulses, or the latter may disappear with exercise. Palpation
may show increased collateral blood flow (palpable geniculate arteries)
near the knee. This distinguishes entrapment from chronic arterial
insufficiency. Active plantar flexion or passive dorsiflexion may
obliterate the pedal pulses and aid the diagnosis. A bruit also
may be heard over the popliteal artery.
++
Arteriography is essential for diagnosis and should be done bilaterally
(25% of cases will be bilateral, even in asymptomatic patients).15 Angiographic
confirmation relies on medial deviation of the popliteal artery
and segmental occlusion of the popliteal artery.
+++
Adventitial
Cystic Disease of the Popliteal Artery
++
Adventitial cystic disease of the popliteal artery is a rare
cause of claudication in young patients.16 The
symptoms are produced by a cyst within the adventitial layer of
the popliteal artery, leading to gradual occlusion. These mostly
male patients describe a rapid onset of severe claudication. A murmur
in the popliteal fossa and the absence of pedal pulses help make
the diagnosis. If pedal pulses are present, they can be eliminated
by acute knee flexion. The cysts contain mucoproteins and mucopolysaccharides;
their exact cause is unclear. Radiographic evidence for the diagnosis
includes an “hourglass” appearance using angiography.16
+++
Thromboangiitis
Obliterans (Buerger’s Disease)
++
Buerger’s disease involves the entire neurovascular
bundle of the small vessels of the hands and feet. It appears as
an intermittent claudication of the arch of the foot and can progress
to ischemic digital pain at rest and frank gangrene. Buerger’s
disease usually affects more than one limb of men younger than 40
who are heavy smokers.17,18 In contrast to atherosclerosis,
Buerger’s disease can cause ischemic lesions of the fingers,
and recurrent episodes of superficial thrombophlebitis. Angiography
shows many small artery occlusions with tapering proximal to the
occlusion and the absence of plaques.19 Its pathologic
features include a panangiitis that preserves vessel architecture
and infiltration of the vessel walls by giant cells and lymphocytes.
++
Raynaud’s disease is defined as episodic digital vasospasm
precipitated by cold or stress that affects mostly the fingers and
hands. It also may affect the feet and toes. The classic attack
has three components: (1) initial blanching with relative numbness
secondary to arterial vasoconstriction, (2) cyanosis resulting from
the desaturation that occurs because of insufficient blood entering
the capillaries and small veins, and (3) reactive hyperemia.20 Usually,
neither pallor nor cyanosis predominates. Between 70% and
90% of patients with Raynaud disease are women.21 The
pain, which initially may be mild, becomes more severe and constant
as the condition progresses.
++
The underlying pathophysiology in an attack is digital artery
closure.22 This closure may occur secondary to
a vasoconstrictive mechanism (generally in younger women with connective
tissue disease) or an obstructive mechanism (usually in older patients
with atherosclerosis). The former may be caused by abnormal arterial
adrenoreceptors or adrenoreceptor-immune complex interactions. Baseline
proximal luminal obstructions are found in the latter group.
++
Raynaud’s phenomenon is associated with various other
diseases23 (Table 32-1) and with occupational hazards,
such as operating a chain saw or pneumatic drill. The vibration
frequency of these tools (110–140 Hz) presumably causes
severe sheer stresses in the arteries of the hands and fingers.24 Pathologic
studies show subintimal fibrosis after long-term exposure to these
tools.
++
++
The diagnosis is confirmed by the ice-water immersion test. Using
a thermistor probe, a baseline digital tip pulp temperature is determined
(which must be greater than 32°C, even if external warming
must be used). The patient’s fingers are submerged in ice
water for 30 seconds. Pulp temperature recordings are then made
every 5 minutes for up to 45 minutes.25 A normal
patient’s digital temperature returns to baseline within
10 minutes. In contrast, patients with Raynaud’s syndrome
have a prolonged return to baseline temperature.
++
Other laboratory diagnostic tests include an erythrocyte sedimentation
rate, complete blood count, antinuclear antibody, and rheumatoid
factor. Hand radiographs are useful for detecting subcutaneous calcinosis
typical of scleroderma or CRST syndrome (Calcinosis cutis, Raynaud
phenomena, Sclerodactyly, and Telangiectasia).
++
Thrombophlebitis of the superficial venous system can occur in
either the upper or the lower extremities. The factors responsible
for both thrombosis of the superficial venous system and deep vein
thrombosis are defined in the Virchow triad: stasis, abnormalities
of the vessel wall, and hypercoagulability. Thrombophlebitis may
occur after an injury to a limb or secondary to intravenous cannulation.
Other causes include varicose veins and carcinoma. Patients may
experience pain and redness along the course of a superficial vein,
which may feel firm to the touch. Doppler studies show diminished
or absent flow through the vein. Treatment is directed toward the
underlying disease process and should involve bed rest, elevation
of the extremity, and application of moist compresses.
+++
Deep Venous
Thrombosis (DVT)
++
DVT develops commonly near valves in the lower extremity. Initial
platelet aggregation elicits fibrin thrombus formation. Both platelets
and fibrin contribute to the growing thrombus. In the calf, venous
thrombosis usually produces tenderness but minimal swelling. The
skin temperature may be increased in the extremity secondary to
diversion of blood flow from the deep veins to the superficial veins.
Increased tenderness with dorsiflexion (Homan’s sign) is
notoriously unreliable in the diagnosis of DVT.26 Femoral
vein thrombosis usually results in both calf and popliteal fossa
tenderness, and leg swelling. Ileofemoral vein thrombosis is accompanied
by sudden severe pain, edema, and discoloration. Patients also may
feel tingling, numbness, and weakness. The pain begins in the area
of the femoral triangle or in the calf, but rapidly involves the
entire leg. This acute venous outflow obstruction can progress to
venous gangrene with interference of arterial inflow and limb cyanosis
(phlegmasia cerulea dolens).
++
Conditions that predispose to DVT include obesity, the postpartum
state, pelvic surgery, lower extremity fractures, prolonged bed
rest, estrogen use, and carcinoma. Detection depends on the following
noninvasive laboratory tests.27–30
++
- 1. Doppler ultrasonography recognizes the distorted flow
patterns
- 2. Impedance plethysmography quantifies venous obstruction
by measuring the rate at which a vein empties when a pneumatic cuff
at the thigh is released
- 3. Radioactive fibrinogen uptake tests involve the use of
labeled fibrinogen that is taken up by newly formed thrombi. This
is the most sensitive test to detect below-the-knee thrombi.
++
Ascending contrast phlebography also can be used to diagnose
DVT, but it is invasive, often painful, and difficult to interpret.
++
Cellulitis in an extremity, although it does not have a vascular
cause, must be differentiated from both superficial and deep venous
thrombi. These infections occur after trauma to the skin and subcutaneous
tissue. Inflammation is accompanied by edema, hyperemia, and leukocytic
infiltration. The hallmarks of infection (swelling, tenderness,
heat, and redness) are apparent. Lymphangitis may be evident, with
reddish painful streaks and regional node tenderness and enlargement. These
patients generally have more systemic symptoms than those with superficial
thrombophlebitis. Gram staining of needle aspirates is helpful in
diagnosing this disorder and is crucial for further therapy.
++
Compartment syndrome is defined as a condition in which increased
tissue pressure in a confined space compromises the circulation,
resulting in muscle necrosis and neurologic injury. Of the compartment
syndromes described (acute, subacute, and chronic Volkmann’s
contracture), only the acute compartment syndromes are painful.
Acute compartment syndromes are seen after tibial fractures, supracondylar
fractures, brachial arteriograms, gunshot wounds, circumferential
burns, snake bites, reflow after limb reattachment, and crush injuries.
++
The pathophysiology involves raised tissue pressure leading to
altered microcirculation in the compartment.31–33 Early
investigators believed the increased tissue pressure led to arterial
spasm and subsequent compromised tissue perfusion. However, newer
hypotheses describe increasing tissue pressure that compromises
transmural pressure across the walls of the arterioles. At a critical
transmural pressure, the vessels close. Small arterioles close at
a lower transmural pressure than larger arteries. Hence, tissue
ischemia may occur in the presence of palpable pulses. Another hypothesis involves
a rise in venous pressure in a compartment in response to the rise
in tissue pressure. The venous pressure increase allows blood flow
to continue. However, this venous hypertension in the compartment
soon disturbs the normal capillary arteriovenous gradient. This,
in turn, compromises capillary blood flow and tissue perfusion.
Disruption of the Starling gradients leads to decreased extracellular
fluid absorption, increased extracellular fluid transudation, and
a further increase in compartment tissue pressure.
++
Acute compartment syndromes usually provoke intense pain, which
is well localized to the involved muscle groups. Passive stretching
of the involved muscle groups greatly aggravates the pain. For example,
passive finger extension in a patient who has flexor forearm compartment
syndrome leads to excruciating pain. The second typical finding
is induration over the involved muscle groups. Less importantly,
patients may have weakness of the involved muscles and paresthesias
in the distribution of the involved nerves. Palpable pulses are
an unreliable clinical sign (see earlier discussion).
++
Measuring the tissue pressure in the compartment can aid in the
diagnosis. Normal tissue pressure is between 0 and 10 mm Hg. Permanent
nerve dysfunction can occur with tissue pressures as low as 30 mm
Hg for 6 to 8 hours. The tissue pressure may be measured by the
injection method of Whitesides and associates,34 the
wick catheter method of Owen and colleagues,35 or
the continuous infusion method of Matsen and colleagues.36,37
+++
Arterial Thrombosis
in the Drug Abuser
++
Extremity pain after drug injection can result from a number
of complications38 (Table 32-2). Intraarterial
injection of many agents can result in extremity pain and gangrene. The
theoretical mechanisms cited include (1) vasospasm, (2) norepinephrine
release, (3) intimal damage, (4) necrotizing arteritis, and (5)
particulate embolism. However, the final common pathway is arterial
thrombosis. Diluents used in street drugs (lactose, quinine, starch,
and talcum powder) compound the vascular insult.39
++
++
The diagnosis requires eliciting the appropriate history. For
example, with an intraarterial injection, patients may describe
a so-called hand trip that begins with a burning from the point
of insertion of the needle to the tip of the fingers.40,41 This
burning is followed immediately by blanching, severe pain, and cyanosis.
Addicts also use belts or other vigorous tourniquets for injections;
these inadvertently may be left on during the postinjection stupor
and further compromise the vascular supply. Pressure necrosis from
an abnormal posture after sedation may lead to muscle breakdown
and ischemia. Finally, the needle itself, which causes perivascular
hematomas, production of an intimal flap, or a false aneurysm, can
also lead to thrombosis.42
++
The so-called puffy hand syndrome results from widespread destruction
of lymphatic vessels and veins in an extremity used for injections.43,44 Extremity
drainage depends on the deep venous system after the superficial
lymphatic vessels and veins are destroyed. When perivascular injection
or hematomas compromise the deep venous system, swelling and venous
hypertension can lead to gangrene. The diagnosis of extremity pain in
drug abusers depends on the history and signs of acute ischemia.
Identification of the drug used may be helpful. Laboratory tests
that may be helpful include Doppler ultrasonography, digital temperature
readings, plethysmography, and angiography.
++
Mycotic aneurysms in the extremities can arise through several
recognized mechanisms.45,46,47,48
++
- 1. Septic embolization in the arterial lumen, such as
occurs with bacterial endocarditis, causes a gradual weakening of
the arterial wall, subsequent aneurysm formation, and enlargement
of the artery.49
- 2. Local spread from an abscess or area of cellulitis destroys
the arterial wall with resulting aneurysm formation.50
- 3. Trauma to an artery and subsequent contamination can cause
the formation of a mycotic aneurysm. This commonly occurs after
penetrating trauma, radiologic procedures, or inadvertent arterial
injection by drug abusers.51
++
Most mycotic aneurysms are arterial, rather than venous, because
the high pressure promotes dilation. Aneurysms that result from
repeated punctures of arteriovenous dialysis fistulas constitute an
exception to this rule. The venous punctures coupled with the high
venous pressure seen in these fistulas can cause aneurysm formation.
++
Patients with a history of rheumatic fever, intravenous drug
abuse, immunosuppression, prolonged illness, penetrating trauma,
and invasive radiologic procedures may develop mycotic aneurysms.
A warm, tender, palpable, pulsatile mass should alert the physician
to the diagnosis. A systolic bruit heard over the mass distinguishes
aneurysms from arteriovenous fistulas, which have both systolic
and diastolic components to their bruits. Signs and symptoms of
generalized sepsis also may be present. Occasionally, septic arthritis
or petechial skin lesions can develop from emboli originating in
the aneurysms. An arteriogram is a useful aid to confirm the diagnosis. Needle
aspiration also may be warranted.
++
Traumatic aneurysms are actually false aneurysms produced by
arterial penetration. The perivascular hematomas that result may
be classified as follows: (1) acute traumatic hematomas, in which
through-and-through disruption of the arterial wall leads to a gradual
enlarging hematoma contained by surrounding tissue; or (2) chronic
traumatic aneurysms, in which the perivascular hematoma is absorbed,
and a tissue sac and surrounding fibrosis provide boundaries.52,53
++
Traumatic aneurysms result from penetrating trauma, invasive
radiologic procedures, placement of intra-aortic balloon pumps,
vascular procedures, orthopedic reconstructive procedures, and internal
fixation of bones.53
++
The interval from initial insult to aneurysm detection is longer
than 1 month in more than 50% of cases. Affected patients
have a tender pulsatile mass near the course of the artery. As in
mycotic aneurysms, a systolic bruit is present. Occasionally, compression
by the expanding aneurysm leads to a secondary peripheral neuropathy
or venous occlusion. Suspected traumatic aneurysms in the extremity
can be evaluated using percutaneous angiography.
+++
Brachial Plexus
Lesions
++
Several anatomic relationships become important when referring
to brachial plexus disorders. The plexus is superficial in the supraclavicular
fossa and protected by skin, subcutaneous tissues, and fascia. Also,
the brachial plexus is in close proximity to the subclavian artery
in the fossa, and both structures lie near the apex of the lung.
More distally, the plexus lies close to the first and second parts
of the axillary artery, and a thick pad of fat and connective tissue
surrounds both. Therefore, many causes can lead to brachial plexus
neuropathies (Table 32-3). For example, traction on the upper cervical
roots when the shoulder is depressed forcibly and the head turned
to the opposite side can lead to neuropathy. Apical lesions of the
lung also may depress both the plexus and the vessels that run close
to it.
++
++
Generally, all lesions of the brachial plexus cause partial or
total paralysis of the shoulder. Any lesion involving the T1 root
or sympathetic trunk will be accompanied by Horner’s syndrome. Sensory
deficits will be combined with disturbances of sweating. Most plexus
lesions also have long-term complications54 (Table
32-4).
++
++
Plexus lesions can be classified based on anatomic location regardless
of their etiology. Superior plexus lesions (Duchenne-Erb) result
from damage to the fifth and sixth cervical roots. The deltoid,
biceps, brachioradialis, and brachialis muscles are affected. There
is an inability to abduct and externally rotate the shoulder and
an inability to flex the elbow or pronate the forearm. The arm hangs
loose, internally rotated, and the palm is visible from behind (so-called
porter’s-tip position). Sensory loss may be apparent over
the deltoid and radial side of the forearm. An isolated middle brachial
plexus lesion (C7) is unusual. It is manifested by sensory deficits
on the back of the forearm or the radial aspect of the dorsum of
the hand. Inferior plexus lesions (C8 to T1) include paralysis of
small hand muscles and finger flexors with preservation of finger
and wrist extensors. These lesions, therefore, result in hyperextension
at the metacarpophalangeal joints and flexion at the interphalangeal
joints. Horner’s syndrome may be seen. These inferior plexus
lesions may result from sudden upward pulling on the shoulder.
++
Lower plexus lesions are divided anatomically into three types.
Firstly, posterior cord lesions cause sensory deficits along the
distribution of the axillary and radial nerves, weakness of abduction
of the arm, and inability to extend the wrist or fingers. Secondly,
medial cord lesions cause weakness of the muscles innervated by
the ulnar nerve and medial head of the median nerve, thereby leading
to severe hand disability. Sensory deficits produce dysfunction
of the medial cutaneous nerve of the upper arm and forearm. Isolated
medial cord lesions are rare except after radiotherapy. Thirdly,
lateral cord lesions involve the lateral part of the median nerve
and musculocutaneous nerve, causing weakness of flexion and pronation
of the forearm, wrist, and fingers. Sensory loss is limited to the
radial aspect of the forearm (Table 32-5).
++
++
Because of its superficial position in the supraclavicular fossa,
the brachial plexus can be susceptible to traction and exogenous
compression. Upper brachial plexus injuries have been reported in laborers
who carry heavy loads on their shoulders and U.S. football players.
Paralysis from the heavy backpacks carried by soldiers (so-called
rucksack paralysis) has been recognized since World War 11.55–57 The
whole plexus (usually on the nondominant side) is affected initially.
However, soon only the upper plexus lesions remain, and it is common
to see involvement of the nerve to the serratus anterior with winging
of the scapula.
++
Hematomas after anticoagulation or percutaneous axillary artery
cannulation may lead to plexus injuries.58,59 Of
special concern to physicians are brachial plexus injuries occurring
during general anesthesia. There are three causes. Firstly, shoulder
braces may be placed too far medially near the posterior triangle,
injuring the plexus before it descends behind the clavicle. Secondly,
if the arm is abducted to 90 degrees or more, the head of the humerus
descends into the axilla and presses into the plexus as it passes
from the supraclavicular area to the axilla. Thirdly, excessive depression
of the shoulder girdle with the patient in the Trendelenburg position
can stretch the upper roots of the brachial plexus.60,61
++
Vascular insufficiency is a rare cause of brachial plexus injury,
but may occur after acute axillary artery occlusions secondary to
emboli. Intravenous injection of contaminated heroin can lead to
a painless paresis of muscles supplied by the posterior and medial
cord.62 Radiotherapy to the clavicular region or
axilla can injure the brachial plexus. Distinguishing radiation
injury from direct tumor infiltration can be difficult. Post-radiation
intervals shorter than 3 months or longer than 5 years favor metastases.
Intense pain, lower plexus lesions, and Horner’s syndrome
also favor metastases. Skin changes, lymphedema of the extremity,
induration over the supraclavicular fossa, and upper plexus lesions
favor radiotherapy as the source of the neuropathy. Paresthesias frequently
can be elicited by tapping the supraclavicular fossa after radiation-induced
lesions63,64 (Table 32-6).
++
+++
Inherited Brachial
Plexus Neuropathy
++
A form of recurrent brachial plexus neuropathy can display familial
predilection.65–69 It is similar to neuralgic
amyotrophy except for several distinguishing features. In contrast
to neuralgic amyotrophy, the familial form of brachial plexus neuropathy
is characterized by recurrent episodes over several years separated
by intervals of full recovery. Both diseases occur most commonly
during the third and fourth decades of life, but in the familial
form, affected patients may have their first attacks during the
first decade of life. The familial form does not seem to be precipitated
as commonly by infections as is neuralgic amyotrophy. However, several
authors have reported a dramatic onset of attacks in women several
hours after childbirth.67,70 There may be minor
dysmorphic features (e.g., hypotelorism, epicanthic folds, and cleft
palate) associated with the familial form of the disease.67 Finally,
there is nerve involvement outside the brachial plexus with such
diverse manifestations as Horner’s syndrome, Bell’s
palsy, and lumbosacral weakness in the familial form of the disease.
++
Pain is the initial manifestation of a familial attack. It is
described as sharp and burning, particularly in the shoulder. Movement
exacerbates the pain; therefore, affected patients keep their shoulders
immobile. Weakness soon follows, and although any muscles controlled
by the plexus may be involved, those innervated by the upper trunk
of the plexus generally are affected. Sensory dysfunction is not
a prominent feature. Affected patients usually have an excellent
recovery of strength, but they may accumulate deficits after multiple
attacks.68
+++
Guillain-Barré Syndrome
++
Guillain-Barré syndrome occurs worldwide, with an incidence
of 1 to 1.5 cases per 100,000 persons annually. There is no age
or gender preference; 60% to 70% of cases are
preceded by an upper respiratory or gastrointestinal illness 1 to
3 weeks before the onset of the syndrome.71 An
ascending weakness involving both proximal and distal muscles distinguishes
Guillain-Barré syndrome. The weakness generally begins
in the lower extremities and then can progress to upper extremity,
intercostal, and neck muscles. Affected patients also have decreased
sensation and possibly transient autonomic dysfunction.
++
Pain occurs in one third of the cases of Guillain-Barré syndrome
as a result of involvement of the posterior roots. There may be
tenderness after deep pressure on the muscles. Paresthesias are common.
Affected patients also describe a burning, radiating pain.
++
The clinical diagnosis is aided by examination of cerebrospinal
fluid. Normal pressures, increased protein, and acellular fluid
are found. Nerve conduction studies show slowing after the paralysis begins.72 A
syndrome identical to Guillain-Barré can occur after infectious
mononucleosis.
+++
Fabry’s
Disease (Angiokeratoma Corporis Diffusum)
++
Fabry’s disease is an X-linked recessive disorder characterized
by accumulation of a lipid, ceramide trihexoside, in many organs.
Patients are young boys or men with intense burning pain in their feet
and lower legs.73
++
The enzymatic defect in Fabry’s disease is a deficiency
of the enzyme ceramide trihexosidase; the terminal molecule of galactose
is missing from this enzyme.74 Stored glycolipid
accumulates in different organ systems. Renal involvement initially
is characterized by albuminuria and inability to concentrate urine,
which progresses to uremia. Glycolipid accumulates in the endothelial
cells of the glomeruli and distal tubular cells. The first manifestations
of this disease, angiokeratomas, are found over the perineum, upper
thighs, and buttocks. Less commonly, they may be seen on the lip
and oral mucosa.75
++
The vascular elements that supply the ganglions of the peripheral
nervous system accumulate the lipid. The ganglion cells themselves
and the perineural cells may contain the storage material, possibly
causing the anhidrosis and pain that are features of this disease.76
++
Other systems that accumulate glycolipid include the eye, liver,
and reticuloendothelial system. The diagnosis can be confirmed by
enzyme assays done on biopsy specimens of small intestinal mucosa.74 Tissue α-galactosidase
activity is decreased in patients with Fabry’s disease.
+++
Compression
Neuropathies
++
Compression neuropathies are caused by pressure damage to peripheral
nerves. The pressure may be external (a brace or cast), or the nerves
may be compressed by adjacent body tissues (tumors, muscle, or synovial
thickening). Entrapment neuropathies occur at sites where the nerves
normally would be somewhat confined (Table 32-7).
++
++
Three degrees of compression neuropathy can be described: neurapraxia,
axonotmesis, and neurotmesis. In neurapraxia, functional impairment
without axonal structural loss can recover in days to weeks by removing
the inciting compressing stimulus. In axonotmesis, wallerian degeneration follows
axonal loss and functional restoration may occur only after axonal
regeneration, which takes months or years. In neurotmesis, severance
of the entire nerve and supporting connective tissue occurs. Such
injuries spontaneously regenerate poorly, if at all.
++
Individual peripheral nerves are more susceptible to compression
when already involved by disease states associated with generalized
peripheral neuropathies (e.g., diabetes mellitus, renal failure,
or alcoholism).77,78 Affected patients have symptoms
of sensory nerve dysfunction. Paresthesias and numbness usually
are confined to the cutaneous distribution of the nerve. Pain can
occur at rest and is localized, but may be referred to other sites.
++
Electrophysiologic studies can help localize and assess these
neuropathies.79 Nerve conduction studies may reveal
(1) slowing of conduction secondary to focal demyelination, (2)
reduced amplitudes of both sensory action potentials and compound
muscle potentials secondary to axonal damage, and (3) the presence
of a generalized polyneuropathy. Electromyographic studies may show
(1) denervation potentials in the muscle secondary to anterior horn
cell loss, and (2) motor unit potential variation secondary to reinnervation
of the muscle by axons. Computed tomography (CT) scans and radiography
may reveal bone or joint abnormalities responsible for compression.80
+++
Ulnar Nerve
Syndromes
++
The ulnar nerve derives from the C7, C8, and T1 roots. It courses
medially in the upper arm without giving off any branches. At the
elbow, it lies behind the medial epicondyle in the ulnar groove.
It then descends under a roof formed by the aponeurosis of the flexor
carpi ulnaris muscle in the cubital tunnel. Motor branches arise
in the cubital tunnel and supply the flexor carpi ulnaris. The nerve
then gives off branches to the flexor digitorum profundus of the
fourth and fifth digits. The palmar cutaneous branch arises and
supplies the hypothenar region. More distally, the dorsal cutaneous
branch arises and innervates the medial half of the back of the
hand and half of the fourth and fifth digits. The nerve enters the
hand superficial to the flexor retinaculum and runs between the
hook of the hamate and pisiform bone into Guyon’s canal,
where it bifurcates and gives rise to a superficial terminal branch
and deep motor branch that supplies the hypothenar muscles, third
and fourth lumbricales, adductor pollicis, and all the interossei.
+++
Compression
above the Elbow and at the Elbow
++
The elbow is the most common site of ulnar nerve entrapment,
particularly in the condylar groove and cubital tunnel. The nerve
lies superficially in the groove and is susceptible to compression
by leaning on the elbow or improper arm positioning during general
anesthesia. Deformities from injuries to the elbow can cause the
ulnar nerve to stretch, with a neuropathy appearing long after the
actual time of injury (so-called tardy ulnar palsy).81 The
ulnar nerve also may be compressed in the cubital tunnel (so-called
idiopathic cubital tunnel syndrome); this may be caused by prolonged
flexion tightening of the aponeurosis at the proximal end of the
tunnel.82,83
++
Ulnar nerve injuries during anesthesia may result when the patient’s
arm is adducted along the side of the body and the hand supinated.
The patient’s elbow may slip out of the restraints, and with
the ulnar groove located posteromedially, the edge of the table
may compress the nerve. Pronating the forearm will rotate the ulnar
groove more posteriorly and laterally and prevent compression by
the table or equipment rail.84 Patients with entrapment
neuropathies at or above the elbows may have pain at the elbow,
which may spread to other parts of the arm. Tingling and numbness
along the medial portion of the palm and the fourth and fifth digits
also occurs. Muscle wasting is prominent in the hypothenar eminence,
and affected patients have weakness of the interossei. Severe ulnar
neuropathy at the elbow results in a so-called claw-hand deformity.
Proximal ulnar entrapment is characterized by weakness of the flexor
carpi ulnaris and flexor digitorum profundus muscles; this distinguishes
it from more distal entrapments.
+++
Ulnar Nerve
Compression in the Wrist or Hand
++
Ulnar nerve compression in the wrist or hand may result in intermittent
paresthesias along the volar aspect of the fifth digit and half
or all the volar aspect of the ring finger.85 The
sensory branch of the ulnar nerve to the hand courses through Guyon’s
canal encased by fibrous tissue. Repetitive trauma to the area (e.g.,
striking a stapler) can lead to compression. Other causes include
pressure from a wristwatch band or overuse of the flexor carpi ulnaris. Finally,
space-occupying lesions (e.g., ganglions or lipomas), thrombosis
of the ulnar artery, or a rapid weight gain may cause nerve compression
at the edge of Guyon’s canal.
+++
Radial Nerve
Syndromes
++
The radial nerve receives contributions from the C5 to T1 roots.
It spirals around the shaft of the humerus in the spiral groove
and descends along the lateral aspect of the humerus superficially.
It passes distally in front of the lateral epicondyle and divides
into the deep motor nerve (posterior interosseous nerve) and superficial
radial nerves variably 4 to 5 cm above or below the lateral epicondyle.
The deep motor branch (posterior interosseous nerve) passes into
the supinator muscle through the arcade of Frohse and finally supplies
the extensor muscles of the digits. The superficial radial nerve
passes over the supinator and pronator teres muscles along the lateral
forearm and supplies sensation to the dorsal aspect of the hand,
the thumb, and adjacent fingers.
++
The radial nerve may be compressed in the axilla secondary to
the misuse of crutches. Along with the signs and symptoms described
subsequently for more distal radial neuropathies, these patients characteristically
have triceps weakness.
++
Most radial nerve compressions occur between the mid to upper
arm and elbow, where the nerve courses laterally around the spiral
groove and then passes superficially along the humerus. Improper
positioning of the arm during sleep or intoxication (so-called Saturday-night
palsy) results in involvement of the extensors of the wrist and
fingers and the brachioradialis muscles, with resultant wrist drop
and associated variable sensory disturbances.86 Misuse
of tourniquets, external pressure from ether screens and Mayo stands,
and failure to pad the dependent arm when a patient is in the lateral
decubitus position can produce a radial nerve palsy during anesthesia.
Fractures of the shaft of the humerus with callus formation may
compress the nerve and cause a neuropathy.
++
The posterior interosseous nerve (deep motor branch) can be compressed
in the radial tunnel between the superficial and deep heads of the
supinator. Radial tunnel syndrome is characterized by deep aching
pain of the extensor supinator muscles in the dorsal forearm. Affected
patients are unable to extend their thumbs and fingers at the metacarpophalangeal
joints and cannot deviate their hands in the ulnar direction. Superficial
radial nerve compressions can be caused by wearing handcuffs or
watchbands or by fractures of the radius. Affected patients feel
pain and paresthesias on the dorsum of the thumb and index finger.
+++
Median Nerve
Syndromes
++
The median nerve receives contributions from the C5 to T1 roots.
It courses medially in the upper arm where it gives off no branches.
The nerve crosses the elbow anteriorly and passes between the two
heads of the pronator teres. It then passes deep to the tendon (so-called
subliminis bridge) and runs distally between the flexor digitorum
profundus muscles and flexor digitorum superficialis muscles. Motor
nerves branch off before the median nerve passes between the pronator
teres, the muscles responsible for wrist and finger flexion. A purely
motor branch, the anterior interosseous nerve, is given off just
after the median nerve emerges from the pronator teres. It innervates
the flexor digitorum profundus to the second and third digits. The
median nerve passes under the flexor retinaculum at the wrist and
innervates the first two lumbrical muscles and the adductor pollicis
brevis. The digital nerves then provide sensory innervation to the
distal palm and palmar surfaces of the first through fourth digits.
+++
Compression
in the Carpal Tunnel
++
Compression of the median nerve in the carpal tunnel is the most
common compression neuropathy of the upper extremity.87 Women
between the ages of 40 and 60 years are affected predominantly.
Any condition that reduces the capacity of the carpal tunnel can
precipitate the symptoms.88 These conditions include
(1) fractures, (2) ganglions, (3) xanthomas, and (4) synovial disorders. Systemic
conditions predisposing to carpal tunnel syndrome include (1) obesity,
(2) pregnancy, (3) hypothyroidism, (4) acromegaly, (5) myeloma,
(6) amyloidosis, (7) Raynaud’s disease, (8) chronic renal
failure, and (9) diabetes mellitus.
++
Paresthesias and pain occurring during sleep characterize the
syndrome. The paresthesias usually are localized to the palmar aspects
of the fingers and hands. These patients, however, may complain
of wrist and forearm pain. The paresthesias and pain are aggravated
by repeated wrist and finger flexion. Affected patients also may
feel clumsy and have hand weakness. The symptoms usually begin in
the dominant hand, although in more than half of the cases, the
disorder is bilateral.89
++
Physical examination reveals decreased sensation over the palmar
aspect of the thumb through the ring finger. Atrophy of the thenar
muscles can occur as a late sign of median neuropathy. Tinel’s sign
and Phalen’s test help make the diagnosis. Tinel’s
sign refers to distal paresthesias elicited by percussion of the
median nerve either proximal to the flexor retinaculum in the wrist
or distally at the base of the palm. Phalen’s test is performed
by applying a tourniquet to the arm at 60 mm Hg pressure.90 The
venous congestion will elicit paresthesias in patients with carpal
tunnel syndrome. Alternatively, acute flexion of the wrist for 60
seconds will accomplish the same goal.
+++
Median Nerve
Compression Proximal to the Carpal Tunnel
++
The median nerve may be compressed proximally, too. For example,
compression in the axilla may result from the misuse of crutches.
The pronator syndrome, which may appear spontaneously or be caused
by excessive forearm pronation (e.g., in tennis players), results
from median nerve entrapment between the two heads of the pronator
teres.91 These patients have unlocalized forearm
pain combined with numbness in the fingers innervated by the median
nerve.92 Anterior interosseous syndrome is caused
by damage to this purely motor branch from fractures or fibrous
band compression. Affected patients have proximal forearm pain that
increases with exercise.93
++
Diagnostically, these proximal nerve compressions can be distinguished
from carpal tunnel syndrome by the characteristic weakness of the
flexor digitorum muscles and flexor pollicis longus. These patients
are asked to oppose the tip of the thumb to the second digit and
are unable to flex both distal phalanges (so-called circle test).
Weakness of pronation also is characteristic of proximal median
nerve entrapment.93,94
+++
Digital Nerve
Compression of the Thumb and Fingers
++
So-called bowler’s thumb is caused by constant irritation
of the digital nerve at the thumb. Perineural fibrosis and painful
nodule formation results. So-called harp player’s thumb
is caused by strumming musical instruments; painful nodules or hypersensitivity
to touch may occur.
++
The suprascapular nerve is a purely motor nerve arising from
the upper branch of the brachial plexus. It runs under the trapezius
muscle through a notch on the upper border of the scapula and supplies
the supraspinatus and infraspinatus muscles.
++
Damage to the scapula may injure the nerve to produce a syndrome
characterized by weakness confined to spinatus muscles without sensory
loss. Affected patients have pain after shoulder abduction.95,96 Tenderness
may be elicited by palpating the suprascapular notch. Needle electromyography (EMG)
shows denervation of the spinatus muscles.
+++
Femoral Nerve
Entrapment Syndrome
++
The femoral nerve is formed from the posterior branches of L2
to L4 behind the psoas muscle. It then courses around the lateral
wall of the psoas muscle into the iliacus compartment located between
the psoas and iliacus muscles and covered by the iliacus fascia.
It then gives off branches that supply the quadriceps and sensation
to the anterior thigh. The nerve terminates as the saphenous nerve,
which supplies sensation to the skin on the medial aspect of the
leg.
++
Femoral neuropathy leads to wasting of the quadriceps muscles
and sensory disturbances over the anteromedial aspect of the thigh
and medial aspect of the lower leg. The patellar reflex also is diminished
or absent.
++
Diabetes is the most common cause of femoral neuropathy.97 Other
causes include injury of the nerve beneath the inguinal ligament
as a result of scar tissue or prolonged lithotomy position98 and
compression of the nerve in the iliacus compartment from hematomas
secondary to trauma or anticoagulants.99
++
Femoral neuropathy must be differentiated from L3 to L4 radiculopathy.
EMG studies can help determine whether motor dysfunction is confined
to the femoral nerve distribution. CT scans and radiographs of the
lumbosacral spine may help exclude disk disease.
+++
Meralgia Paresthetica
or Lateral Femoral Cutaneous Nerve Entrapment (Roth’s Disease
or Bernhardt’s Disease)
++
The lateral femoral cutaneous nerve, which supplies the anterolateral
aspect of the thigh, is a purely sensory nerve formed from the posterior
division of the L2 and L3 roots. The nerve emerges along the lateral
border of the psoas muscle and courses peripherally around the pelvis between
the iliac muscle and its overlying fascia (Fig. 32-1). The nerve
then descends under the lateral aspect of the inguinal ligament
to the anterior-superior iliac spine; finally, it runs beneath the
deep fascia and subcutaneous tissue of the upper thigh.100 The
nerve divides into anterior and posterior branches, which supply
the anterolateral and posterior aspect of the thigh, respectively.
Affected patients have burning pain and dysesthesias along the lateral
aspect of the thigh, which are exacerbated by prolonged walking
or standing.
++
++
The most common site of lateral femoral cutaneous nerve entrapment
occurs as the nerve passes from the pelvis into the thigh.101 Thus,
pressure from belts, girdles, and tight pants is cited as a precipitating
cause. Also, direct trauma to the area of the anterior-superior
iliac spine can lead to increased tension on the nerve. The diagnosis
can be confirmed by blocking the nerve with a local anesthetic.
A wheal is raised medially and inferiorly to the anterior-superior
iliac spine. After the fascia above the inguinal ligament is pierced,
10 to 12 mL of a local anesthetic are injected in a fanlike distribution.
+++
Sciatic Nerve
Syndromes
++
Two distinct nerves, the tibial and common peroneal, comprise
the sciatic nerve. The latter arises from the posterior divisions
of L4, L5, S1, and S2. The former arises from the anterior divisions of
L4 and L5, and S1 to S3. The sciatic nerve leaves the pelvis through
the sciatic notch below the piriformis muscle, where it may be compressed
by masses. Then it courses between the greater trochanter and ischial
tuberosity covered by the gluteus maximus muscle and hamstrings.
The fact that the superior and inferior gluteal nerves and posterior
cutaneous nerve of the thigh pass with the sciatic nerve through
the notch can help to localize sites of sciatic compression.
++
Aside from penetrating trauma, most injuries to the sciatic nerve
occur as a result of fracture dislocations of the hip joint and
hip arthroplasty. Deep injections into the buttock may directly
injure the nerve or cause muscle fibrosis that compresses the nerve.102 Masses,
such as endometriomas, may compress the nerve at the sciatic notch.103 In
addition to the buttock pain and paresthesias along the back of
the leg, a sciatic nerve injury can cause foot drop, impaired hip
extension, and decreased sensation over the lateral leg and foot.
++
Piriformis syndrome is caused by spasm or scarring of the piriformis
muscle. Affected patients have symptoms similar to “sciatica,” such
as buttock pain and burning dysesthesias down the back of the leg.104,105
++
The common peroneal nerve diverges from the tibial nerve in the
upper popliteal fossa and passes laterally to the head of the fibula,
close to the median margin of the tendon of the biceps femoris. Then
it passes superficially to the neck of the fibula. Distal to this,
it divides into the superficial peroneal nerve (musculocutaneous
nerve) and the deep peroneal nerve. The superficial peroneal nerve
courses along the shaft of the fibula with the peroneal muscles
that it supplies. Its cutaneous nerve innervates the skin of the
lateral and distal portion of the lower leg and the dorsal aspect
of the foot. The deep peroneal nerve descends in the anterior compartment
of the leg and supplies the tibialis anterior, extensor hallucis
longus, and extensor digitorum brevis muscles in the foot.
++
The common peroneal nerve may be compressed near the neck of
the fibula during general anesthesia or coma. Less common causes
include prolonged squatting106 or crossing of the
legs.107 The nerve also may be compressed by ganglions
or cysts in the knee joint. Affected patients have foot drop and
sensory deficits over the anterolateral aspect of the lower leg
and dorsum of the foot (Fig. 32-2).
++
++
Anterior tibial syndrome involves compression of the deep peroneal
nerve caused by muscle swelling in the anterior compartment of the
leg. These patients have exquisite anterior lower leg pain and motor
dysfunction. The syndrome may occur after trauma, reperfusion after
arterial occlusion, or excessive exercise.
++
Tibial nerve syndromes involve the tibial nerve, which branches
from the sciatic nerve, descends through the popliteal fossa, and
passes deep between the heads of the gastrocnemius muscle, which
it supplies. The nerve becomes superficial along the medial aspect
of the ankle and passes under the flexor retinaculum into the foot.
The flexor retinaculum forms the roof of the tarsal tunnel. Distal
to this site, the tibial nerve divides into plantar nerves and sensory
branches that supply the sole of the heel. The plantar nerve innervates
motor and sensory elements of the anterior two thirds of the sole.
The sural nerve leaves the tibial nerve in the popliteal fossa and
descends in the middle of the calf to supply the skin over the lateral
aspect of the ankle.
++
Compression of the distal part of the tibial nerve or two plantar
nerves can cause diffuse foot pain and paresthesias in the sole
of the foot. Weakness of foot muscles may be noticed, and physical examination
shows plantar nerve sensory abnormalities. Compression or palpation
over the medial aspect of the Achilles tendon may elicit pain and
paresthesias. This syndrome is called the tarsal tunnel syndrome,
and it can result from ill-fitting footwear or compression by tendon sheaths.108,109
++
Morton’s neuroma (or neuralgia) is caused by compression
of the interdigital nerves by adjacent metatarsal heads (generally
between the third and fourth toes). The pain radiates from the site
of the neuroma into the toes. Initially, the pain occurs while walking,
but eventually it becomes continuous.
++
Sural neuropathy causes paresthesias and pain over the lateral
aspect of the ankle and foot. This results from prolonged pressure
over the posterior lower calf.110
+++
Complex Regional
Pain Syndrome
++
++
In 1994, the International Association for the Study of Pain
(IASP) recommended two important changes in the taxonomic classification
of pain to reflect more accurately current understanding of the
entities. For example, the constellation of signs and symptoms eliciting
the diagnosis of reflex sympathetic dystrophy seemed to imply an
underlying mechanism, which investigations have so far failed to
support. Hence, the terms complex regional pain syndrome (CRPS),
types 1 and 2, have replaced reflex sympathetic dystrophy and causalgia,
respectively. At one time, clinicians made the diagnosis of CRPS
only if a trial of sympathetic blockade ameliorated the pain. Subsequently,
it has been discovered that the role of the sympathetic nervous
system may vary during the natural course of the chronic pain syndrome.
For example, in some patients, early sympatholysis may obliterate
the perceived pain, whereas the same intervention later in the course
of the disease fails to produce a positive response. Hence, for
the same CRPS, a period of sympathetically maintained pain may be
followed by a phase of sympathetically independent pain.
++
Normally, injury stimulates afferent sensory fibers that travel
to the dorsal root ganglia and synapse in the posterior horn of
the spinal cord. The impulse is relayed as well to sympathetic neurons
in the lateral columns, which send efferent impulses through the
anterior root. After synapsing in the sympathetic ganglion, these
efferent signals can mediate vasoconstriction in the affected extremity.
Over time, however, the role of the sympathetic nervous systems
becomes less clear.111
++
Pain, swelling, discoloration, and stiffness comprise the four
major hallmarks of CRPS. Patients commonly experience constant pain,
which has a burning, cramping, or cutting quality. Passive motion
of the extremity aggravates the pain. Hyperpathia and tenderness
elicited over the joints commonly develop. Swelling often begins
at the point of initial trauma and initially feels soft. Eventually
it can involve the whole extremity and usually becomes firm. Skin
tone changes from red to white as early capillary vasodilation gives
way to later vasoconstriction. Stiffness results from the combination
of increased swelling and disuse because of the intense pain caused
by motion.112 As the disease progresses, fibrosis
of ligamentous structures and adhesion formation further limit joint
motion. Forearm and shoulder motion are limited to a much greater
extent than elbow motion.
++
Affected patients also have other signs and symptoms, such as
cool skin and positive responses to cold and the ice-water immersion
test, and there is decreased skin temperature in the affected extremity.
Trophic skin changes may be seen as tight, shiny skin. Later features
include atrophy of subcutaneous tissue producing tight, shiny skin
and tapering of the pulp area of the fingers (the so-called pencil-pointing
sign).
++
CRPS, type 2 (causalgia), was first described in 1864 among Union
soldiers when gunshot wounds to extremities directly injured peripheral
nerves. A so-called major form involved proximal nerve injury with
resultant pain in the entire extremity.113,114 Minor
causalgia involved injury to distal sensory nerves and is generally
confined to one or several fingers.
+++
Hypothyroid
Neuropathy
++
The peripheral nervous system manifestations of myxedema are
well described. Affected patients may have either mononeuropathy
or polyneuropathy.
++
The most common mononeuropathy involves compression of the median
nerve as it passes through the carpal tunnel at the wrist. With
myxedema, the extracellular tissue in the perineurium, endoneurium,
and tendons acquires increased amounts of acid mucopolysaccharides.
These attract fluid and diminish the available space for nerve in
the carpal tunnel.115
++
The extremity pain associated with the polyneuropathy of hypothyroidism
has two distinct origins: (1) skeletal muscle, and (2) peripheral
nerve. In the first case, affected patients may have edema of the
skeletal muscle that is manifested as cramping.116 Prolonged
relaxation and contraction times produce slowed movement. Patients
display proximal weakness. The relaxed muscles feel firmer and larger
than normal. In the second case, distal extremity pain has a neuropathic
origin marked by slowed conduction velocity, decreased tendon reflexes,
dysesthesias, and sensory deficits.
++
A distinct type of muscle cramping has been noticed in patients
with both hypo- and hyperthyroidism. These patients experience an
undulatory muscular twitching, or so-called myokymia, which may
be produced by repetitive discharges from many single motor nerve
fibers. The cramping is accompanied by excessive sweating.117
+++
Neuropathy in
Acromegaly
++
Patients with acromegaly may have intense pain and tingling in
their extremities as a result of hypertrophic neuropathy.118 In
addition, bilateral carpal tunnel syndrome has been reported to
be associated with acromegaly.119 Presumably, the
overabundance of growth hormone causes proliferation of the connective
tissue and synovium, diminishing the available space in the carpal
tunnel. Hypertrophic connective tissue also may compress axons,
resulting in sensorimotor disturbances.
+++
Thoracic Outlet
Syndrome
++
Thoracic outlet syndrome results from compression or irritation
of the brachial plexus and subclavian vessels as they pass through
the costoclavicular space and thoracic outlet.120,121 Actual compression
of the plexus accounts for the symptoms in most patients. Therefore,
the disease probably should be viewed as a neuropathy122 (Fig.
32-3). The syndrome primarily affects young and middle-aged women.
The history is essential to separate thoracic outlet syndrome from
other causes of upper extremity pain, such as carpal tunnel syndrome
and cervical disc disease123 (Table 32-8). The
symptoms may occur spontaneously or after trauma124 to
the shoulder and neck, resulting in chronic muscle spasms.124,125 The
pain initially is unilateral and intermittent, but it increases
in severity and frequency with time. It begins over the anterior
and posterior shoulder region and radiates down the lateral arm
to the hand. The pain also may radiate up the back of the neck to
the mastoid and occipital region of the skull and cause severe headaches.
Paresthesias accompany the pain, and because the compression typically
involves C8 to T1 of the plexus, affected patients localize their
numbness and tingling to the ulnar nerve distribution.
++
++
++
A striking feature of the history is that elevating the arm and
increased arm activity can initiate or aggravate the symptoms. Muscle
cramping, per se, is not a feature of the syndrome. The hands may
or may not show increased sensitivity to cold.
++
Frank arterial occlusion rarely, if ever, accounts for the signs
and symptoms of thoracic outlet syndrome. Exertion, which can cause
cyanosis and edema of the extremity, may produce subclavian vein
thrombosis126 (the so-called effort thrombotic
syndrome of Paget and Schroetter). The physical examination should
include blood pressure measurement in both arms to identify any
differences. Muscle atrophy of ulnar-innervated interosseous muscles
can be assessed by an interphalangeal card test or by spreading
the digits against resistance. Triceps strength may be diminished.
Bruits may be heard over the supraclavicular fossa. Moderate pressure
over the supraclavicular fossa for 15 seconds may reproduce the
symptoms. The reflexes generally are normal. Pinprick sensation
may be diminished over the C8 to T1 dermatome.
++
Several maneuvers that have questionable diagnostic value should
be mentioned.127 Adson’s maneuver consists
of monitoring the radial pulse while patients take deep breaths, extend
their necks, and then turn their chin toward the affected side.
A decrease or disappearance of the pulse is a positive test result.
A bruit may be heard over the supraclavicular area using this maneuver.
The deep breath elevates the first rib, and turning the neck narrows
the interscalene triangle. The costoclavicular compressive maneuver
consists of monitoring the radial pulse while the patient throws
back the shoulders and presses them downward. A positive test result
is a decrease or disappearance of the radial pulse with or without
a bruit. This maneuver compresses the subclavian artery between
the clavicle and the first rib.
++
By contrast, the elevated-arm stress test described by Roos125 seems
to have some diagnostic value. This test involves a 90-degree abduction
and external rotation of the arms. The patient is then instructed
to open and close the hands for 3 minutes. A reproduction of symptoms
of the thoracic outlet syndrome constitutes a positive test result.
++
In addition to the history and physical examination, some other
tests should be discussed when diagnosing thoracic outlet syndrome.
Although thoracic outlet syndrome can be considered an ulnar neuropathy,
the actual irritation of the plexus is intermittent and rarely results
in neuropathic changes. Hence, nerve conduction studies generally
are not useful.128,129 Also, because the C8 to
T1 part of the plexus is both inferior and deep, stimulation would
be difficult technically. Only a small minority of patients with
thoracic outlet syndrome has disease that involves subclavian arterial
compression; therefore, angiograms generally are not indicated.
The two exceptions to this rule are when there is (1) a large differential
blood pressure between the arms, or (2) interest in excluding a
subclavian artery aneurysm. Cervical spine films generally are valuable
in patients with thoracic outlet syndrome to exclude any coexisting
cervical disc disease.
+++
Cervical Disc
Disease
++
++
Cervical disc disease is another common cause of neck, shoulder,
and arm pain. The root or cord compression may result from ruptured
disc material or a degenerative osteophytic lesion. The radiculopathy
usually involves, in descending order, C7, C6, C5, and C8. The symptoms
may occur after trauma or sudden hyperextension.130,131
++
One common syndrome involving lateral disc lesions between C5
and C6 includes pain felt at the trapezium ridge, tip of the shoulder,
radial forearm, and thumb. Affected patients have sensory loss and
paresthesias in the same distribution. Unilateral paracervical muscle
spasm is present. The patient may experience biceps tenderness in
the supraclavicular regions, motor deficit, and loss of deep tendon
reflex. The patient has a secondary weakness after forearm flexion.
++
Another common syndrome is caused by lateral protrusion between
the sixth and seventh cervical vertebrae, with involvement of the
seventh cervical root. The pain occurs in the shoulder and radiates
down the elbow and dorsal forearm to the index and middle fingers.
There is tenderness over the third and fourth thoracic spinous processes
and the triceps region. The patient has sensory deficits and paresthesias
in the second and third fingers. Physical examination shows an absent
triceps reflex, with weakness in forearm extension, wrist extension,
and hand grip Regardless of the cervical root involved, affected
patients relate a history of chronic sharp pain. Events such as coughing
or sneezing tend to exaggerate the pain. Most changes in head position
(particularly hyperextension) intensify the pain. On examination,
turning the head to one side and hyperextending the neck produce
neck pain and characteristic radicular paresthesias (Table 32-9).
++
++
Neuralgic amyotrophy is a syndrome characterized by the acute
onset of shoulder pain, which can be severe or aching. Although
it frequently affects the shoulder alone, it may also involve the
arm, neck, and back. The pain is worse at night and intensifies
with movement.132 The syndrome involves mostly
the right side, but almost 25% of cases are bilateral.
++
Proximal motor weakness in the shoulder and arms, particularly
affecting the muscles innervated by the axillary and suprascapular
nerves, follows the pain at varying intervals.133 Complete
limb paralysis is rare. Pain relief often occurs after resting the
limb with the elbow flexed and the shoulder adducted; however, this
may aggravate the weakness. Sensory involvement is not a characteristic
feature of this syndrome. The cause remains unknown. However, a brachial
neuritis similar to neuralgic amyotrophy may appear after serum
inoculations or infections caused by influenza, typhus, or variola
viruses.
++
The diagnosis depends on obtaining a history consistent with
neuralgic amyotrophy. The physical diagnosis is aided by eliciting
pain after arm abduction, external rotation at the shoulder, and
then extension of the elbow (the so-called flexion-adduction sign
described by Waxman).134 EMG studies show a peripheral
plexus lesion with normal spinal roots.135
+++
Neuropathy of
Serum Sickness
++
Before the age of antibiotics, bacterial infections often were
treated with large volumes of horse or rabbit antisera. The serum
sickness that patients developed occasionally was accompanied by neuropathy,
usually of the brachial plexus.136 Heterologous
serum rarely is used today, but neuropathies still may occur as
a sequela of typhoid or paratyphoid vaccinations or from drugs that form
complexes with serum proteins.137
++
The usual clinical features of serum sickness (e.g., lymph node
swelling, joint pain, myalgias, and albuminuria) generally are present
when the neuropathy appears. There is no relationship between the
amount of serum given, the severity of systemic manifestations,
and the development of neuropathy.
++
Pain onset occurs suddenly. It generally starts in the shoulder
girdle or upper arm. The pain should be distinguished from more
typical myalgic or arthritic types seen during serum sickness in
other joints and muscles. Physical examination may reveal tenderness
over the brachial plexus. Weakness involving the shoulder muscles
soon follows the onset of pain, and affected patients may be paralyzed
totally and have striking atrophy. The reflexes also are decreased
or absent, and vasomotor changes may appear. Sensory signs are not
prominent, a feature that is found in other brachial neuropathies.
The radial nerve is a less common site of involvement.
++
The pathologic basis of the neuropathy of serum sickness seems
to be that immune-complex deposition causes vasculitis and perivascular
edema. This, in turn, leads to edema of the nerves. This swelling
impinges on the nerves as they exit from the foramina. If the swelling
progresses, it may compromise flow further and lead to frank necrosis
of the nerves, which explains why severe lancinating pain can be
such a prominent feature of this neuropathy.136,137
+++
Neuropathy in
Connective Tissue Diseases
++
Peripheral neuropathy may occur in conjunction with various connective
tissue diseases. The clinical manifestations and histopathologic
findings are similar regardless of the disease. The pathogenic lesion
is arteritis involving the small nutrient arteries of the nerves.
Thus, it is described as an angiopathic neuropathy that occurs with
varying frequencies in rheumatoid arthritis, polyarteritis nodosa,
Churg-Strauss vasculitis, systemic lupus erythematosus, and giant
cell arteritis.138
++
Patients with rheumatoid arthritis and peripheral neuropathy
have certain distinguishing features. Firstly, they usually have
had rheumatoid arthritis for an average of 10 years before the onset
of neuropathy. Secondly, rheumatoid nodules and destructive joint
changes are present. Thirdly, elevated titers of rheumatoid factor
are common.139 Fourthly, these patients have other
complications of arteritis (such as nail-bed infarctions, skin ulcers,
and Raynaud’s phenomenon). Finally, these patients often
describe a change in their clinical status involving fever, anorexia,
or weight loss. It previously was believed that patients receiving
corticosteroids were at risk for an increased incidence of neuropathy.
However, these are patients with severe disease, and it is thought
currently that corticosteroids may help to check the progression
of the arteritis. Thus, rapid tapering of these drugs may exacerbate
the arteritis and precipitate the onset of the neuropathy.
++
The latter usually includes a gradual onset of numbness and tingling
confined to the lower extremities. The sensory deficits are symmetric
and not accompanied by motor deficits. Patients with rheumatoid
arthritis and other connective tissue diseases also may have mononeuritis
multiplex or a sudden onset of pain and paresthesias along the course
of a peripheral nerve, followed by wrist or foot drop.
++
Although only a small percentage of patients with rheumatoid
arthritis have symptomatic neuropathy, a large percentage have histologic
evidence of disease involving the peripheral nerves at autopsy.139 The
range of arterial pathologic changes in the peripheral nerves includes
perivascular infiltration with mononuclear cells, fibrinoid necrosis
of the media with infiltration of eosinophils and mononuclear cells,
intimal proliferation and reduplication of the internal elastic
lamina, and hemorrhage around the vessel walls. The damage to nutrient
vessels results in both segmental demyelination and wallerian degeneration
in the affected nerves.140
++
The diagnosis of rheumatoid arthritis generally is well established
before the neuropathy appears. However, patients with neuropathy
have an elevated erythrocyte sedimentation rate; mild normochromic,
normocytic anemia; and significantly elevated titers of rheumatoid
factor.
++
Polyarteritis nodosa is a multisystem disease characterized by
a vasculitis of small and medium-sized muscular arteries, with particular
involvement of the kidneys and gastrointestinal tract. Clinical
neuropathy is a common manifestation of this disease. The clinical
presentation may be similar to that of rheumatoid arthritis. One
important distinguishing feature is that the neuropathy of polyarteritis
nodosa involves the upper extremities as frequently as the lower
extremities. The neuropathy may occur in conjunction with other
manifestations of this disease, such as fever, weight loss, renal
insufficiency, and skin lesions.141 Patients with
both polyarteritis nodosa and rheumatoid arthritis also may have
an accompanying arthritis. The arthritis of polyarteritis nodosa
is mild and of short duration. It does not cause the extensive joint
destruction and nodule formation seen with rheumatoid arthritis.
++
The pathologic changes seen in the peripheral nerves involve
an arteritis of nutrient arteries that is similar to that described
in rheumatoid arthritis. The diagnosis depends on a histologic demonstration
of vasculitis in the involved organs. Peripheral neuropathy may
be associated with Churg-Strauss vasculitis (eosinophilic granulomatosus).
It is considered a variant of polyarteritis nodosa that is characterized
by peripheral eosinophilia and a strong association with severe
asthma.142 Both systemic lupus erythematosus and
giant cell arteritis (involving the temporal arteries) may include
secondary neuropathy.
++
The porphyrias are a group of metabolic disorders characterized
biochemically by an overproduction of porphyrins and porphyrin precursors.
Recurrent attacks, which are often precipitated by drugs (such as
barbiturates, phenytoin, sulfonamides, and estrogens), are common.
The neuropathy and extremity pain is a feature only of one subgroup,
the so-called hereditary hepatic porphyrias, which include (1) acute
intermittent porphyria, (2) variegate porphyria, and (3) hereditary coproporphyria.143
++
Acute intermittent porphyria, inherited as an autosomal dominant
trait, is most common in women of English and Scandinavian origin.144 Attacks
are rare before puberty and are distinguished temporally by three
phases: (1) abdominal pain, (2) psychologic disturbances, and (3) polyneuropathy.
Abdominal pain initiates the attack. The pain is described as colicky
and may be diffuse or confined to one region of the abdominal wall.
It often radiates to the back but is not accompanied by abdominal
wall guarding or tenderness. Tachycardia is a constant physical
sign during attacks.145 Radiographic studies show
distended loops of bowel. Psychologic manifestations follow the
acute abdominal attacks. This phase is characterized by restlessness,
insomnia, hallucinations, and confusion.146 Neuropathy
is the final phase of the attack. It is symmetric, progressive,
and initially involves mostly motor nerves. The upper extremities
are affected more than the lower extremities and the proximal, more
so than the distal muscles. Tendon reflexes are diminished or absent.147,148 The
extremity pain that occurs can result from various factors. Proximal
muscle aching and cramps are common. Paresthesias and dysesthesias
also occur in half the cases.
++
The diagnosis depends on the characteristic history and is confirmed
by demonstrations of increased levels of porphobilinogen and δ-aminolevulinic
acid in the urine. Variegate porphyria is most common among European
descendants in South Africa. The acute attacks are similar to those
of acute intermittent porphyria, but in addition, they are accompanied
by cutaneous photosensitivity. Hereditary coproporphyria is a rare cause
of neuropathy and is distinguished by a predominantly fecal excretion
of porphyrins.
++
Several types of peripheral neuropathy may accompany hepatic
dysfunction. These are distinct from alcoholic neuropathy or illnesses
that affect both the liver and peripheral nervous system concomitantly.149 Specifically,
the conditions are (1) a painless demyelinating neuropathy that accompanies
hepatic dysfunction, regardless of the cause150,151;
(2) an acute polyneuritis identical to that seen with Guillain-Barré syndrome
occurring late in the course of viral hepatitis as jaundice is regressing152,153;
and (3) a rare but painful neuropathy that occurs with biliary infections.154
++
Patients with biliary cirrhosis and neuropathy have the other
common manifestations of this disease: hepatomegaly, pruritus, jaundice,
and cutaneous xanthomatosis. Hypersensitivity and paresthesias have
been recognized for a long time as a feature of biliary cirrhosis.
However, Thomas and Walker154 also documented the
presence of sensory deficits. Xanthomatous involvement of the connective tissue
sheaths of the cutaneous nerves is the cause of the painful dysesthesias.
+++
Burning Feet
Syndrome
++
Investigators initially thought that the so-called burning feet
syndrome described among prisoners of war after World War II represented
a distinct deficiency syndrome. Currently, experts agree that it
is merely one manifestation of vitamin B deficiency and can be found
in patients with (1) alcoholic neuropathy, (2) beriberi, (3) pellagra,
and (4) Strachan’s syndrome. The symptom of burning feet,
or acrodysesthesia, begins as a persistent burning pain over the
metatarsals on the soles of the feet. Various other dysesthesias,
tingling, electric shocks, or coldness may accompany this pain.
Soon, the entire soles and dorsal surface of the feet are involved
symmetrically. The pain worsens at night. Affected patients try
a number of methods to relieve the burning: immersing their feet
in ice water, constant massage, or walking (despite pain caused
by contact). Many authors believed the syndrome had a causalgic
basis as a result of findings such as cyanosis and hyperhidrosis.
Other features of peripheral neuropathy (e.g., absent reflexes,
impairment of sensation, and muscle wasting) may or may not be present.
Occasionally, the patient’s hands may be involved, too.
+++
Isoniazid- or
Hydralazine-Induced Neuropathy
++
The occurrence of isoniazid-induced neuropathy was discovered
shortly after the drug was first used to treat tuberculosis. The
neuropathy generally involved the motor function, sensation, and reflexes
of the lower extremities. The initial symptoms consisted of numbness
and tingling, which began in the toes and feet, followed by calf
tenderness, and finally continuous burning paresthesias and painful
dysesthesias caused by contact stimuli. Increasing severity of symptoms
paralleled proximal spread of the neuropathy to the knees. Patients
displayed weak toe movements and dorsiflexion and loss of the Achilles
reflex.155 The incidence of the neuropathy varies
with the dose of drug administered. It ranges from less than 10% of
patients treated with a dose of 4 to 9 mg/kg per day to
40% with doses of 20 mg/kg per day.156 Vitamin
B6 deficiency causes the neuropathy, which can be prevented
by vitamin B6 supplementation.157 Isoniazid
produces marked excretion of pyridoxine.
++
Pyridoxine deficiency presumably is the basis for the neuropathy
that complicates therapy with hydralazine, which is chemically related
to isoniazid.158
++
The first description of pellagra among peasants in northwestern
Spain whose diet consisted almost entirely of corn appeared in 1730.
The role of sunlight, the seasonal variation (highest in the spring),
and the rash that appeared on exposed areas (so-called Casal’s
collar) were noticed. The first reports of pellagra in the United
States were made in the late 1800s, and the disease soon attained
epidemic proportions among alcoholic and farming populations. Currently,
the disease rarely is seen in the continental United States (except
among food faddists). It does occur commonly among poorer vegetarians
and the black population of South Africa.
++
Initially, it was believed that pellagra was caused solely by
a niacin-deficient diet. Subsequently, it was shown that (1) administration
of tryptophan to humans resulted in increased urinary excretion
of niacin metabolites, and (2) the dermal and gastrointestinal manifestations
of pellagra responded to large doses of tryptophan. Thus, currently,
investigators believe that pellagra is the result of a deficiency
of niacin and its amino acid precursor, tryptophan.
++
Pellagra shows the clinical triad of dermal, gastrointestinal,
and neurologic lesions. The skin lesions first appear erythematous,
then become brown and hyperkeratotic. They are seen on the face,
neck, sternum, and dorsum of the hands and feet. Affected patients
have anorexia, diarrhea, weight loss, and dysphagia. The neurologic
manifestations consist variously of depression, insomnia, irritability,
and signs of spinal cord involvement. The neuropathy, which is identical
to that observed with beriberi, is the most common neurologic finding.
Affected patients have exquisite tenderness to palpation of the
muscles of their calves and feet. Many also feel an intense burning
pain in a so-called glove-and-stocking distribution. Diminution
or loss of vibratory sensation and deep tendon reflexes occur.
+++
The Syndrome
of Amblyopia, Painful Neuropathy, and Orogenital Dermatitis (Strachan’s
Syndrome)
++
Strachan (in 1888) and Scott (in 1918) both described a deficiency
syndrome among Jamaicans—consisting of amblyopia, painful
neuropathy, and orogenital lesions—that was distinct from
beriberi and pellagra. These manifestations since have been described
among World War II prisoners in Johore and Singapore, in survivors
of German concentration camps, and in natives in Trinidad and Senegal.
Currently, the syndrome has not been related to a specific vitamin
deficiency, although a riboflavin deficiency has been suggested.
The few neuropathologic studies performed reveal spinal cord posterior
column demyelination, particularly in the cervical region.
++
Patients with pellagra classically have numbness and tingling
in their hands and feet. The dysesthesias consist of severe burning
in the soles and palms, which often is worse at night. The numbness
extends progressively to the knees or hips, and the patient’s
gait may be impaired. Often, the symptoms are confined to the lower
extremities, or alternatively, they may begin in the fingertips and
involve the hands and arms symmetrically. Muscle wasting is progressive,
and extremity cramps are common.
++
Amblyopia is the other constant feature of this syndrome. Visual
impairment is accompanied by central and centrocecal scotomas that
progress to complete blindness. Ophthalmologic evaluation shows
little, except occasionally disc hyperemia is found.
++
The dermatitis involves the corners of the mouth and eyes, prepuce,
anus, and vulva. Deafness and vertigo (so-called camp dizziness)
are common features of some outbreaks of the syndrome.
++
In a consecutive series of 1,030 alcoholic patients admitted
to Boston City Hospital,159 a 9% incidence
of peripheral neuropathy was observed, with a disproportionately
higher incidence in women. Nutritional deficiency and the toxic
effect of the alcohol, per se, account for the major findings of
alcoholic neuropathy. Alcoholic patients not only subsist on a diet
of carbohydrates, they also have an impaired capacity to absorb
folate and thiamine and to digest fats. Axonal degeneration, with
destruction of both myelin and axons, results. The changes are seen predominantly
in the longest and largest myelinated fibers. As the neuropathy
advances, anterior and posterior nerve root involvement occurs.
++
Alcoholic neuropathy is a progressive symmetric disorder of the
extremities that generally spares both the cranial and truncal nerves.
The lower extremities (particularly the feet and ankles) are affected
more than the upper extremities; in one study 70% of patients
had lower extremity involvement alone. Motor disability and sensory
deficits occur concomitantly. These signs can range from mild asymptomatic
depression of the Achilles reflex to gross motor deficits (wrist
and foot drop). All sensory modalities, both superficial and deep,
may be affected with a characteristic distribution (so-called glove
and stocking).
++
The pain that accompanies alcoholic neuropathy typically occurs
in several areas. Affected patients have a characteristic tenderness
when pressure is applied to the muscles of their feet and calves.
The distal lower extremity dysesthesias may have a dull aching quality
or a sharp, lancinating, tabes-like pain. These patients also describe
a burning feet syndrome that consists of severe paresthesias of
the soles aggravated by contact stimuli. Excessive sweating on the
volar surfaces of the feet and hands may occur, which presumably
is related to postganglionic sympathetic involvement. Other signs,
such as stasis edema, glossiness, and pigmentation changes of the skin,
and dystrophic changes in the feet, may be present.
++
++
Herpes zoster, or shingles, is an infection by the DNA virus
varicella-zoster that occurs with an annual incidence of approximately
125 cases per 100,000. Herpes zoster is thought to be a reactivation
of the varicella-zoster virus that also causes chickenpox in children,
which has remained dormant in the dorsal root ganglia for many years.
++
When viral antibody titers decline in elderly or immunocompromised
patients, the virus may reactivate and begin to replicate. A painful
neuralgia results from damage to the sensory ganglia. The virus
then spreads peripherally to cutaneous sensory nerve endings, causing
vesicular eruptions. Most affected patients are healthy, but the
course may be more severe in immunosuppressed patients (Table 32-10).
++
++
Zoster-affected patients usually have pain and dysesthesias along
the dermatomal distribution of a single spinal or cranial sensory
nerve. The pain at first is usually mild, but it increases in intensity over
the succeeding days. Occasionally, patients have accompanying systemic
symptoms such as fever, malaise, adenopathy, or headache. After
4 to 5 days, the typical skin lesions appear. Swelling and erythema
give way to red papules that progress to clear vesicles, blebs,
and pustules that crust over in 2 to 3 weeks. The lesions are unilateral
in a dermatomal distribution. The most common dermatomes affected
are the thoracic, followed by the cranial, lumbosacral, and cervical. During
the acute phase, patients feel continuous dysesthesias that are
aggravated by movement or pressure on the skin. As the blebs begin
to dry and scale, the intense pain subsides, but many patients still
have hyperesthesias and, only gradually, become asymptomatic.
++
Paresis may accompany the rash, particularly in elderly patients.
It follows the appearance of the rash and usually occurs with cervical
and lumbosacral eruptions rather than thoracic. Involvement of the
facial nerves is common (Ramsay Hunt syndrome). The virus may be
recovered from early vesicles, cerebrospinal fluid, and blood. The
base of the skin lesions contains multinucleated giant cells and
eosinophilic intranuclear inclusions.
++
Postherpetic neuralgia develop in 10% to 50% of
patients with acute herpes zoster; the incidence increases with
advancing age. The syndrome consists of pain persisting for 4 to
6 weeks after the skin lesions have disappeared. Such patients generally
suffer from a burning pain associated with hyperesthesia.
++
++
Peripheral neuropathies are a common source of extremity pain.
Several unique features of the peripheral nervous system make it
particularly susceptible to trauma or metabolic derangements. Firstly,
it is composed of long axons (1–2 m). Secondly, the spinal
roots pass through narrow foramina centrally and many ligaments
and tendon sheaths peripherally, making them susceptible to compression.
Thirdly, the axons depend on a complex longitudinal network of nutrient
arteries that run in the epineurium and perineurium.
++
The peripheral neuropathies involving smaller afferent fibers
are usually painful. Those affecting large-diameter afferent fibers
and Schwann cells are generally painless. The pain of a peripheral neuropathy
is usually not distinctive, and the diagnosis must, therefore, be
based on other criteria.
++
Regardless of their cause, peripheral neuropathies have several
characteristics: (1) paresthesias and dysesthesias, (2) sensory
loss, (3) loss or diminution of tendon reflexes, and (4) impaired motor
function. Paresthesias and dysesthesias commonly accompany certain
types of neuropathies, such as those resulting from diabetes and
alcohol. The paresthesias can manifest as tingling, lancinating
pain, or numbness. Perversion of sensation may also occur, such
as when a tactile stimulus causes a burning or tingling. Commonly,
the pain persists after the stimulus is withdrawn. Hyperpathia may
be prominent.
++
The cause of paresthesias remains poorly understood. One hypothesis
suggests that the loss of large touch-pressure fibers no longer
inhibits pain-sensing cells in the posterior horn. Another states
that ectopic discharges may result from regenerated nociceptive
fibers. Some type of sensory loss accompanies most neuropathies.
Only one or all sensory modalities (touch-pressure, vibratory, joint
position, pain, and temperature) may be affected. Deep tendon reflex
loss or diminution characterizes peripheral neuropathy, especially
when both sensory and motor involvement exists. The Achilles reflex
serves as a particularly sensitive index of polyneuropathy. Tremors
and disorders of autonomic function also may be seen with peripheral
neuropathies. Useful diagnostic laboratory tests include nerve conduction
studies, nerve biopsies, and cerebrospinal fluid examination.160,161
++
Diabetic neuropathy includes a wide range of clinical manifestations.
Traditionally, it has been categorized anatomically (Table 32-11).
For our purposes, the diabetic neuropathies can be classified into
separate pain syndromes: polyneuropathy, mononeuropathy, radiculopathy,
and amyotrophy162,163 (Table 32-12).
++
++
++
Depending on the criteria used to establish the diagnosis, the
incidence of diabetic neuropathy varies from 5% to 60% of
patients with the disease. Pirart noticed that the neuropathy rarely occurred
in the young, and its prevalence increased from 7.5% at
the time of discovery of diabetes mellitus to almost 50% after
25 years.164 Neuropathy may accompany both type
1 and type 2 diabetes mellitus. It also may occur in patients with
diabetes after pancreatectomy and hemochromatosis. Several authors
have noted the common concurrence of neuropathy, nephropathy, and retinopathy
(diabetic triopathy).165
+++
Symmetric Sensory
Polyneuropathy
++
A symmetric sensory polyneuropathy is the most frequent form
of peripheral nerve disorder in diabetic patients. It may occur
acutely after a diabetic coma, as a result of poor serum glucose control,
after initiation of therapy, or during periods of emotional stress.166
++
A loss of ankle jerks and vibratory sense in the feet should
direct the clinician toward the diagnosis. Symptoms, which consist
of tingling, numbness, and burning paresthesias, are generally confined
to the lower extremities. A deep aching pain (described by patients
as “arising from the bones”) that intensifies
at night can affect the feet and legs. Symmetric distal sensory
impairment occurs in a glove-and-stocking distribution.
++
Signs and symptoms of diabetic sensory neuropathy display considerable
variability. At one extreme, patients show loss of position sense,
decreased reflexes, and no pain. At the other end, they manifest
cutaneous hyperesthesia, distal burning pain, and autonomic dysfunction
but preserved reflexes and large fiber sensory function. Sural nerve
biopsies from these patients reveal the involvement of both small
myelinated and unmyelinated fibers.167
++
Other less common variants have been described. For example,
Archer168 documented severe distal burning pain
without sensory loss or autonomic features that occurred after rapid
weight loss in men. The neuropathy subsided after these patients
gained weight and had improved diabetic control.
++
The term diabetic pseudotabes refers to a variant that includes
symmetric distal loss of cutaneous sensibility, joint position,
and vibration, all leading to gait abnormalities and foot ulcers.
Autonomic signs and symptoms, including atonic bladder and Argyll
Robertson pupils, also may occur.
++
Neuropathy arthropathy, seen in advanced cases of sensory polyneuropathy,
affects mainly the joints of the feet and, less commonly, the ankle.
The interphalangeal and metatarsophalangeal joints are affected.169
++
Autonomic dysfunction almost always accompanies the sensory polyneuropathy
in diabetes and has a wide range of clinical manifestations (Table
32-13). The disease affects both the longer sensory and autonomic
fibers first. Some of the earliest changes involve vascular and
sudomotor innervation of the legs. Hence, anhidrosis and an absence
of piloerection may be first detected in the feet, but eventually
ascend the legs in a symmetric fashion. Peripheral edema of unknown
origin also frequently occurs with diabetic neuropathy.170
++
+++
Focal and Multifocal
Neuropathies
++
Diabetes most commonly affects the ulnar, median, radial, femoral,
lateral femoral cutaneous, and peroneal nerves. The onset may be
abrupt or insidious. These isolated peripheral nerve lesions often
occur at sites common for external pressure palsies (e.g., carpal
tunnel).
+++
Diabetic Amyotrophy
and Proximal Motor Neuropathy
++
Diabetic amyotrophy connotes a syndrome usually encountered in
older patients that consists of asymmetric proximal muscle wasting
in the lower limbs. The muscles commonly affected include the iliopsoas,
quadriceps, and adductor muscles but not the hamstrings.171,172 Patients
complain of pain, which is generally most severe at night, in the
thigh muscles and lumbar region. The patellar reflex may be depressed,
but sensation is maintained.
++
Sixty to 70% of patients about to begin dialysis for
chronic renal failure display neuropathic features.173,174 The
progression of the neuropathy depends solely on the duration and
severity of renal failure. Men seem to have a several-fold higher
incidence than women.
++
The combined motor and sensory dysfunction that occurs with uremic
neuropathy invariably occurs in a distal, symmetric distribution.175 The
legs are affected before and more often than the upper extremities.
This correlates with histopathologic studies that show a distal
axonal degeneration, with shrinkage and nerve fiber loss predominantly
involving larger fibers.
++
The exact cause of the neuropathy is unknown, although the accumulation
of toxic substances with molecular weights of 300 to 2000 Daltons
(the so-called middle-molecule hypothesis) that are not removed
during hemodialysis have been implicated.176 Two
other observations support the middle-molecule hypothesis as the
source of neuropathy. One entails the striking remission of neuropathy
after successful renal transplantation and the other the fact that
peritoneal dialysis, which presumably passes toxic molecules more
selectively than hemodialysis, is not associated with neuropathy
despite having higher blood levels of urea and creatinine.
++
Uremic patients can have extremity pain from various causes.
Nielsen177 noticed muscular cramps and the restless-leg
syndrome in two thirds of patients in his series. The cramps, which also
can occur during acute uremia, probably reflect muscular irritability
in the presence of uremic toxins. They are not necessarily associated
with any other signs and symptoms of neuropathy (e.g., slowing of
conduction velocity). The restless-leg syndrome of Ekbom,178 characterized
by night pain relieved by movement, is associated with clinical
neuropathy. Dysesthesias can occur that range from the burning-feet
type identical to that seen in alcoholic patients to painful tingling,
electric shocks, or constrictive feelings around the ankles and
feet. The diagnosis depends on demonstrating a neuropathy with symptomatic
uremia and excluding other causes of neuropathy, such as toxins.
++
Gold has been used traditionally to treat rheumatoid arthritis.
Common side effects of this drug include fever and rashes. The incidence
of patients who have peripheral neuropathy after gold therapy is
less than 1%. Such patients have painful paresthesias,
followed by sudden onset of asymmetric weakness. They may have fever
and rashes before the onset of the neuropathy.179 Controversy
exists as to whether the neuropathy results from the direct toxic
effect of the drug or from a hypersensitivity reaction.180
+++
Perhexiline
Neuropathy
++
Perhexiline maleate was introduced for the treatment of angina
in the early 1970s. Peripheral neuropathy was seen in some patients
who were treated with doses of 300 to 400 mg/day for 4 months
to 1 year. These patients had pain and distal paresthesias, followed
by severe distal and proximal muscle weakness. They also had a high
incidence of bilateral papilledema, abnormal liver function tests,
and weight loss. Perhexiline apparently causes cellular accumulation
of abnormal gangliosides, particularly in Schwann cells and liver
cells.181
++
Nitrofurantoin may cause peripheral neuropathy characterized
by distal weakness and sensory loss. Pain and paresthesias are the
common presenting symptoms.182 The neuropathy may
occur soon after drug therapy begins. It is most commonly seen in
patients with impaired renal function who have higher blood levels
of the drug.183
++
Disulfiram therapy for alcohol abuse rarely causes neuropathy.184 Affected
patients generally have taken 1.0 or 1.5 g/day of this
drug. They have paresthesias beginning in the lower extremities.
The mechanism is unclear; however, carbon disulfide, a by-product
of disulfiram, is a known neurotoxin.185
+++
Carcinomatous
Neuropathy
++
An association between malignant disease and peripheral neuropathy
independent of metastases has been recognized for a long time. In
1948, Denny-Brown186 described two patients with
carcinoma of the lung and sensory neuropathy from degeneration of
dorsal root ganglion cells. Studies among different groups of workers
revealed an incidence of clinical peripheral neuropathy in the range
of 1.7% to 5% of patients with cancer.187,188 The
highest incidence occurs among those with carcinoma of the lung,
followed by those with carcinoma of the stomach, colon, and breast.
++
Most commonly, a combined sensorimotor neuropathy develops, but
a pure sensory type also may occur.188 Painful
dysesthesias that begin distally and spread proximally and aching
pains characterize the sensory component. Tendon reflexes are depressed,
and position and vibratory sense may be impaired. The neuropathy
often precedes other symptoms of the neoplasm by a year. Women more
commonly display this type of neuropathy. Its course is unaffected
by the underlying disease state.
++
Pathologic changes associated with the sensory neuropathy include
severe degeneration of dorsal nerve roots and the posterior columns.186 Axonal
degeneration and segmental demyelination occur with the sensorimotor
neuropathy.189 The etiology of these neuropathies
remains unclear.
++
Casey and associates190 demonstrated that vincristine,
a cancer chemotherapeutic agent, predictably produced a peripheral
neuropathy distinct from that caused by the malignancy per se. Affected
patients developed finger paresthesias, then painful cramping and
weakness in the extensor muscles of their hands and wrists, and
commonly lost their ankle reflexes. Symptoms improved somewhat after
decreasing or discontinuing the drug. Presumably, the vincristine-induced
breakdown of neurotubules and proliferation of neurofilaments in
nerve cells plays a role in its neuropathic mechanism.191
+++
Polymyalgia
Rheumatica
++
++
Polymyalgia rheumatica is a clinical syndrome characterized by
morning stiffness in the proximal portion of the extremities or
torso.192 It occurs relatively commonly in persons
older than 50; one study documented an annual incidence of 53.7
cases per 100,000 persons and a prevalence of 500 per 100,000.193 A
close relationship exists between polymyalgia rheumatica and giant
cell arteritis; polymyalgia rheumatica occurs in 40% to
60% of patients with giant cell arteritis.194 Hence,
some authors suggest that polymyalgia rheumatica may be an expression
of an underlying arteritis.
++
The presence of symptoms in two of the three commonly affected
areas (neck, hip, or shoulder) for at least 1 month and evidence
of a systemic process, such as an increased erythrocyte sedimentation
rate (>40 mm/hour using the Westergren
method) confirm the diagnosis.195 Some definitions
also require a rapid response to small doses of corticosteroids.
The presence of other diseases, such as rheumatoid arthritis, polymyositis,
malignancy, or chronic infection, excludes the diagnosis.
++
The cause remains unknown. Reports of familial aggregation and
the finding that the disease appears almost exclusively in whites
suggest a genetic predisposition. Several results suggest a humoral
or cellular immune basis. These include (1) the granulomatous histopathologic
features of giant cell arteritis, (2) the presence of immunoglobulins
and complement deposits adjacent to the elastic lamina in some involved
temporal arteries, and (3) the finding that sera from patients with
polymyalgia rheumatica contains increased levels of circulating
immune complexes during active disease.196
++
These patients are generally in good health before polymyalgia
rheumatica develops. Arthralgias and myalgias may occur either slowly
or abruptly; they generally begin in one shoulder girdle. However,
the disease soon becomes bilateral and eventually involves most
of the tendinous attachments, and there is proximal muscle pain
with movement (compare the joint pain in rheumatoid arthritis).197,198 Muscular
strength is normal. Synovitis in the knees or sternoclavicular joints
may be found. More than half the patients have systemic symptoms
such as weight loss or a low-grade fever before the onset of muscle
pain.197,198
++
Laboratory findings during the active phase include (1) a markedly
elevated erythrocyte sedimentation rate (>100 mm/hour
using the Westergren method), (2) a mild-to-moderate normochromic
anemia, and (3) an increase in α2-globulin
and fibrinogen.199 Significant normal laboratory
values include serum creatine kinase, muscle biopsies, and EMG studies.
++
The differential diagnosis of polymyalgia rheumatica includes
rheumatoid arthritis, polymyositis, and systemic processes (such
as bacterial endocarditis). The absence of swelling and peripheral joint
pain should distinguish polymyalgia rheumatica from arthritis. Polymyositis
is characterized by muscle weakness, elevated muscle enzyme studies,
and abnormal EMG studies.
++
Psoriatic arthritis is an inflammatory asymmetric polyarthritis
found in patients with psoriasis. The cause is unknown, but up to
30% of patients are positive for HLA-B27 antigen.200 The
onset of the arthritis generally follows the psoriasis by months
or years. The course of arthritis may or may not parallel that of
the skin lesions. The pattern of the arthritis is that of a typical
inflammatory arthritis that affects predominantly the upper extremities.
The proximal joints of the hands and feet are tender and swollen.
The arthritis is limited to several joints and is asymmetric. There are
no rheumatoid nodules. Laboratory tests do not show rheumatoid factor.
Affected patients may have an increased erythrocyte sedimentation
rate and anemia.200
++
The radiologic features of psoriatic arthritis include erosions
of the articular surfaces and the so-called pencil-in-cup deformity
observed in joints of the fingers and toes. The diagnosis depends on
findings consistent with psoriasis and an accompanying inflammatory
arthritis without rheumatoid factor or nodules.
++
Reiter’s syndrome is an asymmetric inflammatory arthritis
coupled with urethritis or cervicitis. Classically, the syndrome
also included conjunctivitis. The syndrome has two clinical forms.
The postvenereal form occurs predominantly in young men; the postdysenteric
form affects both sexes in all age groups. The actual pathogenesis
of the disease involves infection of the urogenital tract or gut
with one of several organisms in genetically susceptible patients.
Sufferers generally have the HLA-B27 alloantigen.201
++
Clinically, the syndrome begins with an asymptomatic serous urethral
discharge usually followed by conjunctivitis.201 Finally,
the patient has an acute onset of inflammatory arthritis of the
lower extremities. Keratoderma blennorrhagia frequently appear on
the palms or soles. Painless mucocutaneous lesions may appear in
the mouth, on the palms and soles, or on the glans penis.201
++
Synovial fluid analysis reveals an increased leukocyte count
and inflammatory arthritis. The diagnosis, therefore, relies on
documenting nonspecific urethritis or cervicitis without rheumatoid
factor.
++
Gout is a painful disorder of the joints secondary to deposition
of crystals of monosodium urate monohydrate. Urate values greater
than 7.0 mg/dL in the plasma cause saturation; chronically
elevated uric acid leads to gouty attacks. Hyperuricemia, per se,
is not synonymous with gout, and most hyperuricemic patients are
asymptomatic. Men tend to have higher serum uric acid levels, and
more than 95% of cases occur in adult men. Hyperuricemic
patients also are prone to acute nephrolithiasis, and approximately
20% of gout sufferers have attacks of renal colic before
gouty attacks.202
++
The pathogenesis of an acute gouty attack after years of chronically
elevated uric acid levels probably involves crystal deposition and
resultant phagocytosis by leukocytes, leading to activation of Hageman
factor, coating of crystals with gamma globulins, and complement
activation.202 Lowering the local tissue pH then
results in additional precipitation of urate crystals.
++
Initially, gouty arthritis usually attacks a single joint and
is exquisitely painful. Affected patients may describe prior mild
attacks (twinges). The distal lower extremities, particularly the
great toe (podagra), bear the brunt of the attacks. The following
are involved in order of decreasing frequency: instep, ankle, heel,
knee, and upper extremities. The attacks may be triggered by trauma, alcohol,
surgery, or dietary excesses. Affected patients may have accompanying
systemic signs, such as fever, increased erythrocyte sedimentation
rate, and leukocytosis. The attacks abate spontaneously and are
separated by periods when the patient is completely asymptomatic.203
++
In untreated patients, the hyperuricemia causes deposits of monosodium
urate (tophi) in tendons, membranes, and soft tissues. However,
these tophi rarely occur before the onset of acute gouty attacks.
++
Monosodium urate crystals detected using polarized-light microscopy
in the leukocytes from synovial aspirates confirms the diagnosis.
These crystals appear needle shaped and negatively birefringent.
The leukocyte count of the synovial fluid during attacks may vary
from 1,000 to 70,000/dL. Extracellular crystals may be
found in the synovial fluid during asymptomatic periods. In the absence
of microscopic confirmation, the diagnosis can be presumed by the
combination of (1) the presence of hyperuricemia, (2) a history
typical of gout, and (3) response to colchicine.
++
Pseudogout is a crystalline arthritis seen in elderly patients
that is characterized by calcium deposits in articular cartilage
and caused by release of calcium pyrophosphate crystals into the
joint space. There is a definite association with hyperparathyroidism,
osteoarthritis, and hemochromatosis. Pseudogout also is seen in
metabolic disorders such as Wilson’s disease, hypothyroidism, gout,
and ochronosis.204
++
Patients with pseudogout have elevated fluid levels of inorganic
pyrophosphate. Crystals then form in articular cartilage (chondrocalcinosis).
The crystals found in synovial fluid are released from the cartilage,
possibly after trauma that disrupts the cartilage or as a result
of lowering the Ca2+ levels
in the synovium. Regardless, the presence of calcium pyrophosphate
crystals then causes a classic inflammatory response, and polymorphonuclear
leukocytes enter the joint.204
++
The acute arthritic attacks of pseudogout are usually monoarticular.
The knee is the most common site. The joint is warm, swollen, and
painful. The attacks may be preceded by surgery or trauma.
++
Showing calcium pyrophosphate dihydrate crystals in the synovial
fluid during acute attacks confirms the diagnosis. Under a polarized-light
microscope, the crystals appear as positive birefringent blunt rods.
They may be intra- or extracellular. Radiologically, these patients
have calcium deposits in their articular cartilage.204
++
Osteoarthritis affects predominantly older patients. Articular
cartilage absorbs the bulk of joint stress, but over time degenerates.
Increased mechanical pressure appears to provoke an elaboration
of chondrocytes and synovial fluid. The water and proteoglycan content
decreases, and focal cartilage erosions appear. Eventually, joint
margins reveal new bone and thickened synovium. The end point of
this process is a progressive loss of chondrocytes, development
of fissures, osteophyte formation, and replacement of cartilage
with bone.205
++
Patients complain of a diffuse, aching pain that usually is limited
to one or several joints. Rest relieves the pain, and activity aggravates
it. Affected individuals may describe an increase in symptoms with
changes in weather. Stiffness generally does not become a major
symptom.206
++
Painless Heberden’s nodes, which are prominent knobs
along the medial and lateral aspect of distal interphalangeal joints,
and Bouchard’s nodes, which are found on the proximal interphalangeal joints,
are a common finding. Occasionally, the joints may appear swollen
and warm as a result of the inflammatory synovitis that accompanies
an exacerbation of symptoms. The pattern of joint involvement (proximal
interphalangeal and distal interphalangeal involvement with sparing
of the wrist joint) helps distinguish osteoarthritis from rheumatoid
arthritis.206
++
Radiologic findings typical of osteoarthritis include loss of
joint space, presence of osteophytes, and subchondral sclerosis.
Synovial fluid aspirate shows a low leukocyte count and predominantly
mononuclear cells.
++
Inflammatory synovitis, which results in eventual cartilage and
bone destruction, distinguishes rheumatoid arthritis. The cause
remains unknown, but genetics plays a role, as witnessed by its association
with HLA-DR4.207 Women are affected threefold more
than men. Symptoms most frequently begin between the ages of 35
and 50 years.
++
Systemic symptoms, such as fatigue, generalized weakness, and
anorexia, generally precede the joint pain of rheumatoid arthritis.
The pain affects joints in a symmetric distribution and is aggravated
by passive or active motion.208 Morning stiffness
is a universal feature and is an important criterion for the diagnosis.
Physical examination reveals synovitis with accompanying swelling,
tenderness, and increased warmth in the joints. The pain is secondary
to joint swelling, which stretches the joint capsule. The wrist joints,
proximal interphalangeal joints, and metacarpophalangeal joints
usually are involved, but rarely the distal interphalangeal joints.
Hand involvement with destruction of cartilage, tendons, and ligaments
can cause a number of typical deformities: (1) boutonnäire
deformity (which results from flexion deformity of the proximal
interphalangeal joints and extension of the distal interphalangeal
joints), (2) swan-neck deformity (which results from hyperextension
of proximal joint and flexion of distal interphalangeal joints),
and (3) radial deviation at the wrist with ulnar deviation at the
digits.
++
Although no specific diagnostic tests exist, the American Rheumatism
Association has developed a list of criteria to aid in the diagnosis
(Table 32-14). Affected patients may carry the rheumatoid factor
(autoantibodies to immunoglobulin G) in their serum. In addition,
there may be a normochromic normocytic anemia. Most patients also
have increased erythrocyte sedimentation rates. Evaluation of the
synovial fluid shows increased leukocytes with polymorphonuclear
leukocytes, suggesting an inflammatory process.
++
+++
Muscular Disorders: Introduction
++
Most skeletal muscle pain is associated with exercise or trauma.209 The
pain is related temporally to exercise and is of limited duration.
Muscle pain is transmitted by the thin myelinated fibers (group
III or Aδ) and unmyelinated fibers (group IV or
C). These afferent fibers have unencapsulated branching endings
throughout the muscle with increasing density in the region of fascia,
tendons, and aponeuroses. There are two types of muscle pain receptors:
chemoreceptors and mechanoreceptors. The former respond to chemical
changes in the environment; the latter are affected by mechanical changes.
These receptors can be stimulated by potassium ions, hydrogen ions,
histamine, serotonin, or bradykinin.210–213
++
Patients most often describe muscle pain or myalgia as dull or
aching in quality. The term cramp214 refers to
an acute onset of a painful contraction, and although they can be
intensely painful, the quality of pain is described as dull. A muscle
contracture is similar to a cramp, but of longer duration; it is
seen in disorders of muscle metabolism. Muscle spasms are reflex
contractions of muscles surrounding injured tissues or structures
(e.g., abdominal muscle spasm associated with an inflamed appendix).
Myotonia is tonic spasm of a muscle after voluntary contraction
caused by a high-frequency firing of muscle fibers. Tetany refers
to involuntary cramplike spasms associated with reductions in ionizable
calcium or magnesium and attributed to repetitive firing in motor axons.
Dystonia is an involuntary contraction of muscle that involves both
agonist and antagonist activities.
++
Myalgias can be difficult to distinguish from pain arising from
other sites. Pain from the joints is well localized and exacerbated
by movement. Patients poorly localize bone pain, but it tends to have
a deep, boring quality that generally worsens at night. One must
determine whether the muscle pain is accompanied by weakness (failure
to achieve strength) or fatigue (failure to maintain strength).
As a rule, proximal muscle weakness suggests primary muscle disease;
peripheral and localized pain and weakness tend to occur with nerve
entrapments. Excessive fatigability is seen in disorders of muscle
metabolism, myotonic disorders, and mitochondrial myopathies.
++
The relationship of diet, alcohol intake, and fasting to muscle
pain should be determined. Drinking bouts may precipitate myopathy
and myoglobinuria in alcoholic patients. Fasting or prolonged exercise
with fasting may precipitate pain and weakness in patients with
carnitine palmityl transferase deficiency. A diet lacking in vitamin
D may lead to osteomalacic myopathy with bone and muscle pain.
++
Signs of muscle pain are confined to weakness, fatigability,
tenderness, and swelling. Muscle swelling per se is rare, but it
may occur in the polymyositis-dermatomyositis complex, acute alcoholic
myopathy, phosphofructokinase deficiency, and myophosphorylase.
++
Useful clinical tests to evaluate muscle pain and disease include
(1) presence of myoglobinemia and myoglobinuria, (2) serum creatine
kinase levels, (3) erythrocyte sedimentation rate, (4) EMG, (5)
quantitation of muscle force generation, (6) exercise testing, (7)
ischemic forearm tests, and (8) muscle biopsy.
++
Myoglobin is a muscle protein involved in oxygen storage. Muscle
breakdown or rhabdomyolysis can release myoglobin molecules, which
may pass into the urine as a result of their small size (molecular
weight 17,500 Daltons) and precipitate oliguric renal failure. Myoglobinemia
and myoglobinuria also may arise from various other causes.215
++
Creatine kinase is a muscle enzyme that catalyzes the breakdown
and synthesis of phosphoryl creatine. Abnormal increases in serum
levels of creatine kinase may indicate muscle damage; however, exercise
and intramuscular injections may also cause elevated serum levels.216 This
enzyme is elevated in muscular dystrophies, acute rhabdomyolysis,
McArdle’s disease, and polymyositis-dermatomyositis complex.
++
EMG helps distinguish myopathic from neuropathic diseases. Fibrillation
and giant action potentials characterize denervation from entrapment;
myopathies are associated with brief, small-amplitude motor unit
potentials. EMG can also provide information about which nerve roots
are involved.
++
Quantitation217 of muscle force generation can
be done using a hand-held dynamometer or muscle-testing chair. The
latter involves electrical activation of the quadriceps with large
surface electrodes and provides data concerning muscle fatigability
and frequency characteristics. These tools can track the progression
of the disease or the distribution of muscle weakness.
++
Exercise testing uses submaximal effort at approximately 70% of
previously determined maximal rate while simultaneously measuring
heart rate and blood pressure and levels of blood lactate and pyruvate.
Exercise testing can elicit symptoms in patients with muscle disorders,
and it is a particularly useful tool in those with suspected metabolic
disorders.
++
The simplicity and advantages of muscle biopsy, particularly
in the diagnosis of inflammatory myopathies and mitochondrial myopathies,
have been well described. Percutaneous needle biopsy is atraumatic
and appears to be as reliable clinically as an open biopsy of muscle.
+++
Muscle Pain
and Exercise
++
Normally, muscle pain with exercise can occur under two situations.
Firstly, it can occur with exercise and increase in intensity until
the muscle relaxes. When the voluntary contraction stops, the pain
disappears immediately. This type of concentric contraction or positive
work has a high metabolic cost.218 The mechanism
for this type of ischemic pain appears to be an accumulation of
metabolites that occludes blood vessels and stops the blood supply
to the muscle. Secondly, vigorous exercise leads to delayed muscle
pain. This results from eccentric muscle contractions or negative
work where the muscle is lengthened during a contraction.219 The
mechanism of this delayed soreness after eccentric contraction is
unknown; however, the muscles show evidence of damage, both biochemically
and morphologically.220
++
Cramps are painful involuntary contractions of acute onset that
occur more often at night. Stretching of voluntary muscle produces
an involuntary contraction that cannot be relaxed. The cramping results
from spontaneous firing of groups of anterior horn cells with motor
unit contractions. Cramps in the calf muscles generally are considered
benign. More generalized cramps, however, may be a sign of muscle
disease.214 Cramps that recur and are confined
to one specific muscle group may indicate nerve root entrapment.
They also occur with increasing frequency during pregnancy, with
electrolyte imbalances, and in patients undergoing hemodialysis.
Physical examination during muscle cramping shows a taut, contracted
muscle. This can be a distinguishing feature of the cramps caused
by intermittent claudication, in which patients have cramplike pain
without muscle contraction. The cause of the pain is not understood
completely, but it may involve an accumulation of metabolites or
a relative ischemia of the muscle. There is a benign form of muscle
cramping (idiopathic cramp syndrome) in which no neuromuscular disorder
is apparent.
++
The stiff-person syndrome refers to a progressive form of painful
muscle spasm.221,222 These patients have a boardlike
stiffness of their muscles, paroxysms of cramping, and a normal
sensory examination. The muscle stiffness resolves during sleep
or after the administration of large doses of diazepam. Isaac’s
syndrome is manifested by excessive sweating, widespread fasciculations, generalized
stiffness, and continuous motor unit activity that persists during
sleep and anesthesia.223
++
Tetany results from a reduction in ionizable calcium and magnesium.
This leads to increased neuromuscular irritability and involuntary,
cramplike spasms. The actual level of ionizable calcium needed to
produce tetany varies individually and is related to the concentration
of other electrolytes in the extracellular fluid. Hyperventilation
and ischemia increase the tendency for spasm to occur. The full
clinical spectrum of tetany is manifested by perioral and peripheral
paresthesias, carpal spasm, pedal spasm, laryngospasm, Chvostek’s
and Trousseau’s signs, and Q-T prolongation on an electrocardiogram.
Hypocalcemia causes unstable depolarization of the nerve fiber axons.
Thus, there is increased sensitivity of the facial nerve to percussion
(Chvostek’s sign) and spasm with ischemia (Trousseau’s
sign).
++
Drugs also may be a source of muscle pain. Focal myopathy may
occur after intramuscular injections from local irritation (e.g.,
paraldehyde) or after histamine release (opiates).
++
Painful proximal myopathy with tenderness and weakness can occur
after administration of clofibrate, aminocaproic acid, and emetine,
particularly after prolonged treatment and elevated serum blood
levels. Serum levels of muscle enzymes are elevated, and myoglobinuria
may occur. Muscle biopsy reveals multifocal muscle-fiber necrosis.
A painful, necrotizing proximal myopathy with an associated peripheral
neuropathy has been reported in patients treated with vincristine.224 Chronic
hypokalemia from drug use generally results in painless weakness
and hypotonia. However, painful quadriparesis and myoglobinuria
have been reported after administration of amphotericin B and chlorthalidone.224 Finally,
some drugs may cause myalgias and cramps from unknown mechanisms.
These drugs include lithium carbonate, danazol, isoetharine, cimetidine,
and the diuretics metolazone and bumetanide.224
++
The glycogen storage diseases constitute a group of diseases
in which an inborn error of glycogen metabolism exists. When the
energy supply for muscle contractions is compromised, muscle fatigue
and pain may result.
++
McArdle’s disease, or type V, first manifests during
adolescence with cramps, weakness, and contractions induced by vigorous
exercise. The cramps and pain are relieved by rest, but the contractions
may persist for hours. Moderate exercise may be well tolerated.
This disorder is caused by a deficiency of the enzyme myophosphorylase.
Tarui’s disease, or type VII, is a rare enzyme deficiency
that begins during early childhood and is characterized by exercise-induced
pain without muscle contractions.
+++
Idiopathic Polymyositis
and Dermatomyositis
++
Idiopathic polymyositis and dermatomyositis refer to a category
of relatively common diseases that may affect striated muscle only
(polymyositis) or skin and muscle (dermatomyositis). They also may
occur associated with arthritis, connective tissue diseases, or
malignancy. Pain may be a prominent feature.225
++
The cause of polymyositis-dermatomyositis is unknown. Theories
include autoimmune processes or a possible viral mechanism.226 Polymyositis-dermatomyositis
may have several different clinical presentations. Polymyositis,
confined to striated muscles, begins with an insidious onset over 3
to 6 months of a symmetric weakness of the proximal limb and trunk
muscles. In a minority of patients, a febrile illness precedes this
subacute muscle weakness. Women outnumber men by 2 to 1, and the
age range is generally 30 to 60 years.226 Rarely,
severe muscle weakness occurs acutely with associated myoglobinuria.
++
Affected patients first notice weakness of the proximal limb
muscles when climbing steps, rising from chairs, or combing their
hair. The muscle pain that occurs in a minority of patients is of
a constant aching quality and follows the same distribution as the
weakness.227
++
Physical examination shows a symmetric weakness of the muscles
of the hips, shoulders, and thighs. Weakness of the facial and pharyngeal
muscles is also common. The muscles are not tender to examination,
and atrophy is not a prominent feature.
++
Dermatomyositis is characterized by skin lesions that may precede,
accompany, or follow the muscle involvement. The rash may take one
of several forms: localized erythema, maculopapular eruption, or
exfoliative dermatitis. The areas most predisposed include the eyelids,
the bridge of the nose, and the cheeks. The extensor surfaces of
elbows, knees, and knuckles may develop flat plaques known as Gottron’s
papules.228 The myositis that accompanies these
skin changes is indistinguishable from polymyositis.
++
Polymyositis or dermatomyositis may occur associated with an
underlying neoplasm (group 3) (Table 32-15). The muscle and skin
manifestations may antedate the discovery of a carcinoma by 1 to
2 years. This generally occurs with bronchogenic carcinoma.229 The
actual incidence of underlying carcinomas with polymyositis is 2% to
3%; it rises to 15% to 20% with dermatomyositis.
Idiopathic polymyositis and dermatomyositis occur less frequently
in children than in adults. The childhood form constitutes 8% to
22% of cases in most large series. The clinical features
of the disease in children are similar to those in adults; however,
children have a high incidence of vasculitis.230
++
++
Finally, polymyositis or dermatomyositis may occur in collagen
vascular disease. Mixed connective tissue diseases also may have
an accompanying arthritis that limits joint motion and further diminishes
strength.
++
Laboratory findings common to all the clinical subsets of dermatomyositis-polymyositis
include (1) elevated serum levels of skeletal muscle enzymes, particularly
creatine kinase (which may be elevated 10–80 times normal);
(2) sometimes positive tests for circulating rheumatoid factor and antinuclear
antibody; (3) myoglobinuria; (4) EMG studies showing an increase
in the insertional activity of the muscle with numerous fibrillation
potentials and positive sharp waves at rest231; and
(5) resultant muscle biopsy consisting of inflammatory infiltrates
(lymphocytes and histiocytes) between the muscle fibers and around
the small blood vessels in the muscle.232
+++
Other Forms
of Polymyositis
++
Trichinosis in humans is contracted by ingesting meat (usually
pork) containing the larvae of Trichinella spiralis. Once freed
from their cysts by gastric digestion, the larvae migrate into the
intestinal mucosa, where copulation occurs. The offspring (up to
1,500 per female) enter the circulation and are distributed to muscles
throughout the body. After entering the muscle, the larvae grow
and become encysted and eventually calcified. The life cycle then
ends. The muscles most affected include the eye muscles, diaphragm,
deltoid, pectorals, and gastrocnemius.233
++
The clinical severity of the symptoms correlates well with the
number of larvae disseminated to the tissues. Patients with less
than 10 larvae per gram of muscle are asymptomatic; those with greater
than 50 larvae per gram of muscle display gastrointestinal symptoms
(e.g., diarrhea and abdominal pain) 1 to 2 days after the infected
meat is eaten. This brief period is followed by a stage of muscular
invasion that may last up to 6 weeks. Affected patients have muscle
pain and tenderness with accompanying weakness. They also may have
fever, periorbital edema, conjunctivitis, and a maculopapular rash.
Severe cases develop various central nervous system manifestations.
Finally, myocarditis may occur, with resultant congestive heart
failure and electrocardiographic changes.
++
Laboratory findings include an eosinophilic leukocytosis (>500
eosinophils/μL) within the first few weeks.
Serologic tests may turn positive within the first month and remain
positive for years. A definitive diagnosis is made by muscle biopsy.
A portion of muscle is excised from the gastrocnemius or deltoid
and examined microscopically for the presence of larvae or calcified
cysts.234
+++
Eosinophilic
Myositis
++
Eosinophilic myositis consists of three separate clinical entities:
(1) eosinophilic fasciitis, (2) eosinophilic monomyositis, and (3)
eosinophilic polymyositis.235 The first entity
involves tenosynovitis with local pain and stiffness of unknown
cause. It progresses from one muscle to another but generally is
confined to an extremity. These patients have no systemic manifestations.
The muscle, per se, is not involved, and biopsy of fascia and tendon
sheaths reveals an inflammatory process with eosinophilic leukocytes.
++
The second entity includes muscle pain confined to one calf muscle
and associated with a tender mass. A muscle biopsy shows an inflammatory
necrosis and edema of interstitial tissues. Eosinophilic polymyositis,
as described by Layzer and colleagues,236 is characterized
by multiple systemic problems (congestive heart failure, anemia,
and pulmonary infiltrates) plus painful proximal muscle weakness.
The muscles themselves are swollen and exquisitely tender.237