Management of PNS disorders depends on the specific diagnosis.
However, a few general principles apply. When a peripheral disorder
is suspected or diagnosed in the ED, arrange for neurologic consultation
for further specific treatments. Careful supportive care is needed
for severe, life-threatening neuromuscular diseases and should begin
in the ED. Patients with the potential for respiratory failure,
aspiration, and cardiac dysrhythmias should be monitored appropriately.
Where the presentation warrants, baseline forced vital capacity
or negative inspiratory pressure should be measured in the ED to
assess whether there is need for imminent respiratory support or
admission to an intensive care unit (ICU). Hospital admission is
generally required for acute peripheral neurologic conditions in
which there is danger of respiratory or autonomic compromise or
in cases of debilitating or rapidly progressing weakness.
Botulism is a toxin-mediated illness that can
cause acute weakness leading to respiratory failure. In 2006, the
Centers for Disease Control and Prevention (CDC) reported 170 cases
of botulism, 106 of which were categorized as infantile botulism.2 Clostridium
botulinum, the causative organism, is an anaerobic spore-forming
bacterium found naturally in soil. Three of the eight known toxins
produced by C. botulinum cause human disease. These
are toxin types A, B, and E. Botulinum toxin A is used in the cosmetic
injection form, Botox® (Allergan, Irvine, CA). Most cases
of botulism are isolated events associated with improperly preserved canned
foods, although recently there has been an increased incidence of botulism
from wound infections. From 1995 to 1996, 42 cases of wound botulism
were reported in heroin users who injected subcutaneously, and in
2006 alone, 43 cases related to injection drug use were reported.
Toxin type E is associated with preserved or fermented fish and
marine mammals, and the latter are the most important sources of
botulism in Alaska, Japan, Russia, and Scandinavia. The botulinum
toxin works by binding irreversibly to the presynaptic membrane
of peripheral and cranial nerves inhibiting the release of acetylcholine
at the peripheral nerve synapse. With time, as new receptors are
generated, patients improve.
In classic botulism, because the disorder is at the neuromuscular
junction, there is no sensory deficit and no pain. Onset of symptoms
occurs 6 to 48 hours after the ingestion of tainted food. The
signs and symptoms of the disease—nausea, vomiting, abdominal
cramps, and diarrhea or constipation—might as easily
represent an acute gastroenteritis. Classically, botulism
also produces a descending, symmetric paralysis. The muscles first
affected are the cranial nerves and bulbar muscles. The patient
presents with diplopia, dysarthria, and dysphagia and may report “blurred
vision.” Deep tendon reflexes are normal or diminished.
Toxin-mediated decrease in cholinergic output results in anticholinergic
signs, such as constipation, urinary retention, dry skin and eyes,
and hyperthermia. Pupils are often dilated and nonreactive to light.
Pupil findings provide an important point of differentiation from myasthenia
gravis, which does not affect the pupil.
Infantile botulism occurs due to ingestion of C.botulinum spores
that germinate and produce toxin in the higher pH of the GI tract
of infants. The same spores do not result in disease in adults due
to the lower gastric pH in adults. Infantile botulism is usually
seen in infants between the ages of 1 week and 11 months and has
been implicated as a cause of sudden infant death syndrome. The
clinical presentation includes constipation, poor feeding, lethargy,
and weak cry; consequently, this diagnosis must be in the differential
of the “floppy” infant.
C. botulinum is classified as a category A bioweapon,
among the most lethal,3 by the CDC.
The diagnosis of C. botulinum intoxication is
made on the basis of clinical findings and exclusion of other processes.
The toxin can be identified in both serum and stool, but the assay
is not commonly available in most hospitals, and the assay process
is lengthy. If the suspected food source is available, it should
be tested for toxin. Treatment is initially focused on evaluating
respiratory effort and securing the airway if there is respiratory compromise. Botulinum
antitoxin can shorten the course of disease. The CDC recommends
giving one 10-mL vial of trivalent equine antitoxin as soon as the
diagnosis is made. Perform skin testing before administration to
assess for horse serum sensitivity. Recent experience with IV immunoglobulin
has shown a decrease in mechanical ventilation requirements and
lengths of ICU and hospital stays.4 A disease-specific human botulism
immune globulin has been developed and proven safe and effective
at decreasing severity of illness and resultant hospital stay.5 Patients diagnosed
with botulism require admission to the ICU and intubation for respiratory
failure. Suspected cases should be reported to the local health department
so that further exposures can be prevented.
Tick paralysis, also known as tick toxicosis, is an uncommon
disease. Multiple tick species can cause the disease process. The
responsible neurotoxin has not been well defined and there may be
more than one neurotoxin, based on the number of species involved.
Symptoms are first noticed 2 to 6 days after attachment of the tick. The
process may begin as ataxia and may lead to progressive lower then
upper extremity weakness. Infants and children may be listless
or irritable. When the bulbar nerves and diaphragm become involved,
respiratory failure ensues. There is significant mortality, up to
10%, associated with untreated tick paralysis.
Diagnosis is based on symptoms, and finding the culprit tick.
If no tick is found, the differential diagnosis includes other acute
neuropathies that can result in respiratory failure, such as Guillain-Barré syndrome,
botulism poisoning, and myasthenia gravis. Treatment is immediate
and complete removal of the attached tick. Local wound care and
supportive care (including intubation and mechanical ventilation
if necessary) results in excellent recovery within hours to days.6
Guillain-Barré syndrome (Landry-Guillain-Barré syndrome)
is an acute polyneuropathy characterized by immune-mediated peripheral
nerve myelin sheath destruction. Today, along with classic Guillain-Barré syndrome,
several variants are recognized. Although the exact cause is unknown,
there is a clear association with preceding triggering events, such
as viral or febrile illness, Campylobacter jejuni infection,
or vaccination. The syndrome normally affects men and women equally.
It is a monophasic illness with symptoms at their worst in 2 to
4 weeks and recovery that can vary from weeks to a year. Reported mortality
is 2% to 5%.
The classic Guillain-Barré syndrome is generally
preceded by a viral illness, followed by subacutely ascending symmetric
weakness or paralysis and loss of deep tendon reflexes. Paralysis may ascend to the diaphragm,
compromising respiratory function and requiring mechanical ventilation
in one third of patients. Table 166-2 lists
the specific diagnostic criteria for Guillain-Barré syndrome.
The diagnosis is mostly historical, but lumbar puncture and electrodiagnostic
information can improve confidence in the diagnosis. The ascending
weakness of Guillain-Barré syndrome is associated with
normal or hyporeflexic deep tendon reflexes and normal or decreased
muscle tone. Autonomic dysfunction may be present (Table
166-2). The Miller-Fisher syndrome variant is associated with C.
jejuni infection. It is more likely to be preceded by diarrhea
rather than a viral prodrome and is characterized by ophthalmoplegia,
ataxia, and decreased or absent reflexes. Weakness is less severe and
the disease course is milder than Guillain-Barré syndrome.
When Miller-Fisher syndrome is suspected, antibody testing for C.
jejuni can confirm the diagnosis. Acute motor axonal neuropathy is
a pure motor variant of Guillain-Barré syndrome, also associated
with C. jejuni infection, and is seen more commonly
in Japan and China. The acute motor and sensory axonal neuropathy variant
of Guillain-Barré syndrome involves loss of both motor
and sensory function. This disorder begins abruptly, progresses
rapidly, and has a prolonged course and poor prognosis.
Table 166-2 Diagnostic
Criteria for Classic Guillain-Barré Syndrome |Favorite Table|Download (.pdf)
Table 166-2 Diagnostic
Criteria for Classic Guillain-Barré Syndrome
|Progressive weakness of more than one limb|
|Progression over days to weeks|
|Recovery beginning 2–4 wk after cessation
|Relative symmetry of symptoms|
|Mild sensory signs and symptoms|
|Cranial nerve involvement (Bell’s palsy,
dysphagia, dysarthria, ophthalmoplegia)|
|Autonomic dysfunction (tachycardia, bradycardia,
dysrhythmias, wide variations in blood pressure, postural hypotension,
urinary retention, constipation, facial flushing, anhydrosis, hypersalivation) |
|Absence of fever at onset|
|Cytoalbuminologic dissociation of cerebrospinal
fluid (high protein and low white cell count)|
|Typical findings on electromyogram and nerve
conduction studies |
Lumbar puncture results show high protein (>45 milligrams/dL)
and white cell counts typically <10 cells/mm3,
with predominantly mononuclear cells. When there are >100
cells/mm3, other considerations include HIV, Lyme
disease, syphilis, sarcoidosis, tuberculous or bacterial meningitis,
leukemic infiltration, or CNS vasculitis.
Electrodiagnostic testing performed to support the clinical diagnosis
will show typical demyelination characteristic of Guillain-Barré syndrome.
In patients with the acute motor or acute motor and sensory axonal
neuropathy variants, electromyogram and nerve conduction studies
demonstrate axonal injury rather than demyelination. Early electrodiagnostic testing
may be falsely negative. Biopsy of the affected nerve reveals a mononuclear
inflammatory infiltrate. MRI performed to rule out differential
diagnostic possibilities will show enhancement of affected nerves.
The first step in the management of the patient with suspected
Guillain-Barré syndrome, or one of its variants, is assessment
of respiratory function, as airway protection in advance of respiratory
compromise decreases the incidence of aspiration and other complications. The most
well studied monitoring parameter is vital capacity, in which the
normal values range from 60 to 70 mL/kg. However, a simple
bedside assessment of ventilatory status is obtained by having the
patient count from 1 to 25 with a single breath, trending the values
they reach. Table 166-3 lists the indications
for intubation and ICU admission in Guillain-Barré syndrome.
If a patient does not initially meet criteria for intubation, ICU admission
may still be needed to avoid sudden, unmonitored respiratory failure.7
Table 166-3 Managing Respiratory
Failure in Guillain-Barré Syndrome |Favorite Table|Download (.pdf)
Table 166-3 Managing Respiratory
Failure in Guillain-Barré Syndrome
|Indications for intubation|
|Vital capacity <15 mL/kg|
|Pao2 <70 mm Hg on
|Bulbar dysfunction (difficulty with breathing,
swallowing, or speech)|
|Indications for admission to intensive care unit|
|Autonomic dysfunction (Table
|Initial vital capacity <20 mL/kg|
|Initial negative inspiratory force <–30
cm of water|
|Decrease of >30% of vital capacity
or negative inspiratory force|
|Inability to ambulate|
|Treatment with plasmapheresis|
IV immunoglobulin (IVIG) and plasmapheresis are used to treat
Guillain-Barré syndrome.8 IVIG and plasmapheresis
provide an equivalent but not an additive reduction in duration
of symptoms. IVIG is administered as 2 grams/kg over 2
days. For plasmapheresis, 200 to 250 mL/kg of plasma is
exchanged during five sessions over 7 to 14 days. There are adverse
effects seen with both modalities of treatment. IVIG has been associated
with thromboembolism and aseptic meningitis. Plasmapheresis is associated
with greater hemodynamic instability, but a lower rate of relapse.
Corticosteroids are of no benefit and may be harmful.
Patients with acute Guillain-Barré syndrome require
admission. This decision should be made in consultation with a neurologist
and may be based on clinical criteria alone, or with the confirmation
by CSF analysis and nerve conduction studies.
Mononeuropathies, unlike the processes above, are more likely
due to focal compression of a nerve, although systemic processes certainly
lead to mononeuropathy. Diabetes is the most common cause of noncompressive
focal neuropathy. Focal mononeuropathy can occur at any point of
compression along the course of a peripheral nerve. It is seen most
commonly along the ulnar, median, radial, and peroneal nerves. Other
nerves involved include the iliohypogastric, ilioinguinal, genitofemoral,
lateral femoral cutaneous, femoral, saphenous, obturator, common
peroneal, posterior tibial, superficial peroneal, and deep peroneal.
The most common form of any focal mononeuropathy is carpal tunnel
syndrome, which results from compression of the median nerve at
the wrist where it traverses the carpal tunnel. The carpal tunnel
is bounded by the carpal bones and the flexor retinaculum. The most
common etiology is injury due to repetitive use, but other causes
include diabetes mellitus, amyloidosis, trauma, and edema.
The classic signs of carpal tunnel syndrome are pain, paresthesias,
and numbness in the distribution of the median nerve—the
palmar aspect of the thumb, index, middle, and radial aspect of
the fourth finger. Patients may report symptoms in the entire hand,
but careful examination will reveal preserved sensation in the fifth
and ulnar fourth digits. Provocative testing, such as Tinel sign
and Phalen maneuver, can confirm the diagnosis (Figure
166-1). In Tinel sign, tapping on the palmar aspect of the wrist
will result in an electric shock sensation shooting into the hand when
there is compression of the median nerve. Reported sensitivity is 53% to
67%, and specificity is 55% to 100%.9 The Phalen
maneuver is positive when holding the wrists in flexion for 60 seconds
evokes or worsens symptoms. Reported sensitivity is 10% to
91%, and specificity is 93% to 100%.9 Electrodiagnostic
testing demonstrates slowing of nerve conduction across the carpal
tunnel. Testing is typically performed on an outpatient basis to
confirm the diagnosis or to aid in the decision for operative repair.
A. Tinel sign. The Tinel test is performed
by tapping the volar surface of the wrist over the median nerve. B. Phalen
maneuver. The Phalen maneuver is performed by compressing the opposing
dorsal surfaces of the hand with the wrists flexed together as shown.
This causes tingling over the median nerve distribution. (Reproduced
with permission from Simon RR, Sherman SC, Koenigsknecht SJ: Wrist.
In: Emergency Orthopedics: The Extremities, 5th ed. © 2007,
McGraw-Hill Inc., New York.)
The initial treatment of carpal tunnel syndrome
is conservative.10 For newly diagnosed patients,
behavioral modification is recommended, including weight loss and
avoidance of caffeine, nicotine, and alcohol. Encourage evaluation
of workplace ergonomics. Provide a wrist splint, with the wrist in
neutral position (Figure 166-2). NSAIDs are
given but are not clearly effective.11 Consider
diuretics if edema is a significant contributor to the patient’s
symptoms. Wrist splints, oral steroids, ultrasound therapy, and yoga
are reportedly effective in the short term compared with placebo.11 A dose
of 20 milligrams/d of prednisone for 1 week followed by
10 milligrams/d for another week was thought to be effective,
but the number of patients studied was small.10 Patients
with carpal tunnel syndrome are at long-term risk for impairment
and disability. Patients may be safely discharged from the ED, but
require close follow-up with a primary care physician or hand specialist.
If conservative treatment fails, the hand specialist will consider
corticosteroid injection and surgical release.
Typical wrist splint with wrist in neutral position,
for treatment of carpal tunnel syndrome. (Courtesy of Barbara Steckler
and Judy Tintinalli.)
Cubital tunnel syndrome is the most common ulnar mononeuropathy
and the second most common compressive mononeuropathy after carpal
tunnel syndrome. The ulnar nerve extends from the medial cord of
the brachial plexus and courses through the cubital tunnel behind
the medial epicondyle at the elbow before entering the forearm.
At the wrist, it passes through the Guyon canal, bounded by the
hamate and pisiform bones and the ligament connecting them. It supplies
cutaneous innervation to the medial palm via the superficial terminal
branch and to the fifth and medial fourth fingers via the deep terminal
branch and innervates the palmaris brevis muscle. The median nerve
is most vulnerable to repetitive stress inflammation and trauma
in the cubital tunnel and Guyon canal.
The classic symptoms of cubital tunnel syndrome include
tingling in the fifth and lateral fourth fingers. With time,
numbness and weakness of the intrinsic muscles of the hand develop.
In severe cases, paralysis and wasting of the intrinsic muscles
of the hand may occur. As in the case of carpal tunnel syndrome,
provocative testing is useful. Evoke a Tinel sign by tapping on
the cubital tunnel at the elbow. A positive elbow flexion
sign is seen when symptoms recur within 3 minutes when the elbow
is held in flexion with the wrist in extension. Froment sign may be
noted during resistance testing when the thumb intraphalangeal joint flexes
to compensate for weakness of the adductor pollicis brevis. In Guyon
canal syndrome, also known as handlebar palsy,
compression of the ulnar nerve in the eponymic canal is more likely
to spare sensory fibers and present as intrinsic weakness. In the
patient with suspected cubital tunnel syndrome, consider C8 entrapment
and thoracic outlet syndrome. C8 entrapment can be differentiated
by the presence of neck pain and worsening symptoms with neck flexion.
Thoracic outlet syndrome worsens with shoulder abduction. Electrodiagnostic
testing serves to precisely localize the lesion.
In most cases of ulnar nerve mononeuropathy, the goal of treatment
in the ED is to initiate conservative treatment and to ensure appropriate
follow-up. Pain is not a common component of this syndrome, but
anti-inflammatory medication may reduce the patient’s symptoms.
Rest the elbow by reducing repetitive use at work or home and by
splinting with a long arm posterior splint. For a chronic or long-standing
injury, a sling may suffice for support. The patient may benefit
from physical therapy and occupational therapy referrals. In cases
in which nerve compression is acute and likely due to fracture or
hematoma, seek immediate surgical consultation. If this is not the
case, prompt surgical referral still remains important. If the patient’s
symptoms persist beyond 3 to 6 weeks despite conservative treatment
and therapy, surgical treatment with nerve decompression, transposition,
or medial epicondylectomy is usually required.
of the Deep Peroneal Nerve
Compression of the deep peroneal nerve may result from trauma,
rapid weight loss, or habitual crossing of the legs. The nerve may
become entrapped at several locations along its course, including
the fibular head, anterior to the ankle joint, as it passes beneath
the extensor retinaculum (anterior tarsal tunnel syndrome), and
distal to this point. Patients develop foot drop or numbness of
the web between the great and second toes. Conservative treatment
is initially recommended. Prompt follow-up with a neurologist is
important, as nerve conduction studies should be performed to differentiate this
syndrome from lumbar root or motor neuron disease.
Meralgia paresthetica is the name given to entrapment, usually
in the inguinal canal, of the lateral femoral cutaneous nerve. The
etiology of this syndrome can be intrapelvic (pregnancy, enlarging
mass, aneurysm), extrapelvic (trauma, tight garment or belt, obesity),
or systemic (diabetes). Meralgia paresthetica presents with numbness
and pain of the anterolateral thigh. On examination, the
patient may note hyperesthesia in the area of pain and may exhibit
a Tinel sign over the anterior superior iliac spine. The pelvic
compression test supports this diagnosis. Turn the patient on his
or her side, compress the pelvis, and if the patient’s
symptoms are relieved after 30 seconds of lateral compression of
the pelvis, the diagnosis is confirmed.
Conservative management with NSAIDs, weight loss, relief from
tight garments, and physiotherapy is usually successful. Tricyclic
antidepressants may provide some benefit in the management of the
associated dysesthesias. Local injection of lidocaine and corticosteroid
near the insertion of the inguinal ligament into the anterior superior
iliac spine provides relief. Ultimately, surgical decompression
or nerve resection may be required for relief of symptoms.
Mononeuritis multiplex is a group of disorders that have in common
the dysfunction of multiple peripheral nerves separated both temporally
and in anatomic location. Signs and symptoms include weakness, paresthesias,
numbness, aches, and spasms of sharp pain. Early in the disease,
the affected nerves may be separated out by careful history and
physical examination. As the disorder progresses, signs and symptoms
become confluent and more symmetric. Symptoms may progress over
minutes to days and resolve over weeks to months. Diabetes mellitus
is the most common cause of mononeuropathy multiplex, but other
systemic diseases are also associated with the disorder (Table 166-4). The diagnosis of mononeuritis
multiplex usually requires specialty referral and electrodiagnostic
testing. Treatment is management of the underlying cause.
166-4 Etiologies of Mononeuritis Multiplex |Favorite Table|Download (.pdf)
166-4 Etiologies of Mononeuritis Multiplex
|Human immunodeficiency virus|
|Intraneural neoplastic infiltration|
|Connective tissue disorders|
|Systemic lupus erythematosus|
The cervical, brachial, and lumbosacral plexuses are formed by
the convergence of nerve roots, which then branch into peripheral
nerves. In the case of the brachial plexus, the process of mixing
and dividing is repeated in the stages of trunks and cords before
peripheral nerves take off. Plexopathies share many etiologies,
the most common being penetrating trauma, surgery, neoplasm, and
radiation therapy. Despite this similarity they can differ significantly
in diagnosis and management.
The cervical plexus, formed by the C1-C4 nerve roots, is the
least frequently noted location of plexopathies. Apart from trauma
or neoplasm, the condition is occasionally seen postoperatively due
to positioning during surgery. Patients may have very few symptoms.
Neoplastic lesions may cause a deep boring and constant pain. Due to
anatomic parameters, electrodiagnostic assessment is difficult and
unreliable. A concern for neoplastic process should prompt imaging
with CT, MRI, or PET scan. The management of cervical plexopathy
is usually non-operative.
The brachial plexus, formed by the C5-T1 nerve roots, is the
most common site of plexopathy. The brachial plexus is made complex
by the nerve roots merging into upper middle and lower trunks, which
split and merge into lateral posterior and medial cords that split again
and form five peripheral nerves (Figure 166-3).
Injury at each of these anatomic locations will result in differing
symptoms. Brachial plexopathies generally manifest as weakness first,
but pain and paresthesias may also develop. On examination, the
patient has weakness in various distributions of the brachial plexus.
The upper trunk is the more common site of involvement, affecting
strength of proximal arm and shoulder musculature. Infraclavicular
plexopathy due to trauma is frequently associated with injury to
the axillary vessels. Causes of brachial plexopathy include
trauma (penetrating, humeral neck fracture, or dislocation), shoulder
reduction, neoplasm (Pancoast tumor), radiation, or surgery. Several
syndromes have been well described. Rucksack palsy is seen in military
personnel, hikers and climbers, and people carrying a heavy load in
a pack. Unilateral weakness, which may lead to paresthesias and
atrophy, usually resolves within months. Burner syndrome is seen
in athletes (football players in particular) who suffer
sudden axial impact of the shoulder. This results in a short-lived burning
and anesthesia of the affected limb and resolves spontaneously. Neurogenic thoracic
outlet syndrome results from the stretching of the T1 root over
either a cervical rib or a band from C7 to the first rib. Patients
may report a long-standing ache, but usually atrophy of the hand musculature
is noted first.
The anatomy of the brachial plexus. [Reproduced
with permission from Reichman EF, Tolson DR: Regional nerve blocks,
in Reichman EF, Simon RR (eds): Emergency Medicine Procedures.
New York, McGraw-Hill, 2004.]
Spine imaging and electrodiagnostic testing may be performed
outside the ED setting. Many brachial plexopathies can be managed
conservatively. Those due to cervical rib, midshaft clavicular fracture,
or penetrating trauma may require exploration for associated injuries.
The L1-S4 nerve roots form the lumbosacral plexus. Causes of
lumbosacral plexopathy are less likely traumatic and more likely
to include radiation, diabetic amyotrophy, aortic aneurysm, retroperitoneal
hemorrhage, or compression from arteriovenous malformations. The
differential diagnosis also includes the cauda equina and conus
medullaris syndromes. Lesions affecting the lumbar portion of
the plexus result in weakness of hip adduction and flexion and knee extension,
decreased sensation at the top and inner thigh, and decreased patellar
reflexes. Lesions affecting the sacral portion of the plexus result
in inability to abduct the thigh at the hip joint, weakness of hip
extension and knee flexion, and decreased sensation of the back of
the thigh and below the knee.
Plain radiographs of the lumbar spine are useful to screen for
spine compression from degenerative or neoplastic disease. MRI should
be performed when cord injury is a concern. CT scanning of the abdomen
is useful to exclude aortic aneurysm and psoas muscle masses or
retroperitoneal hemorrhage, which can also lead to asymmetric lower
extremity weakness. Electrodiagnostic testing is not of great utility.
Management of plexopathies is usually directed at the underlying
Virus–Associated Peripheral Neurologic Disease
HIV infection, its complications, and its pharmacologic
treatments are associated with a number of peripheral neurologic
disorders. The most common of these, HIV neuropathy and antiretroviral
drug-induced neuropathy, are chronic processes that do not cause
sudden disability or symptoms. HIV-infected patients have
a high rate of mononeuritis multiplex and an inflammatory myopathy
resembling polymyositis. In late-stage acquired immunodeficiency
syndrome, almost all patients manifest neuropathy. Occasionally,
patients will complain of weakness that progresses over the course
of days. Patients in the early stages of HIV infection have greater
susceptibility to Guillain-Barré syndrome. The presentation
is similar to that of the non–HIV-infected patient, except
that a CSF pleocytosis is commonly seen. Treatment is conservative. Gabapentin
may be useful, and topical Lidoderm appears to be ineffective.
In the latter stages of acquired immunodeficiency syndrome, patients
may suffer from an acute polyradiculopathy caused by cytomegalovirus
(CMV) infection. Evidence of systemic CMV infection, including retinitis,
is almost always present. As opposed to the more common chronic
neuropathy of HIV, patients with CMV radiculitis become acutely
weak, with primarily lower extremity involvement, and may have variable
degrees of bowel and bladder dysfunction. The examination
shows primarily lower extremity weakness and hyporeflexia, with
decreased sensation in the lower extremities and groin. Rectal tone
may be impaired. Lumbar puncture reveals a pleocytosis with predominantly
polymorphonuclear cells and modestly increased protein. Viral DNA
is detected by polymerase chain reaction in most patients and is
highly specific. MRI of the lumbosacral spine demonstrates swelling
and clumping of the cauda equina. Imaging of these patients is mandatory
to exclude mass lesions of the lower spine or nerve roots. Early
identification is important, as antiviral treatment is effective. The
treatment of CMV radiculitis is IV ganciclovir, started at 5 milligrams/kg
every 12 hours for 3 to 6 weeks, which may be initiated before definitive
Neuropathies can also be chronic or subacute associated with
an underlying medical disorder. A detailed discussion of neuropathies associated with underlying
medical illness is worthy of an entire text. Table 166-5 shows
the expected presentations for some diseases associated with peripheral
Table 166-5 Framework
to Approach Chronic Neuropathies |Favorite Table|Download (.pdf)
Table 166-5 Framework
to Approach Chronic Neuropathies
|Etiologies||Sensory||Motor||Sensory and Motor||Autonomic|
|Infectious ||Human immunodeficiency virus||Lyme disease||Syphilis||Chagas disease (American trypanosomiasis)|
|Nutritional ||Beriberi||—||B12 deficiency||—|
|Neoplastic ||Paraneoplastic ganglionopathy||—||Paraneoplastic polyneuropathy||—|
|Hereditary ||Hereditary sensory neuropathy||—||Charcot-Marie-Tooth disease||Amyloidosis|
|Inflammatory||Sjögren syndrome||Chronic inflammatory demyelinating polyneuropathy||Mononeuritis multiplex||—|
|Paraproteinemias, dysproteinemias||Anti-MAG sensory neuropathy||Anti-GM1 motor neuropathy||Waldenström macroglobulinemia||Amyloidosis|
Diabetes mellitus, due to its associated microvasculopathy, remains
the most common cause of noncompressive focal neuropathy. Half of
patients with diabetes have symptoms of neuropathy, and 15% require treatment
for their symptoms. A variety of mechanisms contribute to the pathophysiology
of diabetic neuropathy. Chronic hyperglycemia and glycemic variability
lead to oxidative stress and neuroinflammatory processes that result
in a variety of neuropathic syndromes.
Diabetic peripheral neuropathy is the term used
for any neuropathy in a diabetic patient. The most common
manifestation of diabetic peripheral neuropathy is a distal symmetric
polyneuropathy, but it may also lead to focal neuropathies
and mononeuropathy multiplex. Diabetic peripheral neuropathy is
seen in patients with type 1 diabetes after 5 years and early on
in the course of type 2. It is associated with significant morbidity.
The most common cause of nontraumatic amputation is injury resulting
from impaired sensation due to diabetic peripheral neuropathy that
fails to heal because of the impaired blood flow of diabetic vasculopathy.
Diabetic peripheral neuropathy is an example of a distal axonopathy
resulting in length-dependent “dying back” of
the affected nerves. This phenomenon produces the typical stocking
and glove distribution of diabetic neuropathy.
Hyperglycemic neuropathy is seen in newly diagnosed diabetics
and normally improves with glycemic control. Insulin neuritis is
a small fiber neuropathy with pain and paresthesias associated with
insulin therapy. Painful diabetic neuropathy is a chronically painful
neuropathy seen in 10% of diabetics. It is usually intermittent,
worse when attentive and at night. It can be experienced variably
as pins and needles, throbbing, burning, achy, or cramping. Duration
is <6 months. Beyond 6 months, the same process is termed chronic
painful diabetic neuropathy. Diabetic neuropathic cachexia is
a rare syndrome causing weight loss and painful dysesthesias of
the limbs and trunk.
Diabetic amyotrophy is a lumbosacral plexopathy seen in patients
with a long-standing history of diabetes and presents with back
pain followed by weakness. Patients report the acute onset of ipsilateral
back pain, followed within days by progressive leg weakness. Sensory
findings are absent. The examination reveals decreased leg power
in a variety of patterns reflecting impairment of plexus function
with relatively symmetric sensation. There may be muscle wasting
in affected limbs in long-standing disease. Deep tendon reflexes
may be diminished on the affected side. Bowel and bladder functions
are not affected.
There is a clear relationship between glycemic control and neuropathy. The
Diabetes Control and Complications Trial12 showed
a 60% reduction in risk of developing neuropathy with tight
glycemic control. Foot care should be stressed to the patient who
has already developed neuropathy. Neuropathy-associated anesthesia
may result in inadvertent trauma. Injuries lead to the development
of ulcers, cellulitis, and eventually amputation. Symptomatic management
is an ED patient’s most immediate concern. NSAIDs may alleviate
discomfort, but are relatively contraindicated in the diabetic patient.
Narcotics carry addictive potential. Tricyclic antidepressants,
anticonvulsants, and topical capsaicin all have proven beneficial
(Table 166-6). The best evidence supports
the use of duloxetine, pregabalin, tricyclic antidepressants, or
oxycodone. For further discussion of neuropathies in diabetics,
see Chapter 219, Type 2 Diabetes Mellitus.
Table 166-6 Medications
Used in the Treatment of Painful Diabetic Neuropathy |Favorite Table|Download (.pdf)
Table 166-6 Medications
Used in the Treatment of Painful Diabetic Neuropathy
|Anticonvulsants||Pregabalin, 50 milligrams three times daily||May cause somnolence, dizziness, weight gain.|
|Gabapentin, 300 milligrams at bedtime||Similar adverse effects to pregabalin.|
|Antidepressants||Duloxetine, 30 milligrams daily||Consider with concomitant depression.|
|Desipramine, 10–25 milligrams before bedtime||Tricyclic antidepressant with fewest side effects.|
|Topical therapy||Capsaicin, 0.075% up to four times daily||Apply using gloved hand.|
|Lidocaine, 5% two to four patches daily||Cut in half to save cost.|
CR®, 10 milligrams twice daily||May cause constipation, somnolence.|
|Tramadol, 50 milligrams twice daily||Avoid in patients with seizure or on selective serotonin reuptake