Pathology Lab IV - Diseases of the Peripheral Nerve DISEASES OF ...
Pathology Lab IV - Diseases of the Peripheral Nerve
DISEASES OF THE PERIPHERAL NERVE.
Dr Alden W Dudley Jr
3. Case presentation: Adam A with back pain, weakness in the right arm, and cranial nerve palsies
4. Differential diagnosis
5. Neuroborreliosis (Lyme disease)
6. Case presentation: Helen L with paralysis after diarrhea for one week
7. Differential diagnosis of Guillain-Barre syndrome (GBS)
1. Recognize the impact of direct and indirect insults to peripheral nerves.
2. Learn how to use Clinical Pathology Laboratory tests to make diagnoses.
3. Separate central from peripheral causes ofperipheral neuropathies.
4. Understand how nerves can be vulnerable to metabolic, toxic, infectious, autoimmune, and tumor factors.
5. Realize that multi-system disease may be induced by a single agent or biological phenomenon.
1. Anthony DC, Frosch PM, DeGirolami U. Peripheral nerve and skeletal muscle. In Robbins and Cotran Pathologic
Basis of Disease, Elsevier Saunders,Phil, 7th ed. 2005:1325-1335
2. Greer DM, Schaefer PW, Plotkin SR, et al. Case 11-2007. A 59 yo man with neck pain, weakness in the arms, and
cranial nerve palsies. New Engl J Med 2007;356:1561-70
3. Griggs, RC. Neuromuscular diseases:Disorders of the motor neuron and plexus and peripheral nerve disease.In
Andreoli and Carpenter’s Cecil Essentials of Medicine, Saunders Elsevier, Phil, 7th ed 2004:1143-1151
4. Hauser SL, Asbury AK. Guillain-Barre syndrome and other immune-mediated neuropathies.In Harrison’s
Principles of Medicine, 16th ed. 2005: 2513-2517.
5. Mosca L, et al. Evidence-based guidelines for cardiovascular disease prevention in women: 2007 update.
6. Ropper AH, Cros DP, Palmer-Toy DE. Case 39-1999: A 74 yo woman with acute, progressive paralysis after
diarrhea for one week. N Engl J Med 1999;341:1996-2003
7. Steere AC. Lyme borreliosis. In Harrison’s Principles of Internal Medicine, 16th ed. McGraw-Hill, NY. 2005:995-
Illustrations are from the authorand the above.
3. Case presentation: Adam A with back pain, weakness in the right arm, and cranial nerve palsies
Adam is a 44 yo male in good health who developed five weeks ago fever to 39.4oC and neck stiffness.
The primary care physician noted thrombocytopenia and lymphocytosis on his Differential and diagnosed a viral
illness, not otherwise specified (NOS). He was given antiviral agents, the fever declined over five days, and the
platelet count returned to normal over two weeks. However, the discomfort in his neck gradually worsened. One
week before admission, numbness of the right hand developed, followed by weakness of the right hand and
neck during the next three days. He was married, a land surveyor, owned two dogs, and played golf frequently.
He had many tick bites in the past but none recently, and the bites had not been followed by any rash. He had been
diagnosed one year ago with diabetes mellitus and was treated with 5 mg glipizide daily.
Four days before admission, Adamwas evaluated by an orthopedist. MRI of the neck revealed degenerative
changes of the spine at multiple levels from C3 to T2 with broad-based central herniation at C3-C4 and mild
protrusions at other levels. He was treated with ibuprofen, methocarbamol, and oxycodone-acetaminophen. The
right arm became weaker, the neck pain more severe (9 / 10 with 10 the most severe possible), radiating down
The day before admission, left ptosis and diplopia developed. On the day of admission, Adam did not
have fever, headache, nausea, vomiting, or a skin rash. Vital signs showed BP 156/85, P 101, R 20, and T
36.1oC. Gaze was directed to the right and strength in the right hand was decreased. CT scan of the head
uncovered no abnormalities.
On examination, Adam was alert but uncomfortable with pain in the neck, back, and left eye. His BP had
climbed to 163/89, but other vital signs were normal. There was left ptosis and tenderness to palpation of the left
orbit and globe. He kept his right lid shut because of diplopia. He was unable to adduct, fully elevate, or depress
his left eye; there was no nystagmus. The left nasolabial fold was flattened and the smile was asymmetric. Muscle
strength was reduced in both arms, particularly the right wrist flexors and extensors and interosseous muscles.
Light touch, pinprick, and temperature sense were decreased in the right hand and forearm and right biceps
and triceps tendon reflexes were absent. Index finger-to-nose testing revealed marked dysmetria bilaterally and
the gait was unsteady.
A lumbar puncture had an elevated opening pressure of 266 mm H2O. Four tubes of fluid were drawn
and the first had 42 RBC while the fourth had only 10 (Table 3.1). This was attributed to breaking a small artery on
entry (common, part of why you draw four tubes). However, there were many more WBCs with a lymphocytosis
and elevated monocyte count (Fig 3.1). The abnormal lymphocytes gave brief consideration for a lymphoma, but
abnormal plasma cells and monocytes made the reaction too widespread for a stem cell malignancy. The B
lymphocyte chemoattractant CXCL13 has been found in the CSF of Lyme disease patients, but not other infectious
diseases. This favored a subacute or chronic disorder. In view of the leukocyte response, an elevated protein was
expected. Tube 2 was spun and the sediment viewed microscopically for bacteria (Gram and acid fast stains) and
fungi (India ink preparation for dark background where fungal cocci would displace the black ink to stand out).
Cultures of the CSF were negative. A battery of serum antibody tests was ordered for viral agents that commonly
affect the CNS (Table 3.2).
Magnetic imaging resonance (MRI) scanning of the brain showed enhancement of the bilateral fifth and
third cranial nerves and microangiopathic disease (Fig 3.2). MRI of Adam’s spine showed leptomeningeal
enhancement that extended from the lower thoracic portion to the conus medullaris and roots of the cauda
On the third hospitalday, a repeat LP had an opening pressure of 24 mm (patient relaxed). Recurrent
lymphocytosis and cells of uncertain origin prompted flow cytometry for separation of cells by type.This revealed
large CD19+ but CD20- cells, CD4+ and CD8+ T cells, and polyclonal CD20+ cells with cytoplasmic kappa and
lambda light chain expression (plasma cells).
On the fourth hospital day, dyspnea and dysarthria developed. Pulmonary vital capacity had been 3.4
L on admission, but was now 2.8 L.A chest x-ray showed low lung volumes and bibasilar opacities consistent with
atelectasis. On the sixth day, Adam was unable to raise his head, the gag reflex was diminished, and dyspnea
increased. The next day, respiratory failure developed with a vital capacity of only 1 L and partial pressure of
CO2 of 64 mm Hg. Adam was transferred to the ICU where he was given sedation, tracheal intubation, and
mechanical ventilation. Doxycycline and acyclovir were given to treat bacterial and viral agents in a shotgun
fashion. The diagnoses under consideration are given in Table 3.3.
4. Differential diagnosis
There are two autoimmune disorders to consider in Adam: acute inflammatory demyelinating
polyradiculopathy (ADIP; Guillain-Barre syndrome or GBS) and myasthenia gravis. GBS commonly presents with
rapidly developing weakness over hours or weeks, as in Adam. The weakness usually is ascending but the arms
and face or face only can be affected first. Oropharyngeal weakness can develop, as can weakness of the
diaphragm. Like Adam, it typically has a prodrome of a viral weakness or vaccination a few weeks earlier.
However, there is no acute fever, the CSF is acellular, and the CSF protein is even more highly elevated and MRI
is most often normal or very subtle.
Myasthenia gravis is a disorder of the myoneural junction that presents with progressive or fluctuating
weakness with particular involvement of extraocular and cranial muscles. Facial and neck weakness are
common and respiratory failure can occur. However, sensory nerves are not involved so it is completely painless.
Because it is not a disorder of the CNS, the lumbar puncture is normal.
Inflammatory disorders for consideration are Wegener’s granulomatosis and sarcoidosis. Wegener’s is
a systemic autoimmune vasculitis that frequently involves the CNS. The orbits are affected in 50% of patients
for proptosis and do produce Adam’s pain and tenderness. Cranial nerves II, VI, and VII are often involved, as in
Adam’s MRI. However, the lungs are also involved, he had thrombocytopenia instead of thrombocytosis with
venous thrombi, and antinuclear antibody testing is positive.
Sarcoidosis often affects the CNS, particularly the sella turcica and leptomeninges. Facial nerve palsies
occur in one-third of patients and are often bilateral. However, sarcoidosis starts in the lungs with marked hilar
lymphadenopathy that was not present on Adam’s chest films. Also, his serum angiotensin converting enzyme
(ACE) level was normal whereas this is elevated in 50% of sarcoid patients.
Potential infectious causes of Adam’s picture include neurosyphilis, brucellosis, cryptococcal meningitis,
and neuroborreliosis. Syphilitic meningitis usually occurs one year after the primary chancre on the genitalia and
secondary rash on the hands and feet. (Not just palms and soles: that is Rocky Mt spotted fever.) These patients
develop pachy- as well as leptomeningitis and have small vascular strokes. Adamhad not the symptoms of primary,
secondary, or classical tertiary syphilis. Serologic tests were negative.
Brucellosis certainly causes moderately severe neck pain and acute, subacute, or chronic
granulomatous inflammation of the meninges. However, Adam had not worked with cattle, consumed raw milk,
or had other risk factors, and had negative serologic tests for Brucella agglutination. Similarly, cryptococcal
antigen tests were negative and the CSF India ink test showed no cocci.
5. Neuroborreliosis (Lyme disease)
Lyme disease (neuroborreliosis) has 15% of its patients develop the three cardinal signs of: lymphocytic
meningitis, cranial neuropathies (most often bilateral VII), and a painful radiculitis. Peripheral neuropathies
can present as radiculopathy, plexopathy, diffuse polyneuropathy, or acute inflammatory demyelinating
polyradiculopathy (GBS). MRI may show enhancement of nerve roots, focal brain, or spinal cord. The CSF has
a lymphocytic pleocytosis up to several hundred cells, while the protein is only moderately elevated or normal.
Respiratory failure and neck weakness are uncommon.
Most patients develop expanding skin lesions (erythema migrans) at the tick bite. The deer tick, Ixodes
ricinus, is the size of a poppy seed and is easily missed when examining the lower leg after a walk in the woods in
the northeastern United States or eastern Canada. After several days or weeks, there may be disseminated infection
with flu-like symptoms of fever, malaise, headache, and myalgias. Vague or migratory arthralgias are common
and Lyme disease should be at the top of your differential list for woodsmen, farmers, campers, and pet owners
of all ages.
In clinical practice antibody testing is used for confirmation of Lyme borreliosis. The CDC recommends
two-tier testing by enzyme-linked immunosorbent assay (ELISA) and by Western blotting. On the 11th hospital
day, Adam’s CSF was reported positive for B burgdorferi antibody and nucleic acid (Table 5.1). The positive
PCR for B burgdorferi DNA in CSF suggests large numbers of organisms in the meninges. The positive IgM
antibody response and early IgGrise by ELISA and Western blot were consistent with a subacute infection.
Management is by IV ceftriaxone (2 g daily) for 2-4 weeks. Adam received it for 6 weeks because of the severity
of disease. Neuropathic pain improves within days, but weeks are required for correction of the CSF pleocytosis.
Months may be necessary for total or nearly complete resolution of sensory or motor neuropathies. Most patients
have nearly complete recovery.
Adam remained hospitalized for thirty days, was discharged to a rehabilitation facility for three weeks, and
is now living at home independently. However, he has residual weakness and decreased dexterity of the hands
and continues to have pain in the neck and shoulder. The pain may diminish slightly and slowly over the rest of
6. Case presentation: Helen L with paralysis after diarrhea for one week
Helen is a 74 yo woman admitted to the hospital because of diarrhea and fever followed by progressive
multiple cranial nerve palsies. She had a one week history of fever (40oC), watery diarrhea, nausea, abdominal
pain, weakness, and fatigue. The day before admission, Helen could speak normally. She later applied a benzocaine-
eugenol preparation to her gums because of dental pain. She awakened at 3 AM not feeling well and was unable
to speak. However, she could write complete, coherent sentences.
Helen’s medical history included hypertension and aortic stenosis for which she had replacement with a
porcine valve five years ago. She smoked heavily, developed emphysema, and had the right upper lobe of her lung
removed six years ago for cancer. Herpes zoster (shingles) developed on the right side of her back four months ago.
Additional problems included gallstones, peptic ulcer disease, and gastroesophageal reflux disease. She was taking
hydrochlorothiazide-triamterene and verapamil for hypertension, and KCl to offset potassium loss from the diuretic.
There was no history of ingestion of chicken or unusual or canned foods, exposure to pets, recent foreign
travel, use of alcohol or drugs, exposure to ticks, previous neurologic problems, chest pain, or loss of vision.
Examination in the Emergency Room found vital signs of T 36.6, P 105, R 25, and BP 210/150. Helen was
able to drink water, walk, and she was oriented. She understood complex commands and gave positive or negative
responses by thumbs up or down. She reported in writing perioral numbness and dysphagia. Bilateral ptosis,
greater on the right side, and left skew deviation were present. She could not move either eye in any direction and
the doll’s head maneuver elicited no movement. Corneal and pupillary reflexes were absent; there was
bilateral facial weakness. The gag reflex was intact, but the tongue deviated to the left. The vocal cords were
normal. Muscle strength was 4/5, except bilateral deltoid, biceps, and triceps where it was 2/5. Deep tendon and
plantar reflexes were normal the day before, but absent in the arms on admission.
The results of laboratory tests are shown in Tables 6.1-3 in their order of receipt from the labs.
Hematological abnormalities of interest were the elevated Sed Rate and WBC indicative of infection. The shift
toward neutrophils favored an acute bacterial infection. The blood chemistries showed elevation of glucose (fasting
and diabetic or receiving IV saline with glucose?). Also, the enzymes were uniformly mildly elevated to suggest
tissue injury in the liver, gallbladder, pancreas, and skeletal muscle. The CSF was surprisingly normal. MRI of the
brain showed diffuse enlargement of ventricles, sulci, and cisterns (atrophy in the elderly) and foci of hyperintensity
in periventricular white matter, right pons, and midbrain consistent with s mall vessel ischemia. An MRA found no
occlusion of neck or intracranial arteries.
On the second hospital day, BP was 150/75, and T 37.7. Both arms were flaccid with strength 1/5 in the wrists
and 2/5 in the fingers. Motor conduction studies of the right median and tibial nerves showed a low amplitude
compound response. Sensory nerve action potentials were normal (Table 6.4). Botulinum toxin, penicillin, and
ofloxacin were given.
On the third hospital day, Helen’s mental status was normal and cranial nerves were unchanged.
However, she could now move her right thumb only minimally, could not lift either leg, and could only wiggle
her feet up and down. The legs no longer had deep tendon reflexes.
Until recently, this would have been diagnosed at many medical centers as an obvious case of poliomyelitis
destroying motor neurons and causing some sensory symptoms by edema around sensory pathways. So, what is the
7. Differential diagnosis of Guillain-Barre syndrome (GBS)
Muscle weakness must be explained by a lesion at one of four sites: central (and spinal) motor neurons
and their pathways,the nerves, neuromuscular junctions, or the muscles themselves. When one evaluates each site in
this case, the diagnosis becomes apparent.
Primary muscle disease can result in oropharyngeal weakness and ptosis, but not over a period of two or three
days. Further, ocular paralysis is not a feature of muscle disease except in select heritable myopathies that progress
over years. Therefore, primary muscle disease is highly unlikely.
Disorders of the neuromuscular junction, like myasthenia gravis, preferentially involve ocular and
cranial muscles and may progress rapidly. However, they do not affect corneal and pupillary reflexes. Botulism
causes a nasal quality of the voice, dysarthria, dysphagia, strabismus, ptosis, and fixed pupils, usually within 24
hours of eating the contaminated food. Helen had a much longer interval after her diarrhea, no dryness of the mouth
and throat, and had a fever (absent in botulism). The addition of sensory loss ruled out botulism. Neuromuscular
junction disorders have a normal CSF.
Poliomyelitis certainly would have killed motor neurons in the cord, brainstem, and cortex. But it would
also have caused fever and definite changes in the CSF. Rarely did it cause unilateral or especially bilateral
ophthalmoplegia. Basilar artery occlusion with ischemia to the brainstem nuclei would not spare ascending and
descending sensory pathways or the limbic systemto leave the patient fully alert.
We must, therefore, conclude Helen had a cranial nerve disorder. Metastatic tumors can ultimately
surround most cranial nerves, but this starts asymmetrically and slowly and reveals malignant cells in the CSF.
Infections such as tuberculosis, sarcoidosis, fungi, syphilis, Lyme disease, and idiopathic granulomatous disease can
focus on the cranial nerves, but again they are slower, change the CSF, and cause fever.
Diphtheria is a close contender, especially with palatal paralysis as an early symptom. Extraocular
paralysis occurs in 15% of patients with diphtheria, but it is sequential rather than simultaneous. Also, there should
be an exudative patch on the pharynx as the source of the organismand its toxin.
Predominant weakness of the ocular and oropharyngeal muscles characterizes one of the several
variants of GBS in which weakness is purely or predominantly regional. Guillain et al described afebrile (to
distinguish it from polio) generalized paralysis in 1916. Fisher in 1956 identified a syndrome of ataxia, external (and
sometimes internal) ophthalmoplegia, and areflexia. Additional variants have been delineated with all sharing
areflexic weakness, shared EMG abnormalities only in the weakened regions, and elevated CSF protein. The
oculomotor and lower cranial nerve variants have a proclivity to coalesce, as in Helen.
An absence of diplopia is common because of complete ophthalmoplegia characteristic of Guillain-
Barre and loss of reflexes from one day to the next is almost diagnostic of GBS. While 70% of patients with GBS
have CSF proteins below 45 mg / dL, it tends to climb slowly beyond that point. This is in part due to autoantibodies
directed against gangliosides accumulating on myelin around the nodes of Ranvier.
The enteric pathogen Campylobacter jejuni is the most common infectious trigger for GBS. The
lipopolysaccharide coat of C jejuni shares epitopes with gangliosides of Schwann cells, specifically GQ1b and
GM1. Different concentrations of ganglioside variants in certain nerves may account for the regional variants by
molecular mimicry with different strains of C jejuni or other organisms. Helen tested positive for autoantibodies to
GQ1b to strongly suggest her prior diarrhea was due to C jejuni. In fact, stool cultures done on this admission did
grow out C jejuni.
GBS is a syndrome rather than a specific disease because different strains of different bacteria create
different epitopes for antibody formation. Most cases of acute inflammatory demyelinating polyneuropathy (ADIP)
are associated with polyclonal production of IgG to GM1. More severe destruction of the peripheral nerve for acute
motor axonal neuropathy (AMAN) is due to polyclonal IgG to GD1a, GM1, GM1b, or Ga1NAc-GD1a. The Fisher
syndrome affecting oculomotor muscles is linked to GQ1b (as in Helen), while acute pharyngeal cervicobrachial
neuropathy is related to polyclonal IgG reacting to GT1a.
Some patients go on to a chronic form of neuropathy that is most discouraging. About 75% of patients
develop pure chronic inflammatory demyelinating polyneuropathy (CIDP) and have antibodies to Po. Others have
sensory affects more than motor and they have IgM antibodies to SPGP or SGLPG. Chronic sensory atoxic
neuropathy has IgM to GD1b, GQ1b, and other b-series gangliosides. Multifocal motor neuropathy (MMN) has IgM
to GM1, Ga1NAc-GD1a, and others.
Because of the many variants (most involving the legs and arms), there have been developed “Diagnostic
Criteria for GBS”. They are as follows:
1. Progressive weakness of 2 or more limbs due to neuropathy
3. Disease course less than 4 weeks
4. Exclusion of other causes
1. Relatively symmetric weakness
2. Mild sensory involvement
3. Facial nerve or other cranial nerve involvement
4. Absence of fever
5. Typical CSF profile of acellular with mild protein elevation
6. EMG evidence of demyelination
Helen presented initially with all of the Supportive features and developed the Required elements over the next
8.0 Other forms of polyneuropathy
GBS is a form of autoimmune polyneuropathy due to epitopic mimicry after an infection by one of several
types of organisms. Lyme disease is due to a direct attack by B burgdorferi on cranial nerve roots and related
structures. Other infectious diseases affecting nerves include (but are not limited to) diphtheria, tuberculosis, leprosy
(Fig 8.0.1), sarcoidosis (Fig 8.0.2), syphilis, herpes simplex, and varicella-zoster. We all see (and some of us have)
recurring cold sores on the lips. These are due to Herpes simplex virus residing in the Gasserian ganglion. They
seem to be provoked by sunlight or stress to return to the lip for replication and start as a tingling at the site. Because
the capsule of the virus is lipid based,the recurrence can be aborted by dabbing the site with an alcohol-soaked swab
or cloth. The alcohol easily penetrates the epidermis, dissolves the virus capsule and inactivates it to stop the
tingling. Varicella-zoster resides in the dorsal root ganglion of a nerve root of the spine (Fig 8.0.3). It goes out many
of the nerve fibers to the skin to create vesicles and severe pain (Fig 8.0.4). There is now a vaccination to prevent
8.1 Alcoholic neuropathy
Over 10% of Americans are alcoholic and over 50% of alcohol consumed is non-tax paid moonshine.
Because so many calories are consumed with alcohol, foods are eaten in smaller quantities. Thus, we have direct
toxic effects of ethanol and methanol on nerves, heavy metal contaminants poisoning nerves (Fig 8.1), and a host of
vitamin deficiencies. In addition, desperate inebriates grab wrong containers and imbibe pesticides. Thiamine
deficiency seems to cause most problems with both CNS (Wernicke’s encephalopathy) and PNS (axonal
neuropathy) complications. Physicians must remember to start thiamine therapy before multivitamin care.
Multivitamins ratchet up all metabolism and exaggerate the thiamine deficiency for a more severe permanent
8.2 Multifocal motor neuropathy
This multifocal pure motor neuropathy may cause wrist drop on one side and foot drop on the other side.
It is often mistaken for ALS, but should not be because of its asymmetry. The inflammatory demyelination
resembles CIDP but spares sensory fibers. It responds favorably to IgGor Cytotoxic therapy, but not corticosteroids
8.3 Monoclonal gammopathies
Some older men (and a few women) develop MGUS, monoclonal gammopathies of uncertain significance.
These can be IgM, IgG, or IgA with kappa or lambda light chains.The IgM-kappa proteins attach to sugars on
myelin-associated glycoprotein (MAG) to cause sensory loss and mild weakness. Some patients later present
multiple myeloma in bones or plasmacytomas in soft tissues.Others have a cryoglobulinemia for their paraprotein
formation. Some present as though they have CIDP while others have the POEMS syndrome (Polyneuropathy,
Organomegaly, Endocrinopathy [hirsutism, testicular atrophy], Monoclonal IgM, and scleroderma-like Skin changes
Amyloid is a class of misfolded proteins produced in a variety of conditions you have already studied
thoroughly. These extracellular fibrillary deposits not only accumulate around vessels, but also directly around
peripheral nerves and autonomic ganglia (Fig 8.4). They block diffusion of oxygen and nutrients to the nerves,
especially small nerves that are easily surrounded. Thus, the patient first loses sensations for pain and temperature
and develops painless injuries of the feet or hands that can become chronic infections requiring amputation. This is a
complication of rheumatoid arthritis and renal dialysis where patients can develop the carpal tunnel syndrome. For
reasons not at all understood, there can be highly focal amyloid deposits around one or a pair of cranial nerves. In
fact, I had one patient with both eyes bulging from the sockets and corneal lacerations because of amyloid
thickening of the oculomotor nerve!
8.5 Renal failure
By the time a patient needs their first dialysis, s/he has already accumulated so many catabolites there is a
diffuse dying back of axons in the extremities. The distance from the neuron cell body is too far to maintain
intracellular hygiene. Symptoms are more sensory than motor, but are significant. Dialysis relieves the symptoms,
but they continue to have muscle cramps and slowly lose muscle mass. Then, of course, they start to deposit
amyloid. Investigators are looking for ways to reduce cramps, muscle loss, and amyloid, usually by attacking one of
those three problems.
8.6 Paraneoplastic neuropathy
These are usually diffuse, symmetric neuropathies with proximal weakness in the legs and distal sensory
loss. They are often associated with small cell carcinoma of the lung (2-5% of lung cancer patients) and may
precede identification of the tumor by up to 18 months. This is due to production of anti-Hu IgG, a 35-38 kDa RNA-
binding protein, that binds to tumor cells and to dorsal root ganglion neurons. It is also seen in a lower percentage of
patients with other tumors. I have also had a cerebellar ataxia as a paraneoplastic problem.
Our case studies involved polyneuropathies and that is reasonable. However, more common are the
mononeuropathies and mononeuritis multiplex. This is because of trauma and diabetes mellitus, but especially
trauma. Not only do we have acute, obvious injuries, but also chronic pressure phenomena through tight spaces in
the vertebral column, carpal tunnel, metatarsal joints, etc. Selected toxins affect single cranial nerves with one being
totally due to physicians. Streptomycin therapy must be limited to avoid iatrogenic deafness (Fig 9.0.1)
9.1 Peripheral nerve trauma
The previous lab discussed accidental (or deliberate) nerve transection where the distal axon would wither
by Wallerian degeneration, but then regenerate. While it could return to the original site, it might get close or scar
tissue could derail it to form an amputation neuroma (Fig 9.1). We will now consider chronic trauma, usually by
compression within a tight compartment.
We hear most often about herniated discs and spinal stenosis. In the former, the nucleus pulposus (formerly
notochord)of the intervertebral space has been exposed to fluid by development of a crack in the dense annulus.The
crack is usually caused by lifting something heavy, like a refrigerator, so this is more common in men. The pulp
imbibes liquid to swell about tenfold, spurt out of the intervertebral space, and squeeze around nerve roots. The
result is a radicular neuropathy with pain perceived as extending along the entire pathway of the nerve and often
described as radiating from the back to the foot or hand or trunk. Needle aspiration of the pulp would suffice, but it
is difficult to locate and often is approached surgically.
Older adults have progressive thickening of bone around the vertebral bodies and arches. This often
encroaches upon the spinal canal to trap nerve roots (stenosis) for chronic pain of increasing severity. While surgery
would seem indicated, it rarely provides much relief because of post-operative scarring and frequently makes the
pain worse. These patients become depressed, bedbound, and have progressive cardiac atrophy of disuse until they
develop congestive heart failure.
Less common than discs but more than stenosis are the several entrapment neuropathies. The most common
is carpal tunnel syndrome in the wrist. The median nerve travels through a narrow canal at the wrist that suffices for
normal conditions. However, if the wrist swells from rheumatoid arthritis or premenstrual edema and the hands are
being used extensively (typing, knitting, gardening, millwork), the median nerve will be trapped, suffer injury,
attract leukocytes, develop fibrosis, and follow a path to permanent painful entrapment. This is more common in
women and is easily corrected by outpatient surgery on the wrist. Similarly, pointed toe shoes and high heels putting
all of the weight on the toes will rub metatarsal heads together and pinch nerves to the toes. As fibers break and try
to return through increasing scar tissue, the woman develops Morton’s neuromas that require surgical extirpation.
Tennis elbow of the ulnar nerve, soldier’s shoulder from firing rifles, ballet dancer’s ankle, and nun’s knee represent
similar phenomena. The peroneal nerve in the knee may be compromised by a Baker’s cyst (herniation of the
synovial wall to the posterior space of the knee).
Bell’s palsy is not due to trauma but inflammation of the facial nerve (VII) in the bony canal or at the
stylomastoid foramen. Often idiopathic, this can be part of AIDS, sarcoidosis, or Lyme disease. If bilateral, it is
almost certainly Lyme disease. The patient presents with drooping of the corner of the mouth and drooling, inability
to close one eye, and difficulty speaking because of the tongue. This usually clears with treatment but may have a
permanent partial component.
9.2 Diabetic neuropathy (mononeuritis multiplex)
Section 5 described a series of mononeuropathies, usually by entrapment. The diabetic patient develops
progressive mononeuritis multiplex because of the diffuseness of his/her disease. This is a symmetric
polyneuropathy due to several factors. Focal atherosclerosis of medium-sized arteries and thromboemboli from the
aorta cause ischemic atrophy of the feet and lower legs. Basement membrane thickening around capillaries and
nerves adds to the insult everywhere, especially the small sensory fibers (Fig 9.2). Autonomic nerve dysfunction for
similar reasons causes peripheral edema to further tighten nerve compartments. Loss of peripheral sensation leads to
trauma of the foot and inflammation. Poor blood supply to the skin causes sloughing, ulcers, and infection. How
could the individual nerves possibly survive? The rate of progression is proportional to the height of the serum
glucose level. This is best monitored by getting Hemoglobin A1c levels that change slowly but dependably
according to the glucose level over a three month period. Without a radical change in lifestyle, the final product is
The brachial plexus has nerve roots from C5 to T1 that crisscross to form upper, middle, and lower trunks
and cross again for posterior, medial, and lateral cords. While brachial plexopathy occurs with neck trauma (forceps
delivery), tumor invasion from the lungs (Pancoast’s syndrome), and radiation therapy for lung tumors, it most often
happens as an autoimmune post-infectious inflammation. Symptoms are weakness, pain, and sensory los s in the
shoulders and arms. Most patients are young males that had an upper respiratory infection or immunization and are
now complaining of severe pain in the lateral shoulder that may extend down the arm. Weakness may include the
diaphragm but symptoms subside over days to 2 weeks and total recovery occurs in several months to two years.
The lumbosacral plexus is much less often involved by the autoimmune form, but has its share of trauma,
radiation, malignancy, hemorrhage, diabetes mellitus, leprosy, and vasculitis complications. Pain and weakness tend
to be proximal and either anterior or posterior to include the buttocks.
King Olaf has never had ulcer symptoms, but now has paresthesias and macrocytic anemia. You perform
upper GI endoscopy and take a biopsy of the gastric mucosa. You expect to find in your microscope a
Evidence of lactose intolerance
Thin mucosa with lymphocytosis and intestinal metaplasia
George W is a 35 year old alcoholic who has been on a serious binge for three months. He presents with
symptoms of subacute combined degeneration. To avoid irreversible exaggeration of his symptoms, he
should first be treated with:
Canal laminectomy so the swollen cord can expand
Aggressive multivitamin therapy
Eating large, balanced meals
Subacute combined degeneration of the spinal cord is due to:
Defect in transportation of nutrients to distal axons
Absence of succinyl-CoA
Shortage of methionine
Excessive alcohol intake
The paraneoplastic syndrome is thought to be due to:
Catabolic agents from malignant cells
Vitamin deficiency secondary to chemotherapeutic drugs
Byproducts of tumor anabolism
Antibodies to tumor cell antigens
Causes of macrocytic anemia include all of the following EXCEPT:
Diseases of the thyroid
Bone marrow failure
0 5 0 21 mdavis
905516262 admin2 Pathology OMS I 0 0 999999