|
|
PERIPHERAL NEUROPATHY |
Peripheral nerve disorders are among the most common neurologic
problems seen, most in the out-patient setting. Many patients presenting themselves
with complaints of numbness or weakness will eventually be shown to have a
disorder of the peripheral nervous system. Although the differential diagnosis
is large in these disorders, the combination of a directed neurologic history exam along
with relatively simple ancillary testing will quickly narrow the differential
diagnosis. As many of these disorders are treatable or curable, prompt
recognition, especially early in the clinical course, is important.
Peripheral neuropathies (a.k.a.,
polyneuropathy, neuropathy) represent a more diffuse injury to the peripheral nervous system.
Many disease processes may preferentially attack either the
axon or the myelin
sheath of the peripheral nerve. As a rule, axonal peripheral neuropathies
affect the longest axons first. These are the so called
"dying back" neuropathies. Transport of
proteins and nutrients from the cell body is affected early, with subsequent
breakdown and loss of the most distal peripheral nerve fibers. Patients develop
numbness or weakness of the toes and feet initially which then slowly progresses
up the leg. When the process reaches the upper calf, the finger tips become
involved as well (i.e., the length from the spinal cord to upper calf is the same
as that from spinal cord to finger tips). This results in the classic
"stocking-glove" distribution of symptoms and
signs. |
|
Above: The typical distribution of most
peripheral neuropathies are "length-dependent" (i.e., the longest nerves are
affected the most). This leads to the stocking glove pattern (note - the legs
are always affected more than the arms). In more severe cases, sensory loss may
be found over the anterior chest and abdomen, reflecting degeneration of the
distal thoracic intercostal nerves.
|
Symptoms and Signs
When nerve is diseased, it can react in a limited number of ways. Thus, many
peripheral nerve disorders present with similar symptoms. Peripheral nerve may
be viewed as supplying motor,
sensory, as well as
autonomic function. In
addition, it is helpful to consider nerve on the basis of large and small
fibers. All motor fibers are large fibers. All autonomic fibers are small
fibers. However, sensory fibers are both of the large and small fiber type.
Large sensory fibers mediate vibration, proprioception and touch, whereas small
sensory fibers convey pain and temperature sensations. Pathology of these fiber
types may create symptoms and signs by lack of function (negative symptoms and
signs) or by extra or abnormal function (positive symptoms and signs).
Everyone can
relate to falling asleep on their arm which initially causes numbness or lack of
feeling (negative symptom) followed by intense pins and needles paresthesias
(positive symptom). Likewise, symptoms and signs in the different nerve fiber
types can be divided into positive and negative (see table below).
|
Signs and Symptoms of Peripheral Nerve Disease |
Nerve Type |
Negative |
Positive |
Motor |
Weakness
Atrophy
Clumsiness
Areflexia
Hypotonia
Deformities (pes cavus, kyphoscoliosis) |
Fasciculations
Myokymia
Cramps |
Sensory (Large Fiber) |
Sensory loss to vibration and
proprioception
Ataxia
Clumsiness
Areflexia
Hypotonia |
"Tingling"
"Pins and needles"
|
Sensory (Small Fiber) |
Sensory loss to pain and
temperature |
"Burning"
"Stabbing" |
Autonomic |
Postural hypotension
Anhidrosis
Impotence
Bowel or bladder disturbance |
Hyperhidrosis
Gustatory sweating |
Trophic |
|
Foot ulceration
Charcot
arthropathy |
|
|
Thus, all of the above symptoms and signs are typically seen in the
stocking-glove distribution. Most often, the ankle reflex is absent or diminished
with the remaining reflexes normal, unless the neuropathy is severe. Likewise,
muscle weakness and atrophy is most prominent distally, more in the feet than
the hands. |
Evaluation
There are well over 100 causes of peripheral neuropathy, including metabolic
disorders, infections, vitamin deficiencies, toxic and drug-induced conditions,
genetic abnormalities, inflammatory autoimmune conditions, dysproteinemias, and
neoplasia.
To narrow the differential to a more reasonable number of conditions, one
should first characterize the neuropathy for the following attributes:
•
Temporal course
acute, subacute or chronic
progressive, relapsing/remitting or step-wise
progressive
•
Fiber types involved
motor
sensory large
fiber
sensory small fiber
autonomic
•
Localization
symmetric/asymmetric
proximal/distal
•
Pathology
axonal
demyelinating
mixed
•
Family history
•
Occupational or exposure history
•
Possible associated medical conditions
|
Nearly all the information above can be obtained from the history and physical
examination. Electromyography (EMG) and Nerve Conduction Studies (NCS) can help
clarify the exact localization of the lesion and will often suggest the
underlying type of pathology (axonal or demyelinating).
First in regards to the temporal course, most peripheral neuropathies are
progressive and chronic. An relapsing/remitting course suggests an autoimmune
etiology or an intermittent exposure. A step-wise progression course suggest a
mononeuropathy multiplex pattern. Acute neuropathies are very uncommon and are
associated with a limited diagnosis including:
Acute Peripheral
Neuropathies
● GBS
● Porphyria
● Diphtheria
● Drugs (Dapsone, Nitrofurantoin, Vincristine)
● Toxins (Arsenic, Thallium,
Triorthocresylphosphate)
● Tick Paralysis
|
Regarding fiber type involvement, most peripheral neuropathies are motor and
sensory. For instance, pure motor or pure sensory neuropathies have a limited differential.
In analyzing polyneuropathies, one needs to concentrate on the overall
pattern (i.e., the localization). Is there a distal/proximal gradient? Is there
any asymmetry which might imply a mononeuritis multiplex pattern, or a
superimposed radiculopathy or mononeuropathy? Most peripheral neuropathy have
the typical stocking-glove pattern.
|
Next is the underlying pathology. Almost all peripheral neuropathies are
associated with axonal loss. Very few have primary demyelinative pathology.
Demyelination may be demonstrated either by pathological examination of nerve or
more easily by EMG testing. On nerve conduction studies, demyelination is
associated with markedly markedly slowed conduction velocities and conduction
block between distal and proximal stimulation sites. Such a finding readily
narrows the differential diagnosis.
Peripheral Neuropathies
with Primary Demyelination
● Acute Inflammatory Demyelinating
Polyradiculoneuropathy (Guillain Barré Syndrome)
● Charcot-Marie-Tooth Polyneuropathy
● Childhood Leukodystrophies
● Diphtheria
● Chronic Inflammatory Demyelinating
Polyradiculoneuropathy (CIDP)
Idiopathic
Associated with HIV infection
Associated with MGUS (especially IgM)
Associated with anti-MAG antibodies
Associated with osteosclerotic myeloma
Associated with GM1 antibodies
|
Next family history is important. Over 25% of all peripheral neuropathies are
inherited.
Clinical Clues to an
Inherited Peripheral Neuropathies
● Several slow progression over years or decades
● Often the absence of "positive symptoms"
● Associated bony deformities, especially pes cavus
● History in the family of similar symptoms, or a
family history of "polio", "rheumatism" (it is not unusual that inherited peripheral
neuropathies were missed by past physicians)
|
Left: Pes cavus which is combination of a
foreshortened foot; high arch and cocked-up toes. This skeletal deformity occurs
when there is intrinsic foot muscle weakness present as a child during
development. Pes cavus is highly associated with inherited peripheral
neuropathies. |
|
Of course, it is important to review any past medical history in a patient
with a peripheral neuropathy. Several medical conditions are highly associated
with peripheral neuropathy.
Common Medical Conditions
Associated with Peripheral Neuropathies
● Diabetes (the most common cause of peripheral
neuropathy in the US)
● Thyroid disease
● Cancer
● Renal Disease
● Liver Disease
● Lupus and other connective tissue disease
● HIV
|
Lastly, all patients should be questioned about toxic and occupational
exposures. The most common toxin is alcohol. In addition, there are a large
number of prescription medicines that may induce a peripheral neuropathy.
Regarding occupational exposure, this is clearly much less frequent in the
modern day due to rigorous OSHA standards. However, an occasional patient will
be exposed to heavy metals or hexacarbons that result in their neuropathy.
Once all of the above information is known, the list of possible etiologies
is often markedly reduced, so that more intelligent use of further laboratory
testing can be employed to reach a diagnosis.
|
For instance, the differential diagnosis is markedly different among the
following cases:
◊ A 25 year-old woman with the onset acute of a motor > sensory peripheral
neuropathy with demyelinating on the EMG
vs.
◊ A 60 year-old man with slowly progressive motor neuropathy over 30 years and
an exam showing pes cavus
vs.
◊ A 45 year-old woman with Sjogren's syndrome and a pure sensory neuropathy
vs.
◊ A 50 year-old alcoholic with a small fiber sensory neuropathy
In the cases above, the first is most likely GBS; the second an inherited
neuropathy; the third an autoimmune sensory neuropathy associated with the
patient's
connective tissue disease, and the last patient is likely a small fiber
neuropathy associated with alcohol abuse and poor nutrition. The subsequent
evaluation and treatment would be markedly different among these four
individuals. |
|
|
|