RESIDENT

& FELLOW
SECTION
Pearls and Oy-sters:
Section Editor Evaluation of peripheral neuropathies
Mitchell S.V. Elkind,
MD, MS

Michelle L. Mauermann, Peripheral neuropathy is common, with an estimated and utilization of problem representations will
MD prevalence of !2% in the general population and also serve as anchor points in memory that should
Ted M. Burns, MD prevalence as high as 8% in those over the age of 55 allow the physician to more efficiently evaluate fu-
years.1 Residents and fellows will undoubtedly evalu- ture cases and particularly to identify subtle but
ate many patients with various types of peripheral meaningful variations in similar cases.7
Address correspondence and neuropathies during their careers. The evaluation for
reprint requests to Dr. Michelle
the etiology of a patient’s peripheral neuropathy can PEARLS FOR EVALUATING PERIPHERAL NEURO-
L. Mauermann, Mayo Clinic, 200
First Street SW., Rochester, MN be challenging given the vast number of potential PATHY What? Determine what nerve fiber modali-
55902
etiologies2,3 and the fact that despite an appropriate ties—motor, sensory, or autonomic—are involved.
[Link]@[Link]
evaluation, a high percentage of cases will remain id- If sensory fibers are involved, sensory symptoms
iopathic.4,5 In this article, we provide a simple, easy-to- should be characterized into those with a positive
remember algorithm that can simplify the evaluation of sensation, such as prickling, tingling, or buzzing, vs
peripheral neuropathy. those with a negative sensation, such as loss of sensa-
tion or imbalance. This differentiation is helpful be-
PERIPHERAL NEUROPATHY ALGORITHM The eva- cause these positive sensory symptoms often suggest
luation of peripheral neuropathy should begin with a neuropathy is acquired rather than inherited.4 Ac-
the gathering of clinical data including the history of quired neuropathies with large fiber dysfunction
present illness, past medical history, family history, (either motor or sensory with loss of vibration, pro-
and physical examination. The determination of prioception, or light touch) due to demyelination of-
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what of that clinical data is relevant requires knowl- ten have symptoms of weakness with or without
edge of various diseases and the risk factors for those ataxia with positive sensory symptoms such as tin-
diseases. The information then needs to be synthe- gling. Those with small fiber dysfunction (loss of
sized in order to characterize the complaints and pain or temperature) often have symptoms such as
findings and determine an appropriate workup. The burning without weakness or ataxia. Small fiber neu-
appropriate characterization of the complaints and ropathies can have positive sensory symptoms such as
findings is essential in order to perform an efficient, burning, regardless of whether they are acquired or
cost-effective, and successful evaluation. We recom- inherited. However, most types of inherited neu-
mend characterizing the neuropathy by answering ropathies tend to have more signs (examination
four basic questions about the neuropathy: What? abnormalities) than symptoms. The identification
Where? When? What setting? (figure).6 This simple of sensory nerve fiber involvement in almost all
algorithm should facilitate the early step in clinical instances excludes disorders of the anterior horn
reasoning of creating a mental abstraction—that cell, neuromuscular junction, and muscle. Decid-
is, a problem representation or one-sentence sum- ing whether weakness or sensory symptoms are
mary of the defining and discriminating character- more prominent can also be helpful because the
istics of the case.7 The creation of an accurate inflammatory demyelinating neuropathies often
problem representation will allow the evaluating manifest with weakness overshadowing sensory
physician to focus on a small list of potential etiol- nerve fiber disturbance. Autonomic nerve involve-
ogies. This critical step in diagnostic reasoning ment can be an important clue because only a
will usually guide the physician down the correct small number of neuropathic processes affect both
diagnostic path, but it must be kept in mind that autonomic and somatic nerves such as diabetes,
our algorithm is not absolute and there will always amyloidosis, acquired inflammatory demyelinat-
be cases that prove to be exceptions. The creation ing polyneuropathies, paraneoplastic syndromes,

From the Mayo Clinic (M.L.M.), Rochester, MN; and University of Virginia (T.M.B.), Charlottesville.
Disclosure: The authors report no disclosures.

e28 Copyright © 2009 by AAN Enterprises, Inc.

 Figure Pearls for classification of peripheral neuropathies
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A suggested construct for the approach to neuropathy, using the “what, where, when, and what setting” approach to characterizing the neuropathy and
placing the neuropathy into a presumed etiologic category. PNSS " positive neuropathic sensory symptoms; CMT " Charcot-Marie-Tooth; HMSN "
hereditary motor and sensory neuropathies; HNPP " hereditary neuropathy with liability to pressure palsy; GBS " Guillain-Barré syndrome; CIDP " chronic
inflammatory demyelinating polyradiculoneuropathy; MMN " multifocal motor neuropathy; PAN " polyarteritis nodosa; SLE " systemic lupus erythemato-
sus; RA " rheumatoid arthritis. Modified and reprinted with permission from Mauermann ML, Burns TM. The evaluation of acquired neuropathies. Semin
Neurol 2008;28:133–151.6

Sjögren syndrome, porphyria, HIV, and heredi- gression, so it is best to ask the patient to describe the
tary sensory and autonomic neuropathies. location of onset of symptoms followed by the distribu-
tion of subsequent progression.
Where? Next decide if the distribution is length-
dependent and symmetric or not. Length-dependent When? The onset of the neuropathy should be classi-
neuropathies manifest first in the feet and are symmetric. fied. The neuropathies that are acute or subacute in
Non-length-dependent neuropathies may be asymmetric, onset are more typical of an immune-mediated or
focal, or multifocal. The etiology of length-dependent infectious etiology. As patients have difficulty recall-
neuropathies is usually inherited, metabolic/toxic, or id- ing the course, it is helpful to determine whether the
iopathic, whereas a neuropathy that is not length- symptoms had a definite date of onset. A less-exact
dependent is often caused by an immune-mediated date of onset suggests a gradual or insidious onset,
or infectious process. Some examples of non-length- indicative of inherited, idiopathic, or toxic/metabolic
dependent neuropathies are polyradiculoneuropathies etiologies. The tempo following symptom onset is
(e.g., acquired inflammatory demyelinating polyneu- also an important consideration. Symptom onset and
ropathies), plexopathies (often inflammatory), sensory
tempo often correlate in a predictable manner, owing
polyganglionopathies (e.g., paraneoplastic subacute sen-
largely to the underlying mechanism.6
sory neuronopathy caused by small cell lung cancer),
and mononeuritis multiplex (caused by vasculitis). At What setting? The neuropathy has to be considered
times it may be difficult to determine whether the neu- within the context of the patient’s unique clinical
ropathy is symmetric or asymmetric due to clinical pro- circumstances. This is aided by determining what is

Neurology 72 February 10, 2009 e29

 relevant in the patient’s medical history, medication !40% will have confirmatory findings on examina-
list, social history, family history, and the review of tion.9 Do not let that dissuade you from timely diag-
systems. An understanding of the significance of nosis and treatment. The second point about the
these clinical factors requires knowledge of the risk sensory examination is that it is frequently misgraded
factors of neuropathy and knowledge of the clinical as abnormal in the unaffected elderly patient and
features of the diseases that may be risk factors for conversely misgraded as normal in the affected young
neuropathy. For example, unexplained weight loss patient. Age (and to a lesser extent height and other
raises concern for immune or neoplastic causes such anthropomorphic features) must be factored into the
as vasculitis, lymphoma, diabetic and nondiabetic judgment of whether sensory testing is normal or ab-
lumbosacral radiculoplexus neuropathy, or a para- normal. Also remember that myelopathies can mimic
neoplastic autoimmune process. The clinician should peripheral neuropathy, particularly acute-onset neu-
always consider the most common causes of neurop- ropathies such as acute inflammatory neuropathies.
athy such as diabetes, alcohol use, or inherited etiolo- Myelopathies often have more profound propriocep-
gies. Family members should be examined whenever tive loss compared to vibration but this is not abso-
possible. It is important for the neurologist to obtain an lute and the physician should have a low threshold
accurate alcohol consumption history and smoking his- for obtaining imaging of the spinal cord in cases of
tory in a nonthreatening, nonjudgmental manner. Al- possible myelopathy. The presence of bowel and
coholism is a very common problem and neuropathies bladder impairment can be a helpful differentiator as
due to alcohol use or secondary nutritional deficiencies it strongly favors a myelopathy as the cause.
can occur, so appropriate effort must be spent during 2. Not all asymmetric neuropathies are acquired.
the clinic visit investigating this possibility.6,8 While most inherited neuropathies cause symmetric
symptoms and impairments, hereditary neuropathy
Clinical neurophysiologic assessment. Characteriza-
with liability to pressure palsies (HNPP) often presents
tion using electrodiagnostic testing (EDX) is usually
with multiple compressive mononeuropathies (e.g., ul-
helpful in confirming the presence of a neuropathy
nar, median, and peroneal nerves). Thus, HNPP is a
and to further define motor and sensory involve-
relatively common neuropathy that does not conform
ment. EDX testing can be normal in small fiber neu-
well to our paradigm. However, family history, foot de-
ropathies, very distal length-dependent neuropathies,
formity, subtle details about the history, and the specific
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and early neuropathic processes, particularly within

EDX characteristics of HNPP usually provide enough
the first few days. Normal EDX testing can also
clues to prompt consideration and eventual diagnosis.
point to another etiology for the patient’s com-
Electrodiagnostic studies demonstrate multiple monon-
plaints, for example a myelopathy. EDX aids in de- europathies with focal conduction blocks as well as gen-
termining if the neuropathy is primarily axonal or eralized prolongation of distal latencies.
demyelinating. EDX can also help with defining
symmetry, length-dependence, and subclinical in- 3. If it does not fit, acquit. If the characterization of a
volvement and provide baseline parameters in case particular neuropathy does not fit well with the clin-
future EDX in needed to monitor the patient’s ical context, for example the medical history or an
course. Autonomic function may be assessed through associated laboratory abnormality, one needs to look
autonomic reflex testing or other provocative testing, elsewhere. Conditions such as diabetes mellitus, hy-
such as a thermoregulatory sweat test, which specifi- pothyroidism, and renal insufficiency are common in
cally assess the autonomic nervous system. the general population and are most often associated
with a length-dependent sensorimotor neuropathy
AVOID THE OY-STERS There are three important tips without other systemic features. However, just be-
to keep in mind when evaluating peripheral cause these conditions are common does not mean they
neuropathies. are always the cause of the neuropathy. Furthermore,
these patients are not immune to the development of
1. Do not let your sensory examination mislead you. other acquired neuropathies such as Guillain-Barré syn-
First, your patient almost certainly has sensory in-
drome, chronic inflammatory demyelinating polyneu-
volvement if he or she complains of sensory symp- ropathy, amyloidosis, or B12 deficiency. For example,
toms, regardless of what you find on examination. It approximately 2% of patients with type 1 diabetes and
is well known that symptoms of sensory involvement approximately 6% of patients with type 2 diabetes have
are more sensitive for detecting sensory nerve dys- other causes of neuropathy.10
function than signs on examination. For example,
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