Page 531 - Motor Disorders Third Edition

neuropathies. The determination of such disorders should
be approached systematically by obtaining serum and sero-
logical studies, imaging of the body by computed tomog-
raphy (CT) after adequate hydration and determination of
renal function, and appropriate urinary studies, all of which
are generally relatively inexpensive and informative from
the outset. Determination of heart rate by auscultation and
electrocardiography (ECG) may reveal a resting tachycar-
dia in patients with autonomic cardiac parasympathetic
neuropathy, whereas those with both parasympathetic and
sympathetic involvement may have slightly less rapid rates.
Whereas autonomic cardiac neuropathy contributes to the
mortality of diabetes by heightening the risk of malignant
ventricular arrhythmia due to prolongation of the QTc
interval of the resting electrocardiogram (EKG), and to
sudden cardiac death following general anesthesia or after
use of medications that suppress baroreceptors, autonomic
neuropathy heightens the risk of orthostatic intolerance
(OI) with the ensuing propensity for syncope. The second-
ary retinal, peripheral vascular and renal complications of
diabetes also confer independent long-term morbidity and
mortality in a given patient. Those with retinopathy should
undergo full ophthalmological testing, including retinogra-
phy. Patients with occlusive vascular disease, as suggested
by absence of distal leg pulsations, should undergo Dop-
pler studies. Diabetic patients with clinical and laboratory
evidence of nephropathy should undergo measurement of
total urinary protein and creatinine, with 24-hour clear-
ance of the latter before exposure to contrast dye or IVIG,
and those with known paraproteinemia should have urine
electrophoresis for Bence Jones proteinuria. Cerebrospinal
fluid (CSF) analysis should be considered in patients with
suspected CIDP.
All newly diagnosed patients should undergo elec-
trodiagnostic studies employing baseline NCS along the
median, ulnar, fibular, tibial, and femoral mixed nerves for
motor parameters, and along corresponding sensory nerve
branches using standard surface recording techniques at
skin temperature of 34 degrees centigrade. Since compres-
sion of the median nerve at the wrist and the ulnar nerve at
the elbow are frequent occurrences in diabetics and in the
general population with age, the radial nerve is probably the
most useful determinant of motor and sensory function in
the arms. Femoral nerve motor and saphenous sensory stud-
ies are useful in confirming or excluding clinically significant NEUROPATHOLOGY
DLSRPN. When the distal fibular motor responses are not
obtainable, proximal conductions along the fibular nerve
at the fibula head and knee, while recording to the tibialis
anterior muscle can provide an accurate estimate of nerve
velocity. Patients with conduction block, segmental motor
nerve slowing, and excessive temporal dispersion should
be suspected of CIDP. Concentric needle electromyography
(EMG) is the most sensitive measure of focal or asymmetrical
DIABETIC NEUROPATHY / 513
lesions and of active motor axonal degeneration, and assists
in the confirmation of demyelinating neuropathy. Quantita-
tive sensory testing (QST) by computer-assisted techniques,
and quantitative autonomic testing (QAT) for determination
of the heart-rate response to Valsalva maneuver, deep breath-
ing, and erect stance; and blood pressure changes with head-
up tilting (HUT), and the quantitative sudomotor axon reflex
testing (QSART) all amplify conventional electrophysiology
and bedside testing.
Peripheral nerve and muscle biopsy are useful in selected
patients with progressive, disabling symptoms, especially
when electrodiagnostic studies suggest a possible alterna-
tive or coexisting diagnosis with morphologically distinc-
tive findings such as hereditary neuropathy, vasculitis, and
CIDP. Contrary to popular belief, diabetics probably have
no greater risk of healing or complications after nerve and
muscle biopsy. However, such procedures should be under-
taken at centers with an experienced neuropathologist able
to process and evaluate paraffin, frozen, and epoxy-embed-
ded tissue for histologic, histochemical, ultrastructural,
morphometric, and teased nerve fiber analysis, necessary
to address all of the possible diagnoses, including diabetes.
Similarly, the neurologist or surgeon performing the biopsy
should be skilled in biopsy techniques to reduce morbid-
ity, provide optimal specimens adequate for analysis, and
reduce handling artifacts. Nerve biopsy is the only means of
providing an accurate assessment of the density of myelin-
ated fibers, the presence of multifocal fiber loss, state of
myelination of large and small fibers, cellular infiltration,
and nerve fiber degeneration and regeneration. Immu-
nohistochemistry, useful in elucidating the different pat-
terns of humoral and cell-mediated immunity in selected
patients, can be performed on snap-frozen tissue using a
battery of monoclonal and polyclonal antibodies against
antigens specific for T- and B-cells, macrophages, cyto-
kines, immunoglobulin classes, and complement compo-
nents (28). Skin biopsy obtained by a simple 3-mm punch
can be placed in cold paraformaldehyde and picric acid
solution, thick-sectioned, and immunologically stained for
epidermal nerve fiber (ENF) density, histology, and amyloi-
dosis employing Congo red stain (29).
There are few modern series of diabetic neuropathy con-
firmed by nerve tissue obtained at biopsy or postmortem
examination available to allow examination of the different
neuropathic syndromes. In 1996, Younger and coworkers
(30) reported the clinicopathologic and immunohisto-
chemical findings of sural nerve biopsy in a cohort of 20
patients with diabetic neuropathy. That series was contin-
ued to a total of 107 patients (31), the detailed clinicopath-