Page 530 - Motor Disorders Third Edition

512 / chapter 28
femoral sciatic neuropathy (16–18), and most recently
DLRPN or the equivalent abbreviation DLSRPN (19, 20).
With the availability of ultrastructural and biochemical
analysis of nerve biopsy specimens from affected patients,
it appeared that metabolic derangements played important
roles in the pathogenesis of diabetic neuropathy (21, 22).
The earliest morphological alterations in epineurial and
endoneurial blood vessels inferred local hypoxia, cellular
disturbances, and changes in vascular permeability. Some
investigators (23, 24) attempted to correlate chronic hyper-
glycemia with metabolic derangements, particularly in the
polyol pathway responsible for the conversion of glucose to
sorbitol by aldose reductase and sorbitol to fructose. Such
were associated with alterations of intrinsic nerve lipids,
alcoholic sugars, and a series of biochemical consequences
leading to altered protein synthesis, abnormal glycosyl-
ation, slowed axon transport, axoglia dysjunction, osmotic
swelling and thickened axolemmal and endoneurial base-
ment membranes.
EPIDEMIOLOGY
Estimates of the prevalence of diabetic peripheral neu-
ropathy vary widely in the literature, largely because of
the discrepancy in diagnostic criteria, methods of patient
selection, and assessment. The consensus statement of the
San Antonio conference on diabetic peripheral neuropathy
proposed guidelines for epidemiologic studies (25). Thirty
percent of 1184 subjects with type I DM, of mean age 47
years and duration of disease of 26 years, screened by the
Michigan Neuropathy Screening Instrument (MNSI), had
confirmed neuropathy employing neurological examina-
tion and nerve conduction studies (NCS) (26) compared
to 10.5% of 1414 subjects with newly diagnosed DM,
comprising 17.5% of the cohort, and the remainder with
known DM, employing vibration pressure thresholds (27).
Although increasing age is an independent risk factor for
diabetic neuropathy, others such as longer duration of DM,
retinopathy, and nephropathy are generally considered to
correlate with a higher frequency of neuropathy as well.
CLINICAL PRESENTATION
Patients with DSPN present with distal leg weakness and
wasting, in association with neuropathic pain, paresthesias,
hyperesthesia, proprioceptive defect, weakness, atrophy, gait roliferative disease, including benign and malignant plasma
disturbance, imbalance, hyporeflexia, and impaired auto-
nomic function. In its most advanced form, it can resemble
tabes dorsalis as there may be Charcot foot joint deformity
and ulceration. The presence of fasciculation should lead to
the suspicion of CIDP. Patients with DLSRPN have prominent
pelvifemoral pain followed by weakness, beginning focally in
the upper leg or thigh with spread to the contralateral limb,
and variable weight loss (20). Those with MNM present with
a stepwise pattern of neuropathic motor and sensory loss and
weakness in the distribution of named peripheral nerves,
especially in the femoral, sciatic, and upper limb nerves
accompanied by asymmetrical weakness, wasting and, at a
later stage, by the coalescence of lesions resembling severe
DSPN. Diabetic autonomic neuropathy may be subclinical or
clinically evident, with cardiovascular, ocular, gastrointesti-
nal, genitourinary, sudomotor, and hypoglycemic symptoms.
Carpal tunnel syndrome and other entrapment neuropa-
thies may go unheeded because of an elevated threshold
to ischemic pain. Oculomotor nerve palsy occurs with the
abrupt onset of ocular pain, and headache, followed by par-
tial paralysis of eye movement, with papillary sparing. Some
patients develop truncal radiculopathy manifested by girdle-
like pain, abdominal wall weakness, and hyperesthesia due
to root infarction, which when combined with a neurogenic
bladder, can raise suspicion of cord compression by a rup-
tured thoracic disc. When manifested in lumbar segments,
affected patients may similarly be thought to harbor lumbar
root entrapment or compression by a ruptured disc with
radicular weakness, hyporeflexia, and dermatomal sensory
loss. Generalized weakness may accompany acute painful
neuropathy and diabetic neuropathic cachexia, manifested
by precipitous and profound weight loss, followed by severe
and unremitting cutaneous pain due to primarily small nerve
fiber involvement, often with superimposed large fiber dis-
ease and dysautonomia. Symptoms of autonomic neuropa-
thy in the order of frequency at occurrance, include nausea,
incomplete bladder emptying, urinary frequency, orthostatic
dizziness, impotence, hyperhydrosis, and early satiety.
CLINICAL AND LABORATORY EVALUATION
The assessment of patients with diabetic neuropathy of any
type should begin with a thorough history and examina-
tion. All new patients should have baseline and serial fast-
ing serum glucose and glycosylated hemoglobin levels to
assess glycemic control. Since up to 10% of diabetic patients
may have an alternative cause for the neuropathy, various
other potential pathogenic causes or associated contribu-
tory condition should be considered as appropriate for a
given patient. Those with prominent motor involvement
should be evaluated for B12 deficiency, heavy metal intoxi-
cation, malnutrition, uremia, occult cancer and lymphop-
cell dyscrasia, systemic vasculitis, thyroid disease, human
immunodeficiency virus (HIV)-1 neuropathy, serologi-
cally specific connective tissue disorders, anti-GM1 gan-
glioside and anti-myelin-associated glycoprotein (MAG)