Bilateral Diabetic Proximal Neuropathy
ABSTRACT & COMMENTARY
Source: Pascoe MK, et al. Subacute diabetic proximal neuropathy. Mayo Clin Proc 1997;72;1123-1132.
Forty-four out of 368 diabetic patients evaluated by autonomic and electromyographic (EMG) examination at the Mayo Clinic between 1983 and 1995 had subacute, progressive, bilateral leg weakness with lower extremity hypo- or areflexia and electrodiagnostic evidence of polyradiculopathy. Patients with predominant sensory symptoms, normal reflexes, and clinical or EMG evidence of myopathy or length-dependent neuropathy were excluded, as were other causes for neuropathy, including hereditary neuropathy, alcoholism, and paraproteinemia. Evaluation of the 44 patients included some or all of the following: neurologic examination, nerve conduction studies, EMG, autonomic reflex screen for sudomotor, cardiovagal, and adrenergic function, lumbar puncture, and sural nerve biopsy.
Among the 25 men and 19 women, the mean age was 63.1 years, and all but four had non-insulin-dependent diabetes for a mean of 11 years. Weight loss of greater than 4.5 kg was associated with the onset of the proximal neuropathy in 37, with proximal weakness being the initial complaint in the same number. Five denied weakness but had distal weakness on examination. Two had distal weakness with unilateral proximal weakness. Axonal neuropathy was documented in 28 on electrodiagnostic studies, with demyelinating changes in an additional 14 and fibrillation potentials in 35. Autonomic studies revealed severe generalized autonomic failure in 21 of 28 studied (75%). Spinal fluid was abnormal in all 26 patients so examined, with mean protein concentration of 92.5 mg/dL, and sural nerve biopsy was abnormal in eight of nine patients. Pathological findings included loss of myelinated fibers and increased axonal degeneration in six, onion bulb formation in two, and demyelination in four. Two specimens demonstrated perivascular mononuclear inflammatory infiltrates without demyelination.
Two of three patients given immunosuppressive doses of prednisone improved, as did four of seven who underwent plasma exchange and three of four who received intravenous immune globulin. Seventeen of 29 untreated patients (59%) also improved, though at a slower rate. Subacute diabetic proximal neuropathy appears to be a variant of bilateral lumbosacral radiculoplexopathy with features of an autoimmune pathogenesis. Immunotherapy, though of unproved efficacy, may be warranted in severely progressive cases.
Neurologically, diabetes is most commonly complicated by a distal symmetric sensorimotor polyneuropathy whose other forms include focal or multi-focal (mononeuritis multiplex) cranial and peripheral nerve palsies, and autonomic gastrointestinal, genitourinary, or cardiac neuropathy (Nathan DM. N Engl J Med 1993;328:1676-1685). Diabetic amyotrophy is a relatively uncommon asymmetric proximal neuropathy with a prevalence of less than 1% (O'Hare JA, et al. Ir J Med Sci 1994;163:132-135). The uncertainty of its pathoanatomy is attested to by the plethora of terms by which it has been historically referred, including diabetic neuritis, diabetic myelopathy, femoral neuropathy, and ischemic neuropathy and mononeuritis multiplex (N Engl J Med 1930;202:1049-1053; BMJ 1953;1:1405-1408; Diabetes 1954;3:266-273; N Engl J Med 1968;279:17-22). Electrodiagnostic studies usually reveal lumbosacral radiculopathy, plexopathy, or both, but pathogenesis remains unknown, with ischemia presently holding sway over a metabolic hypothesis (Neurology 1987;37:20-28; Ann Neurol 1995;37:498-504). Of possible significance is the suggestion that etiology may be autoimmune. Although untreated patients also improved, their neuropathy impairment score (NIS), obtained by summating deficits in strength, sensation, and reflexes, was significantly lower than for the treated group, and yet the treated group improved within two weeks as opposed to over six months for the untreated group. Immunosuppression appears to play a role in the management of this unusual complication of diabetes and may be beneficial in the unilateral variant of diabetic lumbosacral and brachial plexopathy, as well. Multicenter studies will be necessary to examine this question, if enough patients are to be accrued, before this safe but expensive therapy can be generally recommended. -mr