Diabetic lumbosacral radiculoplexus neuropathy: a postmortem studied patient and review of the literature

Peripheral neuropathy is an important complication of diabetes mellitus. A particular type of proximal diabetic neuropathy, lumbosacral radiculoplexus neuropathy (DLSRPN), presents with pelvi-femoral pain followed by weakness, beginning focally in the upper leg or thigh with spread to the contralateral limb, and variable weight loss [1]. Ischemic nerve injury due to microscopic vasculitis has been a widely postulated unifying hypothesis of DLSRPN and derived from one well studied postmortem case reported 4 decades ago, the finding of microscopic vasculitis in proximal or distal cutaneous nerve biopsy tissue and the favorable response to immunotherapy. A 59 year old man with diabetes mellitus for 15 years treated with oral hypoglycemic medication noted left thigh pain, paresthesia, and impotence commencing in January 1995. This was followed by sensory changes and weakness first in the left leg then in the other in a stepwise fashion leading first to the necessity of a cane, then walker accompanied by a 15 lb weight loss, until he was essentially bed-bound and admitted to the hospital in June 1995. Admission neurological examination showed wasting and near-flail weakness in the legs from the thighs to the toes with rare limb fasciculation, mild distal weakness of the hands in the distribution of the distal median and ulnar nerves, mild stocking sensory loss to light touch, vibratory and cold temperature stimulation to just above the knee, areflexia, and otherwise intact cranial nerves and cognition. Admission laboratory studies showed erythrocyte sedimentation rate 60 mm/hour (normal \20), fasting blood glucose 250 mg/dL (normal \105), and hemoglobin A1C level 7.1% (normal \6). Causes of neuropathy other than diabetes mellitus were excluded by appropriate investigations. Nerve conduction studies and electromyography (EMG) of the right arm and leg showed axonal neuropathy with acute and chronic denervation in proximal and distal limb muscles including lumbosacral paraspinal muscles. Cerebrospinal fluid showed total protein 122 mg/dL (normal\45) and glucose 88 mg/dL with 12 white blood cells/ mm (normal \5). Right sural nerve biopsy showed features of microvasculitis (MV). Inflammatory cells surrounded a small epineurial artery with extension into the vascular wall, with reactive luminal connective tissue suggesting recanalization of a thrombus. An adjacent nerve fascicle showed marked loss of myelinated nerve fibers. The patient was treated for painful diabetic lumbosacral plexopathy and peripheral nerve vasculitis according to prevailing standards with 2 g/kg intravenous immunoglobulin for 5 days, followed by 750 mg of intravenous cyclophosphamide and 1,000 mg of methylprednisolone intravenously for 3 additional days. This was followed by acute tubular necrosis, increasing lethargy, unresponsiveness, and aspiration pneumonia requiring mechanical ventilation. He expired 4 weeks after admission. General autopsy showed no evidence of systemic or peripheral nerve vasculitis. The brain showed diffuse loss of neurons in all sampled cortical areas, including the cerebellum, consistent with anoxia secondary to cardiac arrest. Sections of extradural lumbar plexus, sciatic, and femoral nerve tissue showed perivascular epineurial inflammation with infiltration of adjacent endoneurium (Fig. 1a, b). Perivascular inflammation, not MV, was noted in postmortem nerve tissue in our patient. Although the D. S. Younger (&) Department of Neurology, New York University School of Medicine, 333 East 34th Street, Suite 1J, New York, NY 10016, USA e-mail: david.younger@nyumc.org