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Sural, super cial peroneal, and lateral femoral cutaneous nerve biopsies reveal loss of myelinated nerve bers, which is often asymmetric between and within nerve fascicles52,54 58 Active axonal degeneration and clusters of small thinly myelinated regenerating bers are appreciated Mild perivascular in ammation and less commonly frank vasculitic change involving epineurial and perineurial blood vessels have been noted on some nerve biopsies (Fig 19 3)55,58,62
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Some authorities have speculated that diabetic radiculoplexus neuropathy is an immune-mediated microangiopathy; however, the pathogenic mechanism is unclear54,58,62
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Lumbar puncture usually reveals an elevated CSF protein with a normal cell count Erythrocyte sedimenta-
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Figure 19 3 Lumbosacral radiculoplexus neuropathy Super cial peroneal nerve biopsy reveals perivascular in ammation of a small epineurial vessel H&E stain
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Treatment
Small retrospective studies have reported that intravenous immunoglobulin (IVIG), prednisone, and other forms of immunosuppressive therapy appear to be helpful in some patients with diabetic amyotrophy51,53,54,58,62 We have been impressed by the fact that short courses of corticosteroids ease the pain associated with the severe radiculoplexus neuropathy and this can allow the patients to undergo physical therapy However, the natural history of this neuropathy is gradual improvement, so the actual effect, if any, of these immunotherapies on the radiculoplexus neuropathy is not known Prospective, double-blinded, placebo-controlled trials are necessary to de ne the role of various immunotherapies in this disorder
and temporal dispersion are found55,63,66 Occasionally, the electrophysiological features can ful ll research criteria for demyelination, but these are generally more axonal in nature than seen in idiopathic CIDP63,65,66 EMG reveals brillation potentials and positive sharp waves diffusely, including multiple levels of the paraspinal musculature Autonomic studies may demonstrate abnormalities in sudomotor, cardiovagal, and adrenergic functions53,55
Histopathology
Sural nerve biopsies demonstrate a loss of large and small myelinated nerve bers, with axonal degeneration and clusters of small regenerating bers53 55,63,65 Nerve biopsies may show immunoreactivity for matrix metalloproteinase-9 as seen in idiopathic CIDP69 Occasionally, demyelinated bers and onion-bulb formations are appreciated along with scant perivascular mononuclear in ammatory cells in the peri- and epineurium Nevertheless, these nerve biopsy abnormalities are not speci c for symmetric diabetic polyradiculopathy or CIDP, as similar ndings can be seen in DSPN and diabetic amyotrophy
SYMMETRIC, PAINLESS, DIABETIC POLYRADICULOPATHY OR RADICULOPLEXUS NEUROPATHY Clinical Features
The second major group of diabetic polyradiculopathy or radiculoplexus neuropathy presents with a progressive, relatively painless, symmetrical proximal and distal weakness that typically evolves over weeks to months such that it clinically resembles chronic in ammatory demyelinating polyneuropathy (CIDP)51,53 55,63,64 69 Whether this neuropathy represents the coincidental occurrence of CIDP in a patient with DM or this is a distinct form of diabetic neuropathy is unclear This type of neuropathy occurs in both types 1 and type 2 DM but may be more common in the former The pattern of weakness resembles CIDP in that there is symmetric distal and proximal weakness affecting the legs more than the arms Distal muscles are more affected than proximal muscles In our experience there is usually distal arm weakness, but proximal arm involvement is often less noticeable than seen in patients with idiopathic CIDP Unlike the more common diabetic amyotrophy discussed in the previous section, the onset of weakness is not heralded or accompanied by such severe back and proximal leg pain and the motor weakness is relatively symmetric However, distal dysesthesias, perhaps secondary to a superimposed DSPN, are occasionally present
Pathogenesis
The pathogenic basis for this form of polyradiculoneuropathy is unknown and perhaps is multifactorial This neuropathy may just represents a spectrum of diabetic amyotrophy We suspect that some cases represent CIDP occurring coincidentally in patients with DM, as some appear to improve with various immunotherapies However, this apparent response does not imply that the patients have CIDP, because these patients can improve spontaneously without treatment53,55 Alternatively, the disorder may be a distinct form of diabetic neuropathy caused by the associated metabolic disturbances such as uremia
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