Distal Symmetric Sensorimotor Polyneuropathy Research Articles

Update on diabetic neuropathy.

This review will focus on recent advances in the field of diabetic neuropathy, with an emphasis on distal symmetric sensory and sensorimotor polyneuropathy. Some new information in the areas of diabetic amyotrophy and diabetic autonomic neuropathy will also be reviewed. The pathogenesis of diabetic neuropathy is multifactorial. There is increasing evidence to link abnormalities in the polyol pathway to the pathogenesis of diabetic neuropathy. In addition, there appear to be abnormalities of nerve regeneration and of sodium and calcium channels. Aldose reductase inhibitors have shown promise in animal models for reversing neuropathy if started early and used for a sufficient time, but those used to date in human trials are probably not of sufficient potency. Neurotrophic factors and vascular endothelial growth factor both also show promise. Specific recommendations and pathways for diabetic foot care have been devised. Lamotrigine and bupropion represent new treatments for neuropathic pain. The role of impaired glucose tolerance is being explored as it relates to polyneuropathy. An increasing understanding of the pathogenetic mechanisms holds out promise for the effective treatment of diabetic neuropathy. The early detection of abnormal glucose metabolism is particularly important, as treatments will probably be most effective if administered early in the course of the neuropathy, when abnormalities of peripheral nerves are more likely to be reversible.

Multifocal Conduction Block in Peripheral Nerve Vasculitis

Peripheral nervous system (PNS) vasculitis and Guillain-Barré syndrome (GBS) are two distinct entities. Although there may be similarities in clinical presentation, the two are rarely confused. PNS vasculitis typically presents as a mononeuritis multiplex, as an overlapping mononeuritis multiplex, or as a distal symmetric sensorimotor polyneuropathy. Electrophysiologic studies are consistent with a primary axonal pathophysiologic process. In contrast, GBS typically presents with variable, mild sensory symptoms followed by symmetric progressive weakness. Early electrophysiologic studies, when abnormal, usually demonstrate findings consistent with demyelination. We describe two cases of PNS vasculitis in which the initial clinical presentation and the presence of multifocal conduction block on electrophysiologic studies led to the incorrect diagnosis of GBS early in the hospital course. Although GBS must always be considered in patients with rapidly progressive weakness, physicians must remain vigilant for alternative diagnoses, as illustrated by our cases.

Diabetic neuropathy: scope of the syndrome

Diabetic neuropathy is a common complication of diabetes that may be disabling and even contribute to mortality. Diabetic peripheral neuropathy encompasses a group of clinical and subclinical syndromes, each characterized by diffuse or focal damage to peripheral somatic or autonomic nerve fibers. None of these syndromes is pathognomonic for diabetes, and they may occur idiopathically or in association with other disorders in nondiabetic persons. Distal symmetric sensorimotor polyneuropathy is the most common form of peripheral neuropathy and is the leading cause of lower limb amputation. The characteristic slowing of sensory and motor nerve conduction velocities and advancing distal symmetric sensorimotor deficits are ascribed to an underlying insidious, chronically progressive, length-dependent, distal axonopathy of the dying-back type primarily, but not exclusively, affecting sensory nerve fibers. The cumulative prevalence of clinical diabetic neuropathy parallels the degree and duration of antecedent hyperglycemia, and the Diabetes Control and Complications Trial definitively established an important role of improved metabolic control in the primary prevention of clinical neuropathy. Improved blood glucose control substantially reduces the risk of developing diabetic polyneuropathy in type 1 diabetes mellitus, thereby strongly implicating hyperglycemia as the important causative factor in this degenerative disease process. Studies in experimental animal models reveal several glucose-related metabolic mechanisms that could initiate neurochemical, neurotrophic, and/or neurovascular defects culminating in a peripheral sensorimotor and autonomic neuropathy. Other than improved blood glucose control, therapy for diabetic neuropathy remains palliative and supportive, although this is expected to change radically as new insights into the pathogenetic mechanisms of diabetic neuropathy give rise to specific new mechanism-based therapies.

A Practical Two-Step Quantitative Clinical and Electrophysiological Assessment for the Diagnosis and Staging of Diabetic Neuropathy

Early diagnosis of distal symmetric sensorimotor polyneuropathy, a common complication of diabetes, may decrease patient morbidity by allowing for potential therapeutic interventions. We have designed an outpatient program to facilitate diagnosis of diabetic neuropathy. Patients are initially administered a brief questionnaire and screening examination, designated the Michigan Neuropathy Screening Instrument (MNSI). Diabetic neuropathy is confirmed in patients with a positive assessment by a quantitative neurological examination coupled with nerve conduction studies, designated the Michigan Diabetic Neuropathy Score (MDNS). In this study, 56 outpatients with confirmed type I or II diabetes were administered the standardized quantitative components required to diagnose and stage diabetic neuropathy according to the San Antonio Consensus Statement (1) and the Mayo Clinic protocol (2). These same patients were then assessed with the MNSI and the MDNS. Of 29 patients with a clinical MNSI score > 2, 28 had neuropathy. Twenty-eight patients with an MDNS of > or = 7 had neuropathy, while 21 non-neuropathic patients had a score < or = 6. Of 35 patients with diabetic neuropathy, 34 had > or = 2 abnormal nerve conductions. Twenty-one normal patients and one patient with neuropathy had < or = 1 abnormal nerve conduction. The results indicate that the MNSI is a good screening tool for diabetic neuropathy and that the MDNS coupled with nerve conductions provides a simple means to confirm this diagnosis.

Complications: neuropathy, pathogenetic considerations.

The most common form of neuropathy associated with diabetes mellitus is distal symmetric sensorimotor polyneuropathy, often accompanied by autonomic neuropathy. This disorder is characterized by striking atrophy and loss of myelinated and unmyelinated fibers accompanied by Wallerian degeneration, segmental, and paranodal demyelination and blunted nerve fiber regeneration. In both humans and laboratory animals, this progressive nerve fiber damage and loss parallels the degree and/or duration of hyperglycemia. Several metabolic mechanisms have been proposed to explain the relationship between the extent and severity of hyperglycemia and the development of diabetic neuropathy. One mechanism, activation of the polyol pathway by glucose via AR, is a prominent metabolic feature of diabetic rat peripheral nerve, where it promotes sorbitol and fructose accumulation, myo-inositol depletion, and slowing of nerve conduction by alteration of neural Na(+)-K(+)-ATPase activity or perturbation of normal physiological osmoregulatory mechanisms. ARIs, which normalize nerve myo-inositol and nerve conduction slowing, are currently the focus of clinical trials. Other specific metabolic abnormalities that may play a role in the pathogenesis of diabetic neuropathy include abnormal lipid or amino acid metabolism, superoxide radical formation, protein glycation, or potential blunting of normal neurotrophic responses. Metabolic dysfunction in diabetic nerve is accompanied by vascular insufficiency and nerve hypoxia that may contribute to nerve fiber loss and damage. Although major questions about the pathogenesis of diabetic neuropathy remain unanswered and require further intense investigation, significant recent progress is pushing us into the future and likely constitutes only the first of many therapies directed against one or more elements of the complex pathogenetic process responsible for diabetic neuropathy.

Peripheral neuropathy in essential mixed cryoglobulinemia.

Sixteen patients with essential mixed cryoglobulinemia were studied and followed up clinically and electrophysiologically for 4.2 years. Peripheral neuropathy was diagnosed in seven cases. Five of these patients had distal symmetrical sensorimotor polyneuropathy. Nerve conduction velocities were normal and therefore indicative of pure axonal neuropathy. Sural nerve biopsy showed moderate loss of myelinated axons in two patients and severe loss in one. This patient also had necrotizing arteritis. The remaining two had both clinical and electrophysiologic signs of overlapping mononeuritis multiplex with severe denervation in the territory of the involved nerves, but normal conduction velocities. Sural nerve biopsy in one of these two patients showed marked loss of myelinated fibers and signs of vasculitis. Two types of neuropathy were noted: (1) a mild distal neuropathy with relatively minor neurologic deficit, probably due to vasa nervorum microcirculation occlusion caused by intravascular deposits of cryoglobulins and (2) a severe distal symmetrical sensorimotor neuropathy or overlapping mononeuritis multiplex, associated with necrotizing vasculitis.

The clinical spectrum of necrotizing angiopathy of the peripheral nervous system.

The peripheral neuropathy seen with necrotizing angiopathy is said to begin classically as a mononeuritis multiplex, usually associated with polyarteritis nodosa, rheumatoid arthritis, or systemic lupus erythematosus. Our experience, however, suggests that a large number of these patients do not have a well-defined collagen vascular disease or the typical clinical pattern. In 350 consecutive nerve biopsies (sural or superficial radial), 16 patients showed a necrotizing angiopathy in the epineurial blood vessels. Six of these 16 patients had a distal symmetrical sensorimotor polyneuropathy. The remaining 10 had a mononeuritis multiplex, although in 8 overlapping nerve involvement somewhat obscured the picture of mononeuritis. In 12 patients, no specific underlying collagen vascular disease could be diagnosed by accepted criteria despite extensive clinical, radiological, and serological evaluations. The peripheral neuropathy was the only objective evidence of vasculitis in 7 of these 12 patients. Our findings suggest that patients with a peripheral neuropathy secondary to necrotizing angiopathy often do not have a definable collagen vascular disease. In fact, peripheral neuropathy may be the sole manifestation of vasculitis. Furthermore, the neuropathy was found to be a distal symmetrical sensorimotor neuropathy in a higher proportion of cases than has been documented previously.