30 trials. Although controlled trials of the aldose reductase inhibitors sorbinol and tolrestat were found to improve electrophysiologic or morphometric markers of DSPN, any clinically meaningful improvement in pain or sensation has been inconsistent. Rx with recombinant nerve growth factor was ineffective. Alpha lipoic acid (thioctic acid), an antioxidant, has been shown to improve experimental diabetic neuropathy, and a meta-analysis of clinical trials suggested that the Rx (600 mg/ d IV for 3 weeks) is safe and improves symptoms and signs of neuropathy. Pancreatic transplantation can halt progression of DSPN but is a realistic therapy only for patients who have renal failure and are undergoing combined kidney and pancreas transplantation.# Glycemic control is essential for the prevention of diabetic autonomic neuropathy. Once neuropathy is established, few effective Rxs exist.Classification of Neuropathy by Histopathology DemyelinatingAxonalNeuronalPatternProximal = distalDistal > proximal; length- dependentNon-length-dependent; UE, LE, faceOnsetAcute/subacuteSlow evolutionRapidSymptomsParesthesia and weaknessDysesthesias and distal weaknessParesthesias, gait ataxiaSensory signsVibration and proprioception > pain and temperaturePain and temperature affected > vibration and proprioceptionVibration and proprioception > pain and temperatureMotorDistal and proximal weaknessDistal weaknessProprioceptive weaknessDTRsAreflexiaDistal areflexiaAreflexiaNCSVelocity affected > amplitudeAmplitudes affected > velocitySensory amplitudes affected; radial > suralNerve biopsyDemyelination and remyelinationAxonal degeneration and regenerationAxonal degeneration but no regenerationPrognosisRapid recoverySlow recoveryPoor recoveryCausesGBS, diphtheria, CIDP, DM, MMNToxic, metabolic, HIV, CMT2, DMSjogren's, cisplatin, pyridoxineNote: Although there is evidence of immune activation in CIDP, the precise mechanisms of pathogenesis are unknown.Biopsy typically reveals little inflammation and "onion-bulb" changes (imbricated layers of attenuated Schwann cell processes surrounding an axon) that result from recurrent demyelination and remyelination. The response to therapy suggests that CIDP is immune-mediated; CIDP responds to glucocorticoids, whereas GBS does not.Classification of Neuropathy by Fiber TypeSmall-fiber sensory (painful neuropathies and dissociated sensory loss)# Hereditary sensory neuropathies (early)# Lepromatous leprosy# Diabetic (includes glucose intolerance) small-fiber neuropathy# Amyloidosis# Analphalipoproteinemia (Tangier disease)# Fabry's disease (pain predominates)# Dysautonomia (Riley-Day syndrome)# HIV and antiretroviral therapy neuropathyLarge-fiber sensory (ataxic-neuropathies)# Sjogren's syndrome# Vitamin B12 neuropathy (from dorsal column involvement)# Cisplatin neuropathy# Pyridoxine toxicity# Friedreich's ataxiaSmall- and large-fiber: Global sensory loss# Carcinomatous sensory neuropathy# Hereditary sensory neuropathies (recessive and dominant)# Diabetic sensory neuropathy# Vacor intoxication# Xanthomatous neuropathy of primary biliary cirrhosis (tabes dorsalis)Motor-predominant neuropathies# Immune neuropathies: acute (Guillain-BarrA(c) syndrome); relapsing# Heritable motor-sensory neuropathies# Acute intermittent porphyria# Diphtheritic neuropathy# Lead neuropathy# Brachial neuritis# Diabetic lumbosacralplexus neuropathy (diabetic amyotrophy)Autonomic# Acute: Acute pandysautonomic neuropathy, botulism, porphyria, GBS, vacore, amiodarone, vincristine# Chronic: Amyloid, diabetes, SjAUgren's, HSAN 1 and III (Riley-Day), Chagas, paraneoplastic">