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Thiamine (vitamin B1) deficiency is a common condition in alcohol abusers, which can lead to damage of both the peripheral and the central nervous systems. Here we describe the case of an alcoholic patient who presented with acute onset of ataxia, severe weakness of the four limbs, and hypoesthesia and dysesthesia of the distal portion of the upper and lower extremities. The clinical picture also included mental confusion and amnesia. A diagnosis of Wernicke-Korsakoff syndrome was made based on clinical symptoms and brain RMI findings. Electromyography and electroneurography revealed signs of subacute axonal sensory-motor polyneuropathy that were compatible with a rare acute presentation of beriberi. Patient immediately received parenteral thiamine administration, which resulted in rapid clinical amelioration of ataxia and confusion and also in a significant improvement of motor and sensory deficits. The association between Wernicke-Korsakoff syndrome and acute axonal polyneuropathy is a very rare condition that could make less recognizable the clinical picture of a thiamine deficiency. However, the diagnosis of thiamine deficiency should be suspected in every alcoholic patient presenting with acute onset symptoms of central and/or peripheral nervous system involvement. This because the immediate replacement treatment can be life-saving and reverse the clinical symptoms., (Copyright © 2017 Elsevier B.V. All rights reserved.)

Thiamine deficiency (vitamin B1) is common in patients with alcohol dependence. Cognitive impairments may be an early consequence of thiamine deficiency. Wernicke's encephalopathy is underdiagnosed and undertreated. In patients with established Wernicke's encephalopathy, parenteral thiamine 200-500mg three times a day should be given for 3-5 days, followed by oral thiamine 250-1000mg/day. In patients with suspected Wernicke's encephalopathy, parenteral thiamine 250-300mg should be given two times a day for 3-5 days, followed by oral thiamine 250-300mg/day. In patients at high risk of thiamine deficiency, parenteral thiamine 250-500mg/day should be given for 3-5 days, followed by oral thiamine 250-300mg/day. In patients at low risk (with uncomplicated alcohol dependence), oral thiamine 250-500mg/day should be given for 3-5 days, followed by oral thiamine 100-250mg/day., (Copyright © 2016. Published by Elsevier Masson SAS.)

The aim of the present investigation was to evaluate the effect of Coenzyme Q10 and its combination with vitamin E in alcohol-induced chronic neuropathic pain. Male Wistar rats were orally treated with alcohol (10 g/kg, 35% v/v, b.i.d.) for 10 weeks. Coenzyme Q10 (25, 50, and 100 mg/kg) and vitamin E (100 mg/kg) were coadministered orally for 1 h after ethanol administration for 10 weeks. Various nerve functions, biochemical, and molecular parameters were assessed. Chronic administration of ethanol for 10 weeks resulted significant development of neuropathic pain. Treatment with Coenzyme Q10 (50 and 100 mg/kg) for 10 weeks showed significant and dose dependently increased in level of nociceptive threshold, endogenous antioxidant, and Na,K-ATPase enzyme. Coenzyme Q10 (50 and 100 mg/kg) significantly restored the levels of motor nerve conduction velocity and sensory nerve conduction velocity. It also showed significant decrease in levels of endogenous calcium, oxidative-nitrosative stress, TNF-α, IL-1β, and IL-4 level. Alteration in protein expression of polymerase gamma (pol γ) was significantly restored the Coenzyme Q10 treatment. The important finding of the study is that, Coenzyme Q10 (100 mg/kg) and α-tocopherol (100 mg/kg) combination-treated rats showed more significant prevention of behavioral, biochemical, and molecular neurotoxic effect of alcohol administration than Coenzyme Q10 or α-tocopherol alone treated group. It is evident from the finding of present investigation that plethora of mechanism including inhibition of oxido-nitrosative stress, release of pro-inflammatory cytokine, modulation of endogenous biomarker, and protection of pol γ protein expression simultaneously orchestrate to exhibits neuroprotective effect of Coenzyme Q10, vitamin E and their combination., (© 2012 The Authors Fundamental and Clinical Pharmacology © 2012 Société Française de Pharmacologie et de Thérapeutique.)

Objective: The objective of the present investigation was to study the neuroprotective effect of the quercetin in alcohol induced neuropathy in rats., Materials and Methods: Male Wistar rats were administered alcohol (10 gm/kg, 35% v/v, p.o. b.i.d.) for 10 weeks. Alpha tocopherol (vitamin E) was used as a standard drug. Vitamin E (100 mg/kg) and quercetin (10, 20 and 40 mg/kg) were co-administered 1 h after ethanol administration for 10 weeks. Behavioral assessment parameters, such as motor incoordination, tactile allodynia, mechanical and thermal hyperalgesia were recorded in all groups of animals. Meanwhile, motor nerve conduction velocity was also recorded. Biochemical parameters, such as nitric oxide (NO), Na(+)-K(+)-ATPase, malondialdehyde (MDA) and myeloperoxidase (MPO) were estimated in sciatic nerve. Apoptosis index was determined with help of DNA fragmentation in sciatic nerve., Results and Discussion: Chronic ethanol administration for 10 weeks resulted in significant (P < 0.001) development of neuropathic pain. Chronic treatment with quercetin (20 and 40 mg/kg) for 10 weeks significantly (P < 0.001) attenuated allodynia, hyperalgesia as well as motor coordination and impaired nerve conduction velocity along with decreased level of membrane-bound Na(+)-K(+)-ATPase. It also significantly (P < 0.001) decreased elevated levels of MDA, MPO as well as pro-inflammatory mediators, such as NO. It also decreased the extent of DNA fragmentation. This alteration was more significant in vitamin E treated rats (100 mg/kg). Quercetin is a proven antioxidant that might have decreased the oxidative stress produced by chronic alcoholism., Conclusion: The present investigation elucidates neuroprotective effect of quercetin in alcohol induced neuropathy through modulation of membrane-bound inorganic phosphate enzyme and inhibition of release of oxido-inflammatory mediators, such as MDA, MPO and NO.

Small-fiber painful peripheral neuropathy is one of the long-term complications of alcohol for which there is no reliable successful therapy available. The precise mechanisms by which chronic alcohol consumption produces peripheral nerve fiber damage and loss remain unclear. Emerging data from clinical and preclinical studies suggest that increased oxidative-nitrodative stress mediated release of proinflammatory cytokines from damaged neural tissues may play a central role in the pathogenesis of alcoholic neuropathy. The present study investigated the effect of both the isoforms of vitamin E (α-tocopherol and tocotrienol) against chronic alcohol-induced peripheral neuropathy in rats. Ethanol treated rats showed a significant decrease in paw-withdrawal threshold in both Randall-Selitto and von-Frey hair tests along with a significant reduction in tail flick latency in the tail-immersion test. A decreased pain threshold was associated with significant alterations in oxidative-nitrodative stress markers and an increase in proinflammatory cytokines (TNF-α and IL-1β). The 4-week treatment with tocotrienol significantly ameliorated behavioral, biochemical and molecular alterations in alcohol treated rats. However, α-tocopherol failed to produce any protective effect. The results of the present study suggest that oxidative-nitrodative stress mediated cytokine signaling may be responsible for alcohol-induced peripheral neurotoxicity and tocotrienol treatment might be beneficial in chronic alcoholics exhibiting neuropathy., (Copyright © 2012 John Wiley & Sons, Ltd.)

Painful peripheral neuropathy induced by chronic ethanol consumption is a major medico-socioeconomical problem. The objective of present investigation was to study the effect of curcumin (20, 40 and 80mg/kg; p.o.) in alcohol-induced neuropathy in rats. Ethanol (35% v/v, 10g/kg; p.o.) was administered for 10 weeks which showed a significant decrease in thermal hyperalgesia, mechanical hyperalgesia, mechanical allodynia and nerve conduction velocity. It caused enhanced malondialdehyde, oxidative-nitrosative stress, total calcium levels, inflammatory mediators (TNF-α and IL-1β levels) along with DNA damage. Co-administration of curcumin and α-tocopherol for 10 weeks significantly and dose-dependently improved nerve functions, biochemical as well as molecular parameters and DNA damage in sciatic nerve of ethanol treated rats. Hence, it was concluded that curcumin is of potent therapeutic value in the amelioration of alcoholic neuropathy in rats and acts by inhibition of pro-inflammatory mediators like TNF-α and IL-1β., (Copyright © 2012 Elsevier Ireland Ltd. All rights reserved.)

Long term alcohol consumption leads to decreased nociceptive threshold characterized by spontaneous burning pain, hyperalgesia and allodynia. The mechanism involved in this pain includes increased oxidative-nitrosative stress, release of pro-inflammatory cytokines and neuronal apoptosis. The present study was designed to explore the protective effect of epigallocatechin-3-gallate against alcoholic neuropathic pain in rats. Rats fed with alcohol (35%) for 10 weeks showed markedly decreased tail flick latency in tail-immersion test (thermal hyperalgesia), vocalization threshold in Randall-Sellito test (mechanical hyperalgesia) and paw-withdrawal threshold in von-Frey hair test (mechanical allodynia) along with enhanced oxidative-nitrosative stress and inflammatory mediators (TNF-α, IL-1β and TGF-β1 levels). Co-administration of epigallocatechin-3-gallate (25-100 mg/kg) significantly and dose-dependently prevented functional, biochemical and molecular changes associated with alcoholic neuropathy. In conclusion, the current findings suggest the neuroprotective potential of epigallocatechin-3-gallate in attenuating the functional, biochemical and molecular alterations associated with alcoholic neuropathy through modulation of oxido-inflammatory cascade., (Copyright © 2010 European Federation of International Association for the Study of Pain Chapters. Published by Elsevier Ltd. All rights reserved.)

A major dose-limiting side effect of human immunodeficiency virus/acquired immunodeficiency syndrome (HIV/AIDS) chemotherapies, such as the nucleoside reverse transcriptase inhibitors (NRTIs), is a small-fiber painful peripheral neuropathy, mediated by its mitochondrial toxicity. Co-morbid conditions may also contribute to this dose-limiting effect of HIV/AIDS treatment. Alcohol abuse, which alone also produces painful neuropathy, is one of the most important co-morbid risk factors for peripheral neuropathy in patients with HIV/AIDS. Despite the prevalence of this problem and its serious impact on the quality of life and continued therapy in HIV/AIDS patients, the mechanisms by which alcohol abuse exacerbates highly active antiretroviral therapy (HAART)-induced neuropathic pain has not been demonstrated. In this study, performed in rats, we investigated the cellular mechanism by which consumed alcohol impacts antiretroviral-induced neuropathic pain. NRTI 2',3'-dideoxycytidine (ddC; 50 mg/kg) neuropathy was mitochondrial-dependent and PKCε-independent, and alcohol-induced painful neuropathy was PKCε-dependent and mitochondrial-independent. At low doses, ddC (5 mg/kg) and alcohol (6.5% ethanol diet for 1 week), which alone do not affect nociception, together produce profound mechanical hyperalgesia. This hyperalgesia is mitochondrial-dependent but PKCε-independent. These experiments, which provide the first model for studying the impact of co-morbidity in painful neuropathy, support the clinical impression that alcohol consumption enhances HIV/AIDS therapy neuropathy, and provide evidence for a role of mitochondrial mechanisms underlying this interaction., (© 2010 The Authors. European Journal of Neuroscience © 2010 Federation of European Neuroscience Societies and Blackwell Publishing Ltd.)

Investigation of therapeutic effectiveness of cortexin in chronic alcohol encephalopathy and chronic alcohol polyneuropathy was conducted in an open randomized study. The aim of the study was to compare these disorders with diabetic and professional polyneuropathy. Cortexin was prescribed in dose 10 mg/d intramuscular during 10 days, along with standard therapy. The group of patients consisted of 15 people with alcohol disorders, 15 people with diabetic polyneuropathy and 15 people with professional polyneuropathy. The control group included 15 patients with alcohol disorders who did not receive cortexin. Encephalography (EEG) and electroneuromyography (ENMG) were used in addition to the clinical examination. Cortexin had the positive effect on clinical symptoms, EEG and ENMG. The drug was well-tolerated, no side-effects were observed.

Chronic alcohol consumption produces a painful peripheral neuropathy for which there is no reliable successful therapy, which is mainly due to lack of understanding of its pathobiology. Alcoholic neuropathy is characterized by spontaneous burning pain, hyperalgesia (an exaggerated pain in response to painful stimuli) and allodynia (a pain evoked by normally innocuous stimuli). Chronic alcohol intake is known to decrease the nociceptive threshold with increased oxidative-nitrosative stress and release of proinflammatory cytokines coupled with activation of protein kinase C. The aim of the present study is to investigate the effect of both isoforms of vitamin E, alpha-tocopherol (100mg/kg; oral gavage) and tocotrienol (50, 100 and 200mg/kg; oral gavage) against alcohol-induced neuropathic pain in rats. Male Wistar rats, were administered 35% v/v ethanol (10 g/kg; oral gavage) for 10 weeks, and were treated with alpha-tocopherol and tocotrienol for the same duration. Ethanol-treated animals showed a significant decrease in nociceptive threshold as evident from decreased tail flick latency (thermal hyperalgesia) and decreased paw-withdrawal threshold in Randall-Sellito test (mechanical hyperalgesia) and von-Frey hair test (mechanical allodynia) along with the reduction in nerve glutathione and superoxide dismutase levels. TNF-alpha and IL-1beta levels were also significantly increased in both serum and sciatic nerve of ethanol-treated rats. Treatment with alpha-tocopherol and tocotrienol for 10 weeks significantly improved all the above-stated functional and biochemical deficits in a dose-dependent manner with more potent effects observed with tocotrienol. The study demonstrates the effectiveness of tocotrienol in attenuation of alcoholic neuropathy.

Aims: To evaluate the therapeutic efficacy and safety of BEFACT Forte 'new formulation' and BEFACT Forte 'old formulation' in the treatment of sensory symptoms of alcoholic polyneuropathy., Methods: A multi-centre, randomised, double-blind, placebo-controlled study was conducted on 325 patients with sensory symptoms and signs of alcoholic polyneuropathy. Patients were randomised to the 'old formulation' (i.e. vitamins B1, B2, B6, and B12), 'new formulation' [i.e. identical to the 'old formulation' with additional folic acid (vitamin B9)], or placebo in a 1:1:1 ratio. One tablet of the study medication ('new formulation' or 'old formulation') or placebo was taken orally, three times a day, over a 12-week treatment period., Results: Therapeutic efficacy was assessed in 253 patients by measuring vibration perception threshold (biothesiometry), intensity of pain, sensory function, co-ordination, and reflex responses. Patients treated with the 'new formulation' or 'old formulation' showed significant improvement in the primary efficacy endpoint (vibration perception threshold at the big toe) and secondary efficacy endpoints in comparison to placebo. The active treatment groups were comparable to placebo in terms of safety., Conclusions: A specific vitamin B complex (with and without folic acid) significantly improved symptoms of alcoholic polyneuropathy over a 12-week treatment period.

A 34-year-old alcoholic man had neurological and cardiac symptoms. The patient was admitted to the hospital for acute painful sensory disturbances and severe weakness of the feet. Neurological and electrophysiological investigation revealed axonal sensorimotor polyneuropathy that was most prominent in the legs. Cardiac assessment showed signs and symptoms of heart failure due to a high-output state. Blood analysis showed a low thiamine concentration of 58 nmol/l (lower reference limit: 80). Therefore, a diagnosis of combined wet beriberi with cardiomyopathy and dry beriberi with axonal polyneuropathy was made. The treatment of beriberi is simple and effective and consists of thiamine supplementation in conjunction with diuretic treatment. With this approach, the patient recovered fully. Patients with beriberi have a good prognosis, particularly when the diagnosis is made at an early stage.

A comparison study of efficacy and tolerability of the drug berlition 300 oral and berliton 300 U and vitamin B1 has been conducted in 56 patients with alcohol polyneuropathy (15 female, 41 male, mean age 42.6 years). The key mechanisms of berlition action are increasing of endoneural blood flow, strengthening of antioxidant system functioning and reduction of "oxidative stress" intensity; improvement of glucose consumption and restoring of nerve energetic balance as well as intensification of nerve growth factor releasing and nerve growth acceleration after its experiment cutting or squeezing. Usage of berlition in the cohort studied was accompanied by a positive dynamics of both subjective and objective clinical symptoms. Comparing to vitamin B1, the drug was significantly more effective by clinical and electrophysiological indices. Berlition therapy is tolerable and safe. The results of the study confirm an assumption of berlition efficacy in alcohol polyneuropathy and allow to recommend the drug for a wide clinical application.

In the first instance, polyneuropathies are treated causally. The most common underlying cause is diabetes mellitus or alcohol abuse. In a large number of patients with polyneuropathy, however, the underlying cause cannot be definitively identified. For these--but equally for patients with etiologically clear polyneuropathy--a stock-taking of clinical symptoms should be carried out and, where indicated, symptomatic treatment initiated. In addition to medication aimed at combating pain, muscular spasm, autonomic functional disorders, and for the prevention of thrombosis, physical measures (physiotherapy, foot care, orthopedic shoes) are of primary importance.

Benfogamma efficacy in alcoholic polyneuropathy therapy with pain syndrome and other sensor disorders has been studied. Fourteen males with stage II-III chronic alcoholism (mean age 41.2 +/- 9 years, mean alcoholism duration 20.6 +/- 6 years, mean alcoholic polyneuropathy therapy duration 6.8 +/- 4.9 years) have been examined, 93% of the cases having positive family history of alcoholism. Clinical neurophysiological examination was conducted at the beginning and at the end of 6-week therapy, 450 mg/day (2 weeks) and 300 mg/day (4 weeks). During the treatment the regress of algic, other sensor and movement disorders, as well as some neuropathy symptoms has been observed. The evidence of positive dynamics at peripheral and segmental nerve system level was supported by neurophysiological data.