Search

Alcoholic neuropathy emerges following the persistent alcohol imbibing, and triggers nerve damage through de-escalating the receptors situated in the central nervous system (CNS), which consecutively evolves into debilitating neuropathic state and further precipitates hyperalgesia, allodynia, dysesthesia, ataxia, numbness, immobility, and decline in certain body functions. Existing pharmacotherapy, such as anticonvulsants (gabapentin and topiramate), and antidepressant drugs (duloxetine, and venlafaxine) render short-lasting benefits; however, their continual use is not favoured nowadays because of their detrimental outcomes and habit-forming behaviour. Consequently, the research is being shifted towards exploring novel propitious targets which entirely assist in the cessation of the disease. This review discloses the multitudinous pathways implicated in the pathogenesis of alcoholic neuropathy, with special emphasis on purinergic and orexinergic receptors. Moreover, the review focuses on targeting purinergic (P2X 3 , P2X 2/3 , P2X 4 , P2X 7 , and P2Y 12 ), and orexinergic (OX1 and OX2) receptors associated with the evolution of alcoholic neuropathy, and to incentivize further investigation to attain novel propitious strategy in alcoholic neuropathy treatment. The mechanisms implicated in the progression of alcoholic neuropathy comprises malnourishment (B vitamins scarcity), direct pernicious outcomes of alcohol, increased oxidative-nitrosative stress, protein kinase C epsilon (PKCε), and extracellular signal-regulated kinase (ERK)/mitogen activated protein kinase (MAPK) functioning, abnormalities in the axonal transport and cytoskeleton system, activation of nuclear factor-kappa B (NF-κB) and caspase pathway, stimulation of the sympathoadrenal and hypothalamo-pituitary-adrenal (HPA) axis, and microglial cells of spinal column. The purinergic receptor antagonists, orexins/orexinergic receptor antagonists eliminate/modulate hyperalgesia, allodynia, inflammatory pain, liberation of inflammatory mediators, NF-κB signalling pathway, ROS formation, nerve cell deterioration, and craving for alcohol consumption, thereby ceasing the evolution of alcoholic neuropathy. The authors focus to highlight the importance of this alternative strategy as a novel target in alcoholic neuropathy, and to incentivize researchers to scrutinize the possible benefits of purinergic and orexins/orexinergic receptors in the therapy of alcoholic neuropathy., (© 2022. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.)

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.)

Background: Alcohol-related peripheral neuropathy (ALN) is generally characterized as an axonal large-fiber polyneuropathy caused by thiamine deficiency. We hypothesized, based on clinical observations, that ALN is associated with a small-fiber polyneuropathy that can be diagnosed with skin biopsy in heavy alcohol drinking subjects with normal thiamine status., Methods: Eighteen individuals (9 heavy alcohol drinking subjects and 9 healthy control subjects) were assessed for the potential utility of skin biopsies in detecting ALN-associated small nerve fiber degeneration. Heavy drinking was defined as greater than 4 drinks/d and 5 drinks/d in women and men, respectively, as determined by the Timeline Follow-Back and lifetime drinking history. All subjects underwent neurological examination, nerve conduction studies, and skin biopsies to quantify end nerve fiber densities (ENFD). Other causes of neuropathy were excluded and thiamine status was assessed., Results: Average ENFD were significantly decreased at the calf in the alcohol group as compared with control group (p < 0.0001). Histological sections demonstrated striking attrition and architectural simplification of intraepidermal nerve fibers in the heavy alcohol drinking subjects. There were no significant intergroup differences with respect to clinical assessments of neuropathy or thiamine status., Conclusions: ALN is associated with a small-fiber neuropathy that can be detected with skin biopsy in heavy alcohol drinking individuals with normal thiamine status. Skin biopsy is a useful, minimally invasive biomarker that could extend studies to understand the effect of alcohol on the peripheral nerves and to evaluate potential therapeutic agents in larger clinical trials., (Copyright © 2014 by the Research Society on Alcoholism.)

Background: Axon degeneration is a characteristic feature of multiple neuropathologic states and is also a mechanism of physiological neurodevelopmental pruning. The vast majority of in vivo studies looking at axon degeneration have relied on the use of classical silver degeneration stains, which have many limitations including lack of molecular specificity and incompatibility with immunolabeling methods. Because Wallerian degeneration is well known to involve cytoskeletal disassembly and because caspases are recently implicated in aspects of this process, we asked whether antibodies directed at caspase-generated neoepitopes of beta-actin and alpha-tubulin would be useful immunohistochemical markers of pathological and developmental axon degeneration., Results: Here we demonstrate that several forms of axon degeneration involve caspase-mediated cleavage of these cytoskeletal elements and are well-visualized using this approach. We demonstrate the generation of caspase-induced neoepitopes in a) an in vitro neuronal culture model using nerve growth factor-deprivation-induced degeneration and b) an in vivo model using ethanol-induced neuronal apoptosis, and c) during normal developmental pruning and physiological turnover of neurons., Conclusions: Our findings support recent experimental data that suggests caspase-3 and caspase-6 have specific non-redundant roles in developmental pruning. Finally, these findings may have clinical utility, as these markers highlight degenerating neurites in human hypoxic-ischemic injury. Our work not only confirms a common downstream mechanism involved in axon degeneration, but also illuminates the potential utility of caspase-cleavage-neoepitope antibodies as markers of neurodegeneration.

Charcot medial column and midfoot deformities are associated with rocker bottom foot, recurrent plantar ulceration, and consequent infection. The primary goal of surgical intervention is to realign and stabilize the plantar arch in a shoe-able, plantigrade alignment. Different fixation devices, including screws, plates, and external fixators, can be used to stabilize the Charcot foot; however, each of these methods has substantial disadvantages. To assess the effectiveness of rigid, minimally invasive fixation of the medial column and midfoot, 8 cases of solid intramedullary bolt fixation for symptomatic Charcot neuroarthropathy were reviewed. The patients included 6 males (75%) and 2 females (25%), with a mean age of 63 (range 46 to 80) years. The Charcot foot deformity was caused by diabetic neuropathy in 7 cases (87.5%) and alcoholic neuropathy in 1 (12.5%). The mean duration of postoperative follow-up period was 27 (range 12 to 44) months. The mean radiographic correction of the lateral talar-first metatarsal angle was 15° (range 3° to 19°), and the mean radiographic correction of the dorsal midfoot dislocation was 9 (range -4 to 23) mm. The mean loss of correction of the lateral talar-first metatarsal angle and midfoot dislocation after surgery was 7° (range 0° to 26°) and 1 (range 0 to 7) mm, respectively. No bolt breakage was observed, and no cases of recurrent or residual ulceration occurred during the observation period. Bolt removal was performed in 3 cases (37.5%), 2 (25%) because of axial migration of the bolt into the ankle joint and 1 (12.5%) because of infection. The results of the present review suggest that a solid intramedullary bolt provides reasonable fixation for realignment of the medial column in cases of Charcot neuroarthropathy., (Copyright © 2013 American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

We report the case of a 63-year-old patient admitted to the ICU for an acute respiratory failure one week after an outpatient cataract surgery that revealed a nemaline rod myopathy. We present this rare myopathy whose particularities are its aetiology, which can be inherited, mostly with a congenital onset, or sporadic, and the variability of the age at presentation. We discuss the exceptional onset of severe unknown underlying diseases in the context of outpatient surgery., (Copyright © 2012 Société française d’anesthésie et de réanimation (Sfar). Published by Elsevier SAS. 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.)

Chronic alcohol consumption induces a painful small-fiber peripheral neuropathy, the severity of which increases during alcohol withdrawal. Chronic alcohol consumption also produces a sustained increase in stress hormones, epinephrine and corticosterone, that is exacerbated during alcohol withdrawal. We report that adrenal medullectomy and administration of a glucocorticoid receptor antagonist, mifepristone (RU 38486), both prevented and reversed a model of painful peripheral neuropathy in alcohol binge-drinking rats. Chronic administration of stress levels of epinephrine to rats that had undergone adrenal medullectomy and were being fed the alcohol diet reconstituted this phenotype. Intrathecal administration of oligodeoxynucleotides antisense to the beta(2)-adrenergic- or glucocorticoid-receptor also prevented and reversed the pro-nociceptive effects of ethanol. Our results suggest a convergence of the effects of mediators of the hypothalamic-pituitary- and sympathoadrenal-stress axes on sensory neurons in the induction and maintenance of alcohol-induced painful peripheral neuropathy.

Alcohol neuropathy has been thought to involve decreased nerve function following chronic ethanol consumption. However, there is no reliably successful therapy, largely due to a lack of understanding of the central underlying mechanisms. The aim of this study was to investigate the mechanisms that contribute to the neuropathic pain-like state induced by chronic ethanol treatment in rats. Rats were chronically treated with ethanol diet (1.25-5% of ethanol) for over 70 days. Mechanical hyperalgesia was observed during ethanol consumption and even after ethanol withdrawal. Under these conditions, an immunohistochemical study showed an increase in metabotropic glutamate receptor 5 (mGluR5) immunoreactivity in the superficial spinal dorsal horn of chronic ethanol-fed rats. Furthermore, immunoblot analysis revealed that the protein level of mGluR5 was clearly increased following chronic ethanol consumption. These findings support the idea that the increased levels of mGluR5 in the spinal cord may be, at least in part, involved in the induction of ethanol-dependent neuropathic pain-like state.

Purpose of Review: The concept of alcoholic neuropathy has been obscured because of an often undetected or overestimated influence of thiamine deficiency. We describe clinicopathologic features of alcoholic neuropathy, taking the effect of thiamine status into consideration, and recent progress associated with the pathogenesis., Recent Findings: Clinical features of alcoholic neuropathy without thiamine deficiency are characterized by slowly progressive, sensory-dominant symptoms. Superficial sensation is predominantly impaired and painful symptoms are the major complaint. Pathologic features are characterized by small-fiber-predominant axonal loss. In contrast, the clinicopathologic features of alcoholic neuropathy with concomitant thiamine deficiency are variable, constituting a spectrum ranging from a picture of a pure form of alcoholic neuropathy to a presentation of nonalcoholic thiamine-deficiency neuropathy. One possible mediator of the direct neurotoxic effects among the metabolites of ethanol is acetaldehyde. Axonal transport and cytoskeletal properties are impaired by ethanol exposure. Protein kinase A and protein kinase C may also play a role in the pathogenesis, especially in association with painful symptoms., Summary: Nutritional deficiency as well as the direct neurotoxic effects of ethanol or its metabolites can cause alcoholic neuropathy. Although clinicopathologic features of the pure form of alcoholic neuropathy are uniform, they show extensive variation when thiamine deficiency is present.

We conducted spinal MR imaging on a 35-year-old man with Lhermitte's sign that had manifested over the previous 4 years. He had consumed more than 500 ml of whisky daily for at least 10 years. However, he did not show any evidence of severe liver disease with hepato-systemic blood shunting. Neurologic examination revealed markedly depressed sense of vibration in the feet and mild spasticity in the lower limbs, together with Lhermitte's sign. MR imaging revealed abnormal signal intensity in the posterior column spanning the whole length of the upper cervical cord, which is consistent with Lhermitte's sign.

A 51-year-old ASA physical status II, non-insulin-dependent diabetic male patient manifested lower limb nerve injury after receiving postoperative epidural analgesia with ropivacaine 0.2%. The case is presented, including a discussion of the relation between local anesthetic toxicity and diabetic neuropathy.

Characteristics of alcoholic neuropathy have been obscured by difficulty in isolating them from features of thiamine-deficiency neuropathy. We assessed 64 patients with alcoholic neuropathy including subgroups without (ALN) and with (ALN-TD) coexisting thiamine deficiency. Thirty-two patients with nonalcoholic thiamine-deficiency neuropathy (TDN) also were investigated for comparison. In ALN, clinical symptoms were sensory-dominant and slowly progressive, predominantly impairing superficial sensation (especially nociception) with pain or painful burning sensation. In TDN, most cases manifested a motor-dominant and acutely progressive pattern, with impairment of both superficial and deep sensation. Small-fiber-predominant axonal loss in sural nerve specimens was characteristic of ALN, especially with a short history of neuropathy; long history was associated with regenerating small fibers. Large-fiber-predominant axonal loss predominated in TDN. Subperineurial edema was more prominent in TDN, whereas segmental de/remyelination resulting from widening of consecutive nodes of Ranvier was more frequent in ALN. Myelin irregularity was greater in ALN. ALN-TD showed a variable mixture of these features in ALN and TDN. We concluded that pure-form of alcoholic neuropathy (ALN) was distinct from pure-form of thiamine-deficiency neuropathy (TDN), supporting the view that alcoholic neuropathy can be caused by direct toxic effect of ethanol or its metabolites. However, features of alcoholic neuropathy is influenced by concomitant thiamine-deficiency state, having so far caused the obscure clinicopathological entity of alcoholic neuropathy.

Neurophysiological study of all links of afferent somatosensory systems in neuropathies of different genesis was conducted. Patients with alcoholic (APN) and diabetic (DNP) polyneuropathies have been examined and selected as follows: 19 patients with intensive spontaneous pain syndrome (scoring over 6 on VAS); 20--without pain; 22 patients with allodiny caused by neuropathic pain and 38--without allodiny. Control group included 20 healthy subjects. Symptom complex of pain syndrome encompassed pronounced disorders of cutaneous sensitivity, minus symptoms in deep sensory sphere and high depression level. Neurophisiological appearances of spontaneous pain syndrome in APN and DPN are characterized by generalized mixed damage of peripheral sensible nerves and of 1 beta-afferents of H-reflex arch. Insufficiency of function of pain control system was mainly of deafferent character. Allodiny and spontaneous pain syndrome are reciprocally combined, the former being distinguished by involvement in pathology of 1-[symbol: see text] fibers (motor nerves and efferent links of H-reflex).

The aim of the investigation was to determine electroneuromyographic diagnostic criteria of conduction block (CB) and temporal dispersion on the basis of 78 healthy volunteers and 82 patients with alcoholic polyneuropathy examination. We investigated motor fiber ulnar, median, peroneal and tibial nerves on distal segments of extremities at the level of forearm and leg, respectively. We determined a percentage of the maximal degree of negative peak (NP) and "peak to peak" amplitude reduction, the NP area and the total M-response as well as the degree of NP duration increase and the total M-response obtained from proximal nerve stimulation point versus to distal one. The area of M-response was shown to be the less changeable index, while the degree of amplitude, area and M-response duration changes depended on the nerve studied. The greatest changes of these parameters were revealed during a tibial nerve study in the controls and in the patients with alcohol polyneuropathy. The CB presence proves being identified when the proximal NP area reduction and the total M-response is over than 30 and 35%, respectively. The temporal dispersion can be confirmed if NP duration increase is over than 30%. CB is likely suspected when the proximal NP area and the total M-response reduction is greater than 20 and 25% for the peroneal, ulnar and median nerves.

Alcohol misusers frequently have difficulties in gait, and various muscle symptoms such as cramps, local pain and reduced muscle mass. These symptoms are common in alcoholic patients and have previously been ascribed as neuropathological in origin. However, biochemical lesions and/or the presence of a defined myopathy occur in alcoholics as a direct consequence of alcohol misuse. The myopathy occurs independently of peripheral neuropathy, malnutrition and overt liver disease. Chronic alcoholic myopathy is characterized by selective atrophy of Type II fibres and the entire muscle mass may be reduced by up to 30%. This myopathy is arguably the most prevalent skeletal muscle disorder in the Western Hemisphere and occurs in approximately 50% of alcohol misusers. Alcohol and acetaldehyde are potent inhibitors of muscle protein synthesis, and both contractile and non-contractile proteins are affected by acute and chronic alcohol dosage. Muscle RNA is also reduced by mechanisms involving increased RNase activities. In general, muscle protease activities are either reduced or unaltered, although markers of muscle membrane damage are increased which may be related to injury by reactive oxygen species. This supposition is supported by the observation that in the UK, alpha-tocopherol status is poor in myopathic alcoholics. Reduced alpha-tocopherol may pre-dispose the muscle to metabolic injury. However, experimental alpha-tocopherol supplementation is ineffective in preventing ethanol-induced lesions in muscle as defined by reduced rates of protein synthesis and in Spanish alcoholics with myopathy, there is no evidence of impaired alpha-tocopherol status. In conclusion, by a complex series of mechanisms, alcohol adversely affects skeletal muscle. In addition to the mechanical changes to muscle, there are important metabolic consequences, by virtue of the fact that skeletal muscle is 40% of body mass and an important contributor to whole-body protein turnover.

A case of middle aged male who developed swelling and weakness of muscles in the lower limbs following a heavy binge of alcohol is being reported. He had myoglobinuria and developed acute renal failure for which he was dialyzed. Acute alcoholic myopathy is not a well recognized condition and should be considered in any intoxicated patient who presents with muscle tenderness and weakness.