Alcohol-related peripheral neuropathy: Clinico-neurophysiological characteristics and diagnostic utility of the neuropathy symptoms score and the neuropathy impairment score.

Alcohol overconsumption is well known to cause damage to the peripheral nervous system, affecting both small and large nerve fibers. The aim of this descriptive study was to investigate peripheral nerve damage, and to correlate clinical, epidemiological and neurophysiological findings, in patients diagnosed with Alcohol Use Disorder (AUD). Ninety alcohol-dependent subjects on inpatient basis were enrolled in this prospective study over a 3-year period. Every subject was assessed by the Neuropathy Symptoms Score (NSS) questionnaire and the Neuropathy Impairment Score (NIS) clinical examination grading scale, followed by Nerve Conduction Studies, Quantitative Sensory Testing and Sympathetic Skin Response (SSR) testing. Peripheral neuropathy was diagnosed in 54 subjects (60%), by abnormal neurophysiological tests and presence of clinical signs or symptoms. Among them, pure large fiber neuropathy (LFN) was found in 18 subjects, pure small fiber neuropathy (SFN) in 12 subjects, and both large and small fiber neuropathy was diagnosed in 24 subjects. Using linear regression, we found that higher NSS and NIS scores correlated with lower amplitudes of the sural sensory nerve action potential and of the SSR. We also found a significant longer duration of alcohol abuse in subjects with neuropathy, using Student's t-test (p = 0.024). Additionally, applying NIS abnormal cut-off score ≥4, using ROC analysis, we predicted the majority of subjects with LFN, confirming 95.23% sensitivity and 93.75% specificity. Our study confirmed that peripheral neuropathy involving large and small nerve fibers, with a symmetrical length-dependent pattern, is common between patients with AUD and related to the duration of the disorder. We suggest that NSS and NIS scales could be used for the assessment of neuropathy in clinical practice, when the essential neurophysiological testing is not available.

Exploring the Therapeutic Potential of Targeting Purinergic and Orexinergic Receptors in Alcoholic Neuropathy.

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 (P2X3, P2X2/3, P2X4, P2X7, and P2Y12), 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.

Characterization and quantification of alcohol-related polyneuropathy by magnetic resonance neurography.

BACKGROUND: We characterized and quantified peripheral nerve damage in alcohol-dependent patients (ADP) by magnetic resonance neurography (MRN) in correlation with clinical and electrophysiologic findings. METHODS: Thirty-one adult patients with a history of excessive alcohol consumption and age-/sex-matched healthy controls were prospectively examined. After detailed neurologic and electrophysiologic testing, the patient group was subdivided into ADP with alcohol-related polyneuropathy (ALN) and without ALN (Non-ALN). 3T MRN with anatomical coverage from the proximal thigh down to the tibiotalar joint was performed using dual-echo 2-dimensional relaxometry sequences with spectral fat saturation. Detailed quantification of nerve injury by morphometric (cross-sectional area [CSA]) and microstructural MRN markers (proton spin density [ρ], apparent T2-relaxation-time [T2app ]) was conducted in all study participants. RESULTS: MRN detected nerve damage in ADP with and without ALN. A proximal-to-distal gradient was identified for nerve T2-weighted (T2w)-signal and T2app in ADP, indicating a proximal predominance of nerve lesions. While all MRN markers differentiated significantly between ADP and controls, microstructural markers were able to additionally differentiate between subgroups: tibial nerve ρ at thigh level was increased in ALN (p < 0.0001) and in Non-ALN (p = 0.0052) versus controls, and T2app was higher in ALN versus controls (p < 0.0001) and also in ALN versus Non-ALN (p = 0.0214). T2w-signal and CSA were only higher in ALN versus controls. CONCLUSIONS: MRN detects and quantifies peripheral nerve damage in ADP in vivo even in the absence of clinically overt ALN. Microstructural markers (T2app , ρ) are most suitable for differentiating between ADP with and without manifest ALN, and may help to elucidate the underlying pathomechanism in ALN.

Alcoholic Neuropathy: Involvement of Multifaceted Signalling Mechanisms.

BACKGROUND: Alcoholic neuropathy is a chronic disorder caused by the excessive consumption of alcohol. Damage to the nerves results in unusual sensations in the limbs, decreased mobility and loss of some body functions. OBJECTIVE: Alcohol is considered a major cause for exclusively creating the debilitating condition of the neuropathic state. This review critically examines the key mediators involved in the pathogenesis of alcoholic neuropathy and the targets, which, upon selective inhibition, alleviate the progression of alcoholic neuropathy. METHODS: A thorough study of research and review articles available on the internet from PubMed, MEDLINE, and concerned sites was performed on alcoholic neuropathy. RESULT: Impairment in axonal transportation is quite common with the progression of alcoholic neuropathy. Nutritional deficiencies lead to axonal neuropathies that escalate a variety of complications that further worsen the state. PKC and PKA play a significant role in the pathogenesis of alcoholic neuropathy. PKC plays a marked role in modulating NMDA receptor currents, manifesting excitations in neurons. MMPs are involved in the number of pathologies that destroy the CNS and reduction in the level of endogenous antioxidants like α-tocopherol, vitamin E with ethanol, promotes oxidative stress by generating free radicals and lipid peroxidation. CONCLUSION: Oxidative stress is implicated in the activation of MMPs, causing disruption in the blood-brain barrier, the latter are involved in the trafficking and passage of molecules in and out of the cell. Chronic alcohol consumption leads to the downregulation of CNS receptors, consequently precipitating the condition of alcoholic neuropathy.

Mechanical characteristics of BMSCs-intervened sciatic nerve in chronic alcohol-intoxicated animal model.

OBJECTIVE: To study the mechanical properties of sciatic nerve in rats with chronic alcoholism (CA) and intervened with bone marrow mesenchymal stem cells (BMSCs) and to provide biomechanical basis for clinical practice. METHODS: the serum of the BMSCs-intervened CA rats was sampled and determined the contents of malondialdehyde (MDA), metallothionein (CAS, MT), and Glutathione/r -glutamyl cysteinyl/glycine (GSH); meanwhile, the rats' sciatic nerve was tested the tensile and observed the histomorphological changes. RESULTS: The mechanical properties of sciatic nerve in BMSCs-intervened CA rats, as well as the serum levels of MT and GSH, were significantly different from those in the basic fibroblast growth factor (bFGF)-intervened CA rats (p < 0.05). CONCLUSIONS: BMSCs intervention can restore the levels of MT, GSH, MDA, histomorphology, and tensile mechanical properties in CA animal model, and its effects on repairing sciatic nerve are obvious.

Not Always as It Seems: A Case of Ascending Paralysis.

Although generally presenting as a chronic, progressive peripheral neuropathy, we present a case of acute alcoholic neuropathy initially mistaken for acute Guillain-Barré syndrome. Electrodiagnostic evaluation of alcoholic neuropathy reveals an axonal neuropathy and may be complicated by demyelination if comorbid nutritional deficiencies are present. This is in contrast to the significant demyelination classically associated with Guillain-Barré syndrome. F waves, which are absent or prolonged in Guillain-Barré syndrome, are unaffected in alcoholic neuropathy. Further evaluation with lumbar puncture demonstrates normal protein and white blood cell counts in alcoholic neuropathy, as opposed to albuminocytologic dissociation characteristically present in acute Guillain-Barré syndrome.

Alcohol-related peripheral neuropathy: a systematic review and meta-analysis.

The primary aim of this systematic review was to establish the prevalence, character, and risk factors of peripheral neuropathy amongst chronic alcohol abusers and to identify the most appropriate management strategies. In this review, possible pathogenetic mechanisms are also discussed. A systematic, computer-based search was conducted using the PubMed database. Data regarding the above parameters were extracted. 87 articles were included in this review, 29 case-control studies, 52 prospective/retrospective cohort studies and 2 randomised control trials, 1 cross sectional study, and 3 population-based studies. The prevalence of peripheral neuropathy amongst chronic alcohol abusers is 46.3% (CI 35.7- 57.3%) when confirmed via nerve conduction studies. Alcohol-related peripheral neuropathy generally presents as a progressive, predominantly sensory axonal length-dependent neuropathy. The most important risk factor for alcohol-related peripheral neuropathy is the total lifetime dose of ethanol, although other risk factors have been identified including genetic, male gender, and type of alcohol consumed. At present, it is unclear what the pathogenetic mechanisms for the development of neuropathy amongst those who chronically abuse alcohol are, and therefore, it is unknown whether it is attributed to the direct toxic effects of ethanol or another currently unidentified factor. There is presently sparse data to support a particular management strategy in alcohol-related peripheral neuropathy, but the limited data available appears to support the use of vitamin supplementation, particularly of B-vitamin regimens inclusive of thiamine.

Chronic Neurologic Effects of Alcohol.

Chronic alcohol use induces silent changes in the structure and function of the central and peripheral nervous systems that eventually result in irreversible, debilitating repercussions. Once identified, nutritional supplementation and cessation measures are critical in preventing further neurologic damage. The proposed mechanisms of neuronal injury in chronic alcohol abuse include direct toxic effects of alcohol and indirect effects, including those resulting from hepatic dysfunction, nutritional deficiencies, and neuroinflammation. Clinical manifestations include cerebellar ataxia, peripheral neuropathy and Wernicke-Korsakoff encephalopathy. Continued exploration of the pathophysiologic mechanisms may lead to the discovery of early interventions that can prevent permanent neurologic injury.

Wernicke-Korsakoff syndrome complicated by subacute beriberi neuropathy in an alcoholic patient.

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.

Acute nutritional axonal neuropathy.

INTRODUCTION: This study describes clinical, laboratory, and electrodiagnostic features of a severe acute axonal polyneuropathy common to patients with acute nutritional deficiency in the setting of alcoholism, bariatric surgery (BS), or anorexia. METHODS: Retrospective analysis of clinical, electrodiagnostic, and laboratory data of patients with acute axonal neuropathy. RESULTS: Thirteen patients were identified with a severe, painful, sensory or sensorimotor axonal polyneuropathy that developed over 2-12 weeks with sensory ataxia, areflexia, variable muscle weakness, poor nutritional status, and weight loss, often with prolonged vomiting and normal cerebrospinal fluid protein. Vitamin B6 was low in half and thiamine was low in all patients when obtained before supplementation. Patients improved with weight gain and vitamin supplementation, with motor greater than sensory recovery. DISCUSSION: We suggest that acute or subacute axonal neuropathy in patients with weight loss or vomiting associated with alcohol abuse, BS, or dietary deficiency is one syndrome, caused by micronutrient deficiencies. Muscle Nerve 57: 33-39, 2018.

[Thiamine (vitamin B1) treatment in patients with alcohol dependence]. / Le traitement par thiamine (vitamine B1) dans l'alcoolodépendance.

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.

Overview of symptoms, pathogenesis, diagnosis, treatment, and prognosis of various acquired polyneuropathies / 한양의대학술지

Polyneuropathy includes a lot of diseases damaging peripheral nerves. It shows roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. Polyneuropathy is known to usually begin in the hands and feet and progress to the arms and legs. Sometimes it can involve other parts of the body such as the autonomic nervous system. Lots of causes can induce acute or chronic polyneuropathy, so finding the original cause is most important for the treatment of polyneuropathy. There are too many different types of polyneuropathies to be discussed in this review, so we will discuss some of various acquired polyneuropathies such as diabetic neuropathy, vasculitic neuropathy, alcoholic neuropathy, Vitamin B12 deficiency neuropathy, and drug-induced neuropathy, with special focus on symptoms, pathogenesis, diagnosis, treatment, and prognosis.

Chronic alcoholics retain dyspeptic symptoms, pan-enteric dysmotility, and autonomic neuropathy before and after abstinence.

OBJECTIVE: To carry out a comprehensive study on gastrointestinal symptoms, motility and autonomic neuropathy in chronic alcoholics before and one year after abstinence. METHODS: Dyspeptic symptoms (questionnaires), fasting and postprandial gallbladder and gastric motility (ultrasonography), oro-cecal transit time (lactulose H2 -breath test), stool form score (indirect marker of colonic transit), and autonomic neuropathy (sweat spot test, R-R ratio) were assessed at baseline in 268 subjects (136 chronic alcoholics and 132 healthy controls). A subgroup of 39 patients was re-evaluated after 12 months of abstinence. RESULTS: Chronic alcoholics had increased dyspepsia, delayed gastric emptying and oro-cecal transit time but faster gallbladder emptying, with slightly accelerated colonic transit. Sympathetic, but not parasympathetic, autonomic dysfunction was found. Dyspeptic symptoms and functional alterations of gastric emptying and oro-cecal transit tests were still present after 12-month abstinence, whereas gallbladder motility, stool form score and sympathetic function improved. CONCLUSIONS: Chronic alcoholics exhibit combined and interdependent presence of dyspeptic symptoms, impaired motility at different levels of the gastrointestinal tract, with sympathetic dysfunction. Only a few of these abnormalities improve after one year of abstinence from alcohol.

Inflammatory responses to alcohol in the CNS: nuclear receptors as potential therapeutics for alcohol-induced neuropathologies.

Fetal alcohol spectrum disorder (FASD), which results from ethanol exposure during pregnancy, and alcohol use disorder (AUD), which includes both binge and chronic alcohol abuse, are strikingly common and costly at personal and societal levels. These disorders are associated with significant pathology, including that observed in the CNS. It is now appreciated in both humans and animal models that ethanol can induce inflammation in the CNS. Neuroinflammation is hypothesized to contribute to the neuropathologic and behavioral consequences in FASD and AUD. In this review, we: 1) summarize the evidence of alcohol-induced CNS inflammation, 2) outline cellular and molecular mechanisms that may underlie alcohol induction of CNS inflammation, and 3) discuss the potential of nuclear receptor agonists for prevention or treatment of neuropathologies associated with FASD and AUD.

[EXPERIMENTAL MODELS OF ALCOHOLIC NEUROPATHY IN RATS.]

The aim of this work was to study the behavioral and histopathomorphological signs of peripheral neuropathy development in male Wistar rats on the model of alcoholic neuropathy. Chronic consumption of ethanol solution with concentration increasing from 7.47 to 26.2% (w/w) resulted in neuropathy (allodynia) de- velopment after 8 weeks of chronic alcohol administration. The behavioral signs of allodynia became significant on the 8th week and were retained up to the end of experiment (15 weeks of ethanol administration). The reference drug gabapentin effectively reduced the manifestation of allodinia. Histological exami- nation of sciatic nerve preparations from animals killed after ethanol consumption for 5, 10 and 15 weeks revealed the development of histopathomorphological pattern with increasing duration of chronic alcoholization. At the initial stage, the morphological basis of observed behavioral manifestations was provided by excess lipid deposition in peri/epineurium of nerve specimens). The further increase in treatment duration (up to 10 and 15 weeks) was associated with demye- lination and development of inflammation of the sciatic nerve. This experimental model allows one to investigate the efficacy of new neuroprotective and ana- lgesic substances - potential drugs for both prevention and management of neuropathy.

[Neurological diseases and nutrition -- what can we do?]. / Neurológiai kórképek és táplálás -- Mit tehetünk?

Neurological diseases and nutrition are in complex relationship. In the first part of this review the nutritional consequences of acute neurological diseases is presented, with special emphasis on traumatic injuries of the nervous system and stroke. Nutritional therapy of these patients is described in detail. In addition, chronic, degenerative neurological pathological conditions are also discussed, including nutritional consequences and possibilities of therapy. Some ethical and legal issues are also considered. The second part of this review article describes neurological consequences of nutritional problems, both deficits of macro- and micronutrients and toxic effects.

Peripheral systems: neuropathy.

Long-term, excessive consumption of alcoholic beverages produces a peripheral neuropathy with symptoms of decreased superficial sensation, hyperalgesia, and weakness. Alcoholic neuropathy is characterized by axonal degeneration with reduced density of both small and large fibers and axonal sprouting. Electrophysiologic studies reveal a marked reduction in the amplitude of sensory potentials and moderate slowing of nerve conduction, mainly in the lower extremities. Dietary deficiency of vitamins, which are often associated with chronic alcoholism, can contribute to the pathogenesis. Recent studies using animal models have identified several mechanisms by which ethanol impacts peripheral nerve function. Ethanol can exert direct neurotoxic effects on peripheral nerves via its metabolite acetaldehyde and by enhancing oxidative stress. Ethanol activation of protein kinase Cε signaling in primary afferent nociceptors plays an important role in lowering nociceptive threshold. Further, ethanol causes cytoskeletal dysfunction and inhibits both anterograde and retrograde axonal transport. Alcoholic neuropathy is potentially reversible and treatments include abstinence from alcoholic beverages and consumption of a nutritionally balanced diet supplemented with B vitamins. However, response to these treatment strategies can be variable, which underscores the need for novel therapeutic strategies. In this review, we provide an overview of the clinical findings and insights on molecular mechanisms from animal models.