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.

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.

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.

Small-fiber degeneration in alcohol-related peripheral neuropathy.

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.

[Peripheral neuropathies, from diagnosis to treatment, review of the literature and lessons from the local experience]. / Les neuropathies périphériques, du diagnostic au traitement, revue de la littérature et enseignements de l'expérience locale.

Peripheral neuropathy implies damages to neurons belonging to the peripheral nervous system which includes cranial nerves, spinal nerves' roots, spinal ganglia, nerve trunks and their divisions, and, the autonomic nervous system. Peripheral neuropathies are frequent in the general population (prevalence: 2,4%). We present a review of the recent literature and highlight diagnostic approaches for certain types of neuropathies particularly the most frequent ones or those requiring peculiar attention in first-line medicine. We also present epidemiologic data and data related to sural nerve biopsies from our centre. The determination of the location and the topography of the affected sites, integrated into the global context of the patient, is essential to provide an etiologic diagnosis. The median nerve compression within the carpal tunnel and polyneuropathies are the most frequent forms of peripheral neuropathies. More than one hundred causes of polyneuropathies are described and they are divided into acquired, genetically determined and idiopathic. We highlight a largely adopted diagnostic strategy concerning polyneuropathies and describe the Guillain-Barre syndrome, the alcohol-related polyneuropathy and the controversies about the benefit of the B vitamin therapy and its dangers. At the Hôpital Erasme, since 2008, more than 1372 patients with peripheral neuropathy were identified. Results of sural nerve biopsies performed in seventeen of them do not largely differ from those of other centres of expertise. We conclude that the diagnosis of peripheral neuropathy usually requires the expertise of a neurologist, but, first line caregivers must be able to recognize and refer patient when needed.

[Peripheral nerve disorders as common diseases].

Peripheral neuropathy occurs as a component of several common and rare diseases. It is heterogeneous in cause, diverse in pathology, and varied in severity. The term peripheral neuropathy includes symmetric polyneuropathy, single and multiple mononeuropathy, and radiculopathy. The major disorders include diabetic neuropathy, alcoholic neuropathy, and carpal tunnel syndrome. The incidence of cancer chemotherapy-induced neuropathy has been increasing substantially. Although the estimated prevalence of all different peripheral neuropathies is considerably high, possibly affecting 10% of the entire population, there is no existing systematic epidemiological study on all the aspects of peripheral nerve disorders. Neurologists should contribute to both fundamental and symptomatic treatments of patients seen in other sections. The important symptomatic therapies include treatments for neuropathic pain and autonomic dysfunction. There is increasing role for neurologists in treating HIV-related and anti-HIV drug-induced neuropathy. More active collaboration with neurologists, oncologists, and general physicians is necessary to improve the quality of life in patients with peripheral nerve disorders.

[Nemaline rod myopathy revealed by acute respiratory failure after an outpatient cataract surgery]. / Révélation d'une myopathie à bâtonnets de l'adulte par une insuffisance respiratoire aiguë après chirurgie ambulatoire de la cataracte.

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.

The significance of folate deficiency in alcoholic and nutritional neuropathies: analysis of a case.

OBJECTIVE: To elucidate the significance of folate deficiency in alcoholic and nutritional neuropathies. METHODS: We preformed a comprehensive clinical screening of a patient with chronic alcoholism who manifested neuropathy, macrocytic anemia, liver dysfunction, and folate deficiency. RESULTS: A 33-y-old woman with chronic alcoholism presented with acutely progressive glove- and stocking-type sensorimotor polyneuropathy. Although an episode of neuropathy preceded the current episode by 2 y, its cause was never determined. The findings of nerve conduction studies were indicative of axonal neuropathy. Laboratory findings revealed macrocytic anemia and liver dysfunction. Her serum level of folate was reduced, whereas thiamine, riboflavin, and cobalamin levels were within normal range. The neuropathy and anemia showed gradual recovery after the initiation of folic acid supplementation. CONCLUSIONS: This case study indicates that folate deficiency should be monitored closely in patients with chronic alcoholism and associated malnutrition. Additionally, folate deficiency should be considered as a differential diagnosis of neuropathy.

Cambio de paradigma en el tratamiento del alcoholismo de baja gravedad / A change of paradigm in the tretment of low-severity alcoholdependent patients

Introducción: Los avances en farmacoterapia del alcoholismo podrían propiciar un cambio de paradigma, basado en los nuevos programas de reducción del consumode alcohol. Material y Método: Este estudio revisa los fundamentos neurobiológicos y farmacoterapéuticos del alcoholismo, centrándose en los antagonistas opioides, el tratamiento orientado a la abstinencia y el orientado hacia la reducción del consumo de alcohol. Resultados: 1. Los programas de tratamiento de la dependencia del alcohol presentan sólo una eficacia pequeña o moderada.2. Los pacientes presentan una elevada motivación para reducir el consumo de alcohol pero una baja motivación para abandonar de manera continuada al consumo de alcohol.3. El programa de reducción continuada del consumo de alcohol, asociado a un tratamiento intermitente con naltrexona, puede ser de utilidad en los pacientes con una baja gravedad de la dependencia del alcohol. Discusión: Aunque los pacientes que presentan una grave dependencia del alcohol deberían ser tratados en programas orientados hacia la abstención continuada, los que presentan una baja gravedad pueden beneficiarse de los programas de reducción del consumo de alcohol, los cuales pueden conseguir a corto plazo una reducción el número de consumiciones por día de consumo y, a largo plazo, incluso una progresiva reducción de la “obsesión” por beber, la conducta de búsqueda de alcohol y los trastornos médicos, conductuales y sociales, causados por el consumo excesivo de alcohol. Para poder llevar a cabo este cambio de paradigma en el tratamiento del alcoholismo, se requieren futuros ensayos clínicos controlados para evaluar su eficacia y su tolerabilidad (AU)

Introduction: Recent pharmacotherapy findings from new alcohol reduction programmes could change the paradigm of alcohol-dependence treatment. Material and Method: This study reviews the neurobiological background and pharmacotherapy of alcohol-dependence disorder, focusing on opioid receptor antagonists, abstinence-oriented treatment and moderation-oriented treatment. Results: 1. Alcohol-dependence treatment programs show only low to moderate efficacy. 2. Patients usually show low motivation to sustain abstinence but high motivation to reduce alcohol use.3. A treatment program based on continued reduction of drinking and associated with intermittent treatment with naltrexone can be useful for low-severity alcohol-dependent patients. Discussion: Although high severity alcohol-dependent patients should stop drinking alcohol, low severity patients may have the option of reducing their alcohol consumption if they take an opioid antagonist medication everyday that they decide to drink alcohol. In the short term, the continuing drinking-reduction programmes may reduce the number of drinks per drinking day and in the long term, they may progressively decrease the obsession for drinking, alcohol seeking behavior, and related medical, behavioral and social disorders. To change the paradigm in the treatment of alcohol–dependence disorder there is a need for further randomized controlled trials in order to assess their efficacy and tolerability (AU)

Dry beriberi mimicking the Guillain-Barre syndrome.

A 44-year-old man is described with severe flaccid quadriparesis that evolved over 3 weeks. He had regularly binged on alcohol-up to 20 cans of beer per day with occasional consumption of spirits-for more than 15 years but had balanced this with regular food intake. However, for a week prior to the current episode he had not eaten anything of significance. Nerve conduction studies revealed a background peripheral, mainly sensory, neuropathy with a superimposed acute motor axonopathy. CSF was normal. He improved with high dose vitamin replacement and physiotherapy but remains dependent on a Zimmer frame for mobility and a splint for wrist drop.

Strength-duration properties of sensory and motor axons in alcoholic polyneuropathy.

OBJECTIVE: The strength-duration time constant (SDTC) is a measure of axonal excitability and depends on the biophysical properties of the axonal membrane. The strength-duration time constant can provide information about Na+ channel function. We aimed to examine changes in the SDTCs of motor and sensory fibers in the median nerves in patients with alcoholic polyneuropathy. METHODS AND RESULTS: We measured the SDTCs of motor and sensory fibers in 17 patients with alcoholic polyneuropathy (15 men and two women) after stimulating the right median nerve at the wrist. The results were compared with ten healthy age-matched subjects (six men and four women). In patients, the SDTC and rheobase for the motor fibers were 370.8+/-97.4 micros and 3.9+/-1.7 mA; for the sensory fibers, the SDTC and rheobase were 464.7+/-104.3 micros and 3.3+/-1.9 mA. In controls, the SDTC and rheobase for the motor fibers were 359.3+/-103.5 micros and 3.5+/-1.9 mA; for the sensory fibers, the SDTC and rheobase were 478.9+/-113.9 micros and 2.1+/-1.5 mA. Sensory fibers had significantly longer SDTCs and lower rheobase than motor fibers in patients and controls. However, when the values of the patients and controls were compared, a statistically significant difference was only found for the rheobase of sensory fibers (p=0.037). CONCLUSIONS: Although alcoholic neuropathy corresponds to the pattern of axonopathy, it did not act on the SDTC of the median nerve, which depends on the biophysical properties of the axonal membrane at the node of Ranvier. The process causing axonal degeneration in alcoholic neuropathy may affect internodal channels other than nodal channels or the Na+ -K+ ATP pump.

A 74-year-old man with memory loss and neuropathy who enjoys alcoholic beverages.

Adverse effects of alcohol on the peripheral and central nervous system can be direct (ie, neurotoxicity) or indirect (eg, nutritional deficiency). Using the case of Mr E, an older, moderate to heavy drinker experiencing memory difficulty, the diagnostic considerations, which include mild cognitive impairment, early Alzheimer dementia, Wernicke-Korsakoff syndrome, and "alcoholic dementia," are discussed. These disorders are not mutually exclusive, and in a patient with either mild cognitive impairment or dementia, the contributory role of alcohol can be difficult to determine. In fact, epidemiological studies suggest that mild to moderate intake of alcohol actually reduces the risk of developing mild cognitive impairment or dementia, including Alzheimer dementia. Appropriate management includes measures to reduce alcohol dependence (eg, behavioral or pharmacological therapy) and to delay progression of the cognitive impairment (eg, engaging in healthy behaviors such as cognitive leisure activities).

Illicit alcohol consumption and neuropathy--a preliminary study in Sri Lanka.

AIMS: To compare the effects on peripheral and autonomic nerve functions of Sri Lankan illicitly distilled alcohol consumption versus legal spirit consumption. METHODS: Peripheral nerve conduction and autonomic nerve functions were assessed in 40 healthy control subjects and two groups of chronic heavy drinkers: 41 illicit spirit drinkers and 17 legal spirit drinkers. RESULTS: Lower-limb motor and sensory nerve conduction parameters were affected in both groups of alcoholics. When compared with controls, in illicit spirit drinkers the mean heart rate indexes of all parasympathetic tests were lower while in legal spirit drinkers the heart rate response to standing was affected. There were no differences in the results of the above tests when the two groups of heavy drinkers were compared. CONCLUSIONS: Though chronic alcoholism results in peripheral and autonomic nerve damage, the damage caused by consumption of illicitly distilled spirit is not worse than the damage caused by consumption of legal spirits.

[Metabolic neuropathies]. / Neuropathies métaboliques et carentielles.

Due to the high prevalence of diabetic neuropathies, metabolic neuropathies are common. "Diabetic neuropathy" is a slowly progressive painful sensory neuropathy evolving with a length dependent pattern. Slight distal weakness of toes extensor can be observed. Trophic changes and autonomic neuropathy can lead to severe complications (diabetic foot ulceration or symptomatic postural hypotension). Multifocal neuropathies can also be encountered with diabetes. With such neuropathic pattern, other causes of neuropathy should be excluded and patients should be referred to specialised centres. Other metabolic neuropathies can occur, especially alcoholic neuropathies and uremic neuropathies. Laboratory tests are an important part in the diagnostic procedure to look for a metabolic cause.

Treatment of alcoholic polyneuropathy with vitamin B complex: a randomised controlled trial.

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 man with the combination of dry and wet beriberi]. / Een man met de combinatie van droge en natte beriberi.

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.

Multiple lipomas, alcoholism, and neuropathy: Madelung's disease or MERRF?

We report a 51-year-old alcoholic man with a 10-year history of cervical lipomas and progressive symmetrical sensory neuropathy, initially diagnosed with Madelung's disease, an idiopathic syndrome often attributed to chronic alcoholism. The eventual development of proximal weakness led to pathological and genetic testing which identified a A8344G mutation in the mitochondrial tRNA lysine gene, associated with MERRF (myoclonic epilepsy with ragged-red fibers). This case demonstrates how the varied terminology for this syndrome has resulted in a lack of consistent recognition and assessment for mitochondrial cytopathy.

Alcohol y sistema nervioso central / Alcohol and central nervous system

El alcohol tiene una alta afinidad por el sistema nervioso, lo que explica las alteraciones en la conducta que provoca su consumo. Esta afinidad es debida a las características de su molécula: 1)se distribuye rápida y homogéneamente por el organismo, atravesando todas las barreras, incluida la hematoencefálica 2) su alta liposolubilidad provoca que interaccione con el componente lipídico de la membrana neuronal, provocando a corto plazo cambios en la conductancia neuronal y a más largo plazo cambios en su estructura. Las alteraciones de conducta que podemos encontrar en las personas que hacen un consumo abusivo están relacionadas con 1)el efecto agudo que tiene el aumento de alcohol en sangre sobre la membrana neuronal y sobre la sinapsis, ya que provoca alteraciones transitorias sobre el potencial de membrana y sobre la neurotrasmisión, 2) el efecto a más largo plazo, causado por los procesos de neuroadaptación a nivel de la transmisión sináptica , 3) las alteraciones más o menos irreversibles inducidas por el daño estructural a nivel sináptico, 4) otras condiciones relacionadas con el consumo abusivo de alcohol, aunque no causadas directamente por este, como son los estados carenciales o la patología frecuentemente asociada al consumo. En la clínica encontramos trastornos que obedecen al efecto agudo del etanol sobre el cerebro, como son los distintos cuadros relacionados con el estado de intoxicación, o trastornos que son consecuencia del desarrollo de tolerancia, fundamentalmente las diversas manifestaciones del síndrome de abstinencia y por último enfermedades de curso más crónico debidas a daños cerebral más o menos estructural, que presentan distintos grados de reversibilidad y que en general obedecen a una etiología multicausal, como son la encefalopatía de Wernicke-Korsakoff, las neuropatías o los distintos tipos de demencias asociadas al alcoholismo

Alcohol shows a high affinity by nervous system, and that explains the behaviour-altering effects of drinking. Te nervous system affinity of alcohol is due to biochemical and metabolic characteristics of this substance: 1) Alcohol is rapidly and homogeneously distributed by body tissues and fluids, penetrating through body barriers, including the hematoencephalic one. 2) Because of its great liposolubility, it interacts with lipoid component in neuronal membrane causing long-term changes in neuronal conductance, and long-term structural changes. Behaviour disturbances in alcohol-abusing persons are related with: 1) Alcohol acute effects on neuronal membrane and synapses consisting in transitional disturbances on membrane potential and neurotransmission function. 2) Alcohol longterm effect causing by brain adjustment in synaptic transmission. 3) The relative irreversible disturbances induced by structural synaptic damage. 4) Other conditions related with alcohol abuse but not directly causing by it, such as nutritional deficiencies, and pathologic conditions seen in chronic alcoholism. In clinical practice we usually find disorders due to acute effects of ethanol on brain like different disorders related with alcohol intoxication; disorders due to tolerance development, such as withdrawal syndrome; and those chronic ad multicausal conditions with different degree of reversibility which are consequences of structural brain damage, like Wernicke-Korsakoff encephalopathy, alcoholic neuropthaty, and alcohol induced dementia