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1 Gastroenterol Hepatol. 2017;xxx(xx):xxx---xxx
2

Gastroenterología y Hepatología
www.elsevier.es/gastroenterologia

REVIEW

3 Neurological manifestations of excessive alcohol

4 consumption夽
5 Q1 Anna Planas-Ballvé a,∗ , Laia Grau-López a , Rosa María Morillas b , Ramón Planas b

a
6 Unidad de Neurociencias, Servicio de Neurología, Hospital Germans Trias i Pujol, Badalona (Barcelona), Spain
b
7 Unidad de Hepatología, CIBERehd, Servicio de Aparato Digestivo, Hospital Germans Trias i Pujol, Badalona (Barcelona), Spain

8 Received 5 March 2017; accepted 19 May 2017

9 KEYWORDS Abstract This article reviews the different acute and chronic neurological manifestations of
10 Excessive alcohol excessive alcohol consumption that affect the central or peripheral nervous system. Several
11 consumption; mechanisms can be implicated depending on the disorder, ranging from nutritional factors,
12 Neurological alcohol-related toxicity, metabolic changes and immune-mediated mechanisms. Recognition
13 complications; and early treatment of these manifestations is essential given their association with high
14 Hepatic morbidity and significantly increased mortality.
15 encephalopathy © 2017 Elsevier España, S.L.U. All rights reserved.

16 PALABRAS CLAVE Manifestaciones neurológicas del alcoholismo

Alcoholismo;
17
Complicaciones Resumen En este artículo se revisan las distintas manifestaciones neurológicas del consumo
18
neurológicas; excesivo de alcohol, que pueden ser agudas o crónicas y afectar al sistema nervioso central o
19
Encefalopatía periférico. El mecanismo por el cual se producen varía de un grupo de trastornos a otro. Destacan
20
hepática factores nutricionales, efectos tóxicos del alcohol, factores metabólicos e incluso inmunológi-
21 cos. Estas manifestaciones pueden conllevar una gran morbilidad y un aumento significativo de
22 la mortalidad, por lo que es importante reconocerlas y tratarlas precozmente.
23 © 2017 Elsevier España, S.L.U. Todos los derechos reservados.

夽
Please cite this article as: Planas-Ballvé A, Grau-López L, Morillas RM, Planas R. Manifestaciones neurológicas del alcoholismo. Gastroen-
terol Hepatol. 2017. https://doi.org/10.1016/j.gastrohep.2017.05.011
∗ Corresponding author.

E-mail address: annaplanasb@gmail.com (A. Planas-Ballvé).

2444-3824/© 2017 Elsevier España, S.L.U. All rights reserved.

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24 Introduction inhibition of certain subcortical structures (perhaps the mid- 59

brain reticular formation) that modulate the activity of the 60

25 Excessive or harmful alcohol consumption is defined as cerebral cortex.3 However, as more alcohol is consumed, 61

26 the consumption of 40---60 g/day of alcohol in women or this inhibitory action extends to cortical and other brain 62

27 60---100 g/day in men. Although it does not meet the criteria stem and spinal neurons, and can cause decreased alertness 63

28 for alcohol dependency, this level of consumption can pro- and coma with respiratory failure. Some susceptible indi- 64

29 duce clinical changes. Alcohol use disorder appears when viduals may experience amnesic lacunae and seizures after 65

30 excessive alcohol consumption causes the deterioration of relatively mild alcohol intoxication.4 66

31 an individual’s social, work and family relationships.1 The severity of symptoms of acute alcohol intoxication 67

32 The World Health Organization’s report on excessive alco- are related to blood alcohol levels5 (Table 2). These levels 68

33 hol consumption identified more than 60 alcohol-related should be taken merely as a guide, and will vary between 69

34 diseases.2 The systemic effects of alcohol include changes in individuals according to sex, habitual consumption, and 70

35 the digestive tract and the liver, the heart and vascular sys- genetic and metabolic factors. 71

36 tem, the skeletal and muscular systems, nutritional status, Acute alcohol intoxication should be treated with sup- 72

37 the immune, endocrine and haematological systems, and in portive measures and monitoring of the individual’s level 73

38 the central and peripheral nervous systems. of consciousness. Alcoholic coma, with its associated res- 74

39 Several alcohol-related neurological complications have piratory depression, is a medical emergency that requires 75

40 been described (Table 1), and pathogenesis varies greatly appropriate life support measures. 76

41 among the different disorder groups, although one of the

42 most frequent causes is nutritional deficiency. Alcohol can Alcohol withdrawal syndrome 77
43 produce alcoholic liver disease that can be accompanied Alcohol withdrawal syndrome, or abstinence syndrome, is 78
44 by a wide variety of neurological manifestations, including the clinical manifestation of abruptly terminating or sub- 79
45 hepatic encephalopathy (HE). stantially reducing intake in patients who have developed 80
46 In this article, we will examine the different neurological tolerance and dependence. Alcohol acts basically through 81
47 manifestations of excessive alcohol consumption, the neu- 2 specific neuronal receptors. On the one hand, it regu- 82
48 rological alterations most frequently found in alcoholic liver lates the neurotransmitter gamma-aminobutyric acid type A 83
49 disease --- such as HE --- and the best diagnostic approach in receptor that inhibits neuronal excitability, which explains 84
50 clinical practice. its sedative and hypnotic effects. On the other hand, 85

alcohol increases glutamate N-methyl-d-aspartate recep- 86

51 Central nervous system involvement tor expression, which in turn increases glutamate activity 87

and causes hyperexcitation. Chronic alcohol consump- 88

52 Acute complications tion induces neuroadaptive changes (tolerance), increases 89

glutamate N-methyl-d-aspartate receptor expression, and 90

53 Acute intoxication desensitises the response and the expression of gamma- 91

54 The symptoms of alcohol intoxication are the result of aminobutyric receptors.6 92

55 the inhibitory effect of alcohol on the nerve cells of the The manifestations of withdrawal syndrome (a wide 93

56 brain and spinal cord. Some of the immediate effects of range of severe symptoms, ranging from distal hand tremor, 94

57 acute alcohol ingestion --- such as loquacity, loss of social anxiety, insomnia and visual hallucinations to psychomo- 95

58 inhibition, and aggressiveness --- appear to be due to the tor agitation, autonomic hyperactivity, seizures or coma)

Table 1 Neurological manifestations secondary to exces-

sive alcohol consumption.
Central nervous system Peripheral nervous system Table 2 Manifestations of acute alcohol intoxication.

Acute Blood alcohol, in mg/dl Effects

Acute intoxication Acute alcoholic neuropathy <50 Difficulty in performing tasks
Withdrawal syndrome and Alcohol-related compressive that require skill, euphoria,
delirium tremens neuropathy loquacity
Wernicke’s >100 Loss of self-control, loss of
encephalopathy coordination, mental slowness,
Chronic mild dysarthria, ataxia, altered
Korsakoff syndrome Chronic alcoholic perception
neuropathy >200 Amnesia, confusion, diplopia,
Alcohol-related dementia Disulfiram neuropathy dysarthria, hypothermia,
Marchiafava---Bignami nausea, vomiting
disease >400 Stupor, respiratory depression,
Cerebellar degeneration coma

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Neurological manifestations of excessive alcohol consumption 3

96 appear to be mediated by an increase in excitatory neuro- the liver.11 Other clinical situations that lead to thiamine 154
97 transmitters at the expense of inhibitory neurotransmitters. deficiency should also be borne in mind. These generally 155
98 Symptoms typically onset 6---24 h after interruption or involve poor intestinal absorption (gastrointestinal surgery, 156
99 reduction of alcohol consumption. The most serious form, hyperemesis gravidarum) or an increase in body requirement 157
100 which usually appears 72 h after withdrawal, is delirium (systemic diseases).12 158
101 tremens, characterised by disorientation, agitation and From the clinical point of view, WE is characterised 159
102 visual hallucinations, accompanied by autonomic signs such by the classic triad of oculomotor disturbance, ataxia and 160
103 as hyperventilation, tachycardia and diaphoresis. It can confusion, although the complete triad occurs only in 16% 161
104 also be accompanied by metabolic and electrolyte alter- of patients.13 Ocular alterations are complex, and consist 162
105 ations, such as hypomagnesaemia. The mortality rate is mainly of a combination of alterations such as, for exam- 163
106 5---15%, mainly due to metabolic, cardiovascular and infec- ple, horizontal or vertical nystagmus, unilateral or bilateral 164
107 tious complications.7 oculomotor paresis, or conjugate gaze palsy. Ataxia mainly 165
108 According to the European Association for the Study affects the trunk by altering gait and balance; limb ataxia 166
109 of the Liver, the treatment of choice in patients with and dysarthria are less common. Confusion or encephalo- 167
110 acute withdrawal syndrome and alcoholic liver disease is pathic symptoms, meanwhile, develop within days or weeks 168
111 benzodiazepines,8 since they reduce the risk of epileptic and are characterised by profound disorientation, inability 169
112 seizures. Long-acting benzodiazepines, such as diazepam, to concentrate, apathy, indifference, inattention, drowsi- 170
113 are used, and the dose should be tapered over time. How- ness and coma. Other signs and symptoms are hypothermia 171
114 ever, in elderly patients, in patients with hepatic failure, resulting from posterior hypothalamic involvement, tachy- 172
115 or when excessive sedation must be avoided, the lowest cardia or postural hypotension due to autonomic nervous 173
116 possible dose of short- or intermediate-acting benzodi- system dysfunction, or polyneuropathy due to multiple vita- 174
117 azepines, such as lorazepam, is recommended. In the case min deficiency.12 175
118 of hallucinations and agitation that do not respond to ben- Diagnosis is mainly clinical. Some additional tests can 176
119 zodiazepines, haloperidol may be added, although it should help confirm or rule out other suspicions, but should never 177
120 only be used in combination with benzodiazepines, because delay the start of treatment. A thiamine blood test will show 178
121 administration of antipsychotics alone may increase the risk thiamine serum levels and transketolase enzyme activity in 179
122 of seizures. Other drugs, such as alpha-2 agonists (cloni- peripheral blood. This test, however, usually takes time and 180
123 dine and dexmedetomidine) and beta-blockers, can be used is of little practical use since normal ranges do not rule out 181
124 as adjuvant treatments to control autonomic hyperactivity. a diagnosis of WE. As far as brain imaging tests are con- 182
125 Studies in other drugs, such as carbamazepine, gabapentin cerned, the most useful complementary test for confirming 183
126 and topiramate, have so far yielded promising results.9 diagnosis is magnetic resonance imaging (MRI). The most dis- 184

tinctive lesion is reversible cytotoxic oedema, visualised in 185

127 Wernicke’s encephalopathy T2, FLAIR and DWI sequences in the periventricular region 186

128 Wernicke’s encephalopathy (WE) and Korsakoff syndrome, and diencephalon (Fig. 1). Furthermore, mammalian body 187

129 which were originally described as separate entities, are atrophy, which is usually present in patients with chronic 188

130 now considered the acute and chronic stages, respectively, lesions, can start to be detected within the first week after 189

131 of Wernicke---Korsakoff syndrome. The real prevalence of WE onset of the disease.14 190

132 cannot be accurately estimated, although different studies WE is a medical emergency because it is potentially 191

133 have observed typical WE lesions in 0.2---2.8% of the autop- reversible and delayed treatment or no treatment at all can 192

134 sies performed in the general population compared with a cause serious sequelae and even death. 193

135 prevalence of 12.5% in autopsies performed on alcoholics.10 Treatment consists of urgent thiamine replacement. Thi- 194

136 WE is caused by a vitamin B1 (thiamine) deficiency, which amine therapy has been evaluated in a single randomised 195

137 plays a key role in carbohydrate metabolism as an essen- double-blind study in 107 patients, in which the efficacy of 196

138 tial coenzyme in the Krebs cycle and the pentose phosphate different intramuscular doses (5, 20, 50, 100 and 200 mg) of 197

139 pathway (transketolase, ␣-ketoglutarate dehydrogenase, thiamine daily for 2 days was compared. Response, defined 198

140 pyruvate dehydrogenase, etc.). Since these enzymes reg- as improved neuropsychological test score, was evaluated 199

141 ulate energy metabolism in the brain, thiamine deficiency on the third day after treatment. The authors concluded 200

142 can cause brain damage, mainly in regions with greater that the 200 mg dose was superior to the other dosages.15 201

143 metabolic demand, such as the paraventricular region of Although there is no clear consensus on the ideal thiamine 202

144 the thalamus and hypothalamus, the mammillary bodies, dose, pharmacokinetic studies have shown the half-life of 203

145 the periaqueductal grey, the floor of the fourth ventricle, thiamine to be around 96 min, so 2 or 3 daily doses are con- 204

146 and the cerebellar vermis. Thiamine is found in both animal sidered appropriate.16 Given the higher incidence of adverse 205

147 and plant foods. It is absorbed by the duodenum, and bodily effects in intramuscular administration (high volume and 206

148 reserves can be depleted in 2---3 weeks. painful administration), intravenous infusion of thiamine 207

149 In developed countries, more than 80% of cases of WE diluted in 100 ml of physiological saline or 5% dextrose over 208

150 occur in the context of malnutrition associated with alco- 30 min is recommended. According to evidence from pub- 209

151 hol consumption. However, studies have shown that WE in lished series and the recommendations of the European 210

152 alcoholics can involve mechanisms other than malnutrition, Federation of Neurological Societies, the administration of 211

153 such as impaired gastrointestinal absorption of thiamine and between 100 and 200 mg of intravenous thiamine is con- 212

a reduced capacity to store and metabolise the vitamin in sidered adequate in non-alcoholic patients, while alcoholic

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Figure 1 Brain magnetic resonance image from a patient with Wernicke’s encephalopathy. Bilateral thalamic hyperintensities
around the third ventricle are seen on fluid attenuation inversion recovery (FLAIR) weighted axial (A) and coronal (B) images. (C)
T1-weighted axial image showing no lesions. (D) Diffusion-weighted (DWI) axial image showing hyperintensity in bilateral symmetric
thalami.

213 patients require doses of up to 500 mg 3 times daily.10 the aftermath of WE, although it can sometimes appear in 223

214 Other recommendations are a speedy return to a normal patients with no history of WE, or with sub-acute, undi- 224

215 diet and continuous treatment until clinical improvement agnosed episodes. However, it can also be a symptom of 225

216 is observed. According to the literature, when untreated or malnutrition due to other causes or a symptom of dis- 226

217 insufficiently treated, WE-induced brain damage can lead to eases involving ischaemic, neoplastic or other injury to the 227

218 death in 20% of cases or to the chronic form of WE (Korsakoff medial and inferomedial thalamic regions in the temporal 228

219 syndrome) in 80% of cases.17 lobes.18 229

From a clinical point of view, it is characterised by 230

220 Chronic complications memory impairment that is out of proportion to other 231

cognitive functions in an awake, attentive and respon- 232

221 Korsakoff syndrome sive patient. Important manifestations are learning deficits 233

222 Korsakoff syndrome, which is mainly caused by malnutri- and memory loss, affecting both anterograde and retro- 234

tion associated with chronic alcoholism, usually emerges in grade events. Recent memory is usually more affected than

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235 remote memory, and the creation of false memories, or chronic alcohol consumption on the brain. Studies have 292

236 confabulation, in speech that can even be induced by ques- shown that consumption of 140 g or more of alcohol per 293

237 tions about the patient’s recent activities is characteristic day for a prolonged period of time can produce moderate 294

238 of this syndrome. Other cognitive functions, such as concen- cognitive alterations.26 295

239 tration, spatial organisation, visual or verbal abstraction, However, alcohol-related dementia has never been accu- 296

240 may also be affected, and patients are usually apathetic rately defined from a clinical or pathological perspective, 297

241 and lacking in initiative, spontaneity and self-criticism.19 and the diagnosis of this entity has sparked considerable 298

242 Korsakoff syndrome is often thought to be untreatable; controversy in recent years. Furthermore, the interaction 299

243 however, after thiamine administration, only 25% show no between nutritional deficiencies, consumption of other sub- 300

244 recovery, 25% experience discrete improvement, 25% sig- stances, psychiatric comorbidity and repeated head injuries 301

245 nificant improvement, and in 25% memory is completely in chronic alcoholic patients raise doubts about the exis- 302

246 recovered.20 tence of alcohol-related dementia per se. Some authors, 303

therefore, prefer to use the term ‘‘alcohol-related brain 304

247 Marchiafava---Bignami disease damage’’ to describe both the aetiology and symptoms of 305

248 Marchiafava---Bignami disease was first described in 1903 in the widely differing alcohol-related cognitive disorders pre- 306

249 Italian alcoholic wine drinkers, and since then it has been sented in these patients. 307

250 observed in other nationalities in association with abuse of Neuronal damage or depletion, from a physiopatholog- 308

251 any alcoholic beverage. It affects chronic alcoholics almost ical perspective, is believed to be related to glutamate 309

252 exclusively, although cases have occasionally been described neurotoxicity, oxidative stress and diminished neurogenesis, 310

253 in non-alcoholics with malnutrition.21 It is a rare entity that triggered by chronic alcohol abuse.27 311

254 is characterised by progressive demyelination and necrosis Post-mortem anatomopathological studies of patients 312

255 of the central part of the corpus callosum. On brain imaging diagnosed with alcohol-related dementia often show non- 313

256 studies, it manifests as a well defined area of demyelination specific findings, such as predominantly frontal cerebral 314

257 in the body of the corpus callosum, which can then extend atrophy, typical Wernicke---Korsakoff syndrome lesions, 315

258 to various regions of the subcortical white matter. communicating hydrocephalus, Alzheimer’s disease, or trau- 316

259 The aetiology is unknown and widely debated, with some matic injuries of variable severity.28 317

260 experts suggesting the existence of a toxic factor, not yet From a clinical point of view, it is characterised by 318

261 identified, which is present in some alcoholic beverages as an insidious onset with stepwise progression of symptoms 319

262 the culprit. However, given the low prevalence of this entity that overlap with other neurodegenerative dementias. In 320

263 in alcoholics, and the fact that it has also been described in the early stages, neuropsychological studies usually reveal 321

264 some non-alcoholics, it probably has an unidentified nutri- frontal-subcortical cognitive impairment, with slowing of 322

265 tional, metabolic or enzymatic aetiology.22 mental processes, attention deficit, changes in immedi- 323

266 The clinical characteristics of this disease vary, and ate or short-term memory, decline in visual spatial skills, 324

267 there is no well-defined clinical syndrome. Most patients and decline in executive functions, such as planning and 325

268 present progressive dementia, usually subacute at onset, organisation.29 326

269 with predominance of apractic or aphasic disorders, opposi-

270 tional hypertonia, dysarthria, frontal release reflexes and,
271 sometimes, hemiparesis or signs of interhemispheric dis- Alcohol-related cerebellar degeneration 327

272 connection. Some patients also present decreased alertness Alcohol-related cerebellar degeneration is a common 328

273 and seizures. The clinical course is variable; some patients complication that affects up to 25% of alcoholics, and is 329

274 will become comatose and die, others can survive several one of the most frequent causes of acquired ataxia in 330

275 years with dementia, while in others partial recovery is adults.30 331

276 possible.23 The pathogenesis of this entity is complex and not 332

277 The diagnosis is difficult because of the wide spectrum entirely clear, although a synergistic mechanism involving 333

278 of symptoms. Diagnosis was hitherto based on post-mortem both the toxic effect of alcohol and the consequences of 334

279 studies, but today a history of alcoholism together with clin- vitamin B1 deficiency may be involved. Recent studies have 335

280 ical manifestation and, above all, brain imaging studies, shown the presence of anti-tissue transglutaminase 2 anti- 336

281 specifically MRI, are essential to confirm diagnosis. Typical bodies in chronic alcoholics, which raises the possibility 337

282 lesions seen on MRI are demyelination, swelling and necrosis of alcohol-induced hypersensitivity to gluten.31 According 338

283 of the corpus callosum, with varying degrees of subcortical to the hypothesis put forward by some authors to explain 339

284 white matter involvement.24 this phenomenon, increased gut permeability caused by 340

285 Given its uncertain aetiology, there is no specific treat- alcohol-induced intestinal mucosa lesions found in alcoholic 341

286 ment for Marchiafava---Bignami disease, although abstinence patients could increase exposure of the immune system 342

287 and vitamin supplements are recommended. Good response to pathogenic antigens (including gliadin peptides). Then, 343

288 to high doses of corticosteroids has also been reported in blood---brain barrier impairment induced by chronic alcohol 344

289 some studies.25 consumption would, by as yet unknown mechanisms, allow 345

the passage of these antibodies to the brain, thus causing 346

290 Alcohol-related dementia cerebellar degeneration similar to gluten-induced cerebel- 347

291 The term alcohol-related dementia is used to describe lar ataxia.32 In fact, one study has shown a higher prevalence 348

a form of dementia attributable to the direct effects of of anti-gliadin antibodies in patients with alcohol-induced

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349 cerebellar degeneration compared to the general population Chronic alcoholic polyneuropathy 379

350 (44% vs. 12%).33

351 From a clinical perspective, cerebellar degeneration is Chronic polyneuropathy is the most common complication in 380
352 characterised by trunk ataxia with wide-based gait, instabil- alcoholic patients.36 Recently, strong evidence has come to 381
353 ity and variable degrees of lower limb dysmetria. Dysmetria light to show alcoholic polyneuropathy to be the result of a 382
354 in the upper limbs, dysarthria or oculomotor disturbance multifactorial process primarily mediated by the toxic effect 383
355 are less common. In most cases, cerebellar degeneration of alcohol and modulated by other factors, such as genetic 384
356 evolves over a period of several weeks or months and persists predisposition, thiamine deficiency, malnutrition and other 385
357 for years. systemic diseases.37 386
358 Both anatomopathological and neuroimaging studies This is a predominantly axonal, sensorimotor polyneu- 387
359 show degeneration of all the neurocellular elements of the ropathy with distal, symmetric features. The onset of 388
360 cerebellar cortex, and particularly Purkinje cells in the ante- symptoms is insidious and symmetric, predominantly sen- 389
361 rior and superior surface of the vermis.34 Cerebellar atrophy sory, in the form of dysesthesia, burning sensation and 390
362 is easily observed on CT and brain MRI scans (Fig. 2). No burning pain on the soles of the feet that later develops into 391
363 specific treatment has been defined, although administra- cramp in the calves and the hands. Motor symptoms usually 392
364 tion of vitamin supplements and abstinence from alcohol manifest later, and are characterised by muscle weakness 393
365 are recommended. and atrophy, especially in the distal muscles of the upper or 394

lower limbs. Vegetative vascular and skin defects (sweaty, 395

366 Peripheral nervous system involvement atrophic, glossy, almost hairless skin) with associated dysau- 396

tonomia are also typical. 397

367 Acute compressive neuropathy The treatment consists of a balanced diet with vita- 398

min supplements, rehabilitation and alcohol abstinence. 399

However, recovery is slow and often incomplete. Patients 400

368 Excessive alcohol consumption is traditionally associated
presenting with neuropathic pain can be treated with drugs 401
369 with ‘Saturday night palsy’, caused by compression of the
such as gabapentin or amitriptyline. 402
370 radial nerve against the humerus for several hours. It usu-
371 ally occurs when the individual falls asleep with their arm
372 hanging over the armrest of a chair, or being compressed by Disulfiram neuropathy 403
373 the weight of the body. Clinically, it is characterised by an
374 inability to perform dorsiflexion of the wrist and extension of
Disulfiram, a drug used to facilitate alcohol abstinence, 404
375 the fingers. Neurophysiological studies using electromyogra-
has very occasionally been associated with peripheral neu- 405
376 phy is useful both for diagnosis and prognosis, although the
ropathy. The physiopathological mechanism behind this 406
377 condition is self-limiting and most patients recover within
is unknown, but it manifests as an axonal sensorimotor,
378 3---6 months.35

Figure 2 Brain MRI of a patient with alcohol-related cerebellar degeneration. T1-FLAIR (A) sagittal and (B) coronal images showing
predominantly cerebellar vermian atrophy.

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407 dose-dependent polyneuropathy that onsets a few weeks

Table 3 West Haven criteria for hepatic encephalopathy.
408 or months after the start of disulfiram treatment. Clin-
409 ically, it is characterised by distal paresthesias in a Grades of hepatic encephalopathy
410 stocking-glove distribution together with predominantly
411 distal muscle weakness and distal areflexia. Prognosis I Euphoria, anxiety, shortened attention span, reversal of
412 will depend on severity and the degree of axonal loss, sleep---wake cycle. Sporadic flapping
413 although it is usually reversible after suspension of disulfiram II Lethargy, apathy, disorientation in time and space,
414 therapy.38 behaviour disorder. Evident flapping
III Deep somnolence, stupor, confusional state,
inappropriate behaviour, gross disorientation. Flapping at
415 Muscle involvement times impossible to evaluate due to lack of collaboration
IV Coma
416 Acute or chronic alcoholic myopathy

417 Alcohol can damage skeletal muscles by altering calcium

418 channels or the integrity of the muscle fibre membrane
419 or sarcolemma. Clinically, alcoholic myopathy can be char- tachycardia, visual hallucinations and postural tremor. Dif- 460
420 acterised by acute myalgia, rhabdomyolysis and elevated ferential diagnosis between HE and Marchiafava---Bignami 461
421 creatine kinase (CK). In severe cases, it can lead to disease does not generally present any difficulty, since the 462
422 acute kidney failure and myoglobinuria. The chronic form latter is clinically characterised by the presence of dementia 463
423 presents as muscle atrophy, usually proximal, which fre- and spasticity. 464
424 quently coexists with neuroperipheral alterations, such Brain neuroimaging using computed tomography (CT) or 465
425 as chronic alcoholic polyneuropathy. Diagnosis is per- MRI makes it possible to rule out structural alterations, 466
426 formed with neurophysiological tests (electromyography) such as space-occupying lesions, subdural haematomas or 467
427 and histopathological study of muscle biopsy. In some ischaemic/haemorrhagic strokes, which can be suspected 468
428 cases, skeletal myopathy is accompanied by dilated car- when neurological focal signs are observed in the exam- 469
429 diomyopathy. Treatment is based on alcohol abstinence, ination. These imaging studies can also rule out viral or 470
430 physiotherapy and a balanced diet. Prognosis is cautious, autoimmune encephalitis that can clinically overlap HE. A 471
431 since some patients experience an improvement in clini- typical MRI finding in HE is hyperintense basal ganglia on 472
432 cal weakness, but others do not recover muscle strength T1-weighted images, especially in the globus pallidus. This 473
433 or mass.39 is related to manganese deposits caused by portosystemic 474

shunts, and could explain the existence of parkinsonian signs 475

434 Hepatic encephalopathy in these patients.41 476

An electroencephalogram, a neurophysiological test that 477

435 Hepatic encephalopathy (HE) is a common, serious compli- shows the electrical activity of the brain, can rule out 478

436 cation of liver cirrhosis and an indicator of poor prognosis in a non-convulsive status epilepticus or findings typical of 479

437 these patients. It is a complex syndrome involving neurolog- a post-critical state. However, HE produces alterations in 480

438 ical and psychiatric manifestations, and occurs in patients brain activity that are shown on the electroencephalogram 481

439 with advanced liver disease and portosystemic shunting.40 as slow frequency, high amplitude waves and three-phase 482

440 Symptoms fluctuate over time and vary greatly, ranging waves --- findings that can also be found in other metabolic 483

441 from tremor and dysarthria to hepatic coma, and include comas.42 484

442 (a) altered level of consciousness that can progress from Finally, the study of cerebrospinal fluid will rule out 485

443 mild confusion to coma; (b) neuropsychiatric symptoms, meningitis or bacterial or viral meningoencephalitis, which 486

444 such as behavioural changes, mental slowness, reversal of should be suspected when fever and meningeal signs are 487

445 the sleep---wake cycle, or psychomotor agitation, and (c) present. 488

446 neuromuscular symptoms, such as flapping. The West Haven

447 criteria stratifies HE into 4 grades, from mild to most severe
448 (Table 3). Because the clinical manifestations of HE are non- Conclusions 489

449 specific and can be observed in other diseases or metabolic

450 disorders, diagnosis is made on the basis of complemen- Chronic alcohol consumption can produce numerous neu- 490

451 tary tests that can reasonably exclude other potential rological manifestations. The most common are polyneu- 491

452 causes. ropathy, cerebellar degeneration and dementia, and 492

453 Diagnosis of WE in patients with chronic alcoholism is the most serious are WE, Korsakoff syndrome and 493

454 challenging, since the differential diagnosis is extensive. Marchiafava---Bignami disease. All these are associated with 494

455 Clinically, the diagnosis of WE can be difficult because, significant morbidity and mortality, and therefore must 495

456 as explained previously, the classic triad is often absent. be correctly diagnosed and treated in order to avoid 496

457 The presence of alterations in ocular motility, nystagmus irreversible complications. They are caused by vitamin 497

458 and ataxia should raise suspicion of WE, while the presence deficiencies, the direct toxic effects of alcohol, immune 498

459 of flapping or pyramidal syndrome is suggestive of HE. Clin- alterations and unknown mechanisms, among others. In 499

ical findings suggestive of alcohol withdrawal are anxiety, addition, the differential diagnosis of HE can be difficult

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500 due to its similarity with alcohol-related neurological 17. Thomson AD, Marshall EJ. The natural history and pathophysi- 558

501 disorders. ology of Wernicke’s encephalopathy and Korsakoff’s psychosis. 559

Alcohol. 2006;41:151. 560
18. Kopelman MD. The Korsakoff syndrome. Br J Psychiatry. 561
502 Conflicts of interest 1995;166:154---74. 562
19. Kopelman MD, Thomson A, Guerrini I, Marshall E. The Korsakoff 563

503 The authors declare that they have no conflicts of interest. syndrome: clinical aspects, psychology and treatment. Alcohol 564
Alcoholism. 2009;44:148---54. 565
20. Victor M, Adams RD, Collins GH. The Wernicke---Korsakoff syn- 566

504 Acknowledgements drome and related neurologic disorders due to alcoholism and 567
malnutrition. 2nd ed. Philadelphia, PA: FA Davis; 1989. 568
21. Noble J, Weimer L. Neurologic complications of alcoholism. 569
505 We would like to thank the Institute of Diagnostic Imag-
Continuum (Minneap Minn). 2014;20:624---41. 570
506 ing (IDI), Magnetic Resonance Unit, Hospital Germans Trias 22. Navarro J, Noriega S. Enfermedad de Machiafava---Bignami. Rev 571
507 i Pujol (Badalona, Barcelona, Spain), and particularly Fidel Neurol. 1999;28:519---23. 572
508 Núñez. 23. Heinrich A, Runge U, Khaw A. Clinicoradiologic subtypes of 573
Marchiafava---Bignami disease. J Neurol. 2004;251:1050---9. 574
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