Gastroenterol Hepatol.

2017;40(10):709---717

Gastroenterología y Hepatología
[Link]/gastroenterologia

REVIEW

Neurological manifestations of excessive alcohol

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

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

Received 5 March 2017; accepted 19 May 2017

Available online 26 November 2017

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

PALABRAS CLAVE Manifestaciones neurológicas del alcoholismo

Alcoholismo;
Complicaciones Resumen En este artículo se revisan las distintas manifestaciones neurológicas del consumo
neurológicas; excesivo de alcohol, que pueden ser agudas o crónicas y afectar al sistema nervioso central o
Encefalopatía periférico. El mecanismo por el cual se producen varía de un grupo de trastornos a otro. Destacan
hepática factores nutricionales, efectos tóxicos del alcohol, factores metabólicos e incluso inmunológi-
cos. Estas manifestaciones pueden conllevar una gran morbilidad y un aumento significativo de
la mortalidad, por lo que es importante reconocerlas y tratarlas precozmente.
© 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;40:709---717.

∗ Corresponding author.

E-mail address: annaplanasb@[Link] (A. Planas-Ballvé).

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

710 A. Planas-Ballvé et al.

Introduction inhibition of certain subcortical structures (perhaps the mid-

brain reticular formation) that modulate the activity of the
Excessive or harmful alcohol consumption is defined as cerebral cortex.3 However, as more alcohol is consumed,
the consumption of 40---60 g/day of alcohol in women or this inhibitory action extends to cortical and other brain
60---100 g/day in men. Although it does not meet the criteria stem and spinal neurons, and can cause decreased alertness
for alcohol dependency, this level of consumption can pro- and coma with respiratory failure. Some susceptible indi-
duce clinical changes. Alcohol use disorder appears when viduals may experience amnesic lacunae and seizures after
excessive alcohol consumption causes the deterioration of relatively mild alcohol intoxication.4
an individual’s social, work and family relationships.1 The severity of symptoms of acute alcohol intoxication
The World Health Organization’s report on excessive alco- are related to blood alcohol levels5 (Table 2). These levels
hol consumption identified more than 60 alcohol-related should be taken merely as a guide, and will vary between
diseases.2 The systemic effects of alcohol include changes in individuals according to sex, habitual consumption, and
the digestive tract and the liver, the heart and vascular sys- genetic and metabolic factors.
tem, the skeletal and muscular systems, nutritional status, Acute alcohol intoxication should be treated with sup-
the immune, endocrine and haematological systems, and in portive measures and monitoring of the individual’s level
the central and peripheral nervous systems. of consciousness. Alcoholic coma, with its associated respi-
Several alcohol-related neurological complications have ratory depression, is a medical emergency that requires
been described (Table 1), and pathogenesis varies greatly appropriate life support measures.
among the different disorder groups, although one of the
most frequent causes is nutritional deficiency. Alcohol can
produce alcoholic liver disease that can be accompanied Alcohol withdrawal syndrome
by a wide variety of neurological manifestations, including Alcohol withdrawal syndrome, or abstinence syndrome, is
hepatic encephalopathy (HE). the clinical manifestation of abruptly terminating or sub-
In this article, we will examine the different neurolog- stantially reducing intake in patients who have developed
ical manifestations of excessive alcohol consumption, the tolerance and dependence. Alcohol acts basically through
neurological alterations most frequently found in alcoholic 2 specific neuronal receptors. On the one hand, it regu-
liver disease----such as HE----and the best diagnostic approach lates the neurotransmitter gamma-aminobutyric acid type A
in clinical practice. receptor that inhibits neuronal excitability, which explains
its sedative and hypnotic effects. On the other hand,
alcohol increases glutamate N-methyl-d-aspartate recep-
tor expression, which in turn increases glutamate activity
Central nervous system involvement and causes hyperexcitation. Chronic alcohol consump-
tion induces neuroadaptive changes (tolerance), increases
Acute complications glutamate N-methyl-d-aspartate receptor expression, and
desensitises the response and the expression of gamma-
Acute intoxication aminobutyric receptors.6
The symptoms of alcohol intoxication are the result of The manifestations of withdrawal syndrome (a wide
the inhibitory effect of alcohol on the nerve cells of the range of severe symptoms, ranging from distal hand tremor,
brain and spinal cord. Some of the immediate effects of anxiety, insomnia and visual hallucinations to psychomo-
acute alcohol ingestion----such as loquacity, loss of social tor agitation, autonomic hyperactivity, seizures or coma)
inhibition, and aggressiveness----appear to be due to the appear to be mediated by an increase in excitatory

Table 1 Neurological manifestations secondary to exces-

sive alcohol consumption.
Table 2 Manifestations of acute alcohol intoxication.
Central nervous system Peripheral nervous system
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
Neurological manifestations of excessive alcohol consumption 711

neurotransmitters at the expense of inhibitory neurotrans- the liver.11 Other clinical situations that lead to thiamine
mitters. Symptoms typically onset 6---24 h after interruption deficiency should also be borne in mind. These generally
or reduction of alcohol consumption. The most serious involve poor intestinal absorption (gastrointestinal surgery,
form, which usually appears 72 h after withdrawal, is delir- hyperemesis gravidarum) or an increase in body requirement
ium tremens, characterised by disorientation, agitation and (systemic diseases).12
visual hallucinations, accompanied by autonomic signs such From the clinical point of view, WE is characterised
as hyperventilation, tachycardia and diaphoresis. It can by the classic triad of oculomotor disturbance, ataxia and
also be accompanied by metabolic and electrolyte alter- confusion, although the complete triad occurs only in 16%
ations, such as hypomagnesaemia. The mortality rate is of patients.13 Ocular alterations are complex, and consist
5---15%, mainly due to metabolic, cardiovascular and infec- mainly of a combination of alterations such as, for exam-
tious complications.7 ple, horizontal or vertical nystagmus, unilateral or bilateral
According to the European Association for the Study oculomotor paresis, or conjugate gaze palsy. Ataxia mainly
of the Liver, the treatment of choice in patients with affects the trunk by altering gait and balance; limb ataxia
acute withdrawal syndrome and alcoholic liver disease is and dysarthria are less common. Confusion or encephalo-
benzodiazepines,8 since they reduce the risk of epileptic pathic symptoms, meanwhile, develop within days or weeks
seizures. Long-acting benzodiazepines, such as diazepam, and are characterised by profound disorientation, inability
are used, and the dose should be tapered over time. to concentrate, apathy, indifference, inattention, drowsi-
However, in elderly patients, in patients with hepatic fail- ness and coma. Other signs and symptoms are hypothermia
ure, or when excessive sedation must be avoided, the resulting from posterior hypothalamic involvement, tachy-
lowest possible dose of short- or intermediate-acting ben- cardia or postural hypotension due to autonomic nervous
zodiazepines, such as lorazepam, is recommended. In the system dysfunction, or polyneuropathy due to multiple vita-
case of hallucinations and agitation that do not respond min deficiency.12
to benzodiazepines, haloperidol may be added, although it Diagnosis is mainly clinical. Some additional tests can
should only be used in combination with benzodiazepines, help confirm or rule out other suspicions, but should never
because administration of antipsychotics alone may increase delay the start of treatment. A thiamine blood test will show
the risk of seizures. Other drugs, such as alpha-2 agonists thiamine serum levels and transketolase enzyme activity in
(clonidine and dexmedetomidine) and beta-blockers, can be peripheral blood. This test, however, usually takes time and
used as adjuvant treatments to control autonomic hyper- is of little practical use since normal ranges do not rule out
activity. Studies in other drugs, such as carbamazepine, a diagnosis of WE. As far as brain imaging tests are con-
gabapentin and topiramate, have so far yielded promising cerned, the most useful complementary test for confirming
results.9 diagnosis is magnetic resonance imaging (MRI). The most dis-
tinctive lesion is reversible cytotoxic oedema, visualised in
T2, FLAIR and DWI sequences in the periventricular region
Wernicke’s encephalopathy and diencephalon (Fig. 1). Furthermore, mammalian body
Wernicke’s encephalopathy (WE) and Korsakoff syndrome, atrophy, which is usually present in patients with chronic
which were originally described as separate entities, are lesions, can start to be detected within the first week after
now considered the acute and chronic stages, respectively, onset of the disease.14
of Wernicke---Korsakoff syndrome. The real prevalence of WE WE is a medical emergency because it is potentially
cannot be accurately estimated, although different stud- reversible and delayed treatment or no treatment at all can
ies have observed typical WE lesions in 0.2---2.8% of the cause serious sequelae and even death.
autopsies performed in the general population compared Treatment consists of urgent thiamine replacement. Thi-
with a prevalence of 12.5% in autopsies performed on amine therapy has been evaluated in a single randomised
alcoholics.10 double-blind study in 107 patients, in which the efficacy of
WE is caused by a vitamin B1 (thiamine) deficiency, which different intramuscular doses (5, 20, 50, 100 and 200 mg) of
plays a key role in carbohydrate metabolism as an essen- thiamine daily for 2 days was compared. Response, defined
tial coenzyme in the Krebs cycle and the pentose phosphate as improved neuropsychological test score, was evaluated
pathway (transketolase, ␣-ketoglutarate dehydrogenase, on the third day after treatment. The authors concluded
pyruvate dehydrogenase, etc.). Since these enzymes reg- that the 200 mg dose was superior to the other dosages.15
ulate energy metabolism in the brain, thiamine deficiency Although there is no clear consensus on the ideal thiamine
can cause brain damage, mainly in regions with greater dose, pharmacokinetic studies have shown the half-life of
metabolic demand, such as the paraventricular region of thiamine to be around 96 min, so 2 or 3 daily doses are con-
the thalamus and hypothalamus, the mammillary bodies, sidered appropriate.16 Given the higher incidence of adverse
the periaqueductal grey, the floor of the fourth ventricle, effects in intramuscular administration (high volume and
and the cerebellar vermis. Thiamine is found in both animal painful administration), intravenous infusion of thiamine
and plant foods. It is absorbed by the duodenum, and bodily diluted in 100 ml of physiological saline or 5% dextrose over
reserves can be depleted in 2---3 weeks. 30 min is recommended. According to evidence from pub-
In developed countries, more than 80% of cases of WE lished series and the recommendations of the European
occur in the context of malnutrition associated with alco- Federation of Neurological Societies, the administration of
hol consumption. However, studies have shown that WE in between 100 and 200 mg of intravenous thiamine is con-
alcoholics can involve mechanisms other than malnutrition, sidered adequate in non-alcoholic patients, while alcoholic
such as impaired gastrointestinal absorption of thiamine and patients require doses of up to 500 mg 3 times daily.10
a reduced capacity to store and metabolise the vitamin in Other recommendations are a speedy return to a normal
712 A. Planas-Ballvé et al.

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.

diet and continuous treatment until clinical improvement patients with no history of WE, or with sub-acute, undi-
is observed. According to the literature, when untreated or agnosed episodes. However, it can also be a symptom of
insufficiently treated, WE-induced brain damage can lead to malnutrition due to other causes or a symptom of dis-
death in 20% of cases or to the chronic form of WE (Korsakoff eases involving ischaemic, neoplastic or other injury to the
syndrome) in 80% of cases.17 medial and inferomedial thalamic regions in the temporal
lobes.18
From a clinical point of view, it is characterised by
memory impairment that is out of proportion to other
Chronic complications cognitive functions in an awake, attentive and respon-
sive patient. Important manifestations are learning deficits
Korsakoff syndrome and memory loss, affecting both anterograde and retro-
Korsakoff syndrome, which is mainly caused by malnutri- grade events. Recent memory is usually more affected
tion associated with chronic alcoholism, usually emerges in than remote memory, and the creation of false memories,
the aftermath of WE, although it can sometimes appear in or confabulation, in speech that can even be induced by
Neurological manifestations of excessive alcohol consumption 713

questions about the patient’s recent activities is charac- chronic alcohol consumption on the brain. Studies have
teristic of this syndrome. Other cognitive functions, such shown that consumption of 140 g or more of alcohol per
as concentration, spatial organisation, visual or verbal day for a prolonged period of time can produce moderate
abstraction, may also be affected, and patients are usu- cognitive alterations.26
ally apathetic and lacking in initiative, spontaneity and However, alcohol-related dementia has never been
self-criticism.19 accurately defined from a clinical or pathological per-
Korsakoff syndrome is often thought to be untreatable; spective, and the diagnosis of this entity has sparked
however, after thiamine administration, only 25% show no considerable controversy in recent years. Furthermore,
recovery, 25% experience discrete improvement, 25% sig- the interaction between nutritional deficiencies, consump-
nificant improvement, and in 25% memory is completely tion of other substances, psychiatric comorbidity and
recovered.20 repeated head injuries in chronic alcoholic patients raise
doubts about the existence of alcohol-related demen-
tia per se. Some authors, therefore, prefer to use
Marchiafava---Bignami disease the term ‘‘alcohol-related brain damage’’ to describe
Marchiafava---Bignami disease was first described in 1903 in both the aetiology and symptoms of the widely differ-
Italian alcoholic wine drinkers, and since then it has been ing alcohol-related cognitive disorders presented in these
observed in other nationalities in association with abuse of patients.
any alcoholic beverage. It affects chronic alcoholics almost Neuronal damage or depletion, from a physiopatholo-
exclusively, although cases have occasionally been described gical perspective, is believed to be related to glutamate
in non-alcoholics with malnutrition.21 It is a rare entity that neurotoxicity, oxidative stress and diminished neurogenesis,
is characterised by progressive demyelination and necro- triggered by chronic alcohol abuse.27
sis of the central part of the corpus callosum. On brain Post-mortem anatomopathological studies of patients
imaging studies, it manifests as a well defined area of diagnosed with alcohol-related dementia often show non-
demyelination in the body of the corpus callosum, which specific findings, such as predominantly frontal cerebral
can then extend to various regions of the subcortical white atrophy, typical Wernicke---Korsakoff syndrome lesions,
matter. communicating hydrocephalus, Alzheimer’s disease, or trau-
The aetiology is unknown and widely debated, with some matic injuries of variable severity.28
experts suggesting the existence of a toxic factor, not yet From a clinical point of view, it is characterised by
identified, which is present in some alcoholic beverages as an insidious onset with stepwise progression of symptoms
the culprit. However, given the low prevalence of this entity that overlap with other neurodegenerative dementias. In
in alcoholics, and the fact that it has also been described in the early stages, neuropsychological studies usually reveal
some non-alcoholics, it probably has an unidentified nutri- frontal-subcortical cognitive impairment, with slowing of
tional, metabolic or enzymatic aetiology.22 mental processes, attention deficit, changes in immedi-
The clinical characteristics of this disease vary, and ate or short-term memory, decline in visual spatial skills,
there is no well-defined clinical syndrome. Most patients and decline in executive functions, such as planning and
present progressive dementia, usually subacute at onset, organisation.29
with predominance of apractic or aphasic disorders, opposi-
tional hypertonia, dysarthria, frontal release reflexes and,
sometimes, hemiparesis or signs of interhemispheric dis-
connection. Some patients also present decreased alertness Alcohol-related cerebellar degeneration
and seizures. The clinical course is variable; some patients Alcohol-related cerebellar degeneration is a common
will become comatose and die, others can survive several complication that affects up to 25% of alcoholics, and is
years with dementia, while in others partial recovery is one of the most frequent causes of acquired ataxia in
possible.23 adults.30
The diagnosis is difficult because of the wide spectrum The pathogenesis of this entity is complex and not
of symptoms. Diagnosis was hitherto based on post-mortem entirely clear, although a synergistic mechanism involving
studies, but today a history of alcoholism together with clin- both the toxic effect of alcohol and the consequences of
ical manifestation and, above all, brain imaging studies, vitamin B1 deficiency may be involved. Recent studies have
specifically MRI, are essential to confirm diagnosis. Typical shown the presence of anti-tissue transglutaminase 2 anti-
lesions seen on MRI are demyelination, swelling and necrosis bodies in chronic alcoholics, which raises the possibility
of the corpus callosum, with varying degrees of subcortical of alcohol-induced hypersensitivity to gluten.31 According
white matter involvement.24 to the hypothesis put forward by some authors to explain
Given its uncertain aetiology, there is no specific treat- this phenomenon, increased gut permeability caused by
ment for Marchiafava---Bignami disease, although abstinence alcohol-induced intestinal mucosa lesions found in alcoholic
and vitamin supplements are recommended. Good response patients could increase exposure of the immune system
to high doses of corticosteroids has also been reported in to pathogenic antigens (including gliadin peptides). Then,
some studies.25 blood---brain barrier impairment induced by chronic alcohol
consumption would, by as yet unknown mechanisms, allow
the passage of these antibodies to the brain, thus causing
Alcohol-related dementia cerebellar degeneration similar to gluten-induced cerebel-
The term alcohol-related dementia is used to describe lar ataxia.32 In fact, one study has shown a higher prevalence
a form of dementia attributable to the direct effects of of anti-gliadin antibodies in patients with alcohol-induced
714 A. Planas-Ballvé et al.

cerebellar degeneration compared to the general population Chronic alcoholic polyneuropathy

(44% vs 12%).33
From a clinical perspective, cerebellar degeneration is Chronic polyneuropathy is the most common complication in
characterised by trunk ataxia with wide-based gait, instabil- alcoholic patients.36 Recently, strong evidence has come to
ity and variable degrees of lower limb dysmetria. Dysmetria light to show alcoholic polyneuropathy to be the result of a
in the upper limbs, dysarthria or oculomotor disturbance multifactorial process primarily mediated by the toxic effect
are less common. In most cases, cerebellar degeneration of alcohol and modulated by other factors, such as genetic
evolves over a period of several weeks or months and persists predisposition, thiamine deficiency, malnutrition and other
for years. systemic diseases.37
Both anatomopathological and neuroimaging studies This is a predominantly axonal, sensorimotor polyneu-
show degeneration of all the neurocellular elements of the ropathy with distal, symmetric features. The onset of
cerebellar cortex, and particularly Purkinje cells in the ante- symptoms is insidious and symmetric, predominantly sen-
rior and superior surface of the vermis.34 Cerebellar atrophy sory, in the form of dysesthesia, burning sensation and
is easily observed on CT and brain MRI scans (Fig. 2). No burning pain on the soles of the feet that later develops into
specific treatment has been defined, although administra- cramp in the calves and the hands. Motor symptoms usually
tion of vitamin supplements and abstinence from alcohol manifest later, and are characterised by muscle weakness
are recommended. and atrophy, especially in the distal muscles of the upper or
lower limbs. Vegetative vascular and skin defects (sweaty,
atrophic, glossy, almost hairless skin) with associated dysau-
tonomia are also typical.
The treatment consists of a balanced diet with vita-
Peripheral nervous system involvement min supplements, rehabilitation and alcohol abstinence.
However, recovery is slow and often incomplete. Patients
Acute compressive neuropathy presenting with neuropathic pain can be treated with drugs
such as gabapentin or amitriptyline.
Excessive alcohol consumption is traditionally associated
with ‘Saturday night palsy’, caused by compression of the
radial nerve against the humerus for several hours. It usu- Disulfiram neuropathy
ally occurs when the individual falls asleep with their arm
hanging over the armrest of a chair, or being compressed by Disulfiram, a drug used to facilitate alcohol abstinence,
the weight of the body. Clinically, it is characterised by an has very occasionally been associated with peripheral neu-
inability to perform dorsiflexion of the wrist and extension of ropathy. The physiopathological mechanism behind this
the fingers. Neurophysiological studies using electromyogra- is unknown, but it manifests as an axonal sensorimo-
phy is useful both for diagnosis and prognosis, although the tor, dose-dependent polyneuropathy that onsets a few
condition is self-limiting and most patients recover within weeks or months after the start of disulfiram treat-
3---6 months.35 ment. Clinically, it is characterised by distal paresthesias

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.
Neurological manifestations of excessive alcohol consumption 715

Table 3 West Haven criteria for hepatic encephalopathy. disorders, diagnosis is made on the basis of complemen-
tary tests that can reasonably exclude other potential
Grades of hepatic encephalopathy causes.
Diagnosis of WE in patients with chronic alcoholism is
I Euphoria, anxiety, shortened attention span, reversal of
challenging, since the differential diagnosis is extensive.
sleep---wake cycle. Sporadic flapping
Clinically, the diagnosis of WE can be difficult because,
II Lethargy, apathy, disorientation in time and space,
as explained previously, the classic triad is often absent.
behaviour disorder. Evident flapping
The presence of alterations in ocular motility, nystagmus
III Deep somnolence, stupor, confusional state,
and ataxia should raise suspicion of WE, while the pres-
inappropriate behaviour, gross disorientation. Flapping at
ence of flapping or pyramidal syndrome is suggestive of HE.
times impossible to evaluate due to lack of collaboration
Clinical findings suggestive of alcohol withdrawal are anxi-
IV Coma
ety, tachycardia, visual hallucinations and postural tremor.
Differential diagnosis between HE and Marchiafava---Bignami
disease does not generally present any difficulty, since the
latter is clinically characterised by the presence of dementia
in a stocking-glove distribution together with predomi- and spasticity.
nantly distal muscle weakness and distal areflexia. Prognosis Brain neuroimaging using computed tomography (CT) or
will depend on severity and the degree of axonal loss, MRI makes it possible to rule out structural alterations,
although it is usually reversible after suspension of disulfiram such as space-occupying lesions, subdural haematomas or
therapy.38 ischaemic/haemorrhagic strokes, which can be suspected
when neurological focal signs are observed in the exam-
Muscle involvement ination. These imaging studies can also rule out viral or
autoimmune encephalitis that can clinically overlap HE. A
Acute or chronic alcoholic myopathy typical MRI finding in HE is hyperintense basal ganglia on
T1-weighted images, especially in the globus pallidus. This
is related to manganese deposits caused by portosystemic
Alcohol can damage skeletal muscles by altering calcium
shunts, and could explain the existence of parkinsonian signs
channels or the integrity of the muscle fibre membrane
in these patients.41
or sarcolemma. Clinically, alcoholic myopathy can be char-
An electroencephalogram, a neurophysiological test that
acterised by acute myalgia, rhabdomyolysis and elevated
shows the electrical activity of the brain, can rule out
creatine kinase (CK). In severe cases, it can lead to
a non-convulsive status epilepticus or findings typical of
acute kidney failure and myoglobinuria. The chronic form
a post-critical state. However, HE produces alterations in
presents as muscle atrophy, usually proximal, which fre-
brain activity that are shown on the electroencephalogram
quently coexists with neuroperipheral alterations, such
as slow frequency, high amplitude waves and three-phase
as chronic alcoholic polyneuropathy. Diagnosis is per-
waves----findings that can also be found in other metabolic
formed with neurophysiological tests (electromyography)
comas.42
and histopathological study of muscle biopsy. In some
Finally, the study of cerebrospinal fluid will rule out
cases, skeletal myopathy is accompanied by dilated car-
meningitis or bacterial or viral meningoencephalitis, which
diomyopathy. Treatment is based on alcohol abstinence,
should be suspected when fever and meningeal signs are
physiotherapy and a balanced diet. Prognosis is cautious,
present.
since some patients experience an improvement in clini-
cal weakness, but others do not recover muscle strength
or mass.39
Conclusions
Hepatic encephalopathy
Chronic alcohol consumption can produce numerous neu-
rological manifestations. The most common are polyneu-
Hepatic encephalopathy (HE) is a common, serious compli-
ropathy, cerebellar degeneration and dementia, and
cation of liver cirrhosis and an indicator of poor prognosis
the most serious are WE, Korsakoff syndrome and
in these patients. It is a complex syndrome involving neu-
Marchiafava---Bignami disease. All these are associated with
rological and psychiatric manifestations, and occurs in
significant morbidity and mortality, and therefore must
patients with advanced liver disease and portosystemic
be correctly diagnosed and treated in order to avoid
shunting.40
irreversible complications. They are caused by vitamin
Symptoms fluctuate over time and vary greatly, ranging
deficiencies, the direct toxic effects of alcohol, immune
from tremor and dysarthria to hepatic coma, and include
alterations and unknown mechanisms, among others. In
(a) altered level of consciousness that can progress from
addition, the differential diagnosis of HE can be difficult due
mild confusion to coma; (b) neuropsychiatric symptoms,
to its similarity with alcohol-related neurological disorders.
such as behavioural changes, mental slowness, reversal of
the sleep---wake cycle, or psychomotor agitation, and (c)
neuromuscular symptoms, such as flapping. The West Haven
criteria stratifies HE into 4 grades, from mild to most severe Conflicts of interest
(Table 3). Because the clinical manifestations of HE are non-
specific and can be observed in other diseases or metabolic The authors declare that they have no conflicts of interest.
716 A. Planas-Ballvé et al.

Acknowledgements 19. Kopelman MD, Thomson A, Guerrini I, Marshall E. The Korsakoff

syndrome: clinical aspects, psychology and treatment. Alcohol
We would like to thank the Institute of Diagnostic Imag- Alcoholism. 2009;44:148---54.
20. Victor M, Adams RD, Collins GH. The Wernicke---Korsakoff
ing (IDI), Magnetic Resonance Unit, Hospital Germans Trias
syndrome and related neurologic disorders due to alco-
i Pujol (Badalona, Barcelona, Spain), and particularly Fidel holism and malnutrition. 2nd ed. Philadelphia, PA: FA Davis;
Núñez. 1989.
21. Noble J, Weimer L. Neurologic complications of alcoholism.
Continuum (Minneap Minn). 2014;20:624---41.
22. Navarro J, Noriega S. Enfermedad de Machiafava---Bignami. Rev
References Neurol. 1999;28:519---23.
23. Heinrich A, Runge U, Khaw A. Clinicoradiologic subtypes
1. Diagnostic and statistical manual of mental disorders, 5th of Marchiafava---Bignami disease. J Neurol. 2004;251:
ed, DSM-5. Arlington: American Psychiatric Association; 1050---9.
2013. 24. Hillbom M, Saloheimo P, Fujioka S, Wszolek Z, Juleva S, Leone
2. WHO Collaborative Project on Identification and Management M. Diagnosis and management of Machiafava---Bignami disease:
of Alcohol-Related Problems in Primary Health Care. Report on a review of CT/MRI confirmed cases. J Neurol Neurosurg Psychi-
phase IV: development of country-wide strategies for imple- atry. 2014;85:168---73.
menting early identification and brief intervention in primary 25. Gerlach A, Oehm E, Wattchow J, Ziyeh S, Glocker FX, Els T. Use
health care. Ginebra: WHO; 2006. of high-dose cortisone in a patient with Machiafava---Bignami
3. Vonghia L, Leggio L, Ferruli A, Bertini M, Gasbarrini G, Addo- disease. J Neurol. 2003;260:758---60.
lorato G, Alcoholism Treatment Study Group. Acute alcohol 26. Parsons OA, Nixon SJ. Cognitive functioning in sober social
intoxication. Eur J Intern Med. 2008;19:561---7. drinkers: a review of the research since 1986. J Stud Alcohol.
4. Welch K. Neurological complications of alcohol and misuse of 1998;59:180---90.
drugs. Pract Neurol. 2011;11:206---19. 27. Vetreno RP, Hall JM, Savage LM. Alcohol-related amnesia and
5. Vonghia L, Leggio L, Ferruli A, Bertini M, Gasbarrini G, dementia: animal models have revealed the contributions of
Addolorato G. Acute alcohol intoxication. Eur J Intern Med. different etiological factors on neuropathology, neurochemical
2008;19:561---7. dysfunction and cognitive impairment. Neurobiol Learn Mem.
6. Becker H, Mulholland P. Neurochemical mechanisms of alcohol 2011;96:596---608.
withdrawal. Handb Clin Neurol. 2014;125:133---56. 28. Ridley N, Draper B, Withall A. Alcohol-related dementia: an
7. Schuckit M. Recognition and management of withdrawal update of the evidence. Alzheimers Res Ther. 2013:5.
delirium (delirium tremens). N Engl J Med. 2014;371: 29. Munro CA, Saxton J, Butters MA. Alcohol dementia: corti-
2109---13. cal or subcortical dementia. Arch Clin Neuropsychol. 2001;16:
8. European Association for the Study of the Liver. EASL clinical 523---33.
practical guidelines: management of alcoholic liver disease. 30. Klockgether T. Sporadic ataxia with adult onset: classification
J Hepatol. 2012;57:399---420. and diagnostic criteria. Lancet Neurol. 2010;9:94---104.
9. Mirijiello A, D’Angelo C, Ferrulli A, Vassallo G, Antonelli M, 31. Koivisto H, Hietala J, Anttila P, Niemela O. Co-occurrence
Caputo F, et al. Identification and management of alcohol with- of IgA antibodies against ethanol metabolites and tissue
drawal syndrome. Drugs. 2015;75:353---65. transglutaminase in alcohol consumers: correlation with proin-
10. Galvin R, Brathen G, Ivashynka A, Hillbom M, Tanasescu R, flammatory cytokines and markers of fibrogenesis. Dig Dis Sci.
Leone MA. EFNS guidelines for diagnosis, therapy and pre- 2008;53:500---5.
vention of Wernicke encephalopathy. Eur J Neurol. 2010;17: 32. Sianmugaraiah P, Hoggard N, Currie S, Aeschlimann D,
1408---18. Aeschlimann P, Gleeson D, et al. Alcohol-related cerebellar
11. Thomson AD. Mechanisms of vitamin deficiency in chronic degeneration: not all down to toxicity? Cerebellum Ataxias.
alcohol misusers and the development of Wernicke---Korsakoff 2016;3:17.
syndrome. Alcohol Suppl. 2000;35, 7. 33. Currie S, Hoggard N, Clark M, Sanders D, Wilknson I, Griffiths
12. Sechi G, Serra A. Wernicke’s encephalopathy: new clinical sett- P, et al. Alcohol induces sensitization to gluten in geneti-
ings and recent advances in diagnosis and management. Lancet cally susceptible individuals: a case control study. PLoS One.
Neurol. 2008;6:442---55. 2013;8:e77638.
13. Gascón-Bayarri J. Encefalopatía de Wernicke en pacientes 34. Yokota O, Tsuchiva K, Terada S, Oshima K, Ishizu H, Matsushita
no alcohólicos: una serie de 8 casos. Neurología. 2011;26: M, et al. Frequency and clinicopathological characteristics of
540. alcoholic cerebellar degeneration in Japan: a cross-sectional
14. Zuccoli G, Galluci M, Capellades J, Regnicolo L, Tumiati B, study of 1509 postmortems. Acta Neuropathol. 2006;11:
Cabada T, et al. Wernicke encephalopathy: MR findings at 43---51.
clinical presentation in twenty-six alcoholic and nonalcoholic 35. McIntosh C, Chick J. Alcohol and the nervous system. J Neurol
patients. Am J Neurorradiol. 2007;28:1328---31. Neurosurg Psychiatry. 2004;75 Suppl. III:iii16---21.
15. Ambrose ML, Bowden SC, Whelan G. Thiamin treatment and 36. Vittadini G, Buonocore M, Colli G, Terzi M, Fonte R, Biscaldi G.
working memory function of alcohol-dependent people: prelim- Alcoholic polyneuropathy: a clinical and epidemiological study.
inary findings. Alcohol Clin Exp Res. 2001;25:112---6. Alcohol Alcohol. 2001;36:393---400.
16. Tallaksen C, Sande A, Bahmer T, Bell H, Karlsen J. Kinetics of thi- 37. Mellion M, Gilchrist H, de la Monte S. Alcohol-related periph-
amin and thiamin phosphate esters in human blood, plasma and eral neuropathy: nutritional, toxic or both. Muscle Nerve.
urine after 50 mg intravenously or orally. Eur J Clin Pharmacol. 2011;43:309---16.
1993;44:73---8. 38. Thu A, Rison R, Beydoun S. Disulfiram neuropathy: two case
17. Thomson AD, Marshall EJ. The natural history and pathophysi- reports. J Med Case Rep. 2016;19:72.
ology of Wernicke’s encephalopathy and Korsakoff’s psychosis. 39. Preedy VR, Adachi J, Ueno Y, Ahmed S, Mantle D, Mullati N,
Alcohol. 2006;41:151. et al. Alcoholic skeletal muscle myopathy: definitions, features,
18. Kopelman MD. The Korsakoff syndrome. Br J Psychiatry. contribution of neuropathy, impact and diagnosis. Eur J Neurol.
1995;166:154---74. 2001;8:677---87.
Neurological manifestations of excessive alcohol consumption 717

40. Hepatic encephalopathy in chronic liver disease: 2014 Practice 41. Rovira A, Alonso J, Córdoba J. MRI imaging findings in hepatic
Guideline by the European Association for the study of the liver encephalopathy. Am J Neuroradiol. 2008;39:1612---21.
and the American Association for the study of liver diseases. 42. Amlodio P, Gatta A. Neurophysiological investigation of hepatic
J Hepatol. 2014;61:642---59. encephalopathy. Metab Brain Dis. 2005;20:369---79.