Radiología.

2017;59(1):17---30

www.elsevier.es/rx

UPDATE IN RADIOLOGY

The addicted brain: Imaging neurological complications

of recreational drug abuse夽
A. Montoya-Filardi ∗ , M. Mazón

Área Clínica de Imagen Médica, Hospital Universitario y Politécnico La Fe, Valencia, Spain

Received 12 January 2016; accepted 14 September 2016

KEYWORDS Abstract Recreational drug abuse represents a serious public health problem. Neuroimaging
Recreational drugs; traditionally played a secondary role in this scenario, where it was limited to detecting acute
Biochemical vascular events. However, thanks to advances in knowledge about disease and in morpholog-
mechanisms; ical and functional imaging techniques, radiologists have now become very important in the
Magnetic resonance diagnosis of acute and chronic neurological complications of recreational drug abuse.
imaging; The main complications are neurovascular disease, infection, toxicometabolic disorders, and
Functional imaging; brain atrophy. The nonspecific symptoms and denial of abuse make the radiologist’s involve-
Infarction; ment fundamental in the management of these patients. Neuroimaging makes it possible to
Hemorrhage; detect early changes and to suggest an etiological diagnosis in cases with specific patterns of
Leukoencephalopathy; involvement.
Atrophy; We aim to describe the pattern of abuse and the pathophysiological mechanisms of the drugs
Marchiafava---Bignami with the greatest neurological repercussions as well as to illustrate the depiction of the acute
and chronic cerebral complications on conventional and functional imaging techniques.
© 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.

PALABRAS CLAVE El cerebro adicto: imagen de las complicaciones neurológicas por el consumo de
Drogas de abuso; drogas
Mecanismo
bioquímico; Resumen Las drogas constituyen un gran problema sociosanitario. Tradicionalmente, la neu-
Resonancia roimagen ha tenido un papel secundario limitado a la detección de eventos vasculares agudos.
magnética; En la actualidad, el radiólogo ha adquirido gran relevancia en el diagnóstico de las complica-
Imagen funcional; ciones neurológicas agudas y crónicas, debido al avance en el conocimiento de la enfermedad
Infarto; y al desarrollo de las técnicas de imagen morfológicas y funcionales. Las principales com-
plicaciones son la patología neurovascular, la infección, los trastornos tóxico-metabólicos y

夽 Please cite this article as: Montoya-Filardi A, Mazón M. El cerebro adicto: imagen de las complicaciones neurológicas por el consumo de
drogas. Radiología. 2017;59:17---30.
∗ Corresponding author.

E-mail address: montoyafilardi@gmail.com (A. Montoya-Filardi).

2173-5107/© 2016 SERAM. Published by Elsevier España, S.L.U. All rights reserved.
18 A. Montoya-Filardi, M. Mazón

la atrofia cerebral. La sintomatología inespecífica y la negación del consumo hacen que la

Hemorragia;
Leucoencefalopatía;
Atrofia;
Marchiafava---Bignami
implicación del radiólogo pueda resultar fundamental en la atención de estos pacientes. La
neuroimagen permite detectar alteraciones precoces y plantear el diagnóstico etiológico ante
patrones de afectación específicos. Nuestro objetivo es describir el patrón de consumo y el
mecanismo fisiopatológico de las drogas con mayor repercusión neurológica, así como ilustrar
las complicaciones cerebrales agudas y crónicas mediante técnicas de imagen convencional y
funcional.
© 2016 SERAM. Publicado por Elsevier España, S.L.U. Todos los derechos reservados.

Introduction The main cerebral complications derived from cocaine

Human kind has always wanted to experience new sensa-
tions, to reach different states of consciousness and, on
occasion, to mask reality. The substances used with this
purpose have targeted, whether intentionally or not, the
central nervous system (CNS). Consumption patterns have
changed and conditions of use have improved, but they all
have deleterious effects that we can see and quantify.
Each substance has multiple forms of presentation which
are modified all the time, the absorption pathways of the
body are limited and they cause complications that over-
lap one another. Neuro-imaging findings frequently pose the
possibility of consumption, and even in view of character-
istic patterns, it would be possible to suggest the specific
type of drug. The role of the radiologist, therefore, is ever
more relevant both finding urgent conditions and visualizing
chronic effects.
Our goal is to describe the consumption pattern and the
physiopathological mechanisms of the drugs that have the
most neurological repercussion (cocaine, amphetamines,
heroin, alcohol, cannabis and toluene), as well as to illus-
trate the acute and chronic cerebral complications through
conventional and functional image modalities (positron
emission tomography [PET], single photon emission com-
puted tomography [SPECT] and perfusion by magnetic
resonance [MRI]).
Cocaine
Cocaine is the main alkaloid obtained from the leaves of a
shrub belonging to the family Erithroxylon coca, present in
the Western regions of South America. There are two forms
of presentation: hydrochloride (with the appearance of a
fine powder) and alkaloid (also known as crack).1 The most
popular route of administration is intranasal, which reaches
concentrations in the CNS in 3---5 min. The main action
of cocaine is summarized in the sympathomimetic effect
due to the blockage of catecholamine reuptake.1---4 It also
blocks the reuptake of serotonin and dopamine transmitters,
increasing their extracellular concentrations, especially in
the accumbens nucleus.2,5,6
Addiction caused by cocaine is due to its rapid action
mechanism, since its effect is almost immediate after
administration.1 A feeling of euphoria or high is experienced
after its consumption mediated mainly by the occupation of
dopamine receptors called DA-D2.1,3---5
abuse are vascular ones, especially subarachnoid hem-
orrhages and intraparenchymatous hemorrhages; overall
hemorrhagic events are twice as frequent as ischemic
infarctions.1,7,8 Nevertheless, the form of the drug and the
route of absorption influence on the type of adverse event.
When cocaine is smoked in the form of crack the incidence
of hemorrhagic events is greater, while there are no signifi-
cant differences between ischemic and hemorrhagic events
when the drug is sniffed.9,10
The physiopathological mechanisms involved in the pro-
duction of ischemic cerebrovascular accidents are multiple
and synergic, but vasoconstriction or vasospasm stand out
among them2,11 (Table 1). This phenomenon can cause
endothelial damage consisting of disruption of the tunica
media and arteriolar fibrosis, among other alterations.12
However, the significant vasculitis component stands out,
confirmed by the existence of focal stenoses of the vascu-
lar lumen and enhancement of vessel walls in angiographic
studies.5,13
Ischemic infarctions commonly affect the territories
of mid and posterior cerebral arteries (Fig. 1), and the
border territories, the internal capsule and the hippocam-
pus, without a specific disorder pattern.1,5,9 Mesencephalic
infarction has been associated with the simultaneous use of
cocaine and amphetamines.14 Since it does not show a char-
acteristic distribution, concomitant findings are specially
relevant, such as perforation of the nasal septum, acceler-
ated atherosclerosis in young people without cardiovascular
risk factors (Fig. 2) and generalized vasospasm.
Table 1 Mechanisms implied in the production of cocaine-
induced ischemic cerebrovascular accidents.
Ischemic mechanism Biochemical phenomenon
Vasoconstriction Calcium channel blockade1,4
Increase of serotonin levels2,5
Prothrombotic Increase of thromboxane levels
phenomena and platelet aggregation5,9,10
Procoagulant diathesis Reduction of antithrombin III
and protein C7,8
Atherosclerosis Nitric oxide inhibition in the
endothelium11
Vasculitis Impurity-activated paracrine
and immune mechanisms5,9,13
The addicted brain: Imaging neurological complications of recreational drug abuse 19

A B C D

Arteria

MTT

Figure 1 Acute ischemic cerebrovascular accident in the territory of the left medial cerebral artery associated with cocaine
consumption. (A) CT without IV contrast showing hypodensity of the caudate head, the left lenticular nucleus and the insula
(arrowheads). (B) Parametric map of the mean transit time (MTT) showing a large ischemic area with an increased MTT (in blue),
mostly corresponding to salvable tissue (represented in green in C), and a small ischemic core of unviable tissue mass with diminished
cerebral blood volume (red in C). (D) Diffusion-weighted images identifying restriction of the ischemic area in the Sylvian territory.

Figure 2 Thirty-eight-year-old man with accelerated atherosclerosis without the classical cardiovascular risk factors --- usual
cocaine consumer. (A) Doppler duplex ultrasound image of the cervical segment of the internal carotid artery showing a relatively
homogeneous soft plaque (white arrows), with irregular surface, ulceration (arrowhead) conditioning a serious stenosis of the lumen
with high-speed turbulent flow (black arrow) and peak systolic speed of approximately 300 cm/s. (B) CT volumetric reconstruction of
both carotid arteries showing marked bilateral atherosclerotic damage (plaques marked with arrows). (C) Detail of the transversal
image of a CT study in bone window where we can identify perforation of the nasal septum (arrow).
20 A. Montoya-Filardi, M. Mazón

Figure 3 Thirty-three-year-old woman showing intense headache and left hemiparesis whose toxic urine analysis reveal cocaine
consumption. (A) Transversal CT image without IV contrast showing right intraparenchymatous cortico-subcortical frontal parafal-
cine hematoma (arrows). (B) T2-weighted transversal MRI showing the markedly hypointense hematoma (arrows), vasogenic edema
on its lateral edge and, on its medial edge, one tubular flow vacuum nidus corresponding to an arteriovenous malformation (arrow-
heads). (C) T1-weighted sagittal MRI with IV contrast showing the nidus of the malformation (arrow) with drainage into the superior
longitudinal sinus. (D) Digital subtraction arteriography sagittal image confirming the arteriovenous malformation (arrow).

Up to 50% of patients with cocaine-induced hemorrhagic
complications show underlying vascular condition such as
aneurysms and vascular malformations.1 The greater preva-
lence of aneurysms is explained by the maintained increase
of blood pressure.1,2,15 The mechanism involved in aneuris-
mal rupture and arteriovenous malformations is high systolic
peak and increase of heart rate after acute consumptions4,5
(Fig. 3). The combined abuse of cocaine and ethanol is not
uncommon, which increases synergically the odds of suffer-
ing subarachnoid hemorrhages.10
The intraparenchymatous hematoma is usually lobar and
subcortical while there is greater incidence of bleeding in
the encephalon.5,16 Hematomas are larger and they tend
to spread themselves to the ventricles more easily than in
non-users, which conditions greater neurological deficits.16
Hemorrhagic transformations of the ischemic areas is not
uncommon due to damage to hematoencephalic barrier and
increase of arterial pressure.7,9
Chronic addicts characteristically show structural atro-
phy in the frontal lobes and to a lesser extent, in
the temporal ones,8,9 where reduction of metabolic
activity has been confirmed in PET examinations with 18-
fluorodeoxyglucose.17 Perfusion studies with SPECT with
hexamethyl propylene or amino oxyme marked with
metastable technetium 99 (99mTc-HMPAO) have shown a
generalized reduction of 30% in global cerebral blood flow
adding a specific reduction of the relative cerebral blood
flow in the prefrontal cortex, anterior cingulate gyrus, the
The addicted brain: Imaging neurological complications of recreational drug abuse 21

thalami, the basal ganglia, the occipital cortex and the
cerebellum.18
In addition to the withdrawal syndrome, many users
experience an intense crave to consume after it has gone
(the so-called craving stage), which can be triggered by
multiple stimuli. In this complex stage, there is a selec-
tive activation of the limbic system in perfusion studies,19
hypermetabolism in the orbitofrontal cortex19,20 and even
involvement of the mu opioid system.21 Functional studies
based on oxygen consumption (BOLD sequence) in active
users confirm an increase of activity in the craving stage and
dependence located in the limbic, paralimbic regions, the
accumbens nucleus, the frontal and inferior frontal orbital
circumvolutions and the anterior cingulum.22 This activation
has also been shown during the craving for consumption
when videos showing the drug were played.23 However,
after administration of the substance, these regions are
deactivated.22
Amphetamines and derivatives
Amphetamine was synthesized for the first time in
1887 and it was the first substance of a group that
shares properties, called the same way as a whole.
Later there appeared methamphetamine and MDMA (3,4-
methylenedioxymetanphetamine), commonly known as
‘‘ecstasy’’ or ‘‘crystal’’. There is rigorous legal control of
amphetamine derivatives in research studies and for the
treatment of disease (obesity and hyperactivity). The con-
sumption profile of MDMA is associated with night-time
leisure; it is the second most consumed illegal drug among
young people after cannabis.24 The most common route of
administration is orally, in the form of powder or ‘‘crystal’’
or pills. It causes a rapid feeling of euphoria and an increased
sensory perception this is why it is considered both stimulant
and hallucinogenic.8,25
Amphetamines, as a whole, increase the synaptic con-
centrations of biological amines (dopamine, noradrenalin
and serotonin/5-hydroxytryptamine); the main and most
characteristic action of MDMA is the release of 5-
hydroxytryptamine.8,11,25 This neurotransmitter is the amine
with the greatest vasoconstrictor effect in the brain.5
Although the biochemical mechanism of amphetamines
causes long-term ischemia, the most common urgent
complications are hemorrhages due to blood pressure
increase. Just as it happens with cocaine consumption,
blood pressure increases after consumption conditions
greater risk of rupture of arteriovenous malformations and
preexisting aneurysms.9,26
Vasoconstriction in cerebral microcirculation ultimately
causes necrosis of irrigated tissue.8,9,26 The areas that are
more commonly affected by this ischemia are the globus pal-
lidus (as it happens with heroin) and the occipital cortex,
where the largest concentration of 5-hydroxytryptamine
receptors are located (called 5HT 2A)8,9 ; in fact, the most
common finding in autopsies is necrosis of the globus
pallidus26 (Appendix B Fig. S2 online). This spatial speci-
ficity explains why it is in these areas where structural and
functional complications develop.
Another complication that stems from blood pressure
increase is posterior reversible encephalopathy syndrome
(Fig. 4). This is an unspecific disorder of cerebrovascular
self-regulation showing a preference for posterior circu-
lation and borderline cortical areas. On the computed
tomography (CT), findings can be subtle, identifying hypo-
density non-confluent cortical---subcortical, bilateral areas
often located in the posterior parietal occipital lobes.

Figure 4 Forty-two-year-old woman---sporadic consumer of 3,4-methylenedioxymetanphetamine (MDMA) going to hospital with

headache, visual alteration and hypertensive crisis due posterior reversible encephalopathy syndrome. The urine toxicology exam
reveals 3,4-metilendioximetanfetamine (MDMA). (A) T2-weighted transversal MRI showing extensive confluent cortico-subcortical
bilateral edema predominantly parieto-occipital posterior (arrows). (B) T2-weightred FLAIR coronal MRI showing the edema (arrows)
and its mass effect with fissure collapse (arrowheads). The clinical manifestations and the radiological findings were resolved a few
days later with support measures and blood pressure control.
22
The MRI is more sensitive for its diagnosis and findings
are detected early, showing high signal intensity in T2-
weighted/FLAIR sequences.
When it comes to long-term effects, selective atrophy in
the occipital and frontal cortex, the left temporal lobe and
the brainstem has been confirmed compared to users that
abused other substances exclusively or jointly (polyabuse).25
Methamphetamines can cause gray matter volume loss which
can range from generalized to unilobar.25,27,28 However,
an increase in the volume of the striatum has been con-
firmed (caudate and putamen) in adult methamphetamine
consumers for over two years. Volume increase is due to
mechanisms of initial response to neurotoxicity --- above all
swelling. This reaction evolves subsequently to atrophy if
the neurotoxic dose continues to increase.25,29 In children
exposed to methamphetamines in utero there is striatum
volume loss initially, since there is no such compensation to
dopaminergic damage.25,30
With PET, it is possible to observe selective dam-
age in serotoninergic neurons and a reduction of its
transmitters.31,32 When it comes to SPECT-measured per-
fusion we have been able to confirm a decrease of the
relative cerebral blood flow in the visual cortex, the
caudate, the superior parietal lobe and the dorsolateral
region of the frontal lobe, associated with MDMA-induced
vasoconstriction.31,33 Keeping with it, we have been able to
detect reduction in relative cerebral blood volume of such
dorsolateral region of the frontal cortex through MRIs as the
first functional manifestation after the first contacts with
MDMA in young subjects.34
Heroin
Heroin or diacetylmorphine is the most widely consumed
illegal compound within the opioid group. It was commer-
cialized for the first time in 1898 as an analgesic substitute
to morphine, but it was withdrawn after the physical and
psychological dependence that it caused was confirmed.
Its appearance is that of a white, fine crystalline powder,
although it can vary. There are three main types: number
two or freebase; number three, known as brown sugar due
to its earthy aspect; and number four or Thai variety of a 90%
purity. The IV is the most effective, filling route of adminis-
tration with respect to its effect, and it was the most widely
used until AIDS appeared. Today, the inhaled and smoked
routes of administration are more widely used.
The mechanism of action of heroin is mediated by the
activation of three types of receptors: mu, kappa and delta.
Mu receptors are responsible for the feeling of euphoria and
positive reinforcement, in addition to analgesia, respiratory
depression and miosis.35,36 Kappa and delta receptors con-
tribute to the analgesic effect, the feeling of dysphoria and
the psychomimetic effect.35,36
A sharp, positive feeling after the first contacts (hon-
eymoon) occurs initially. When the state of intoxication
advances, the effects fade. The degree of tolerance turns
the drug into a means to avoid withdrawal syndrome and
less and less often into a source of pleasure.
Ischemic conditions, toxic leukoencephalopathies and
atrophies are among the most common complications asso-
ciated with heroin abuse.
A. Montoya-Filardi, M. Mazón
Ischemia is the most common neurovascular complication
of the compounds derived from opioids and morphine.8,11
The physiopathological mechanisms involved are vasospasms
due to smooth muscle contraction, vasculitis phenomena
and embolisms due to additives.37---39 Borderline vascular ter-
ritories are the most vulnerable ones, but the anatomical
structure that is most commonly affected is the globus pal-
lidus (up to 5---10% in chronic users).40 Chronic ischemia is
common which is shown on the MRI as confluent hyperinten-
sities in the periventricular and subcortical white matter.
This finding gains special importance if patients are young
and without any other risk factors.11,35
A specific complication of the heroin addict who uses
the inhaled route is a phenomenon known as chasing the
dragon. This denomination comes from the way the smoke
is inhaled when the heroin is heated over an open flame.
It became popular as an alternative to IV administration
to avoid HIV contagion. The neurological complication con-
sists in a leukoencephalopathy with edema. It is probably
due to a mechanism of mitochondrial toxicity, triggered
by impurities that are activated when heating aluminum
foil.41 These manifestations can occur with cerebellar and
extrapyramidal signs, and in the most serious cases pseudo
bulbar manifestations, spasms, hypotonic muteness or even
death occur.11 Anatomopathologically, a spongiform degen-
eration of the corticospinal tracts and of the cerebral and
cerebellar white matter has been reported.8,41 T2/FLAIR MRI
sequences show bilateral symmetric hypersignal of white
matter in these locations. Cerebellar disorders and of the
posterior limb of the internal capsule --- not affecting the
anterior limb, is the most characteristic sign.42 These find-
ings are not exclusive to heroin-induced leukopathy and they
can be secondary other substance abuse. Spectroscopy find-
ings complement diagnosis and increase their specificity;
they show an abnormal descent of the N-acetylaspartate
peak, an increase of lactate and myoinositol, and stability
of lipid peaks11 (Fig. 5). Resolution of the clinical disorder
has been described when heroin use is interrupted though
image findings can persist.43
In addition to the complications derived from the sub-
stance itself, both the impurities (lipophilic substances)
used in the mixture and the unsterile conditions in the IV
administration make infections be relatively common and
especially important.8,11,41 Half the users develop endocardi-
tis, occlusion of small vessels due to septic emboli and
formation of abscesses. In the MRI, abscesses are shown
as rounded lesions that are enhanced in a ring shape after
the administration of contrast, they show perilesional vaso-
genic edema and its purulent content restricts diffusion
(Fig. 6). The organism involved in most cases is Staphylo-
coccus aureus, which enters the blood stream from the skin
through the needle.44
The chronic consumption of heroin leads to encephalic
atrophy, hypometabolism and hypoperfusion. Gray-matter
loss, confirmed through volumetry on the MRI, prevails in
the prefrontal bilateral cortex, the temporal lobes and the
insulae,45 with a correlation between the duration of use and
the degree of atrophy suggestive of a cumulative effect.46
White matter has been assessed in image studies through
diffusion tensor imaging, in which it has been possible to
observe a reduction in the fractional anisotropy translating
a disruption of fibers in bilateral frontal regions, the right
The addicted brain: Imaging neurological complications of recreational drug abuse 23

A B

C D E
Cho

NAA

Cr
Cr2 Ins
Glx Lipids

4 3 2 1 0

Figure 5 Man with predominantly supratentorial leukoencephalopathy associated with heroin consumption---typically known as
chasing the dragon. (A) and (B) CT transversal images without IV contrast showing generalized white matter hypodensity of the corona
radiata (asterisks) spreading throughout the corticospinal tracts into the posterior limbs of the internal capsules (arrowheads). (C)
and (D) T2-weighted transversal MRIs in the same locations where we can more clearly see white matter damage with signal increase.
(E) The single-voxel spectroscopy study with short echo time showed a decrease of the N-acetylaspartate peak and a slight increase
of lipids and lactate.

precentral gyrus and the left cingulum.47 Studies in chronic
addicts have confirmed a global decrease of perfusion48 and
ometabolism31,49 and a greater reduction of both parameters
in the frontal and temporal lobes (Fig. 7). When it comes to
acute effects, it has been confirmed that there is a drop in
perfusion quantified through ASL (arterial spin labeling) in
the anterior left cingulate cortex, the left prefrontal cortex
and the insulae.50
Alcohol
Alcohol is a socially accepted legal drug. Excessive, chronic
consumption of alcohol is associated with an increase of
morbimortality and it reduces life expectancy in up to 15
years.51 Based on its process of manufacturing, alcoholic
beverages are divided into fermented and distilled. The
main component of alcohol is ethanol, a CNS depressor that
progressively numbs brain and sensory functions. It is mis-
takenly confused with a stimulant because at the onset of
intoxication there is lack of behavioral inhibition.
There are three main neurological damage mechanisms:
direct toxicity, derivative-mediated damage (methanol
and acetaldehyde) and effects secondary to cirrhosis
and nutritional deficits. There are multiple direct dam-
age mechanisms proposed, but the common outcome is
greater susceptibility of N-methyl-d-aspartate receptors of
excitement and glutamate cytotoxicity, the so-called upre-
gulation.
Wernicke’s encephalopathy is one of the main
complications of chronic alcoholics due to deficit of thi-
amine coenzyme (vitamin B1). Wernicke’s encephalopathy
causes the classic triad of ophthalmoplegia, confusion and
gait disorder though the complete clinical manifestations
only occur in one third of the patients.52 Delayed diagnosis
and treatment can lead to Korsakoff’s psychosis, charac-
terized by memory alterations and confabulation. Osmotic
changes due to thiamine reduction cause intracellular and
extracellular edema, especially in areas near the cere-
brospinal fluid, where the hematoencephalic barrier is more
patent. Lesions are commonly located around the third ven-
tricle and the lateral ventricles, the thalamus dorsomedial
24 A. Montoya-Filardi, M. Mazón

Figure 6 Habitual IV heroin consumer going to the ER with disorientation. (A) CT without IV contrast where we can identify
multiple subcortical supratentorial abscesses (arrows)-predominantly right and mesencephalic. (B) T2-weighted transversal MRI
confirming the findings and showing an important vasogenic perilesion edema. (C) In the diffusion sequence, the content of the
abscesses shows restriction since it consists of purulent material. (D) After the administration of contrast the abscesses are totally
enhanced looking like ring shapes. The microorganism involved is Staphylococcus aureus.

pulvinar nuclei, the mammillary bodies, and the pineal and
periaqueductal region.52 In the most serious cases, the deep
white matter and even the cortex can also be affected.
In the affected areas, the MRI will show hyperintensity
in T2/FLAIR,8,11 and after the administration of contrast
they can be enhanced due to rupture of hematoencephalic
barrier, and intense enhancement of mammillary bod-
ies is pathognomonic of this disorder in acute stages
and even in the absence of T2 hyperintensity51---53
(Fig. 8).
Another manifestation of chronic alcohol abuse is
Marchiafava---Bignami disease, consisting of corpus callosum
demyelination and necrosis.51,54 A toxic agent from red wine
has been identified that, in conjunction with vitamin defi-
ciency, can be the cause of these manifestations.55 The
disorder begins in the trunk and it can spread to the knee and
even the splenius.51,54 The corpus callosum necrosis occurs
in three stages characteristically (layer necrosis), typical
of this disease. There are two subtypes: A, where there is
complete damage of the corpus callosum showing greater
impairment of consciousness and leading to worse progno-
sis; and B, where damage of the corpus callosum is partial
showing less impairment of consciousness and more favor-
able evolution. MRIs are especially important due to the fact
The addicted brain: Imaging neurological complications of recreational drug abuse 25

Figure 7 Forty-eight-year-old man chronic heroin male consumer showing cognitive impairment and behavioral alterations. (A)
T1-weighted transversal MRI where we can identify an important frontal bilateral atrophy with anteroposterior damage gradient.
See dilation of the subarachnoid spaces of frontal convexities and Sylvian fissures (arrows). (B) PET transversal image with 18F-
fludeoxyglucose where we can see frontal bilateral hypometabolism (arrows) with the same distribution as the atrophy in the
structural image.

that clinical manifestations are unspecific. Hyperintensity in
T2/FLAIR without mass effect in the central region of the
corpus callosum is the common presentation (Fig. 9); it can
be enhanced peripherally after the administration of con-
trast on the acute stage.55 The white matter in the brain
hemispheres can also be damaged --- a finding described in up
to 40% of necropsies of patients with Marchiafava---Bignami
disease. Spread to the cortex --- known as Morel’s cortical
laminar sclerosis consists of gliosis of the third cortical layer
in the frontal and lateral regions.56 In PET studies with FDG
it has been possible to confirm a metabolic reduction in
the cortex frontal of temporo-parieto-occipital association
due to the disruption of commissural fibers that alter this
association network.51,57
Chronic hepatic encephalopathy is due to and inade-
quate cleansing of nitrogenated compounds and other toxins
that accumulate in the brain parenchyma. Image findings
of this disease are practically undetectable through CT and
MRI T2-weighted sequences. In the T1-weighted sequences
there is bilateral and symmetrical hyperintensity compati-
ble with manganese deposits, located in the base ganglia
(in particular in the globus pallidus), the hypothalamus, the
mesencephalon and the adenohypophysis51 (Appendix B Fig.
S1 online). MRI spectroscopy study obtained with short echo
time is characteristic in patients with chronic hepatic ence-
phalopathy, who show a significant reduction of myoinositol
and choline, and an increase of glutamine/glutamate
peaks.51
Lastly, chronic alcoholism is associated with neuronal
loss and atrophy, especially of the frontal superior and
motor cortex, and with white matter, bridge, thalamus,
mammillary body and cerebellum volume loss, and greater
damage of the vermis superior.51 Concomitant use of alcohol
with other drugs, in particular with cocaine, contributes to
greater white matter loss, due to the formation of a long-
lasting vasoactive metabolite, cocaethylene, resulting from
the co-administration of both substances.11
Cannabis
Cannabis is the most consumed illegal drug worldwide.58 It
is obtained from Cannabis sativa, a dioecious herb. Its main
psychoactive component is a lipophilic substance called
delta-9-tetrahydrocannabinol. The products obtained from
cannabis are marihuana (prepared with dry leaves), hashish
(derived from its resin) and hashish oil (obtained from dis-
tilling organic solvents).
All the parts of the plant contain delta-9-
tetrahydrocannabinol. The most commonly used form
of cannabis abuse is smoked marihuana. Its resin is used
in food for oral consumption; this form of administration
causes a great amount of intoxications since the user does
not control the time elapsed between ingestion and effects.
Chronic consumption increases the risk of schizophrenia
and behavioral changes.11
After its consumption a feeling of wellbeing is obtained
due to the activation of cannabinoid receptors CB1, present
in the black matter, the hippocampus, the limbic cortex and
the cerebellum.8,9
Its wide use and polyconsumption are factors that make
it difficult to establish a direct connection between cannabis
and cerebrovascular disease.9,58 It causes orthostatic
hypotension, which in people with little cerebral blood
26 A. Montoya-Filardi, M. Mazón

Figure 8 Chronic alcoholic man with manifestations of confusion and ataxia due to Wernicke’s encephalopathy. (A) T2-weighted
transversal MRI where signal hyperintensity is identified around the Sylvian aqueduct (arrowheads). (B) T2-weighted coronal FLAIR
MRI where periventricular signal hyperintensity of the third ventricle can be easily identified (arrowhead). (C) and (D) Sagittal and
transversal MRIs with IV contrast showing bilateral enhancement of mammillary bodies (arrowheads and arrow).

Figure 9 Chronic red wine male consumer with Marchiafava---Bignami’s disease in subacute stage. (A) and (B) T2-weighted
FLAIR coronal and sagittal MRIs showing marked hyperintensity of the corpus callosum trunk posterior portion (arrowheads). No
enhancement after the administration of contrast.
The addicted brain: Imaging neurological complications of recreational drug abuse 27

Figure 10 Thirty-eight-year-old man who is a chronic consumer of cannabis showing hypoperfusive ischemic infarctions in the
right internal borderline territory. (A) CT transversal image without IV contrast in which a hypodensity area can be seen on the
right corona radiata (arrow). (B) T2-weighted transversal MRI showing infarctions as hyperintense. (C) Transversal diffusion-weighted
images showing restriction of the infarctions which in turn allows us to assess the typical linear distribution of the internal borderline
territory. See cortical atrophy---uncommon in a middle-aged patient (arrows).

reserve can cause cerebral infarctions---being this is the
main mechanism of ischemic cerebrovascular accidents59
(Fig. 10). In addition to high blood pressure that acts as a
trigger, there are other predisposing vascular alterations;
in this sense, the presence of intracranial stenosis has been
confirmed in 31% of cannabis consumers who have developed
ischemic cerebrovascular accidents.60 Vasospasms, vasculi-
tis, development of arrhythmias and high concentrations
of carboxyhemoglobin are other factors that predispose
to adverse cerebrovascular events.8,9,61,62 The location of
these ischemic infarctions is not specific: basal ganglia
predominate, as well as periventricular white matter,
the cerebellum and the temporal, parietal and occipital
lobes.
Perfusion studies through PET and SPECT confirm an
increase of relative cerebral blood flow with acute
consumption.63 However, there is reduction of generalized
relative cerebral blood flow among chronic users that can be
reverted with abstinence.31,58 Glucose metabolism in spo-
radic users is usually diminished except for the cerebellum,
probably due to the large number of cannabinoid receptors
in this area.31
Toluene
Toluene or methylbenzene is an aromatic hydrocarbon used
in the industry as antiknock agent in fuels, as paint thin-
ner and adhesive solvent, among other uses. It can be
used as a drug mainly by teenagers due to its low cost
and wide availability.64 It is inhaled and easily absorbed by
the lungs from which it spreads rapidly to nearby tissues
with a high lipid concentration such as the central nervous
system.
Acute effects include behavioral changes, euphoria,
headache and ataxia; during this stage, there are usually
no identifiable structural alterations.8 Chronic consumption
causes irreversible lesions due to cumulative toxic effect,
and it can occur clinically with cerebellar dysfunction,
psychiatric diseases, spasticity, cognitive changes and
secondary Parkinsonism. In the MRI it is possible to identify
white matter lesions that begin in the periventricular region
and in time, spread to U fibers; the degree of damage is
associated with the seriousness of the neurological deficits
and cognitive impairment.64,65 It causes white and gray
matter atrophy without any specific distribution patterns.
In morphometric studies it has been confirmed that there is
gray matter loss in multiple locations of the brain cortex,
while volume loss in frontal and parietal cortex is associ-
ated with greater cognitive deficits.64 Using spectroscopic
techniques low N-acetylaspartate levels in the white matter
have been identified as caused by neuroaxonal integrity
impairment though this finding is of non-specific nature.66
In SPECT studies, perfusion alteration in the frontal,
parietal and temporal lobe cortex has been identified; also
hypoperfusion in the prefrontal region is associated with
greater behavioral alteration.67
Conclusion
Drugs are a serious social health issue, because they have
important short and long-term repercussions on the CNS.
The main acute complications are ischemia and hemor-
rhages whose early detection and urgent treatment is
especially important for the prognosis of the patient. At
times image findings are specific like the spectroscopic pro-
file of leukoencephalopathy due to heroin consumption,
T1 hyperintensity in chronic hepatic encephalopathy or
contrast uptake in mammillary bodies in Wernicke’s ence-
phalopathy. However in most cases diagnosis comes from
integrating the images with the clinical context, such as
the posterior reversible encephalopathy syndrome in young
28
patients without other cardiovascular risk factors or pallidus
necrosis in heroin or MDMA addicts (Appendix B Table S2
online). Functional modalities such as PET and MRI perfusion
play an ever more important role by showing the deleterious
effects that have spatial specificity in some substances.
Ethical disclosure
Protection of people and animals. The authors declare that
no experiments with human beings or animals have been
performed while conducting this investigation.
Confidentiality of data. The authors confirm that they have
followed their center protocol on the publication of data
from patients.
Right to privacy and informed consent. The authors con-
firm that in this article there are no data from patients.
Authorship contribution
1. Manager of the integrity of the study: AMF and MM.
2. Study idea: AMF and MM.
3. Study design: AMF and MM.
4. Data mining: AMF and MM.
5. Data analysis and interpretation: N/A.
6. Statistical analysis: N/A.
7. Reference: AMF and MM.
8. Writing: AMF and MM.
9. Critical review of the manuscript with intellectually rel-
evant remarks: AMF and MM.
10. Approval of final version: AMF and MM.
Conflicts of interests
The authors declare no conflict of interests associated with
this article whatsoever.
Appendix A. Supplementary data
Supplementary data associated with this article can be
found, in the online version, at http://dx.doi.org/10.1016/
j.rxeng.2016.12.003.
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