The Addicted Brain: Imaging Neurological Complications of Recreational Drug Abuse 19

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Radiología. 2017;59(1):17---30

www.elsevier.es/rx

UPDATE IN RADIOLOGY

The addicted brain: Imaging neurological complications

ଝ

of recreational drug abuse

∗

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.

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-

ciones neurológicas agudas y crónicas, debido al avance en el conocimiento de la enfermedad

Imagen funcional;

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

ଝ

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: montoyaﬁ[email protected] (A. Montoya-Filardi).

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18 A. Montoya-Filardi, M. Mazón

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

Hemorragia; implicación del radiólogo pueda resultar fundamental en la atención de estos pacientes. La

Leucoencefalopatía; neuroimagen permite detectar alteraciones precoces y plantear el diagnóstico etiológico ante

Atroﬁa; patrones de afectación especíﬁcos. Nuestro objetivo es describir el patrón de consumo y el

Marchiafava---Bignami 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.

Introduction

The main cerebral complications derived from cocaine

abuse are vascular ones, especially subarachnoid hem-

Human kind has always wanted to experience new sensa-

orrhages and intraparenchymatous hemorrhages; overall

tions, to reach different states of consciousness and, on

hemorrhagic events are twice as frequent as ischemic

occasion, to mask reality. The substances used with this 1,7,8

infarctions. Nevertheless, the form of the drug and the

purpose have targeted, whether intentionally or not, the

route of absorption inﬂuence on the type of adverse event.

central nervous system (CNS). Consumption patterns have

When cocaine is smoked in the form of crack the incidence

changed and conditions of use have improved, but they all

of hemorrhagic events is greater, while there are no signiﬁ-

have deleterious effects that we can see and quantify.

cant differences between ischemic and hemorrhagic events

Each substance has multiple forms of presentation which 9,10

when the drug is sniffed.

are modiﬁed all the time, the absorption pathways of the

The physiopathological mechanisms involved in the pro-

body are limited and they cause complications that over-

duction of ischemic cerebrovascular accidents are multiple

lap one another. Neuro-imaging ﬁndings frequently pose the

and synergic, but vasoconstriction or vasospasm stand out

possibility of consumption, and even in view of character- 2,11

among them (Table 1). This phenomenon can cause

istic patterns, it would be possible to suggest the speciﬁc

endothelial damage consisting of disruption of the tunica

type of drug. The role of the radiologist, therefore, is ever 12

media and arteriolar ﬁbrosis, among other alterations.

more relevant both ﬁnding urgent conditions and visualizing

However, the signiﬁcant vasculitis component stands out,

chronic effects.

conﬁrmed by the existence of focal stenoses of the vascu-

Our goal is to describe the consumption pattern and the

lar lumen and enhancement of vessel walls in angiographic

physiopathological mechanisms of the drugs that have the studies.5,13

most neurological repercussion (cocaine, amphetamines,

Ischemic infarctions commonly affect the territories

heroin, alcohol, cannabis and toluene), as well as to illus-

of mid and posterior cerebral arteries (Fig. 1), and the

trate the acute and chronic cerebral complications through

border territories, the internal capsule and the hippocam-

conventional and functional image modalities (positron 1,5,9

pus, without a speciﬁc disorder pattern. Mesencephalic

emission tomography [PET], single photon emission com-

infarction has been associated with the simultaneous use of

puted tomography [SPECT] and perfusion by magnetic 14

cocaine and amphetamines. Since it does not show a char-

resonance [MRI]).

acteristic distribution, concomitant ﬁndings are specially

relevant, such as perforation of the nasal septum, acceler-

Cocaine ated atherosclerosis in young people without cardiovascular

risk factors (Fig. 2) and generalized vasospasm.

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

Table 1 Mechanisms implied in the production of cocaine-

of presentation: hydrochloride (with the appearance of a

induced ischemic cerebrovascular accidents.

ﬁne powder) and alkaloid (also known as crack). The most

popular route of administration is intranasal, which reaches Ischemic mechanism Biochemical phenomenon

concentrations in the CNS in 3 --- 5 min. The main action 1,4

Vasoconstriction Calcium channel blockade

of cocaine is summarized in the sympathomimetic effect 2,5

Increase of serotonin levels

1 --- 4

due to the blockage of catecholamine reuptake. It also

Prothrombotic Increase of thromboxane levels

blocks the reuptake of serotonin and dopamine transmitters, 5,9,10

phenomena and platelet aggregation

increasing their extracellular concentrations, especially in

III Procoagulant diathesis Reduction of antithrombin

2,5,6

the accumbens nucleus. 7,8

and protein C

Addiction caused by cocaine is due to its rapid action

Atherosclerosis Nitric oxide inhibition in the

mechanism, since its effect is almost immediate after endothelium11

administration. A feeling of euphoria or high is experienced

Vasculitis Impurity-activated paracrine

after its consumption mediated mainly by the occupation of 5,9,13

and immune mechanisms

1,3---5

dopamine receptors called DA-D2.

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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).

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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 non-users, which conditions greater neurological deﬁcits.

complications show underlying vascular condition such as Hemorrhagic transformations of the ischemic areas is not

aneurysms and vascular malformations. The greater preva- uncommon due to damage to hematoencephalic barrier and

7,9

lence of aneurysms is explained by the maintained increase increase of arterial pressure.

1,2,15

of blood pressure. The mechanism involved in aneuris- Chronic addicts characteristically show structural atro-

mal rupture and arteriovenous malformations is high systolic phy in the frontal lobes and to a lesser extent, in

4,5 8,9

peak and increase of heart rate after acute consumptions the temporal ones, where reduction of metabolic

(Fig. 3). The combined abuse of cocaine and ethanol is not activity has been conﬁrmed in PET examinations with 18-

uncommon, which increases synergically the odds of suffer- ﬂuorodeoxyglucose. Perfusion studies with SPECT with

ing subarachnoid hemorrhages. hexamethyl propylene or amino oxyme marked with

The intraparenchymatous hematoma is usually lobar and metastable technetium 99 (99mTc-HMPAO) have shown a

subcortical while there is greater incidence of bleeding in generalized reduction of 30% in global cerebral blood ﬂow

5,16

the encephalon. Hematomas are larger and they tend adding a speciﬁc reduction of the relative cerebral blood

to spread themselves to the ventricles more easily than in ﬂow in the prefrontal cortex, anterior cingulate gyrus, the

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The addicted brain: Imaging neurological complications of recreational drug abuse 21

thalami, the basal ganglia, the occipital cortex and the or pills. It causes a rapid feeling of euphoria and an increased

cerebellum. sensory perception this is why it is considered both stimulant

8,25

In addition to the withdrawal syndrome, many users and hallucinogenic.

experience an intense crave to consume after it has gone Amphetamines, as a whole, increase the synaptic con-

(the so-called craving stage), which can be triggered by centrations of biological amines (dopamine, noradrenalin

multiple stimuli. In this complex stage, there is a selec- and serotonin/5-hydroxytryptamine); the main and most

tive activation of the limbic system in perfusion studies, characteristic action of MDMA is the release of 5-

19,20 8,11,25

hypermetabolism in the orbitofrontal cortex and even hydroxytryptamine. This neurotransmitter is the amine

21 5

involvement of the mu opioid system. Functional studies with the greatest vasoconstrictor effect in the brain.

based on oxygen consumption (BOLD sequence) in active Although the biochemical mechanism of amphetamines

users conﬁrm an increase of activity in the craving stage and causes long-term ischemia, the most common urgent

dependence located in the limbic, paralimbic regions, the complications are hemorrhages due to blood pressure

accumbens nucleus, the frontal and inferior frontal orbital increase. Just as it happens with cocaine consumption,

circumvolutions and the anterior cingulum. This activation blood pressure increases after consumption conditions

has also been shown during the craving for consumption greater risk of rupture of arteriovenous malformations and

23 9,26

when videos showing the drug were played. However, preexisting aneurysms.

after administration of the substance, these regions are Vasoconstriction in cerebral microcirculation ultimately

22 8,9,26

deactivated. causes necrosis of irrigated tissue. The areas that are

more commonly affected by this ischemia are the globus pal-

lidus (as it happens with heroin) and the occipital cortex,

Amphetamines and derivatives where the largest concentration of 5-hydroxytryptamine

8,9

receptors are located (called 5HT 2A) ; in fact, the most

common ﬁnding in autopsies is necrosis of the globus

Amphetamine was synthesized for the ﬁrst time in

pallidus (Appendix B Fig. S2 online). This spatial speci-

1887 and it was the ﬁrst substance of a group that

ﬁcity explains why it is in these areas where structural and

shares properties, called the same way as a whole.

functional complications develop.

Later there appeared methamphetamine and MDMA (3,4-

Another complication that stems from blood pressure

methylenedioxymetanphetamine), commonly known as

increase is posterior reversible encephalopathy syndrome

‘‘ecstasy’’ or ‘‘crystal’’. There is rigorous legal control of

(Fig. 4). This is an unspeciﬁc disorder of cerebrovascular

amphetamine derivatives in research studies and for the

self-regulation showing a preference for posterior circu-

treatment of disease (obesity and hyperactivity). The con-

lation and borderline cortical areas. On the computed

sumption proﬁle of MDMA is associated with night-time

tomography (CT), ﬁndings can be subtle, identifying hypo-

leisure; it is the second most consumed illegal drug among

24 density non-conﬂuent cortical---subcortical, bilateral areas

young people after cannabis. The most common route of

often located in the posterior parietal occipital lobes.

administration is orally, in the form of powder or ‘‘crystal’’

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.

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22 A. Montoya-Filardi, M. Mazón

The MRI is more sensitive for its diagnosis and ﬁndings Ischemia is the most common neurovascular complication

8,11

are detected early, showing high signal intensity in T2- of the compounds derived from opioids and morphine.

weighted/FLAIR sequences. The physiopathological mechanisms involved are vasospasms

When it comes to long-term effects, selective atrophy in due to smooth muscle contraction, vasculitis phenomena

37---39

the occipital and frontal cortex, the left temporal lobe and and embolisms due to additives. Borderline vascular ter-

the brainstem has been conﬁrmed compared to users that ritories are the most vulnerable ones, but the anatomical

abused other substances exclusively or jointly (polyabuse). structure that is most commonly affected is the globus pal-

Methamphetamines can cause gray matter volume loss which lidus (up to 5---10% in chronic users). Chronic ischemia is

25,27,28

can range from generalized to unilobar. However, common which is shown on the MRI as conﬂuent hyperinten-

an increase in the volume of the striatum has been con- sities in the periventricular and subcortical white matter.

ﬁrmed (caudate and putamen) in adult methamphetamine This ﬁnding gains special importance if patients are young

11,35

consumers for over two years. Volume increase is due to and without any other risk factors.

mechanisms of initial response to neurotoxicity --- above all A speciﬁc complication of the heroin addict who uses

swelling. This reaction evolves subsequently to atrophy if the inhaled route is a phenomenon known as chasing the

25,29

the neurotoxic dose continues to increase. In children dragon. This denomination comes from the way the smoke

exposed to methamphetamines in utero there is striatum is inhaled when the heroin is heated over an open ﬂame.

volume loss initially, since there is no such compensation to It became popular as an alternative to IV administration

25,30

dopaminergic damage. to avoid HIV contagion. The neurological complication con-

With PET, it is possible to observe selective dam- sists in a leukoencephalopathy with edema. It is probably

age in serotoninergic neurons and a reduction of its due to a mechanism of mitochondrial toxicity, triggered

31,32

transmitters. When it comes to SPECT-measured per- by impurities that are activated when heating aluminum

fusion we have been able to conﬁrm a decrease of the foil. These manifestations can occur with cerebellar and

relative cerebral blood ﬂow in the visual cortex, the extrapyramidal signs, and in the most serious cases pseudo

caudate, the superior parietal lobe and the dorsolateral bulbar manifestations, spasms, hypotonic muteness or even

region of the frontal lobe, associated with MDMA-induced death occur. Anatomopathologically, a spongiform degen-

31,33

vasoconstriction. Keeping with it, we have been able to eration of the corticospinal tracts and of the cerebral and

8,41

detect reduction in relative cerebral blood volume of such cerebellar white matter has been reported. T2/FLAIR MRI

dorsolateral region of the frontal cortex through MRIs as the sequences show bilateral symmetric hypersignal of white

ﬁrst functional manifestation after the ﬁrst contacts with matter in these locations. Cerebellar disorders and of the

MDMA in young subjects. posterior limb of the internal capsule --- not affecting the

anterior limb, is the most characteristic sign. These ﬁnd-

ings are not exclusive to heroin-induced leukopathy and they

Heroin can be secondary other substance abuse. Spectroscopy ﬁnd-

ings complement diagnosis and increase their speciﬁcity;

Heroin or diacetylmorphine is the most widely consumed they show an abnormal descent of the N-acetylaspartate

illegal compound within the opioid group. It was commer- peak, an increase of lactate and myoinositol, and stability

cialized for the ﬁrst time in 1898 as an analgesic substitute of lipid peaks (Fig. 5). Resolution of the clinical disorder

to morphine, but it was withdrawn after the physical and has been described when heroin use is interrupted though

psychological dependence that it caused was conﬁrmed. image ﬁndings can persist.

Its appearance is that of a white, ﬁne crystalline powder, In addition to the complications derived from the sub-

although it can vary. There are three main types: number stance itself, both the impurities (lipophilic substances)

two or freebase; number three, known as brown sugar due used in the mixture and the unsterile conditions in the IV

to its earthy aspect; and number four or Thai variety of a 90% administration make infections be relatively common and

8,11,41

purity. The IV is the most effective, ﬁlling route of adminis- especially important. Half the users develop endocardi-

tration with respect to its effect, and it was the most widely tis, occlusion of small vessels due to septic emboli and

used until AIDS appeared. Today, the inhaled and smoked formation of abscesses. In the MRI, abscesses are shown

routes of administration are more widely used. as rounded lesions that are enhanced in a ring shape after

The mechanism of action of heroin is mediated by the the administration of contrast, they show perilesional vaso-

activation of three types of receptors: mu, kappa and delta. genic edema and its purulent content restricts diffusion

Mu receptors are responsible for the feeling of euphoria and (Fig. 6). The organism involved in most cases is Staphylo-

positive reinforcement, in addition to analgesia, respiratory coccus aureus, which enters the blood stream from the skin

35,36 44

depression and miosis. Kappa and delta receptors con- through the needle.

tribute to the analgesic effect, the feeling of dysphoria and The chronic consumption of heroin leads to encephalic

35,36

the psychomimetic effect. atrophy, hypometabolism and hypoperfusion. Gray-matter

A sharp, positive feeling after the ﬁrst contacts (hon- loss, conﬁrmed through volumetry on the MRI, prevails in

eymoon) occurs initially. When the state of intoxication the prefrontal bilateral cortex, the temporal lobes and the

advances, the effects fade. The degree of tolerance turns insulae, with a correlation between the duration of use and

the drug into a means to avoid withdrawal syndrome and the degree of atrophy suggestive of a cumulative effect.

less and less often into a source of pleasure. White matter has been assessed in image studies through

Ischemic conditions, toxic leukoencephalopathies and diffusion tensor imaging, in which it has been possible to

atrophies are among the most common complications asso- observe a reduction in the fractional anisotropy translating

ciated with heroin abuse. a disruption of ﬁbers in bilateral frontal regions, the right

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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. Studies in chronic There are three main neurological damage mechanisms:

addicts have conﬁrmed a global decrease of perfusion and direct toxicity, derivative-mediated damage (methanol

31,49

ometabolism and a greater reduction of both parameters and acetaldehyde) and effects secondary to cirrhosis

in the frontal and temporal lobes (Fig. 7). When it comes to and nutritional deﬁcits. There are multiple direct dam-

acute effects, it has been conﬁrmed that there is a drop in age mechanisms proposed, but the common outcome is

perfusion quantiﬁed through ASL (arterial spin labeling) in greater susceptibility of N-methyl- -aspartate receptors of

the anterior left cingulate cortex, the left prefrontal cortex excitement and glutamate cytotoxicity, the so-called upre-

and the insulae. gulation.

Wernicke’s encephalopathy is one of the main

complications of chronic alcoholics due to deﬁcit of thi-

Alcohol amine coenzyme (vitamin B1). Wernicke’s encephalopathy

causes the classic triad of ophthalmoplegia, confusion and

gait disorder though the complete clinical manifestations

Alcohol is a socially accepted legal drug. Excessive, chronic

only occur in one third of the patients. Delayed diagnosis

consumption of alcohol is associated with an increase of

and treatment can lead to Korsakoff’s psychosis, charac-

morbimortality and it reduces life expectancy in up to 15

terized by memory alterations and confabulation. Osmotic

years. Based on its process of manufacturing, alcoholic

changes due to thiamine reduction cause intracellular and

beverages are divided into fermented and distilled. The

extracellular edema, especially in areas near the cere-

main component of alcohol is ethanol, a CNS depressor that

brospinal ﬂuid, where the hematoencephalic barrier is more

progressively numbs brain and sensory functions. It is mis-

patent. Lesions are commonly located around the third ven-

takenly confused with a stimulant because at the onset of

tricle and the lateral ventricles, the thalamus dorsomedial

intoxication there is lack of behavioral inhibition.

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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.

51,54

pulvinar nuclei, the mammillary bodies, and the pineal and demyelination and necrosis. A toxic agent from red wine

periaqueductal region. In the most serious cases, the deep has been identiﬁed that, in conjunction with vitamin deﬁ-

white matter and even the cortex can also be affected. ciency, can be the cause of these manifestations. The

In the affected areas, the MRI will show hyperintensity disorder begins in the trunk and it can spread to the knee and

8,11 51,54

in T2/FLAIR, and after the administration of contrast even the splenius. The corpus callosum necrosis occurs

they can be enhanced due to rupture of hematoencephalic in three stages characteristically (layer necrosis), typical

barrier, and intense enhancement of mammillary bod- of this disease. There are two subtypes: A, where there is

ies is pathognomonic of this disorder in acute stages complete damage of the corpus callosum showing greater

51---53

and even in the absence of T2 hyperintensity impairment of consciousness and leading to worse progno-

(Fig. 8). sis; and B, where damage of the corpus callosum is partial

Another manifestation of chronic alcohol abuse is showing less impairment of consciousness and more favor-

Marchiafava---Bignami disease, consisting of corpus callosum able evolution. MRIs are especially important due to the fact

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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 damage of the vermis superior. Concomitant use of alcohol

T2/FLAIR without mass effect in the central region of the with other drugs, in particular with cocaine, contributes to

corpus callosum is the common presentation (Fig. 9); it can greater white matter loss, due to the formation of a long-

be enhanced peripherally after the administration of con- lasting vasoactive metabolite, cocaethylene, resulting from

55 11

trast on the acute stage. The white matter in the brain the co-administration of both substances.

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 Cannabis

laminar sclerosis consists of gliosis of the third cortical layer

56 58

in the frontal and lateral regions. In PET studies with FDG Cannabis is the most consumed illegal drug worldwide. It

it has been possible to conﬁrm a metabolic reduction in is obtained from Cannabis sativa, a dioecious herb. Its main

the cortex frontal of temporo-parieto-occipital association psychoactive component is a lipophilic substance called

due to the disruption of commissural ﬁbers that alter this delta-9-tetrahydrocannabinol. The products obtained from

51,57

association network. cannabis are marihuana (prepared with dry leaves), hashish

Chronic hepatic encephalopathy is due to and inade- (derived from its resin) and hashish oil (obtained from dis-

quate cleansing of nitrogenated compounds and other toxins tilling organic solvents).

that accumulate in the brain parenchyma. Image ﬁndings All the parts of the plant contain delta-9-

of this disease are practically undetectable through CT and tetrahydrocannabinol. The most commonly used form

MRI T2-weighted sequences. In the T1-weighted sequences of cannabis abuse is smoked marihuana. Its resin is used

there is bilateral and symmetrical hyperintensity compati- in food for oral consumption; this form of administration

ble with manganese deposits, located in the base ganglia causes a great amount of intoxications since the user does

(in particular in the globus pallidus), the hypothalamus, the not control the time elapsed between ingestion and effects.

mesencephalon and the adenohypophysis (Appendix B Fig. Chronic consumption increases the risk of schizophrenia

S1 online). MRI spectroscopy study obtained with short echo and behavioral changes.

time is characteristic in patients with chronic hepatic ence- After its consumption a feeling of wellbeing is obtained

phalopathy, who show a signiﬁcant reduction of myoinositol due to the activation of cannabinoid receptors CB1, present

and choline, and an increase of glutamine/glutamate in the black matter, the hippocampus, the limbic cortex and 51 8,9

peaks. the cerebellum.

Lastly, chronic alcoholism is associated with neuronal Its wide use and polyconsumption are factors that make

loss and atrophy, especially of the frontal superior and it difﬁcult to establish a direct connection between cannabis

9,58

motor cortex, and with white matter, bridge, thalamus, and cerebrovascular disease. It causes orthostatic

mammillary body and cerebellum volume loss, and greater hypotension, which in people with little cerebral blood

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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.

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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 causes irreversible lesions due to cumulative toxic effect,

main mechanism of ischemic cerebrovascular accidents and it can occur clinically with cerebellar dysfunction,

(Fig. 10). In addition to high blood pressure that acts as a psychiatric diseases, spasticity, cognitive changes and

trigger, there are other predisposing vascular alterations; secondary Parkinsonism. In the MRI it is possible to identify

in this sense, the presence of intracranial stenosis has been white matter lesions that begin in the periventricular region

conﬁrmed in 31% of cannabis consumers who have developed and in time, spread to U ﬁbers; the degree of damage is

ischemic cerebrovascular accidents. Vasospasms, vasculi- associated with the seriousness of the neurological deﬁcits

64,65

tis, development of arrhythmias and high concentrations and cognitive impairment. It causes white and gray

of carboxyhemoglobin are other factors that predispose matter atrophy without any speciﬁc distribution patterns.

8,9,61,62

to adverse cerebrovascular events. The location of In morphometric studies it has been conﬁrmed that there is

these ischemic infarctions is not speciﬁc: basal ganglia gray matter loss in multiple locations of the brain cortex,

predominate, as well as periventricular white matter, while volume loss in frontal and parietal cortex is associ-

the cerebellum and the temporal, parietal and occipital ated with greater cognitive deﬁcits. Using spectroscopic

lobes. techniques low N-acetylaspartate levels in the white matter

Perfusion studies through PET and SPECT conﬁrm an have been identiﬁed as caused by neuroaxonal integrity

increase of relative cerebral blood flow with acute impairment though this finding is of non-specific nature.

consumption. However, there is reduction of generalized In SPECT studies, perfusion alteration in the frontal,

relative cerebral blood ﬂow among chronic users that can be parietal and temporal lobe cortex has been identiﬁed; also

31,58

reverted with abstinence. Glucose metabolism in spo- hypoperfusion in the prefrontal region is associated with

radic users is usually diminished except for the cerebellum, greater behavioral alteration.

probably due to the large number of cannabinoid receptors

in this area. Conclusion

Toluene

Drugs are a serious social health issue, because they have

Toluene or methylbenzene is an aromatic hydrocarbon used important short and long-term repercussions on the CNS.

in the industry as antiknock agent in fuels, as paint thin- The main acute complications are ischemia and hemor-

ner and adhesive solvent, among other uses. It can be rhages whose early detection and urgent treatment is

used as a drug mainly by teenagers due to its low cost especially important for the prognosis of the patient. At

and wide availability. It is inhaled and easily absorbed by times image ﬁndings are speciﬁc like the spectroscopic pro-

the lungs from which it spreads rapidly to nearby tissues ﬁle of leukoencephalopathy due to heroin consumption,

with a high lipid concentration such as the central nervous T1 hyperintensity in chronic hepatic encephalopathy or

system. contrast uptake in mammillary bodies in Wernicke’s ence-

Acute effects include behavioral changes, euphoria, phalopathy. However in most cases diagnosis comes from

headache and ataxia; during this stage, there are usually integrating the images with the clinical context, such as

no identiﬁable structural alterations. Chronic consumption the posterior reversible encephalopathy syndrome in young

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28 A. Montoya-Filardi, M. Mazón

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