Key-words:
Cocaine - decompressive craniectomy - ischemic stroke - Saudi Arabia
Introduction
Illicit drugs are illegally produced, trafficked, and/or consumed. These drugs are
under international control. According to the United Nations statistics, around 200
million people use illegal drugs yearly around the world, with 25 million being classed
as problem users. This number represents approximately 4.8% of the world's population
aged 15–64 years.[[1]] Intake of illicit drugs has led to major health and social issues due to its increased
consumption among young people.[[2]] The major causes of death in drug users are overdose, suicide, acquired immunodeficiency
syndrome, and violence.[[3]] It has been associated with several cardiovascular complications, including myocardial
infarction, arrhythmias, endocarditis, dilated cardiomyopathy, major vessel rupture
and dissection, including the aorta, sudden cardiac death, arterial thrombosis, and
kidney or spleen infarction. Cerebrovascular disorders, both hemorrhagic and ischemic
stroke, also contribute to the disability, morbidity, and mortality associated with
illicit drug use.[[4]] Cocaine-induced ischemic stroke has multiple underlying pathophysiological mechanisms
that result in various complex neurological presentations.[[5]] In this article, we describe a case of a young man who had a massive ischemic multi-territorial
stroke who was managed successfully with decompressive craniectomy with a favorable
outcome. We also describe the mechanisms of the detrimental effects of cocaine and
identify the mechanisms of stroke associated with cocaine abuse.
Case Report
A 32-year-old soldier was found unconscious in his military campus while performing
night duties. It was estimated that the last time being well was more than 10 h. On
arrival to the emergency department, he had dense right hemiplegia with multiple facial
traumatic lacerations but no signs of a base of skull fracture, including the battle
sign or raccoon eye sign. His blood pressure was high at 180/100 with normal heart
and respiratory rates. His breathing pattern was normal with normal pulse oximetry.
His Glasgow coma scale was 9/15, and his pupils were equal and reactive. His power
was 0/5 on the right side with the right Babinski sign. His modified Rankin scale
score was 5. Systemic examination was normal, including skin, bones, cardiovascular
system, and abdomen. On questioning the emergency medical services personnel regarding
the presence of illegal drugs, they informed us of the presence of alcohol bottles
and cocaine powder on the scene. The family admitted illicit drug abuse, but he was
never admitted to a hospital for any medical reason.
Initial blood work, including complete blood count, renal function test, electrolytes,
glucose, liver function test, thyroid function test, and HIV were all unremarkable.
An urgent computed tomography (CT) scan of the brain showed a massive ischemic stroke
in the distribution of the left-sided middle and posterior cerebral arteries with
right-sided midline shift and impending herniation [[Figure 1]]. CT angiography of the cerebral circulation showed a patent arterial system. CT
of the neck, chest, abdomen, and pelvis was unremarkable. Transthoracic echocardiography
was reported as normal with no systolic or diastolic dysfunction and no intracardiac
thrombus.
Figure 1: Computed tomography scan of the brain showing a massive ischemic stroke in the distribution
of the left-sided middle and posterior cerebral arteries with right-sided midline
shift and impending herniation
The patient was taken to the intensive care unit, where he was intubated, sedated,
and mechanically ventilated. Immediate decompressive craniectomy was done to save
the patient's life, which was uneventful [[Figure 2]]. After a stormy course in the intensive care unit, the patient improved in all
aspects, including higher mental functions, alertness, awareness, and cooperation
with the medical staff. He was extubated and sent for an aggressive physiotherapy
program. He was discharged home on secondary preventive measures, including aspirin
and statins after 2 months of hospital stay. At discharge, his modified Rankin scale
score improved to 4.
Figure 2: Computed tomography scan of the brain after decompressive craniectomy showing evolutionary
changes of the massive left-hemispheric infarction with persistent rightwards midline
shift and left uncal herniation
He was admitted electively 3 months later for cranioplasty using an autologous bone,
which was performed successfully. A follow-up CT scan showed remarkable improvement
of the midline shift and herniation with residual ischemic infarction in the territory
of middle and posterior cerebral arteries on the left side [[Figure 3]].
Figure 3: Computed tomography scan of the brain 3 months later showing remarkable improvement
of the midline shift and herniation with residual ischemic infarction in the territory
of middle and posterior cerebral arteries on the left side
Discussion
Cocaine is the second most frequently used illicit drug in both the United States
of America and the United Kingdom (after cannabis) with approximately 5%–10% of the
American population used illicit cocaine. It is used by around 14 million people around
the world which represents 0.3% of the global population between 15 and 64 years old.[[6]] It is originally extracted from an Erythroxylon coca bush that grows primarily
in South America, and coca leaves have been chewed by South American Indians for several
centuries.[[7]] It is consumed in two chemical forms: cocaine hydrochloride (a water-soluble crystal
powder that is absorbed by mucous membranes) and cocaine alkaloid (produced by dissolving
cocaine hydrochloride in water, ammonia, and ether to obtain a “free base” or in water
and baking soda to produce “crack"). Both forms can be smoked. The alkaloidal form
of cocaine known as crack was introduced in 1983 which has led to a major surge in
its use, followed by an increase in the incidence of medical, neurologic, and psychiatric
complications.[[8]] Addiction to stimulants such as cocaine is a chronic disorder that is difficult
to treat with exceedingly high rates of relapse that can happen following months or
even years of abstinence.[[9]]
The increasing use of crack cocaine with a subsequent rise in the complications rate
has been reflected in the medical literature. The earliest isolated case reports were
replaced by a series of accounts of systemic complications of crack cocaine. These
accounts were followed by publications describing specific complications such as cardiac,
neurological complications, and rhabdomyolysis.[[10]] Cocaine toxicity may affect almost every organ system in the body, with the most
substantial changes seen in the cardiovascular system, liver, and brain. Cocaine appears
to be hepatotoxic in both humans and animals, and this hepatotoxicity is enhanced
by concomitant drug abuse, including alcohol, barbiturates, and cocaine adulterants.
Cocaine abuse may lead to several pulmonary disorders, including barotrauma, pneumonia,
pulmonary congestion, edema, hypertrophy of pulmonary arteries, and pulmonary necrosis.[[7]]
Neurological complications related to cocaine use include neurovascular events (cerebral
or spinal), seizures, hyperpyrexia, headache, movement disorders, and peripheral neuropathy.[[11]] Cocaine is associated with 14 times more probability of developing a stroke than
that noncocaine-using subjects of the same age recruited from the same patient pool.
Ischemic strokes represent between 25% and 60% of cocaine-induced strokes with about
80% of the infarcts occur in the regional distribution of the middle cerebral artery.
They typically occur in young adults without preexisting vascular malformations or
other risk factors for strokes.[[12]] In 1977, the first report of a cocaine-related stroke was published by Brust and
Richter, which was accepted with skepticism.[[13]] A few years later, several isolated case reports were published which suggested
that this was an extremely rare complication. However, since 1985 the incidence of
cocaine-related cerebrovascular complications has reached epidemic proportions.[[14]]
The main mechanism of cocaine action is explained by its capability of blocking sodium
channels leading to the inhibition of the reuptake of norepinephrine, 5-hydroxytryptamine,
and dopamine, also known as a triple reuptake inhibitor. This may result in massive
sympathetic overactivity and catecholamine release, leading to tachycardia, arrhythmia,
profound hypertension, intense vasoconstriction, acute coronary syndrome, and even
sudden cardiac death. This mechanism may trigger transient cardiac ischemia resulting
in partial or global ventricular wall abnormality far better than any other stimulant
drug due to its unique lipophilic efficiency.[[15]] Cocaine may cause platelet activation, a-granule release, and platelet containing
microaggregate formation producing a prothrombogenic state and predisposition to ischemic
events. This mechanism is likely responsible for both middle and posterior cerebral
artery strokes in our patient, given his long-standing cocaine use.[[16]] Cocaine also induces apoptosis in the cerebral vascular smooth muscles, leading
to ischemia and activation of endothelin-1-dependant receptors and subsequent cerebral
vasoconstriction.[[17]] Cocaine can cross the blood–brain barrier faster leading to cerebral vasculitis,
accelerated atherosclerosis, cocaine-induced cardiomyopathy, intracranial bleeding,
and ischemic stroke.[[18]]
Alcohol use (both recent and long-term heavy drinking) is an important cause of ischemic
stroke in the young. The main mechanisms of alcohol association with stroke are cardiac
arrhythmias as well as effects on hemostasis, fibrinolysis, and blood clotting.[[19]] Combining alcohol with cocaine leads to the formation of a pharmacologically active
substance in the body known as cocaethylene. This substance is stronger than either
alcohol or cocaine separately. Cocaethylene raises the risk of stroke due to its longer
plasma elimination half-life.[[20]],[[21]] In our patient, using alcohol along with cocaine may have triggered the stroke.
The treatment of confirmed acute thrombotic or thromboembolic stroke induced by cocaine
abuse is to establish reperfusion thrombolytic therapy rapidly within the standard
window of time.[[22]] Computerized tomography or magnetic resonance imaging (MRI) diffusion and perfusion-weighted
imaging should be obtained prior to such a decision to assess the ischemic penumbra
and identify threatened but salvageable tissue that might benefit from thrombolysis
or thrombectomy.[[23]] In two published reports, intra-arterial thrombolysis and aspiration were successfully
performed in patients with basilar artery thrombosis induced by cocaine. In both case
reports, the patients were young, had no reported significant medical history, and
were not comatose at the initial presentation. In addition, there was no early hemorrhagic
conversion seen in the brain images. In such patients, intra-arterial thrombolysis
with or without mechanical thrombectomy can be considered as a therapeutic option.[[24]],[[25]] In our case, due to the late presentation, further endovascular interventions were
not offered.
Conclusion
Cocaine abuse is a significant health hazard with multiple cardiac and neurological
complications. Several pathophysiological mechanisms for cocaine-induced ischemic
stroke have been implicated, including triple reuptake inhibitor with subsequent massive
sympathetic overactivity. Cocaine use should be routinely suspected in young patients
presenting with ischemic stroke, and a urine toxicology screen should be part of the
initial workup for such patients. Brain MRI is an essential neuroimaging modality,
which is very helpful in confirming the ischemic insult and planning management. Early
diagnosis and treatment are crucial due to potential reversibility and reduction of
the size of infarcted tissue. In addition, multidisciplinary care, including a vascular
neurosurgeon should be implicated.
