Acquired Brain Injury Secondary to Substance Use Disorder
BENJAMIN A. PYYKKONEN
The Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5; American Psychiatric Association [APA], 2013) identifies 10 separate classes of substances related to significant substance abuse concerns (p. 481). Each of these separate classes of substances has unique cognitive and behavioral profiles and sequelae. Of the 10 separate substance classes, four have more clearly documented patterns of pathophysiological sequelae and demonstrated impact on cognitive functioning. These substance categories include alcohol, inhalants, sedatives/hypnotics/anxiolytics, and stimulants. The following chapter discusses the specific impact of each of these separate classes of drugs and related acquired brain injury on cognitive and emotional functioning. The remaining six substance clusters include caffeine, cannabis, opioids, hallucinogens, tobacco, and other or unknown substances. Although these classes present with clear short-term cognitive, behavioral, and emotional impact, their cognitive impact is relatively transient in nature in comparison to the permanence of the impact associated with the other substance classes just noted. As such, the current review specifically examines only the impact of these four substance classes with clearly demonstrated cognitive profiles associated with acquired brain injury.
In addition, substance use and related inebriation puts one at remarkably increased risk for acquired brain injury secondary to head injury. Although in many cases this type of injury may be closely related to substance abuse, this manner of acquired head injury is not discussed here, but will be discussed in other chapters of this text (see Chapters 1 and 2).
The profound cost of substance use disorders is immense and has been documented to be in excess of several hundreds of billions of dollars annually (Kalechstein & van Gorp, 2007). Kalechstein and van Gorp (2007) also report a remarkably large number of admissions for substance misuse, with more than 1.7 million substance treatment-related admissions in 2003. These admissions likely reflect more acute intervention and not the chronic impact of substance misuse, and therefore underrepresent the actual impact. Although significant variation exists in the proportions of substance misuse from specific substance clusters, substance misuse is considerable across all geographic, ethnic, racial, financial, and age categories.
As already noted, substance use disorders, as described by the DSM-5, pertain to 10 distinct clusters of substance, in which there is problematic use characterized by four criteria (DSM-5, p. 485). Whereas previous classification systems emphasized tolerance and withdrawal symptoms, the current system emphasizes problematic use whether there is related dependence or not. The DSM-5 criteria include impaired control (use exceeding intended use, cravings, unsuccessful attempts to reduce use, time spent acquiring, using, and recovering from substance use), social impairment (failure to fulfill major role obligations), risky use (physical hazard associated with use, persistent use despite experiencing negative consequences), and pharmacological criteria (increased tolerance to the substance and signs/symptoms of withdrawal) (5th ed.; DSM-5; APA, 2013).
Despite these well-documented consequences associated with it, substance use appears to have been evident in the archaeological records for many millennia around the world. Despite the long history of substance use and misuse, actual prevalence has fluctuated over time, and more recent data suggest that both use and misuse may be in slight decline after increases in previous decades (samhsa.gov). It is, however, worth noting that these Substance Abuse and Mental Health Services Administration (SAMHSA) data were collected largely prior to recent changes in state laws in which recreational marijuana use was decriminalized. Despite the political and legal attention given to marijuana use, this chapter focuses on other classes of drugs with a more clearly identified relationship to acquired brain injury or impact.
The pathophysiology of each aforementioned substance class (alcohol, inhalants, sedatives, and stimulants) will be discussed in turn by class in the sections that follow.
Alcohol is a central nervous system (CNS) depressant. The CNS depressant effects of alcohol may cause impaired coordination, gait ataxia, slurred speech, and impaired saccadic movements of the eyes. In addition to the physical presentation associated with the acute effects of alcohol, intoxicated individuals demonstrate reduced capacity for response inhibition, which has been identified in studies of event-related potentials (ERP; Oscar-Berman & Marinković, 2007). However, of greater significance to acquired brain injury are the effects of long-term alcohol abuse/misuse characterized by dependence and withdrawal. The most extreme presentation of alcohol-related cognitive deficits is reflected in Wernicke–Korsakoff’s syndrome in which profound anterograde memory loss is evident. Wernicke–Korsakoff’s syndrome is attributable to a deficiency of thiamine caused by a dietary pattern in which the vast majority of calories consumed are alcohol related rather than more nutrient-rich foods. This thiamine deficiency results in “bilateral necrosis of the mammillary bodies and of a variety of medial diencephalic and other periventricular nuclei” (Blumenfeld, 2002). This deficiency and related Wernicke–Korsakoff’s syndrome characterized by gait ataxia, acute confusion, lasting and profound impairment in memory consolidation, and confabulation represent the most significant cognitive presentation of acquired brain injury secondary to alcohol misuse. However, less significant cognitive presentations are associated with cerebral atrophy, white and gray matter loss, and reduced volume in the prefrontal cortex (Allen, Frantom, Forrest, & Strauss, 2006). In addition to the direct impact of prolonged exposure of the brain to alcohol, the indirect impact of alcohol on the brain caused by impaired liver functioning is also a significant potential source of acquired brain injury associated with alcohol exposure. Allen et al. (2006) identify significant impairment of memory, eye tracking, and hand–eye coordination in individuals with cirrhosis related to alcohol use when compared with individuals with non–alcohol-induced cirrhosis.
In addition to the potential long-term impact on the individual consuming alcohol, significant dysfunction of the CNS, craniofacial anomalies, disrupted free and postnatal growth, and markedly increased risk of intellectual disability and behavioral problems are associated with prenatal alcohol exposure, and may be described as fetal alcohol syndrome (FAS) or alcohol-related neurodevelopmental disorder (ARND) (Guerri, Bazinet, & Riley, 2009). These significant impairments and developmental disruption may be attributable to impaired functioning of glial cells, resulting in hypoplasia of the corpus callosum and anterior commissure, and microglial apoptosis (Wilhelm & Guizzetti, 2016).
Inhalants are broad and varied with regard to chemical type. The National Institute on Drug Abuse (NIDA, 2012) defines inhalants as “the wide variety of substances—including solvents, aerosols, gases, and nitrites—that are rarely, if ever, taken via any other route of administration” (www.drugabuse.gov/publications/drugfacts/inhalants). The pathophysiology of the particular inhalants is varied and related specifically to the particular inhalant. However, the most commonly inhaled substances for recreational use is toluene, which has a direct effect on the CNS as it readily passes through the blood–brain barrier, where it inhibits glutamate-activated ion channels (Cruz, Rivera-García, & Woodward, 2014). “In rat studies, acute and repeated toluene exposure markedly reduces metabolic function in the brain, especially the hippocampus, pons and thalamus. Toluene also increases dopamine release and the activity of dopaminergic neurons. Repeated exposure to toluene can lead to white matter damage (solvent vapor/toluene leukoencephalopathy), which may involve axonal damage rather than demyelination” (McKeown & Tarabar, 2015). Poor oxygenation related to inhalant use is also a strong risk factor for significant cognitive impairment and death due to anoxia (Cruz et al., 2014). Inhalant abuse can cause cardiac arrhythmias, hypoxia, hypothermia, and “sudden sniffing death” (Cruz et al., 2014). Organic solvent exposure (toluene being the most common), because of its lipophilic nature, preferentially impacts white matter (Yucel, Takagi, Walterfang, & Lubman, 2008). Periventricular white matter appears to be at particular risk in chronic toluene exposure (Yucel et al., 2008).
Sedatives are a group of central nerve depressants that work primarily by facilitating the inhibitory gamma-aminobutyric acid (GABA) (Weaver, 2015). Sedative intoxication is manifest by unsteady gait, slowed reflexes, and nystagmus (Weaver, 2015). Severe overdose may result in impaired autonomic control of respiration and may cause anoxic injury, coma, or death (Weaver, 2015). Anoxic injury most significantly impacts areas of the brain that metabolize oxygen at higher rates and have reduced blood flow in comparison to other regions. The regions of the brain most sensitive to anoxia include the hippocampus, frontal regions, and thalamus (Mendoza & Foundas, 2008). Of these regions, those involved in memory (hippocampus) and executive functioning (neocortex, frontal regions, and thalamus) are most likely impacted by sedative overdose.
The stimulant class of substances includes drugs such as cocaine and methamphetamine. Each of the stimulant medications has its own particular risk profile. Among the greatest risks to cognitive and functional capacity from this class of substances is the increased risk for cerebral infarct and stroke related to the use of these substances. Cocaine, in particular, is a significant risk factor for stroke because of its capacity as a vasoconstrictor (Allen et al., 2006). Furthermore, cocaine use has been correlated with long-term reductions in cerebral metabolism in multiple regions including the orbitofrontal cortex, the anterior cingulate, dorsolateral prefrontal cortex, amygdala, putamen, and cerebellum (Bolla & Cadet, 2007). In their review, Bolla and Cadet (2007) identified the impact on multiple neurotransmitters including dopamine, serotonin, and norepinephrine. This constriction reduces arterial volume, thereby increasing blood pressure and risk for hemorrhage and stroke. Cocaine and amphetamine users are also at increased risk for seizures, which in turn may cause cell death. Amphetamines such as MDMA (ecstasy) may cause permanent damage to serotonergic systems through excitotoxicity. Further cellular damage may occur because of disruption of temperature regulation, causing hyperthermia, which may result in diffuse brain damage, coma, or death.
Inherent to the ideology of acquired brain injury secondary to substance use is substance misuse. In general, the risk is directly proportionate to the amount of the substance used. Despite this rather direct and positive correlation between quantity and risk of acquired brain injury, there is significant interindividual variability in the risk of developing a pattern of habitual misuse, the development of tolerance to the substance, and chronicity of misuse. Allen et al. (2006) identify many risk factors for substance abuse including increased age as it relates to risk for abuse and dependence on benzodiazepines and younger age for alcohol and non–prescription drug misuse. It is also worth noting that there is a certain circular nature to the risk for substance use, as the acute and short-term deficits associated with substance misuse, namely impaired judgment and decreased inhibition, increase the likelihood of subsequent misuse/abuse.
Costs associated with substance use exceed 300 billion US dollars annually (Allen et al., 2006).
The harmful use of alcohol results in 3.3 million deaths each year (World Health Organization [WHO], 2012).
According to the annual report of the WHO (2012), individuals 15 years old or older consume 6.2 L of pure alcohol per year. This average consumption is noted in the context of large percentages of the world’s population drinking little, if any, alcohol, which suggests that 38.3% of the population consumes an average 17 L of pure alcohol annually (United Nations Office on Drugs and Crime [UNODC], 2012; WHO, 2012).
Alcohol consumption (UNODC, 2012; WHO, 2012):
Worldwide, 61.7% of the population aged 15 years or older did not drink alcohol in 12 months preceding the survey. In all WHO regions, females are more often lifetime abstainers than males. There is considerable variation in the prevalence of abstention across WHO regions.
16.0% of drinkers aged 15 years or older engage in regular heavy episodic drinking (UNODC, 2012; WHO, 2012).
Documented health consequences of alcohol consumption (UNODC, 2012; WHO, 2012):
Approximately 3.3 million deaths, or 5.9% of deaths, globally, were attributable to alcohol consumption.
Significant gender-based differences in the proportion of deaths throughout the world are attributable to alcohol, with men being at roughly twice the risk for injury related to alcohol use/misuse.
Non–alcohol substance use (UNODC, 2012; WHO, 2012):
Recent estimates from 2008 suggest that 155 to 250 million people, or 3.5% to 5.7% of the world’s population aged 15 to 64, used other psychoactive substances, including cannabis, amphetamines, cocaine, opioids, and nonprescribed psychoactive prescription medication. Cannabis continues to be the most commonly used substance of abuse, followed by amphetamine-type stimulants, then cocaine and opioids. Within this there is marked variability regionally.
With estimated annual prevalence rates ranging from 0.6% to 0.8% of the population aged 15 to 64 years, the use of opioids has remained stable (UNODC, 2012).
Epidemiological data reviewed by Crowe and Barker (2007) indicate somewhere between 1.6% and 5% of the adult population regularly use benzodiazepines.
Data published from a survey conducted in 2008 by the National Institute on Drug Abuse (2010) estimate 1.4 million Americans met the criteria for cocaine abuse/dependence over a 12-month period.
Data published from the 2012 National Survey on Drug Use and Health (SAMHSA, 2013) estimate that more than 12 million individuals aged 12 years or older have used methamphetamine in their lifetimes and 1.2 million used methamphetamine in the last year.