US Pharm. 2017;42(1):37-40.

ABSTRACT: Each year, 1.7 million people in the United States sustain a traumatic brain injury (TBI), which is twice as likely in men compared with women. TBI is an injury to the head that results in a disruption of normal functioning of the brain. The terms concussion, the most common form of TBI, and mild TBI are often used interchangeably. A concussion results most often from a blow or jolt to the head that causes the brain to collide with the skull. The signs and symptoms of a concussion may be physical, cognitive, emotional, or relating to sleep. Both pharmacologic approaches (medication management for cognitive, emotional, and neurologic symptoms) and nonpharmacologic approaches (cognitive and physical rest) are essential for treatment.

Traumatic brain injury (TBI) is a major cause of death and illness in the United States. Each year, 1.7 million people sustain a TBI, and 52,000 of them die. It is estimated that 5.3 million people in the U.S. are living with disabilities associated with brain injury.^1,2 The incidence of TBI varies according to age group: Children aged 0 to 4 years, adolescents aged 15 to 19 years, and adults aged 65 years and older are more likely to experience a TBI. TBI is twice as likely in men than in women, and men have a greater incidence of TBI than women in each age group. TBIs are not just a physical and emotional burden, but
a financial burden as well. The estimated direct and indirect medical costs of TBIs in 2010 totaled approximately $76.5 billion.³

TBI is an injury to the head that results in a disruption of normal brain functioning. TBIs may be classified according to their cause, prognosis, or—most commonly—severity. TBI severity is typically evaluated with the Glasgow Coma Scale (GCS). The GCS is a 15-point instrument that assesses a patient’s level of consciousness via motor, verbal, and eye responses. A GCS score of 13 to 15 is considered mild TBI, 9 to 12 is moderate TBI, 3 to 8 is severe TBI, and <3 is considered a vegetative state.⁴ The terms concussion—the most common form of TBI—and mild TBI are often used interchangeably. Although no standard definition exists, concussion may be described as a clinical syndrome characterized by immediate and transient alteration in brain function—including changes in mental status and level of consciousness—resulting from mechanical force or trauma.⁵

ETIOLOGY AND PATHOPHYSIOLOGY

A concussion usually results from a blow or jolt to the head that causes the brain to collide with the skull. The three most common causes of concussion are falls, motor vehicle accidents, and sports-related injuries. Falls are more common in elderly patients, and sports-related injuries are seen more frequently in younger patients.^3,6 When the brain collides with the skull, neuronal dysfunction occurs as a result of axonal stretching. Multiple ionic, metabolic, and physiologic changes take place. Following the flux of ions, more neurotransmitters are released, namely, glutamate. Glutamate release leads to the influx of calcium ions into the cells and the efflux of potassium ions out of the cells. To restore membrane potential, the sodium-potassium pump begins to work overtime. The sodium-potassium pump requires energy via adenosine triphosphate, leading to an increase in glucose metabolism. The resulting sequence of events causes an imbalance between oxygen supply and demand. The mitochondrion becomes overloaded with calcium, altering membrane permeability, which results in uncoupling of oxidative phosphorylation and organelle swelling. The dysfunctional mitochondrion then produces reactive oxygen species, causing oxidative stress.⁷

DIAGNOSIS AND CLINICAL MANIFESTATIONS

The signs and symptoms of a concussion may be physical (blurred vision, dizziness, fatigue), cognitive (confusion, slurred speech, amnesia), emotional (anxiety, depression, personality changes), or related to sleep (increased or decreased sleep). The most common symptom of a concussion is headache. Other common signs and symptoms include dizziness, changes in balance, and disorientation. Loss of consciousness occurs in fewer than 10% of patients. The signs and symptoms of concussion may overlap with those of other conditions, such as migraines and sleep disorders. For a concussion to be diagnosed, a mechanism of injury (e.g., a fall) must be identified and related to the onset of symptoms.⁶

There is no standard test or biomarker for the diagnosis of concussion. A concussion may present with subtle changes, rendering diagnosis even more challenging. Diagnosis is made primarily by recognition of the signs and symptoms associated with concussions. Self-reporting symptom checklists for patients may be used. Various symptom checklists have been developed, but there is no gold standard. Neuropsychological assessment tools, most commonly the GCS, are used to evaluate cognitive symptoms. The GCS should be given prior to the administration of narcotics or muscle relaxants, which could alter the score. An assessment of balance is beneficial, as impaired balance may occur for 3 to 5 days post injury. Laboratory data may also be helpful in assessing the injury. An arterial blood gas test will reveal the presence of hypoxia or hypercapnia, which indicates impaired ventilation. A urine toxicology screen can determine whether alcohol or drugs may be contributing to the neurologic events. An electrolyte panel should also be considered because an electrolyte imbalance may result in mental-status changes. CT or MRI may be used to identify lesions, fractures, or other skull injuries that require surgical intervention.^6,8

TREATMENT AND PREVENTION

Nonpharmacologic Treatment

Nonpharmacologic management is an essential part of concussion treatment. Because of the effects of concussion on the brain, a combination of cognitive and physical rest is necessary for recovery. Limiting activities that involve concentration and action is recommended to promote cognitive rest and relaxation.^9,10 Examples of such activities include reading, schoolwork, television watching, texting, and video games, all of which should be avoided. For the first couple of days after the incident, staying home from school or work is recommended. It is advisable to use a stepwise approach to reintroduce regular routines of activity. For school-age patients, short periods of reading and studying may be allowed, accompanied by frequent breaks. In addition, extended time periods should be allowed for homework and test taking.⁹

Physical rest involves refraining from all activities that could contribute to a second concussion, including labor-intensive exercise such as resistance training and aerobic activity. Resistance training comprises a wide range of activities in which resistance to an external force causes muscle contractions. Examples of resistance training are water exercises, bench presses, leg extensions, and squats. Lower neurocognitive test scores have been reported in persons who performed strenuous physical activity after a concussion.¹¹ Aerobic activity involves movement of the body’s large muscles in a rhythmic manner for a sustained period of time. This includes any activity in which the heart rate and breathing rate are increased in order to sustain the exercise session (i.e., cardio exercises). Since aerobic activity generates changes in the brain, such as neurogenesis, angiogenesis, and increased hippocampal volume and connectivity, it is necessary to avoid aerobic exercise in order to prevent mental exhaustion during concussion recovery.¹²

Concussion patients usually may return to their regular schedule of work or school once they are able to perform activities without symptoms or medications for concussion. Recovery time varies from patient to patient, but most patients recover spontaneously within a week.^9,10

Pharmacologic Treatment

Pharmacotherapy is usually indicated when symptoms have exceeded the expected duration or are interfering with the ability to function. Concussion symptoms that are responsive to treatment include sleep disturbances, headaches, mood disturbances, and posttraumatic seizures and epilepsy.^9,10

Sleep Disturbances: Common sleep disturbances include excessive sleep, daytime drowsiness, difficulty falling asleep, and frequent nighttime awakenings. Before medication management is considered, proper sleep hygiene should be discussed with the patient (TABLE 1). If medical management is still necessary after a trial of proper sleep hygiene, then sleep aids such as melatonin, diphenhydramine, or another appropriate medication may be beneficial. It is essential to avoid sleep agents that can cause cognitive impairment, such as sedatives and some anxiolytics (i.e., benzodiazepines and nonbenzodiazepine hypnotics). These medications can negatively affect cognition and mood.^10,13

Headaches: The most common concussion symptom, headache, may require only simple analgesics (acetaminophen and nonsteroidal anti-inflammatory drugs) for relief of pain. For persistent headaches, 5HT (serotonin) agonists (i.e., triptans) may be used with caution to avoid medication-overuse headaches, which can occur when these agents are used along with simple analgesics. In general, opioids are not recommended for postconcussion headache. If chronic headaches persist, then prophylaxis may be initiated with medications such as amitriptyline and topiramate. It may be beneficial to treat multiple symptoms with a single agent, such as amitriptyline for sleep disturbances and depression. Caution is advised with the use of Topamax in this patient population because of its cognition-dulling effects and the anticholinergic cognitive effects of tricyclic antidepressants (TCAs). Beta-blockers used as prophylactic agents may not be the best option in athletes because of their effects on heart rate.¹⁰

Mood Disturbances: Mood disturbances that may occur in postconcussive patients include mood swings, irritability, anxiety, depression, mental fatigue, and memory/attention disturbances. Depression and anxiety symptoms can be managed with selective serotonin reuptake inhibitors or TCAs. In some situations, referral to a psychiatrist may be necessary. Methylphenidate and amantadine have been studied in post-TBI patients for treatment of mental fatigue and attention or memory disturbances, with varying results.^10,13

Posttraumatic Seizures and Epilepsy: Posttraumatic seizures are defined as early-onset (within 1 week postconcussion) or late-onset (>1 week postconcussion). Seizures resulting from a head injury can be difficult to control with standard antiepileptic drug therapy. Usually, the patient is placed on prophylactic phenytoin or levetiracetam for 1 week post-TBI to prevent early-onset seizures or progression to epilepsy in those at high risk for seizures.^10,13 If seizures do not occur while the patient is on therapy, tapering of medication can begin.

Preventive Strategies: Preventive strategies are aimed at providing education, using protective equipment, monitoring injury patterns, following or changing rules of sports, taking legislative action, and preventing and/or monitoring for complications such as second-impact syndrome (described below), chronic traumatic encephalopathy (CTE), and postconcussive syndrome. It is extremely important to ensure that staff who are involved with players of contact sports, as well as the players themselves, are educated about the frequency and dangers of concussion. Education of healthcare and sports-medicine providers has improved concussion management.¹⁴ It is essential to train individuals who play contact sports on proper technique to prevent or minimize injury. For this reason, coaching staff must stay up-to-date on the latest strategies and teach these skills to their players to improve performance and, more importantly, minimize danger to the player or others he or she comes in contact with. Using protective equipment, such as a helmet when playing football or a seatbelt when riding in a car, can be lifesaving. In addition, the continued assessment of products used for protection in contact-related sports is important to ensure that the equipment is meeting standards of protection.

Monitoring the pattern of injuries becomes important for prevention of concussions because this will provide decision makers with areas of safety improvement for future strategies. Ensuring that existing rules are being followed or new rules are being established for contact sports is imperative so that players are not injured because of dangerous contact during games. Following state legislative regulations on management can help prevent disastrous concussion sequelae.⁹ Several states require that a player be cleared by a licensed healthcare professional before returning to sports activity.⁶ In the event that regulations are not currently in place, advocating for or assisting in the establishment of necessary regulations can be most important.

Second-impact syndrome, which is a controversial topic, is extremely important to consider and prevent. This catastrophic brain swelling can occur if a player returns to sports activity while symptomatic and suffers a second impact to the head or body, leading, in severe cases, to coma or death. The risk for this condition is highest within the first 7 to 10 days post concussion.⁹ Therefore, it is recommended that athletes or players not be permitted to return to sports activity while they are experiencing postconcussive symptoms.⁶

CTE is a progressive neurodegenerative disease caused by repeated mild head injury. It can occur decades after an injury and may manifest as behavioral, cognitive, or movement conditions.⁹ Suicidality and dementia are highly associated with this condition. Postconcussion syndrome, a complication that must be monitored for, involves the continuance of symptoms beyond the expected recovery period, which is about 1 to 6 weeks.⁹

PHARMACIST’S ROLE

As one of the most trusted and accessible healthcare professionals, the pharmacist fills the unique role of counseling patients on the management of concussion and concussion-related sequelae. In particular, pharmacists in the community setting can educate patients and/or parents regarding current and relevant guidelines for sports-related concussion in school-age children and adolescents. Pharmacists in inpatient and ambulatory settings who are part of interdisciplinary teams can help make appropriate recommendations on pharmacotherapy for concussion-related comorbidities.¹⁵ Most importantly, pharmacists in all practice settings can help prescribers and patients be aware of and identify medications that impair cognition and should be avoided (TABLE 2), as well as alcohol.

Since community pharmacists are typically most accessible because of their continuity of care in filling prescriptions and providing counseling on basic healthcare needs, they should keep abreast of current management strategies for common conditions that may affect their patients. It has been well documented that pharmacists can assist in the management of other common conditions, such as diabetes, asthma, and mental health disorders. Therefore, pharmacists who are highly familiar with common neurologic disorders, such as concussions and brain-related injuries, can provide additional support to other healthcare providers and, more importantly, to the patients they serve.

REFERENCES

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