US Pharm. 2014:39(1):20-23.
In the United States, traumatic brain injury (TBI) is a common cause of death and disability.1
Of those patients admitted to head injury units, between 9% and 14% are
over the age of 65 years, and this group has the worst prognosis.2
Causes of TBI include transportation-related causes (e.g., motor
vehicle and bicycle accidents, collisions with pedestrians), falls
(especially in senior adults and young children), physical assaults, and
sports activities.1 Repetitive brain trauma, as seen in
persons who have engaged in contact sports and participated in the
military, is associated with progressive neurologic deterioration in
some individuals.3 An overview of TBI and chronic traumatic
encephalopathy (CTE), a neurodegenerative disease thought to be caused
in part by TBI and in its later stages associated with dementia, is
discussed below. The role of the pharmacist may be of particular benefit
when resistant headache in an elderly person requires pharmaceutical
intervention beyond simple analgesia.
TYPES OF TRAUMATIC BRAIN INJURY
TBI is physical injury to brain tissue that temporarily or permanently impairs brain function; various types include1:
Concussion: A transient and
reversible posttraumatic alteration in mental status (e.g., loss of
consciousness or memory) a concussion may last from seconds to minutes,
but by arbitrary definition, <6 hours. Symptoms, referred to as postconcussion syndrome,
include nausea, headache, dizziness, and memory disturbance and may
cause temporary disability and have an impact on physical, emotional,
cognitive, and social domains.
Brain contusions: These are
bruises of the brain secondary to open or closed injuries. Brain
function impairment can occur based on contusion size and location and
cancause brain edema and increased intracranial pressure (ICP).
Enlargement of a contusion can occur within hours or days after injury,
and neurologic deterioration may ensue.
Diffuse axonal injury: As
seen in shaken baby syndrome, diffuse axonal injury results in
generalized, widespread disruption of axonal fibers and myelin sheaths.
Associated edema increases ICP.
Hematomas: Collections of
blood in or around the brain that may occur with open or closed
injuries, hematomas may be epidural, subdural, or intracerebral.
Subarachnoid hemorrhage (SAH) is common in TBI, with a different
appearance from aneurysmal SAH as seen on computed tomography (CT). A
consideration pharmacists should be aware of when reviewing the
medication regimen of a senior with TBI is that selective serotonin
reuptake inhibitors (SSRIs) are among the most commonly prescribed
medications in the U.S., and while the SSRI-associated elevated risk for
hemorrhage has been small, it is especially linked to concomitant use
of nonsteroidal anti-inflammatory drugs (NSAIDs) or warfarin.4,5,6
Skull fractures: These are
penetrating injuries, although closed injuries may also cause skull
fractures. Some skull fractures may cause damage to the middle and inner
ear structures and may impair nerve function (i.e., facial, acoustic,
SELECTED SYMPTOMS AND IMPLICATIONS
In the first few days after a moderate or
severe injury, maintaining adequate brain perfusion and oxygenation and
preventing and treating complications of altered sensorium are
important.1 While many patients require rehabilitation
subsequent to traumatic head injury, those with mild injuries are
discharged and observed.1 The following effects may be encountered by clinicians in a variety of practice settings:
Posttraumatic headache is frequently a
conspicuous feature of closed head injury, without regard to whether
consciousness is lost.7 The appearance of symptoms (TABLE 1)
usually occurs within a day or so following injury and may persist for
months. In some cases, there may be difficulty in obtaining information
about headache in the early phase after return of consciousness, owing
to the presence of concomitant medications that may affect pain
perception.8 CT scan or MRI of the head usually does not show
abnormal findings. CT brain scan should be reserved for those with
focal signs or fluctuating consciousness.9 Optimistic
encouragement and rehabilitation (based on occupational circumstances)
are advised; frequently, symptoms resolve spontaneously within several
While treatment with simple analgesics
such as acetaminophen or the NSAID ibuprofen may show positive
therapeutic outcomes, the increased risk of intracranial bleeding post
head trauma should be considered, as well as the NSAID’s ability to
alter platelet function and prolong bleeding time. If headaches are
severe, prophylactic treatment of migraine may be necessary; treatment
options may include antiepileptic agents such as topiramate (50 mg
orally twice daily) and off-label valproic acid (250-500 mg orally twice
daily); off-label amitriptyline (e.g.10-150 mg orally per day); beta
blockers such as propranolol (80-240 mg orally divided twice to four
times daily) and timolol (10-30 mg orally per day); calcium channel
blockers (CCBs) such as verapamil (80-240 mg orally divided three times
daily); or others (e.g., onabotulinumtoxinA injected IM by a trained
clinician).7,10,11 Of note, amitriptyline is associated with
considerable sedation, anticholinergic effects, orthostasis, and
conduction abnormalities, which may be especially problematic in the
elderly and in those with certain medical histories and comorbidities
(e.g., myocardial infarction [MI], stroke, tachycardia, conduction
abnormalities). Furthermore, sedative effects may be additive with other
central nervous system (CNS) depressive agents and/or alcohol. Owing to
its CNS penetration and nonselective action, propranolol may not be the
beta-blocker of choice for use in the elderly. CCBs do not cause
significant CNS effects, which may be an advantage over some other
agents.11 Resistant headache may require psychological management and the use of psychotropic agents.9
Clinicians should refer a patient with a
headache in the following circumstances: 1) acute onset reported as
“worst headache in my life”; 2) history of trauma, hypertension, fever,
or visual changes; 3) increasing headache unresponsive to basic
measures; and 4) the presence of neurologic signs or tenderness of the
scalp. The patient should be admitted to the hospital if SAH is
Traumatic vertigo is most commonly caused
by concussion of the labyrinth. Symptoms generally diminish within
several days of incident but may persist for up to a month or more. If a
skull fracture traverses the inner ear, severe vertigo usually results
and may last several days to a week; deafness in the involved ear
usually ensues. Chronic posttraumatic vertigo pre-sents clinically as
episodic positioning vertigo. Management of this condition consists of
1) supportive care; 2) vestibular suppressant medication (e.g.,
meclizine or diazepam, which may cause confusion and increase the risk
of falls in the elderly); and 3) vestibular rehabilitation, a therapy
involving exercises designed to retrain the brain to recognize and
process signals from the vestibular system and coordinate them with
information from vision and proprioception (see RESOURCES).12,13
Neck injury may induce cervical vertigo
triggered by neck movements. Diagnosis may be confused with
migraine-associated, head movement–induced vertigo.12,14 Cervical vertigo is managed with neck movement exercises as permitted by orthopedic considerations.12,14
Head trauma may also precipitate episodic
vertigo with or without migraine-type headache. Visual and motion
sensitivity, auditory sensitivity, photosensitivity, and head pressure
may accompany the vertigo. Foods triggering migrainous vertigo include
caffeine, chocolate, and alcohol; stress, anxiety, and sleep deprivation
may exacerbate symptoms. Management consists of dietary and lifestyle
modifications (avoiding triggers, reducing stress, improving sleep) and
prophylactic antimigraine medication therapy.7,12,15-17
Hearing and Vision Loss
Following simple concussion, some degree
of sensory hearing loss may occur; after skull fracture, hearing loss is
a frequent occurrence. Hearing loss has also been associated with the
deployment of air bags during an automobile accident. Following moderate
or severe concussion, vision is rarely altered or lost, and symptoms
usually resolve spontaneously over weeks to months; acute traumatic
blindness seldom resolves after 3 to 4 months.1,12,18
Head trauma is responsible for <5% of cases of hyposmia, reduced sense of smell; it is more frequently associated with anosmia, the loss of smell.12 Posttraumatic anosmia seldom resolves after 3 to 4 months.1 (Of
note, the subject of olfactory dysfunction in the neurologic disorders
Parkinson disease and Alzheimer disease is a recent research focus.)
Many medications can contribute to olfactory dysfunction, including
systemic or inhaled drugs (e.g., aminoglycosides); many other
medications and compounds may alter smell sensitivity, including
alcohol, nicotine, organic solvents, and directly applied zinc salts.19 Endocrine
disturbances commonly seen in the elderly (e.g., hypothyroidism,
diabetes mellitus) may affect olfactory function as well.19
While there is no specific treatment
recommended for primary disruption of olfaction, clinicians may discuss
supportive measures with patients, including 1) use of spices (e.g.,
pepper) to stimulate the trigeminal and olfactory chemoreceptors; 2)
avoiding overuse of table salt for seasoning; 3) use of smoke alarms for
safety; and 4) replacing gas appliances with electric ones for safety. 12,20-22
Trauma-induced seizures can occur in patients of any age; however, they are an especially important cause in young adults.7
Since seizures can worsen brain damage and increase ICP, prompt
treatment is warranted. It is not necessarily implied that if seizures
appear within the first week following injury, future seizures will
occur; if the dura mater has been penetrated, however, posttraumatic
epilepsy is more likely to develop, manifesting within 2 years after
injury.1,7 In a small percentage of patients, late seizures
(>7 days after the injury) develop often weeks, months, or even years
While there is at present no definitive
evidence that the use of prophylactic anticonvulsant medication therapy
reduces the incidence of posttraumatic epilepsy, a prophylactic
anticonvulsant (e.g., phenytoin, fosphenytoin) should be considered in
patients with significant structural injury (e.g., larger contusions or
hematomas, brain laceration, depressed skull fracture) or a Glasgow Coma
Scale (GCS) score <10 (see RESOURCES).1,7
Duration of treatment depends on the type
of injury and EEG results; if no seizures develop within one week,
anticonvulsants should be discontinued since their benefit in preventing
future seizures is not established.1
Other Associated Symptoms
Other symptoms may occur following moderate or severe
concussion, including fatigue, difficulty concentrating, amnesia
(variable), anxiety, apathy, and depression; gait and balance
disturbances, spastic motor impairment, and ataxia can also occur.1 Except in elderly patients, hemiparesis and aphasia usually resolve at least to some extent.1
Cognitive and neuropsychiatric deficits
can persist, especially if structural damage was significant; long-term
symptoms include amnesia (retrograde and anterograde), behavioral
changes (e.g., agitation, impulsivity, disinhibition, lack of
motivation), emotional lability, sleep disturbances, and decreased
intellectual function.1 Of note, disability in social
relations and employment are attributed more to cognitive deficits and
various personality changes than focal motor or sensory impairments.1
In some cases, a TBI may result in a
persistent vegetative state with preservation of autonomic and motor
reflexes and normal sleep-wake cycles, while self-awareness and other
mental activity are absent.1 Normal neurologic function
rarely returns after a vegetative state lasting 3 months after injury;
after 6 months, almost no patients recover.
Neurologic function may continue to improve for a few years after TBI, but is most rapid during the initial 6 months.1 For a detailed discussion of TBI including management based on the severity of injury, see Reference 1.
REPETITIVE HEAD TRAUMA AND CTE
Chronic traumatic encephalopathy
(CTE) is a neurodegenerative disease that is thought to be partially
caused by repetitive symptomatic concussive and asymptomatic
subconcussive brain injury.3,23,24 While repetitive brain trauma appears necessary for the development of CTE, it is not solely the cause of the disease.3 Originally referred to as dementia pugilistica,
CTE has long been known to affect boxers and has recently been
confirmed in other athletes, including retired professional football
players.24,25 Recent research suggests that CTE is more likely to occur as a result of repeated mild injuries, rather than one or two severe ones. 25,26
Further, according to recent postmortem
findings, CTE may affect a broader population than was initially
conceptualized, particularly among contact sport athletes and those with
a history of military combat.3 Researchers Baugh et al
indicate that given the large population that could potentially be
affected, CTE may represent an important issue in public health.3
Additional risk factors that may also play a role in the development of
CTE and require further research include 1) longer duration of exposure
to head trauma; 2) age at first exposure; and 3) genetic
Neuropathologic changes in various areas
of the brain occur, including tissue degeneration and a buildup of
abnormal tau protein (referred to as tau tangles), which are also found in patients with Alzheimer disease.23,24 Researchers have noted that CTE has a clear environmental etiology.25
The neuropsychologic and neuropsychiatric
symptoms associated with this disorder—generally beginning years or
decades after repeated brain trauma and suggesting it during an
individual’s lifetime—fall into three categories3:
changes: learning and memory impairment; executive dysfunction such as
planning, organizing, multitasking, and judgment early in the course of
disease; dementia late in the course
Mood changes: depression, apathy, irritability, and suicidality
changes: poor impulse control (e.g., described as having a “short fuse”
or being “out of control”), aggression, increased violence,
disinhibition, and problems with substance and other forms of abuse.
Symptoms worsen later in the course of
CTE; later stages are associated with dementia. Currently, there are no
validated clinical diagnostic criteria or biomarkers for CTE, and like
other forms of dementia, it cannot be officially diagnosed until
autopsy.3 Some patients with CTE have been noted to have a
concomitant neurodegenerative disease, such as Alzheimer disease,
frontotemporal dementia (FTD), Lewy body disease, or Parkinson disease.
Researchers observe that CTE may not produce the same changes in all
patients; it does not progress at the same rate in all patients, and it
may not progress at all in some individuals.26
Pharmacists should be aware of TBI as an
important issue in older adults in light of the cognitive, mood, and
behavioral changes that may occur. In addition to providing accessible,
cost-effective, and high-quality pharmaceutical care services,
pharmacists can enhance their role in the community as patient advocates
and community educators to seniors and their caregivers, as well as to
veterans, students, parents, and athletes, by raising awareness of the
risks associated with head injury and CTE.
To comment on this article, contact firstname.lastname@example.org.
1. Traumatic brain injury. MerckManual.com. Modified
brain injuryhead &alt=sh. Accessed January 2, 2014.
2. O’Neill P. Cranio-cerebral trauma. In: Tallis RC, ed. The Clinical Neurology of Old Age. Chichester, England: John Wiley;1989:285-296.
3. Baugh CM, Stamm JM, Riley DO, et al. Chronic traumatic
encephalopathy: neurodegeneration following repetitive concussive and
subconcussive brain trauma. Brain Imaging Behav. 2012;6:244-254.
4. Auerbach AD, Vittinghoff E, Maselli J, et al.
Perioperative use of selective serotonin reuptake inhibitors and risks
for adverse outcomes of surgery. JAMA Intern Med. 2013;173:1075-1081.
5. SSRIs linked to bleeding risk, death in surgical patients. Medscape. Apr 30, 2013. www.medscape.com/viewarticle/803334. Accessed October 4, 2013.
6. Zagaria ME. Bleeding risk with SSRIs: surgery and seniors. US Pharm. 2013;38(11):20-22.
7. Aminoff MJ, Kerchner GA. Nervous system disorders. In: McPhee SJ, Papadakis MA, Rabow MW, eds. 2011 Current Medical Diagnosis & Treatment. 50th ed. New York: McGraw Hill Medical;2011:936-1009.
8. Formisano R, Bivona U, Catani S., et al. Post-traumatic headache: facts and doubts. J Headache Pain. 2009;10:145-152.
9. Saldanha GJ. Headache and facial pain. In: Fillit HM, Rockwood K, Woodhouse K, eds. Brocklehurst’s Textbook of Geriatric Medicine and Gerontology. 7th ed. Philadelphia, PA: Saunders Elsevier; 2010:466-477.
10. Epocrates Essentials, Version 4.5. Epocrates, Inc. www.epocrates.com. Accessed January 2, 2014.
11. Semla TP, Beizer JL, Higbee MD. Geriatric Dosage Handbook. 17th ed. Hudson, OH: Lexi-Comp, Inc; 2012.
12. Lustig LR, Schindler JS. Ear, nose & throat disorders. In: McPhee SJ, Papadakis MA, Rabow MW, eds. 2011 Current Medical Diagnosis & Treatment. 50th ed. New York: McGraw Hill Medical;2011:205.
13. Scherer MR, Schubert MC. Traumatic brain injury and vestibular pathology as a comorbidity after blast exposure. Phys Ther. 2009;89:980-992.
14. Schikora N, Eysel-Gosepath K, Klünter H, et al.
Influence of cervical spine stabilization via stiff neck on the postural
system in healthy patients: compensation or decompensation of the
postural system? Eur Arch Otorhinolaryngol. 2010; 267:1623-1628.
15. Felisati G, Pipolo C, Portaleone S. Migraine and vertigo: two diseases with the same pathogenesis? Neurol Sci. 2010;31(suppl 1):S107-S109.
16. Fotuhi M et al. Vestibular migraine: a critical review of treatment trials. J Neurol. 2009;256:711-716.
17. Jeong SH, Oh SY, Kim HJ. Vestibular dysfunction in migraine: effects of associated vertigo and motion sickness. J Neurol. 2010;257:905-912.
18. Mick P, Morham P, Luderman J. Penetrating and blast ear trauma: a 7-year review of two pediatric practices. J Otolaryngol Head Neck Surg. 2008;37:774-776.
19. Leopold D, Holbrook EH, Noell CA. Etiology of smell and taste disorders. Medscape.com.
http://emedicine.medscape.com/article/861242-overview#aw2aab6b4. Updated: Apr 12, 2012. Accessed January 2, 2014.
20. Doty RL. The olfactory system and its disorders. Semin Neurol. 2009;29:74-81.
21. Hummel T, Lotsch J. Prognostic factors of olfactory dysfunction. Arch Otolaryngol Head Neck Surg. 2010;136:347-351.
22. Lafreniere D, Mann N. Anosmia: loss of smell in the elderly. Otolaryngol Clin North Am. 2009; 42:123-131.
23. Lupkin S. CTE, a degenerative brain disease, found in
34 pro football players. Dec. 3, 2012.
Accessed December 9, 2013.
24. What is CTE? Boston University Center for the Study of
Traumatic Encephalopathy. www.bu.edu/cste/about/what-is-cte/. Accessed
January 2, 2014.
25. McKee AC, Cantu RC, Nowinski AB, et al. Chronic
traumatic encephalopathy in athletes: progressive tauopathy following
repetitive head injury. J Neuropathol Exp Neurol. 2009 July; 68:709-735.
26. Walton AG. The stages of traumatic brain injury:
learning from the brains of athletes, veterans, and one head-banger.
Forbes.com. December 5, 2012.
Accessed December 9, 2013.