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10 Articles in Volume 15, Issue #1
Psoriatic Arthritis: Current Strategies for Diagnosis and Treatment
Traumatic Brain Injury: Evaluation, Treatment, and Rehabilitation
Pain Management in the Elderly: Treatment Considerations
9 Best Practices in Evaluating and Treating Pain in Primary Care
Rationale for Medical Management
New York State Enacts New Law to Prevent Drug Diversion
Editor's Memo: Acknowledging the Failure of Standard Pain Treatment
PPM Editorial Board Discusses Epidural Steroid Injections and Blindness
Ask the Expert: False Positive Amphetamine Urine Screens
Letters to the Editor: Pregnenolone, Acute Porphyria, Opioid Calculator, Arachnoiditis

Traumatic Brain Injury: Evaluation, Treatment, and Rehabilitation

Traumatic brain injury (TBI), or concussion, can leave a person with lifelong symptoms. In this segment, specialists in 3 areas discuss TBI-induced cellular damage to the brain and the management of its sequalae.

A traumatic brain injury (TBI), or concussion, can leave a person with lifelong symptoms and disability, requiring a multidisciplinary approach to the management of this condition. In this, our third installment in our series on TBI, we will describe the evaluation and treatment of mild TBI from different clinical perspectives. The three authors come from different training and medical backgrounds (neurology, neuropsychology, and physical medicine & rehabilitation). Using their unique backgrounds, the authors describe the cellular mechanism of TBI as gleaned from high-grade imaging devices, review neuropsychological evaluation for patients with TBI, and provide an overview of a comprehensive approach to lifelong treatment within a comprehensive physical medicine and rehabilitation model.1

Part 1 of this series described the biomechanics and pathophysiology of traumatic brain injuries, as well as their symptoms: post-concussion syndrome, post-traumatic headache, and migraine. Part 2 of this article series discussed treatments for TBI-related headaches.

Introduction

TBIs can occur any time, any place, and from myriad sources. The recent coverage of sports-related concussions and improvised explosive device/combat-related explosions in the armed forces has brought more awareness of the subject to the public eye. But, TBIs are not new. According to the Centers for Disease Control and Prevention, approximately 1.7 million TBIs occur every year in the US,2 accounting for close to a million and a half emergency room visits, and over 50,000 deaths.3 Sports-related TBI raises the specter of repeated TBIs, which can lead to chronic traumatic encephalopathy (CTE).4

The majority of mild TBI survivors recover fully 3 to 4 weeks after the injury, but a significant minority (10%-20%) continue to experience symptoms months (acute post-concussion disorder [PCD]) and even years (chronic PCD) after their injury.5

Physical complaints after mild TBI include headache, dizziness, photophobia, phonophobia, fatigue, nausea, insomnia, vision impairment, and seizures. Cognitive complaints include decreased arousal, attention, and concentration, as well as short-term memory loss.

Despite its high incidence and profile, TBI and its many post-concussional clinical issues (Table 1) are not addressed in medical school training. The available pool of clinicians who are interested and actively work in this area of medicine is quite small but growing. The good news is that the specialized tools for evaluation and treatment of the many symptoms that result from TBI are expanding. Indeed, this has been a multidisciplinary effort.

Cellular Mechanism

Cellular and Neurotransmitter Changes

In the period after a TBI, there are multiple changes in neurotransmitters (glutamate, serotonin, norepinephrine, acetylcholine, histamine, opioid receptors, etc), as well as cellular and neuronal dysfunction, all of which contribute to behavioral and executive function impairments. For example, extracellular glutamate is profoundly altered after TBI. This contributes to the acute pathophysiology of TBI and its symptoms. (Editor’s Note: for more on the pathophysiology of concussion, see Part 1 of this series.>6 Research in the rat model indicates that inflammation-induced alterations in calcium-mediated glutamate release and glial regulation of extracellular glutamate contribute to increased extracellular glutamate in the striatum.7 In addition, blockade of dopamine5receptors in the hippocampus eliminates late long-term potentiation, suggesting that synaptic plasticity in the hippocampus depends upon on interaction between glutamate and dopamine.8

Diaschisis—functional depression or loss of neuronal activity in an area of the brain that, although removed from the site of TBI, is anatomically connected via neuronal pathways—can be permanent or may improve over time due to synaptic plasticity, changes in cortical reorganization, or properties of neurotransmitter function and cerebral glucose utilization. Thus, recovery from a TBI requires a form of brain plasticity and, presumably, can be influenced by rehabilitation and/or medications.9

Calcium influx into injured neurons can result from activation of the N-methyl-D-aspartate (NMDA)-type glutamate receptor,10-12 as well as from opening of voltage-gated calcium channels (VGCCs)13 and release of intracellular calcium stores.14 This excess calcium contributes to cell damage and death.15

One of the authors (JCK) has presented data showing improvement of impairments in executive function, attention, concentration, and memory with treatment using either acetylcholinesterase inhibitors or NMDA-type glutamate receptor antagonists.16,17 After treatment, patients had clear-cut improvements in many subtests of the Halstead-Reitan Neuropsychology Battery (HRB), a widely used assessment of cognitive function.

In addition, limited pre-clinical data indicates that specific L- and N-type VGCC antagonists have potential for treating TBI patients. The mechanisms of action for these antagonists, however, have not been well characterized.

Another neurotransmitter system that is profoundly altered after severe TBI is norepinephrine. A recently proposed double-blind placebo-controlled study (DASH After TBI study) will look at the beta-blocker propranolol (Inderal, others), and the alpha2 agonist clonidine (Catapres, others) in the treatment of severe TBI and prevention of norepinephrine rise after injury.18

Immunologic Changes

TBI of any form can cause cognitive, behavioral, and immunologic changes at any point after the injury. This complicates the problem of misdiagnosis of mild TBI, which can cause long-term neurological deficits. TBI of any severity disrupts the blood-brain barrier, leading to infiltration of immune cells into the brain and subsequent inflammation and neurodegeneration. TBI-induced central and peripheral immune responses affect the disease outcome. Much more active research is needed in this area, as outlined recently in an excellent review.19

Diagnostic Workup

One aspect of a detailed workup for TBI is often overlooked: use of high-grade electroencephalography (EEG). This includes EEG with 26-8 channels of data or more. Observationally, over 50%—and as many as 80%—of these studies are abnormal after a TBI. The drawback is that only about 5% of neurologists are board-certified in reading EEG and evoked potential data. Thus, even if EEG is performed, abnormalities may be missed by an inexperienced reader. Abnormal studies open the possibility of treatment with so-called anticonvulsants (better described as neuronal stabilizing agents), which can be calming and promote sleep in the post-concussional state.

High-grade brain imaging, such as 3-tesla magnetic resonance imaging (MRI), fluid attenuated inversion recovery (FLAIR) MRI, and diffusion MRI tensor imaging with fractional anisotropy, read by an experienced neuroradiologist also may be indispensable for detecting a subtle bleed related to the TBI, or post-traumatic anatomical changes, known as dilated Robin-Virchow spaces in the brain tissue. Imaging of a more dynamic nature, such as functional MRI or positron emission tomography/single photon emission computerized tomography scanning, provides metabolic data on brain functions and are highly correlative to a thorough history and physical and neurological evaluation and EEG results.

Many biologic neuromodulators can be measured with proton magnetic resonance spectroscopy (1H-MRS). If these substances can be used as biomarkers of TBI, then there may be a tool for looking at molecular changes after brain injury. In one study, researchers used high-field in vivo 1H-MRS to measure neurochemical profiles in contused cortex and the normal-appearing perilesional hippocampus after experimental TBI in rats. The study found significant changes in 19 out of 20 neurochemicals in the cortex, and 9 out of 20 neurochemicals in the hippocampus. The results provided evidence of altered cellular metabolic status after TBI and reflect edema, excitotoxicity, neuronal and glial integrity, mitochondrial status and bioenergetics, oxidative stress, inflammation, and cell membrane disruption.20 In addition, the results support the utility of 1H-MRS for monitoring cellular mechanisms of TBI pathology in animal models, and the potential of this approach for preclinical evaluation of novel therapies.

Neurocognitive Assessment And Rehabilitation

As noted, TBIs have many different sources of impacting events. In addition to the general label TBI, the latest edition of the Diagnostic Statistical Manual of Mental Disorders (5th Edition) has proposed that a TBI be placed in a new category (neurocognitive disorders), which includes trauma sources, degenerative origins, vascular etiologies, and so forth.3 Under the neurocognitive disorders category, common symptoms are defined by what is termed neurocognitive domains—at least 6 in all (Table 2). This terminology is important because it relates to neurocognitive rehabilitation and the presenting of particular domains can focus rehabilitation efforts.

Neurocognitive, or neuropsychological, tests have a long history dating back to the late 1930s. At that time, the first neuropsychology instruments were recruited to measure cognitive effects of leucotomies done by Moniz, Freeman, Watts, and others.21 Most of the more recent neuropsychological tests consist of batteries or arrays of accepted measures that attempted to assess neurocognitive domains. The renowned psychologist, David Wechsler, the pioneer of intelligence and neurocognitive testing, divided intelligence into a collection of brain functions. Wechsler’s approach to measuring intelligence (not a single score but a collection of scores) led to the development of neuropsychological tests.

Since the days of Wechsler, neuropsychological testing can be separated into 2 approaches to collecting neurocognitive data: fixed batteries of specific procedures and flexible batteries that have no specifically required methods. For example, traditional intelligence tests are fixed, employing specifically required methods. Proponents of this approach argue that neuropsychological tests should have standard, fixed procedures. Hence, a fixed battery would use the same fixed procedures to measure spatial perception, various types of memory, attention capacity, executive functioning, attention, processing speed and perception, and so on. While there are many different “fixed” batteries, each preset battery measures different brain functions with specific procedures. Typically, these batteries have norms for age and education. Percentile ranks also usually are given and a graph of scores often is illustrated for easy examination of the patient’s deficits and strengths. By contrast, flexible batteries involve a type of mix and matching of instruments, selected from a differential possibility of instruments, selected by the neuropsychologist. The flexible batteries have no specific name because the collection of subtests varies according the neuropsychologist’s assumptions. However, even if one uses a flexible battery of tests, common ancillary procedures are used. Most commonly, clinicians will use a mixture of flexible and fixed procedures together.

Malingering tests—used to determine the degree of symptom-magnification, the level of effort displayed by the patient, or, more crudely put, whether the patient is faking—often are superimposed on the neuropsychological procedures used. Typical malingering tests include the instruments such as the Test of Memory and Malingering (TOMM),22 the Symptom Validity Scale (SVS),23 and Validity Indicator Profile.24

The HRB is the seminal fixed battery, and generally does not allow “flexible” additions to the procedure, although with the HRB a neuropsychologist often uses a standard measure of intelligence, a test of psychopathology such as the Minnesota Multiphasic Personality Inventory (MMPI), and other important options, such as collateral interviews and a significant review of the patient’s past history of medical or neurological disorders.25 There is no “screening” option. The HRB has the main disadvantage of not having recent norms involving age and education co-variations, and it does not clearly indicate the neurocognitive domains that each of its parts measures. For example, how does memory or executive function compare with the patient’s normal cohort? These significant limitations can skew measures of TBI and affect the measurable impact of a TBI due to age achievements and chronological decline.

The newer fixed batteries feature a “screening” element and more precise norms that take into consideration education and age. Most significantly, newer fixed batteries may have the feature of being “repeatable,” or having alternate forms. This permits re-administration without as much concern for practice effect. The repeatable feature also makes it easier to measure the effects of neurocognitive rehabilitation, medications, and other treatments.

Two popular forms of fixed batteries include the Neuropsychological Assessment Battery (NAB)26 and the Repeatable Battery of Assessment of Neuropsychological Status (RBANS) (Tables 3 and 4).27 The NAB, unlike the RBANS, has both a screening function and a more detailed longer version. Both can be used for patients up to about 90 years of age and the Updated RBANS has norms dropping down to 12 years of age; the NAB lacks this low age level for assessing possible problems in early adolescence. The RBANS and the screening NAB can be completed in less than an hour.

 

It is important to note that the NAB and the RBANS, unlike the HRB, are repeatable and have domains or index scores that parallel very closely the neurocognitive domains in the 2013 DSM-5. Indeed, the NAB’s profile of scores is almost equivalent in terminology to the DSM-5 neurocognitive domains. However, neuropsychological tests do not quantify “social cognition” or personality, social, or impulse control changes following the TBI. Collateral data collected from caregivers and others who knew the patient prior to the injury often are essential.

Neurocognitive Rehabilitation

The goal of neurocognitive rehabilitation is to improve the motor, sensory, and cognitive deficits caused by TBI. Particular neurocognitive domains mentioned in Table 2 may be the focus, as can occupational therapy goals or return to work. Also, speech and family therapies to address personality and impulse control dysfunction or apathy can be helpful. Nootropic medications to improve dementia and other problems have been tried in small trials.

Individual package programs are available to improve specific neurocognitive losses, including some practicing test items missed on neuropsychological tests. Newer computerized neurocognitive programs have been developed (ie, Luminosity). Collectively, these have not been systematically compared against other rehabilitation methods that show significant results.28

Treatment of Cognitive Disorders

There are a few general rules that should be followed when treating patients with cognitive disorders after mild TBI (Table 5). Cognitive sequelae of mild TBI include problems with arousal, attention, and memory.

Deficits in Arousal

Dysregulation of information input and/or processing affect arousal, which is at the basis of cognition. Deficits in arousal preclude the TBI survivor from meaningful interaction with their external environment.

Problems with arousal have been linked to direct damage to the thalamus, mid brain, and/or brain stem. This involves a complex network of cholinergic reticulothalamic, glutaminergic, thalamocortical, and reticulocortical projections in these bodies as well as dopaminergic, noradrenergic, serotonergic, and cholinergic projections. Damage to these neurons block the input and initial processing of all external stimuli.

In addition, diffuse axonal injury affecting the axons, which convey information from the mid brain and thalamus to the higher brain where external stimuli are interpreted, can also produce problems with arousal. Disruption of the dopaminergic and serotonergic systems have been shown to play a role in lack of arousal.

Treatments for decreased arousal can be divided into 3 categories: psychostimulants, dopaminergic agonists, and norepinephrine reuptake inhibitors.29

Among the psychostimulants are methylphenidate (Ritalin, others), amphetamine-dextroamphetamine (Adderall, others), and lisdexamfetamine (Vyvance). Several small-scale studies have shown that methylphenidate enhances attention and processing speed in TBI survivors. One advantage of this drug is that it seems to have few negative side effects.30 Dextroamphetamine has been shown to be effective in treating depression and apathy in TBI. A couple of studies report dextroamphetamine at a dosage of 0.1 to 0.2 mg/kg improved memory, processing speed, attention and mood.31 Both medications [methylphenidate and dextroamphetamine] also increase the release of dopamine and norepinephrine. Lisdexamfetamine has been shown to be effective in treating ADHD in children and adults.32 This drug is thought to work by increasing the local concentration of dopamine and norepinephrine. Side effects are generally mild and similar to those of amphetamine.

Atomoxetine (Strattera) is a norepinephrine reuptake inhibitor approved for treating ADHD in adults. Atomoxetine generally is well tolerated and has been shown to be effective in individuals who do not respond to stimulants. Atomoxetine works by inhibiting norepinephrine reuptake, thus increasing localized concentrations of norepinephrine. A few clinical studies have reported a positive effect of atomoxetine in treating arousal and attention disorders in TBI survivors. Unfortunately, many of the side effects attributed to atomoxetine are common problems in the TBI survivors (such as decreased appetite, insomnia, dry mouth, etc); thus, caution should be exercised when prescribing atomoxetine, especially when these problems are already present.33

Modafinil (Provigil) is a medication used to treat narcolepsy, and some clinicians have suggested a role for this drug in treating problems of arousal in TBI survivors.34 Modafinil’s mode of action is not entirely clear. It has little effect on catecholamine, serotonin, histamine, adenosine, or monamine oxidase B systems. Studies have shown it to inhibit the posterior hypothalamus and the medial preoptic regions and to stimulate glutamate levels in those areas. Animal studies have shown that modafinil stimulates activity in the anterior hypothalamus, hippocampus, and amygdala. Modafinil has been studied in patients with excessive sleepiness associated with narcolepsy, multiple sclerosis, and Parkinson’s disease as well as in a few unpublished studies in TBI survivors. One potential advantage of modafinil is the lack of any major reported adverse side effects.

Recommended dopaminergic medications include amantadine, bromocriptine (Parlodel, others), and carbidopa/L-dopa. Amantadine increases dopamine release and inhibits dopamine reuptake, resulting in an indirect increase in this transmitter. It is also a weak NMDA receptor antagonist. A double blind, placebo controlled, cross over study by Meythaler et al showed benefit with a 6-week course of amantadine in the acute phase of severe TBI based on Mini Mental State Exam, Disability Rating Scale (DRS) and the Glascow Outcome Scale (GOS) testing.35 Zafonte et al showed a reversible, dose-dependent response leading to emergence from minimal conscious states.31 Kraus and Maki documented improvement in motivation, attention, alertness and executive function in 6 TBI survivors.36 Guiltier et al showed benefits in arousal, fatigue, distractibility, and assaultiveness in 30 TBI survivors.37 Patrick et al reported improved responses of pediatric TBI survivors in a low-response state treated with amantadine or pramipexole.38

Dosing should start at 100 mg BID and increase by 100-mg increments on a weekly basis until improvement in function is documented or intolerance is reached. The maximum dosage should not exceed 400 mg. Side effects include headache, dizziness, orthostatic hypotension, and GI problems. Anxiety, hallucinations, depression, confusion, and psychosis have also been reported, but these are rare.

Bromocriptine, an older medication, acts directly on the D2 dopamine receptors. Several studies have shown efficacy in improving initiation, arousal, and cognitive function. Dosing starts at 2.5 mg/day and may be titrated slowly. Side effects include dizziness, faintness, syncope, nausea, galactorrhea and GI problems.

L-dopa is a metabolic precursor of dopamine. It generally is combined with carbidopa to inhibit dopamine’s metabolism in the peripheral nervous system and thus maximize dopamine levels in the CNS. In a study of 12 TBI survivors, there were improvements in concentration, attention, fatigue, hypomania, as well as memory, posture, speech, and motion.39 Krimchansky et al reported on 8 TBI survivors who were in a vegetative state and treated with incremental doses of L-dopa.40 All 8 could follow commands 2 weeks after starting treatment, and 7 progressed to the point of reciprocal interaction. Dosing of carbidopa/L-dopa (Sinemet) should start around 10/100 mg twice a day and slowly increased up to 25/250 mg four times a day. The patient should be closely monitored.

Attention Deficits

Attention deficits following TBI are categorized as selective, sustained, and spatial.41 Selective attention deficits are thought to be due to damage of the cholinergic systems in the hippocampus and refer to the person’s ability to direct attention to a given stimulus. Sustained attention deficits occur when there is damage to the inferior frontal, subcortical, and dorsolateral cortices, the medial temporal areas, the primary and secondary sensory cortices, and the connections between them. Sustained deficits refer to the inability to maintain attention to a stimulus immediately after the withdrawal of the stimulus (vigilance and concentration). Spatial attention deficits occur with damage to the thalamus, right hemisphere, superior colliculus, striatum, and posterior parietal cortex and refers to the inability to identify the exact location of a given stimulus. Attention deficits often present with comorbidities of arousal, perception, recognition, memory and/or executive function.

There are 2 types of memory deficits associated with TBI—deficits in declarative memory (who, what, when and where) and deficits in procedural memory (how). Declarative memory can be subdivided into working memory and long-term memory. Declarative memory problems have been linked to disruption of the glutamate and cholinergic systems in the hippocampus and the dopamine and norepinephrine systems in the frontal cortex. Cholinergic inhibitors have been shown to have some positive benefit on attention/declarative memory in TBI survivors. Two studies have shown significant and lasting positive effects on attention and memory with donepezil. Procedural memory deficits are inflexibly linked to the specific sensorimotor system involved with the given process, so every procedural memory problem is due to a specific focal lesion. The recommended treatments for procedural memory are psychostimulants.

Methylphenidate, dextroamphetamine, and amantadine all have demonstrated efficacy in treating attention deficits. Several random double-blind trials have reported improvements in concentration, motor memory, vigilance, arousal, attention, and distractibility in mild, moderate, and severe TBI following treatment with methylphenidate. Bleiberg et al reported improvements in attention and working memory in survivors of mild TB, treated with dextroamphetamine 5 years after their injury compared with those treated with lorazepam (Ativan) or placebo.42

Memory Loss

Acetylcholinesterase inhibitors have shown some efficacy in improving memory in patients with TBI.43 Physostigmine was shown in one study to provide some improvement in cognitive ability and memory after TBI.43 Donepezil (Aricept, others) has shown improvement in declarative memory in a number of studies in TBI patients.44 Rivastigmine (Exelon, others) showed efficacy in a prospective, randomized, double-blind, placebo-controlled trial of 157 TBI survivors with moderate to severe memory deficits.45

Memantine (Namenda), a NMDA receptor antagonist, also has shown promise in helping TBI survivors with memory deficits, and one of the authors (JCK) has studied it in his TBI patients with cognitive deficits with very positive results.46

In addition to pharmacological treatment, patients with mild TBI who present with cognitive complaints also should be provided with physical rehabilitation and occupational therapy, either in an outpatient or a residential setting.47 They should be provided with assistive technology, including smartphones, electronic note pads, and GPS devices and trained in how to use them.48,49

Treatment of Noncognitive Sequalae

Post-Traumatic Headache

By far the greatest physical complaint after mild TBI is post-traumatic headache (PTH). In a prospective study by Sheedy and Faux of 100 sequential patients with mild TBI, 100% complained of headache upon presentation.50 In a recent prospective study, Lucas et al reported that 58% of individuals who presented for mild TBI at a level 1 trauma center reported headaches 1 year after the injury.51

Most PTHs can be categorized as either tension type headache (TTH) or post-traumatic migraine headache (PTM), with the remainder either referred (ie, cervicogenic) or medication-overuse headache (MOH).52

TTH typically presents as bilateral pressure type pain that is mild to moderate in intensity. It can be either episodic or chronic and often occurs daily, especially in the setting of frequent use of products with acetaminophen, ibuprofen, and opioids; it is then referred to as MOH. Generally TTH is not associated with nausea or photo/phonophobia, and usually is not initiated by physical activity. Treatment generally is pharmacologic and should include prophylactic and palliative therapies.53 Both tricyclic antidepressants (TCAs) and topiramate (Topamax, others) have shown efficacy in reducing the incidence and severity of TTH in patients with mild TBI. Among the TCAs, nortriptyline (Pamelor, others) has the least number of side effects. NSAIDS and acetaminophen (Tylenol, others) are not recommended for breakthrough pain. Tramadol (Ultram, others) or tizanidine (Zanaflex, others) may be useful, off-label, to treat these frequent headaches.

PTMs typically are episodic headache attacks presenting with or without aura. They generally are described as pulsating and unilateral. Comorbidities, such as nausea, emesis, photophobia, and phonophobia, frequently are present, and symptoms are aggravated by physical activity. Treatment again is pharmacologic, with acute, abortive treatment with NSAIDS and triptans. Opioids should be employed only when other medications are ineffective.5

Prophylactic, or preventive medications for migraine include TCAs, anticonvulsants, calcium channel blockers, beta-blockers, and serotonin norepinephrine reuptake inhibitors. Selective serotonin reuptake inhibitors have not had very good efficacy in general, although they may improve anxiety and depression.

MOH, once referred to as rebound headache, is defined by the International Headache Society as headache pain at least 15 days per month, treated pharmacologically for more than 3 months, either developed or worsened during the period of pharmacologic treatment and returned to baseline within 2 months of discontinuing treatment.54 Individuals who self-treat their PTHs with over-the-counter medications are at a particularly high risk for the development of MOH, although patients under supervised care also can develop MOH. Treatment consists of gradual weaning from the overused drug(s).

Other Pain Conditions

Other pain problems associated with mild TBI include neck and back pain, complex regional pain syndrome (CRPS), fibromyalgia, and temporomandibular pain. These may be a result of the trauma from the original injury or sequelae of the mild TBI. Treatment for neck, back, and temporomandibular pain should include NSAIDS, acetaminophen, muscle relaxants, and physical therapy followed by a home exercise program.55 CRPS and fibromyalgia are much more difficult to treat. Both should be treated with a course of physical therapy. Then, for CRPS, pharmacologic intervention includes TCAs, anticonvulsants, NSAIDS, steroids, free radical scavengers, calcitonin, and bisphosphonates.56 For the management of fibromyalgia, low-dose TCAs, fluoxetine (Prozac, others), duloxetine (Cymbalta, others), tramadol (Ultram, others), gabapentin (Neurontin, others), and pregabalin (Lyrica) have been effective.57 Opioids should be considered when other medications and therapies are ineffective.

Comorbid psychological problems, such as depression and anxiety, arising from mild TBI can complicate both the diagnosis and treatment of headache and other pain conditions after mild TBI.58 The treating physician should be on alert for these issues and ready to refer the patient to a mental health professional experienced in providing psychological treatment for TBI as part of a pain management program.

Post-Traumatic Seizures

Approximately 10% to 15% of patients with TBI experience seizures or seizure-like episodes. An elegant overview of post-traumatic epilepsy recently was published, discussing how TBI results in long-term multiple changes in the organization of brain circuits in the cortex and hippocampus that create an imbalance between excitatory and inhibitory neurotransmission, and, therefore, a markedly increased risk for seizures.59

While post-traumatic seizures (PTS) generally are associated with moderate and severe TBI, there is a small, but statistically significant, occurrence after mild TBI, especially in young children, among whom the incidence has been reported to be up to 10%.60 While most mild TBI patients will have their first seizure within a few day of injury, late-onset seizures can occur. It has been reported that 66% of individuals who develop PTS will experience the first episode within the first year after their injury and 80% within 2 years of the injury.2,6

Evaluation should include a thorough EEG workup and brain imaging by either CT or MRI to rule out intracranial bleeds—CT is more sensitive in the very acute phase after the injury.

Treatment should be aimed at controlling seizure activity with a single medication.61 There are many choices for treatment, including lamotrigine (Lamictal, others), topiramate (Topamax, others), tiagabine (Gabitril, others), levetiracetam (Keppra, others), zonisamide (Zonegran, others), oxcarbazepine (Trileptal, others), lacosamide (Vimpat), and older medications such as carbamazepine (Tegretol, others) or divalproex sodium (Depakote, others). In one retrospective study of 30 TBI survivors with active seizure disorders, methylphenidate appeared to decrease seizure rates.62

Dizziness and Photo/Phonophobia

Dizziness is a common complaint after TBI, with 15% to 30% of patients with mild TBI complaining of some form of dizziness or balance problem in the first 12 months after the injury.63 The most common cause of post-concussive dizziness is benign paroxysmal positional vertigo. This occurs when there is damage to the semicircular canals, rendering them sensitive to gravity. Treatment by canalith repositioning maneuvers generally is effective in treating this disorder. A less common cause of dizziness after mild TBI is labyrinthine concussion, which occurs when the trauma damages the tissues of the inner ear. It is marked by acute hearing loss and vertigo.64 Labyrinthine concussion typically resolves spontaneously over the course of a few weeks. In some cases, patients need to be treated with vestibular and balance rehabilitation therapy. Individuals presenting with complaints of dizziness, balance problems, and hearing loss should be evaluated by electronystagmography, videonystagmography, rotary chair testing, and tilt table testing. Treatment generally involves exercise and therapy. In cases where there is a visual component, ocular exercises and/or glasses may useful.

Photo and phonophobia occur in about 15% of patients with mild TBI within 3 months of injury.63 For the majority of individuals, light and sound hypersensitivity will resolve over time without treatment.

Fatigue and Sleep Disorders

The incidence of fatigue after mild TBI is a somewhat controversial topic, with estimates ranging from 2% to 98%.65 A recent study by Englander et al reported an incidence of 30% to 50%.65 This is partially due to the fact that other sequelae, such as PTSD, depression, and insomnia, can cause and/or augment post-concussive fatigue. Patients presenting with persistent complaints of fatigue after mild TBI should undergo a thorough psychological evaluation to rule out other potential causes. Treatment typically consists of physical therapy (PT) and a home exercise program, combined with education about sleep hygiene. In cases that do not respond to conservative treatment, amantadine or modafinil (Provigil, others) may be effective.

There also is a large range in the reported number of patients suffering from post-traumatic sleep disorders because sleep disturbances are part of a post-concussional syndrome (see Table 1). Individuals presenting with post-traumatic sleep disorders should undergo a thorough neurological and neuropsychological examination to rule out any neurological or psychological comorbidities.66 One of the authors (JCK) has presented data on sleep disorders and headaches after mild TBI in a prior article.1

If neurological and neuropsychological studies are negative, patients can be referred for polysomnographic testing. Pharmacological treatments include hypnotic sleep aids such as tizanidine, eszopiclone (Lunesta, others) and benzodiazepines. A home exercise program and education in sleep hygiene may also be very useful.

Patients with mild TBI who present with post injury vision complaints, including double vision and blurred vision, should be referred to a neuro-ophthalmologist or neuro-optometrist for a thorough examination.

Summary

The past 10 to 15 years have seen a renaissance in the diagnosis and treatment of mild TBI. There is a growing acceptance in the existence of both acute and chronic PCD within the medical community. While the tools to diagnose and treat chronic PCD have improved greatly in recent years, the best treatment is prevention A number of controlled, blinded studies have shown that providing a patient with education about mild TBI, what symptoms to expect, and the general duration of those symptoms in either verbal or written form as well as providing support and treatment in the acute phase significantly lessens the progression of those symptoms to the chronic stage.67 A study by Gronwall showed that these kinds of interventions resulted in a 9-fold reduction in the progression to the chronic phase in patients with mild TBI.68 Perhaps patient education coupled with medical, social and psychological support can be the best preventive medicine.

Editor’s note: Part 1 of the TBI series described the general mechanisms of TBI and concussion symptoms generated.6 Part 2 focused on outpatient clinic treatment using various IV medications.46 In this segment, specialists in 3 areas discuss TBI-induced cellular damage to the brain and the management of its sequalae.

Last updated on: June 15, 2015
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