Handbook of Clinical Neurology, Vol. 127 (3rd series) Traumatic Brain Injury, Part I J. Grafman and A.M. Salazar, Editors © 2015 Elsevier B.V. All rights reserved

Chapter 26

Rehabilitation after traumatic brain injury MARY ALEXIS IACCARINO1, SAURABHA BHATNAGAR2, AND ROSS ZAFONTE3* Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital and Harvard Medical School, Boston, MA, USA

1

2

Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Veterans Administration, Boston and Harvard Medical School, Boston, MA, USA

3

Department of Physical Medicine and Rehabilitation, Spaulding Rehabilitation Hospital, Massachusetts General Hospital, Brigham and Woman’s Hopsital, and Harvard Medical School, Boston, MA, USA

EPIDEMIOLOGY Traumatic brain injury (TBI) is a significant cause of morbidity and mortality. Approximately 2.5 million people sustained a head injury in 2010 according to the US Centers for Disease Control and Prevention in the United States. This incidence of TBI is on the rise, revealing approximately a 15% increase from earlier studies. The majority of TBIs are caused by falls, with a bias towards children (0–4 years) and the elderly (over 75 years). Of those who sustain a TBI, approximately 275 000 will require hospitalization and another 50 000 will die. Motor vehicle accidents are the most common cause of TBI-related death, usually associated with ejection from the vehicle. Males are four times more likely to sustain a TBI than females (Faul et al., 2010). In the US, approximately 5.3 million people are living with a TBI-related disability; this represents 2% of the population (Langlois et al., 2006). This is a conservative estimate, with a large portion of injuries, particularly concussions and mild TBIs, going unreported each year. Persons between ages 15 and 44 years represent the majority of new TBIs. In a 5 year follow-up study of braininjured patients requiring acute rehabilitation, about 12% required long-term care. TBIs result in a significant socioeconomic burden due to the relatively young average age of injury coupled with high morbidity and need for long-term care (Corrigan et al., 2014). It is estimated that the direct and indirect cost of TBI in the US is between $60.4 and $221 billion (Coronado et al., 2012). Overall,

the increasing incidence of TBI and expanding cost burden contribute to TBI being labeled as an epidemic with far reaching public health implications.

EARLY REHABILITATION AFTER TRAUMATIC BRAIN INJURY There has been increasing emphasis on the importance of early rehabilitation interventions and neurorehabilitation care. Goals of early rehabilitation include guiding prognosis and reducing the complications of immobility, contractures, bowel and bladder dysfunction, skin breakdown, and sleep disturbances. The neurorehabilitation team meets with the patients and families to help manage expectations, facilitate transitions through stages of recovery, and try to provide a reasonable picture about the recovery process. Studies on early rehabilitation show both reduced intensive care unit (ICU) and hospital length of stay, improved ambulation, and return to independence (Bernhardt et al., 2008; Schweickert et al., 2009). Early rehabilitation strategies include practicing bed mobility, transferring to a chair, ambulation, and activities of daily living. For patients with severe cognitive and functional limitations, there are alternative modalities such as passive range of motion, bracing, and neuromuscular electrical stimulation (Mendez-Tellez et al., 2012). A mobility score may be utilized and has been shown to predict surgical ICU mortality and length of stay (Kasotakis et al., 2012). Barriers to early rehabilitation

*Correspondence to: Ross Zafonte, 125 Nashua Street, Boston, MA 01742, USA. Tel: +1-617-573-2754, Fax: +1-617-573-2759, E-mail: [email protected]

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in patients with TBI include concerns with intracranial pressure, cerebral blood flow, and cerebral perfusion pressure. No large randomized control trials (RCTs) exist to determine the correct time for early mobilization in these individuals. However, with careful monitoring, early rehabilitation can offer significant benefit to critically ill patients (Brimioulle et al., 1997).

PROGNOSIS AND RECOVERY TBI can be a significant burden to patients and families and it is helpful to provide information to them regarding the course of recovery. Factors used to predict long-term recovery include initial physical and cognitive deficits, imaging findings, early improvement, and demographics. Among the best indicators of recovery and outcome after TBI is the length of post-traumatic amnesia (PTA). PTA less than 2 months correlates with a low likelihood of severe disability while PTA greater than 3 months correlates with a low likelihood of a good outcome (Kothari and DiTommaso, 2013). Resolution of PTA is the period when patients can incorporate new events into their working memory. Two short questionnaires can be used to assess recovery from PTA. The Galveston Orientation and Amnesia Test (GOAT) evaluates global orientation and recall of preinjury, postinjury, and hospitalization events. Scored on a scale of 0 to 100, two successive scores greater than 75 indicate resolution of PTA. The Orientation Log (O-Log) provides 10 orientation and circumstance questions with a score of up to 30 points. Two consecutive scores of 25 indicate a resolution of PTA. Time to follow commands has been found to be among the most important predictors of outcome in pediatric TBI (Austin et al., 2013). Among adults, time to follow commands has also been felt to contribute in a significant way to prognosis (Sherer et al., 2008). The Glasgow Coma Scale (GCS) is a measure of the depth of coma and is used in early assessments after a TBI. Scores recorded within the first 24 hours of injury correlate with outcomes, with lower scores predicting worse outcomes. The GCS incorporates motor, verbal, and eye-opening responses. Of the three categories, the motor score is the most accurate predictor of early outcomes. However, some patients with low GCS scores do progress to make good recoveries. The Glasgow Outcome Scale (GOS) is a 5 point scale that divides patients into broad groups based on function (Table 26.1). In studies, this scale is used because the categories are easily generalizable and it has high inter-rater reliability. It correlates with outcomes at 6 months and with other injury severity measures, such as GCS and length of PTA. However, from a rehabilitation perspective, the broad strokes of severity enveloped in each category of the GOS do not accurately allow the

Table 26.1 Glasgow Outcomes Scale Dead Vegetative state – alive but without any awareness of self or environment (unconscious) Severely disabled – conscious but fully dependent on others; unable to be independent for 24 hours Moderately disabled – disabled but independent; can travel by public transit and work in a supported environment Good recovery – mild to no deficits; able to resume normal physical and social activities

measurement of functional capacity. Additionally, the abilities listed for each category may not match an individual’s functional goals. Thus, this scale may be less useful for patients, families, therapists, and clinicians. Perhaps more useful and universally utilized is the Glasgow Outcome Scale-Extended (GOS-E). It is a 1–8 point scale and provides for a more extended examination of functional status (Wilson et al., 1998). The Disability Rating Scale (DRS) assesses eight categories of function, not limited to physical and cognitive impairments. It also evaluates performance in activities of daily living and community reintegration. The DRS is applicable in the acute, subacute, and community settings to assess progress in rehabilitation and predict ability to return to employment. The Functional Independence Measure (FIM) is another rehabilitation-oriented scale that scores motor and cognitive skills based on the amount of assistance required to complete a task. Unlike the DRS, the FIM is not designed specially for brain-injured patients. However, it is a more sensitive measure of functional capacity and may be more sensitive to changes over time (Kothari and DiTommaso, 2013). A prolonged duration of coma is associated with worse outcome. As a threshold for predicting recovery, patients in coma for greater than 4 weeks are very unlikely to make a good recovery as defined by GOS while coma less than 2 weeks is rarely associated with severe disability. However, recent data regarding longterm outcomes among those with the most severe injuries raises doubts about this finding (Hart et al., 2014b). Age at injury is also a strong prognostic indicator. In general, older age is associated with worse outcomes and age over 65 is rarely associated with good recovery (Chuang et al., 2011). Neuroimaging is also important in assessing injury severity. The presence of bilateral brainstem lesions on magnetic resonance imaging (MRI) is not associated with a good recovery as measured by the GOS. Similarly, computed tomography (CT) scan findings of epidural hematoma, subdural, or subarachnoid hemorrhage, cisternal effacement, and significant midline shift are

REHABILITATION AFTER TRAUMATIC BRAIN INJURY associated with worse outcomes (Bigler and Maxwell, 2013). For further discussion regarding prognostic indicators, the reader is referred to Chapter 29. Ultimately, educating patients and families about prognosis after TBI requires providing both general trends and specific benchmarks by which to monitor recovery. However, despite our best efforts, wide variability in patient outcomes exists. Severely injured patients sometimes make miraculous recoveries while those with milder injuries can suffer with debilitating and persistent symptoms. In discussion about prognosis, it is extremely important to acknowledge these variables to patients and their families.

REHABILITATION AND DISORDERS OF CONSCIOUSNESS Disordered consciousness includes patients in a coma, vegetative state, or minimally conscious state. The definitions of these states and assessments of disorders of consciousness (DOC) patients are reviewed in Chapter 25. DOC patients benefit from rehabilitation despite their low level of interaction. Currently, there are few large RCTs that capture the level of improvement that rehabilitation provides. However, the lack of data is presumed to be more indicative of the challenge in conducting these types of trials and not necessarily due to lack of efficacy of therapy. The goal of rehabilitation in this setting is to establish a reliable form of communication and to have patients participate in self-care. Taking what we know of the neurophysiology of TBI, it is presumed that pathways which involve dopamine and similar activating neurotransmitters allows for wakefulness and command following. Thus, rehabilitation interventions in severe brain injury use neuromodulation to target and possibly restore these pathways. Commonly used neuromodulatory therapies include pharmacologic interventions, deep brain stimulation, and noninvasive brain stimulation. Amantadine is a dopamine agonist and that has been shown to accelerate recovery in patients with DOC (Giacino et al., 2012). Bromocriptine, methylphenidate, levodopa, and apomorphine are other dopaminergic agents that have smaller, nonrandomized trials to support their use for physical and cognitive recovery (Giacino et al., 2013). Medications that potentiate g-aminobutyric acid (GABA), such as zolpidem and baclofen, have also been effective in improving arousal for some severely injured patients (Sara et al., 2009; Whyte and Myers, 2009). Although generally considered sedating, these drugs may have a paradoxical effect on severe TBI. A recent study of zolpidem suggested a 4.8% response rate among those with DOC (Whyte et al., 2014). Neuromodulation can also be achieved through brain stimulation. Deep brain stimulation (DBS) provides

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electrical stimulation to structures that regulate cortical activity to promote arousal. Stimulation of the thalamus and midbrain reticular formation has been shown to improve command following in vegetative patients (Yamamoto and Katayama 2005; Schiff et al., 2007). Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive, extracranial modality that uses magnetic fields to deliver an electrical stimulus to the brain. Several case studies have shown improvement in arousal with rTMS and it is thought that a trial of rTMS may help identify patients likely to respond to implanted stimulators (Louise-Bender Pape et al., 2009; Piccione et al., 2011). Physical therapy interventions such as range of motion exercises and splinting are mainstay therapies in rehabilitation of the severely injured. In patients with DOC, they are a form of sensory stimulation and may provide sensorimotor feedback. There are no robust studies which show that these intervention impact consciousness. However, they are effective in reducing complications of immobility, including contracture, spasticity, and heterotopic ossification (HO), and therefore should be used in patients with DOC.

REHABILITATION STRATEGIES FOR COGNITIVE DYSFUNCTION Cognitive dysfunction after TBI includes impairments in memory, attention, concentration, communication, executive function, and processing speed. Many patients will experience deficits in multiple areas that will persist long into their rehabilitation course. Strategies to improve cognitive function can be pharmacologic or therapy-based. Individual responses to cognitive rehabilitation vary and are heavily influenced by premorbid cognitive function and the ability of the patient to participate in therapy. Evaluating a patient with cognitive deficits should include a thorough medical evaluation, a review of current medications, and obtaining a history of premorbid cognitive function and psychological disease. The presence of infection, metabolic derangements, endocrine dysfunction, seizures, mood disturbance, sleep–wake cycle dysregulation, and sedating medications can exacerbate cognitive impairments. Every effort should be made to identify these comorbidities to reduce confounding the diagnosis of cognitive dysfunction. Pharmacotherapy can play an important role in cognitive rehabilitation. There is limited level 1 evidence for most medications and the majority of studies are limited to small RCTs or case series. The most evidence exists for the use of methylphenidate, a monoamine agonist. Methylphenidate has been shown to increase attention and concentration for TBI patients in both a small

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RCT and case series (Rees et al., 2007, Willmott and Ponsford, 2009). Amantadine has been shown to be effective in arousal in DOC, but less evidence exists for its use in cognitive rehabilitation. Case series support its role in improving short-term memory, attention, planning, and impulsivity (Kraus and Maki, 1997); however, a RCT did not find significant improvement in overall cognitive function (Schneider et al., 1999). Cholinergic agonists, such as donepezil and rivastigmine, are used in a variety of neurologic disorders that have cognitive manifestations. In TBI patients, both medications have been suspected to improve working memory and sustained attention (Zhang et al., 2004; Tenovuo et al., 2009). A large study by Silver did not show an overall benefit to rivastigmine based on the primary outcome metrics; however, a secondary analysis among those with the most significant deficits suggested a possible effect (Silver et al., 2009). A randomized double-blind placebo-controlled trial on donepezil is now underway (National Rehabilitation Information Center, 2013). Medications such as selective serotonin reuptake inhibitors (SSRIs), modafinil, and citicoline have some theoretical basis for use in cognitive dysfunction after TBI but evidence is lacking. There is one small series showing cognitive improvement with fluoxetine in TBI patients. Modafinil has not been shown to improve cognitive function but does appear to benefit excessive daytime fatigue, which impede therapies and mimic cognitive dysfunction (Sheng et al., 2013). A recent large RCT on citicoline did not show significant benefit in cognition (Zafonte et al., 2012). The focus of therapy for impairments in cognition is remediation. This refers to behavioral treatments that use practice with cognitive and adaptive strategies to improve specific cognitive skills. A systematic review by Cicerone analyzed 112 studies to derive evidencebased practice guidelines for cognitive therapy. Table 26.2 lists strategies based on these practice guidelines (Cicerone et al., 2011). One note is the fact that some controversy exists regarding the role of cognitive therapy itself, efficacy, subpopulation specific need and optimal timing (Salazar et al., 2000). (The reader is also referred to Ch. 37.)

MOTOR RECOVERY AFTER TRAUMATIC BRAIN INJURY Motor recovery in TBI patients is variable. However, as compared to other neurologic disorders such as stroke, TBI patients have lower incidence, decreased severity, and better prognosis for recovery of motor function. In general, the majority of motor recovery occurs in the first 6 months after TBI. In a review by Katz, mechanism of injury was found to be a predictor of upper

Table 26.2 Cognitive recovery strategies Attention Visuospatial

Language and communication

Memory

Executive functioning

Direct attention training Metacognitive strategies Scanning techniques in hemi-neglect Increased attention and cueing of areas of visuospatial neglect Social communication skills training Initiation of linguistic therapy during acute rehabilitation Target therapies for specific language deficits such as reading comprehension and language formation Training of internal (visual imagery) and external (notations) compensatory strategies Externally directed stimulation devices Training of metacognitive strategies for behavior and emotion Incorporate formal problem solving strategies into daily life

(From Cicerone et al., 2011.)

extremity motor recovery time with focal lesions averaging 3 months for maximal motor recovery and diffuse axonal injury recovering more gradually, generally 6 months (Katz et al., 1998). Shorter duration of loss of consciousness and mild initial deficits are also associated with faster recovery (Jang, 2009). Regarding ambulation, a significant portion of TBI patients will ambulate postinjury. A study of 112 TBI patients admitted to inpatient rehabilitation found that 73% were independently ambulating at 5 months. Predictors of ambulation include younger age, higher admission gait scores, and shorter duration of PTA (Katz et al., 2004). Recovery of motor function is an active process. Patients should participate in both occupational and physical therapy with the goals of improving strength, endurance, mobility, balance, and coordination. The various types of therapy intervention are beyond the scope of this chapter; however, the overall theme for functional rehabilitation is task-specific and practice-based therapy. In one large randomized trial of stroke patients with upper extremity impairments, 2 weeks of constraint induced movement therapy, in which the affected arm was forced to perform specific tasks, was associated with greater functional motor recovery than nontaskoriented usual care (Wolf et al., 2006). This technique remains somewhat controversial in stroke and has had limited studies in TBI. However, in general, several decades of research shows strong evidence for usedependent and skill-dependent modulation of the motor cortex. In addition, task-oriented therapy incorporates

REHABILITATION AFTER TRAUMATIC BRAIN INJURY motor programming, which is required for accurate timing, speed, and coordination of a task. As patients progress with motor recovery they may require various assistive devices for mobility and performing activities of daily living. For low functioning individuals, equipment needs are extensive and may include hospital bed, wheelchair, mechanical lift, shower chair, bracing to maintain positioning, and adaptive technologies for communication. For those that ambulate, assistive devices include those needed for balance and weight support, such as walkers and canes, and those that aid in limb positioning such as hip, knee, ankle, and foot orthoses. Determining the appropriate assistive device requires coordination from many clinicians involved in the patient’s care: physical therapists, occupational therapists, speech therapists, orthotists, device vendors, physiatrists, and caregiver knowledge of the home environment. It is the responsibility of the physician, to incorporate knowledge of the primary pathology and input from other specialists to determine the appropriate assistive devices.

POST-TRAUMATIC AGITATION Agitation is a form of delirium characterized by extreme emotional, aggressive, or disinhibited behaviors. It is a common problem in TBI patients and it tends to occur during the early stages of recovery as patients emerge from a minimally conscious state or PTA is resolving. Generally post-traumatic agitation lasts days to weeks. However, patients can remain in an agitated state much longer. Agitation is more likely in patients with longer duration of PTA and in those with frontal or temporal lesions. Evaluation of an agitated patient requires ruling out other causes for behavior change. Like cognitive dysfunction, aggressive behavior and confusion can be precipitated by infection, metabolic derangements, pain, sleep disturbances, bowel or bladder dysfunction, seizures, new intracranial pathology, and medications. Once the diagnosis of post-traumatic agitation is made, each episode of agitation should be described and quantified using an objective measure such as the agitated behavior scale (ABS). The ABS was designed to monitor post-traumatic agitation in the rehabilitation setting. The score consists of 14 items rated on a 1–4 scale with a score greater than 21 indicating agitation (Corrigan, 1989). Use of the ABS allows for objective measurement of treatment effectiveness (Lombard and Zafonte, 2005). As with all aspects of the rehabilitation care, it is important that agitation and its treatment strategies are explained to the patient and their family. Environmental management is often the initial treatment for post-traumatic agitation since many medications that manage aggression can be deleterious to the

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recovering brain. The goal is to provide a supportive environment that keeps the patient and caregivers safe. The patient should be placed in a quiet room to reduce environmental sensory input. Visual and auditory stimuli from television, radio, hospital alarms, and even visitors should be limited. Restraints should be avoided as they can often escalate the aggressive behavior. Using a dedicated floor bed, net bed, or placing the mattress on the floor if other options are not available, can protect patients from falling without limiting their ability to move their extremities. For akathisia, patients should be allowed to thrash, pace, and have verbal outbursts, as long as they are not causing harm to themselves or others. The patient requires frequent reorientation to their situation and surroundings and reassurance that they are in a safe place. Ideally, a single provider, who the patient is already familiar with, should conduct all conversation with the patient. When environmental adaptation alone is insufficient to manage agitation pharmacotherapy is added. b-Blockers, antiepileptics, neurostimulants, and antidepressants are commonly used, while typical antipsychotics and benzodiazepines are avoided due to their potentially adverse effects on cognitive recovery. Below is a list of commonly used medications for agitation.

b-Blockers A Cochrane review in 2006 determined that b-blockers are the most efficacious treatment for post-traumatic agitation and aggression because they modulate the hyperadrenergic state that occurs after brain injury. Lipophilic b-blockers are most commonly used due to their propensity to cross the blood–brain barrier. Of the studies used to support the conclusion of this Cochrane review, both propranolol and pindolol showed efficacy (Fleminger et al., 2006). Caution should be exercised when using these medications in patients with certain cardiovascular conditions such as arrhythmias, bradycardia, or hypotension.

Neuroleptics The use of antipsychotics seems a logical treatment approach given that post-traumatic agitation is a form of delirium driven by excess dopamine. However, the deleterious effects of antipsychotics are thought to outweigh their benefits. In animal models, typical antipsychotics are associated with slower motor recovery (Feeney et al., 1982). In humans with TBI, haloperidol has been correlated with longer periods of PTA (Rao et al., 1985). Small trials and case series support the use of quetiapine, droperidol, and methotrimeprazine for acute and subacute agitation (Chew and Zafonte, 2009). If antipsychotics are required, atypical antipsychotics are preferred over typical antipsychotics because

416 M.A. IACCARINO ET AL. they pose a lower risk of extrapyramidal side-effects and Other medications in comparative animal studies show less cognitive There are a host of other psychotropic medications that impairment (Wilson et al., 2003). are used for post-traumatic agitation such as SSRIs, tricyclic antidepressants, trazodone, lithium, and buspirAntiepileptics one. Often these may be utilized because they treat a concurrent disease process, such as depression, baseline Valproic acid and carbamazepine are the most commood disorder, or sleep disturbance. However, evidence monly used antiepileptics in post-traumatic agitation. of their use for agitation is limited to case studies and Valproic acid is well known for its use in bipolar mania small series. A review of the side-effect profiles for and acts via modulation of GABA. In a retrospective these drugs is advised before their use. review of 29 patients with TBI, 26 had improvement in agitation with 1250 mg/day valproic acid (Chatham Showalter and Kimmel, 2000). Carbamazepine has been SPASTICITY shown to decrease angry outburst and combativeness in two small case series of TBI patients (Azouvi et al., Spasticity is a common complication of moderate or severe TBI. It is defined as a velocity-dependent increase 1999). Antiepileptics have also been implicated in stuntin a muscle’s resistance to stretch. In injuries above the ing recovery. Both phenytoin and carbamazepine have level of the a motor neuron, brain, and spinal cord, there been shown to slow motor and speed tasks (Smith et al., 1994). Valproate has not shown a negative or posis loss of descending inhibitory signals to the spinal itive effect on neurorecovery (Dikmen et al., 2000). stretch reflex. Thus, with voluntary muscle contraction, antagonist muscles are not inhibited. Instead, they involuntarily contract in response to stretch and a significant Neurostimulants resistance is felt when trying to move or position a limb. Methylphenidate has been shown to reduce anger in Spasticity tends to develop days to weeks after injury. chronic TBI but evidence in post-traumatic agitation is It impairs functional mobility, causes pain, and interlacking (Mooney and Haas 1993). Amantadine is effecferes with nursing care. It also increases the risk for tive for memory and initiation after a TBI and has been decubitus ulcers, fractures, heterotopic ossification, used by some experts for excessive behaviors. However, and contractures. Patients who suffer the detrimental there is no definitive evidence for its use in agitation. effects of spasticity will often require long-term follow-up for spasticity management. Appropriate determination of muscles that require treatment is parBenzodiazepines amount. In some situations, the patient’s tone may conBenzodiazepines are commonly used to treat agitated fer a functional advantage and tone reduction may not behavior. However, like some antipsychotics, benzodiazbe desired. epines pose significant harm to TBI patients. Both animal Evaluation of muscle tone may be scored using the and human studies show acute and chronic cognitive Modified Ashworth Scale (MAS). The MAS provides impairments with their use. Benzodiazepines also have a 1–5 grading of muscle tone based on resistance in range significant cognitive impact when discontinuing their of motion. Grading spasticity helps to determine treatuse and can be habit forming. Thus, they are not approment effectiveness and monitor for a change in symppriate for chronic use in post-traumatic agitation, which toms. Acute increase in spasticity can occur in the is usually a temporary state. Overall, the negative effects setting of infection or noxious stimuli, such as fracture, of benzodiazepines are substantial and many experts deep venous thrombosis, intra-abdominal pathology, or consider them contraindicated in the TBI population. even an ingrown toenail. Patients and caregivers should be educated regarding this phenomenon, as it can be a warning sign for illness or injury. Amantadine Treatments for spasticity are divided into nonpharAmantadine is a pre- and postsynaptic dopaminergic macologic modalities and systemic and locally delivered agent with weak N-methyl-D-aspartate (NMDA) antagmedications (Tables 26.3–26.5). In the TBI population, onist properties. Its use in agitation was reported to be local pharmacotherapy and physical modalities are often effective in two cases (Chandler et al., 1988). A recent, favored over systemic medications because many oral single-site randomized trial by Hammond and coldrugs are centrally acting thus delaying neurorecovery leagues has shown a possible benefit (Hammond et al., and resulting in cognitive side-effects. Many patients 2014). A randomized, multisite clinical trial is awaiting will require a combination of multiple strategies for results. spasticity management.

REHABILITATION AFTER TRAUMATIC BRAIN INJURY Modalities used for spasticity treatment Stretching Splinting Serial casting Direct muscle loading

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DYSAUTONOMIA

Table 26.3

Heat Anatomical joint positioning Electrical stimulation

Biofeedback Direct muscle pressure Tendon vibration

After a TBI, patients can develop episodic hypertension, tachycardia, hyperthermia, perspiration, and increased muscle tone. Although the exact mechanism by which this occurs is not completely understood, these symptoms are thought to be the result of either direct injury or functional miscommunication of the autoregulatory centers in the brain that control sympathetic responses

Table 26.4 Systemic antispasticity medications Drug

Mechanism of action

Therapeutic considerations

Oral baclofen

Centrally acting GABA analog. Binds GABAB receptor at presynaptic terminal to inhibit the muscle stretch reflex Centrally acting GABA analog. Binds GABAB receptor at presynaptic terminal to inhibit the muscle stretch reflex

Can cause somnolence Abrupt discontinuation can cause seizure

Intrathecal baclofen

Dantrolene

Blocks calcium ion release from the sarcoplasmic reticulum of muscle

Gabapentin

GABA analog, indirect effect on GABAergic transmission

Clonidine

Centrally acting a2 agonist

Tizanidine

a2 agonist that inhibits excitatory influences of the sensory afferent arc of the motor neuron

Reduced systemic side-effects compared to oral Lower extremity effect greater than upper extremity effect Implanted device requiring long-term commitment to treatment and maintenance May reduce autonomic dysfunction Only peripherally acting Often preferred for brain injury mediated spasticity Can cause liver toxicity Favorable side-effect profile Minimal drug–drug interaction Antiepileptic properties Oral or transdermal May cause hypotension Withdrawal can cause rebound hypertension Can cause dizziness, hypotension, sedation Slow up-titration of medication reduces side-effects

GABA, g-aminobutyric acid.

Table 26.5 Local antispasticity medications Medication

Mechanism of action

Therapeutic considerations

Botulinum toxin type A

Inhibits release of neurotransmitter chemicals by disrupting the functioning of the SNARE complex required for exocytosis of synaptic vesicles Neurotoxin, denatures proteins in the area in which it is injected

Highly selective for individual muscles Temporary effect (3–6 months) Improved with concurrent stretching program Few side-effects Can cause dysesthesias if injected near sensory nerves Longer effect period, may be permanent

Phenol

SNARE, SNAP (soluble NSF attachment protein) receptor.

418 M.A. IACCARINO ET AL. and catecholamine release (Blackman et al., 2004). In the all useful for symptom management. Particularly, intraliterature, dysautonomia is synonymous with paroxysthecal baclofen may be a good long-term therapeutic mal autonomic instability and dystonia (PAID), autooption because it has the added benefit of treating spasnomic instability syndrome, sympathetic storming, ticity with a relatively low side-effect profile and minihypothalamic-midbrain dysregulation syndrome, and mal systemic effects. A small clinical series has diencephalic epilepsy. suggested benefit from the utilization of gabapentin Few studies have looked at the incidence and outas early treatment (Baguley et al., 2007). comes for patients that develop dysautonomia. Two recent retrospective reviews assessing DOC patients at HETEROTOPIC OSSIFICATION acute rehabilitation revealed between 8% and 34% of patients had dysautonomia (Nakase-Richardson et al., Heterotopic ossification (HO) is a common and some2013; Whyte et al., 2013). In a retrospective review of times functionally disabling complication of TBI. It is 35 TBI patients, dysautonomia was associated with the the formation of lamellar bone in extraskeletal soft tispresence of diffuse axonal injury, preadmission hypoxia, sues. Myositis ossificans is a similar process that occurs and brainstem injury. Dysautonomia was associated with in muscle. HO occurs most often at the hips, elbows, and shoulders. It has variable severity with some patients longer ICU and rehabilitation lengths of stay, worse GOS developing asymptomatic HO while others have fusions and FIM scores at rehabilitation discharge, and greater persistence of PTA (Baguley et al., 1999). of joints, nerve and muscle entrapment, and a complete Strict clinical criteria for dysautonomia are lacking, loss of functional limb use. The incidence of HO in TBI but Chuang et al. (2011) propose that the diagnosis patients is between 10% and 70% with about 10–20% of should be based on the “operational definition of paroxpatients having clinically significant disease. Decreased ysmal increases”: heart rate greater than 120 beats/ ambulation is a major risk factor for developing HO minute, respiratory rate greater than 30 per minute, temafter TBI. Other factors that are associated with HO include longer duration of coma, increased spasticity, perature elevation, systolic blood pressure greater than pressure ulcers, infections, and decubitus ulcers 160 mmHg, the presence of sweating or flushing, elevation in baseline muscle tone, and posturing (either decer(Dizdar et al., 2013). ebrate or decorticate). Recognizing this constellation The pathophysiology of HO is not fully understood of symptoms and promptly treating them are important and the various contributing theories are beyond the for patient outcomes. Persistent tachycardia can lead scope of this chapter. However, in pathologic specimens, to dysrhythmias and chronotropic cardiomyopathy. it has been shown that osteoblasts and fibroblasts begin Uncontrolled hypertension can lead to intracranial hemto form in soft tissue areas that have undergone microvascular and edematous changes. Ultimately osteoblast orrhage. Increased metabolic demands that occur from accumulation develops into osteoid and ectopic bone increased muscle tone and posturing can lead to a highly catabolic state, with one study noting up to 25% reduc(Sakellariou et al., 2012). tion in body weight. Dehydration and loss of total body The most common presenting symptom of HO is water will occur with persistent sweating and hypertherpain. Other signs include swelling, erythema, and loss mia. It is also prudent to rule out other disorders of range of motion. Since HO is considered a noxious that cause similar symptoms such as post-traumatic stimulus, spasticity and dysautonomia can also be prehydrocephalus, other causes of increased intracranial senting complaints. Radiographs are able to capture mature HO but are not sensitive for early disease. pressure, seizure, malignant hyperthermia, serotonin synA three phase bone scan is a more sensitive study for drome, and sepsis. Similar to spasticity, dysautonomia can also be a sign of an infection, uncontrolled pain, uriearly HO but will eventually lack utility as the ectopic nary retention, bowel dysfunction, and pressure ulcers. bone matures. Elevated alkaline phosphatase, Immediate interventions to emergently treat dysautog-glutamyl transferase, creatinine phosphokinase, and nomia include repositioning the patient in bed, placing erythrocyte sedimentation rate can be elevated but are the limbs in a neutral anatomic position, removing noxnot specific for HO. ious stimuli, and reducing sensory input from the surEvidence for specific treatments of HO in TBI is limited and most interventions are extrapolated from work rounding environment. In the critical care setting, in the spinal cord injury population. Preventative meastimuli such as ventilators, catheters, and other monitors may not be easily removed and thus patients may require sures include reducing spasticity, muscle stretching, presedation to control their symptoms. In the rehabilitaserving joint range of motion, and avoiding local trauma tion setting, dopaminergic medications (specifically such as fracture or skin breakdown. Once HO develops bromocriptine), clonidine, benzodiazepines, b-blockers, there are no treatments to reverse formation. The goal of intrathecal baclofen, gabapentin, and antiepileptics are treatment is to stop the growth of existing ectopic bone

REHABILITATION AFTER TRAUMATIC BRAIN INJURY and prevent new HO formation in other joints. Splinting and range of motion exercises are the mainstays of therapy. As joints become more rigid, stretching programs need to be intensive and exert significant force on restricted areas. Treatment requires a knowledgeable therapist, as overaggressive stretching may cause further microtrauma and contribute to worsening HO. Since inflammation may be a cause of HO, acute medication therapy consists of anti-inflammatories (usually ibuprofen or indometacin). Bisphosphonates (most studies use etidronate) are also first-line treatments and are thought to disrupt ectopic bone turnover. Once HO has matured (6 months to 1 year), radiation therapy can be used to prevent new bone growth. When function is severely reduced, surgery can be a late intervention to restore motion. However, surgery is not considered until bone formation has terminated and a bone scan is normal for greater than 1 year.

OTHER TRAUMATIC BRAIN INJURY COMPLICATIONS THAT IMPACT REHABILITATION As patients progress from acute care through rehabilitation there are many other medical complications that arise (Table 26.6). These are discussed in other chapters. Many of these sequelae will present with symptoms of cognitive or motor decline and reduction in functional mobility and independence. Physicians in the rehabilitation setting should have a high degree of suspicion to evaluate for these potential complications.

REHABILITATION OF MILD TRAUMATIC BRAIN INJURY AND CONCUSSION While the vast majority of those with mild TBI and concussion recover relatively rapidly, it should be noted that some significant percentage are left with longer term impairments (McMahon et al., 2014). Concerns remain over the long-term sequelae associated with multiple mild TBI or concussions and those with complicated mild TBI may experience prolonged levels of PTA Table 26.6 Other complications after traumatic brain injury Neuroendocrine: Syndrome of inappropriate antidiuretic hormone Cerebral salt wasting syndrome Diabetes insipidus Thyroid dysfunction

Seizure disorder Hydrocephalus Mood disturbance Depression Sleep disorder Headache Neuropathic pain

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previously unsuspected (Hart et al., 2014a). Numerous therapies have been suggested for those with prolonged symptoms after a concussion or mild TBI. These have typically focused on symptomatic interventions such as sleep disturbances, visual and vestibular deficits, headache management, cognitive hurdles, and affective complaints. While having some points worthy of debate, the Ontario Neurotrauma Foundation guidelines form a reasonable construct for therapeutic planning and discussion (Ontario Neurotrauma Foundation, 2013). The reader is referred to the Chapter 9 for further discussion of mild TBI.

HEALTH SYSTEMS CHANGE As with other areas of healthcare, TBI rehabilitation has been impacted by current healthcare payment structures and reimbursement. As noted previously in this chapter, the economic burden of TBI is substantial and thus the balance of providing appropriate care and curbing healthcare expenditures is particularly difficult in this population. Transfer from acute care hospitals to acute rehabilitation facilities is influenced by the patient’s insurer, long-term care needs, and other factors affecting discharge planning (e.g., disposition to home versus various long-term care facilities, level of care needed, and type of short- or long-term aid required). In TBI patients, there is a trend toward reduced number of admissions to inpatient rehabilitation and decreased length of stay. Hoffman et al. found an overall 16% decrease in admission rates for TBI patients to inpatient rehabilitation after the enactment of Medicare’s Inpatient Rehabilitation Facility Prospective Payment System (Hoffman et al., 2012). Similarly, there is a general reduction in number of outpatient therapy visits and increasing difficulty in obtaining funding for necessary equipment and assistance in the home. It is unclear as to the impact that these shifts have had on the functional outcome of patients. However, the improvements made with rehabilitation, including improved return to work, decreased comorbidities, and reduction of complications of TBI, should reduce overall cost of care for these patients. If one evaluates a long-term, patient-oriented outcomes view, it is quite possible that rehabilitation strategies would be cost-effective. Research and outcomes studies are needed to further determine the cost-benefit of rehabilitation and the appropriate level of care.

FUTURE DEVELOPMENTS IN TRAUMATIC BRAIN INJURY REHABILITATION Rehabilitation for those with TBI will likely develop a more refined understanding of injury mechanism and recovery allowing us to deal with the heterogeneity of

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this disease in a more logical manner. Biomarkers, neuroimaging, and electrophysiologic techniques will allow us to better target specific interventions and link mechanism to clinical delivery and outcome. It is likely that no single intervention or agent will provide a panacea for postacute TBI care. Rather, a logical refinement of multiple interventions modeled on a precision-based understanding of the injured person and injury factors will be needed.

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