Key points

Traumatic brain injury (TBI) in the United States is well publicized for the potential long-term effects. With incidence of TBI as defined by emergency department visits, hospitalization, and deaths rising ongoing attention from public and private organizations continues. These data show increasing rates of brain injury driven by emergency department visits gaining 56% from 2007 to 2010. The rates of TBI-related hospitalization have been relatively stable over that period of time and associated deaths have decreased. It is postulated that deaths have decreased owing to a focus on primary prevention and improving acute management.

The management of moderate-severe TBI in the acute care setting is shared by critical care physicians, neurosurgeons, trauma surgeons, neurologists, and physiatrists. The initial goals of acute care management are prevention of the secondary injury by surgical management, management of intracranial pressures, respiratory support, and management of concurrent injuries. The other providers typically manage these conditions while the brain injury rehabilitation specialist assists in management of many other brain injury–specific complications in the acute and subacute periods. Various domains including physical, cognitive, behavioral, and somatic can be involved.

Once the patient is stabilized medically after the brain injury, transitions to the next level of care are planned. Despite decreasing numbers of patients post-TBI transferring to acute rehabilitation in the postprospective payment system, acute inpatient rehabilitation is a consideration for all patients after moderate-severe TBI. Management of medical complications after TBI continues in this setting as well. This process can include the management of posttraumatic seizures, paroxysmal sympathetic hyperactivity, spasticity, hydrocephalus, agitation, neuroendocrine dysfunction, heterotopic ossification, venous thromboembolism, and CN dysfunction.

Posttraumatic seizures

Posttraumatic seizures and posttraumatic epilepsy can develop after TBI with an incidence described between 4% and 53%. Risk factors for seizure development include hydrocephalus, intracranial hemorrhage, depressed skull fracture, surgical hematoma evacuations, lower Glasgow Coma Scale levels, dural penetration, parietal lesions, and focal neurologic deficits. Additionally, late seizures—those that develop after day 7 post injury—are also associated with prolonged duration of posttraumatic amnesia and a lower Glasgow Coma score. Late seizures are defined as those seizures arising after day 7. Immediate and early seizures are described as in the first 24 hours and between 24 hours through 7 days, respectively. Classic research showed that seizure prophylaxis beyond the first 7 days does not add any additional benefit in the prevention of late posttraumatic seizures. Traditionally, phenytoin was used based on the classic studies ; however, recently other medications were shown to have equal/better seizure control. Late development of seizures after TBI continues at a higher rate than the general population. Based on the veterans of the Vietnam era, this increased incidence continues decades later. The treatment of seizures is recommended with the development of early and late seizures. First-line treatment is antiepileptic medication; however, for medication-refractory seizures, surgical resection of the seizure focus and vagal nerve stimulators have also been described. There is lack of consensus of timing of medication discontinuation. Withdrawal of antiepileptics after seizure development is typically delayed 1 to 2 years after the last seizure. Electroencephalography can provide more information and it is reasonable to include neurologists in this decision.

Posttraumatic seizures

Posttraumatic seizures and posttraumatic epilepsy can develop after TBI with an incidence described between 4% and 53%. Risk factors for seizure development include hydrocephalus, intracranial hemorrhage, depressed skull fracture, surgical hematoma evacuations, lower Glasgow Coma Scale levels, dural penetration, parietal lesions, and focal neurologic deficits. Additionally, late seizures—those that develop after day 7 post injury—are also associated with prolonged duration of posttraumatic amnesia and a lower Glasgow Coma score. Late seizures are defined as those seizures arising after day 7. Immediate and early seizures are described as in the first 24 hours and between 24 hours through 7 days, respectively. Classic research showed that seizure prophylaxis beyond the first 7 days does not add any additional benefit in the prevention of late posttraumatic seizures. Traditionally, phenytoin was used based on the classic studies ; however, recently other medications were shown to have equal/better seizure control. Late development of seizures after TBI continues at a higher rate than the general population. Based on the veterans of the Vietnam era, this increased incidence continues decades later. The treatment of seizures is recommended with the development of early and late seizures. First-line treatment is antiepileptic medication; however, for medication-refractory seizures, surgical resection of the seizure focus and vagal nerve stimulators have also been described. There is lack of consensus of timing of medication discontinuation. Withdrawal of antiepileptics after seizure development is typically delayed 1 to 2 years after the last seizure. Electroencephalography can provide more information and it is reasonable to include neurologists in this decision.

Paroxysmal sympathetic hyperactivity

Paroxysmal sympathetic hyperactivity is thought to result from uninhibited sympathetic outflow after a central nervous symptom insult. It has been described after stroke, anoxic brain injury, and encephalitis, in addition to TBI. First described in 1954 as an “autonomic seizure,” more than 30 terms for this condition have been found in review of the literature, including sympathetic storming and dysautonomia. Not surprisingly, definitions and diagnostic criteria also vary and recommendations have been made to more clearly define this syndrome. In general, it is agreed that the diagnosis is based on paroxysmal cycling of agitation/dystonia in association with autonomic symptoms including tachycardia, tachypnea, elevation in systolic blood pressure, hyperthermia, and diaphoresis occurring for at least 3 consecutive days, 2 weeks or greater after injury. This is a diagnosis of exclusion with a differential diagnosis including infection, agitation, and seizure, among others. The pathophysiology is still being explained with more recent literature suggesting an excitatory:inhibitory ratio where spinal cord circuits are left unopposed by the damage to the inhibitory centers in the brainstem. This allows amplification of previously nonnoxious or mildly noxious stimuli, causing the paroxysmal sympathetic hyperactivity. Other theories suggest some form of disconnection through alternative pathways. Incidence reported varies owing to the lack of consensus diagnostic criteria with 8% to 32% described.

Treatment algorithms first suggest monitoring and ruling out other causes. Afterward, treatment is based on inhibiting the uninhibited sympathetic outflow and blocking the end-organ responses to the uninhibited outflow. Gabapentin, baclofen, clonidine, propranolol, morphine, and bromocriptine have been described. For prolonged symptoms of paroxysmal sympathetic hyperactivity unresponsive to noninvasive measures, intrathecal baclofen use has also been described.

Spasticity

Muscle overactivity is one “positive” sign after TBI in contrast with weakness or loss of muscle control, which is considered a “negative” sign. Spasticity is one of those positive signs. Defined as a velocity-dependent increase in muscle tone, spasticity must be monitored closely to ensure that no complications develop secondary to spasticity, including skin alterations, muscle contractures, or pain. It is postulated that enhanced excitability of monosynaptic pathways is involved in cortically mediated spasticity. Spasticity is often measured using the modified Ashworth scale. Other measurement tools include the Tardieu and Penn spasm frequency scale.

The decision to treat spasticity is not always an easy one because there are some potential benefits as well as negative to spasticity. Positive effects can include assistance with ambulation/transfers, muscle bulk maintenance, deep vein thrombosis (DVT) prevention, and osteoporosis prevention. Negative effects can include pain, poor cosmesis, seating issues, skin disruption, and impaired function. Therefore, clearly identifying the goals of the patient and caregiver is vital. It is proposed that the provider assess the following concerns: is treatment needed, what are the aims of treatment, is the time needed for treatment available, and will treatment disrupt the lives of the patient and caregiver. The goals should be communicated clearly to the patient and their family members.

Treatment approaches vary but include different levels of invasiveness and reversibility. They can be described as treatment for more systemic manifestations of spasticity or more generalized. Requisite nonpharmacologic treatment includes stretching and use of orthoses. Medication management with baclofen, dantrolene, diazepam, and tizanidine has been described. Focal treatment with chemical neurolysis and denervation are also used commonly. Intrathecal baclofen has been used for the severe cases or those with significant lower extremity involvement. Legalization of medical cannabis is changing the landscape of neurologic spasticity treatment, with some states specifically defining an indication for neurologic spasticity.

Posttraumatic hydrocephalus

Posttraumatic hydrocephalus (PTH) can develop after TBI at a rate of 0.7% to 51.4%. Part of this variation results from underdiagnosis and atypical presentation. Additionally, different sets of clinical criteria are used to diagnoses PTH, depending on the study contributing to the variation in incidence. It is especially associated with the presence of subarachnoid hemorrhage. Other risk factors for development of PTH include advanced age, the timing of cranioplasty, higher score on the Fisher grading system, a low postresuscitation Glasgow Coma Scale score, cerebrospinal fluid (CSF) infection, and decompressive craniectomy. Pathophysiology is related to excessive CSF accumulation through either overproduction of CSF, the blockage of normal CSF flow, or insufficient CSF absorption. If the patient has a decline or plateau in function, hydrocephalus should be considered. This is in contrast with the patient without a brain injury, such as those with normal pressure hydrocephalus, where the classic triad of bladder incontinence, cognitive deficits, and gait impairment is noted. Although the symptoms of normal pressure hydrocephalus may be present in the brain injured patient, it is often impossible to disentangle the symptoms from the underlying injury. In PTH, physical examination findings can include papilledema from increased intracranial pressure, changes in level of consciousness, memory deficits, headache, or focal neurologic deficits in addition to the previous stated symptoms. When hydrocephalus is suspected, imaging should be obtained and treatment includes resolution of the underlying increase in intracranial pressure with surgical management with extraventricular drain and/or shunting.

Agitation

Agitation has various definitions. Initially described as “combativeness, arm thrashing, truncal rocking, screaming and signs of sympathetic activation.” Agitation has also been defined as “subjective evidence of one or more of the following behaviors: restlessness, derogatory or threatening demands, verbal abusiveness, sexual inappropriate comments or actions or threats or attempts at physical violence of sufficient severity to disrupt nursing care or therapy,” “post-traumatic amnesia plus an excess of behavior such as aggression, disinhibition and/or emotional lability,” and “a subtype of delirium unique to survivors of TBI in which the survivor is in the state of post-traumatic amnesia and there are excesses of behavior that include some combination of aggression, akathisia, disinhibition and/or emotional lability.” Thought to be an essential part of recovery after brain injury it is also defined as Rancho Los Amigos IV- confused and agitated. A variety of definitions make research in this area very challenging.

The incidence is difficulty to define owing to the inconsistent definitions used. One study indicates an 11% incidence and another describes a 41% incidence of persons hospitalized with TBI had 1 agitated behavior with 9% have significant agitation. Yet another describes a 70% incidence. Assuming agitation is part of the brain recovery process as suggested by the Rancho Los Amigos Scale, then 100% of patients with moderate-severe TBI should experience agitation, which should resolved concurrently with the resolution of the posttraumatic amnesia. Understandably, the wide range of incidence reported is likely owing to the lack of a definitive diagnosis.

The underlying etiology of agitation is postulated to be various causes. Structurally, frontal and temporal involvement seems to be of most interest, although also described is involvement of the interconnections between the frontal cortex and subcortical nuclei in the striatum, globus pallidus, substantia nigra and thalamus, hippocampal mesocortex and temporal neocortex, and frontal limbic cortex. The dopaminergic, noradrenergic, cholinergic, and serotonergic systems have been implicated as playing a role in agitation after brain injury. Multiple other factors can contribute to worsening in agitation including infection, seizures, electrolytes imbalances, drug/nicotine/alcohol withdrawal, and pain, and should be identified and addressed accordingly.

Monitoring of agitation can include the agitated behavior scale and the overt aggression scale. Unfortunately, most practitioners do not use a consistent method to monitor agitation, despite its importance to follow-up treatment effects and determining if further changes need to be made for management.

When treating a patient with agitation, contributing causes of agitation should be investigated first. Investigation may include a complete blood count, electrolytes, urinalysis, and imaging including chest radiographs and computed tomography scans of the head. Other investigations should be based on likelihood within the differential.

Once investigated completely and any complicating factors treated, management should include nonpharmacologic and pharmacologic options. Nonpharmacologic treatment includes environmental modification with minimization of stimuli, consistency of caregivers, and gentle reorientation.

Multiple studies suggest that agitation is time limited ; thus, one could consider watchful monitoring before considering pharmacologic intervention. However, if the patient is at risk for harming themselves or others, pharmacologic management can be considered. Many medications and algorithms have been suggested. Beta-blockers, antidepressants including tricyclic antidepressants, selective serotonin reuptake inhibitors, valproic acid, and antipsychotic agents have been used and reported in the literature for the management of agitation.

Neuroendocrine dysfunction

Recognition of neuroendocrine dysfunction after TBI is becoming more common in both the acute and chronic periods. The hypothalamus and pituitary gland are both implicated in this dysfunction. The suggested pathophysiology is thought to be 3-fold. First, the pituitary gland and hypothalamus are anatomically vulnerable due to their location, structure, and blood supply. Second, the “stress response” related to the stress of injury and hospitalization may contribute. Last, in the acute period many medications used can also contribute. Despite this, screening in the postacute period remains somewhat controversial despite published guidelines.

The posterior pituitary lobe releases antidiuretic hormone. Implicated in regulation of sodium and fluid status after brain injury, many people are aware of the potential for dysregulation and actively monitor for it. Acutely, seen most commonly are problems with sodium regulations—both hyponatremia and hypernatremia. Included are diabetes insipidus from posterior pituitary lobe dysfunction with 21.6% of person with moderate-severe TBI diagnosed acutely. Diabetes insipidus is characterized by excessive urination and thirst. If the patient is able to drink to thirst, sodium remains within normal limits; however, if they are unable to drink or if the thirst mechanism is impaired, hypernatremia and dehydration can result. Treatment consists of trying to match input and output with the addition of desmopressin as needed. In the same study, 12.7% of patients were noted to develop the syndrome of inappropriate antidiuretic hormone, caused by the uncontrolled release of antidiuretic hormone. This release causes hyponatremia in the setting of euvolemia and is first treated with fluid restriction. Completing the discussion about sodium regulation, cerebral salt wasting is also seen. Leading to hypovolemic hyponatremia, its pathophysiology remains uncertain. Cerebral salt wasting is hyponatremia as a result of inappropriate loss of sodium in the urine. Mechanisms postulated are disrupted sympathetic neural input to the kidney and increased secretion of brain natriuretic peptide, causing decreased renal sodium resorption and impaired renin–aldosterone release with subsequent volume depletion. Some authors suggest that cerebral salt wasting may not exist, whereas others consider it a distinct disease. Because cerebral salt wasting as an entity is in dispute, its incidence is unclear. Treatment includes hydration and sodium replacement. Treatment for any sodium abnormality (hyponatremia or hypernatremia) depends on the cause; therefore, identification of the etiology is essential.

Anterior pituitary lobe dysfunction is also seen after TBI, as well as gonadotrophic and somatotrophic axis disorders. Forty percent of persons had gonadotrophin deficiency acutely; however, this improved to 7.7% at 1 year. Consensus guidelines for replacement in the acute period exist. The most commonly deficient hormone, however, is growth hormone. Thyroid-stimulating hormone and cortisol levels can also be abnormal after brain injury.

Screening consensus statements exist and agree that physicians should monitor for symptoms and test for a select group of abnormalities at 0, 3, and 12 months. Outcomes after brain injury have been shown to be affected negatively by neuroendocrine disorders. Therefore, care should be taken to evaluate for and properly manage any deficiencies.