Ronald G. Riechers

Post-traumatic headaches in civilians and military personnel: a comparative, clinical review.

Post‐traumatic headache (PTH) is the most frequent symptom after traumatic brain injury (TBI). We review the epidemiology and characterization of PTH in military and civilian settings. PTH appears to be more likely to develop following mild TBI (concussion) compared with moderate or severe TBI. PTH often clinically resembles primary headache disorders, usually migraine. For migraine‐like PTH, individuals who had the most severe headache pain had the highest headache frequencies. Based on studies to date in both civilian and military settings, we recommend changes to the current definition of PTH. Anxiety disorders such as post‐traumatic stress disorder (PTSD) are frequently associated with TBI, especially in military populations and in combat settings. PTSD can complicate treatment of PTH as a comorbid condition of post‐concussion syndrome. PTH should not be treated as an isolated condition. Comorbid conditions such as PTSD and sleep disturbances also need to be treated. Double‐blind placebo‐controlled trials in PTH population are necessary to see whether similar phenotypes in the primary headache disorders and PTH will respond similarly to treatment. Until blinded treatment trials are completed, we suggest that, when possible, PTH be treated as one would treat the primary headache disorder(s) that the PTH most closely resembles.

A case–control study examining whether neurological deficits and PTSD in combat veterans are related to episodes of mild TBI

Background Mild traumatic brain injury (mTBI) is a common injury among military personnel serving in Iraq or Afghanistan. The impact of repeated episodes of combat mTBI is unknown. Objective To evaluate relationships among mTBI, post-traumatic stress disorder (PTSD) and neurological deficits (NDs) in US veterans who served in Iraq or Afghanistan. Methods This was a case–control study. From 2091 veterans screened for traumatic brain injury, the authors studied 126 who sustained mTBI with one or more episodes of loss of consciousness (LOC) in combat. Comparison groups: 21 combat veterans who had definite or possible episodes of mTBI without LOC and 21 veterans who sustained mTBI with LOC as civilians. Results Among combat veterans with mTBI, 52% had NDs, 66% had PTSD and 50% had PTSD and an ND. Impaired olfaction was the most common ND, found in 65 veterans. The prevalence of an ND or PTSD correlated with the number of mTBI exposures with LOC. The prevalence of an ND or PTSD was >90% for more than five episodes of LOC. Severity of PTSD and impairment of olfaction increased with number of LOC episodes. The prevalence of an ND for the 34 combat veterans with one episode of LOC (4/34=11.8%) was similar to that of the 21 veterans of similar age and educational background who sustained civilian mTBI with one episode of LOC (2/21=9.5%, p-NS). Conclusions Impaired olfaction was the most frequently recognised ND. Repeated episodes of combat mTBI were associated with increased likelihood of PTSD and an ND. Combat setting may not increase the likelihood of an ND. Two possible connections between mTBI and PTSD are (1) that circumstances leading to combat mTBI likely involve severe psychological trauma and (2) that altered cerebral functioning following mTBI may increase the likelihood that a traumatic event results in PTSD.

Relationships between mild traumatic brain injury sustained in combat and post-traumatic stress disorder.

The setting of the trauma is a distinguishing feature between mild traumatic brain injury (mTBI; also called concussion) that occurs in civilian settings compared with that occurring in combat. Combat mTBI is frequently associated with a prolonged stress reaction, post-traumatic stress disorder (PTSD). Individuals with mTBI and PTSD from combat in Operations Iraqi Freedom and Enduring Freedom often develop prolonged post-concussion symptoms (PCSs) such as headache. Both mTBI and PTSD may contribute to PCSs. PTSD may worsen and prolong the PCSs following mTBI by disrupting sleep. It is not known how mTBI predisposes an individual to develop PTSD.

Effective Treatment of Traumatic Brain Injury: Learning From Experience

IN THIS ISSUE OF JAMA, ZAFONTE AND COLLEAGUES 1 PREsent the findings of the Citicoline Brain Injury Treatment Trial (COBRIT), a phase 3, double-blind study comparing citicoline vs placebo. In this trial, 1213 study participants with complicated mild, moderate, or severe traumatic brain injury (TBI) were randomized to receive 2000 mg of citicoline or placebo daily for 90 days. The study, which did not demonstrate any benefits of citicholine treatment, is likely to have implications not only for the use of citicoline in patients with TBI but also for the design of future trials of TBI therapies. Traumatic brain injury is an important national and global health issue for civilian and military populations. Recent estimates for the United States indicate that each year 235 000 patients are hospitalized for nonfatal TBI, 1.1 million are treated in emergency departments, and 53 000 die. Trauma, which often includes TBI, is the leading cause of non–cancerrelated deaths among Americans younger than 40 years. A population-based study conducted in Olmsted County, Minnesota, found that the incidence of TBI requiring medical attention was 558 per 100 000 person-years. Following hospitalization for TBI, approximately 43% of patients in the United States have residual disability; 3.2 million Americans are now living with disability following hospitalization for TBI. A birth cohort study in New Zealand indicated that 32% of people had experienced an episode of TBI requiring medical attention by age 25 years. Clearly, TBI is a potentially severe and disabling health condition, but these estimates of morbidity, mortality, and disability do not consider the large number of mild TBI events for which patients do not seek immediate medical attention but can be associated with persistent problems such as headache. Moreover, US veterans with combat-associated mild TBI often have posttraumatic stress disorder, which can complicate reentry into civilian life. The main causes of TBI are motor vehicle crashes, sports injuries, falls, work-related injuries, assaults, and intentional and unintentional injuries involving firearms, explosives, and other weapons. Traumatic brain injury–related fatalities have declined the past 10 to 15 years in part because of improvements in protection of occupants in motor vehicles, protective helmet design, and other preventive measures. However, there remains an imperative need to further reduce the incidence of TBI. In addition, reducing the severity of TBI morbidity once trauma has occurred and improving the rate and extent of recovery from TBI are major challenges. Experimental therapies have shown some promise. For example, among a few carefully selected individuals with severe TBI who were in a state of minimal consciousness, electrical stimulation of the interstitial thalamic nuclei was associated with improved ability to participate and respond to cognitive and motor therapy. In a double-blind, placebo-controlled trial, amantadine improved the rate of recovery from severe TBI, although improvement attributed to amantadine was incomplete and only applicable for patients with severe TBI. There currently are no effective treatments to reduce the severity of TBI-related deficits among patients with complicated mild or moderate TBI. Therefore, the results of the COBRIT study of citicoline therapy were anticipated with great hope. Citicoline is an intermediate in the generation of phosphatidylcholine from choline. The brain uses choline to synthesize the neurotransmitter acetylcholine and the essential membrane components phosphatidylcholine and sphingomyelin. Citicoline increases choline availability for acetylcholine synthesis and membrane synthesis and repair. Citicoline has little toxicity in humans at doses up to 2000 mg daily. There have been encouraging findings in animal studies and preliminary clinical pilot studies using citicoline to reduce cerebral injury caused by TBI, ischemia, and aging. However, similar to the TBI study by Zafonte et al, a multicenter placebo-controlled study found that citicoline did not improve the extent or speed of recovery following acute stroke. There are several possible explanations for differences in the results of animal and human clinical studies in the efficacy of citicoline to reduce brain injury associated with trauma or ischemia. First, differences between animal and

Prior housing conditions and sleep loss may affect recovery from brain injury in rats: A pilot study

The purpose of this study is to understand the effect of combat-associated conditions such as sleep deprivation (SD) on subsequent traumatic brain injury (TBI). Prior to TBI (or sham surgery) induced by controlled cortical impact (CCI), rats were housed singly in chambers that prevented rapid eye movement sleep or allowed unrestricted sleep (no SD). Sensorimotor function was tested pre-SD and retested on postoperative days (PDs) 4, 7, and 14. Two additional control groups were housed socially prior to either CCI or sham surgery. CCI resulted in immediate performance deficits on sensorimotor tasks. The PD on which performance returned to baseline depended on preinjury conditions. Overall, preinjury SD+CCI resulted in an earlier recovery than no SD+CCI, and the no SD+CCI group (housed singly under conditions comparable with the SD group) recovered slower than all other groups. These data are the first to raise the possibility that recovery of sensorimotor function following TBI is affected by preinjury conditions. The data suggest that preinjury SD 24 h in duration may result in faster recovery and that novel or social isolation conditions may impede recovery. Thus, the combat environment may contribute to complexities associated with TBIs common in U.S. servicemembers.

Post-traumatic headaches.

Chronic pain, especially headache, is an exceedingly common complication of traumatic brain injury (TBI). In fact, paradoxically, the milder the TBI, the more likely one is to develop headaches. The environment of injury and the associated comorbidities can have a significant impact on the frequency and severity of headaches and commonly serve to direct management of the headaches. Trauma likely contributes to the development of headaches via alterations in neuronal signaling, inflammation, and musculoskeletal changes. The clinical picture of the patient with post-traumatic headaches is often that of a mixed headache disorder with features of tension-type headaches as well as migrainous headaches. Treatment of these headaches is thus often guided by the predominant characteristics of the headaches and can include pharmacologic and nonpharmacologic strategies. Pharmacologic therapies include both abortive and prophylactic agents with prophylaxis targeting comorbidities, primarily impaired sleep. Nonpharmacologic interventions for post-traumatic headaches include thermal and physical modalities as well as cognitive behavioral approaches. As with many postconcussive symptoms, headaches can lessen with time but in up to 25% of patients, chronic headaches are long-term residua.

Suicidality and injury of the prefrontal cortex in multiple incidents of mild traumatic brain injury

To the Editor The article by Bryan and Clemans 1 about the relationships between episodes of combat mild traumatic brain injury (mTBI) and suicide augments information on the role of repeated traumatic brain injury episodes in the genesis of brain injury and altered behavior. 2,3 The finding of a relationship between number of mTBI episodes and the likelihood of suicidality is consistent with prior observations demonstrating that the likelihood of an individual developing posttraumatic stress disorder increased with the number of episodes of combat mTBI that were associated with loss of consciousness (LOC). 4 We found that the relationship between posttraumatic stress disorder and the number of mTBI episodes was stronger for mTBI associated with LOC compared with the number of mTBI events that were not accompanied by LOC. We wonder if Bryan and Clemans 1 can comment on whether suicidality was related more strongly to episodes of mTBI with LOC compared with episodes without LOC. We would appreciate the thoughts of Bryan and Clemans 1 on the role of impulsivity in suicidality following mTBI. Our experience has been that impaired impulse control is associated with suicide attempts following combat mTBI. Individuals may flip into a suicidal state following an unpredictable setback. For example, we treated a veteran who had sustained multiple episodes of mTBI who received a note from a former acquaintance. The veteran thought the acquaintance intended to resume a romantic relationship. The veteran attempted suicide after discovering that the acquaintance did not desire romance. The attempted suicide was done impulsively. The veteran did not contact anyone to express distress. Impulsivity can reflect altered frontal lobe function. A recent study reported increased activation of the anterior cingulate and prefrontal cortex in combat veterans with histories of suicidal ideation. 5 We found that impaired olfaction increased with the number of mTBI events associated with LOC. 4 Because the olfactory cortex is located in the ventromedial prefrontal cortex, impaired olfaction may indicate prefrontal injury. The observation that an increased number of traumatic brain injury events are associated with increased risk of suicidality suggests that such individuals, their families, and caregivers should be targeted for interventions to prevent suicide including education to encourage the veteran to alert others when thoughts of suicide emerge. Families need education about mTBI to understand that even though the veteran may

Rehabilitation in the patient with mild traumatic brain injury

Traumatic brain injury (TBI) has garnered increased public attention in the past several years because of high-profile athletes with possible long-term effects of their injuries as well as large numbers of returning combat veterans injured by blast explosions. Most of these injuries are mild in nature and require no specific surgical treatment but may benefit from brief rehabilitation interventions. To appropriately rehabilitate patients with mild traumatic brain injury (mTBI), one must fully understand its clinical course and the factors that accelerate or delay recovery. Education is the centerpiece of mTBI treatment and should be included in the rehabilitation plan. When devising the rehabilitation plan, the neurologist should take into account the goals of the patient and establish a reasonable time frame for treatment paralleling the expected recovery course. Cognitive and vestibular functions are commonly affected after mTBI and are particularly responsive to rehabilitation interventions. Vocational rehabilitation and community reentry planning are aspects of the global rehabilitation plan that should not be neglected. Combat-injured veterans with mTBI present unique challenges to the rehabilitation team, and assessment of these patients often needs to include assessment of psychological function.