Faculty Bibliography

There is currently a lack of evidence-based guidelines to guide the pharmacological treatment of neurobehavioral problems that commonly occur after traumatic brain injury (TBI). It was our objective to review the current literature on the pharmacological treatment of neurobehavioral problems after traumatic brain injury in three key areas: aggression, cognitive disorders, and affective disorders/anxiety/ psychosis. Three panels of leading researchers in the field of brain injury were formed to review the current literature on pharmacological treatment for TBI sequelae in the topic areas of affective/anxiety/ psychotic disorders, cognitive disorders, and aggression. A comprehensive Medline literature search was performed by each group to establish the groups of pertinent articles. Additional articles were obtained from bibliography searches of the primary articles. Group members then independently reviewed the articles and established a consensus rating. Despite reviewing a significant number of studies on drug treatment of neurobehavioral sequelae after TBI, the quality of evidence did not support any treatment standards and few guidelines due to a number of recurrent methodological problems. Guidelines were established for the use of methylphenidate in the treatment of deficits in attention and speed of information processing, as well as for the use of beta-blockers for the treatment of aggression following TBI. Options were recommended in the treatment of depression, bipolar disorder/mania, psychosis, aggression, general cognitive functions, and deficits in attention, speed of processing, and memory after TBI. The evidence-based guidelines and options established by this working group may help to guide the pharmacological treatment of the person experiencing neurobehavioral sequelae following TBI. There is a clear need for well-designed randomized controlled trials in the treatment of these common problems after TBI in order to establish definitive treatment standards for this patient population.

Patients with various neurologic disorders exhibit exaggerated or inappropriate episodes of laughter, crying, or both without an apparent motivating stimulus or in response to stimuli that would not have elicited such an emotional response before the onset of the underlying disease. During these episodes, patients have difficulty controlling their emotional expression according to the contextual information. In contrast, patients with mood disorders have a pervasive and sustained change in their emotional experience and thus exhibit spells of laughter or crying because of an underlying mania or depression. This article focuses on the clinical presentation, diagnosis, prevalence, and proposed pathophysiological mechanisms of and available treatment options for this clinical phenomenon.

Pharmacotherapy may contribute to the rehabilitation of persons with posttraumatic cognitive impairments. This article reviews first the neurobiological consequences of traumatic brain injury with a particular emphasis on acute and long-term posttraumatic neurochemical disturbances. Studies of pharmacotherapies for posttraumatic cognitive impairments are reviewed next, and are organized according to medication class and the neurotransmitter system they affect most. Based on the evidence provided by that review, augmentation of posttraumatic cerebral catecholaminergic and cholinergic function are suggested as potentially useful neurochemical targets for pharmacologic intervention in this population. More specifically, it is suggested that persons with posttraumatic impairments in arousal, speed of processing, and possibly attention may benefit most from treatment with an agent that augments cerebral catecholaminergic function, and that persons whose predominant posttraumatic impairment is in the domain of memory may benefit most from treatment with cholinesterase inhibitors. Practical considerations regarding the use of pharmacotherapies for posttraumatic cognitive impairments are offered, and the need for additional research in this area is highlighted

OBJECTIVE: To compare the efficacy and safety of rivastigmine (3 to 6 mg/day) vs placebo over 12 weeks in patients with traumatic brain injury and persistent cognitive impairment. METHODS: This prospective, randomized, double-blind, placebo-controlled study was conducted in 157 patients at least 12 months after injury. The primary efficacy measures were the Cambridge Neuropsychological Test Automated Battery (CANTAB) Rapid Visual Information Processing (RVIP) A' subtest and the Hopkins Verbal Learning Test (HVLT). The primary efficacy outcome was the proportion of patients who demonstrated 1.0 SD or greater improvement from baseline at week 12 on CANTAB RVIP A' or HVLT. RESULTS: The percentage of responders at week 12 on either the CANTAB RVIP A' or HVLT was 48.7% for rivastigmine and 49.3% for placebo (p = 0.940). Furthermore, for the overall study population, there were no significant differences for any of the secondary efficacy variables. In a subgroup of patients with moderate to severe memory impairment (n = 81), defined as 25% impairment or greater on HVLT at baseline, rivastigmine was significantly better than placebo for a number of measures, including the proportion of HVLT responders and CANTAB RVIP mean latency. CONCLUSIONS: Rivastigmine was safe and well tolerated in patients with traumatic brain injury with cognitive deficits. Rivastigmine shows promising results in the subgroup of patients with traumatic brain injury with moderate to severe memory deficits

PRIMARY OBJECTIVE: To investigate the relationship between the number of dilated Virchow-Robin spaces (VRS) and neurocognitive findings in patients with traumatic brain injury (TBI). RESEARCH DESIGN: Thirty-eight patients with TBI and 21 controls were studied. METHODS AND PROCEDURES: Fifteen patients underwent MRI within a mean interval of 5.4 (range 1-12) days from the brain injury and 23 after an average period of 5.5 (range 0.2-31) years. All subjects were examined with a battery of 13 neuropsychological tests (NP). MAIN OUTCOMES AND RESULTS: The average number of VRS was significantly higher in patients than in controls. There were no significant differences between patients and controls in terms of NP tests. The number of VRS showed a significant inverse correlation with processing speed and a positive correlation with visual perceptual of attention only in patients studied within a short delay of trauma. CONCLUSIONS: VRS are not directly associated to neurocognitive findings, suggesting that they may represent a result of the shear-strain injury