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      Placebo-controlled trial of amantadine for severe traumatic brain injury.

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          Abstract

          Amantadine hydrochloride is one of the most commonly prescribed medications for patients with prolonged disorders of consciousness after traumatic brain injury. Preliminary studies have suggested that amantadine may promote functional recovery.

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          Natural history of recovery from brain injury after prolonged disorders of consciousness: outcome of patients admitted to inpatient rehabilitation with 1-4 year follow-up.

          The natural history of recovery from brain injury typically consists of a period of impaired consciousness, a subsequent period of confusion and amnesia, followed by a period of post-confusional recovery of function. Patients with more severe injuries may have more prolonged episodes of unconsciousness or minimal consciousness and may not fully evolve through this continuum of recovery. There is limited information on the course of recovery and long-term outcome of patients with prolonged unconsciousness, particularly those with extended periods in the minimally conscious state. Further, patients with impaired consciousness are frequently denied access to hospital-based rehabilitation services because of uncertain prognosis and a perceived lack of benefit from rehabilitative interventions. A consecutive series of 36 patients with traumatic (TBI) and non-traumatic brain injury (nonTBI) in a vegetative state (VS) or minimally conscious state (MCS) on admission to a specialized, slow-to-recover brain injury program in an acute rehabilitation hospital was retrospectively reviewed to evaluate course of recovery during rehabilitation hospitalization and in follow-up, 1-4 years post-injury. Independent variables included: time to resolution of VS, MCS and confusional state/posttraumatic amnesia (CS/PTA), based on Aspen criteria, Coma Recovery Scale-Revised (CRS-R) and Galveston Orientation and Amnesia Test (GOAT) scores. Outcome measures (calculated separately for TBI, nonTBI, VS, or MCS on admission subgroups) included: proportion of patients who recover and recovery time to MCS, CS/PTA stages, household independence, and return to school or work, as well as Disability Rating Scale (DRS) scores at 1, 2, 3, and 4 years post-injury. The majority emerged from MCS (72%) and CS/PTA (58%) by latest follow-up. It took significantly longer for patients admitted in VS (means: MCS, 16.43 weeks; CS/PTA, 30.1 weeks) than MCS (means: MCS, 7.36 weeks; CS/PTA, 11.5 weeks) to reach both milestones. Almost all who failed to clear CS/PTA by latest follow-up were patients with nonTBI or TBI with VS lasting over 8 weeks. Duration of MCS was a strong predictor of duration CS/PTA after emergence from MCS, accounting for 57% of the variance. Nearly half the patients followed at least 1 year achieved recovery to, at least, daytime independence at home and 22% returned to work or school, 17% at or near pre-injury levels. Discharge FIM score or duration of MCS, along with age, were best predictors of DRS in outcome models. DRS scores continued to improve after 2 and 3 years post-injury. Patients in VS whose transition to MCS occurred within 8 weeks of onset are likely to continue recovering to higher levels of functioning, a substantial proportion to household independence, and productive pursuits. Patients with TBI are more likely to progress than patients with nonTBI, though significant improvement in the nonTBI group is still possible. Active, higher intensity, rehabilitation should be strongly considered for patients with severely impaired consciousness after brain injury, especially for patients with TBI who have signs of progression to the MCS.
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            Author and article information

            Journal
            N Engl J Med
            The New England journal of medicine
            Massachusetts Medical Society
            1533-4406
            0028-4793
            Mar 01 2012
            : 366
            : 9
            Affiliations
            [1 ] JFK Johnson Rehabilitation Institute, Edison, NJ, USA. jgiacino@partners.org
            Article
            10.1056/NEJMoa1102609
            22375973
            55d12a02-b397-47a3-be79-8af715c1e3b7
            History

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