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

BACKGROUND: 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. METHODS: We enrolled 184 patients who were in a vegetative or minimally conscious state 4 to 16 weeks after traumatic brain injury and who were receiving inpatient rehabilitation. Patients were randomly assigned to receive amantadine or placebo for 4 weeks and were followed for 2 weeks after the treatment was discontinued. The rate of functional recovery on the Disability Rating Scale (DRS; range, 0 to 29, with higher scores indicating greater disability) was compared over the 4 weeks of treatment (primary outcome) and during the 2-week washout period with the use of mixed-effects regression models. RESULTS: During the 4-week treatment period, recovery was significantly faster in the amantadine group than in the placebo group, as measured by the DRS score (difference in slope, 0.24 points per week; P=0.007), indicating a benefit with respect to the primary outcome measure. In a prespecified subgroup analysis, the treatment effect was similar for patients in a vegetative state and those in a minimally conscious state. The rate of improvement in the amantadine group slowed during the 2 weeks after treatment (weeks 5 and 6) and was significantly slower than the rate in the placebo group (difference in slope, 0.30 points per week; P=0.02). The overall improvement in DRS scores between baseline and week 6 (2 weeks after treatment was discontinued) was similar in the two groups. There were no significant differences in the incidence of serious adverse events. CONCLUSIONS: Amantadine accelerated the pace of functional recovery during active treatment in patients with post-traumatic disorders of consciousness. (Funded by the National Institute on Disability and Rehabilitation Research; ClinicalTrials.gov number, NCT00970944.).

Time course and influence of pusher behavior on outcome in a rehabilitation setting: a prospective cohort study.

OBJECTIVE: To examine the prevalence and the time course of pusher behavior (PB) among patients with hemiparesis in a rehabilitation setting and the influence of this behavior on rehabilitation outcome. METHODS: Over a 1-year period, 448 inpatients with hemiparesis after stroke and nonstroke etiologies were screened in the first week after admission to a neurological rehabilitation hospital. The Clinical Scale for Contraversive Pushing was used to differentiate pusher from nonpusher patients. If PB was present, the patient was examined weekly. The prevalence and duration of PB was assessed, and influence on rehabilitation efficiency and effectiveness according to the Motor Function Assessment Scale and Barthel Index was calculated. RESULTS: PB was present in 16% of all examined, in 17% of the stroke patients, and in 31% of patients (33% of stroke patients) unable to stand erect without support. PB duration within the rehabilitation hospital was 5 ± 4.3 weeks (median = 4; range, 1-20). PB is a negative predictor for the rehabilitation outcome: PB patients are only half as efficient and effective as nonpusher patients. The effect worsened if PB had been present for a longer period of time. CONCLUSION: The prevalence of PB and its influence on rehabilitation outcome reveal PB as a relevant disorder in stroke rehabilitation. However, the duration of the behavior differed widely among the PB patients. Further studies are needed to establish prognostic criteria for identifying patients with a potential for developing long-term PB.

Tilt Table Therapies for Patients with Severe Disorders of Consciousness: A Randomized, Controlled Trial.

One major aim of the neurological rehabilitation of patients with severe disorders of consciousness (DOC) is to enhance patients' arousal and ability to communicate. Mobilization into a standing position by means of a tilt table has been shown to improve their arousal and awareness. However, due to the frequent occurrence of syncopes on a tilt table, it is easier to accomplish verticalization using a tilt table with an integrated stepping device. The objective of this randomized controlled clinical trial was to evaluate the effectiveness of a tilt table therapy with or without an integrated stepping device on the level of consciousness. A total of 50 participants in vegetative or minimally conscious states 4 weeks to 6 month after injury were treated with verticalization during this randomized controlled trial. Interventions involved ten 1-hour sessions of the specific treatment over a 3-week period. Blinded assessors made measurements before and after the intervention period, as well as after a 3-week follow-up period. The coma recovery scale-revised (CRS-R) showed an improvement by a median of 2 points for the group receiving tilt table with integrated stepping (Erigo). The rate of recovery of the group receiving the conventional tilt table therapy significantly increased by 5 points during treatment and by an additional 2 points during the 3-week follow-up period. Changes in spasticity did not significantly differ between the two intervention groups. Compared to the conventional tilt table, the tilt table with integrated stepping device failed to have any additional benefit for DOC patients. Verticalization itself seems to be beneficial though and should be administered to patients in DOC in early rehabilitation. Trial Registration: Current Controlled Trials Ltd (www.controlled-trials.com), identifier number ISRCTN72853718.

Comparison of orthostatic reactions of patients still unconscious within the first three months of brain injury on a tilt table with and without integrated stepping. A prospective, randomized crossover pilot trial.

OBJECTIVE: To determine whether passive leg movement during tilt table mobilization reduces the incidence of orthostatic dysfunction in mobilization of patients being comatose or semi-comatose early after brain injury. DESIGN: Randomized crossover pilot trial using sequential testing. SETTING: Neurorehabilitation hospital. SUBJECTS: Nine patients still unconscious within the first three months of brain injury (5 men, 4 women; age 51 +/- 20 years). INTERVENTION: Patients were subjected once to a conventional tilt table and once to a tilt table with an integrated stepping device. MAIN OUTCOME MEASURE: The number of syncopes/presyncopes (orthostatic hypotension, tachypnoea, increased sweating) during interventions. RESULTS: One patient had presyncopes on both devices, six patients had presyncopes on the conventional tilt table but not on the tilt table with integrated stepping, and two patients did not exhibit presyncopal symptoms on either device. There were significantly more incidents on the tilt table without than on the one with an integrated stepping device (P < 0.05) at tilts of 50 or 70 degrees respectively. CONCLUSION: Patients tolerate greater degrees of head-up tilt better with simultaneous leg movement.

Orthostatic circulatory disorders in early neurorehabilitation: a case report and management overview.

Orthostatic circulatory disorders are a common problem in the mobilization of patients with severe neurological diseases such as paraplegia, the vegetative state or the minimally conscious state. They create difficulties when mobilizing the patient out of bed. Although their incidence has not been clearly established and the severity and length of symptoms differ greatly, a relevant number of the patients in a rehabilitation unit is affected. Rehabilitation specialists should therefore be aware of these disorders and the therapeutic alternatives available. This case study reports on a 45-year-old patient who repeatedly suffered from orthostatic hypotension after a severe traumatic brain injury. The pathogenesis and predisposing factors of orthostatic dysfunction in severely disabled neurological patients as well as therapeutic efforts are subsequently reviewed.