How Do Intensity and Duration of Rehabilitation Services Affect Outcomes From Severe Traumatic Brain Injury? A Natural Experiment Comparing Health Care Delivery Systems in 2 Developed Nations.

OBJECTIVE: To determine the effects of inpatient and outpatient treatment intensity on functional and emotional well-being outcomes at 1 year after severe traumatic brain injury (TBI). DESIGN: Prospective, quasiexperimental study comparing outcomes in a U.S. TBI treatment center with those in a Denmark (DK) center providing significantly greater intensity and duration of rehabilitation. SETTING: Inpatient and outpatient TBI rehabilitation. PARTICIPANTS: Persons with severe TBI (N=274). INTERVENTIONS: Inpatient rehabilitation interventions were counted daily by discipline. Outpatient treatments were estimated per discipline using a structured interview administered to patients, caregivers, or both, at 12 months. MAIN OUTCOME MEASURES: FIM, Glasgow Outcome Scale-Extended, Disability Rating Scale, Participation Assessment with Recombined Tools-Objective, Perceived Quality of Life, Medical Outcomes Study 12-Item Short-Form Health Survey, Brief Symptom Inventory-18-item version. RESULTS: Despite identical inclusion criteria, patient severity on admission was greater at the DK site. After adjustment for patient/injury characteristics, there were no site differences in either functional or emotional outcome at 12 months. Significantly more inpatient plus outpatient treatment was administered to DK patients than to those in the U.S. For functional but not emotional treatments, more severely impaired patients received higher doses. One-year outcomes were predicted by admission severity, age, employment, and other baseline characteristics. CONCLUSIONS: Contrary to expectation, DK patients who received significantly more rehabilitation services during the year after severe TBI did not differ in outcome from their less intensively treated U.S. counterparts, after adjusting for initial severity. The negative association of functional treatment dose with extent of early disability suggests that dose was driven by unmeasured factors reflecting need for services. Improved measures of injury-related factors driving treatment allocation are needed to model the independent effects of treatment on outcomes.

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.).

Functional recovery after severe traumatic brain injury: an individual growth curve approach.

OBJECTIVE: To examine person, injury, and treatment characteristics associated with recovery trajectories of people with severe traumatic brain injury (TBI) during inpatient rehabilitation. DESIGN: Observational prospective longitudinal study. SETTING: TBI rehabilitation units. PARTICIPANTS: Adults (N=206) with severe nonpenetrating TBI admitted directly to inpatient rehabilitation from acute care. Participants were excluded for prior disability and intentional etiology of injury. INTERVENTIONS: Naturally occurring treatments delivered within comprehensive multidisciplinary teams were recorded daily in 15-minute units provided to patients and family members, separately. MAIN OUTCOME MEASURES: Motor and cognitive FIM were measured on admission, discharge, and every 2 weeks in between and were analyzed with individual growth curve methodology. RESULTS: Inpatient recovery was best modeled with linear, cubic, and quadratic components: relatively steep recovery was followed by deceleration of improvement, which attenuated prior to discharge. Slower recovery was associated with older age, longer coma, and interruptions to rehabilitation. Patients admitted at lower functional levels received more treatment, and more treatment was associated with slower recovery, presumably because treatment was allocated according to need. Therefore, effects of treatment on outcome could not be disentangled from effects of case mix factors. CONCLUSIONS: FIM gain during inpatient recovery from severe TBI is not a linear process. In observational studies, the specific effects of treatment on rehabilitation outcomes are difficult to separate from case mix factors that are associated with both outcome and allocation of treatment.

Medical complications during inpatient rehabilitation among patients with traumatic disorders of consciousness.

OBJECTIVE: To assess the incidence of medical complications in patients with recent traumatic disorders of consciousness (DOCs). DESIGN: Data on adverse events in a placebo controlled trial of amantadine hydrochloride revealed no group difference, which allowed these events to be reanalyzed descriptively as medical complications experienced by the 2 groups collectively. SETTING: Eleven clinical facilities in the United States, Denmark, and Germany with specialty rehabilitation programs for patients with DOCs. PARTICIPANTS: Patients (N=184) with nonpenetrating traumatic brain injury enrolled from acute inpatient rehabilitation programs between 4 and 16 weeks postinjury. INTERVENTIONS: Participants were randomized to receive 200 to 400mg of amantadine hydrochloride or placebo daily for 4 weeks, and followed for an additional 2 weeks. Adverse events were recorded and categorized with respect to their nature, timing, and severity. MAIN OUTCOME MEASURE: Number, type, and severity of medical complications occurring during the 6-week study interval. RESULTS: A total of 468 medical complications were documented among the patients (.40 events per week per patient). More than 80% of patients experienced at least 1 medical complication, and 41 of these were defined as serious adverse events. New medical complications declined over time in rehabilitation and were not dependent on time since injury. Hypertonia, agitation/aggression, urinary tract infection, and sleep disturbance were the most commonly reported problems. Hydrocephalus, pneumonia, gastrointestinal problems, and paroxysmal sympathetic hyperactivity were the most likely to be severe. CONCLUSIONS: Patients with DOCs have a high rate of medical complications early after injury. Many of these complications require brain injury expertise for optimal management. Active medical management appears to contribute to the reduction in new complications. An optimal system of care for DOC patients must provide expert medical management in the early weeks after injury.

Gabapentin in the management of dysautonomia following severe traumatic brain injury: a case series.

The pharmacological management of dysautonomia, otherwise known as autonomic storms, following acute neurological insults, is problematic and remains poorly researched. This paper presents six subjects with dysautonomia following extremely severe traumatic brain injury where gabapentin controlled paroxysmal autonomic changes and posturing in the early post-acute phase following limited success with conventional medication regimens. In two subjects, other medications were reduced or ceased without a recurrence of symptoms. It is proposed that medications that can block or minimise abnormal afferent stimuli may represent a better option for dysautonomia management than drugs which increase inhibition of efferent pathways. Potential mechanisms for these effects are discussed.

Early endocrine alterations reflect prolonged stress and relate to 1-year functional outcome in patients with severe brain injury.

OBJECTIVE: Severe brain injury may increase the risk of developing acute and chronic hypopituitarism. Pituitary hormone alterations developed in the early recovery phase after brain injury may have implications for long-term functional recovery. The objective of the present study was to assess the pattern and prevalence of pituitary hormone alterations 3 months after a severe brain injury with relation to functional outcome at a 1-year follow-up. DESIGN: Prospective study at a tertiary university referral centre. METHODS: A total of 163 patients admitted to neurorehabilitation after severe traumatic brain injury (TBI, n=111) or non-TBI (n=52) were included. The main outcome measures were endocrine alterations 3.3 months (median) after the brain injury and their relationship to the functioning and ability of the patients at a 1-year follow-up, as measured by the Functional Independence Measure and the Glasgow Outcome Scale-Extended. RESULTS: Three months after the injury, elevated stress hormones (i.e. 30 min stimulated cortisol, prolactin and/or IGF1) and/or suppressed gonadal or thyroid hormones were recorded in 68 and 32% of the patients respectively. At 1 year after the injury, lower functioning level (Functional Independence Measure) and lower capability of performing normal life activities (Glasgow Outcome Scale-Extended) were related to both the elevated stress hormones (P≤0.01) and the reduced gonadal and/or thyroid hormones (P≤0.01) measured at 3 months. CONCLUSION: The present study suggests that brain injury-related endocrine alterations that mimic secondary hypogonadism and hypothyroidism and that occur with elevated stress hormones most probably reflect a prolonged stress response 2-5 months after severe brain injury, rather than pituitary insufficiency per se. These endocrine alterations thus seem to reflect a more severe disease state and relate to 1-year functional outcome.

Patients with severe acquired brain injury show increased arousal in tilt-table training.

INTRODUCTION: Patients with severe acquired brain injury (ABI) are often mobilised using a tilt-table. Complications such as orthostatic intolerance have been reported. The primary objective of this study was to investigate if using a tilt-table was feasible for mobilising patients with severe ABI admitted for sub-acute rehabilitation. We also investigated change in arousal, treatment duration before termination due to orthostatic reactions and change in muscle tone. MATERIAL AND METHODS: A total of 16 patients with severe ABI were included. The patients were tilted head-up, and blood pressure, heart rate, breathing frequency and eye opening were recorded before and during the intervention. Furthermore, muscle tone was recorded before and after the intervention. RESULTS: Fifteen of the 16 patients did not complete the 20-min. session of tilt training due to orthostatic intolerance. There was a significant increase in the proportion of time that the patients had open eyes during treatment as compared with before treatment (p < 0.01). The mean time to occurrence of symptoms at the first, second and third tilt was 244 (standard deviation (SD) = ± 234) sec., 277 (SD = ± 257) sec. and 155 (SD = ± 67) sec., respectively. CONCLUSION: Patients with severe sub-acute ABI show orthostatic intolerance when mobilised on a tilt-table which results in a low mobilisation intensity. However, the patients showed a significant increase in arousal during mobilisation. FUNDING: No external funding was received for this study. All resources were provided by the Department of Neurorehabilitation, Traumatic Brain Injury Unit, Glostrup University Hospital. TRIAL REGISTRATION: not relevant.

[Subacute intensive rehabilitation after severe traumatic brain injury. Follow-up 6 months after discharge]. / Tidlig intensiv rehabilitering efter meget svaer traumatisk hjerneskade. Opfølgning seks måneder efter udskrivelsen.

INTRODUCTION: In September 2000 the Brain Injury Unit at Hvidovre Hospital was established, offering subacute intensive rehabilitation to patients with severe traumatic brain injury. Uptake area: Eastern part of Denmark, the Faroe Islands and Greenland. Outcome 6 months after discharge is presented for patients from the first 2 years, focusing on disability and social factors. MATERIALS AND METHODS: Patients were selected on the basis of the Glasgow Coma Scale after end of sedation to ensure that the most severely-injured were included in the study. Rehabilitation was initiated immediately regardless of the level of consciousness. Patients were assessed using established rating-scales. Local social authorities were involved at discharge. RESULTS: Of 77 consecutive patients, 5 died before follow-up and 6 patients were not seen at follow up. 79% of the remaining group had post-traumatic amnesia lasting more than 4 weeks. Nonetheless, 4 out of 5 were able to walk independently, 79% were living at home under normal conditions and 76% were independent on a personal level. A majority suffered from cognitive dysfunctions, which was often the major remaining disability. 20% had resumed normal work or education. CONCLUSION: The centralisation of rehabilitation in Denmark after very severe brain damage made it possible to conduct a structured plan for treatment and assessment during subacute rehabilitation and 6 months after discharge of patients with very severe traumatic brain injury. This has demonstrated that rehabilitation of even the most severely brain-damaged patients can be valuable.