Post-traumatic Confusional State: A Case Definition and Diagnostic Criteria.

In response to the need to better define the natural history of emerging consciousness after traumatic brain injury and to better describe the characteristics of the condition commonly labeled posttraumatic amnesia, a case definition and diagnostic criteria for the posttraumatic confusional state (PTCS) were developed. This project was completed by the Confusion Workgroup of the American Congress of Rehabilitation Medicine Brain Injury Interdisciplinary Special Interest group. The case definition was informed by an exhaustive literature review and expert opinion of workgroup members from multiple disciplines. The workgroup reviewed 2466 abstracts and extracted evidence from 44 articles. Consensus was reached through teleconferences, face-to-face meetings, and 3 rounds of modified Delphi voting. The case definition provides detailed description of PTCS (1) core neurobehavioral features, (2) associated neurobehavioral features, (3) functional implications, (4) exclusion criteria, (5) lower boundary, and (6) criteria for emergence. Core neurobehavioral features include disturbances of attention, orientation, and memory as well as excessive fluctuation. Associated neurobehavioral features include emotional and behavioral disturbances, sleep-wake cycle disturbance, delusions, perceptual disturbances, and confabulation. The lower boundary distinguishes PTCS from the minimally conscious state, while upper boundary is marked by significant improvement in the 4 core and 5 associated features. Key research goals are establishment of cutoffs on assessment instruments and determination of levels of behavioral function that distinguish persons in PTCS from those who have emerged to the period of continued recovery.

Knee Muscle Stretch Reflex Responses After an Intrathecal Baclofen Bolus in Neurological Patients With Moderate-to-Severe Hypertonia.

OBJECTIVES: To examine the prevalence, onset threshold, and response magnitude of stretch reflex response (SRR) in the knee extensors and flexors before and after an intrathecal baclofen (ITB) bolus injection in patients with moderate-to-severe hypertonia. MATERIALS AND METHODS: SRRs were elicited by reciprocal passive knee extension/flexion movements at preset angular velocities of 5, 60, 120, 180, 240, and 300°/s using an isokinetic dynamometer and recorded with surface electromyographic (EMG) electrodes placed over the knee extensors and flexors in 53 neurologic patients before and at 2.5 and 5 hours after an ITB injection via lumbar puncture. Outcome measures included the number of patients with presence/absence of SRRs, the number of SRRs per session, SRR onset threshold angle and velocity, and response magnitudes (peak EMG and area under the EMG curve) for each muscle. Pre-post comparisons were completed using the Fisher's exact and Wilcoxon signed rank tests. RESULTS: For both knee extensors and flexors, the proportion of patients with present SRRs (p < 0.0001) and the number of SRRs per session (p ≤ 0.027) decreased from pre- to post-ITB. The threshold velocity significantly increased post-injection in both muscles (p ≤ 0.001) without significant changes in the threshold angle. The response magnitudes significantly decreased in the knee extensors (p ≤ 0.016) but not the knee flexors after the injection. CONCLUSIONS: The prevalence and threshold velocity of SRR emerged as the most robust and practical parameters for assessing hyperreflexia during ITB bolus trial that can complement clinical assessment of muscle hypertonia.

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.).

Psychotic symptoms as manifestations of the posttraumatic confusional state: prevalence, risk factors, and association with outcome.

OBJECTIVES: To (1) determine factors associated with psychotic-type symptoms in persons with moderate or severe traumatic brain injury (TBI) during early recovery and (2) investigate the prognostic significance of early psychotic-type symptoms for patient outcome. SETTING: Acute neurorehabilitation inpatient unit. PARTICIPANTS: A total of 168 persons with moderate or severe TBI were admitted for inpatient rehabilitation. Of these, 107 had psychotic-type symptoms on at least 1 examination. One-year productivity outcome was available for 87 of the 107 participants. DESIGN: Prospective, inception cohort, observational study. MAIN MEASURES: Confusion Assessment Protocol, productivity outcome at 1 year postinjury. RESULTS: Presence of sleep disturbance, a shorter interval from admission to assessment, and greater cognitive impairment were associated with a greater incidence of psychotic-type symptoms. Younger age, more years of education, and lower frequency and severity of psychotic-type symptoms were associated with a greater likelihood of favorable productivity outcome. CONCLUSIONS: We identified risk factors for the occurrence of psychotic-type symptoms and extended previous findings regarding the significance of these symptoms for outcome after TBI. These findings suggest that improved sleep in early TBI recovery may decrease the occurrence of psychotic-type symptoms.

Delirium following traumatic brain injury in adolescents: Symptomatology and prediction of ability to return to school or employment 1-year post-injury.

BACKGROUND: There is a limited evidence-base describing clinical features of delirium in youth. What is known is largely extrapolated from studies of adults or samples with heterogeneous etiologies. It is unclear if the symptoms experienced by adolescents differ from those experienced by adults, or the degree to which delirium impacts the ability of adolescents to return to school or work. OBJECTIVE: To describe delirium symptomatology among adolescents following a severe traumatic brain injury (TBI). Symptoms were compared by adolescent delirium status and across age groups. Delirium and its relationship with adolescent employability 1 year post-injury was also examined. DESIGN: Exploratory secondary analysis of prospectively collected data. SETTING: Free-standing rehabilitation hospital. PATIENTS: Severely injured TBI Model Systems neurorehabilitation admissions (n = 243; median Glasgow Coma Scale = 7). The sample was divided into three age groups (adolescents, 16-21 years, n = 63; adults 22-49 years, n = 133; older adults ≥50 years, n = 47). INTERVENTIONS: Not applicable. MEASURES: We assessed patients using Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition (DSM-IV) diagnostic criteria and the Delirium Rating Scale-Revised 98 (DRS-R-98). The employability item from the Disability Rating Scale was the primary 1-year outcome. RESULTS: Most items on the DRS-R-98 differentiated delirious from non-delirious adolescents. Only "delusions" differed among age groups. Among adolescents, delirium status 1 month post-TBI provided acceptable classification of employability prediction 1 year later (area under the curve [AUC]: 0.80, 95% confidence interval [CI]: 0.69-0.91, p < .001). Delirium symptom severity (AUC: 0.86, 95% CI: 0.68-1.03, SE: 0.09; p < .001) and days of post-traumatic amnesia (AUC: 0.85, 95% CI: 0.68-1.01, SE: 0.08; p < .001) provided excellent prediction of outcomes for TBI patients in delirium. CONCLUSIONS: Delirium symptomatology was similar among age groups and useful in differentiating the delirium status within the adolescent TBI group. Delirium and symptom severity at 1 month post-TBI were highly predictive of poor outcomes. Findings from this study support the utility of DRS-R-98 at 1 month post-injury to inform treatment and planning.

Prospective evaluation of the nature, course, and impact of acute sleep abnormality after traumatic brain injury.

OBJECTIVE: To prospectively characterize the prevalence, course, and impact of acute sleep abnormality among traumatic brain injury (TBI) neurorehabilitation admissions. DESIGN: Prospective observational study. SETTING: Freestanding rehabilitation hospital. PARTICIPANTS: Primarily severe TBI (median emergency department Glasgow Coma Scale [GCS] score=7; N=205) patients who were mostly men (71%) and white (68%) were evaluated during acute neurorehabilitation. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Delirium Rating Scale-Revised-98 (DelRS-R98) was administered weekly throughout rehabilitation hospitalization. DelRS-R98 item 1 was used to classify severity of sleep-wake cycle disturbance (SWCD) as none, mild, moderate, or severe. SWCD ratings were analyzed both serially and at 1 month postinjury. RESULTS: For the entire sample, 66% (mild to severe) had SWCD at 1 month postinjury. The course of the SWCD using a subset (n=152) revealed that 84% had SWCD on rehabilitation admission, with 63% having moderate to severe ratings (median, 24d postinjury). By the third serial exam (median, 35d postinjury), 59% remained with SWCD, and 28% had moderate to severe ratings. Using general linear modeling and adjusting for age, emergency department GCS score, and days postinjury, presence of moderate to severe SWCD at 1 month postinjury made significant contributions in predicting duration of posttraumatic amnesia (P<.01) and rehabilitation hospital length of stay (P<.01). CONCLUSIONS: Results suggest that sleep abnormalities after TBI are prevalent and decrease over time. However, a high percent remained with SWCD throughout the course of rehabilitation intervention. Given the brevity of inpatient neurorehabilitation, future studies may explore targeting SWCD to improve early outcomes, such as cognitive functioning and economic impact, after TBI.

Functional outcomes in traumatic disorders of consciousness: 5-year outcomes from the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems.

OBJECTIVE: To characterize the 5-year outcomes of patients with traumatic brain injury (TBI) not following commands when admitted to acute inpatient rehabilitation. DESIGN: Secondary analysis of prospectively collected data from the National Institute on Disability and Rehabilitation Research-funded Traumatic Brain Injury Model Systems (TBIMS). SETTING: Inpatient rehabilitation hospitals participating in the TBIMS program. PARTICIPANTS: Patients (N=108) with TBI not following commands at admission to acute inpatient rehabilitation were divided into 2 groups (early recovery: followed commands before discharge [n=72]; late recovery: did not follow commands before discharge [n=36]). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: FIM items. RESULTS: For the early recovery group, depending on the FIM item, 8% to 21% of patients were functioning independently at discharge, increasing to 56% to 85% by 5 years postinjury. The proportion functioning independently increased from discharge to 1 year, 1 to 2 years, and 2 to 5 years. In the late recovery group, depending on the FIM item, 19% to 36% of patients were functioning independently by 5 years postinjury. The proportion of independent patients increased significantly from discharge to 1 year and from 1 to 2 years, but not from 2 to 5 years. CONCLUSIONS: Substantial proportions of patients admitted to acute inpatient rehabilitation before following commands recover independent functioning over as long as 5 years, particularly if they begin to follow commands before hospital discharge.

Do rehospitalization rates differ among injury severity levels in the NIDRR Traumatic Brain Injury Model Systems program?

OBJECTIVE: To compare the rate and nature of rehospitalization in a cohort of patients enrolled in the National Institute on Disability and Rehabilitation Research Traumatic Brain Injury Model Systems (TBIMS) who have disorders of consciousness (DOC) at the time of rehabilitation admission with those in persons with moderate or severe traumatic brain injury (TBI) but without DOC at rehabilitation admission. DESIGN: Prospective observational study. SETTING: Inpatient rehabilitation within TBIMS with annual follow-up. PARTICIPANTS: Of 9028 persons enrolled from 1988 to 2009 (N=9028), 366 from 20 centers met criteria for DOC at rehabilitation admission and follow-up data, and another 5132 individuals met criteria for moderate (n=769) or severe TBI (n=4363). INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Participants and/or their family members completed follow-up data collection including questions about frequency and nature of rehospitalizations at 1 year postinjury. For the subset of participants with DOC, additional follow-up was conducted at 2 and 5 years postinjury. RESULTS: The DOC group demonstrated an overall 2-fold increase in rehospitalization in the first year postinjury relative to those with moderate or severe TBI without DOC. Persons with DOC at rehabilitation admission have a higher rate of rehospitalization across several categories than persons with moderate or severe TBI. CONCLUSIONS: Although the specific details of rehospitalization are unknown, greater injury severity resulting in DOC status on rehabilitation admission has long-term implications. Data highlight the need for a longitudinal approach to patient management.

Electromyogram-lengthening velocity relation in plantar flexors during stance phase of gait in patients with hypertonia after acquired brain injury.

OBJECTIVE: To examine the velocity-dependent change in medial gastrocnemius (MG) activity during the stance phase of gait in patients with moderate to severe resting hypertonia after stroke or traumatic brain injury (TBI). DESIGN: Cohort study. SETTING: Motion analysis laboratory in a tertiary-care rehabilitation hospital. PARTICIPANTS: Convenience sample of patients with chronic TBI and stroke (n=11 each), and age- and sex-matched healthy controls (n=22). INTERVENTION: Not applicable. MAIN OUTCOME MEASURES: Frequency and gain (steepness) of positive (>0) and significant positive (>0 and goodness of fit P≤.05) electromyogram-lengthening velocity (EMG-LV) linear regression slope in MG during the stance phase of gait. RESULTS: Positive and significant positive slopes were found significantly more often on the more affected (MA) than less affected (LA) side in patients with TBI but not stroke. Both the frequencies of positive and significant positive slopes on the MA side in patients with TBI were also significantly higher than in controls. However, neither the gain of positive nor significant positive EMG-LV slope was different between the MA and LA sides or in comparison with controls. Positive slope parameters were not related to Ashworth score on the MA side. CONCLUSIONS: The frequency and gain of positive EMG-lengthening slope did not effectively differentiate patients from controls, nor were they related to the resting muscle hypertonia. Motor output during MG lengthening in the stance phase of gait is apparently not exaggerated or related to resting hypertonia in patients with chronic TBI and stroke. Thus, changes in gait during stance cannot be ascribed to increased stretch reflex activity in MG muscle after acquired brain injury.

Dose response with onabotulinumtoxinA for post-stroke spasticity: a pooled data analysis.

Clinical trials demonstrate that onabotulinumtoxinA reduces upper limb post-stroke spasticity, with therapeutic response influenced by injected dose. Individual studies provide limited insight regarding muscle group-specific dose-response relationships. Our objective was to characterize dose-response relationships between onabotulinumtoxinA and muscle tone in specific upper limb muscles. Individual patient data from seven multicenter, randomized, double-blind, placebo-controlled trials were pooled. Of 544 post-stroke patients enrolled, 362 received onabotulinumtoxinA and 182 received placebo, injected into the flexor carpi radialis (FCR), flexor carpi ulnaris (FCU), flexor digitorum superficialis (FDS), flexor digitorum profundus (FDP), and/or biceps brachii (BB). Ashworth Scale score change at week 6 (AshworthCBL) was the primary outcome measure for muscle tone. For a broader analysis of response, AshworthCBL/onabotulinumtoxinA dosage relationships were characterized using three techniques: (1) AshworthCBL plotted as a function of onabotulinumtoxinA dose in Units (U) [dose-response curve]; (2) mean AshworthCBL per onabotulinumtoxinA dose depicting the responses seen with specific dose injection clusters/groups for each specific muscle group; and (3) onabotulinumtoxinA dose estimated to produce a mean 1-point decrease in AshworthCBL as an indicator of clinically meaningful benefit of treatment. Increasing onabotulinumtoxinA doses produced greater AshworthCBLs (muscle tone improvements). The maximal week 6 response (E(max)) model indicated a saturating dose-response relationship, with mean E(max) AshworthCBL values of -1.48, -1.48, -0.63, -0.77, and -0.61 in the FCR, FCU, FDS, FDP, and BB, respectively. OnabotulinumtoxinA doses estimated to produce a mean 1-point decrease in AshworthCBL were: 22.5U, 18.4U, 66.3U, 42.5U in the FCR, FCU, FDS, and FDP, respectively, and not determinable in the BB. These analyses demonstrate a saturating effect of greater muscle tone improvements with increasing onabotulinumtoxinA doses in post-stroke spasticity patients. These findings suggest potentially effective onabotulinumtoxinA doses in selected muscle groups in this study population.

Effect of intrathecal baclofen bolus injection on lower extremity joint range of motion during gait in patients with acquired brain injury.

UNLABELLED: Horn TS, Yablon SA, Chow JW, Lee JE, Stokic DS. Effect of intrathecal baclofen bolus injection on lower extremity joint range of motion during gait in patients with acquired brain injury. OBJECTIVES: To evaluate lower extremity joint range of motion (ROM) during gait before and after intrathecal baclofen (ITB) bolus administration, and to explore the relation between changes in ROM and concurrent changes in gait speed and muscle hypertonia. DESIGN: Case series. SETTING: Tertiary care rehabilitation center. PARTICIPANTS: Adults (N=28) with muscle hypertonia due to stroke, trauma, or anoxia. INTERVENTIONS: 50-microg ITB bolus injection via lumbar puncture (75 and 100microg in 2 cases). MAIN OUTCOME MEASURES: Ashworth score, self-selected gait speed, and sagittal plane ROMs in hip, knee, and ankle joints before and 2, 4, and 6 hours after ITB bolus. RESULTS: A significant decrease in the mean Ashworth score on the more involved side (2.0 to 1.3) and an increase in gait speed (41 to 47cm/s) were noted at different intervals after ITB bolus injection. Ankle ROM significantly increased on the more involved (13 degrees to 15 degrees , P<.01) and less involved (22 degrees to 24 degrees , P<.05) sides. ROM significantly improved, significantly worsened, or showed no significant change in 42%, 34%, and 24% of individual joints, respectively. The peak change in ROM did not coincide with the peak decrease in Ashworth score. Peak changes in ROM and speed coincided more often (P<.001) in participants who increased gait speed after ITB bolus compared with those who decreased speed. The absolute change in ROM after ITB bolus injection correlated better with the concurrent changes in speed (r=.41, P<.001) than with the baseline speed (r=.18, P<.05). CONCLUSIONS: ITB bolus injection produces variable changes in joint ROM during gait, with significant improvements in the ankles only. Timing and magnitude of peak changes in ROM are associated with concurrent changes in speed but not muscle hypertonia.

Prophylaxis for venous thromboembolism during rehabilitation for traumatic brain injury: a multicenter observational study.

BACKGROUND: Deep venous thrombosis (DVT) is a major cause of mortality and morbidity after traumatic brain injury (TBI). There is no consensus regarding appropriate screening, prophylaxis, or treatment during acute rehabilitation. METHODS: This prospective observational study evaluated prophylactic anticoagulation during rehabilitation in patients with TBI aged 16 years or older admitted to 12 TBI Model Systems rehabilitation centers (July 2004-December 2007). After propensity score stratification within center, the odds ratio associated with incidence of symptomatic DVT or pulmonary embolism (PE) for patients who did and did not receive prophylactic anticoagulation was estimated using conditional logistic regression in patients who were not screened for DVT on rehabilitation admission or who screened negative; the analysis was repeated in these two subgroups. RESULTS: Patients with identified DVTs at rehabilitation admission (n = 266) were excluded, leaving 1,897 patients: 1,002 screened negative, 895 unscreened; 932 received prophylactic anticoagulation, and 965 did not. Symptomatic DVT/PE was detected in 32 patients (15 of 932 [1.6%] with prophylaxis, 17 of 965 [1.8%] without). After propensity score adjustment, the odds ratio (95% confidence interval) for symptomatic DVT/PE with prophylaxis versus no prophylaxis was 0.80 (0.33-1.94) in the full analytic population and 0.46 (0.12-1.84) in the screened-negative subgroup. The only probable venous thromboembolism-related death occurred in the prophylactic anticoagulation group. Fewer new/expanded intracranial hemorrhages occurred among patients who received prophylactic anticoagulation. CONCLUSIONS: Prophylactic anticoagulation during rehabilitation seemed safe for TBI patients whose physicians deemed it appropriate, but did not conclusively reduce venous thromboembolism. Given the number of DVTs present before rehabilitation, screening and prophylaxis during acute care may be more important.

Temporospatial characteristics of gait in patients with lower limb muscle hypertonia after traumatic brain injury.

OBJECTIVE: To characterize gait characteristics of adults with traumatic brain injury (TBI) and lower limb muscle hypertonia, distinguishing gait adaptations inherent to TBI motor impairment from those of healthy subjects walking at slower speed. METHODS: Temporospatial and kinematic data of 31 patients with TBI (41 ± 30 months post-injury) walking at self-selected speed (free speed) were compared with 31 healthy subjects walking at free and very slow speeds using an optoelectronic motion analysis system. RESULTS: All step parameters differed (p < 0.05) between more affected (MA) and less affected (LA) sides in TBI except foot angle and toe clearance. Significant differences existed between TBI and controls in most parameters regardless of speed. These differences frequently involved the LA side. In TBI, most temporospatial parameters significantly correlated with stride velocity, whereas the averaged lower limb Ashworth score on the MA side (2.1 ± 0.4) showed few significant correlations. CONCLUSIONS: Gait deviations in subjects with TBI and lower limb muscle hypertonia cannot be solely explained by slower walking. The preponderance of changes involving the LA side particularly suggests prevalent use of compensatory walking strategies. Temporospatial gait parameters are not closely related to static measures of muscle hypertonia after TBI.

Patterns of recovery of posttraumatic confusional state in neurorehabilitation admissions after traumatic brain injury.

UNLABELLED: Sherer M, Yablon SA, Nakase-Richardson R. Patterns of recovery of posttraumatic confusional state in neurorehabilitation admissions after traumatic brain injury. OBJECTIVE: To provide preliminary descriptions of patterns of resolution of symptoms of acute confusion after traumatic brain injury (TBI). DESIGN: Prospective, descriptive, cohort study. SETTING: Inpatient neurorehabilitation unit. PARTICIPANTS: Patients (N=107) meeting criteria for posttraumatic confusional state at admission to inpatient rehabilitation. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURE: Patterns of resolution of posttraumatic confusional state symptoms over the first 3 confusion assessment protocol evaluations for patients with mild, moderate, and severe confusion. RESULTS: Posttraumatic confusional state symptoms resolving earliest were psychotic-type symptoms, decreased daytime arousal, and nighttime sleep disturbance. Fluctuation and cognitive impairment were the 2 most persistent symptoms. Seventy-three percent of patients showed improvement of 1 or more symptoms from the first to third evaluation. Confusion severity groups did not significantly differ on indices of injury severity (Glasgow Coma Scale score, time to follow commands) but did differ on functional status at discharge from inpatient rehabilitation. CONCLUSIONS: While posttraumatic confusional state is a heterogeneous disorder, there is a predictable pattern of symptom resolution. Differences in patients' confusion severity and patterns of symptoms may relate to differing underlying neural injury.

Classification schema of posttraumatic amnesia duration-based injury severity relative to 1-year outcome: analysis of individuals with moderate and severe traumatic brain injury.

OBJECTIVE: Early investigations classified traumatic brain injury (TBI) severity according to posttraumatic amnesia (PTA) duration, designating "greater than 7 days" as the most severe. PTA durations of more than 7 days are common in neurorehabilitation populations. Moreover, no study has derived a PTA severity schema anchored to late outcome. The purpose of this study was to develop a PTA severity classification schema. DESIGN: Prospective observational study. SETTING: Rehabilitation hospital. PARTICIPANTS: Sample included TBI Model System participants (N=280) with known or imputed PTA duration during acute hospitalization and 1-year productivity status. Participants were primarily male (70%), median age of 27 years; and the most common mechanism of injury was motor vehicle collisions (79%). For study purposes, 4 injury severity groups were identified by observing differences in productivity associated with different PTA durations. INTERVENTIONS: None. MAIN OUTCOME MEASURE: Productivity status at 1 year postinjury. RESULTS: Fisher exact test comparisons revealed significant differences among 3 of the groups. Most individuals with PTA fewer than 14 days had favorable 1-year outcome (68% productive), whereas worse outcomes were associated with PTA more than 28 days (18% productive). CONCLUSIONS: If validated by other investigators, the proposed schema will be useful in determining prognosis for late functional status based on PTA duration.

Effect of severity of post-traumatic confusion and its constituent symptoms on outcome after traumatic brain injury.

OBJECTIVE: To investigate the prognostic significance of severity of post-traumatic confusion (PTC) and its constituent symptoms for early and late outcome after traumatic brain injury (TBI). DESIGN: Prospective cohort study. SETTING: Inpatient brain injury rehabilitation program. PARTICIPANTS: A total of 168 patients meeting study criteria from 195 consecutive Traumatic Brain Injury Model Systems neurorehabilitation admissions. INTERVENTIONS: Not applicable. MAIN OUTCOME MEASURES: Employability at neurorehabilitation discharge and productivity status at 1 year postinjury. RESULTS: More severely confused patients had poorer outcomes for both employability and productivity. Multivariable logistic regression revealed that after adjustment for all other predictors, time to follow commands, and confusion severity predicted employability at discharge and age and confusion severity predicted productivity status at 1 year. Each symptom showed an unadjusted effect on discharge employability. All symptoms except nighttime sleep disturbance or daytime decreased arousal had effects on productivity at 1 year. Presence of psychotic-type symptoms was associated with especially poor productivity outcomes. CONCLUSIONS: PTC constituent symptoms and severity predict outcome after TBI. Presence or absence of psychotic-type symptoms on a single evaluation at approximately 21 days postinjury may have particular prognostic significance for productivity outcome.

Prospective comparison of acute confusion severity with duration of post-traumatic amnesia in predicting employment outcome after traumatic brain injury.

BACKGROUND: Measurement of the duration of post-traumatic amnesia (PTA) is common practice, serving as an important index of the severity of traumatic brain injury (TBI) and a predictor of functional outcome. However, controversy exists regarding the nature of PTA; some studies indicate that it is a confusional state with symptoms that extend beyond disorientation and amnesia. OBJECTIVE: To evaluate the contribution of the severity of acute confusion 1 month after TBI to prediction of employment at 1 year after injury, comparing it with PTA duration. METHODS: Prospective study involving 171 participants with complete data, who met the study criteria, from 228 consecutive TBI Model System admissions. Outcome measures included weekly administration of the Delirium Rating Scale-Revised-98 (DelRS-R98) to measure the severity of acute confusion. Evaluations closest to 1 month after injury were used for study purposes. Duration of PTA was defined as the interval from injury until two consecutive Galveston Orientation and Amnesia Test scores of > or = 76 were obtained within a period of 24-72 h. Univariable and multivariable logistic regression were used to predict employment status at 1 year after injury. RESULTS: Age, education and DelRS-R98 were significant predictors accounting for 34% of outcome variance. Individuals with greater confusion severity at 1 month after injury, older age and lower levels of education were less likely to be employed at 1 year after injury. Severity of confusion was more strongly associated with employment outcome (r(s) = -0.39) than was PTA duration (r(s) = -0.34). CONCLUSIONS: In addition to demographic indices, severity of acute confusion makes a unique contribution to predicting late outcome after TBI.

Formation of neutralizing antibodies in patients receiving botulinum toxin type A for treatment of poststroke spasticity: a pooled-data analysis of three clinical trials.

OBJECTIVE: The purpose of this study was to investigate the incidence of neutralizing antibody (NAb) formation in patients with poststroke spasticity treated with a specific formulation of botulinum toxin type A (BoNTA). METHODS: Data from 3 previous clinical trials of BoNTA in patients with upper and/or lower limb spasticity were pooled and evaluated. Study 1 was a randomized, double-blind, placebo-controlled, multicenter trial of BoNTA in patients aged >/=21 years who had experienced a stroke >6 months before the initiation of the study. Study 2 was an open-label extension of study 1. Study 3 was a randomized, double-blind, multicenter trial of a specific BoNTA formulation in patients aged >/= 21 years who had experienced a stroke >/=6 weeks before study entry. Patients with a fixed contracture of the studied limb were excluded from participation in studies 1 and 2. Serum samples were obtained from each patient before each BoNTA treatment and at the end of each study. The mouse protection assay (MPA) was used for detection of NAbs to BoNTA in serum. RESULTS: A total of 235 individual patients with post-stroke spasticity were enrolled in the 3 trials, including 126, 111 (all of whom participated in study 1), and 109 in studies 1, 2, and 3, respectively. Study 1 had an equal (50.0%) distribution of male and female patients (63/63). The distribution of male and female patients was 56 (50.5%) and 55 (49.5%), respectively, in study 2, and 55 (50.5%) and 54 (49.5), respectively, in study 3. The mean (SD) ages of patients in studies 1, 2, and 3 were 61.4 (13.8), 61.5 (14.1), and 58.5 (13.9) years, respectively. The MPA was used for detection of NAbs to BoNTA in the serum samples of 191 patients, including 64 from study 1, 111 from study 2 (55 of these patients were placebo recipients and 56 received their first BoNTA injection in study 1), and 72 (a sample was not obtained for 1 patient who had not received an injection) from study 3. The median number of BoNTA treatments received by these patients was 2 (range, 1-4 treatments) over a period lasting from 12 to 42 weeks. The mean dose of BoNTA was 241 U (range, 100-400 U), with a maximum dose of 960 U in any 1 patient. NAbs to BoNTA were detected in the serum sample of 1/191 (0.5%) patient who had participated in studies 1 and 2. Based on muscle-tone scores (3 and 4 for wrist and fingers, respectively) on a 5-point Ashworth Scale (0 = none to 4 = severe), the patient did not appear to exhibit a clinical response to BoNTA at any time during the studies. CONCLUSION: Formation of NAbs was rare (1/191) in this group of adults with poststroke spasticity from three 12- to 42-week clinical trials who received >/=1 treatment with a specific BoNTA formulation at doses ranging from 100 to 400 U.

Intrathecal baclofen bolus reduces exaggerated extensor coactivation during pre-swing and early-swing of gait after acquired brain injury.

OBJECTIVE: To characterize the concurrent activation of rectus femoris (RF) and medial gastrocnemius (MG) muscles (extensor coactivation) during gait in subjects with pronounced resting hypertonia after acquired brain injury (ABI) and examine changes after intrathecal baclofen (ITB) bolus injection. METHODS: Magnitude and duration of extensor coactivation during different phases of gait were assessed by recording gait kinematics and activity in bilateral RF and MG muscles in 18 controls and 18 ABI subjects before and at 2, 4, and 6h after a 50-µg ITB injection. RESULTS: Compared to controls, the magnitude of extensor coactivation was significantly increased in all phases of gait except the single support (p≤0.005), while the duration was significantly prolonged throughout (p≤0.001) in both legs of ABI subjects. After ITB bolus, only the duration of extensor coactivation significantly shortened in the more-affected leg during the late double-support and early swing (p≤0.026). CONCLUSIONS: Extensor coactivation is bilaterally exaggerated during gait in ABI subjects. ITB bolus effectively shortens the extensor coactivation in the more-affected leg during the pre-swing and early swing phases of gait. SIGNIFICANCE: Shortening of the prolonged extensor coactivation during gait may serve as an index of neurophysiological response to ITB bolus injection in subjects with ABI.

Focal Electroencephalographic Changes Index Post-Traumatic Confusion and Outcome.

While the duration and severity of post-traumatic confusional state (PTCS) after traumatic brain injury have well-established implications for long-term outcomes, little is known about the underlying pathophysiology and their role in functional outcomes. Here, we analyzed the delta-to-alpha frequency band power ratios (DAR) from localized scalp areas derived from standard resting electroencephalographic (EEG) data recorded during eyes closed state in 49 patients diagnosed with PTCS. Higher global, occipital, parietal, and temporal DARs were significantly associated with the severity of PTCS, as assessed by the Confusion Assessment Protocol (CAP) observed on the same day, after controlling for injury severity. Also, occipital DARs were positively associated with both the CAP disorientation score 2, and the CAP symptom fluctuation score 4, after controlling for injury severity (n = 35). Posterior DARs were significantly associated with Functional Independence Measure-cognitive subscale average score at 1 (n = 45), 2 (n = 42), and 5 (n = 34) year(s) post-injury. The associations at 1 (temporal left) and 2 (parietal left) years survive after controlling for an injury severity index. Our finding that posterior DAR is a marker of PTCS and functional recovery post-injury, likely reflects functional de-afferentation of the posterior medial complex (PMC) in PTCS. Altered function of the PMC is proposed as a unifying physiological mechanism underlying both acute and chronic confusional states. We discuss the relationship of these findings to electrophysiological markers associated with disorders of consciousness.