Stuart A. Yablon

Practice guideline update summary: Botulinum neurotoxin for the treatment of blepharospasm, cervical dystonia, adult spasticity, and headache Report of the Guideline Development Subcommittee of the American Academy of Neurology

Objective: To update the 2008 American Academy of Neurology (AAN) guidelines regarding botulinum neurotoxin for blepharospasm, cervical dystonia (CD), headache, and adult spasticity. Methods: We searched the literature for relevant articles and classified them using 2004 AAN criteria. Results and recommendations: Blepharospasm: OnabotulinumtoxinA (onaBoNT-A) and incobotulinumtoxinA (incoBoNT-A) are probably effective and should be considered (Level B). AbobotulinumtoxinA (aboBoNT-A) is possibly effective and may be considered (Level C). CD: AboBoNT-A and rimabotulinumtoxinB (rimaBoNT-B) are established as effective and should be offered (Level A), and onaBoNT-A and incoBoNT-A are probably effective and should be considered (Level B). Adult spasticity: AboBoNT-A, incoBoNT-A, and onaBoNT-A are established as effective and should be offered (Level A), and rimaBoNT-B is probably effective and should be considered (Level B), for upper limb spasticity. AboBoNT-A and onaBoNT-A are established as effective and should be offered (Level A) for lower-limb spasticity. Headache: OnaBoNT-A is established as effective and should be offered to increase headache-free days (Level A) and is probably effective and should be considered to improve health-related quality of life (Level B) in chronic migraine. OnaBoNT-A is established as ineffective and should not be offered for episodic migraine (Level A) and is probably ineffective for chronic tension-type headaches (Level B).

Botulinum neurotoxin versus tizanidine in upper limb spasticity: a placebo-controlled study

Background: While spasticity is commonly treated with oral agents or botulinum neurotoxin (BoNT) injection, these treatments have not been systematically compared. Methods: This study performed a randomised, double-blind, placebo-controlled trial to compare injection of BoNT-Type A into spastic upper limb muscles versus oral tizanidine (TZD), or placebo, in 60 subjects with upper-limb spasticity due to stroke or traumatic brain injury (TBI). Wrist flexors were systematically injected, while other upper limb muscles were injected as per investigator judgement. Participants were randomised into three groups: (1) intramuscular BoNT plus oral placebo; (2) oral TZD plus intramuscular placebo; (3) intramuscular placebo plus oral placebo. The primary outcome was the difference in change in wrist flexor modified Ashworth score (MAS) between groups. Other outcome measures included MAS at elbow and finger joints, Disability Assessment Scale (DAS) and adverse events (AE). Results: BoNT produced greater tone reduction than TZD or placebo in finger and wrist flexors at week 3 (p<0.001 vs TZD; p<0.02 vs placebo) and 6 (p = 0.001 vs TZD; p = 0.08 vs placebo), and greater improvement in the cosmesis domain of the DAS at week 6 (p<0.01). TZD was not superior to placebo in tone reduction at either time point (p⩾0.09). The incidence of AE related to study treatment was higher with TZD than in the BoNT (p<0.01) or placebo groups (p = 0.001). Conclusions: BoNT is safer and more effective than TZD in reducing tone and disfigurement in upper-extremity spasticity, and may be considered as first-line therapy for this disorder.

Longitudinal outcome of patients with disordered consciousness in the NIDRR TBI model systems programs

Few studies address the course of recovery from prolonged disorders of consciousness (DOC) after severe traumatic brain injury (TBI). This study examined acute and long-term outcomes of persons with DOC admitted to acute inpatient rehabilitation within the National Institute on Disability and Rehabilitation Research (NIDRR) TBI Model Systems Programs (TBIMS). Of 9028 persons enrolled from 1988 to 2009, 396 from 20 centers met study criteria. Participants were primarily male (73%), Caucasian (67%), injured in motor vehicle collision (66%), with a median age of 28, and emergency department Glasgow Coma Scale (GCS) score of 3. Participant status was evaluated at acute rehabilitation admission and discharge and at 1, 2, and 5 years post-injury. During inpatient rehabilitation, 268 of 396 (68%) regained consciousness and 91 (23%) emerged from post-traumatic amnesia (PTA). Participants demonstrated significant improvements on GCS (z=16.135, p≤0.001) and Functional Independence Measure (FIM) (z=15.584, p≤0.001) from rehabilitation admission (median GCS=9; FIM=18) to discharge (median GCS=14; FIM=43). Of 337 with at least one follow-up visit, 28 (8%) had died by 2.1 years (mean) after discharge. Among survivors, 66 (21%) improved to become capable of living without in-house supervision, and 63 demonstrated employment potential using the Disability Rating Scale (DRS). Participants with follow-up data at 1, 2, and 5 years post-injury (n=108) demonstrated significant improvement across all follow-up evaluations on the FIM Cognitive and Supervision Rating Scale (p<0.01). Significant improvements were observed on the DRS and FIM Motor at 1 and 2 years post-injury (p<0.01). Persons with DOC at the time of admission to inpatient rehabilitation showed functional improvement throughout early recovery and in years post-injury.

Comparison of indices of traumatic brain injury severity: Glasgow Coma Scale, length of coma and post-traumatic amnesia

Background: Classification of traumatic brain injury (TBI) severity guides management and contributes to determination of prognosis. Common indicators of TBI severity include Glasgow Coma Scale (GCS) scores, length of coma (LOC) and duration of post-traumatic amnesia (PTA). Objective: To compare GCS, LOC and PTA by examining distributions and intercorrelations and develop multivariable linear regression models for estimating LOC and PTA duration. Methods: Prospective study of 519 of 614 consecutive patients with TBI. Indices of TBI severity studied were GCS, LOC, PTA and PTA–LOC (the interval from return of command-following to return of orientation). Candidate predictor variables for estimation of LOC, PTA and PTA–LOC intervals were age, years of education, year of injury (before 1997 vs 1997 or later), GCS, LOC (for PTA and PTA–LOC), pupillary responsiveness, type of injury, CT pathology and intracranial operations. Results: Although there was a severity/response relationship between GCS and LOC, PTA and PTA–LOC intervals, there was overlap in these intervals between GCS severity categories. Age, year of injury, GCS, pupillary responsiveness and CT pathology were predictive of LOC. Age, years of education, year of injury, GCS, LOC, pupillary responsiveness and intracranial operations were predictive of PTA duration. Age, years of education, year of injury, GCS, LOC and pupillary responsiveness were predictive of PTA–LOC. GCS and LOC effects were influenced by age. Conclusions: Predictors for estimating LOC, PTA and PTA–LOC intervals were determined and simple equations were developed. These equations will be helpful to clinicians, researchers and those counselling family members of patients with TBI.

Race and productivity outcome after traumatic brain injury: influence of confounding factors.

Objective:Investigate the impact of race on productivity outcome after traumatic brain injury (TBI) and evaluate the influence of confounding factors on this relationship. Design:Inception cohort of 1083 adults with TBI for whom 1-year productivity follow-up data were available. Results:Univariable logistic regression indicated that race was a significant predictor of productivity outcome after TBI. African Americans were 2.76 times more likely to be nonproductive than whites and other racial minorities were 1.92 times more likely to be nonproductive than whites. Multivariable logistic regression analyses revealed that the effect of race on employability was influenced by confounds with preinjury productivity, education level, and cause of injury. After adjustment for other predictors, African Americans were 2.00 times more likely to be nonproductive than whites and other racial minorities were 2.08 times more likely to be nonproductive than whites. The multivariable logistic regression model with all predictors except race accounted for 39% of the variability in productivity outcome (R2-Nagelkerke = 0.39), whereas the full logistic regression model including race accounted for 41% of the variability in productivity outcome (R2-Nagelkerke = 0.41); a difference of only 2%. Conclusion:Any effect of race on productivity is significantly influenced by confounding with preinjury productivity, education level, and cause of injury.

Neuroanatomic basis of impaired self-awareness after traumatic brain injury: findings from early computed tomography.

BackgroundImpaired self-awareness (ISA) is common among patients with severe traumatic brain injury (TBI) and contributes to poorer functional outcome. There is keen interest in improving the understanding of this disorder as the neuroanatomic substrate of posttraumatic ISA is poorly understood. ObjectiveDetermine whether (1) greater number of brain lesions, (2) greater volume of right hemisphere lesions, or (3) greater volume of frontal lesions is associated with greater levels of ISA after TBI. DesignProspective, observational study. ParticipantsNinety-one TBI admissions to one of 2 National Institute on Disability and Rehabilitation Research TBI Model System (TBIMS) programs. Subjects met TBIMS inclusion criteria plus (1) resolution of posttraumatic amnesia (PTA) prior to rehabilitation discharge and (2) initial postinjury computerized tomography (CT) scan available as a hard copy and as an electronic file. MethodsCT scan lesions outlined by a board-certified neuroradiologist were measured using NIH Image, and resulting calculated lesion volumes/scan variables compared against demographic characteristics, TBI severity variables, and ISA variables measured by the Awareness Questionnaire (AQ) at the time of PTA resolution. ResultsMost subjects (78%) had at least 1 lesion on emergent CT, and contusion volumes varied in all regions of interest. Patients rated their functioning as more intact on the AQ than ratings of treating clinicians, consistent with ISA. Greater injury severity was associated with a greater degree of ISA. Multivariable linear regression revealed that, after adjustment for other predictors, the number of brain lesions was predictive of degree of ISA. Right hemisphere contusion or frontal lobe contusion volumes, however, were not predictive of degree of ISA. ConclusionsISA was significantly associated with the number, but not with location or volume of focal lesions early after TBI. Posttraumatic ISA may reflect disruption in the integrated operation of broadly distributed neural networks, with lesion burden in any specific region being less relevant than disruption across multiple regions. Further imaging research is warranted to confirm these findings and to provide insight into the distributed networks required for self-awareness.

Therapeutic alliance in post-acute brain injury rehabilitation: Predictors of strength of alliance and impact of alliance on outcome

Primary objective: To determine factors that influence the strength of therapeutic alliance for patients with traumatic brain injury (TBI) attending post-acute brain injury rehabilitation (PABIR) and to examine the association of therapeutic alliance with outcome after PABIR. Research design: Prospective cohort study. Methods and procedures: The study sample consisted of 69 of 95 patients with TBI admitted to the PABIR programme during the study period. Demographic and injury severity data were abstracted from medical records or obtained through interview. Study questionnaires (the modified California Psychotherapy Alliance Scales–patient, family and clinician forms; the Prigatano Alliance Scale; the Awareness Questionnaire; the Center for Epidemiologic Studies–Depression scale; and the Family Assessment Device–General Functioning Scale) were obtained within 2 weeks of patient admission to the PABIR programme. Main outcomes and results: Study outcomes were functional status (Disability Rating Scale), programme completion and employment status at discharge from PABIR. Higher levels of family discord were associated with poorer therapeutic alliance. Greater discrepancies between family and clinician ratings of patient functioning were associated with poorer therapeutic alliance and poorer effort in therapies. Poor participation was predictive of programme dropout. Productivity status at discharge was predicted by functional status at admission and degree of therapeutic alliance. Conclusions: Findings indicate that family perceptions and family functioning are important determinants of therapeutic alliance for patients in PABIR. These results indicate that therapists in PABIR programmes should address family perceptions and functioning to facilitate patient bonding with the programme.

Acute confusion following traumatic brain injury

Primary objective: To determine the incidence, duration and symptoms associated with acute confusion/delirium among traumatic brain injury (TBI) neuro-rehabilitation admissions. Research design: Prospective evaluation of neurobehavioural impairments following TBI among inpatient neurorehabilitation admissions. Methods and procedures: Eighty-five consecutive TBI model system patients were evaluated using measures of orientation, cognition, motor restlessness and delirium. Main outcomes and results: Fifty-nine individuals met Diagnostic and Statistical Manual of Mental Disorders—Fourth Edition Delirium Diagnostic Criteria (DDC) on initial evaluation and 42 of these resolved delirium during inpatient rehabilitation. Multivariable logistic regression analyses revealed significant unique associations of the Galveston Orientation and Amnesia Test (GOAT), Delirium Rating Scale, Cognitive Test for Delirium and time elapsed since injury with DDC status. Conclusions: Findings indicate that delirium is common among neuro-rehabilitation admissions with TBI. Use of a single measure (e.g. GOAT) will result in poor characterization of the multi-faceted symptom complex shown by patients with post-traumatic confusion.

Brief assessment of severe language impairments: Initial validation of the Mississippi aphasia screening test

Primary objective: To validate the Mississippi Aphasia Screening Test (MAST) which includes nine sub-scales measuring expressive and receptive language abilities. Research design: Evaluation of inpatients admitted to neurology, neurosurgery or rehabilitation units at two local hospitals and who were within 60 days of onset of a unilateral ischemic or haemorrhagic stroke (left hemisphere (LH; n = 38); right hemisphere (RH; n = 20)). Additional participants were recruited from the community to comprise a non-patient control sample (NP; n = 36). Methods: Data collection included administration of the MAST and chart review. Results: The LH group showed more impairment than the RH and NP groups on summary scores. The LH group performed worse than the NP group on all sub-scales. The object recognition and verbal fluency sub-scales did not discriminate the stroke groups. Conclusion: Analyses suggest good criterion validity for the MAST in differentiating communication impairments among clinical and control samples.

Utility of post-traumatic amnesia in predicting 1-year productivity following traumatic brain injury: comparison of the Russell and Mississippi PTA classification intervals

Background Duration of post-traumatic amnesia (PTA) correlates with global outcomes and functional disability. Russell proposed the use of PTA duration intervals as an index for classification of traumatic brain injury (TBI) severity. Alternative duration-based schemata have been recently proposed as better predictors of outcome to the commonly cited Russell intervals. Objective Validate a TBI severity classification model (Mississippi intervals) of PTA duration anchored to late productivity outcome, and compare sensitivity against the Russell intervals. Methods Prospective observational data on TBI Model System participants (n=3846) with known or imputed PTA duration during acute hospitalisation. Productivity status at 1-year postinjury was used to compare predicted outcomes using the Mississippi and Russell classification intervals. Logistic regression model-generated curves were used to compare the performance of the classification intervals by assessing the area under the curve (AUC); the highest AUC represented the best-performing model. Results All severity variables evaluated were individually associated with return to productivity at 1 year (RTP1). Age was significantly associated with RTP1; however, younger patients had a different association than older patients. After adjustment for individually significant variables, the odds of RTP1 decrease by 14% with every additional week of PTA duration (95% CI 12% to 17%; p<0.0001). The AUC for the Russell intervals was significantly smaller than the Mississippi intervals. Conclusions PTA duration is an important predictor of late productivity outcome after TBI. The Mississippi PTA interval classification model is a valid predictor of productivity at 1 year postinjury and provides a more sensitive categorisation of PTA values than the Russell intervals.