Behavioural problems in the first year after Severe traumatic brain injury: a prospective multicentre study.

OBJECTIVE: To investigate the occurrence of behavioural problems in patients with severe traumatic brain injury during the first year after injury and potential associations with outcome. An additional post hoc objective was to analyse the frequency of behaviours with need for intervention from staff. DESIGN AND SETTING: In a prospective population based cohort study 114 patients with severe traumatic brain injury were assessed at three weeks, three months and one year after injury. MAIN MEASURES: Assessments included clinical examination and standardised instruments. Agitation was assessed with the Agitated Behaviour Scale, the course of recovery by the Rancho Los Amigo Scale and outcome by Glasgow Outcome Scale Extended. RESULTS: Agitation were most common at 3 weeks post injury and 28% ( n=68) of the patients showed at least one agitated behaviour requiring intervention from staff. Presence of significant agitation at 3 weeks after injury was not associated with poor outcome. At 3 months agitation was present in 11% ( n=90) and apathy in 26 out of 81 assessed patients. At 3 months agitation and apathy were associated with poor outcome at one year. CONCLUSIONS: Most agitated behaviours in the early phase are transient and are not associated with poor outcome. Agitation and apathy are uncommon at three months but when present are associated with poor outcome at one year after injury. In the early phase after a severe traumatic brain injury agitated behaviour in need of interventions from staff occur in a substantial proportion of patients.

Associations between care pathways and outcome 1 year after severe traumatic brain injury.

OBJECTIVE: To assess associations between real-world care pathways for working-age patients in the first year after severe traumatic brain injury and outcomes at 1 year. SETTING AND DESIGN: Prospective, observational study with recruitment from 6 neurosurgical centers in Sweden and Iceland. Follow-up to 1 year, independently of care pathways, by rehabilitation physicians and paramedical professionals. PARTICIPANTS: Patients with severe traumatic brain injury, lowest (nonsedated) Glasgow Coma Scale score 3 to 8 during the first 24 hours and requiring neurosurgical intensive care, age 18 to 65 years, and alive 3 weeks after injury. MAIN MEASURES: Length of stay in intensive care, time between intensive care discharge and rehabilitation admission, outcome at 1 year (Glasgow Outcome Scale Extended score), acute markers of injury severity, preexisting medical conditions, and post-acute complications. Logistic regression analyses were performed. RESULTS: A multivariate model found variables significantly associated with outcome (odds ratio for good outcome [confidence interval], P value) to be as follows: length of stay in intensive care (0.92 [0.87-0.98], 0.014), time between intensive care discharge and admission to inpatient rehabilitation (0.97 [0.94-0.99], 0.017), and post-acute complications (0.058 [0.006-0.60], 0.017). CONCLUSIONS: Delays in rehabilitation admission were negatively associated with outcome. Measures to ensure timely rehabilitation admission may improve outcome. Further research is needed to evaluate possible causation.

Systematic review of the risk of dementia and chronic cognitive impairment after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence regarding the risk of dementia and chronic cognitive impairment (CCI) after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001-2012) using a previously published search strategy and predefined criteria. Peer-reviewed reports in 6 languages were considered. STUDY SELECTION: Systematic reviews, meta-analyses, randomized controlled trials, cohort studies, and case-control studies, with a minimum of 30 MTBI cases in subjects of any age, assessing the risk of dementia or CCI after MTBI were selected. DATA EXTRACTION: Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network criteria. Two reviewers independently reviewed each study and extracted data from accepted articles (ie, with a low risk of bias) into evidence tables. DATA SYNTHESIS: Evidence from accepted studies was synthesized qualitatively according to modified Scottish Intercollegiate Guidelines Network criteria, and prognostic information was prioritized as exploratory or confirmatory according to design. Of 77,914 records screened, 299 articles were eligible and reviewed. Methodological quality was acceptable for 101 (34%) articles, of which 1 article considered dementia and 7 articles considered CCI. The study examining the risk of dementia after MTBI did not find an association. One randomized controlled trial found that being informed about possible cognitive dysfunction after MTBI was associated with worse cognitive performance on standard tests. Children with MTBI and intracranial pathology ("complicated" MTBI) performed worse than did children without intracranial pathology. Children showed higher rates of cognitive symptoms a year after MTBI than did a control group. CONCLUSIONS: There is a lack of evidence of an increased risk of dementia after MTBI. In children, objective evidence of CCI exists only for complicated MTBI. More definitive studies are needed to inform clinical decisions, assessment of prognosis, and public health policy.

Nonsurgical interventions after mild traumatic brain injury: a systematic review. Results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence regarding the impact of nonsurgical interventions on persistent symptoms after mild traumatic brain injury (MTBI). DATA SOURCES: MEDLINE and other databases were searched (2001-2012) with terms including "rehabilitation." Inclusion criteria were original, peer-reviewed research published in English and other languages. References were also identified from the bibliographies of eligible articles. STUDY SELECTION: Controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 MTBI cases and assess nonsurgical interventions using clinically relevant outcomes such as self-rated recovery. DATA EXTRACTION: Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed each study and extracted data from the admissible studies into evidence tables. DATA SYNTHESIS: The evidence was synthesized qualitatively according to the modified SIGN criteria. Recommendations were linked to the evidence tables using a best-evidence synthesis. After 77,914 records were screened, only 2 of 7 studies related to nonsurgical interventions were found to have a low risk of bias. One studied the effect of a scheduled telephone intervention offering counseling and education on outcome and found a significantly better outcome for symptoms (6.6 difference in adjusted mean symptom score; 95% confidence interval, 1.2-12.0), but no difference in general health outcome at 6 months after MTBI. The other was a randomized controlled trial of the effectiveness of 6 days of bed rest on posttraumatic complaints 6 months postinjury, compared with no bed rest, and found no effect. CONCLUSIONS: Some evidence suggests that early, reassuring educational information is beneficial after MTBI. Well-designed intervention studies are required to develop effective treatments and improve outcomes for adults and children at risk for persistent symptoms after MTBI.

Systematic review of prognosis and return to play after sport concussion: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

OBJECTIVE: To synthesize the best available evidence on prognosis after sport concussion. DATA SOURCES: MEDLINE and other databases were searched (2001-2012) with terms including "craniocerebral trauma" and "sports." Reference lists of eligible articles were also searched. STUDY SELECTION: Randomized controlled trials and cohort and case-control studies were selected according to predefined criteria. Studies had to have a minimum of 30 concussion cases. DATA EXTRACTION: Eligible studies were critically appraised using a modification of the Scottish Intercollegiate Guidelines Network (SIGN) criteria. Two reviewers independently reviewed and extracted data from accepted studies into evidence tables. DATA SYNTHESIS: Evidence was synthesized qualitatively according to modified SIGN criteria, and studies were categorized as exploratory or confirmatory based on the strength of their design and evidence. After 77,914 records were screened, 52 articles were eligible for this review, and 24 articles (representing 19 studies) with a low risk of bias were accepted. Our findings are based on exploratory studies of predominantly male football players at the high school, collegiate, and professional levels. Most athletes recover within days to a few weeks, and American and Australian professional football players return to play quickly after mild traumatic brain injury. Delayed recovery appears more likely in high school athletes, in those with a history of previous concussion, and in those with a higher number and duration of postconcussion symptoms. CONCLUSIONS: The evidence concerning sports concussion course and prognosis is very preliminary, and there is no evidence on the effect of return-to-play guidelines on prognosis. Our findings have implications for further research. Well-designed, confirmatory studies are urgently needed to understand the consequences of sport concussion, including recurrent concussion, across different athletic populations and sports.

Methodological issues and research recommendations for prognosis after mild traumatic brain injury: results of the International Collaboration on Mild Traumatic Brain Injury Prognosis.

The International Collaboration on Mild Traumatic Brain Injury (MTBI) Prognosis performed a comprehensive search and critical review of the literature from 2001 to 2012 to update the 2002 best-evidence synthesis conducted by the World Health Organization Collaborating Centre for Neurotrauma, Prevention, Management and Rehabilitation Task Force on the prognosis of MTBI. Of 299 relevant studies, 101 were accepted as scientifically admissible. The methodological quality of the research literature on MTBI prognosis has not improved since the 2002 Task Force report. There are still many methodological concerns and knowledge gaps in the literature. Here we report and make recommendations on how to avoid methodological flaws found in prognostic studies of MTBI. Additionally, we discuss issues of MTBI definition and identify topic areas in need of further research to advance the understanding of prognosis after MTBI. Priority research areas include but are not limited to the use of confirmatory designs, studies of measurement validity, focus on the elderly, attention to litigation/compensation issues, the development of validated clinical prediction rules, the use of MTBI populations other than hospital admissions, continued research on the effects of repeated concussions, longer follow-up times with more measurement periods in longitudinal studies, an assessment of the differences between adults and children, and an account for reverse causality and differential recall bias. Well-conducted studies in these areas will aid our understanding of MTBI prognosis and assist clinicians in educating and treating their patients with MTBI.

Paroxysmal sympathetic hyperactivity during neurorehabilitation for severe acquired brain injury: current Scandinavian practice and Delphi consensus recommendations.

OBJECTIVES: To document current practice and develop consensus recommendations for the assessment and treatment of paroxysmal sympathetic hyperactivity (PSH) during rehabilitation after severe acquired brain injury. DESIGN: Delphi consensus process with three rounds, based on the Guidance on Conducting and REporting DElphi Studies (CREDES) guidelines, led by three convenors (the authors) with an expert panel. Round 1 was exploratory, with consensus defined before round 2 as agreement of at least 75% of the panel. SETTING: A working group within the Nordic Network for Neurorehabilitation. PANEL PARTICIPANTS: Twenty specialist physicians, from Sweden (9 participants), Norway (7) and Denmark (4), all working clinically with patients with severe acquired brain injury and with current involvement in clinical decisions regarding PSH. RESULTS: Consensus was reached for 21 statements on terminology, assessment and principles for pharmacological and non-pharmacological treatment, including some guidance on specific drugs. From these, an algorithm to support clinical decisions at all stages of inpatient rehabilitation was created. CONCLUSIONS: Considerable consensus exists in the Nordic countries regarding principles for PSH assessment and treatment. An interdisciplinary approach is needed. Improved documentation and collation of data on treatment given during routine clinical practice are needed as a basis for improving care until sufficiently robust research exists to guide treatment choices.

Validity, Intra-Rater Reliability and Normative Data of the Neuroflexor™ Device to Measure Spasticity of the Ankle Plantar Flexors after Stroke.

OBJECTIVE: Quantification of lower limb spasticity after stroke and the differentiation of neural from passive muscle resistance remain key clinical challenges. The aim of this study was to validate the novel NeuroFlexor foot module, to assess the intrarater reliability of measurements and to identify normative cut-off values. METHODS: Fifteen patients with chronic stroke with clinical history of spasticity and 18 healthy subjects were examined with the NeuroFlexor foot module at controlled velocities. Elastic, viscous and neural components of passive dorsiflexion resistance were quantified (in Newton, N). The neural component, reflecting stretch reflex mediated resistance, was validated against electromyography activity. A test-retest design with a 2-way random effects model permitted study of intra-rater reliability. Finally, data from 73 healthy subjects were used to establish cutoff values according to mean + 3 standard deviations and receiver operating characteristic curve analysis. RESULTS: The neural component was higher in stroke patients, increased with stretch velocity and correlated with electromyography amplitude. Reliability was high for the neural component (intraclass correlation coefficient model 2.1 (ICC2,1) ≥ 0.903) and good for the elastic component (ICC2,1 ≥ 0.898). Cutoff values were identified, and all patients with neural component above the limit presented pathological electromyography amplitude (area under the curve (AUC) = 1.00, sensitivity = 100%, specificity = 100%). CONCLUSION: The NeuroFlexor may offer a clinically feasible and non-invasive way to objectively quantify lower limb spasticity.

Disorders of consciousness: preliminary data supports added value of extended behavioural assessment.

BACKGROUND: The use of validated behavioural assessment scales in assessment of patients with Disorders of Consciousness (DOC) is well established. However, there is little evidence to guide decisions on total time spent in behavioural assessment. OBJECTIVE: To assess whether brief behavioural assessment was as effective as extended behavioural assessment in detecting non-vegetative behaviours. METHODS: Consecutive patients with suspected DOC were assessed with two standardized instruments: Coma Recovery Scale Revised (CRS-R) and Sensory Modality Assessment and Rehabilitation Technique (SMART). Assessors were blinded to results from the other scale at the point of assessment. Two administrations of CRS-R together took 50-60 minutes ('brief' assessment). One complete SMART assessment took 600 minutes ('extended' assessment). Patients were classified as being in a vegetative state (VS) or minimally conscious state (MCS)/emerged from minimally conscious state (EMCS), following brief and extended assessment. RESULTS: Ten patients were assessed. Brief and extended assessment yielded the same diagnostic category (VS or MCS) for six patients and different categories for four, with extended assessment detecting higher level behaviours. CONCLUSIONS: Brief behavioural assessment was not as effective as extended assessment in detecting non-vegetative behaviours. Total time spent in behavioural assessment is likely important. Further studies and clearer clinical guidance are needed.

Cognitive Reserve, Early Cognitive Screening, and Relationship to Long-Term Outcome after Severe Traumatic Brain Injury.

The objective was to investigate the relationship between early global cognitive functioning using the Barrow Neurological Institute Screen for Higher Cerebral Functions (BNIS) and cognitive flexibility (Trail Making Test (TMT), TMT B-A), with long-term outcome assessed by the Mayo-Portland Adaptability Index (MPAI-4) in severe traumatic brain injury (sTBI) controlling for the influence of cognitive reserve, age, and injury severity. Of 114 patients aged 18-65 with acute Glasgow Coma Scale 3-8, 41 patients were able to complete (BNIS) at 3 months after injury and MPAI-4 5-8 years after injury. Of these, 33 patients also completed TMT at 3 months. Global cognition and cognitive flexibility correlated significantly with long-term outcome measured with MPAI-4 total score (rBNIS = 0.315; rTMT = 0.355). Global cognition correlated significantly with the participation subscale (r = 0.388), while cognitive flexibility correlated with the adjustment (r = 0.364) and ability (r = 0.364) subscales. Adjusting for cognitive reserve and acute injury severity did not alter these relationships. The effect size for education on BNIS and TMT scores was large (d ≈ 0.85). Early screenings with BNIS and TMT are related to long-term outcome after sTBI and seem to measure complementary aspects of outcome. As early as 3 months after sTBI, educational level influences the scores on neuropsychological screening instruments.

Motor inhibition and its contribution to recovery of dexterous hand use after stroke.

Recovery of dexterous hand use is critical for functional outcome after stroke. Grip force recordings can inform on maximal motor output and modulatory and inhibitory cerebral functions, but how these actually contribute to recovery of dexterous hand use is unclear. This cohort study used serially assessed measures of hand kinetics to test the hypothesis that behavioural measures of motor modulation and inhibition explain dexterity recovery beyond that explained by measures of motor output alone. We also investigated the structural and functional connectivity correlates of grip force control recovery. Eighty-nine adults (median age = 54 years, 26% females) with first-ever ischaemic or haemorrhagic stroke and persistent arm and hand paresis were assessed longitudinally, at 3 weeks, and at 3 and 6 months after stroke. Kinetic measures included: maximal grip force, accuracy of precision and power grip force control, and ability to release force abruptly. Dexterous hand use was assessed clinically with the Box and Block Test and motor impairment with the upper extremity Fugl-Meyer Assessment. Structural and functional MRI was used to assess weighted corticospinal tract lesion load, voxel-based lesion symptom mapping and interhemispheric resting-state functional connectivity. Fifty-three per cent of patients had severe initial motor impairment and a majority still had residual force control impairments at 6 months. Force release at 3 weeks explained 11% additional variance of Box and Block Test outcome at 6 months, above that explained by initial scores (67%). Other kinetic measures did not explain additional variance of recovery. The predictive value of force release remained significant when controlling for corticospinal tract lesion load and clinical measures. Corticospinal tract lesion load correlated with recovery in grip force control measures. Lesions involving the parietal operculum, insular cortex, putamen and fronto-striatal tracts were also related to poorer force modulation and release. Lesions to fronto-striatal tracts explained an additional 5% of variance in force release beyond the 43% explained by corticospinal injury alone. Interhemispheric functional connectivity did not relate to force control recovery. We conclude that not only voluntary force generation but also force release (reflecting motor inhibition) are important for recovery of dexterous hand use after stroke. Although corticospinal injury is a main determinant of recovery, lesions to integrative somatosensory areas and fronto-parietal white matter (involved in motor inhibition) explain additional variance in post-stroke force release recovery. Our findings indicate that post-stroke upper limb motor impairment profiling, which is essential for targeted treatment, should consider both voluntary grasp generation and inhibition.

Methodological aspects of using a wearable eye-tracker to support diagnostic clinical evaluation of prolonged disorders of consciousness.

OBJECTIVE: To evaluate the feasibility of using a wearable eye-tracker when assessing patients with prolonged disorders of consciousness using the Coma Recovery Scale Revised (CRS-R), focusing on technical challenges. DESIGN: A methodological investigation with descriptive and analytical elements. SUBJECTS: Four patients with prolonged disorders of consciousness were recruited from the rehabilitation clinic of a regional rehabilitation unit. METHODS: A selection of subtests in the CRS-R were performed while recording eye movements with a wearable eye-tracker. RESULTS: No major adverse reactions were observed, suggesting likely patient acceptability. Calibration was not always possible. However, distinct eye movements were discernible from the recorded data even without calibration, and analysis of these produced results with the potential to support clinical assessment. CONCLUSION: Eye tracking was feasible during clinical assessment for this patient group. Recording eye movement responses in these easily fatigued patients has the potential to add sensitivity for detection of conscious responses and to complement clinical examination. Further study is merited. Current hardware and software limitations can be overcome with manual data processing and analysis; however, significant developments in automating data processing will be required for broader clinical application.

Recovery and Prediction of Bimanual Hand Use After Stroke.

OBJECTIVE: To determine similarities and differences in key predictors of recovery of bimanual hand use and unimanual motor impairment after stroke. METHOD: In this prospective longitudinal study, 89 patients with first-ever stroke with arm paresis were assessed at 3 weeks and 3 and 6 months after stroke onset. Bimanual activity performance was assessed with the Adult Assisting Hand Assessment Stroke (Ad-AHA), and unimanual motor impairment was assessed with the Fugl-Meyer Assessment (FMA). Candidate predictors included shoulder abduction and finger extension measured by the corresponding FMA items (FMA-SAFE; range 0-4) and sensory and cognitive impairment. MRI was used to measure weighted corticospinal tract lesion load (wCST-LL) and resting-state interhemispheric functional connectivity (FC). RESULTS: Initial Ad-AHA performance was poor but improved over time in all (mild-severe) impairment subgroups. Ad-AHA correlated with FMA at each time point (r > 0.88, p < 0.001), and recovery trajectories were similar. In patients with moderate to severe initial FMA, FMA-SAFE score was the strongest predictor of Ad-AHA outcome (R 2 = 0.81) and degree of recovery (R 2 = 0.64). Two-point discrimination explained additional variance in Ad-AHA outcome (R 2 = 0.05). Repeated analyses without FMA-SAFE score identified wCST-LL and cognitive impairment as additional predictors. A wCST-LL >5.5 cm3 strongly predicted low to minimal FMA/Ad-AHA recovery (≤10 and 20 points respectively, specificity = 0.91). FC explained some additional variance to FMA-SAFE score only in unimanual recovery. CONCLUSION: Although recovery of bimanual activity depends on the extent of corticospinal tract injury and initial sensory and cognitive impairments, FMA-SAFE score captures most of the variance explained by these mechanisms. FMA-SAFE score, a straightforward clinical measure, strongly predicts bimanual recovery. CLINICALTRIALSGOV IDENTIFIER: NCT02878304. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that the FMA-SAFE score predicts bimanual recovery after stroke.

Quantitative Assessment of Hand Spasticity After Stroke: Imaging Correlates and Impact on Motor Recovery.

Objective: This longitudinal observational study investigated how neural stretch-resistance in wrist and finger flexors develops after stroke and relates to motor recovery, secondary complications, and lesion location. Methods: Sixty-one patients were assessed at 3 weeks (T1), three (T2), and 6 months (T3) after stroke using the NeuroFlexor method and clinical tests. Magnetic Resonance Imaging was used to calculate weighted corticospinal tract lesion load (wCST-LL) and to perform voxel-based lesion symptom mapping. Results: NeuroFlexor assessment demonstrated spasticity (neural component [NC] >3.4N normative cut-off) in 33% of patients at T1 and in 51% at T3. Four subgroups were identified: early Severe spasticity (n = 10), early Moderate spasticity (n = 10), Late developing spasticity (n = 17) and No spasticity (n = 24). All except the Severe spasticity group improved significantly in Fugl-Meyer Assessment (FMA-HAND) to T3. The Severe and Late spasticity groups did not improve in Box and Blocks Test. The Severe spasticity group showed a 25° reduction in passive range of movement and more frequent arm pain at T3. wCST-LL correlated positively with NC at T1 and T3, even after controlling for FMA-HAND and lesion volume. Voxel-based lesion symptom mapping showed that lesioned white matter below cortical hand knob correlated positively with NC. Conclusion: Severe hand spasticity early after stroke is negatively associated with hand motor recovery and positively associated with the development of secondary complications. Corticospinal tract damage predicts development of spasticity. Early quantitative hand spasticity measurement may have potential to predict motor recovery and could guide targeted rehabilitation interventions after stroke.

The value of incorporating personally relevant stimuli into consciousness assessment with the Coma Recovery Scale - Revised: A pilot study.

OBJECTIVE: To explore whether the use of personally relevant stimuli, for some tasks in the Coma Recovery Scale - Revised (CRS-R), generates more responses in patients with prolonged disorders of consciousness compared with neutral stimuli. DESIGN: Multiple single-case design. SUBJECTS: Three patients with prolonged disorders of consciousness recruited from an inpatient department at a regional brain injury rehabilitation clinic in Stockholm, Sweden. METHODS: Patients were repeatedly assessed with the CRS-R. Randomization tests (bootstrapping) were used to compare the number of responses generated by personally relevant and neutral stimuli on 5 items in the CRS-R. RESULTS: Compared with neutral stimuli, photographs of relatives generated significantly more visual fixations. A mirror generated visual pursuit to a significantly greater extent than other self-relevant stimuli. On other items, no significant differences between neutral and personally relevant stimuli were seen. CONCLUSION: Personally relevant visual stimuli may minimize the risk of missing visual fixation, compared with the neutral stimuli used in the current gold standard behavioural assessment measure (CRS-R). However, due to the single-subject design this conclusion is tentative and more research is needed.

Longitudinal changes in oculomotor function in young adults with mild traumatic brain injury in Sweden: an exploratory prospective observational study.

OBJECTIVES: To assess (1) whether visual disturbances can be demonstrated with objective measures more often in patients with mild traumatic brain injury (mTBI) than in orthopaedic controls and non-injured controls, (2) whether such objectively demonstrated disturbances change over time and (3) whether self-reported visual symptoms after mTBI correlate with objectively measurable changes in visuomotor performance. DESIGN: A prospective, controlled, observational study, with assessments planned 7-10 and 75-100 days after injury. SETTING: Emergency department of a general hospital in Sweden. PARTICIPANTS: 15 patients with mTBI, 15 patients with minor orthopaedic injury, 15 non-injured controls, aged 18-40 years. OUTCOME MEASURES: Visual examination, including assessment of visual acuity, accommodation, eye alignment, saccades and stereoacuity. Symptom assessment using Convergence Insufficiency Symptoms Survey (CISS) and Rivermead PostConcussion Symptoms Questionnaire. RESULTS: Assessments were performed 4-13 and 81-322 days after injury (extended time frames for logistical reasons). No statistically significant difference was found between the mTBI and control groups regarding saccade performance and stereoacuity at any time point. The accommodative amplitude was significantly lower in the mTBI group compared with non-injured controls at baseline. 6 out of 13 patients with mTBI had accommodative insufficiency at follow-up. Near point of convergence in the mTBI group was receded at baseline and improved statistically significantly at follow-up. At baseline, patients with mTBI had significantly higher CISS score than orthopaedic and non-injured controls. For patients with mTBI, the CISS score correlated with fusional vergence. CONCLUSION: There were some transient measurable visual changes regarding convergence in patients with mTBI during the subacute period after the injury. Our findings of persistence of accommodative insufficiency in a considerable proportion of patients with mTBI suggest that this visual function should not be overlooked in clinical assessment.

Effects of acetylcholinesterase inhibitors on cognitive function in patients with chronic traumatic brain injury: A systematic review.

OBJECTIVE: To undertake a systematic review of the evidence for the effect of acetylcholinesterase inhibitors (AChEIs) on cognition late after moderate or severe traumatic brain injury. BACKGROUND: Cognitive impairment after traumatic brain injury has significant consequences for the individual and society. Cholinergic pathways play an important role in cognitive processing and a hypocholinergic state exists in the chronic phases after traumatic brain injury. AChEIs are already used off-label to treat patients with traumatic brain injury. DATA SOURCES AND STUDY SELECTION: PubMed, CINAHL, PsycINFO, the Cochrane Collaboration and Web of Science were searched with pre-specified criteria between 1999 and June 2015. DATA EXTRACTION AND SYNTHESIS: A total of 153 studies were identified. None met pre-specified criteria. The criteria were revised in order to identify studies that may provide useful information despite some risk of bias. Three studies met the revised criteria and were evaluated by 2 reviewers using the Swedish Council on Health Technology Assessment grading system, based on GRADE. Key findings and limitations were tabulated. One study found no effect and 2 found limited effect. CONCLUSION: Large randomized controlled studies are needed to establish whether AChEIs are effective for cognition late after moderate or severe traumatic brain injury. Clinicians should be aware of the weak evidence base when considering the off-label use of AChEIs.

Visual assessment of atrophy on magnetic resonance imaging in the diagnosis of pathologically confirmed young-onset dementias.

OBJECTIVES: To investigate the diagnostic accuracy of visual inspection of magnetic resonance imaging (MRI) in a range of pathologically confirmed diseases causing young-onset dementia and to assess the sensitivity and specificity of atrophy patterns for Alzheimer disease (AD) and frontotemporal lobar degeneration (FTLD). DESIGN: Sixty-two patients with pathologically confirmed diseases that may present as young-onset dementia were selected from a biopsy and postmortem series. The first diagnostic T1-weighted volumetric MRI was obtained for each patient, together with images from 22 healthy control subjects. All MRIs were assessed for regional atrophy independently by 3 neuroradiologists, blinded to all clinical details except age. Observers were also asked to use their clinical judgment to form a diagnosis. RESULTS: Eighty-seven percent of dementia cases were distinguished from controls after visual inspection of MRI, and a correct pathologically confirmed diagnosis was given in 58% of cases. Hippocampal atrophy was noted in 92% of AD cases but was commonly seen in other dementias and controls. A bilateral symmetrical pattern of hippocampal atrophy discriminated AD from FTLD with 47% specificity, while posterior greater than anterior gradient of atrophy was 92% specific for AD. Atrophy of the anterior, inferior, and lateral temporal lobes was suggestive of FTLD pathology (> or =90% sensitivity), while anterior greater than posterior gradient of atrophy and hemispheric asymmetry of atrophy were each at least 85% specific for FTLD. CONCLUSION: Despite variation and overlap of atrophy patterns, visual inspection of regional atrophy on MRI may aid in discriminating AD and FTLD.

Sporadic and familial dementia with ubiquitin-positive tau-negative inclusions: clinical features of one histopathological abnormality underlying frontotemporal lobar degeneration.

BACKGROUND: Frontotemporal lobar degeneration comprises a group of diseases with clinical presentations and underlying histopathologies that overlap. Familial disease occurs in up to 50% of frontotemporal lobar degeneration cases. One of several underlying histopathological abnormalities is of ubiquitin-positive tau-negative inclusions, similar to those in motor neuron disease. OBJECTIVE: To compare clinical features of familial and sporadic cases in this pathological subgroup. DESIGN AND PATIENTS: Case note review of dementia patients with ubiquitin-positive tau-negative inclusion pathological abnormalities proven by autopsy. SETTING: United Kingdom tertiary referral center. MAIN OUTCOME MEASURES: Analysis of clinical features. RESULTS: Eleven familial cases (autosomal dominant) and 18 sporadic cases were identified. Most familial case patients presented with behavioral disturbances similar to those seen in sporadic behavioral cases. Semantic dementia was only seen in sporadic cases. Atypical features occurred in a minority. Sporadic and familial behavioral cases showed no differences in age at onset or disease duration. Neuropsychological test results revealed frontal or temporal deficits in most, but unexpected early parietal deficits in 1. CONCLUSIONS: Behavioral features in familial and sporadic cases were similar, but semantic dementia only occurred in sporadic cases. Diagnostic confusion with Alzheimer disease and corticobasal degeneration occurred in some cases.