Burke Rehabilitation Hospital

This paper is a revision and update of the recommendations developed following the 1st (Vienna 2001), 2nd (Prague 2004) and 3rd (Zurich 2008) International Consensus Conferences on Concussion in Sport and is based on the deliberations at the 4th International Conference on Concussion in Sport held in Zurich, November 2012.1–3
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\nThe new 2012 Zurich Consensus statement is designed to build on the principles outlined in the previous documents and to develop further conceptual understanding of this problem using a formal consensus-based approach. A detailed description of the consensus process is outlined at the end of this document under the Background section. This document is developed primarily for use by physicians and healthcare professionals who are involved in the care of injured athletes, whether at the recreational, elite or professional level.

OBJECTIVE: Cerebral concussion is common in collision sports such as football, yet the chronic neurological effects of recurrent concussion are not well understood. The purpose of our study was to investigate the association between previous head injury and the likelihood of developing mild cognitive impairment (MCI) and Alzheimer's disease in a unique group of retired professional football players with previous head injury exposure. METHODS: A general health questionnaire was completed by 2552 retired professional football players with an average age of 53.8 (+/-13.4) years and an average professional football playing career of 6.6 (+/- 3.6) years. A second questionnaire focusing on memory and issues related to MCI was then completed by a subset of 758 retired professional football players (> or = 50 yr of age). Results on MCI were then cross-tabulated with results from the original health questionnaire for this subset of older retirees. RESULTS: Of the former players, 61% sustained at least one concussion during their professional football career, and 24% sustained three or more concussions. Statistical analysis of the data identified an association between recurrent concussion and clinically diagnosed MCI (chi = 7.82, df = 2, P = 0.02) and self-reported significant memory impairments (chi = 19.75, df = 2, P = 0.001). Retired players with three or more reported concussions had a fivefold prevalence of MCI diagnosis and a threefold prevalence of reported significant memory problems compared with retirees without a history of concussion. Although there was not an association between recurrent concussion and Alzheimer's disease, we observed an earlier onset of Alzheimer's disease in the retirees than in the general American male population. CONCLUSION: Our findings suggest that the onset of dementia-related syndromes may be initiated by repetitive cerebral concussions in professional football players.

OBJECTIVE: Cerebral concussion is common in collision sports such as football, yet the chronic neurological effects of recurrent concussion are not well understood. The purpose of our study was to investigate the association between previous head injury and the likelihood of developing mild cognitive impairment (MCI) and Alzheimer's disease in a unique group of retired professional football players with previous head injury exposure. METHODS: A general health questionnaire was completed by 2552 retired professional football players with an average age of 53.8 (±13.4) years and an average professional football playing career of 6.6 (± 3.6) years. A second questionnaire focusing on memory and issues related to MCI was then completed by a subset of 758 retired professional football players (≥50 yr of age). Results on MCI were then cross-tabulated with results from the original health questionnaire for this subset of older retirees. RESULTS: Of the former players, 61% sustained at least one concussion during their professional football career, and 24% sustained three or more concussions. Statistical analysis of the data identified an association between recurrent concussion and clinically diagnosed MCI (χ2 = 7.82, df = 2, P = 0.02) and self-reported significant memory impairments (χ2 = 19.75, df = 2, P = 0.001). Retired players with three or more reported concussions had a fivefold prevalence of MCI diagnosis and a threefold prevalence of reported significant memory problems compared with retirees without a history of concussion. Although there was not an association between recurrent concussion and Alzheimer's disease, we observed an earlier onset of Alzheimer's disease in the retirees than in the general American male population CONCLUSION: Our findings suggest that the onset of dementia-related syndromes may be initiated by repetitive cerebral concussions in professional football players.

Peer Reviewed

OBJECTIVE: Systematic review of possible long-term effects of sports-related concussion in retired athletes. DATA SOURCES: Ten electronic databases. STUDY SELECTION: 10 years after the injury. DATA EXTRACTION: Study population, exposure/outcome measures, clinical data, neurological examination findings, cognitive assessment, neuroimaging findings and neuropathology results. Risk of bias and level of evidence were evaluated by two authors. RESULTS: Following review of 3819 studies, 47 met inclusion criteria. Some former athletes have depression and cognitive deficits later in life, and there is an association between these deficits and multiple prior concussions. Former athletes are not at increased risk for death by suicide (two studies). Former high school American football players do not appear to be at increased risk for later life neurodegenerative diseases (two studies). Some retired professional American football players may be at increased risk for diminishment in cognitive functioning or mild cognitive impairment (several studies), and neurodegenerative diseases (one study). Neuroimaging studies show modest evidence of macrostructural, microstructural, functional and neurochemical changes in some athletes. CONCLUSION: Multiple concussions appear to be a risk factor for cognitive impairment and mental health problems in some individuals. More research is needed to better understand the prevalence of chronic traumatic encephalopathy and other neurological conditions and diseases, and the extent to which they are related to concussions and/or repetitive neurotrauma sustained in sports.

A 3-oz water swallow test identified 80% (16/20) of patients aspirating during a subsequent videofluoroscopic modified barium swallow examination (sensitivity, 76%; specificity, 59%). It also identified patients with more severe dysphagia aspirating larger amounts (sensitivity, 94%; specificity, 26%) or thicker consistencies (sensitivity, 94%; specificity, 30%) of test material. The 3-oz water swallow test is a sensitive screening tool for identifying patients at risk for clinically significant aspiration who need referral for more definitive modified barium swallow evaluation.

BACKGROUND: We used MIT-Manus, a robot designed to provide interactive, goal-directed motor activity for clinical neurologic applications. OBJECTIVE: To test whether this robotic manipulation of the impaired limb influenced motor recovery in patients with hemiplegia. METHODS: Sequential patients with a history of a single stroke and hemiplegia (N = 20) hospitalized on the same acute care rehabilitation floor were enrolled in a standard rehabilitation program supplemented by either robot-aided therapy or sham robot-aided therapy. These 2 groups were comparable in age, initial physical impairment, and time between onset of the stroke and enrollment in the trial. Patients, clinical team members, and the clinical evaluator were blinded to the treatment group assignments. Standardized assessment tools measured outcomes. RESULTS: Impairment and disability declined in both groups between hospital admission and discharge. The robot-treated group showed a greater degree of improvement in all 3 measures of motor recovery, and the change in motor status measured in the proximal upper limb musculature was significant (P = .002). No adverse events resulted from robot-assisted therapy. CONCLUSIONS: These results suggest that robotic manipulation of the impaired limb may favorably add to recovery following stroke and that robotics may provide new strategies for neurologic rehabilitation.

This paper is a revision and update of the recommendations developed following the 1st (Vienna 2001), 2nd (Prague 2004), and 3rd (Zurich 2008) International Consensus Conference on Concussion in Sport and is based on the deliberations at the 4th International Conference on Concussion in Sport held in Zurich, November 2012.1–3The new 2012 Zurich Consensus statement is designed to build on the principles outlined in the previous documents and to develop further conceptual understanding of this problem using a formal consensus-based approach. A detailed description of the consensus process is outlined at the end of this document under the "Background" section. This document is developed for use by physicians and health care professionals who are primarily involved in the care of injured athletes, whether at the recreational, elite, or professional level.While agreement exists pertaining to principle messages conveyed within this document, the authors acknowledge that the science of concussion is evolving, and therefore, management and RTP decisions remain in the realm of clinical judgment on an individualized basis. Readers are encouraged to copy and distribute freely the Zurich Consensus document, the Pocket Concussion Recognition Tool (CRT), the Sports Concussion Assessment Tool version 3 (SCAT3), and the Child SCAT3 card (Appendix), and none is subject to any restriction, provided it is not altered in any way or converted to a digital format. The authors request that the document and the accompanying tools be distributed in their full and complete format.This consensus paper is broken into a number of sections:The Zurich 2012 document examines sport concussion and management issues raised in the previous Vienna 2001, Prague 2004, and Zurich 2008 documents and applies the consensus questions from Section 3 to these areas.1–3Panel discussion regarding the definition of concussion and its separation from mild traumatic brain injury (mTBI) was held. There was acknowledgement by the Concussion in Sport Group (CISG) that, although the terms mild traumatic brain injury (mTBI) and concussion are often used interchangeably in the sporting context and particularly in the US literature, others use the term to refer to different injury constructs. Concussion is the historical term representing low-velocity injuries that cause brain "shaking," resulting in clinical symptoms, and which are not necessarily related to a pathologic injury. Concussion is a subset of TBI, and the term concussion will be used in this document. It was also noted that the term commotio cerebri is often used in European and other countries. Minor revisions were made to the definition of concussion and it is defined as follows: Concussion is a brain injury and is defined as a complex pathophysiological process affecting the brain, induced by biomechanical forces. Several common features that incorporate clinical, pathologic, and biomechanical injury constructs that may be utilized in defining the nature of a concussive head injury include:The majority (80% to 90%) of concussions resolve in a short (7–10 day) period, although the recovery timeframe may be longer in children and adolescents.2The diagnosis of acute concussion usually involves the assessment of a range of domains including clinical symptoms, physical signs, cognitive impairment, neurobehavioral features, and sleep disturbance. Furthermore, a detailed concussion history is an important part of the evaluation, both in the injured athlete and when conducting a preparticipation examination. The detailed clinical assessment of concussion is outlined in the SCAT3 and Child SCAT3 forms, which are appendices to this document.The suspected diagnosis of concussion can include 1 or more of the following clinical domains:If any 1 or more of these components is present, a concussion should be suspected and the appropriate management strategy instituted.When a player shows any features of a concussion:Sufficient time for assessment and adequate facilities should be provided for the appropriate medical assessment, both on and off the field, for all injured athletes. In some sports, this may require rule change to allow an appropriate off-field medical assessment to occur without affecting the flow of the game or unduly penalizing the injured player's team. The final determination regarding concussion diagnosis and fitness to play is a medical decision based on clinical judgment.Sideline evaluation of cognitive function is an essential component in the assessment of this injury. Brief neuropsychological test batteries that assess attention and memory function have been shown to be practical and effective. Such tests include the SCAT3, which incorporates the Maddocks questions,4,5 and the Standardized Assessment of Concussion (SAC).6–8 It is worth noting that standard orientation questions (eg, time, place, person) have been shown to be unreliable in the sporting situation when compared with memory assessment.5,9 It is recognized, however, that abbreviated testing paradigms are designed for rapid concussion screening on the sidelines and are not meant to replace comprehensive neuropsychological testing, which should ideally be performed by trained neuropsychologists who are sensitive to subtle deficits that may exist beyond the acute episode; nor should they be used as a standalone tool for the ongoing management of sports concussions.It should also be recognized that the appearance of symptoms or cognitive deficit might be delayed several hours after a concussive episode and that concussion should be seen as an evolving injury in the acute stage.An athlete with concussion may be evaluated in the emergency room or doctor's office as a point of first contact after injury or may have been referred from another care provider. In addition to the points outlined above, the key features of this exam should encompass:In large part, the points above are included in the SCAT3 assessment.A range of additional investigations may be used to assist in the diagnosis or exclusion of injury. Conventional structural neuroimaging is typically normal in concussive injury. Given that caveat, the following suggestions are made. Brain computed tomography (CT; or where available, magnetic resonance imaging [MRI]) contributes little to concussion evaluation but should be employed whenever suspicion of an intracerebral or structural lesion (eg, skull fracture) exists. Examples of such situations may include prolonged disturbance of conscious state, focal neurological deficit, or worsening symptoms.Other imaging modalities, such as functional MRI (fMRI) demonstrate activation patterns that correlate with symptom severity and recovery in concussion.10–14 While not part of routine assessment at the present time, they nevertheless provide additional insight to pathophysiologic mechanisms. Alternative imaging technologies (eg, positron emission tomography, diffusion tensor imaging, magnetic resonance spectroscopy, functional connectivity), while demonstrating some compelling findings, are still at early stages of development and cannot be recommended other than in a research setting.Published studies, using both sophisticated force-plate technology, as well as those using less sophisticated clinical balance tests (eg, Balance Error Scoring System), have identified acute postural stability deficits lasting approximately 72 hours after sport-related concussion. It appears that postural-stability testing provides a useful tool for objectively assessing the motor domain of neurologic functioning and should be considered a reliable and valid addition to the assessment of athletes suffering from concussion, particularly where symptoms or signs indicate a balance component.15–21The significance of apolipoprotein (Apo) E4, ApoE promotor gene, tau polymerase, and other genetic markers in the management of sports concussion risk or injury outcome is unclear at this time.22,23 Evidence from human and animal studies in more severe traumatic brain injury demonstrates induction of a variety of genetic and cytokine factors, such as insulin-like growth factor-1 (IGF-1), IGF binding protein-2, fibroblast growth factor, Cu-Zn superoxide dismutase, superoxide dismutase-1 (SOD-1), nerve growth factor, glial fibrillary acidic protein (GFAP), and S-100. How such factors are affected in sporting concussion is not known at this stage.24–31 In addition, biochemical serum and cerebrospinal fluid biomarkers of brain injury (including S-100, neuron specific enolase [NSE], myelin basic protein [MBP], GFAP, tau, etc) have been proposed as means by which cellular damage may be detected if present.32–38 There is currently insufficient evidence, however, to justify the routine use of these biomarkers clinically.Different electrophysiologic recording techniques (eg, evoked response potential, cortical magnetic stimulation, and electroencephalography) have demonstrated reproducible abnormalities in the postconcussive state; however, not all studies reliably differentiated concussed athletes from controls.39–45 The clinical significance of these changes remains to be established.The application of neuropsychological (NP) testing in concussion has been shown to be of clinical value and contributes significant information in concussion evaluation.46–51 Although in most cases, cognitive recovery largely overlaps with the time course of symptom recovery, it has been demonstrated that cognitive recovery may occasionally precede or more commonly follow clinical symptom resolution, suggesting that the assessment of cognitive function should be an important component in the overall assessment of concussion and, in particular, any RTP protocol.52,53 It must be emphasized, however, that NP assessment should not be the sole basis of management decisions. Rather, it should be seen as an aid to the clinical decision-making process in conjunction with a range of assessments of different clinical domains and investigational results.It is recommended that all athletes should have a clinical neurological assessment (including assessment of their cognitive function) as part of their overall management. This will normally be done by the treating physician, often in conjunction with computerized NP screening tools.Formal NP testing is not required for all athletes; however, when this is considered necessary, then it should ideally be performed by a trained neuropsychologist. Although neuropsychologists are in the best position to interpret NP tests by virtue of their background and training, the ultimate RTP decision should remain a medical one in which a multidisciplinary approach, when possible, has been taken. In the absence of NP and other (eg, formal balance assessment) testing, a more conservative RTP approach may be appropriate.Neuropsychological testing may be used to assist RTP decisions and is typically performed when an athlete is clinically asymptomatic. However, NP assessment may add important information in the early stages after injury.54,55 There may be particular situations where testing is performed early to assist in determining aspects of management (eg, return to school in a pediatric athlete). This will normally be best determined in consultation with a trained neuropsychologist.56,57Baseline NP testing was considered by the panel and was not felt to be required as a mandatory aspect of every assessment. However, it may be helpful or add useful information to the overall interpretation of these tests. It also provides an additional educative opportunity for the physician to discuss the significance of this injury with the athlete. At present, there is insufficient evidence to recommend the widespread routine use of baseline NP testing.The cornerstone of concussion management is physical and cognitive rest until the acute symptoms resolve and then a graded program of exertion before medical clearance and RTP. The current published evidence evaluating the effect of rest after a sport-related concussion is sparse. An initial period of rest in the acute symptomatic period after injury (24–48 hours) may be of benefit. Further research to evaluate the long-term outcome of rest and the optimal amount and type of rest is needed. In the absence of evidence-based recommendations, a sensible approach involves the gradual return to school and social activities (before contact sports) in a manner that does not result in a significant exacerbation of symptoms.Low-level exercise for those who are slow to recover may be of benefit, although the optimal timing after injury for initiation of this treatment is currently unknown.As described above, the majority of injuries will recover spontaneously over several days. In these situations, it is expected that an athlete will proceed progressively through a stepwise RTP strategy.58The RTP protocol after a concussion follows a stepwise process as outlined in Table 1.With this stepwise progression, the athlete should continue to proceed to the next level if asymptomatic at the current level. Generally, each step should take 24 hours, so that an athlete would take approximately 1 week to proceed through the full rehabilitation protocol once asymptomatic at rest and with provocative exercise. If any postconcussion symptoms occur while in the stepwise program, then the patient should drop back to the previous asymptomatic level and try to progress again after a further 24-hour period of rest has passed.It was unanimously agreed that no RTP on the day of concussive injury should occur. There are data demonstrating that, at the collegiate and high school level, athletes allowed to RTP on the same day may demonstrate NP deficits postinjury that may not be evident on the sidelines and are more likely to have delayed onset of symptoms.59–65Persistent symptoms (>10 days) are reported in 10%–15% of concussions. In general, symptoms are not specific to concussion, and it is important to consider other conditions. Cases of concussion in sport where clinical recovery falls outside the expected window (ie, 10 days) should be managed in a multidisciplinary manner by health care providers with experience in sports-related concussion.Psychological approaches may have potential application in this injury, particularly with the modifiers listed below.66,67 Physicians are also encouraged to evaluate the concussed athlete for affective symptoms such as depression and anxiety, as these symptoms are common in all forms of traumatic brain injury.58Pharmacologic therapy in sports concussion may be applied in 2 distinct situations. The first of these situations is the management of specific or prolonged symptoms (eg, sleep disturbance, anxiety). The second situation is where drug therapy is used to modify the underlying pathophysiology of the condition with the aim of shortening the duration of the concussion symptoms.68 In broad terms, this approach to management should be considered only by clinicians experienced in concussion management.An important consideration in RTP is that concussed athletes should not only be symptom free but also should not be taking any pharmacologic agents or medications that may mask or modify the symptoms of concussion. Where antidepressant therapy may be commenced during the management of a concussion, the decision to RTP while still on such medication must be considered carefully by the treating clinician.Recognizing the importance of a concussion history and appreciating the fact that many athletes will not recognize all the concussions they may have suffered in the past, a detailed concussion history is of value.69–72 Such a history may pre-identify athletes who fit into a high- risk category and provides an opportunity for the health care provider to educate the athlete in regard to the significance of concussive injury. A structured concussion history should include specific questions as to previous symptoms of a concussion and length of recovery, not just the perceived number of past concussions. It is also worth noting that dependence upon the recall of concussive injuries by teammates or coaches has been demonstrated to be unreliable.69 The clinical history should also include information about all previous head, face, and cervical spine injuries, as these may also have clinical relevance. It is worth emphasizing that in the setting of maxillofacial and cervical spine injuries, coexistent concussive injuries may be missed unless specifically assessed. Questions pertaining to disproportionate effect versus symptom-severity matching may alert the clinician to a progressively increasing vulnerability to injury. As part of the clinical history, it is advised that details regarding protective equipment employed at time of injury be sought, both for recent and remote injuries.There is an additional and often unrecognized benefit of the preparticipation physical examination insofar as the evaluation allows for an educative opportunity with the player concerned as well as consideration of modification of playing behavior if required.A range of modifying factors may influence the investigation and management of concussion and, in some cases, may predict the potential for prolonged or persistent symptoms. However, in some cases, the evidence for their efficacy is limited. These modifiers would be important to consider in a detailed concussion history and are outlined in Table 2.The role of female sex as a possible modifier in the management of concussion was discussed at length by the panel. There was not unanimous agreement that the current published research evidence is conclusive enough for this to be included as a modifying factor, although it was accepted that sex may be a risk factor for injury or influence injury severity (or both).73–75In the overall management of moderate to severe traumatic brain injury, duration of loss of consciousness (LOC) is an acknowledged predictor of outcome.76 While published findings in concussion describe LOC associated with specific early cognitive deficits, it has not been noted as a measure of injury severity.77,78 Consensus discussion determined that prolonged (>1-minute duration) LOC would be considered as a factor that may modify management.There is renewed interest in the role of posttraumatic amnesia and its role as a surrogate measure of injury severity.64,79,80 Published evidence suggests that the nature, burden, and duration of the clinical postconcussive symptoms may be more important than the presence or duration of amnesia alone.77,81,82 Further, it must be noted that retrograde amnesia varies with the time of measurement postinjury and hence is poorly reflective of injury severity.83,84A variety of immediate motor phenomena (eg, tonic posturing) or convulsive movements may accompany a concussion. Although dramatic, these clinical features are generally benign and require no specific management beyond the standard treatment of the underlying concussive injury.85,86Mental health issues as have been reported as a of all of traumatic brain injury, including sports-related concussion. studies using that a after concussion may an underlying pathophysiological with a of While such health issues may be in nature, it is recommended that the treating physician consider these issues in the management of concussed evaluation and management recommendations can be applied to children and to the of that children concussion symptoms different from and would require symptom as a component of assessment. An additional consideration in assessing the or athlete with a concussion is that the clinical evaluation by the health care professional may to include both patient and and and school when A SCAT3 has been developed to assess concussion for those decision to use NP testing is the same as the assessment although there are some of testing may in to assist in school and management. If cognitive testing is then it must be sensitive until to the ongoing cognitive that during this period in the of to the baseline or to In this it is more important to consider the use of trained pediatric neuropsychologists to interpret assessment particularly in children with or who may more sophisticated assessment was agreed by the panel that no return to sport or should occur before the or athlete has managed to return to school In addition, the of was with to a to exertion with activities of that may symptoms. and activities may also to be to of symptoms. should not be to sport until clinically symptom which may require a longer timeframe than for of the different response and longer recovery after concussion and specific (eg, related to head during and a more conservative RTP approach is It is appropriate to the amount of time of asymptomatic rest or the length of the graded exertion in children and It is not appropriate for a or athlete with concussion to RTP on the same day as the injury, of the level of Concussion modifiers more to this than and may more RTP athletes, of level of should be managed using the same treatment and RTP The and in concussion evaluation are of more importance in determining management than a separation and athlete management. Although formal NP testing may be beyond the of many sports or it is recommended that, in all sports, consideration be to this cognitive evaluation, of the or level of to be of the potential for long-term in the management of all athletes. However, it was agreed that traumatic a distinct with an in It was further agreed that a has not been demonstrated and concussions or to contact At present, the interpretation of in the studies should proceed It was also recognized that it is important to the of and athletes from related to the of is no clinical evidence that currently protective equipment will concussion, although have a role in and injury. studies have shown a in to the brain with the use of head and but these findings have not been to a in concussion and there are a number of studies to that provide head and injury and hence should be recommended for in In specific sports, such as and motor and sports, protective may other forms of head injury (eg, skull fracture) that are related to on and may be an important for those of rule changes to the head injury or severity may be appropriate where a is in a particular An of this is in where research studies demonstrated that contact in for approximately of As noted rule changes also may be in some sports to allow an off-field medical assessment to occur without the affecting the flow of the or unduly penalizing the player's team. It is important to that rule may be a aspect of modifying injury risk in these and play an important role in this important consideration in the use of protective equipment is the of risk This is where the use of protective equipment in change such as the of more playing which can result in a in injury The to which this is discussed in more in the published in the of Sports This may be a particular in and athletes, in head injury are often than in nature of sport that it to play and should not be However, sporting should be encouraged to that may concussion play and should be as key of the to or the of concussive injury after the is of athletes, and the is a of progress in this and health care providers must be regarding the of concussion, its clinical features, assessment and principles of RTP. to including and are important in the In addition, concussion the and of sport such as the International International and International that this have value and must be play and for are that should be encouraged in all sports and sporting and play an important part in these are on the of November 2001, the 1st International Conference on Concussion in Sport was held in This was by the in with and the of the As part of the resulting for the the for and were The 2nd International Conference on Concussion in Sport was by the same with the additional of the and was held in in November The of the were to provide recommendations for the of and health of athletes who concussive injuries in and as well as other this a range of were to both to specific issues of basic and clinical injury cognitive assessment, new research protective and long-term 3rd International Conference on Concussion in Sport was held in Zurich, on 2008 and was designed as a formal consensus following the by the US of of the consensus can be at The basic principles the of a consensus development are panel not with any The was for the consensus and the were from clinical and research in the of sports-related concussion. not but were for their and understanding of this 4th International Conference on Concussion in Sport was held in Zurich, on November 2012 and the same as for the 3rd consensus panel and authors were required to an International of for of of information related to each and of will be made on the Concussion in Sport Group and published with the of Sports consensus document the current of and will to be to the development of new It provides an of issues that may be of importance to health care providers involved in the management of sports-related concussion. It is not as a standard of care and should not be as This document is only a and is of a

Despite agreement that dysnomia affects virtually every aphasic patient, there is no consensus about the purpose and effectiveness of techniques to treat it. Semantic feature analysis (SFA), a treatment technique designed to improve retrieval of conceptual information by accessing semantic networks, was used to treat aphasic dysnomia in a 57-year-old male who exhibited Broca's aphasia secondary to a left frontoparietal ischemic infarction. SFA was effective for improving confrontation naming and for generalized improvement to untreated pictures. However, no generalization to connected speech was seen on the measures of mean words per minute, mean correct information units per minute, or the percentage of all words that were correct information units.

BACKGROUND AND PURPOSE: The purpose of this study was to assess the effects of stroke involvement of primary and secondary hemispheric motor systems and corticofugal tracts on arm and hand recovery. METHODS: Forty-one patients participating in an inpatient stroke rehabilitation database, admitted 17+/-2 (SEM) days after initial unilateral hemispheric ischemic stroke, with neuroimaging studies performed >48 hours after stroke and with minimal upper limb (UL) movement (admission Fugl-Meyer UL motor scores </=9; normal score, 58) were studied. Patients were divided into 3 groups according to their UL discharge Fugl-Meyer score: 0 to 9, no/poor recovery; 10 to 18, well-defined flexion-extension synergies; and >18, synergies+isolated movements. Lesions affecting the following structures were recorded: primary motor cortex, premotor area, supplementary motor area, anterior half of the middle third of corona radiata (secondary motor efferents), posterior half of the middle third of corona radiata (primary motor efferents), genu, anterior and posterior limbs of the internal capsule (PLIC), basal ganglia, and thalamus. chi(2) Analysis and ANOVA were used to study the significance of stroke location on UL motor recovery. RESULTS: The effect of involvement of primary, premotor, or supplementary motor areas on motor recovery did not reach statistical significance. Patients with purely cortical stroke were likely to recover UL isolated movement (3 of 4) compared with purely subcortical (1 of 17) or mixed cortical-subcortical stroke location (2 of 20) (P:=0.009). Of those with cortical, subcortical, or mixed cortical plus subcortical lesions sparing the PLIC, 5 of 13 recovered isolated UL movement (P:=0.01). Only 1 of 28 patients with involvement of the PLIC plus adjacent corona radiata, basal ganglia, or thalamus recovered isolated UL movement (P:=0.01). Patients with small lacunar strokes affecting only the PLIC did not have sufficient motor deficits 2 weeks after stroke to meet inclusion criteria. CONCLUSIONS: The probability of recovery of isolated UL movement decreases progressively with lesion location as follows: cortex, corona radiata, and PLIC. This is consistent with our current understanding of redundant cortical motor representation and convergence of corticofugal motor efferents as they pass through the corona radiata to the PLIC.

The activity of the pyruvate dehydrogenase complex (PDHC) was reduced in affected areas of brain from patients with Huntington disease (caudate, putamen) and Alzheimer disease (frontal cortex) where choline acetyltransferase (CAT) activity was low. PDHC was also deficient in an area (Huntington hippocampus) where CAT was not significantly reduced. The activity of fumarase, an inner mitochondrial marker, was normal in all areas examined. The activities of PDHC and CAT correlated well in caudate, putamen, and amygdala but not in hippocampus or frontal cortex. Both total activity and activation of PDHC were below normal in fibroblasts from 4 patients with C-21 trisomy Down syndrome, who are at very high risk to develop Alzheimer disease. However, no abnormality of PDHC was detected in Huntington or Alzheimer fibroblasts. Deficiency of PDHC may play a role in the pathophysiology of Huntington and Alzheimer diseases, although it does not appear to be a primary defect. Loss of tissue oxidative capacity may relate to the reduction in cerebral metabolic rate and blood flow which are characteristic of many dementing illnesses.

OBJECTIVE: To identify enduring prolonged neuropsychological effects of cerebral concussion in high school youth athletes. METHODS: High school athletes (n = 223) underwent baseline neuropsychological evaluation between 1999 and 2000, assigned to independent groups on the basis of concussion history: athletes with no concussion history or present medical and/or neuropsychological complaints (n = 82), symptom-free athletes who experienced one (n = 56) or two or more (n = 45) concussions (not in the prior 6 mo), and those who experienced a concussion 1 week before testing (n = 40). Main outcome measures included a structured clinical interview, demographic form, symptom checklist, the Repeatable Battery for the Assessment of Neuropsychological Status, and the Trail Making Tests A and B. Analyses of variance were used to determine between-group differences. RESULTS: Athletes with recent concussions performed significantly worse on measures of attention and concentration than youth athletes with no concussion history. Symptom-free athletes with a history of two or more concussions performed similar on testing to youth athletes who had just experienced a recent concussion. Similarly, cumulative academic grade point averages were significantly lower not only for youth athletes with two or more previous concussion groups, but for youth athletes who experienced recent concussions, suggesting that athletes with lower grade point averages may be more prone to concussion. CONCLUSION: There seem to be subtle yet significant prolonged neuropsychological effects in youth athletes with a history of two or more previous concussions.

Objectives N‐acetylcysteine (NAC) is a clinically approved thiol‐containing redox modulatory compound currently in trials for many neurological and psychiatric disorders. Although generically labeled as an “antioxidant,” poor understanding of its site(s) of action is a barrier to its use in neurological practice. Here, we examined the efficacy and mechanism of action of NAC in rodent models of hemorrhagic stroke. Methods Hemin was used to model ferroptosis and hemorrhagic stroke in cultured neurons. Striatal infusion of collagenase was used to model intracerebral hemorrhage (ICH) in mice and rats. Chemical biology, targeted lipidomics, arachidonate 5‐lipoxygenase (ALOX5) knockout mice, and viral‐gene transfer were used to gain insight into the pharmacological targets and mechanism of action of NAC. Results NAC prevented hemin‐induced ferroptosis by neutralizing toxic lipids generated by arachidonate‐dependent ALOX5 activity. NAC efficacy required increases in glutathione and is correlated with suppression of reactive lipids by glutathione‐dependent enzymes such as glutathione S ‐transferase. Accordingly, its protective effects were mimicked by chemical or molecular lipid peroxidation inhibitors. NAC delivered postinjury reduced neuronal death and improved functional recovery at least 7 days following ICH in mice and can synergize with clinically approved prostaglandin E 2 (PGE 2 ). Interpretation NAC is a promising, protective therapy for ICH, which acted to inhibit toxic arachidonic acid products of nuclear ALOX5 that synergized with exogenously delivered protective PGE 2 in vitro and in vivo. The findings provide novel insight into a target for NAC, beyond the generic characterization as an antioxidant, resulting in neuroprotection and offer a feasible combinatorial strategy to optimize efficacy and safety in dosing of NAC for treatment of neurological disorders involving ferroptosis such as ICH. Ann Neurol 2018;84:854–872

I used leg and arm paresis to predict outcome measured as extremity function in a prospective study of 75 consecutive hemiplegic patients admitted to an inpatient stroke rehabilitation unit. In each patient, extremity paresis was quantified according to the five-point scoring system advised by the Medical Research Council, upper extremity function was quantified using the Barthel Index subscore for feeding and dressing the upper body, and lower extremity function was quantified according to a five-point scoring of the ability to walk. Improvement was recorded for upper extremity function in 52% of the patients and for lower extremity function in 89%. Best extremity function was reached a mean +/- SEM of 9 +/- 3 and 10 +/- 4 weeks after stroke for the upper and lower extremities, respectively. In patients experiencing complete recovery, this occurred a mean +/- SEM of 7 +/- 2 weeks (for both upper and lower extremities) after the stroke. Only 8-11% of the patients with paresis scores of less than or equal to 2 regained independent extremity function after rehabilitation. Half of the patients with paresis scores of greater than or equal to 3 regained independent extremity function after rehabilitation, while the other half were able to perform extremity function with only minimal assistance. As predictors of extremity function, the Barthel Index subscore was slightly better (r = 0.64) than paresis score (r = 0.58). However, because evaluation of extremity paresis is easy, it appears to be useful as a preliminary predictor of outcome following stroke.

OBJECTIVE: To determine the relative risk of pneumonia, dehydration, and death associated with videofluoroscopic evidence of aspiration, silent aspiration, aspiration of 10% or greater on one or more barium test swallows, and aspiration of thick liquid or more solid consistencies in the subacute phase after stroke. DESIGN: Prospective, longitudinal cohort study. SETTING: Inpatient stroke rehabilitation unit. PATIENTS: There were 114 consecutive patients who met the following criteria: (1) stroke as defined by clinical history and neurological examination with compatible computed tomographic or magnetic resonance imaging scan; (2) age 20 to 90 years, inclusive; (3) no known history of significant oropharyngeal anomaly; and (4) videofluoroscopic evidence of dysphagia. Of 122 eligible patients, eight refused participation. MAIN OUTCOME MEASURES: Development of pneumonia, dehydration, and death. RESULTS: The relative risk for developing pneumonia was 6.95 times greater (P = .027) for those patients who aspirated compared with those who did not, 5.57 times greater (P = .012) for those who aspirated silently compared with those who coughed when aspirating or who did not aspirate, and 8.36 times greater (P = .002) for those who aspirated 10% or greater on one or more barium test swallows compared with those who aspirated less than 10% or did not aspirate. CONCLUSION: Aspiration, silent aspiration, and aspiration of 10% or greater on one or more barium test swallows during videofluoroscopic evaluation are associated with an increased risk of pneumonia, but not dehydration or death, during the subacute phase after stroke.

Chronic traumatic brain injury (CTBI) associated with boxing occurs in approximately 20% of professional boxers. Risk factors associated with CTBI include increased exposure (i.e., duration of career, age of retirement, total number of bouts), poor performance, increased sparring, and apolipoprotein (APOE) genotype. Clinically, boxers exhibiting CTBI will present with varying degrees of motor, cognitive, and/or behavioral impairments. The severe form of CTBI is referred to as dementia pugilistica. The diagnosis of CTBI is dependent upon documenting a progressive neurological condition that is consistent with the clinical symptomatology of CTBI attributable to brain trauma and unexplainable by an alternative pathophysiological process. Pathologically, CTBI shares many characteristics with Alzheimer's disease (i.e., neurofibrillary triangles, diffuse amyloid plaques, acetylcholine deficiency, and/or tau immunoreactivity). The mainstay of treatment of CTBI is prevention, however medications used in the treatment of Alzheimer's disease and/or parkinsonism may be utilized.

Life table analysis is a powerful statistical tool that has become the preferred technique for studying both the natural history of and the effect of treatment on disease outcome. We have found only one report using life table analysis to study rehabilitation outcome after stroke. We assessed the recovery of both independent ambulation and overall self-care function in 95 consecutive patients with unilateral hemispheric stroke using life table analysis. Our results support the segregation of patients into the following prognostic subgroups at the time of entry into the rehabilitation program (mean +/- SD 5 +/- 3 weeks after stroke): 1) motor deficit only, 2) motor deficit plus somatic sensory deficit, and 3) motor deficit plus somatic sensory deficit plus homonymous visual deficit. The probabilities of reaching independence in ambulation, being able to walk 150 feet with assistance, reaching independence in self-care function, and reaching a point of assisted self care (Barthel Index score of greater than or equal to 60) are highly significantly different among subgroups. The interval after stroke required to reach the plateau phase of recovery is also significantly different among subgroups. We propose that life table analysis can be used 1) to define patient outcome goals, 2) to define the time required to reach such goals, 3) to identify patients with medical or behavioral comorbidity who are functioning below their expected level, and 4) to assess the effect of alternative treatment regimens on both final outcome and time to reach that outcome.

This study assessed inter- and intrarater reliability and sensitivity to change of the 2-, 6-, and 12-minute walk tests following stroke. A convenience sample of patients enrolled in an inpatient stroke rehabilitation program participated in the standardization protocol. The 2-, 6-, and 12-minute walk tests were performed and inter- and intrarater reliability and responsiveness to change assessed. The interrater intraclass correlation coefficients (ICCs) for the 2-, 6-, and 12-minute walk tests were, respectively, 0.85, 0.78, and 0.68 (p < 0.0007 for each). The intrarater ICCs were 0.85, 0.74, and 0.71 (p < 0.0003 for each). Responsiveness to change as measured by standardized response mean (SRM) scores was, respectively, 1.34, 1.52, and 1.90 (F = 24.24, p < 0.001). Pearson correlations for the 2-, 6-, and 12-minute walk tests by the same rater on the same day were 2 versus 6 minutes, r = 0.997; 2 versus 12 minutes, r = 0.993; and 6 versus 12 minutes, r = 0.994 (p < 0.0001 for each). The 2-, 6-, and 12-minute walk tests show acceptable inter- and intrarater reliability and high intertest correlations when they are used for the assessment of walking following stroke. The SRM statistic indicates that the 12-minute walk test is the most responsive to change.

The synthesis of whole brain acetylcholine is reduced in two strains (C57BL and BALB/c) of senescent mice. The incorporation of [U-14C]glucose into acetylcholine decreased in both strains by 40 +/- 4 per cent in 10-month-old mice and by 58 +/- 9 percent in 30-month-old mice compared with mice 3 months old. The incorporation of [2H4]choline into acetylcholine declined 60 and 73 percent in 10- and 30-month-old mice, respectively. Deficits in the cholinergic system may contribute to brain dysfunctions that complicate senescence.

Regional protein synthesis was measured in rat brain at intervals up to 48 h following occlusion of the four major arteries to the brain for either 10 or 30 min. Four-vessel occlusions produces ischemia in the cerebral hemispheres and oligemia in the midbrain-diencephalon and brainstem. During the hour following 10 min of ischemia, protein synthesis, measured by incorporation of [14C]valine into protein, was inhibited in the cerebral cortex by 67%. Normal rates of protein synthesis were attained within 4 h of recirculation. In rats subjected to 30 min of ischemia, protein synthesis was inhibited by 83% during the first hour of recirculation in the cortex, caudate-putamen, and hippocampus. Recovery of protein synthesis in these regions was slow (25-48 h). The midbrain-diencephalon showed less inhibition, 67%, and faster recovery (by 12 h). Protein synthesis was unaffected in the brainstem. [14C]Autoradiography revealed that the pyramidal neurons of the hippocampus and areas of the caudate and cortex failed to recover normal rates of protein synthesis even after 48 h. The accumulation of TCA-soluble [14C]valine was enhanced (55-65%) in the cortex, caudate, and hippocampus after 30 min of ischemia; the increase persisted for 12 h. A smaller rise in [14C]valine content (30%) and more rapid normalization of valine accumulation (by 7 h) were observed in the midbrain-diencephalon; no changes were found in the brainstem. In the cortex, recovery was more rapid when the duration of ischemia was reduced. Thus, the degree of inhibition of protein synthesis, the accumulation of valine in the tissue, and the length of time required to reestablish normal values for these processes were dependent on both the severity and the duration of the ischemic insult. Restoration of normal rates of protein synthesis after ischemia was slow compared with the normalization of cerebral energy metabolites.