John Whyte

The minimally conscious state: Definition and diagnostic criteria

ObjectiveTo establish consensus recommendations among health care specialties for defining and establishing diagnostic criteria for the minimally conscious state (MCS). BackgroundThere is a subgroup of patients with severe alteration in consciousness who do not meet diagnostic criteria for coma or the vegetative state (VS). These patients demonstrate inconsistent but discernible evidence of consciousness. It is important to distinguish patients in MCS from those in coma and VS because preliminary findings suggest that there are meaningful differences in outcome. MethodsAn evidence-based literature review of disorders of consciousness was completed to define MCS, develop diagnostic criteria for entry into MCS, and identify markers for emergence to higher levels of cognitive function. ResultsThere were insufficient data to establish evidence-based guidelines for diagnosis, prognosis, and management of MCS. Therefore, a consensus-based case definition with behaviorally referenced diagnostic criteria was formulated to facilitate future empirical investigation. ConclusionsMCS is characterized by inconsistent but clearly discernible behavioral evidence of consciousness and can be distinguished from coma and VS by documenting the presence of specific behavioral features not found in either of these conditions. Patients may evolve to MCS from coma or VS after acute brain injury. MCS may also result from degenerative or congenital nervous system disorders. This condition is often transient but may also exist as a permanent outcome. Defining MCS should promote further research on its epidemiology, neuropathology, natural history, and management.

Clinical Trials in Head Injury

Secondary brain damage, following severe head injury is considered to be a major cause for bad outcome. Impressive reductions of the extent of brain damage in experimental studies have raised high expectations for cerebral neuroprotective treatment, in the clinic. Therefore multiple compounds were and are being evaluated in trials. In this review we discuss the pathomechanisms of traumatic brain damage, based upon their clinical importance. The role of hypothermia, mannitol, barbiturates, steroids, free radical scavengers, arachidonic acid inhibitors, calcium channel blockers, N-methyl-D-aspartate (NMDA) antagonists, and potassium channel blockers, will be discussed. The importance of a uniform strategic approach for evaluation of potentially interesting new compounds in clinical trials, to ameliorate outcome in patients with severe head injury, is proposed. To achieve this goal, two nonprofit organizations were founded: the European Brain Injury Consortium (EBIC) and the American Brain Injury Consortium (ABIC). Their aim lies in conducting better clinical trials, which incorporate lessons learned from previous trials, such that the succession of negative, or incomplete studies, as performed in previous years, will cease.

Hemispatial neglect Subtypes, neuroanatomy, and disability

Objective: To assess the relative frequency of occurrence of motor, perceptual, peripersonal, and personal neglect subtypes, the association of neglect and other related deficits (e.g., deficient nonlateralized attention, anosognosia), and the neuroanatomic substrates of neglect in patients with right hemisphere stroke in rehabilitation settings. Methods: The authors assessed 166 rehabilitation inpatients and outpatients with right hemisphere stroke with measures of neglect and neglect subtypes, attention, motor and sensory function, functional disability, and family burden. Detailed lesion analyses were also performed. Results: Neglect was present in 48% of right hemisphere stroke patients. Patients with neglect had more motor impairment, sensory dysfunction, visual extinction, basic (nonlateralized) attention deficit, and anosognosia than did patients without neglect. Personal neglect occurred in 1% and peripersonal neglect in 27%, motor neglect in 17%, and perceptual neglect in 21%. Neglect severity predicted scores on the Functional Independence Measure and Family Burden Questionnaire more accurately than did number of lesioned regions. Conclusions: The neglect syndrome per se, rather than overall stroke severity, predicts poor outcome in right hemisphere stroke. Dissociations between tasks assessing neglect subtypes support the existence of these subtypes. Finally, neglect results from lesions at various loci within a distributed system mediating several aspects of attention and spatiomotor performance.

Assessment Scales for Disorders of Consciousness: Evidence-Based Recommendations for Clinical Practice and Research

OBJECTIVES To conduct a systematic review of behavioral assessment scales for disorders of consciousness (DOC); provide evidence-based recommendations for clinical use based on their content validity, reliability, diagnostic validity, and ability to predict functional outcomes; and provide research recommendations on DOC scale development and validation. DATA SOURCES Articles published through March 31, 2009, using MEDLINE, CINAHL, Psychology and Behavioral Sciences Collection, Cochrane Database of Systematic Reviews, Database of Abstracts of Reviews of Effects, Cochrane Central Register of Controlled Trials, Biomedical Reference Collection, and PsycINFO. Thirteen primary terms that defined DOC were paired with 30 secondary terms that defined aspects of measurement. Scale names, abbreviations, and authors were also used as search terms. Task force members identified additional articles by using personal knowledge and examination of references in reviewed articles. STUDY SELECTION Primary criteria included the following: (1) provided reliability, diagnostic validity, and/or prognostic validity data; (2) examined a cohort, case control, or case series sample of persons with DOC who were age older than or equal to 18 years; and (3) assessed in an acute care or rehabilitation setting. Articles were excluded if peer review was not conducted, original data were not reported, or an English language article was not available. The initial search yielded 580 articles. After paired rater review of study abstracts, guideline development was based on 37 articles representing 13 DOC scales. DATA EXTRACTION Rater pairs classified studies addressing diagnostic and prognostic validity by using the American Academy of Neurology 4-tier level of evidence scheme, and reliability by using a task force-developed 3-tier evidence scheme. An independent quality review of ratings was conducted, and corrections were made. DATA SYNTHESIS The Coma Recovery Scale-Revised (CRS-R), Sensory Stimulation Assessment Measure (SSAM), Wessex Head Injury Matrix (WHIM), Western Neuro Sensory Stimulation Profile (WNSSP), Sensory Modality Assessment Technique (SMART), Disorders of Consciousness Scale (DOCS), and Coma/Near-Coma Scale (CNC) have acceptable standardized administration and scoring procedures. The CRS-R has excellent content validity and is the only scale to address all Aspen Workgroup criteria. The SMART, SSAM, WHIM, and WNSSP demonstrate good content validity, containing items that could distinguish persons who are in a vegetative state, are in a minimally conscious state (MCS), or have emerged from MCS. The Full Outline of UnResponsiveness Score (FOUR), WNSSP, CRS-R, Comprehensive Levels of Consciousness Scale (CLOCS), and Innsbruck Coma Scale (INNS) showed substantial evidence of internal consistency. The FOUR and the CRS-R showed substantial evidence of good interrater reliability. Evidence of diagnostic validity and prognostic validity in brain injury survivor samples had very high levels of potential bias because of methodologic issues such as lack of rater masking. CONCLUSIONS The CRS-R may be used to assess DOC with minor reservations, and the SMART, WNSSP, SSAM, WHIM, and DOCS may be used to assess DOC with moderate reservations. The CNC may be used to assess DOC with major reservations. The FOUR, INNS, Glasgow-Liege Coma Scale, Swedish Reaction Level Scale-1985, Loewenstein Communication Scale, and CLOCS are not recommended at this time for bedside behavioral assessment of DOC because of a lack of content validity, lack of standardization, and/or unproven reliability.

Working memory impairments in traumatic brain injury: evidence from a dual-task paradigm

Although many individuals with traumatic brain injury (TBI) perform well on standard neuropsychological tests, they often exhibit marked functional difficulties. The functions which are impaired seem to be analogous to the role of the central executive system (CES) in Baddeleys [Working Memory, 1986, Oxford University Press, New York] widely accepted model of working memory. The purpose of this study was to investigate CES function in individuals with TBI with a dual-task paradigm. We studied 25 non-demented persons who were at various stages in their recovery from severe TBI and compared their performance on a dual-task paradigm to a group of age-matched controls. Our dual-task paradigm measured performance on a simple visual reaction time task both alone (baseline) and during concurrent tasks of articulation or digit span. Subjects were also assessed with other neuropsychological tests of executive function. TBI patients had slower reaction times on the primary task when performed alone (P < 0.05) and greater decrements in performance during dual-task conditions (P < 0.01). They also exhibited significantly greater deficits than control subjects on other measures of executive function. Although correlations between dual-task performance and other executive measures were quite low, principle components analysis suggested that a common factor does exist between these measures. These findings support the conclusion that TBI patients have a working memory impairment that is due to dysfunction of the CES and which may be related to executive function deficits as measured by standard neuropsychological testing.

It's more than a black box; it's a Russian doll: defining rehabilitation treatments.

Whyte J, Hart T: It’s more than a black box; it’s a Russian doll: Defining rehabilitation treatments. Am J Phys Med Rehabil 2003;82:639–652.Research on treatment efficacy and effectiveness requires that the treatments of interest be objectively defined. Such definitions are relatively straightforward for pharmacologic and surgical treatments, in which the active ingredients can be specified in terms of chemical structure or anatomic result. Definitions of treatment are more difficult for the many experience-based interventions employed in rehabilitation. This has led to the criticism that much clinical rehabilitation research has characterized the treatments of interest as a “black box,” allowing little insight into the active ingredients contained therein. Moreover, rehabilitation care may involve the simultaneous application of multiple different treatments, raising the question of whether to define the individual components or the service delivery system. In this article, we consider how the levels of analysis considered in rehabilitation (disease, impairment, activity, and participation) and the role of theory shape the definition of treatment, and we address the need to develop protocol-based treatments and tools to objectively verify their contents. Rigorous definition of rehabilitation treatments, supported by theory, will facilitate needed efficacy research, will allow replication of that research, and will ultimately foster dissemination of effective treatments into clinical practice.

Cognitive Rehabilitation Interventions for Executive Function: Moving from Bench to Bedside in Patients with Traumatic Brain Injury

Executive function mediated by prefrontally driven distributed networks is frequently impaired by traumatic brain injury (TBI) as a result of diffuse axonal injury and focal lesions. In addition to executive cognitive functions such as planning and working memory, the effects of TBI impact social cognition and motivation processes. To encourage application of cognitive neuroscience methods to studying recovery from TBI, associated reorganization of function, and development of interventions, this article reviews the pathophysiology of TBI, critiques currently employed methods of assessing executive function, and evaluates promising interventions that reflect advances in cognitive neuroscience. Brain imaging to identify neural mechanisms mediating executive dysfunction and response to interventions following TBI is also discussed.

Effects of methylphenidate on attentional function after traumatic brain injury. A randomized, placebo-controlled trial.

Attention deficits after traumatic brain injury (TBI) are common and disabling. Many pharmacologic agents have been used to ameliorate attention deficits, and considerable interest has focused on methylphenidate (MP) because of its documented efficacy in attention deficit disorder. However, clinical studies of MP in subjects with TBI have yielded mixed results. We examined the effects of MP on attentional function in individuals with TBI referred specifically for attentional assessment and treatment. Subjects were studied in a double-blind, placebo-controlled, repeated crossover design, using five different tasks designed to measure various facets of attentional function. MP produced a significant improvement in the speed of mental processing. Orienting to distractions, most aspects of sustained attention, and measures of motor speed were unaffected. These results suggest that MP may be a useful treatment in TBI but is primarily useful for symptoms that can be attributed to slowed mental processing.

Patterns of spontaneous recovery of neglect and associated disorders in acute right brain-damaged patients

Objectives: The evolutionary pattern of spontaneous recovery from acute neglect was studied by assessing cognitive deficits and motor impairments. Detailed lesion reconstruction was also performed to correlate the presence of and recovery from neglect to neural substrates. Methods: A consecutive series of right brain-damaged (RBD) patients with and without neglect underwent weekly tests in the acute phase of the illness. The battery assessed neglect deficits, neglect-related deficits, and motor impairment. Age-matched normal subjects were also investigated to ascertain the presence of non lateralised attentional deficits. Some neglect patients were also available for later investigation during the chronic phase of their illness. Results: Partial recovery of neglect deficits was observed at the end of the acute period and during the chronic phase. Spatial attention was impaired in acute neglect patients, while non spatial attentional deficits were present in RBD patients with and without acute neglect. A strong association was found between acute neglect and fronto-parietal lesions. Similar lesions were associated with neglect persistence. In the chronic stage, neglect recovery was paralleled by improved motor control of the contralesional upper limb, thus emphasising that neglect is a negative prognostic factor in motor functional recovery. Conclusions: These findings show that spatial attention deficits partially improve during the acute phase of the disease in less than half the patients investigated. There was an improvement in left visuospatial neglect at a later, chronic stage of the disease, but this recovery was not complete.

Structural consequences of diffuse traumatic brain injury: A large deformation tensor-based morphometry study

Traumatic brain injury (TBI) is one of the most common causes of long-term disability. Despite the importance of identifying neuropathology in individuals with chronic TBI, methodological challenges posed at the stage of inter-subject image registration have hampered previous voxel-based MRI studies from providing a clear pattern of structural atrophy after TBI. We used a novel symmetric diffeomorphic image normalization method to conduct a tensor-based morphometry (TBM) study of TBI. The key advantage of this method is that it simultaneously estimates an optimal template brain and topology preserving deformations between this template and individual subject brains. Detailed patterns of atrophies are then revealed by statistically contrasting control and subject deformations to the template space. Participants were 29 survivors of TBI and 20 control subjects who were matched in terms of age, gender, education, and ethnicity. Localized volume losses were found most prominently in white matter regions and the subcortical nuclei including the thalamus, the midbrain, the corpus callosum, the mid- and posterior cingulate cortices, and the caudate. Significant voxel-wise volume loss clusters were also detected in the cerebellum and the frontal/temporal neocortices. Volume enlargements were identified largely in ventricular regions. A similar pattern of results was observed in a subgroup analysis where we restricted our analysis to the 17 TBI participants who had no macroscopic focal lesions (total lesion volume >1.5 cm(3)). The current study confirms, extends, and partly challenges previous structural MRI studies in chronic TBI. By demonstrating that a large deformation image registration technique can be successfully combined with TBM to identify TBI-induced diffuse structural changes with greater precision, our approach is expected to increase the sensitivity of future studies examining brain-behavior relationships in the TBI population.