The evolution of white matter microstructural changes after mild traumatic brain injury: A longitudinal DTI and NODDI study.

Neuroimaging biomarkers that can detect white matter (WM) pathology after mild traumatic brain injury (mTBI) and predict long-term outcome are needed to improve care and develop therapies. We used diffusion tensor imaging (DTI) and neurite orientation dispersion and density imaging (NODDI) to investigate WM microstructure cross-sectionally and longitudinally after mTBI and correlate these with neuropsychological performance. Cross-sectionally, early decreases of fractional anisotropy and increases of mean diffusivity corresponded to WM regions with elevated free water fraction on NODDI. This elevated free water was more extensive in the patient subgroup reporting more early postconcussive symptoms. The longer-term longitudinal WM changes consisted of declining neurite density on NODDI, suggesting axonal degeneration from diffuse axonal injury for which NODDI is more sensitive than DTI. Therefore, NODDI is a more sensitive and specific biomarker than DTI for WM microstructural changes due to mTBI that merits further study for mTBI diagnosis, prognosis, and treatment monitoring.

An Italian multicentre validation study of the coma recovery scale-revised.

BACKGROUND: Rate of misdiagnosis of disorders of consciousness (DoC) can be reduced by employing validated clinical diagnostic tools, such as the Coma Recovery Scale-Revised (CRS-R). An Italian version of the CRS-R has been recently developed, but its applicability across different clinical settings, and its concurrent validity and diagnostic sensitivity have not been estimated yet. AIM: To perform a multicentre validation study of the Italian version of the Coma Recovery Scale-Revised (CRS-R). DESIGN: Analysis of inter-rater reliability, concurrent validity and diagnostic sensitivity of the scale. SETTING: One Intensive Care Unit, 8 Post-acute rehabilitation centres and 2 Long-term facilities POPULATION: Twenty-seven professionals (physicians, N.=11; psychologists, N.=5; physiotherapists, N.=3; speech therapists, N.=6; nurses, N.=2) from 11 Italian Centres. METHODS: CRS-R and Disability Rating Scale (DRS) applied to 122 patients with clinical diagnosis of Vegetative State (VS) or Minimally Conscious State (MCS). RESULTS: CRS-R has good-to-excellent inter-rater reliability for all subscales, particularly for the communication subscale. The Italian version of the CRS-R showed a high sensitivity and specificity in detecting MCS with reference to clinical consensus diagnosis. The CRS-R showed good concurrent validity with the Disability Rating Scale, which had very low specificity with reference to clinical consensus diagnosis. CONCLUSIONS: The Italian version of the CRS-R is a valid scale for use from the sub-acute to chronic stages of DoC. It can be administered reliably by all members of the rehabilitation team with different specialties, levels of experience and settings. CLINICAL REHABILITATION IMPACT: The present study promote use of the Italian version of the CRS-R to improve diagnosis of DoC patients, and plan tailored rehabilitation treatment.

Behavioural improvements with thalamic stimulation after severe traumatic brain injury.

Widespread loss of cerebral connectivity is assumed to underlie the failure of brain mechanisms that support communication and goal-directed behaviour following severe traumatic brain injury. Disorders of consciousness that persist for longer than 12 months after severe traumatic brain injury are generally considered to be immutable; no treatment has been shown to accelerate recovery or improve functional outcome in such cases. Recent studies have shown unexpected preservation of large-scale cerebral networks in patients in the minimally conscious state (MCS), a condition that is characterized by intermittent evidence of awareness of self or the environment. These findings indicate that there might be residual functional capacity in some patients that could be supported by therapeutic interventions. We hypothesize that further recovery in some patients in the MCS is limited by chronic underactivation of potentially recruitable large-scale networks. Here, in a 6-month double-blind alternating crossover study, we show that bilateral deep brain electrical stimulation (DBS) of the central thalamus modulates behavioural responsiveness in a patient who remained in MCS for 6 yr following traumatic brain injury before the intervention. The frequency of specific cognitively mediated behaviours (primary outcome measures) and functional limb control and oral feeding (secondary outcome measures) increased during periods in which DBS was on as compared with periods in which it was off. Logistic regression modelling shows a statistical linkage between the observed functional improvements and recent stimulation history. We interpret the DBS effects as compensating for a loss of arousal regulation that is normally controlled by the frontal lobe in the intact brain. These findings provide evidence that DBS can promote significant late functional recovery from severe traumatic brain injury. Our observations, years after the injury occurred, challenge the existing practice of early treatment discontinuation for patients with only inconsistent interactive behaviours and motivate further research to develop therapeutic interventions.

The minimally conscious state: defining the borders of consciousness.

There is no agreement as to where the limits of consciousness lie, or even if these putative borders exist. Problems inherent to the study of consciousness continue to confound efforts to establish a universally accepted theory of consciousness. Consequently, clinical definitions of consciousness and unconsciousness are unavoidably arbitrary. Recently, a condition of severely altered consciousness has been described, which characterizes the borderzone between the vegetative state and so-called "normal" consciousness. This condition, referred to as the minimally conscious state (MCS), is distinguished from the vegetative state by the presence of minimal but clearly discernible behavioral evidence of self or environmental awareness. This chapter reviews the diagnostic criteria, pathophysiology, prognostic relevance, neurobehavioral assessment procedures and treatment implications associated with MCS.

fMRI reveals large-scale network activation in minimally conscious patients.

BACKGROUND: The minimally conscious state (MCS) resulting from severe brain damage refers to a subset of patients who demonstrate unequivocal, but intermittent, behavioral evidence of awareness of self or their environment. Although clinical examination may suggest residual cognitive function, neurobiological correlates of putative cognition in MCS have not been demonstrated. OBJECTIVE: To test the hypothesis that MCS patients retain active cerebral networks that underlie cognitive function even though command following and communication abilities are inconsistent. METHODS: fMRI was employed to investigate cortical responses to passive language and tactile stimulation in two male adults with severe brain injuries leading to MCS and in seven healthy volunteers. RESULTS: In the case of the patient language-related tasks, auditory stimulation with personalized narratives elicited cortical activity in the superior and middle temporal gyrus. The healthy volunteers imaged during comparable passive language stimulation demonstrated responses similar to the patients' responses. However, when the narratives were presented as a time-reversed signal, and therefore without linguistic content, the MCS patients demonstrated markedly reduced responses as compared with volunteer subjects, suggesting reduced engagement for "linguistically" meaningless stimuli. CONCLUSIONS: The first fMRI maps of cortical activity associated with language processing and tactile stimulation of patients in the minimally conscious state (MCS) are presented. These findings of active cortical networks that serve language functions suggest that some MCS patients may retain widely distributed cortical systems with potential for cognitive and sensory function despite their inability to follow simple instructions or communicate reliably.

Evidence-based cognitive rehabilitation: recommendations for clinical practice.

OBJECTIVE: To establish evidence-based recommendations for the clinical practice of cognitive rehabilitation, derived from a methodical review of the scientific literature concerning the effectiveness of cognitive rehabilitation for persons with traumatic brain injury (TBI) or stroke. DATA SOURCES: A MEDLINE literature search using combinations of these key words as search terms: attention, awareness, cognition, communication, executive, language, memory, perception, problem solving, reasoning, rehabilitation, remediation, and training. Reference lists from identified articles also were reviewed; a total bibliography of 655 published articles was compiled. STUDY SELECTION: Studies were initially reviewed according to the following exclusion criteria: nonintervention studies; theoretical, descriptive, or review papers; papers without adequate specification of interventions; subjects other than persons with TBI or stroke; pediatric subjects; pharmacologic interventions; and non-English language papers. After screening, 232 articles were eligible for inclusion. After detailed review, 61 of these were excluded as single case reports without data, subjects other than TBI and stroke, and nontreatment studies. This screening yielded 171 articles to be evaluated. DATA EXTRACTION: Articles were assigned to 1 of 7 categories according to their primary area of intervention: attention, visual perception and constructional abilities, language and communication, memory, problem solving and executive functioning, multi-modal interventions, and comprehensive-holistic cognitive rehabilitation. All articles were independently reviewed by at least 2 committee members and abstracted according to specified criteria. The 171 studies that passed initial review were classified according to the strength of their methods. Class I studies were defined as prospective, randomized controlled trials. Class II studies were defined as prospective cohort studies, retrospective case-control studies, or clinical series with well-designed controls. Class III studies were defined as clinical series without concurrent controls, or studies with appropriate single-subject methodology. DATA SYNTHESIS: Of the 171 studies evaluated, 29 were rated as Class I, 35 as Class II, and 107 as Class III. The overall evidence within each predefined area of intervention was then synthesized and recommendations were derived based on consideration of the relative strengths of the evidence. The resulting practice parameters were organized into 3 types of recommendations: Practice Standards, Practice Guidelines, and Practice Options. CONCLUSIONS: Overall, support exists for the effectiveness of several forms of cognitive rehabilitation for persons with stroke and TBI. Specific recommendations can be made for remediation of language and perception after left and right hemisphere stroke, respectively, and for the remediation of attention, memory, functional communication, and executive functioning after TBI. These recommendations may help to establish parameters of effective treatment, which should be of assistance to practicing clinicians.

Multiple fregoli delusions after traumatic brain injury.

A 61 year old man after a traumatic brain injury resulting in right frontal and left temporoparietal contusions developed florid Fregoli-type misidentifications. Extensive neuropsychological testing demonstrated significant deficits in executive and memory functions. The patient's neuropsychological profile closely resembled that seen in previously reported patients with Capgras syndrome. Our findings are consistent with the hypothesis that a combination of executive and memory deficits may account for cases of delusional misidentification associated with brain lesions. However, the form which the delusion takes may be influenced by other factors including motivation.

Varieties of deficit unawareness after brain injury.

The failure to recognize the existence of disease is known as anosognosia. This article provides a brief discussion of the evolution of this concept and reviews some qualitative differences in the manner in which the disavowal of neurogenic impairment is expressed. Theoretical explanations for the unawareness of deficit after neurologic illness include motivational-symbolic, cognitive subsystem, and supraordinate system theories. Observations from a clinically derived, structured awareness interview are presented, suggesting three factors that may underlie patients' apparent lack of awareness of deficits after traumatic brain injury. These include diminished awareness of deficits secondary to impaired cognition, especially memory and reasoning deficits; psychological reactance and denial of deficits; and a relatively "pure" inability to recognize areas of impaired functioning as a direct consequence of brain injury. The causes of unawareness are likely to be complex and multiply determined in any given patient, although it may be possible to identify primary, secondary, and even tertiary contributions according to specific behavioral and phenomenological characteristics. The ability of patients to modify their perceptions and acknowledgment of deficits after objective feedback may have particular diagnostic value and clinical utility in this regard.

Disorders of consciousness: differential diagnosis and neuropathologic features.

Disorders of consciousness present intriguing challenges to the neurologist and neurorehabilitation specialist. Assessment is constrained by the lack of reliable methods of assessing consciousness, and there are no treatment interventions known to influence the course of recovery from these conditions. In addition, the relationship between the clinical features associated with these disorders and their corresponding pathophysiologic substrate is also unclear. Our understanding of disorders of consciousness has not kept pace with the advances in neurosurgical management that have decreased mortality following severe injury. There is still considerable confusion regarding differential diagnosis and prognostication concerning states of severely altered consciousness. The purpose of this article is to discuss the content and neural basis of consciousness and to review the terminology most often used to describe altered states of consciousness. The neurobehavioral criteria for differentiating among specific syndromes associated with severe alterations in consciousness are presented. Representative case studies are utilized to illustrate the characteristic clinical profiles of coma, vegetative state, persistent and permanent vegetative state, minimally conscious state, akinetic mutism, and locked-in syndrome. Areas of ambiguity and controversy are emphasized and future directions for research are suggested.

Sensory stimulation: theoretical perspectives and the evidence for effectiveness.

The use of sensory stimulation (SS) to promote recovery from coma has enjoyed widespread acceptance in rehabilitation settings. This has occurred despite the paucity of research regarding its effectiveness as well as opposing viewpoints concerning its utility. The purpose of this article is to: (1) outline the theoretical basis underlying the arguments for and against the use of SS; and (2) to review representative studies on the effectiveness of SS using a scientific evidence-based classification system. It is suggested that few conclusions can be drawn regarding the efficacy of SS because of the lack of well-designed clinical studies on this subject. Consequently, it is incumbent upon clinicians to clearly present to family members the high degree of uncertainty associated with this form of treatment.

Monitoring rate of recovery to predict outcome in minimally responsive patients.

Existing methods of assessing neurobehavioral responsiveness in severely brain-injured patients are limited by their inability to recognize subtle clinical changes over time. This study evaluates the Coma Recovery Scale (CRS), developed for use during acute rehabilitation. The CRS was designed to detect subtle changes in neurobehavioral status and to predict outcome in patients with sever alterations of consciousness. Acceptable levels of concurrent validity were established with the Disability Rating Scale ([DRS], r = -.93) and the Glasgow Coma Scale ([GCS], r = .90). The CRS was also found to have adequate interrater reliability (kappa = .83). Twenty-eight minimally responsive patients, unable to communicate or follow commands reliably, were evaluated on the CRS, the DRS, and the GCS. Although initial scores on all three scales were significantly correlated with outcome at discharge, change scores were more predictive of outcome. In addition, CRS change scores correlated higher with outcome (r = -.78, p less than .01) than DRS and GCS change scores. These findings indicate that the CRS is a sensitive measure of neurobehavioral responsiveness and suggest that rate of change during acute rehabilitation may be an important outcome predictor.