Search PubMed⌕ Search

Biomedical subjects

R D Zafonte

Publications and source records attributed to R D Zafonte.

At least 19 recordsLinked to original sources

Gender and environmental effects on regional brain-derived neurotrophic factor expression after experimental traumatic brain injury.

Alterations in brain-derived neurotrophic factor expression have been reported in multiple brain regions acutely after traumatic brain injury, however neither injury nor post-injury environmental enrichment has been shown to affect hippocampal brain-derived neurotrophic factor gene expression in male rats chronically post-injury. Studies have demonstrated hormone-related neuroprotection for female rats after traumatic brain injury, and estrogen and exercise both influence brain-derived neurotrophic factor levels. Despite recent studies suggesting that exposure post-traumatic brain injury to environmental enrichment improves cognitive recovery in male rats, we have shown that environmental enrichment mediated improvements with spatial learning are gender specific and only positively affect males. Therefore the purpose of this study was to evaluate the effect of gender and environmental enrichment on chronic post-injury cortical and hippocampal brain-derived neurotrophic factor protein expression. Sprague-Dawley male and cycling female rats were placed into environmental enrichment or standard housing after controlled cortical impact or sham surgery. Four weeks post-surgery, hippocampal and frontal cortex brain-derived neurotrophic factor expression were examined using Western blot. Results revealed significant increases in brain-derived neurotrophic factor expression in the frontal cortex ipsilateral to injury for males (P=0.03). Environmental enrichment did not augment this effect. Neither environmental enrichment nor injury significantly affected cortical brain-derived neurotrophic factor expression for females. In the hippocampus ipsilateral to injury brain-derived neurotrophic factor expression for both males and females was half (49% and 51% respectively) of that observed in shams housed in the standard environment. For injured males, there was a trend in this region for environmental enrichment to restore brain-derived neurotrophic factor levels to sham values. However, there were robust increases in hippocampal brain-derived neurotrophic factor expression ipsilateral to the injury for injured females in environmental enrichment compared with both sham and injured females placed in standard housing (P<or=0.005). In the hippocampus contralateral to injury, there were also significant injury-related increases in brain-derived neurotrophic factor expression for females (P<or=0.05) that were not further augmented by environmental enrichment. These results show significant, region-specific gender differences in brain-derived neurotrophic factor expression with both injury and environmental enrichment that may be important for recovery. However, these data do not support a critical role for brain-derived neurotrophic factor in environmental enrichment mediated improvements with spatial learning.

Actins↗

Controlled cortical impact injury affects dopaminergic transmission in the rat striatum.

The therapeutic benefits of dopamine (DA) agonists after traumatic brain injury (TBI) imply a role for DA systems in mediating functional deficits post-TBI. We investigated how experimental TBI affects striatal dopamine systems using fast scan cyclic voltammetry (FSCV), western blot, and d-amphetamine-induced rotational behavior. Adult male Sprague-Dawley rats were injured by a controlled cortical impact (CCI) delivered unilaterally to the parietal cortex, or were naïve controls. Amphetamine-induced rotational behavior was assessed 10 days post-CCI. Fourteen days post-CCI, animals were anesthetized and underwent FSCV with bilateral striatal carbon fiber microelectrode placement and stimulating electrode placement in the medial forebrain bundle (MFB). Evoked DA overflow was assessed in the striatum as the MFB was electrically stimulated at 60 Hz for 10 s. In 23% of injured animals, but no naïve animals, rotation was observed with amphetamine administration. Compared with naïves, striatal evoked DA overflow was lower for injured animals in the striatum ipsilateral to injury (p < 0.05). Injured animals exhibited a decrease in V(max) (52% of naïve, p < 0.05) for DA clearance in the hemisphere ipsilateral to injury compared with naïves. Dopamine transporter (DAT) expression was proportionally decreased in the striatum ipsilateral to injury compared with naïve animals (60% of naïve, p < 0.05), despite no injury-related changes in vesicular monoamine transporter or D2 receptor expression (DRD2) in this region. Collectively, these data appear to confirm that the clinical efficacy of dopamine agonists in the treatment of TBI may be related to disruptions in the activity of subcortical dopamine systems.

Animals↗

The minimally conscious state: definition and diagnostic criteria.

OBJECTIVE: To establish consensus recommendations among health care specialties for defining and establishing diagnostic criteria for the minimally conscious state (MCS). BACKGROUND: There 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. METHODS: An 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. RESULTS: There 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. CONCLUSIONS: MCS 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.

Humans↗

Severe penetrating head injury: a study of outcomes.

OBJECTIVE: To determine and describe the demographics and functional outcomes of persons who require inpatient rehabilitation for severe penetrating head injury resulting from a gunshot wound to the head. DESIGN: Data were collected prospectively from the time of admission to acute care through discharge from inpatient rehabilitation. SETTING: Two sites: an urban, level I, acute care, trauma center and an inpatient rehabilitation hospital with a specialized brain injury unit. PARTICIPANTS: Twenty-seven persons with severe penetrating head injury. MAIN OUTCOME MEASURES: The FIM instrument, the Disability Rating Scale (DRS), and the length of stay (LOS). RESULTS: Demographic data showed our population to be similar to other groups of persons at high risk for violent injury. Eighty-five percent of the subjects were men with a mean age of 34 years. The majority were African American (93%), reflective of our general patient population. Average acute care LOS was 31 days and average rehabilitation LOS was 44 days. Average FIM gain was 40.2 and, on average, DRS scores improved 7.6 points from rehabilitation admission to discharge. All study participants made enough progress to be discharged to private residences. CONCLUSION: Although the mortality rate is high among patients with penetrating head injury, those who survive to receive inpatient rehabilitation can achieve functional improvement.

Activities of Daily Living↗

Verbal recall and recognition following traumatic brain injury: a [0-15]-water positron emission tomography study.

Although several studies exist which have examined static functional neuroimaging following traumatic brain injury (TBI), controlled cognitive activation studies of episodic memory in this population have not been published. The present investigation studied verbal recall using [O-15]-water positron emission tomography (PET) in 5 individuals who sustained severe TBI (M GCS=6.8; M years post-injury=3.18), and 4 non-injured control participants. Statistical image analysis demonstrated changes in frontoparietal regional cerebral blood flow (rCBF) in both groups, but there were interesting differences between groups and across conditions. Frontal lobe rCBF changes in TBI patients were reduced during free recall but enhanced during recognition, when compared to controls. Changes in cerebellar rCBF were observed in the control group during free recall, but not in the TBI sample. In both groups, bifrontal rCBF increases were noted on recognition tasks. The present findings provide evidence of alterations in specific substrates involved in verbal recall following brain injury.

Adult↗

Factors associated with balance deficits on admission to rehabilitation after traumatic brain injury: a multicenter analysis.

OBJECTIVE: To evaluate how demographics, measures of injury severity, and acute care complications relate to sitting and standing balance in patients with traumatic brain injury (TBI). DESIGN: Multicenter analysis of consecutive admissions to designated TBI Model Systems of Care (TBIMS). SETTING: Ten National Institute for Disability and Rehabilitation Research TBI Model System centers for coordinated acute and rehabilitation care. PARTICIPANTS: 908 adults with TBI were included in the study. MAIN OUTCOME MEASURES: Sitting and standing balance were assessed within 72 hours of admission to inpatient rehabilitation. RESULTS: Age less than 50 years had a significant association with normal sitting and standing balance (P =.001 and.05, respectively). Measures of severity of traumatic brain injury, including admission Glasgow Coma Score, length of posttraumatic amnesia (PTA), length of coma, and acute care length of stay were each significantly related to impaired sitting and standing balance ratings (P <.01). Initial abnormalities in pupillary response had a significant relationship with impairment of sitting (P =.009) but not standing balance. Incidence of respiratory failure, pneumonia, soft tissue infections, and urinary tract infections were all related to impaired sitting balance (P <.01). Presence of intracranial hemorrhages did not have a significant relationship with either sitting or standing balance. Intracranial compression had a significant relationship with standing (P =.05) but not sitting balance. A discriminant function analysis, which included neuroradiological findings, injury severity, and medical complications, could not accurately predict impaired balance ratings. CONCLUSIONS: This study demonstrated that rehabilitation admission balance ratings have a significant relationship with age, multiple measures of severity, and acute care medical complications after TBI. Prospective studies are indicated to evaluate the role balance at rehabilitation admission plays in the functional prognosis of patients with TBI.

Activities of Daily Living↗

Long-term recovery course after traumatic brain injury: a comparison of the functional independence measure and disability rating scale.

OBJECTIVES: To study group changes over time after traumatic brain injury (TBI). DESIGN: Prospective cohort. SETTING AND PARTICIPANTS: TBI Model System Database with 1160 subjects using cohort with complete data. MAIN OUTCOME MEASURES: Functional Independence Measure (FIM) and Disability Rating Scale (DRS) at rehabilitation discharge and annually after injury. RESULTS: Statistically significant differences existed between FIM-total, FIM-Motor, FIM-Cognitive subscales, and DRS at rehabilitation discharge and year 1. Comparisons of year-to-year intervals, years 1 and 3, 1 and 5, and 3 and 5, revealed no statistically significant differences except between years 1 and 3 and 1 and 5 with DRS, and years 1 and 5 with FIM. Including only those more dependent at year 1 revealed statistically significant differences between years 1 and 2 and 1 and 5 on FIM-Cognitive and DRS, but not the FIM-Motor. The proportion of change for FIM and DRS items from year 1 to years 2 and 5 revealed DRS Level of Functioning and Employability items accounted for most DRS change, whereas FIM change was more spread across its components. CONCLUSIONS: DRS is more sensitive to changes during a shorter time period than FIM and seems to be more appropriate for detecting long-term deficits. However, research studies aimed at detecting meaningful changes year to year after TBI may need to use other tools or consider changes among individuals instead of group changes. DRS Level of Function and Employability Items represent complex functions expected to recover later than the more basic DRS items. Sole use of these two DRS items might provide an efficient means of measuring long-term recovery when resources are limited, whereas expansion of these two items might allow greater sensitivity and detail.

Activities of Daily Living↗

St. John's wort.

Explore the source record for details and available documents.

Brain Injuries↗

Insomnia screening in postacute traumatic brain injury: utility and validity of the Pittsburgh Sleep Quality Index.

OBJECTIVE: To assess insomnia in a rehabilitation population, the authors examined the utility and validity of the Pittsburgh Sleep Quality Index (PSQI). The assessment of insomnia is relevant to the treatment of traumatic brain injury at the postacute level and routine screening for insomnia may be enhanced by the availability of a standardized, conveniently used, self-report sleep questionnaire. DESIGN: The authors prospectively studied 91 consecutive patients with traumatic brain injury who were admitted to an outpatient neurorehabilitation program. Besides administering the PSQI, Beck Depression Inventory, Epworth Sleepiness Scale, and Multidimensional Pain Inventory, sleep diary and interview data were obtained and used to divide subjects into insomnia and noninsomnia groups according to the criteria established by the Diagnostic and Statistical Manual of Mental Disorders, ed 4. RESULTS: Sensitivity and specificity rates to the clinical diagnosis of insomnia were 93% and 100%, respectively, for a PSQI Global Score of >8, and 83% and 100% for a diagnosis of insomnia based exclusively on PSQI-derived sleep variable data. Sleep diary data provided concurrent validity for PSQI estimates of sleep-onset latency, sleep duration, and sleep efficiency. The Beck Depression Inventory, Epworth Sleepiness Scale, and Multidimensional Pain Inventory established concurrent validity for individual PSQI items pertaining to mood, hypersomnia, and pain disturbance. CONCLUSION: The PSQI was demonstrated to be a valid and useful screening tool for assessing insomnia among postacute patients with traumatic brain injury.

Adolescent↗

Safety and feasibility of craniectomy with duraplasty as the initial surgical intervention for severe traumatic brain injury.

BACKGROUND: Decompressive craniectomy has historically served as a salvage procedure to control intracranial pressure after severe traumatic brain injury. We assessed the safety and feasibility of performing craniectomy as the initial surgical intervention. METHODS: Of 29 consecutive patients undergoing emergent decompression for severe traumatic brain injury with horizontal midline shift greater than explained by a removable hematoma, 17 had traditional craniotomy with or without brain resection and 12 underwent craniectomy. RESULTS: The craniectomy group had lower Glasgow Coma Scale scores at surgery (median, 4 vs. 7; p = 0.04) and more severe radiographic injuries (using specific measures). Mortality, Glasgow Outcome Scale scores, Functional Independence Measures, and length of stay in both the acute care setting and the rehabilitation phase were similar between the surgical groups. CONCLUSION: Despite more severe injury severity, patients undergoing initial craniectomy had outcomes similar to those undergoing traditional surgery. A randomized evaluation of the effect of early craniectomy on outcome is warranted.

Adult↗

Phenol and alcohol blocks for the treatment of spasticity.

The role of neurolytic agents in the treatment of tone disorders is not new. Exploration of their use, however, has been limited, and few studies address use in select populations. In practice use of phenol and alcohol blocks requires considerable experience and skill. This article will focus on mechanism of action, rationale for use, technique of administration, and potential side-effects.

Animals↗

Factors associated with insomnia among post-acute traumatic brain injury survivors.

This study investigated the relationships between insomnia and select demographic, injury and psychosocial variables in post-acute, traumatic brain injury. Clinical assessment of sleep and mood was undertaken via objective measures and a diagnostic interview among 91 consecutive brain injury admissions to an outpatient neurorehabilitation clinic. No associations between insomnia and gender, education, age, and time since injury were found. A logistic regression model of insomnia prediction based upon the Beck Depression Inventory (BDI), self-reported pain disturbance, litigation and Glasgow Coma Score (GCS) correctly classified 87% of the sample with respect to the presence or absence of insomnia; however, depression and injury severity were the only variables that made a significant unique contribution to the prediction of insomnia. It is concluded that among post-acute traumatic brain injury patients, insomnia is linked with both the presence of depression and a history of milder brain injuries. This suggests that the determinants of insomnia may differ from the acute to the post-acute phase, with neurological factors playing a primary role early in the recovery process and psychosocial factors ascending later. Therefore, assessment and treatment of insomnia must give careful attention to the larger psychosocial context in which the sleep disorder emerges, particularly to role of emotional disturbance.

Adolescent↗

Functional neuroimaging and quantitative electroencephalography in adult traumatic head injury: clinical applications and interpretive cautions.

Functional neuroimaging and quantitative electroencephalographic procedures are being used increasingly in brain injury research and clinical care. These procedures are also seeing increased use in the context of forensic evaluations, particularly in cases of mild head trauma. This article provides an overview of the use of procedures such as positron emission tomography, single photon emission computed tomography, and quantitative electroencephalogram in adults. Also discussed are the clinical limitations of each procedure within the context of myriad interpretive confounds that can interfere with accurate differential diagnosis of mild head trauma.

Adult↗

The hippocampus: anatomy, pathophysiology, and regenerative capacity.

Cognitive deficits following insults to the central nervous system-particularly those involving the hippocampus and related structures-are often persistent and severely debilitating. Progress has been made in establishing the role of the hippocampus in integrating information in the formation of memory necessary for subsequent recollection of information. The present article will review anatomic, physiological, and functional aspects of the hippocampus in reference to learning and memory. Both animal and human hippocampal pathophysiological processes will be explored. Adaptive and maladaptive central nervous system responses will be reviewed, with a special emphasis on neurogenesis. Ideally, physiological and cellular compensatory responses ought to parallel clinical observation. However, this association is not clearly established. Finally, the current understanding of neuromodulatory mechanisms (although quite preliminary) will also be discussed.

Animals↗

The effect of cocaine on traumatic brain injury outcome: a preliminary evaluation.

The effect of acute cocaine use on the functional and neuropsychological outcome of persons with traumatic brain injury, (TBI) was examined by comparing persons with TBI who tested positive for cocaine at the time of admission with persons with negative drug and alcohol screens. Subjects were matched for age, admission GCS score, level of education, and aetiology of injury (closed vs penetrating head injury). Dependent measures were: the Disability Rating Scale, the Functional Independence Measure, and selected neuropsychological tests. No group differences were found in DRS, FIM, FIM subsets, or FIM change. However, the cocaine group scored significantly lower than the no-drug group on the Rey Auditory Verbal Learning Test, but did not differ on any of the other neuropsychological tests.

Adolescent↗