Ten-year outcome of early childhood traumatic brain injury: Diffusion tensor imaging of the ventral striatum in relation to executive functioning.

PRIMARY OBJECTIVE: The long-term effects of TBI on verbal fluency and related structures, as well as the relation between cognition and structural integrity, were evaluated. It was hypothesized that the group with TBI would evidence poorer performance on cognitive measures and a decrease in structural integrity. RESEARCH DESIGN: Between a paediatric group with TBI and a group of typically-developing children, the long-term effects of traumatic brain injury were investigated in relation to both structural integrity and cognition. Common metrics for diffusion tensor imaging (DTI) were used as indicators of white matter integrity. METHODS AND PROCEDURES: Using DTI, this study examined ventral striatum (VS) integrity in 21 patients aged 10-18 years sustaining moderate-to-severe traumatic brain injury (TBI) 5-15 years earlier and 16 demographically comparable subjects. All participants completed Delis-Kaplan Executive Functioning System (D-KEFS) sub-tests. MAIN OUTCOMES AND RESULTS: The group with TBI exhibited lower fractional anisotropy (FA) and executive functioning performance and higher apparent diffusion coefficient (ADC). DTI metrics correlated with D-KEFS performance (right VS FA with Inhibition errors, right VS ADC with Letter Fluency, left VS FA and ADC with Category Switching). CONCLUSIONS: TBI affects VS integrity, even in a chronic phase, and may contribute to executive functioning deficits.

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.

Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treatment of Parkinson's disease.

BACKGROUND: We investigated the cognitive and psychiatric outcome 6 months after bilateral subthalamic nucleus deep brain stimulation (DBS) for the treatment of Parkinson's disease (PD) using a disease control group. METHODS: 23 patients who underwent DBS were compared with 28 medically treated patients with PD at baseline and at 6 months for neuropsychological measures. In addition to the group outcomes, we report reliable change indices (RCI) and a dementia caseness analysis. RESULTS: Patients who underwent DBS demonstrated a significant decline in verbal memory compared with the control group (p<0.003), and trends for decline on oral information processing, including verbal fluency, timed transcription and word naming. Patients who underwent DBS demonstrated declines in attention, set shifting and semantic fluency but these changes were similar to the rate of decline in the PD group. RCI indicated that patients who underwent DBS demonstrated clinically significant declines in verbal fluency (p<0.01) and inhibition of a dominant response (p<0.003), with trends for declines in set shifting (p<0.02) and verbal long term recall (p<0.08), indicative of frontostriatal dysfunction. Patients who underwent DBS did not demonstrate significant changes in depression, anxiety or psychological distress scores. The caseness analysis revealed that one of the patients who underwent DBS (4%) converted to dementia over 6 months compared with none of the PD controls. CONCLUSIONS: Our findings demonstrated that patients who underwent DBS experienced declines in verbal recall and trends for declines in oral information processing 6 months following surgery, even when good motor outcome was achieved. Potential candidates should be counselled about the risk of mild frontostriatal cognitive declines following DBS to weigh the risks and benefits of surgery.

cerebellar atrophy after moderate-to-severe pediatric traumatic brain injury.

BACKGROUND AND PURPOSE: Although the cerebellum has not attracted the same degree of attention as cortical areas and the hippocampus in traumatic brain injury (TBI) literature, there is limited structural and functional imaging evidence that the cerebellum is also vulnerable to insult. The cerebellum is emerging as part of a frontocerebellar system that, when disrupted, results in significant cognitive and behavioral consequences. We hypothesized that cerebellar volume would be reduced in children following TBI and wished to examine the relation between the cerebellum and known sites of projection, including the prefrontal cortex, thalamus, and pons. MATERIALS AND METHODS: Quantitative MR imaging was used to measure cerebellar white and gray matter and lesion volumes 1-10 years following TBI in 16 children 9-16 years of age and 16 demographically matched typically developing children 9-16 years of age. Cerebellar volumes were also compared with volumetric data from other brain regions to which the cerebellum projects. RESULTS: A significant group difference was found in cerebellar white and gray matter volume, with children in the TBI group consistently exhibiting smaller volumes. Repeating the analysis after excluding children with focal cerebellar lesions revealed that significant group differences still remained for cerebellar white matter (WM). We also found a relation between the cerebellum and projection areas, including the dorsolateral prefrontal cortex, thalamus, and pons in 1 or both groups. CONCLUSION: Our finding of reduced cerebellar WM volume in children with TBI is consistent with evidence from experimental studies suggesting that the cerebellum and its related projection areas are highly vulnerable to fiber degeneration following traumatic insult.

Combined nested RT-PCR assay for prostate-specific antigen and prostate-specific membrane antigen in prostate cancer patients: correlation with pathological stage.

Nested reverse transcription (RT)-PCR for prostate-specific antigen (PSA) and prostate-specific membrane antigen (PSM) can detect circulating prostatic cells in patients with prostate cancer. We evaluated the role of a combined screening approach for PSA and PSM in prostate cancer staging. We examined the peripheral blood samples from 136 patients with adenocarcinoma of the prostate (PCA), 15 patients with benign prostatic hyperplasia, 15 normal male subjects, and 5 female subjects. The controls (benign prostatic hyperplasias, normal males, and normal females) were negative for both PSA and PSM. In patients with metastatic PCA (n = 11), 100% were positive by combined PSA/PSM (64% by PSA and 91% by PSM). In biochemical failure PCA patients (n = 18), 39% were positive by PSM, compared to only 6% by PSA. In patients with clinically localized PCA (n = 107), 48% were positive by combined PSA/PSM approach (43% by PSM and 14% by PSA). These results show that PSM is a more sensitive marker than PSA in detecting circulating prostatic cells (P < 0.0001). We correlated preoperative RT-PCR results with final pathological stages in 67 prostatectomy patients. RT-PCR positivity was 81.5% in patients with non-organ-confined disease versus 37.5% in organ-confined disease (P = 0.001). PSA/PSM RT-PCR had an odds ratio of 7.3 (95% confidence interval, 2.3-23.4; P = 0.001) in predicting tumor extracapsular extension. PSA/PSM RT-PCR was a better predictor of tumor extracapsular extension than initial serum PSA, clinical stage, and biopsy Gleason score. Our data show that PSA/PSM nested RT-PCR may provide the staging information unavailable from the current modalities. The ultimate impact of this technique in the management of patients with prostate cancer will require continued investigation.

Declining rates of extracapsular extension after radical prostatectomy: evidence for continued stage migration.

PURPOSE: Prostate-specific antigen (PSA)-based screening is responsible for a profound clinical stage migration in newly detected prostate cancers. Extracapsular extension (ECE) is an important predictor of outcome after radical prostatectomy (RP). We examined trends in the rate of ECE for cancers detected by PSA screening in 731 RP specimens between 1987 and 1997, when screening became routine urologic practice in the United States. METHODS: The rates of ECE were examined in 311 prostates with nonpalpable (stage T1c) disease and 420 with palpable but clinically localized (stage T2) disease. Specimens were step-sectioned and examined by a senior pathologist. Rates of ECE were compared with respect to time, and logistic regression was used to identify predictors of ECE. RESULTS: The rate of ECE decreased from 81% to 36% during the 10-year observation period. Multivariateanalysis involving clinical tumor stage, preoperative serum PSA level, and Gleason score demonstrated that year of treatment was an independent predictor of ECE, with a two-fold reduction of risk occurring during the study period (P <. 001; odds ratio, 1.96; 95% confidence interval, 1.37 to 2.78). CONCLUSION: PSA screening has resulted in a downward trend in pathologic stage in clinically localized prostate cancer, independent of preoperative PSA level, tumor stage, and Gleason score. This time-dependent downward stage migration suggests the need for continuous updating of predictive nomograms and caution in interpreting differences in contemporarily treated patients compared with historical controls. Further study is needed to determine whether this trend will translate into improved disease-free survival.

Anxiety associated with exposure to organophosphate compounds.

Acute organophosphate poisoning is known to result in substantial behavioral abnormalities. We assessed psychiatric manifestations of exposure in workers less substantially exposed to organophosphate compounds and showing no obvious signs of toxicity. Commercial pesticide sprayers and farmers recently exposed to organophosphate agents were compared to control subjects on personality tests, a structured interview, and cholinesterase level. The commercial sprayers but not the exposed farmers showed elevated of anxiety and lower plasma cholinesterase than control subjects. Assessment of other behavioral manifestations and red blood cell cholinesterase failed to disclose other group differences. These findings are viewed as tentative until confirmed by additional study, but they point to the possibility that organophosphate compounds may produce subtle defects in workers who are not obviously toxic. The findings do not justify public alarm but do suggest an area warranting more systematic and definitive investigation.

[The neurobehavioral rating scale-revised: assessment of concurrent validity]. / Echelle neurocomportementale révisée: étude de la validité concourante.

UNLABELLED: Cognitive and behavioral impairment are a major source of disability in daily living of patients with traumatic brain injury (TBI). The Neurobehavioral Rating Scale-Revised (NRS-R) is a short, easy-to administer interview tool developed to improve assessment by clinicians. Data are available on its criterion validity and reliability, but the concurrent validity of the French NRS-R was not yet documented. OBJECTIVE: To assess the concurrent validity of the NRS-R with current psychometric tests. METHOD: One hundred and four patients with TBI enrolled in a community adjustment program underwent concurrent examination with the NRS-R, cognitive tests assessing memory, attention, and executive functions, and scales of anxiety (STAI) and depressive mood (CES-D). Intercorrelations were undertaken between these variables and the five factors of the NRS-R: F1, intentional behavior; F2, lowered emotional state; F3, survival-oriented behaviour/hightened emotional state; F4, arousal state; and F5, language. Patients were 82 men and 22 women, the mean age was 28.5 years, and 70% had severe TBI (Glasgow coma score [GCS] below 8 on admission). They were assessed 52 months on average after their injury. RESULTS: Factor F1 was correlated with results on the GCS (P<0.05), the Tower of London test (TL, P<0.01), the Trail Making Test (TMT, P<0.01), divided attention (DA) and inhibition (IN) subscales of the Zimmermann and Fimm's Attention battery (TEA) (P<0.01) and reverse digit span (DS, P<0.05). Factor F2 was positively related to age at injury, time since injury (TSI) (P<0.05) and CESD and STAI scores (P<0.001). Factor F3 was related to DA (P<0.01) TL scores and TSI (P<0.05). Factor F4 was related to TL, TMT, DA, flexibility, DS (P<0.05), TSI, duration of post-traumatic amnesia, CES-D score (P<0.05) and STAI scores (P<0.01). Factor F5 was related to GCS, DA (P<0.05), and reaction time on the subscales IN and Go/nogo (GO) of the TEA battery (P<0.01). The NRS-R total score was related to CESD, STAI scores, TMT score, DA (P<0.01) and TL score, IN and GO scores and TSI (P<0.05). DISCUSSION: As McCauley et al found with the English version of the NRS-R, significant relationships were found between NRS-R factor scores, cognitive tests and emotional scales. Relationships were also found between factor scores and indicators of injury severity and time since injury. These data suggest fair concurrent validity of the NRS-R.

A comparison of psychiatric symptoms in vascular dementia and Alzheimer's disease.

OBJECTIVE: Psychiatric symptoms account for much of the morbidity of vascular dementia and Alzheimer's disease. The goals of this study were to extend previous observations of the psychopathology and behavioral problems associated with vascular dementia and to compare the profile of symptoms in patients with vascular dementia to that in patients with Alzheimer's disease. METHOD: Twenty-eight pairs of patients (one with vascular dementia and one with Alzheimer's disease) were matched with respect to education, age, and severity of dementia. Their psychiatric symptoms were assessed with the Neurobehavioral Rating Scale, a 28-item observer-rated instrument, and the Hamilton Depression Rating Scale, and the symptoms in the two diagnostic groups were compared. RESULTS: Blunted affect, depressed mood, emotional withdrawal, motor retardation, low motivation, anxiety, unusual thoughts, and somatic concerns occurred in more than one-third of the patients with vascular dementia. There was no significant relation between severity of cognitive impairment and severity of these noncognitive symptoms. The patients with vascular dementia had more impairment than the patients with Alzheimer's disease, as indicated by the Neurobehavioral Rating Scale total scores and scores on the behavioral retardation, anxiety/depression, and verbal output disturbance factors. They also had a higher total score on the Hamilton depression scale and higher scores on 14 of the 17 Hamilton depression items. CONCLUSIONS: Patients with vascular dementia have more severe behavioral retardation, depression, and anxiety than those with Alzheimer's disease when the groups have similar levels of cognitive impairment. This probably reflects the contrasting brain regions typically involved in the two disorders.

Behavioral sequelae of closed head injury. A quantitative study.

We determined the profile of behavioral disturbance in relation to closed head injury of graded severity. Patients with severe injuries, as defined by duration of coma and the presence of neurological deficit, were differentiated from a group of mildly injured patients by behavioral ratings that reflected cognitive disorganization, emotional withdrawal, and motor retardation. Neurologic measurements of injury related to the severity of behavioral disturbance included hemiparesis, aphasia, and abnormalities on computerized axial tomography. Agitation during the acute phase of injury was also predictive of residual behavioral disturbance. Hemispheric lateralization of the site of greatest injury had no discernible effect on behavioral sequelae.

Memory enhancement after physostigmine treatment in the amnesic syndrome.

Central anticholinergic agents (eg, scopolamine) are known to produce transient memory deficits in human and animal subjects. Damage to the limbic system frequently results from herpes simplex encephalitis (HSE) and produces a memory deficit. If this deficit is due to limbic cholinergic pathway destruction, it might improve with central cholinergic agonists (eg, physostigmine). In a doubleblind study over a three-week period, we compared memory performance on three days after 0.8-mg subcutaneous physostigmine therapy (three sessions) to baseline performance and that obtained in three randomly interspersed control sessions. Serial assessment of memory by the Selective Reminding Test showed reproducible enhancement of long-term storage and retrieval with physostigmine treatment. Performance after control injections did not exceed baseline levels. Our findings encourage the hypothesis that cholinergic mechanisms subserve memory and that their pharmacological potentiation might favorable influence some amnesic conditions.

Posttraumatic Amnesia as a predictor of outcome after severe closed head injury. Prospective assessment.

OBJECTIVES: To identify the demographic and clinical variables related to the duration of posttraumatic amnesia after severe closed head injury; to evaluate the usefulness of posttraumatic amnesia duration in predicting outcome at the time of hospital discharge and at 6 months after injury. SETTING: Four clinical centers located in primary care hospitals. PATIENTS: Three hundred fourteen severely injured subjects aged 16 years or older who did not have trauma as a result of a penetrating injury and came out of coma before hospital discharge. INTERVENTIONS: Approximately half of the subjects were administered phenytoin sodium for some period after termination of coma; 17% were administered dexamethasone and 41% morphine sulfate. MAIN OUTCOME MEASURES: Galveston Orientation and Amnesia Test scores defined the duration of posttraumatic amnesia. The Glasgow Outcome Scale was used to grade outcome at the time of hospital discharge and at 6 months. RESULTS: Older age, low initial Glasgow Coma Scale score, nonreactive pupil(s), coma duration, and use of phenytoin were associated with a longer duration of posttraumatic amnesia. Poor pupillary response, time in coma, and duration of posttraumatic amnesia and use of phenytoin was predictive of the 6-month outcome. CONCLUSIONS: The results support the prognostic usefulness of prospectively measuring duration of posttraumatic amnesia after termination of coma. Pending replication, our findings suggest that posttraumatic amnesia duration may be a useful surrogate outcome measure for clinical trials involving interventions for acute head injury.

Facial recognition in patients with focal brain lesions.

The performances of patients with radiologically or surgically verified focal lesions on a test requiring the identification of unfamiliar faces were investigated. Nonaphasic patients with posterior right hemisphere lesions and aphasic patients with substantial impairment in language comprehension showed a notably high frequency of defect. The frequency of defective performance in nonaphasic patients with right anterior lesions was higher than normal but less than that of the previously mentioned groups. Nonaphasic patients with left hemisphere lesions and aphasic patients without substantial impairment in language comprehension performed on a level comparable with that of control subjects. It is concluded that the identification of unfamiliar faces is a bihemispheric process, possibly involving linguistic as well as visuoperceptive components.

Ventricular enlargement after closed head injury.

To study the relationship between enlargement of the cerebral ventricles and neuropsychological deficit after closed head injury (CHI), we measured the area of the lateral ventricles on computed tomographic scans obtained at least 30 days after severe CHI in 32 young adults and a control group of similar age. Enlargement of the lateral ventricles was demonstrated in 72% of the head-injured subjects, as defined by the ventricle-brain percent ratio (VBR). Ventricular dilation was related to the duration of coma after high-speed motor vehicle accidents and to intellectual and memory defects. The VBR may be a useful index of the severity of brain damage in certain categories of head-injured patients.

Procedural memory during posttraumatic amnesia in survivors of severe closed head injury. Implications for rehabilitation.

To investigate the possibility that learning of skills (ie, procedural memory) is preserved during posttraumatic amnesia, 16 amnesic survivors of severe closed head injury and 16 control subjects were studied. Procedural learning tasks included mirror reading, mazes, and a pursuit rotor task that involved tracking a rotating target. Declarative memory was assessed by testing recognition of the words used in mirror reading and a questionnaire concerning details of the previous testing session. Learning was evaluated on 3 consecutive days and a fourth session was scheduled after resolution of posttraumatic amnesia. Despite stable impairment of declarative memory during posttraumatic amnesia, the performance of head-injured patients improved across sessions on all procedural tasks and showed transfer to testing after resolution of posttraumatic amnesia.

Evidence for right-hemisphere involvement in recovery from aphasia.

Cortical evoked potentials and dichotic listening test scores were used to assess the extent of activation of the two cerebral hemispheres during various language tasks in a group of 21 recovering aphasics, 15 nonaphasic patients with right-hemisphere stroke, and 17 normal volunteers. In agreement with previous findings, both measures suggest greater right-hemisphere activation during language processing in the recovering aphasics than in nonaphasic patients and normal subjects. These data support the view that restitution of language entails reorganization of brain function with increased participation of the nondominant hemisphere.

Evoked potential correlates of right hemisphere involvement in language recovery following stroke.

A probe evoked potentials procedure was used to assess the relative engagement of both cerebral hemispheres during a language task in the following four groups of dextral adults: left hemisphere (LH)-damaged aphasics recovering from stroke, dysarthrics, right hemisphere (RH)-damaged nonaphasic patients, and normal control subjects. In agreement with previous findings using the probe procedure, the present results indicate greater task-specific RH activation in recovering aphasics and, to a lesser degree, dysarthric patients and greater LH activation in both nonaphasic, RH-damaged patients and normal control subjects. On the basis of these data, we suggest that increasing participation of the nondominant hemisphere may subserve restitution of language in adults sustaining LH lesions.

Dyscalculia and dyslexia after right hemisphere injury in infancy.

OBJECTIVE: To use the findings from neuropsychological evaluation and functional magnetic resonance imaging (fMRI) to assess interhemispheric reorganization of function after early unilateral brain injury. DESIGN AND METHODS: The study focused on one case of early brain injury that resulted in both dyscalculia and dyslexia. Brain injury was studied using both structural and fMRI. Intellectual function was evaluated using the Wechsler Intelligence Scale for Children, Third Edition, while visuospatial skills were assessed using the Block Design subtest of the Wechsler Intelligence Scale for Children, Third Edition, and Judgment of Line Orientation subtest. The Selective Reminding Test and the Recurring Figures Test were used to evaluate memory and orientation; language and speech skills were evaluated using the Boston Naming Test, Controlled Oral Word Association, Gates-MacGinitie Reading Test, and color naming. Various methods were used to study arithmetic skills, including the Wide Range Achievement Test-Revised and the Peabody Individual Achievement Test. The control group for fMRI consisted of nine normal subjects. SETTING: Neuropsychological laboratory in primary care hospital. PATIENT: A 17-year-old boy who had sustained a closed head injury associated with a partially depressed, right parietal skull fracture, and right temporal hemorrhage in a motor vehicle crash at age 7 months (November 9, 1977). Subsequent social behavior was normal, but the patient had difficulty throughout school in mathematics and spelling and was characterized as having a "short attention span." INTERVENTION: None. MAIN OUTCOME MEASURES: Standardized tests of arithmetic and reading supplemented by an assessment of calculation and quantitative skills. While performing calculations, fMRI disclosed predominantly left hemisphere activation involving the frontal and posterior parietal regions, whereas this task produced bilateral activation of the supramarginal gyrus in seven of nine normal subjects. RESULTS: Neuropsychological findings confirmed the presence of dyscalculia and dyslexia despite normal intellectual functioning. Visuospatial skills ranged from the low normal to average level. The fMRI findings were consistent with early interhemispheric transfer of visuospatial skills normally committed to the right parietal area to the left parietal region. The patient's dyscalculia and reading ability raise a question of acquired left parietal dysfunction as a consequence of the competition between verbal and visuospatial functions for left hemisphere representation. CONCLUSION: Interhemispheric reorganization of function may be bidirectional rather than a feature unique to the left hemisphere substrate for language.

Magnetic resonance imaging after 'diffuse' nonmissile head injury. A neurobehavioral study.

The diagnosis of diffuse brain injury is considered when computed tomography provides no evidence of an intracranial mass lesion in acute nonmissile head injury. Magnetic resonance imaging (MRI) of a young woman who had sustained severe diffuse brain injury five years earlier disclosed multifocal lesions involving the frontal, temporal, parietal, and occipital lobes. We report the results of serial neurobehavioral assessment for clinical correlation with the brain lesions visualized by MRI. Pending confirmation of our findings in a series of patients studied by MRI during the acute and chronic stages of recovery from head injury, we postulate that the presence and type of neurobehavioral sequelae of diffuse brain injury are related to the intrahemispheric loci of predominantly white matter lesions and degeneration.

Vegetative state after closed-head injury. A Traumatic Coma Data Bank Report.

To elucidate the clinical course of the vegetative state after severe closed-head injury, the Traumatic Coma Data Bank was analyzed for outcome at the time of discharge from the hospital and after follow-up intervals ranging up to 3 years after injury. Of 650 patients with closed-head injury available for analysis, 93 (14%) were discharged in a vegetative state. In comparison with conscious survivors, patients in a vegetative state sustained more severe closed-head injury as reflected by the Glasgow Coma Scale scores and pupillary findings and more frequently had diffuse injury complicated by swelling or shift in midline structures. Of 84 patients in a vegetative state who provided follow-up data, 41% became conscious by 6 months, 52% regained consciousness by 1 year, and 58% recovered consciousness within the 3-year follow-up interval. A logistic regression failed to identify predictors of recovery from the vegetative state.