Multicenter prospective study of children with sickle cell disease: radiographic and psychometric correlation

After obtaining familial informed consent, between January 1996 and July 1997, 173 children (5 to 15 years old) with sickle cell disease were enrolled in a prospective multicenter study using blood screening, transcranial Doppler ultrasonography (n = 143), cerebral magnetic resonance imaging (n = 144), and neuropsychologic performance evaluation (n = 156) (Wechsler Intelligence tests WISC-III, WIPPSI-R), which were also performed in 76 sibling controls (5 to 15 years old). Among the 173 patients with sickle cell disease (155 homozygous for hemoglobin SS, 8 sickle cell beta0 thalassemia, 3 sickle cell beta+ thalassemia, 7 sickle cell hemoglobin C disease SC), 12 (6.9%) had a history of overt stroke, and the incidence of abnormal transcranial Doppler ultrasonography (defined as mean middle cerebral artery velocity > 200 cm/sec or absent) was 8.4% in the overall study population and 9.6% in patients with homozygous sickle cell anemia The silent stroke rate was 15%. Significantly impaired cognitive functioning was observed in sickle cell disease patients with a history of stroke (Performance IQ and Full Scale IQ), but also in patients with silent strokes (Similarities, Vocabulary, and Verbal Comprehension). However, infarcts on magnetic resonance imaging were not the only factors of cognitive deficit: Verbal IQ, Performance IQ, and Full Scale IQ were strongly impaired in patients with severe chronic anemia (hematocrit < or = 20%) and in those with thrombocytosis (platelets > 500 x 10(9)/L). Multivariate logistic regression analysis showed that abnormal magnetic resonance imaging (odds ratio [OR] = 2.76) (P = .047), hematocrit < or =20% (OR = 5.85) (P = .005), and platelets > 500 x 10(9)/L (OR = 3.99) (P = .004) were independent factors of cognitive deficiency (Full Scale IQ < 75) in sickle cell disease patients. The unfavorable effect of low hematocrit has already been suggested, but this is the first report concerning an effect of thrombocytosis and showing that silent stroke alone is not a factor of cognitive deficit when not associated with low hematocrit or thrombocytosis. The effect of hydroxyurea, which is known to increase hematocrit and decrease platelet count, on cognitive functioning of sickle cell patients should be evaluated prospectively.     

Cognitive deficits in children with sickle cell disease

We tested a hypothesis that children with sickle cell disease who are completely normal by magnetic resonance imaging can still be cognitively impaired, as predicted by a model of diffuse brain injury. Fifty-four patients with hemoglobin SS (average age 10.9 years +/- 2.9 years SD) were examined with the Wechsler Intelligence Scale for Children-III (WISC-III) and were randomly matched by age, race, and gender with healthy children from the Wechsler normative database. Patients were also imaged at 1.5 Tesla with standard imaging sequences. Among 30 patients who were normal by magnetic resonance imaging, there were substantial deficits in Wechsler Full-Scale IQ, Verbal IQ, and Performance IQ (all P < .01) compared with African-American controls. The patient Wechsler Full-Scale IQ was 12.9 points lower than that of controls and decreased as a function of age (probability = .014). The findings suggest that there is diffuse brain injury in patients and that patient deficits increase with age.     

Decreased corpus callosum size in sickle cell disease: relationship with cerebral infarcts and cognitive functioning.

We assessed midsagittal corpus callosum size in sickle cell disease (SCD) and its relationship to lesion volume, lesion location, and cognitive functioning. Twenty-eight children with SCD and 16 demographic controls completed magnetic resonance imaging (MRI) and neuropsychological testing. Corpus callosum (CC) size was smaller for children with silent infarcts (n = 8) or overt stroke (n = 8) than for those without visible infarcts (n = 12) or control participants. Lesion volume was a robust predictor of IQ and other cognitive scores; total CC size did not typically add explanatory power for these measures. The size of the rostral body of the CC, however, independently predicted measures of distractibility, speeded production, and working memory. Posterior CC size was also decreased among many of the children with SCD, even in the absence of visible infarcts in this region. Brain morphology appears to provide additional information about SCD-related effects on the brain above and beyond visible infarcts.     

Central nervous system abnormalities in asymptomatic young patients with Sbeta-thalassemia

Twenty-one children and young adults with sickle/beta-thalassemia without overt stroke were examined with magnetic resonance imaging and angiography (MRA), transcranial Doppler (TCD), visual (VEP) and median nerve somatosensory (SEP)-evoked potential recordings, and neuropsychological testing (Wechsler Intelligence Scale [WISC-III]). Eight (38%) had silent infarction in the parietooccipital cortex, deep white matter, or basal ganglia, including two of three with previous seizures. Of 17 undergoing TCD, none had maximum middle cerebral artery (MCA) velocities greater than 126cm/sec, but 9 were abnormal, with low velocities and difficulty in tracking the MCA and/or asymmetry. Three patients had abnormal MRA, one of whom also had silent infarction. One patient had pathological VEP recordings, whereas all SEP recordings were normal. WISC-III was performed in all 11 children, 4 with silent infarction: all but 1 had IQ scores greater than 85 (mean, 97.7; standard deviation, 14.2). We conclude that Greek children and young adults with Sbeta-thalassemia and no history of clinical stroke have TCD abnormalities and silent infarction similar to those reported in children and adolescents with sickle cell anemia, but cognitive function is not necessarily compromised. International collaboration is needed to establish the risk factors for central nervous system sequelae in patients with sickle cell disease, including Sbeta-thalassemia, leading to evidence-based prevention.     

Poor school and cognitive functioning with silent cerebral infarcts and sickle cell disease

The authors evaluated education attainment and neuropsychological deficits in children with sickle cell disease (SCD) and silent cerebral infarcts. Children with silent infarcts had twice the rate of school difficulties as children without infarcts. Eighty percent of silent infarct cases had clinically significant cognitive deficits, whereas 35% had deficits in academic skills. Children with silent cerebral infarcts show high rates of poor educational attainment, cognitive deficits, and frontal lobe injury. Poor school performance in SCD is one indicator of silent infarcts.     

Cognitive profile in young Icelandic children with cerebral palsy

We describe the cognitive profile in a complete national cohort of children with cerebral palsy (CP). One hundred and twenty-seven Icelandic children (67 females, 60 males) with CP, born between 1985 and 2000 and assessed between the ages of 4 and 6 years 6 months (mean age 5y 5mo, SD 6mo), were included in the study. IQ was measured using the Wechsler Preschool and Primary Scale of Intelligence (WPPSI) and developmental quotient (DQ) was obtained using various developmental scales. Physiological classification of CP in the children was: spasticity, n=104 (82%); dyskinesia, n=14 (11%); ataxia, n=six (4.7%), and unclassified CP, n=3 (2.3%). Spastic diplegia was the most prevalent subtype (35%) followed by hemiplegia and quadriplegia. Forty-five per cent of the group were at Level I of the Gross Motor Function Classification System, 32% were at Levels II and III, and 23% were at Levels IV and V. Sixty per cent of the children had an IQ or DQ >70. Median scores on the WPPSI were Full-scale IQ 84, Verbal IQ (VIQ) 92, and Performance IQ (PIQ) 77. Children with spastic diplegia and quadriplegia had a significantly lower PIQ than VIQ. Of the children who failed to complete the WPPSI, 20% had DQ >85. Thus, cognitive skills can be masked by limitations of movement and motor control in children with CP.     

Cognitive deficits in neurofibromatosis 1

Cognitive deficits and academic learning difficulties are the most common neurologic "complication" of neurofibromatosis 1 in childhood and can be responsible for significant lifetime morbidity. There is a slight increase in the frequency of mental retardation (Wechsler Full-Scale IQ < 70) in children with neurofibromatosis 1, but the mean Full-Scale IQ for the patient group is within 1 SD of the population mean. Academic difficulties are common, as are specific deficits in visuospatial ability, executive function, expressive and receptive language, and attentional skills. Behavioral and psychosocial problems have a major impact on quality of life, although there are few objective studies in this area Current research is focusing on the pathogenesis of the disorder. Clinical studies have identified possible radiologic and pathologic markers for cognitive deficits in neurofibromatosis 1, which can now be explored in animal models.     

Cognitive changes in children treated for acute lymphoblastic leukemia with chemotherapy only according to the Pediatric Oncology Group 9605 protocol

The purpose of this study was to examine cognitive functioning and neuroimaging in children with leukemia treated with the Pediatric Oncology Group 9605 protocol at the Children's Hospital of Eastern Ontario. Mean age at diagnosis was 4.88 +/- 2.54 years. The mean (n = 24) Wechsler Verbal and Performance IQ fell in the low-average range (87.33 +/- 15.69 and 84.83 +/- 19.11, respectively). Mean (n = 20) Verbal and Visual Memory Indexes of 82.95 +/- 15.46 and 88.30+/- 10.80, respectively, were obtained. The proportion of scores on measures of intelligence and memory falling > 1 SD below the normative mean was substantially higher than expected. Paired t-test suggested that Wechsler Verbal IQ and memory remained stable, whereas Wechsler Performance IQ declined significantly. The results of growth curve analyses replicated these findings and suggested a significant adverse effect of cumulative dosage of intrathecal methotrexate on estimated Wechsler Performance IQ. Although only two children experienced seizures, 78% of the group showed leukoencephalopathy on at least one magnetic resonance image. Reliance on seizures as a predictor of leukoencephalopathy might underestimate the incidence of neurotoxicity.     

Sensitivity of the Halstead and Wechsler Test Batteries to brain damage: Evidence from Reitan's original validation sample

The Halstead-Reitan Battery has been instrumental in the development of neuropsychological practice in the United States. Although Reitan administered both the Wechsler-Bellevue Intelligence Scale and Halstead's test battery when evaluating Halstead's theory of biologic intelligence, the relative sensitivity of each test battery to brain damage continues to be an area of controversy. Because Reitan did not perform direct parametric analysis to contrast group performances, we reanalyze Reitan's original validation data from both Halstead (Reitan, 1955) and Wechsler batteries (Reitan, 1959a) and calculate effect sizes and probability levels using traditional parametric approaches. Eight of the 10 tests comprising Halstead's original Impairment Index, as well as the Impairment Index itself, statistically differentiated patients with unequivocal brain damage from controls. In addition, 13 of 14 Wechsler measures including Full-Scale IQ also differed statistically between groups (Brain Damage Full-Scale IQ = 96.2; Control Group Full Scale IQ = 112.6). We suggest that differences in the statistical properties of each battery (e.g., raw scores vs. standardized scores) likely contribute to classification characteristics including test sensitivity and specificity.     

Risk factors for unsuccessful testing during the intracarotid amobarbital procedure in preadolescent children

PURPOSE: Identification of risk factors for unsuccessful testing during intracarotid amobarbital procedure (IAP) in preadolescent children. METHODS: A pediatric IAP protocol was attempted in 42 candidates for epilepsy surgery (5-12 years old; mean, 10 years) based on the ability to pass a practice test. Language dominance was defined by marked asymmetry until first verbal response and paraphasic errors. Intact hemispheric memory was defined by recall of >/=60% of test items. The odds ratios of baseline variables (age at IAP, Full-Scale IQ, side of disease, age at seizure onset, amobarbital dose) were calculated for various IAP outcomes. RESULTS: IAPs were accomplished in 40 children. Language dominance was established in 25 (62.5%) of 40 patients: all 21 focal resection candidates were left language dominant; four hemispherectomy candidates had intact language after injection of the damaged hemisphere. In 12 (30%) of 40 patients, language testing failed because of agitation or obtundation. Compared with the 21 children with language dominance established by bilateral IAP, these 12 children had lower mean Full-Scale IQ (66.4 vs. 87.9; p = 0.014), and more frequently, the epileptogenic lesion in the left hemisphere (presumed dominant by right-handedness; 78 vs. 33%; p = 0.04). Excluding hemispherectomy candidates (intentionally only one injection), memory testing could not be completed in 13 (36%) of 36 children because of obtundation or agitation. These children were significantly younger than the 23 (64%) of 36 with successful bilateral memory testing (mean age, 107.6 vs. 128.7 months; p = 0. 006). The eight (25%) of 32 children with failing retention scores after ipsilateral injection had lower Full-Scale IQ than did the 24 (75%) patients who passed (mean, 59.6 vs. 81.7 months; p = 0.03). CONCLUSIONS: The IAP successfully established hemispheric language dominance and memory representation for just under two thirds of the preselected preadolescent children. Risk factors for unsuccessful testing included low Full-Scale IQ (especially <80), young age (especially <10 years), and seizures arising from the left hemisphere presumed dominant by right-handedness.     

Silent cerebral infarction in chronic atrial fibrillation

Atrial fibrillation (AF) is associated with an increased risk of stroke. In AF patients with acute stroke, cerebral computed tomography (CT) often reveals old asymptomatic infarcts. To investigate the frequency of such lesions, 29 AF patients and 29 controls in sinus rhythm without history of cerebrovascular disease were CT scanned. Fourteen patients with AF (48%) had abnormal CT scans with areas of low density with sharp demarcation from surrounding tissue compared with 8 patients in sinus rhythm (28%) (p greater than 0.10). However, the number of abnormal areas with apparent tissue loss was significantly higher in the AF group (39 lesions) compared with the control group (16 lesions) (p = 0.033). The lesions were mainly located in the cortex with no significant difference in lesion size between AF patients and controls. The abnormal areas probably reflected small, clinically silent infarcts. We conclude that these lesions are present in AF patients without history of cerebrovascular events and occur more frequently than in controls without atrial fibrillation.     

The King's Outcome Scale for Childhood Head Injury and injury severity and outcome measures in children with traumatic brain injury

The aim of this study was to relate discharge King's Outcome Scale for Childhood Head Injury (KOSCHI) category to injury severity and detailed outcome measures obtained in the first year post-traumatic brain injury (TBI). We used a prospective cohort study. Eighty-one children with TBI were studied: 29 had severe, 15 moderate, and 37 mild TBI. The male:female ratio was 1.8:1. The mean age was 11 years 10 months (SD 3.6, range 5-16y). Discharge KOSCHI categories were good (n=34), moderate (n=39), severe (n=6), and unclassifiable (n=2). KOSCHI category correlated strongly with admission Glasgow Coma Score, length of hospital stay, and post-traumatic amnesia. It also correlated significantly with Verbal IQ and Performance IQ (Wechsler); measures of attention; health status (Health Utilities Index [HUI]); health-related quality of life (Pediatric Quality of Life Inventory [PedsQL]); depressive symptoms (Birleson Depression Scale) assessed within 3 months postTBI; and with Verbal IQ, selective attention (map mission), and HUI and PedsQL domains assessed at least 6 months post-TBI discharge. KOSCHI did not correlate with behaviour or executive function. We conclude that the KOSCHI scored at hospital discharge correlates with severity of injury and some cognitive, health status, and HRQL outcomes early after TBI. It is not helpful at predicting later difficulties, or behavioural and emotional problems.     

99mTc-HL91单光子计算机断层扫描对脑梗死灶周围乏氧组织的检测

目的探讨99mTc-HL91单光子计算机断层扫描(SPECT)对脑梗死灶周围乏氧组织的检测。方法应用99mTc-HL91 SPECT对29例脑梗死患者和5名健康对照者进行脑显像检测,并对脑梗死患者进行血压、血糖和血浆纤维蛋白原(Fib)水平检查。结果 SPECT示脑梗死组脑组织乏氧显像阳性18例(62.1%),正常对照组均阴性。Spearman秩相关分析显示,梗死体积≤30 cm3的患者乏氧显像阳性范围与SPECT检测时间呈负相关(rs=-0.624,P<0.05),与脑梗死体积呈正相关(rs=0.715,P<0.001)。结论99mTc-HL91SPECT检测可显示脑梗死灶周围乏氧组织。梗死灶体积≤30 ml的脑梗死患者SPECT检测时间越早,则乏氧显像的阳性率越高。     

Developmental manual dyspraxia: a lesson in mind and brain.

For decades, pediatricians assiduously documented "soft neurologic signs" in children referred for school learning difficulties, although pediatric neurologists, including Charles F. Barlow, pointed out the dissociation between most neuropsychological abnormalities and the motor findings in question. Later, large epidemiologic studies confirmed the independence of soft signs from other neuropsychological defects. We used a standardized dyspraxia battery to study 164 schoolchildren 5 to 12 years old. We found that in the group as a whole there was a positive correlation between motor performance in the dyspraxia battery and IQ on the Wechsler Intelligence Scale for Children--revised (Full-Scale, Verbal, and Performance). In terms of dyspraxia subscales, we found that Performance IQ and Full-Scale IQ correlated with imitation of nonsense gestures and use of actual objects, whereas Verbal IQ correlated positively only with pantomime on command. In contrast, for the group of 24 subjects whose scores on the battery designated them as dyspraxic, there was no correlation between dyspraxia scores and IQ. Together with the existence of specific, dramatically different, types of dyspraxia among the 24 dyspraxic subjects, present findings uphold the earlier neurologic opinion that "motor soft signs" are not evidence for fixed "brain damage" or even for other types of motor dysfunction, and that dissociation of different specific cognitive dysfunctions is the rule within individual patients.     

Short-term intellectual outcome after arterial ischemic stroke and sinovenous thrombosis in childhood and infancy

Arterial ischemic stroke is approximately four times more prevalent than sinovenous thrombosis and has been associated with a worse neurologic outcome than sinovenous thrombosis; however, no data are available comparing intellectual outcome after pediatric arterial ischemic stroke and sinovenous thrombosis. We report the short-term intellectual outcome (mean 5.8 months since stroke) in a sample of 72 children, 47 with arterial ischemic stroke, and 25 with sinovenous thrombosis. Intellectual outcome measures were the Full-Scale IQ of the age-appropriate Wechsler intelligence test for older children and the Mental Developmental Index of the Bayley Scales of Infant Development for younger children. Stroke type did not directly influence intellectual outcome. Intellectual outcome was in the normal range whether the children had suffered an arterial ischemic stroke or a sinovenous thrombosis.     

Wechsler Adult Intelligence Scale-Revised in the Evaluation of Anterior Temporal Lobectomy Candidates

Summary: We wished to (a) determine the ability of the Wechsler Adult Intelligence Scale-Revised (WAIS-R) to discriminate between patients with epilepsy of left or right temporal lobe (LTLE, RTLE) origin and (b) examine the ability of Kaufman's (1990) WAIS-R short forms to estimate actual Full-Scale IQ (FSIQ). We administered the WAIS-R to 215 nonretarded, left hemisphere dominant patients with invasively verified epilepsy of unilateral TL origin without lesions demonstrated by magnetic resonance imaging (MRI) (excluding mesial temporal sclerosis, MTS). LTLE (n = 106) and RTLE (n = 109) groups were compared on the WAIS-R subtests and summary IQ scores, Verbal–Performance IQ (VIQ—PIQ) discrepancies of various magnitudes, and Verbal Comprehension (VC) and Perceptual Organization (PO) scores derived by factor analysis. The LTLE group scored significantly lower on the Vocabulary subtest, and none of the other indexes reliably distinguished LTLE from RTLE patients. The Kaufman 2, 3, and 4 subtest short forms were significant predictors of FSIQ, with the 4 subtest short form having the highest correlation and lowest error of estimate.     

Neuroprotective effects of female gonadal steroids in reproductively senescent female rats

BACKGROUND AND PURPOSE: Young adult female rats sustain smaller infarcts after experimental stroke than age-matched males. This sex difference in ischemic brain injury in young animals disappears after surgical ovariectomy and can be restored by estrogen replacement. We sought to determine whether ischemic brain injury continues to be smaller in middle-aged, reproductively senescent female rats compared with age-matched males and to test the effect of ovarian steroids on brain injury after experimental stroke in females. METHODS: Four groups of 16-month old Wistar rats (males [n=9], untreated females [n=9], and females pretreated with 17beta-estradiol [25-microgram pellets administered subcutaneously for 7 days; n=9] or progesterone [10-mg pellets administered subcutaneously for 7 days; n=9] were subjected to 2 hours of middle cerebral artery occlusion with the intraluminal filament technique, followed by 22 hours of reperfusion. Physiological variables and laser-Doppler cerebral cortical perfusion were monitored throughout ischemia and early reperfusion. In a separate cohort of males (n=3), untreated females (n=3), females pretreated with 17beta-estradiol (n=3), and females pretreated with progesterone (n=3), end-ischemic regional cerebral blood flow was measured by [(14)C]iodoantipyrine autoradiography. RESULTS: As predicted, infarct size was not different between middle-aged male and female rats. Cortical infarcts were 21+/-5% and 31+/-6% of ipsilateral cerebral cortex, and striatal infarcts were 44+/-7% and 43+/-5% of ipsilateral striatum in males and females, respectively. Both estrogen and progesterone reduced cortical infarct in reproductively senescent females (5+/-2% and 16+/-4% in estrogen- and progesterone-treated groups, respectively, compared with 31+/-6% in untreated group). Striatal infarct was smaller in the estrogen- but not in the progesterone-treated group. Relative change in laser-Doppler cerebral cortical perfusion from preischemic baseline and absolute end-ischemic regional cerebral blood flow were not affected by hormonal treatments. CONCLUSIONS: We conclude that the protection against ischemic brain injury found in young adult female rats disappears after reproductive senescence in middle-aged females and that ovarian hormones alleviate stroke injury in reproductively senescent female rats by a blood flow-independent mechanism. These findings support a role for hormone replacement therapy in stroke injury prevention in postmenopausal women.     

Greater burden of white matter lesions and silent infarcts ipsilateral to carotid stenosis

ObjectivesCarotid stenosis may cause silent cerebrovascular disease (CVD) through atheroembolism and hypoperfusion. If so, revascularization may slow progression of silent CVD. We aimed to compare the presence and severity of silent CVD to the degree of carotid bifurcation stenosis by cerebral hemisphere.Materials and methodsPatients age ≥40 years with carotid stenosis >50% by carotid ultrasound who underwent MRI brain from 2011-2015 at Mayo Clinic were included. Severity of carotid stenosis was classified by carotid duplex ultrasound as 50-69% (moderate), 70-99% (severe), or occluded. White matter lesion (WML) volume was quantified using an automated deep-learning algorithm applied to axial T2 FLAIR images. Differences in WML volume and prevalent silent infarcts were compared across hemispheres and severity of carotid stenosis.ResultsOf the 183 patients, mean age was 71±10 years, and 39.3% were female. Moderate stenosis was present in 35.5%, severe stenosis in 46.5% and occlusion in 18.0%. Patients with carotid stenosis had greater WML volume ipsilateral to the side of carotid stenosis than the contralateral side (mean difference, 0.42±0.21cc, p=0.046). Higher degrees of stenosis were associated with greater hemispheric difference in WML volume (moderate vs. severe; 0.16±0.27cc vs 0.74±0.31cc, p=0.009). Prevalence of silent infarct was 23.5% and was greater on the side of carotid stenosis than the contralateral side (hemispheric difference 8.8%±3.2%, p=0.006). Higher degrees of stenosis were associated with higher burden of silent infarcts (moderate vs severe, 10.8% vs 31.8%; p=0.002).ConclusionsWML and silent infarcts were greater on the side of severe carotid stenosis.     

Intelligence and language of individuals who incurred left hemisphere injury at no later than 3 years of age]

It is generally considered that damage to the brain during infancy and young childhood results in milder or different syndromes than does brain injury incurred during adulthood. However, only several past studies employed CT scans to confirm that lesions are confined to one of the two cerebral hemispheres. We examined intelligence and language skills of 5 cases, which sustained nonprogressive damage exclusively to the left cerebral hemisphere before 1 year of age, and 1 case, which incurred nonprogressive left hemisphere injury at 3 years of age. These cases were tested at 9 to 25 years of age, or 8 to 22 years after inflicting injuries. The following scales and tests, all of which are Japanese versions, were employed: the Wechsler Intelligence Scale for Children-Revised (WISC-R) to measure intelligence of 3 cases at 15 years of age or younger, the Wechsler Adult Intelligence Scale (WAIS) for 3 cases older than 15 years of age, the Western Aphasia Bettery (WAB) to measure language skills, and the shortened version of the Token Test to assess auditory comprehension skills. Upon administration of the tests, we obtained the following results: 1) Although 1 case had a large lesion in the left hemisphere, she exhibited a high IQ of 111, and was adapted well as a college student. The result suggested that large lesions, if incurred at no later than 1 year of age, may affect intelligence to only a little or negligible extent. 2) Verbal IQ generally declines from left hemisphere damage in adults. In all of our subjects, however, verbal IQ was similar to performance IQ.(ABSTRACT TRUNCATED AT 250 WORDS)     

Therapeutic effects of environmental enrichment on cognitive function and tissue integrity following severe traumatic brain injury in rats

Postinjury environmental enrichment (EE) has been shown to alter functional and anatomical outcomes in a number of injury paradigms, including traumatic brain injury (TBI). The question of whether EE alters functional outcome following TBI in a model which produces overt histopathological consequences has not been addressed. We investigated this question using the severe, parasagittal fluid percussion injury (FPI) model. Rats (n = 7 per group, enriched and standard for behavior; n = 15 per group for histology) underwent severe (2.2-2.6 atm) FPI, with sham-operated rats (n = 7 per group, enriched and standard for behavior; n = 6 enriched, n = 3 standard for histology) serving as controls. Animals were allowed to recover for 11 days either in standard single housing or together (injured and sham) in an enriched environment consisting of a 92 x 61 x 77-cm ferret cage filled with various stimulatory objects. Consistent with earlier reports, injured animals recovering in the enriched environment showed significantly (P < 0.05) shorter latencies to find the platform in a Morris Water Maze task versus injured/standard animals on day 12 post-TBI. However, both injured groups showed significant deficits versus sham groups (P < 0.05). There were no differences between the sham/enriched and sham/standard groups. No significant group differences in swim speed were observed. At 14 days post-TBI, enriched animals had approximately twofold smaller lesion areas in regions of the cerebral cortex posterior to the injury epicenter (-4.5, -5.8, -6.8 mm relative to bregma; P < 0.05) compared to injured/standard animals. In addition, overall lesion volume for the entire injured cortical hemisphere was significantly smaller in animals recovering in the enriched environment. These results indicate that noninvasive environmental stimulation is beneficial in attenuating cognitive deficits and preserving tissue integrity in a TBI model which causes cerebral contusion and cell death.