Neurocognitive Evaluation Research Articles

Brief neurocognitive screening in youth with brain tumours: A preliminary investigation of the Lebby-Asbell Neurocognitive Screening Examination (LANSE)

Primary objective: It is well-documented that survivors of paediatric brain tumour are at risk for neurocognitive deficits resulting in an increased interest in neurocognitive assessment for these youth. Given the scarcity of well-validated brief assessments for this purpose, this study examines the reliability and validity of a brief neurocognitive screening measure.Research design: Cross-sectional data on youth (aged 6–17.9) administered a brief neurocognitive screening device and broader neurocognitive batteries was collected via chart review to evaluate the reliability and validity of a brief neurocognitive screening device.Methods and procedures: Fifty-one youth with brain tumours and 26 youth with traumatic brain injury (TBI) were administered The Lebby-Asbell Neurocognitive Screening Examination (LANSE) during clinic visits. A sub-set of children were administered a more comprehensive neurocognitive evaluation and scores from the LANSE and these evaluations were compared to assess preliminary validity.Main outcome and results: Most LANSE sub-scales demonstrated adequate reliability and preliminary validity with some exceptions. Comparison of youth with brain tumours to those with a TBI revealed a similar pattern of potential neurocognitive impairment across several cognitive domains.Conclusions: This study demonstrates the preliminary reliability and validity of a brief neurocognitive screening examination for youth with brain tumours.

Comparison of Cognitive Impairment between Patients having Epilepsy and Psychogenic Nonepileptic Seizures.

The aim of this study was to evaluate cognitive impairment in patients having epilepsy or psychogenic nonepileptic seizures (PNESs) using selected neuropsychological tests at different time periods related to the seizure. In this study, selected neurocognitive tests were administered to the patients. Within 24 h, the previously applied neurocognitive tests were repeated within 24 h following the observation of typical seizures when monitoring and normalizing electroencephalography (EEG) activity. Basal neurocognitive tests were also administered to the healthy control group, and repeat neurocognitive evaluation was performed within 24-96 h. The basal neurocognitive evaluation revealed that verbal learning and memory scores as well as Stroop test interference time were significantly lower in the PNES group compared with those in the controls. In the basal cognitive tests administered to the patients with epilepsy, verbal learning and memory scores, long-term memory, and total recognition test scores were significantly lower than those of the controls. Following the repeat cognitive tests, significant progress was found in the verbal categorical fluency score of the PNES group. No significant difference was determined in the epilepsy group. Significant contraction was determined in the Stroop interference time in the control group, but no similar change was recorded in the epilepsy or PNES groups. While memory problems seemed to be most prominent in the assessed patients with epilepsy, attention and executive function problems were more dominant in the patients with PNESs. These findings are probably related to numerous factors such duration of disease, mood disorders, and specific drug use. No deterioration in attention and executive functions was reported in the early post-seizure period in either patient group.

Rapid Cognitive Assessment of Nursing Home Residents: A Comparison of the Brief Interview for Mental Status (BIMS) and Brief Cognitive Assessment Tool-Short Form (BCAT-SF).

In nursing homes, the ability to identify residents with cognitive impairment is critical; however, many providers fail to address symptoms of dementia due to insufficient time to assess cognition. In the current study, the authors compared two rapidly administered instruments, the Brief Interview for Mental Status (BIMS) and Brief Cognitive Assessment Tool-Short Form (BCAT-SF), in predicting specific cognitive stages. Two hundred twenty-five nursing home residents who were referred for neurocognitive evaluation and met inclusion criteria participated in the study. Both cognitive instruments were found to predict cognitive diagnoses generally, but only the BCAT-SF demonstrated sensitivity in differentiating among all cognitive levels. Receiver operating characteristic analyses did not confirm cutoff scores reported in the original BIMS study. However, sensitivity (0.91) and specificity (0.96) values for the BCAT-SF were robust for differentiating between dementia and non-dementia. The BCAT-SF appears to be a more sensitive instrument for predicting cognitive stages than the BIMS for nursing home residents.

Altered Neurochemistry in Former Professional Soccer Players without a History of Concussion.

Soccer is played by more than 250 million people worldwide. Repeatedly heading the ball may place soccer players at high risk for repetitive subconcussive head impacts (RSHI). This study evaluates the long-term effects of RSHI on neurochemistry in athletes without a history of clinically diagnosed concussion, but with a high exposure to RSHI. Eleven former professional soccer players (mean age 52.0±6.8 years) and a comparison cohort of 14 age- and gender-matched, former non-contact sport athletes (mean age 46.9±7.9 years) underwent 3T magnetic resonance spectroscopy (MRS) and neurocognitive evaluation. In the soccer players a significant increase was observed in both choline (Cho), a membrane marker, and myo-inositol (ml), a marker of glial activation, compared with control athletes. Additionally, ml and glutathione (GSH) were significantly correlated with lifetime estimate of RSHI within the soccer group. There was no significant difference in neurocognitive tests between groups. Results of this study suggest an association between RSHI in soccer players and MRS markers of neuroinflammation, suggesting that even subconcussive head impacts affect the neurochemistry of the brain and may precede neurocognitive changes. Future studies will need to determine the role of neuroinflammation in RSHI and the effect on neurocognitive function.

Psychological and neurocognitive evaluation in patients with pituitary adenoma

Psychological and neurocognitive evaluation in patients with pituitary adenoma

You Cannot Go Home: Routine Concussion Evaluation is not Enough

Traditional care of mild traumatic brain injury (MTBI) is to discharge patients from the emergency department (ED) if they have a Glasgow Coma Score (GCS) of 15 and a normal head computed tomography (CT) scan. However, this does not address short-term neurocognitive deficits. Our hypothesis is that a notable percentage of patients will need outpatient neurocognitive therapy despite a reassuring initial presentation. This is a retrospective review of patients with MTBI at an urban Level I trauma center. Inclusion criteria were a diagnosis of MTBI in patients 14 years old or older, GCS 15, negative head CT scan, a completed neurocognitive evaluation, blunt mechanism, and no confounding psychiatric comorbidities. Six thousand thirty-two patients were admitted over 18 months. Three hundred ninety-five patients met inclusion criteria. Average age was 38 years (range, 14 to 93 years), 64 per cent were male, and mean Injury Severity Score (ISS) was 8.1. Forty-one per cent were cleared for discharge without follow-up. Twenty-seven per cent required ongoing neurocognitive therapy. Three per cent were deemed unsafe for discharge home. Of the patients cleared for discharge, 88 per cent had positive/questionable loss of consciousness (LOC), whereas 81 per cent who required additional therapy had positive/questionable LOC (P = 0.20). Age, gender, ISS, and alcohol use were compared between the groups and not found to be statistically different rendering them poor predictors for appropriate discharge from the ED. A surprisingly high percentage (27%) of patients who would have met traditional ED discharge criteria were found to have persistent deficits after neurocognitive testing and were referred for ongoing therapy. We provide evidence to suggest that we should take pause before discharging patients with MTBI without a cognitive evaluation.

Neurocognitive evaluation of long term survivors of atypical teratoid rhabdoid tumors (ATRT): The Canadian registry experience.

Because atypical teratoid rhabdoid tumor(ATRT) is a rare disease of infancy carrying a grim prognosis, focus on long-term outcome, especially neurocognitive remained very limited. With new era of multimodality therapy, an increasing proportion of patients are now long-term survivors. Retrospective review of neuropsychological (NP) status of survivors from the Canadian ATRT registry. Among 77 patients diagnosed between 1995-2012, 16(22%) were survivors. Formal NP assessments were available in eight patients. Partial information on academic achievement was available on three additional patients. There were four girls and seven boys diagnosed at a median age of 27.5 months. Seven patients underwent complete resection and three had metastatic disease. All but one received sequential high dose chemotherapy. Five patients received intrathecal chemotherapy. Three patients underwent radiation. Median age at time of formal NP assessment was 7.6 years (3.9-9.8). Full Scale Intellectual Quotient (FSIQ) ranged from less than 50-119 (mean 78). Simple expressive and receptive language appeared relatively preserved. Three recently diagnosed patients (median time assessment from diagnosis 2.6 years (1.6-4.7)) had average to high average FSIQ, academic and visual spatial skills, visual, and verbal memory. Five other patients diagnosed earlier and tested at a median time of 4.9 years (3.3-8.3) post-diagnosis had a FSIQ ranging from <50 to 71. Approximately 50% of their scores were in the impaired range. Overall this cohort appears significantly impaired at school age despite the absence of systematic radiotherapy. Larger series focusing on neurocognitive outcome are needed in the current context where treatment strategies include adjuvant radiation.

Cerebrospinal fluid (CSF) CD8+ T-cells that express interferon-gamma contribute to HIV associated neurocognitive disorders (HAND).

BackgroundHIV associated neurocognitive disorders (HAND) continue to affect cognition and everyday functioning despite anti-retroviral treatment (ART). Previous studies focused on mechanisms related to monocyte/macrophage mediated inflammation. However, in the ART era, there is increasing evidence for the involvement of CD8+ T-cells in CNS pathogenesis.MethodsTo investigate the relationship between T-cell responses and neurocognitive impairment (NCI), cerebrospinal fluid (CSF) and peripheral blood CD4+ and CD8+ T-cell intracellular cytokine (IFNγ, IL-2, TNFα) and lytic marker (CD107a) expression were assessed in HIV infected subjects who underwent comprehensive neurocognitive (NC) evaluation and either initiated or changed ART.ResultsData were collected from 31 participants at 70 visits. The frequency of cytokine expressing T-cells in CSF was significantly higher than in peripheral blood for CD4+T-cells: TNFα, IL-2, IFNγ and CD8+T-cells: IL-2 and IFNγ. Analysis of T-cell activity and NCI as a function of CSF HIV RNA levels suggested a general association between NCI, high CSF CD8+ (but not CD4+T-cell) cytokine expression and CSF HIV RNA <103 copies/ml (p<0.0001). Specifically, CSF CD8+ T-cell IFNγ expression correlated with severity of NCI (r = 0.57, p = 0.004). Multivariable analyses indicated that CSF CD8+T-cell IFNγ and myeloid activation (CD163) contributed equally and independently to cognitive status and a composite variable produced the strongest correlation with NCI (r = 0.83, p = 0.0001). In contrast, CD8+ cytolytic activity (CD107a expression) was negatively correlated with NCI (p = 0.05) but was dependent on CD4 levels >400/μl and low CSF HIV RNA levels (<103 copies/ml). In our longitudinal analysis of 16 subjects, higher CSF CD8+IFNγ expression at baseline predicted NC decline at follow-up (p = 0.02). Severity of NCI at follow-up correlated with level of residual HIV RNA in CSF.ConclusionsPresence of IFNγ expressing CD8+ T-cells, absence of cytolytic CD8+ T-cells, high myeloid activation, and failure of ART to suppress HIV replication in CSF contribute to increased risk of HAND.

Body focused repetitive behavior disorders and perceived stress: Clinical and cognitive associations

BackgroundHair pulling disorder (trichotillomania) and skin picking disorder are related psychiatric disorders that can be conceptualized as body-focused repetitive behavior disorders (BFRBs). Stress may play a role in the etiology and maintenance of BFRBs, yet the impact of stress on distinct aspects of BRFBs has yet to be clearly delineated. Methods140 participants with BFRBs were recruited and undertook clinical and neurocognitive evaluation. They were grouped according to mild, moderate, or severe levels of perceived stress. ResultsHigher levels of perceived stress during the past month were associated with greater disease severity (Clinical Global Impression, and time spent undertaking the habit per day), greater disability (Sheehan Disability Scale), worse quality of life, and elevated rates of psychiatric comorbidity. Cognitive function (set-shifting and response inhibition) appeared to have no association with stress level. ConclusionsThese results indicate that levels of perceived stress have a strong association with the clinical presentation of BRFBs, even in the absence of confounding differences in demographic features. The lack of association between stress and cognitive dysfunction may support the utility of these selected cognitive measures (set-shifting and response inhibition) as vulnerability (or trait) markers, rather than being directly related to symptom severity or current stress.

Assessment of Long-Term Cognitive Impairment After Off-Pump Coronary-Artery Bypass Grafting and Related Risk Factors

ObjectivesTo assess cognitive impairment after off-pump coronary-artery bypass grafting, with a particular emphasis on long-term follow-up and related risk factors. DesignProspective study. SettingVirgen de la Victoria University Hospital, Málaga, Spain. ParticipantsParticipants were 36 patients undergoing off-pump coronary-artery bypass grafting. MeasurementsChanges in the neuropsychological test battery administered from before to after surgery (1, 6, and 12 months). Postoperative cognitive impairment was defined by a significant decrease. ResultsA significantly multidomain (attention-executive functions, P < .01; immediate and delayed memory, P < .001; and verbal fluency, P < .05) postoperative cognitive impairment was shown, being maximum at 6 months (more than 50% of patients) and still presented at 12 months (more than 30% of patients), but partially recovered. Related risk factors as smoking (P < .01), diabetes mellitus (P < .01), peripheral arteriopathy (P < .01), obesity (P < .05), lower hematocrit (P < .01), and hemoglobin (P < .05) levels and diastolic blood pressure (P < .05) were identified as predictors of cognitive impairment. Better New York Heart Association class (P < .01) and less severity of angina (P < .01) were associated with partial postoperative recovering. ConclusionA multidomain long-term postoperative cognitive impairment and a partial neurocognitive recovering were detected after off-pump coronary-artery bypass grafting and were associated with several nonspecific surgery factors. These findings may be useful when counseling patients before surgery and suggest the importance of long-term neurocognitive evaluation.

Neuroimaging abnormalities, neurocognitive function, and fatigue in patients with hepatitis C.

Objective:This study examined neurologic abnormalities (as measured by proton magnetic resonance spectroscopy imaging and diffusion tensor imaging), neurocognitive performance, and fatigue among a sample of adults with hepatitis C virus (HCV). We hypothesized that HCV+ individuals would demonstrate structural brain abnormalities and neurocognitive compromise consistent with frontostriatal dysfunction as well as increased fatigue compared to controls.Method:Participants were 76 individuals diagnosed with HCV and 20 controls who underwent a comprehensive neurocognitive evaluation and clinical assessments. A subset of the HCV+ participants (n = 29) and all controls underwent MRI.Results:Individuals diagnosed with chronic HCV infection demonstrated greater fractional anisotropy in the striatum as well as greater mean diffusivity in the fronto-occiptal fasciculus and external capsule compared to HCV− controls. HCV+ participants also demonstrated lower levels of N-acetylaspartate in bilateral parietal white matter and elevations in myo-inosital (mI) in bilateral frontal white matter compared to HCV− controls (all p values < 0.05). HCV+ participants also demonstrated significantly poorer neuropsychological performance, particularly in processing speed and verbal fluency. HCV+ patients reported higher levels of fatigue than controls, and fatigue was significantly correlated with diffusivity in the superior fronto-occipital fasciculus, elevations in mI in frontal white matter, and overall cognitive performance.Conclusions:Our results suggest that HCV-associated neurologic complications disrupt frontostriatal structures, which may result in increased fatigue and poorer cognitive performance, particularly in those cognitive domains regulated by frontostriatal regions.

Pediatric tectal plate gliomas: a review of clinical outcomes, endocrinopathies, and neuropsychological sequelae.

Pediatric tectal plate gliomas are indolent slow-growing gliomas that often present with increased intracranial pressure or incidentally on routine brain imaging. We investigated clinical outcomes, endocrinopathies, and neuropsychological sequelae associated with tectal plate gliomas. Twenty-six patients with tectal plate glioma were identified in a 20-year retrospective review. Clinical outcomes, treatments, endocrine function, neuropsychological testing outcomes and radiographic imaging were reviewed for possible signs correlating with tumor progression. Among 26 patients, 19 presented with signs or symptoms of increased intracranial pressure (73 %) versus an incidental finding in 7 (27 %). Median follow-up was 46 months (range 8-143 months). Six of 26 (23 %) experienced progressive disease after diagnosis. Five of 26 (19 %) required more than one surgical procedure due to failure of initial endoscopic third ventriculostomy. Seven of 26 had history of endocrine dysfunction, of which, five presented with endocrine dysfunction (precocious puberty or short stature), 1 developed menstrual irregularities after surgical intervention and 1 had preexisting pan hypopituitarism. Of 12 patients with available neuropsychological testing, eleven had at least one indicator of executive functioning in the low-average to impaired range. While tectal plate gliomas have been considered indolent tumors that are rarely progressive, 23 % of patients in our cohort experienced disease progression and required further therapy. Neurocognitive deficits may occur, while endocrine deficiency is uncommon. Regular multidisciplinary oncology follow-up, routine monitoring with MRI and formal neurocognitive evaluation are imperative to provide early recognition of disease progression or recurrent hydrocephalus and to improve school functioning in this population.

The relationship between the degree of cognitive impairment and retinal nerve fiber layer thickness.

The goal of the present study is to investigate the relationship between the degree of cognitive impairment and retinal nerve fiber layer (RNFL) thickness which is measured by the optical coherence tomography (OCT). Thirty-five patients with Alzheimer's disease (AD), 35 patients with mild cognitive impairment (MCI), and 35 healthy volunteers, between the ages of 60-87, who were examined in the neurology outpatient clinic among 2012-2013 were prospectively involved in our study. Mini mental state examination (MMSE) test, montreal cognitive assessment (MOCA), and also neuropsychological test batteries were used for the neurocognitive evaluation. RNFL thickness was measured by the OCT technique and the differences among groups were studied. The relationship between RNFL thickness and MMSE scores with demographic characteristics was investigated. RNFL thickness was significantly lower in AD and MCI groups compared with the control group (p < 0.01). No significant differences of RNFL were found between the MCI and the AD groups (p > 0.05). Significant correlation was found between MMSE scores and the RNFL values (p < 0.05). Significant thinning in RNFL along with age was detected (p < 0.05). In our study, it is thought that retinal nerve fiber degeneration and central nervous system degeneration may be concurrent according to the thinning of RNFL measured by OCT in AD and MCI groups. RNFL measurement may also be useful for early diagnosis and evaluation of the disease progression. Further studies are needed to optimize the utility of this method as an ocular biomarker in AD.

Correlations between homocysteine and grey matter volume in patients with Alzheimer's disease.

Previous studies have reported that elevated total homocysteine levels are associated with cognitive dysfunction. However, few studies have examined the radiological markers of associated neuropathology in Alzheimer's disease (AD). We hypothesized that elevated levels of homocysteine are associated with cerebral grey matter volume loss. We compared the grey matter in a high homocysteine group and a normal homocysteine group using an optimized voxel-based morphometry. The study included 79 patients with AD who were divided into two groups: a high homocysteine group and a normal homocysteine group. The participants underwent brain magnetic resonance imaging using a standardized protocol and neurocognitive evaluation. Homocysteine tests and other routine laboratory examinations for dementia assessment were carried out in all patients. There was no significant difference in grey matter volume between the patients with high homocysteine levels and those with normal homocysteine levels. A multiple regression analysis also revealed that the levels of homocysteine were not associated with the grey matter volume in patients with AD. Homocysteine levels were not correlated significantly with Mini-Mental State Examination, Global Deterioration Scale, or Clinical Dementia Rating. Our results showed that elevated homocysteine levels are not associated with reduced cerebral grey matter volume in AD. Larger samples will be needed to assess potential correlations between homocysteine and neuroanatomical pathology in the future.

How a Seemingly Minimal Physical Exam Finding Unveiled a More Serious Condition: A Case Report

Cerebral contusion following a concussion is a severely debilitating and possibly life-threatening condition that is not readily uncovered in American football players. We describe the case of a 16-year-old high school male who presented to a university-based concussion clinic 5 days post helmet-to-helmet collision with symptoms of nighttime headaches, dizziness, and difficulties with concentration and word finding. Neurocognitive evaluation demonstrated decreased visual and verbal memory, along with a very high concussion symptom score on the Immediate Post-Concussion Assessment and Cognitive Test (ImPACT ® ). Physical examination findings revealed lower extremity hyperreflexia with pathologic spread to bilateral knees and Achilles tendons. These focal neurologic signs prompted obtention of brain and cervical spine imaging, which demonstrated a right temporal lobe contusion and multiple cervical disc herniations. This case emphasizes the importance of a thorough neurologic examination. Failure to recognize these critical signs could have resulted in premature or unsafe return to play, ultimately exposing the athlete to the risk of additional trauma. Concussion is primarily diagnosed clinically and therefore imaging is not routinely obtained. Thus, fastidious upper motor neuron testing should be a fundamental component of the standard neurologic examination when evaluating players suspected of having a concussion. J Med Cases. 2015;6(6):240-242 doi: https://doi.org/10.14740/jmc2047w

High Failure Rate with Brigance Developmental Screening in 3 Year-Old Children with Sickle Cell Disease

Background: Central nervous system complications of sickle cell disease (SCD) include stroke, silent cerebral infarct, and neurocognitive deficits, but few studies have examined developmental delays in preschool-age children. Using the Brigance developmental screen in 3 year-old children with SCD we found a high frequency of scores below the “normal” cutoff for age, but control data were lacking (Ped. Blood Cancer 2011;56:620). We hypothesized that children with SCD would be more likely to “fail” this screening test than age-matched children from a similar ethnic/socio-economic background.Methods: This prospective study was approved by the St. Jude Children’s Research Hospital (SJCRH) IRB and informed consent obtained for each subject. 3.0-3.9 year-old SCD subjects were tested in the SJCRH Sickle Cell Clinic. Patients receiving chronic transfusion therapy were excluded. Age-matched and race-matched control subjects with similar socio-economic backgrounds were recruited from 8 Memphis daycare centers. The Brigance Preschool Screen was administered by trained examiners in the clinic or the daycare and required about 15 minutes to complete; the primary caretaker simultaneously completed the demographic form. None of the participants had previous exposure to the test. The proportions of subjects who failed the Brigance test (scoring below the age-related “cutoff”) and test raw scores (higher scores indicating better performance) were compared between SCD and control subjects using the exact Chi-square test and the two-sample t-test, respectively; logistic regression was used to model the associations between the Brigance failure proportions and other covariates for the groups. P-values <0.05 were considered significant.Results: Testing was performed on 103 SCD subjects not on treatment, an additional 20 HbSS subjects receiving hydroxyurea (HU), and 109 daycare subjects. Seventy-four percent of children with SCD (not on HU) failed the Brigance screen, compared to 61% of controls (p = 0.04). Mean (SD) Brigance raw scores for the non-HU SCD patients and controls were 45.9 (20.8) and 56.1 (22.5), respectively (p < 0.001). In the non-HU SCD group the pass/fail rate was not significantly different in those with more severe (SS, Sβ0thal) and milder (SC, Sβ+thal) genotypes. Medical factors, including absolute neutrophil count, hemoglobin concentration, %HbF level and O2saturation by pulse oximetry, were not associated with Brigance results. In contrast, socio-economic/demographic factors had a significant effect on the scores: lower income level, more household children under age 18, and more household residents were associated with increased failure (p </= 0.03). Lower caretaker education level showed a similar trend (p = 0.065). None of the socio-economic/demographic factors were associated with failure in the control group, although there was a trend toward failure with more household children under age 18 (p = 0.07). HU-treated SCD children were not significantly different from untreated patients in the failure rate (p = 0.4) and had no significant associations with medical or socio-economic factors.Conclusions: Among 3-year-olds tested with the Brigance Developmental Screen, a higher proportion of children with SCD failed compared to matched controls, but both groups showed a surprisingly high rate. Medical factors, such as hemoglobin level and sickle cell genotype, were not associated with the failure rate, nor was treatment with HU in a limited number of subjects. Socio-demographic factors (income level and numbers of household members) were associated with the failure rate in the SCD group, but not in the control group. These data indicate that preschool children with SCD are at very high risk for developmental delay, and underlying environmental factors seem to contribute more than medical factors. More detailed neurocognitive evaluation of preschool children with SCD and effective ways to enhance their development are needed. DisclosuresOff Label Use: Hydroxyurea for children with sickle cell disease.

ED-17 * GENETIC MODULATION OF NEUROCOGNITIVE FUNCTION AND OUTCOMES IN GLIOMA PATIENTS

BACKGROUND: Genetic polymorphisms associated with neurocognitive function (NCF) in glioma patients have not been studied. Determining such markers may help identify patients at increased risk for treatment related neurotoxicity, suggesting possible targets for treatment, and facilitate development of new neuroprotective therapies to improve the patients' quality of life. METHODS: To identify the effect of genetic variants on NCF, we compared the genotype frequencies of 10,967 SNPs mapping to 580 genes from five pathways: Inflammation, DNA repair, Metabolism, Neurocognitive, and TERT, in 233 newly diagnosed glioma patients with neurocognitive evaluations before surgical resection. Five neuropsychological tests that measured memory (Hopkins Verbal Learning Test – Revised [HVLT-R]), processing speed (Trail Making Test A [TMTA]), and executive function (Controlled Oral Word Association [COWA], and Trail Making Test B (TMTB]) were examined. RESULTS: Nineteen SNPs were associated with TMTA, 12 SNPs with TMTB, two SNPs (MCPH1 rs6999296 and TANK rs270952) were associated with COWA, and one SNP (RAD51L1 rs9323505) was associated with HVLT-R Total Recall (FDR ≤ 0.05). For TMTA, the strongest signals were in IRS1 rs6725330 in the inflammation pathway (P = 2.59E-10; P adjusted = 1.21E-06), ERCC4 rs1573638 in DNA repair pathway (P = 3.46E-07; P adjusted = 0.00036), and ABCC1 rs8187858 in metabolism pathway (P = 6.63E-07; P adjusted = 0.0001). For TMTB, the strongest associations were in NOS1 rs11611788 in inflammation pathway (P = 1.85E-8; P adjusted = 8.63E-05), POLE rs5744761 in DNA repair pathway (P = 6.06E-07; P adjusted = 0.0013), and IL16 rs1912124 in inflammation pathway (P = 6.06E-07; P adjusted = 0.0014). Joint effect analysis found significant gene-dosage effects for TMTA (P trend = 9.46e -16) and TMTB (P trend =6.69e-15). CONCLUSION: Genetic polymorphisms in the Inflammation, DNA repair, Metabolism, Neurocognitive, and TERT pathways are associated with neurocognitive impairment in glioma patients and may affect clinical outcomes.

Regional brain glucose metabolism and neurocognitive function in adult survivors of childhood cancer treated with cranial radiation.

The objective of this study was to examine associations between regional brain metabolism, as measured by (18)F-FDG PET, and neurocognitive outcomes in adult survivors of childhood acute lymphoblastic leukemia (ALL) treated with cranial radiation. Thirty-eight adult survivors of ALL were randomly selected from a large cohort treated with cranial radiation therapy (19 with 18 Gy and 19 with 24 Gy of exposure). At a mean age of 26.4 (range, 22.3-37.4) years, and 23.5 (range, 20.4-32.8) years since diagnosis, patients underwent comprehensive neurocognitive evaluations and brain (18)F-FDG PET imaging during a resting condition. (18)F-FDG PET images were analyzed stereotactically, and pixel values were normalized to global activity. Predefined region-of-interest and voxel-based correlation analyses were performed. Compared with national norms, survivors demonstrated lower vocabulary (P < 0.001), reading (P < 0.001), mathematics (P < 0.001), working memory (P < 0.001), oral naming speed (P < 0.001), and cognitive flexibility (P < 0.001). Metabolic activity was higher in basal gangliar structures for those treated with 24 Gy of cranial radiation therapy (P = 0.04). Metabolic activity was positively correlated with oral naming speed in both lateral frontal lobes (ρ = 0.48 and 0.47 for right and left frontal regions, respectively, P < 0.01) and negatively correlated with cognitive flexibility in the sections of the basal ganglia (P < 0.01 for both caudate and putamen). Neurocognitive impairment in long-term survivors of ALL treated with cranial radiation appears to be associated with increased metabolic activity in frontal cerebral cortical and subcortical regions in the basal ganglia, suggesting decreased efficiency of the frontostriatal brain circuit.

Neurocognitive Evaluation of Long Term Survivor’s Patients with AT/RT

Because AT/RT is a disease of early infancy associated with grim prognosis, very little attention has been placed to date on long term outcome, especially neurocognitive outcome. With the new era of multimodality therapy, some patients are now long term survivors. We reviewed our institutional experience of such patients to describe their neurocognitive status. From the 24 patients diagnosed between 1995 and 2010, 7 were long term survivors and 6 had at least one neurocognitive evaluation. Median age at diagnosis was 28 months (range 11.2-43.3). Three tumors were infratentorial. Four patients underwent a GTR and 2 were metastatic. All patients received postoperative high dose chemotherapy (3 cycles of CB/Thiotepa). Five patients received intrathecal chemotherapy. Only one patient received radiation (focal). Median age at time of neurocognitive assessment was 7.1 years (3.3-9.2). Full Scale Intellectual Quotient (FSIQ) ranged from 60 to 119 (median=71). Simple expressive and receptive language appeared relatively preserved (low average to superior). Two most recently diagnosed (2009-2010) patients assessed at 1.6 and 2.6 years from diagnosis presented with average to high average scores for FSIQ, academic and visual spatial skills, visual and verbal memory. Four other diagnosed earlier (2004, 2005, 2007) tested at a median time of 5 years (3.3-8.3) post-diagnosis had a FSIQ ranging from 60 to 71(median=68). Approximately 50% of their scores were in the impaired range. Whether these findings suggest further decline overtime or reflect an improvement in overall management of the recently diagnosed patients remain unclear. Nevertheless this cohort of infants appears significantly impaired at school age despite the absence of systematic radiotherapy. Larger series focusing on neurocognition are definitely needed before embracing adjuvant radiotherapy as a standard of care.

Multiple prior concussions are associated with symptoms in high school athletes.

ObjectivesThe purpose of this study was to evaluate the association of prior concussion on baseline computerized neurocognitive testing in a large cohort of high school athletes.MethodsThis is a retrospective cohort study of student athletes from 49 Maine High Schools in 2010 who underwent baseline computerized neurocognitive evaluation with Immediate Post-Concussion Assessment and Cognitive Testing (ImPACT®). As part of the ImPACT®, subjects reported a prior history of concussion as well as demographic information and a symptom questionnaire. We used linear regression to evaluate the association of prior concussion with baseline: (1) ImPACT® composite scores; and (2) symptom scores.ResultsSix thousand seventy-five subjects were included in the study, of whom 57% were boys. The majority of student athletes (85.3%) reported no prior history of concussion while 4.6% reported having sustained two or more prior concussions. On simple linear regression, increasing number of concussions was related to worse performance in verbal memory (P = 0.039) and greater symptoms scores (P < 0.001). On multivariate modeling, only the association with baseline symptoms remained (P < 0.001). Other factors associated with baseline symptom reporting in the multivariate model included mental health history, headache/migraine history, gender, developmental and/or learning problems, and number of prior concussions.InterpretationIn this large-scale, retrospective survey study, history of multiple prior concussions was associated with higher symptom burden but not baseline computerized neurocognitive testing. The association between baseline symptom reporting and clinical and demographic factors was greater than the association with a history of multiple concussions.