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Neurology Journal
Neurology® is the official scientific journal of the American Academy of Neurology. As the leading clinical neurology journal worldwide, Neurology is directed to physicians concerned with diseases and conditions of the nervous system.
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| This week in Neurology(R) |
this week in neurology(r): highlights of the december 15 issue.
Pages: 2051
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| Editorials |
apoe [epsilon]4 and bapineuzumab: infusing pharmacogenomics into alzheimer disease therapeutics.
- Kaufer, Dan, Gandy, Sam, MD, PhD. Pages: 2052-2053
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early intervention in alzheimer disease: the importance of apoe4 plus family history.
- Corder, Elizabeth, Caskey, John. Pages: 2054-2055
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equal care for the elderly with low-grade gliomas?.
- Pruitt, Amy, Henson, John, MD, FAAN. Pages: 2056-2057
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the quest for the "holy grail" of ischemic stroke cytoprotection: statins may not be the answer.
- Goldstein, Larry, Suarez, Jose. Pages: 2058-2059
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| In Memoriam |
geoffrey dean, md (1918-2009).
- Hutchinson, Michael. Pages: 2060
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| Articles |
a phase 2 multiple ascending dose trial of bapineuzumab in mild to moderate alzheimer disease symbol .
- Salloway, S, MD, MS, Sperling, R, MD, MMSc, Gilman, S, MD, FRCP, Fox, N, MD, FRCP, Blennow, K, Raskind, M, Sabbagh, M, Honig, L, MD, PhD, Doody, R, MD, PhD, van Dyck, C, Mulnard, R, DNSc, FAAN, Barakos, J, Gregg, K, Liu, E, Lieberburg, I, MD, PhD, Schenk, D, Black, R, Grundman, M, MD, MPH. Pages: 2061-2070
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Show/Hide Abstract
Background: Bapineuzumab, a humanized anti-amyloid-beta (A[beta]) monoclonal antibody for the potential treatment of Alzheimer disease (AD), was evaluated in a multiple ascending dose, safety, and efficacy study in mild to moderate AD.Methods: The study enrolled 234 patients, randomly assigned to IV bapineuzumab or placebo in 4 dose cohorts (0.15, 0.5, 1.0, or 2.0 mg/kg). Patients received 6 infusions, 13 weeks apart, with final assessments at week 78. The prespecified primary efficacy analysis in the modified intent-to-treat population assumed linear decline and compared treatment differences within dose cohorts on the Alzheimer's Disease Assessment Scale-Cognitive and Disability Assessment for Dementia. Exploratory analyses combined dose cohorts and did not assume a specific pattern of decline.Results: No significant differences were found in the primary efficacy analysis. Exploratory analyses showed potential treatment differences (p < 0.05, unadjusted for multiple comparisons) on cognitive and functional endpoints in study "completers" and APOE [epsilon]4 noncarriers. Reversible vasogenic edema, detected on brain MRI in 12/124 (9.7%) bapineuzumab-treated patients, was more frequent in higher dose groups and APOE [epsilon]4 carriers. Six vasogenic edema patients were asymptomatic; 6 experienced transient symptoms.Conclusions: Primary efficacy outcomes in this phase 2 trial were not significant. Potential treatment differences in the exploratory analyses support further investigation of bapineuzumab in phase 3 with special attention to APOE [epsilon]4 carrier status.Classification of evidence: Due to varying doses and a lack of statistical precision, this Class II ascending dose trial provides insufficient evidence to support or refute a benefit of bapineuzumab.(C)2009AAN Enterprises, Inc.
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association of parental dementia with cognitive and brain mri measures in middle-aged adults .
- Debette, S, Wolf, P, Beiser, A, Au, R, Himali, J, Pikula, A, Auerbach, S, DeCarli, C, Seshadri, S. Pages: 2071-2078
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Show/Hide Abstract
Objectives: Studies of autosomal dominant Alzheimer disease (AD) have shown structural and cognitive changes in mutation carriers decades prior to clinical disease. Whether such changes are detectable in offspring of persons with sporadic dementia remains unknown. We related prospectively verified parental dementia to brain MRI and cognitive testing in the offspring, within a 2-generational community-based cohort.Methods: A total of 717 Framingham offspring (mean age: 59 +/- 8 years) were studied. In multivariate analyses, we compared offspring with and without verified parental dementia (and AD) for 1) performance on tests of memory, abstract reasoning, and cognitive flexibility, and 2) volumetric brain MRI measures of total cerebral brain volume (TCBV), hippocampal volume (HV), and white matter hyperintensity volume (WMHV), assessed cross-sectionally and longitudinally.Results: When testing the association of parental dementia and AD with baseline cognitive performance, we observed an interaction of parental dementia and AD with APOE [epsilon]4 status (p < 0.002). In APOE [epsilon]4 carriers only (n = 165), parental dementia was associated with poorer scores on tests of verbal memory (beta = -1.81 +/- 0.53, p < 0.001) and visuospatial memory (beta = -1.73 +/- 0.47, p < 0.001). These associations were stronger for parental AD (beta = -1.97 +/- 0.52, p < 0.001, beta = -1.95 +/- 0.48, p < 0.001), equivalent to 14-16 years of brain aging. Among APOE [epsilon]4 carriers, offspring of participants with dementia were also more likely to show an annual decline in TCBV in the top quartile (odds ratio = 4.67 [1.26-17.30], p = 0.02). Regardless of APOE [epsilon]4 status, participants with parental dementia were more likely to be in the highest quartile of decline in executive function test scores (odds ratio = 1.61 [1.02-2.53], p = 0.04).Conclusions: Among middle-aged carriers of the APOE [epsilon]4 allele, parental dementia and Alzheimer disease were associated with poorer verbal and visuospatial memory and a higher rate of global brain atrophy.(C)2009AAN Enterprises, Inc.
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differential association of [11c]pib and [18f]fddnp binding with cognitive impairment.
- Tolboom, N, van der Flier, W, Yaqub, M, Koene, T, Boellaard, R, Windhorst, A, Scheltens, P, MD, PhD, Lammertsma, A, van Berckel, B, MD, PhD. Pages: 2079-2085
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Show/Hide Abstract
Objective: To evaluate associations of [11C]Pittsburgh compound B (PIB) and [18F]FDDNP with impairment in specific cognitive domains over the broader spectrum comprising cognitively normal elderly subjects, patients with mild cognitive impairment (MCI), and patients with Alzheimer disease (AD).Methods: Twelve patients with AD, 13 patients with MCI, and 15 cognitively normal elderly subjects were included. Paired [11C]PIB and [18F]FDDNP PET scans were performed in all subjects. Binding potential (BPND) was calculated using parametric images of BPND for global, frontal, parietal, and temporal cortex; medial temporal lobe; and posterior cingulate. Cognitive functions were assessed using a battery of neuropsychological tests. Linear regression analyses were used to assess associations of [11C]PIB and [18F]FDDNP binding with cognitive measures.Results: Adjusted for age, sex, and [18F]FDDNP binding, higher global [11C]PIB binding was associated with lower scores on the Mini-Mental State Examination, immediate and delayed recall of the Rey Auditory Verbal Learning Task (RAVLT), Visual Association Task, and Trail Making Test part B. Conversely, higher [18F]FDDNP binding was independently associated with lower scores on immediate recall of the RAVLT. After additional adjustment for diagnosis, higher [11C]PIB binding remained independently associated with delayed recall (standardized [beta] = -0.39, p = 0.01), whereas higher [18F]FDDNP binding remained independently associated with immediate recall (standardized [beta] = -0.32, p = 0.03). When regional binding was assessed using stepwise models, both increased frontal [11C]PIB and temporal [18F]FDDNP binding were associated with memory, whereas increased parietal [11C]PIB binding was associated with nonmemory functions.Conclusion: Increased [18F]FDDNP binding is specifically associated with impairment of episodic memory, whereas increased [11C]Pittsburgh compound B binding is associated with impairment in a broader range of cognitive functions.(C)2009AAN Enterprises, Inc.
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medical decision-making capacity in patients with malignant glioma.
- Triebel, Kristen, Martin, Roy, Nabors, Louis, Marson, Daniel, JD, PhD. Pages: 2086-2092
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Show/Hide Abstract
Objective: Patients with malignant glioma (MG) must make ongoing medical treatment decisions concerning a progressive disease that erodes cognition. We prospectively assessed medical decision-making capacity (MDC) in patients with MG using a standardized psychometric instrument.Methods: Participants were 22 healthy controls and 26 patients with histologically verified MG. Group performance was compared on the Capacity to Consent to Treatment Instrument (CCTI), a psychometric measure of MDC incorporating 4 standards (choice, understanding, reasoning, and appreciation), and on neuropsychological and demographic variables. Capacity outcomes (capable, marginally capable, or incapable) on the CCTI standards were identified for the MG group. Within the MG group, scores on demographic, clinical, and neuropsychological variables were correlated with scores on each CCTI standard, and significant bivariate correlates were subsequently entered into exploratory stepwise regression analyses to identify multivariate cognitive predictors of the CCTI standards.Results: Patients with MG performed significantly below controls on consent standards of understanding and reasoning, and showed a trend on appreciation. Relative to controls, more than 50% of the patients with MG demonstrated capacity compromise (marginally capable or incapable outcomes) in MDC. In the MG group, cognitive measures of verbal acquisition/recall and, to a lesser extent, semantic fluency predicted performance on the appreciation, reasoning, and understanding standards. Karnofsky score was also associated with CCTI performance.Conclusions: Soon after diagnosis, patients with malignant glioma (MG) have impaired capacity to make treatment decisions relative to controls. Medical decision-making capacity (MDC) impairment in MG seems to be primarily related to the effects of short-term verbal memory deficits. Ongoing assessment of MDC in patients with MG is strongly recommended.(C)2009AAN Enterprises, Inc.
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supratentorial low-grade gliomas in older patients.
- Kaloshi, G, Psimaras, D, Mokhtari, K, Dehais, C, Houillier, C, Marie, Y, Laigle-Donadey, F, Taillibert, S, Guillevin, R, Martin-Duverneuil, N, Sanson, M, MD, PhD, Hoang-Xuan, K, MD, PhD, Delattre, J. Pages: 2093-2098
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Show/Hide Abstract
Background: Low-grade gliomas (LGG) are thought to be very rare in elderly patients (>60 years) and have not been thoroughly studied.Methods: A series of 62 elderly (>=60 years of age) LGG patients were identified in a department database collecting information on pathologically identified adult supratentorial LGG. The clinical, radiologic, pathologic, and therapeutic data of these patients were analyzed and compared to those of 704 younger LGG patients (<60 years).Results: Comparisons between older and younger groups showed that elderly patients more often presented with a clinical deficit (p < 0.0001), a lower Karnofsky performance status (p = 0.0002), a larger tumor on MRI (p = 0.03), and a lower rate of tumor resection (p < 0.0001). Chemotherapy was more often used as first line treatment (p = 0.001). Among the patients who died of progressive disease, 55% of the elderly patients had not received radiotherapy compared to 11% in the younger group (p < 0.0001). Survival was shorter in older patients (p < 0.0001), with a 5-year survival rate of 40%. An astrocytic phenotype (p = 0.0097), increasing age (p = 0.0049), and a tumor crossing the midline (p = 0.028) were negative prognostic factors in the older group.Conclusion: We found that 8% of low-grade gliomas (LGG) occur in older patients (>=60 years of age). The clinical-radiologic picture of LGG in the elderly population differs from younger patients. Although long-term survival occurs, the course is generally more severe because elderly patients accumulate negative prognostic factors and because they are probably undertreated.(C)2009AAN Enterprises, Inc.
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statin use and neurologic morbidity after coronary artery bypass grafting symbol: a cohort study.
- Koenig, M, Grega, M, Bailey, M, Pham, L, Zeger, S, Baumgartner, W, McKhann, G. Pages: 2099-2106
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Show/Hide Abstract
Background: Statin use before surgery has been associated with reduced morbidity and mortality after vascular surgery. The effect of preoperative statin use on stroke and encephalopathy after coronary artery bypass grafting (CABG) is unclear.Methods: A post hoc analysis was undertaken of a prospectively collected cohort of isolated CABG patients over a 10-year period at a single institution. Primary outcomes were stroke and encephalopathy. Univariable analyses identified risk factors for statin use, which were applied to a propensity score model using logistic regression and patients were divided into quintiles of propensity for statin use. Controlling for propensity score quintile, the odds ratio (OR) of combined stroke and encephalopathy (primary endpoint), cardiovascular mortality, myocardial infarction, and length of stay were compared between statin users and nonusers.Results: There were 5,121 CABG patients, of whom 2,788 (54%) were taking statin medications preoperatively. Stroke occurred in 166 (3.2%) and encephalopathy in 438 (8.6%), contributing to 604 patients (11.8%) who met the primary endpoint. The unadjusted OR of stroke/encephalopathy in statin users was 1.053 (95% confidence interval [CI] 0.888-1.248, p = 0.582). Adjustment based on propensity score resulted in balance of stroke risk factors among quintiles. The propensity score-adjusted OR of stroke/encephalopathy in statin users was 0.958 (95% CI 0.784-1.170, p = 0.674). There were no significant differences in cardiovascular mortality, myocardial infarction, or length of stay between statin users and otherwise similar nonusers.Conclusions: In this large data cohort study, preoperative statin use was not associated with a decreased incidence of stroke and encephalopathy after coronary artery bypass grafting.(C)2009AAN Enterprises, Inc.
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hla-drb1 and month of birth in multiple sclerosis.
- Ramagopalan, S, Link, J, Byrnes, J, Dyment, D, MD, DPhil, Giovannoni, G, MD, PhD, Hintzen, R, MD, PhD, Sundqvist, E, Kockum, I, Smestad, C, Lie, B, Harbo, H, Padyukov, L, Alfredsson, L, Olsson, T, MD, PhD, Sadovnick, A, Hillert, J, MD, PhD, Ebers, G, MD, FMedSci. Pages: 2107-2111
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Show/Hide Abstract
Background: Multiple sclerosis (MS) displays a month-of-birth effect, with an excess of individuals being born in the spring and a deficit in the winter. This effect was shown to be more pronounced in familial cases of MS. In the present study, we investigated whether this month-of-birth association has any relation to the principal MS susceptibility gene, HLA-DRB1.Methods: A total of 4,834 patients with MS, 4,056 controls, and 659 unaffected siblings from Canada, Sweden, and Norway were genotyped for the HLA-DRB1 gene. Month of birth was compared for patients, controls, and unaffected siblings with and without the MS risk allele HLA-DRB1*15.Results: Significantly fewer patients with MS carrying the HLA-DRB1*15 risk allele were born in November compared with patients not carrying this allele (p = 0.02). Additionally, patients with MS carrying HLA-DRB1*15 had a higher number of April births compared with patients with MS not carrying HLA-DRB1*15 (p = 0.004). These differences were not present in controls or unaffected siblings.Conclusions: Month of birth, HLA-DRB1 genotype, and risk of multiple sclerosis are associated. The interaction of a seasonal risk factor with loci at or near HLA-DRB1 during gestation or shortly after birth is implicated.(C)2009AAN Enterprises, Inc.
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road safety in drivers with parkinson disease.
- Uc, E, Rizzo, M, Johnson, A, Dastrup, E, Anderson, S, Dawson, J. Pages: 2112-2119
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Show/Hide Abstract
Objective: To assess road safety and its predictors in drivers with Parkinson disease (PD).Methods: Licensed, active drivers with PD (n = 84; age = 67.3 +/- 7.8, median Hoehn & Yahr stage II) and controls (n = 182; age = 67.6 +/- 7.5) underwent cognitive, visual, and motor tests, and drove a standardized route in urban and rural settings in an instrumented vehicle. Safety errors were judged and documented by a driving expert based on video data review.Results: Drivers with PD committed more total safety errors compared to controls (41.6 +/- 14.6 vs 32.9 +/- 12.3, p < 0.0001); 77.4% of drivers with PD committed more errors than the median total error count of the controls (medians: PD = 39.5, controls = 31.0). Lane violations were the most common error category in both groups. Group differences in some error categories became insignificant after results were adjusted for demographics and familiarity with the local driving environment. The PD group performed worse on tests of motor, cognitive, and visual abilities. Within the PD group, older age and worse performances on tests of visual acuity, contrast sensitivity, attention, visuospatial abilities, visual memory, and general cognition predicted error counts. Measures of visual processing speed and attention and far visual acuity were jointly predictive of error counts in a multivariate model.Conclusions: Overall, drivers with Parkinson disease (PD) had poorer road safety compared to controls, but there was considerable variability among the drivers with PD, and some performed normally. Familiarity with the driving environment was a mitigating factor against unsafe driving in PD. Impairments in visual perception and cognition were associated with road safety errors in drivers with PD.(C)2009AAN Enterprises, Inc.
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| Clinical/Scientific Notes |
characteristic brain mri appearance of erdheim-chester disease.
- Bianco, F, Iacovelli, E, Tinelli, E, Locuratolo, N, Pauri, F, Fattapposta, F. Pages: 2120-2122
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evolution of oculomotor and clinical findings in autopsy-proven richardson syndrome.
- Hardwick, A, Rucker, J, Cohen, M, Friedland, R, Gustaw-Rothenberg, K, Riley, D, Leigh, R. Pages: 2122-2124
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novel compound heterozygous als2 mutations cause juvenile amyotrophic lateral sclerosis in japan.
- Shirakawa, K, Suzuki, H, Ito, M, Kono, S, Uchiyama, T, Ohashi, T, Miyajima, H. Pages: 2124-2126
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intergenerational contraction of the ctg repeats in 2 families with myotonic dystrophy type 1.
- Puymirat, Jack, MD, PhD, Giguere, Yves, MD, PhD, Mathieu, Jean, MD, MSc, Bouchard, Jean-Pierre, MD, FRCPC. Pages: 2126-2127
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congenital null mutations of the folr1 gene: a progressive neurologic disease and its treatment.
- Cario, H, Bode, H, Debatin, K, Opladen, T, Schwarz, K. Pages: 2127-2129
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| Video NeuroImages |
stimulation of the parietal cortex affects reaching in a patient with epilepsy.
- Dijkerman, H, Meekes, J, Horst, A, Spetgens, W, de Haan, E, Leijten, F, MD, PhD. Pages: 2130
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| NeuroImages |
large choroid plexus teratoma: a rare cause of congenital hydrocephalus.
- Jain, Ashish, Dixit, Sudhir, Devgan, Veena. Pages: 2131
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| Resident & Fellow Section |
teaching neuroimages: molar tooth sign with hypotonia, ataxia, and nystagmus (joubert syndrome) and hypothyroidism.
- Graber, Jerome, MD, MPH, Lau, Heather, Sathe, Swati. Pages: e106
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| Correspondence |
stiff-person syndrome with amphiphysin antibodies: distinctive features of a rare disease.
- McKeon, Andrew, MB, MRCPI, Pittock, Sean, Lennon, Vanda, MD, PhD. Pages: 2132-2133
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the essential neurologic examination: what should medical students be taught?
- Meador, Kimford. Pages: 2133-2134
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| Correction |
practice parameter update: the care of the patient with amyotrophic lateral sclerosis: drug, nutritional, and respiratory therapies (an evidence-based review): report of the quality standards subcommittee of the american academy of neurology.
Pages: 2134
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| Departments |
calendar.
Pages: 2135
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| Future Issues |
in the next issue of neurology(r): volume 74, number 1, january 5, 2010.
Pages: A58
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