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impairment of nonverbal recognition in alzheimer disease: a pet o-15 study.
(PDF Only) - Anderson, K, Brickman, A, Flynn, J, Scarmeas, N, Van Heertum, R, Sackeim, H, Marder, K, MD, MPH, Bell, K, Moeller, J, Stern, Y.
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Objective: To characterize deficits in nonverbal recognition memory and functional brain changes associated with these deficits in Alzheimer disease (AD).Methods: Using O-15 PET, we studied 11 patients with AD and 17 cognitively intact elders during the combined encoding and retrieval periods of a nonverbal recognition task. Both task conditions involved recognition of line drawings of abstract shapes. In both conditions, subjects were first presented a list of shapes as study items, and then a list as test items, containing items from the study list and foils. In the titrated demand condition, the shape study list size (SLS) was adjusted prior to imaging so that each subject performed at approximately 75% recognition accuracy; difficulty during PET scanning in this condition was approximately matched across subjects. A control task was used in which SLS = 1 shape.Results: During performance of the titrated demand condition, SLS averaged 4.55 (+/-1.86) shapes for patients with AD and 7.53 (+/-4.81) for healthy elderly subjects (p = 0.031). However, both groups of subjects were closely matched on performance in the titrated demand condition during PET scanning with 72.17% (+/-7.98%) correct for patients with AD and 72.25% (+/-7.03%) for elders (p = 0.979). PET results demonstrated that patients with AD showed greater mean differences between the titrated demand condition and control in areas including the left fusiform and inferior frontal regions (Brodmann areas 19 and 45).Conclusions: Relative fusiform and inferior frontal differences may reflect the Alzheimer disease (AD) patients' compensatory engagement of alternate brain regions. The strategy used by patients with AD is likely to be a general mechanism of compensation, rather than task-specific.(C)2007AAN Enterprises, Inc.
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congenital neuromuscular disease with uniform type 1 fiber and ryr1 mutation.
(PDF Only) - Sato, I, Wu, S, Ibarra, M, MD, PhD, Hayashi, Y, MD, PhD, Fujita, H, Tojo, M, Oh, S, Nonaka, I, MD, PhD, Noguchi, S, Nishino, I, MD, PhD.
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Background: Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) is a rare form of congenital myopathy, which is pathologically diagnosed by the presence of more than 99% of type 1 fiber, with no specific structural changes. Its pathogenic mechanism is still unknown. We recently reported that almost all patients with central core disease (CCD) with ryanodine receptor 1 gene (RYR1) mutations in the C-terminal domain had type 1 fibers, nearly exclusively, in addition to typical central cores.Objective: To investigate whether CNMDU1 is associated with RYR1 mutation.Methods: We studied 10 unrelated Japanese patients who were diagnosed to have CNMDU1 based on clinical features and muscle pathology showing more than 99% type 1 muscle fibers. We extracted genomic DNA from frozen muscles and directly sequenced all 106 exons and their flanking intron-exon boundaries of RYR1.Results: Four of 10 patients had a heterozygous mutation, three missense and one deletion, all in the C-terminal domain of RYR1. Two missense mutations were previously reported in CCD patients. Clinically, patients with mutations in RYR1 showed milder phenotype compared with those without mutations.Conclusion: Congenital neuromuscular disease with uniform type 1 fiber (CNMDU1) in 40% of patients is associated with mutations in the C-terminal domain of RYR1, suggesting that CNMDU1 is allelic to central core disease at least in some patients.(C)2007AAN Enterprises, Inc.
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significant association between leukoaraiosis and metabolic syndrome in healthy subjects.
(PDF Only) - Park, K, Yasuda, N, Toyonaga, S, Yamada, S, Nakabayashi, H, Nakasato, M, Nakagomi, T, Tsubosaki, E, Shimizu, K.
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Objective: To investigate the relationship between leukoaraiosis (LA), which has been considered as an intermediate substitute of ischemic brain damages, and metabolic syndrome (MetS), which attracts attention as a risk factor for cerebrovascular diseases, in healthy subjects derived from various age groups.Methods: We studied 1,030 healthy persons at ages between 28 and 78 years (mean, 52.7 years) with no history of stroke who visited a health care facility for routine health checkups. MetS was defined using the criteria of the National Cholesterol Education Program Adult Treatment Panel III. LA was assessed using the rating scale of the Atherosclerosis Risk in Communities study on MRI. Logistic regression analysis was performed to examine associations between LA and MetS.Results: A total of 296 (28.8%) subjects had LA on MRI. MetS was significantly associated with the presence of LA (adjusted OR, 3.33; 95% CI, 2.30, 4.84). The association was constant across grades of LA; the adjusted OR was 3.41 (95% CI, 2.30, 5.06) for minimal LA and 3.07 (95% CI, 1.75, 5.38) for LA combining mild, moderate, and severe grades. As for MetS components, elevated blood pressure (adjusted OR, 2.16; 95% CI, 1.57, 2.99), impaired fasting glucose (adjusted OR, 1.64; 95% CI, 1.13, 2.39), and hypertriglyceridemia (adjusted OR, 1.56; 95% CI, 1.08, 2.28) were independently associated with all grades of LA.Conclusions: Metabolic syndrome (MetS) was significantly associated with every grade of leukoaraiosis (LA), including the minimal LA. Impaired fasting glucose and hypertriglyceridemia were associated with LA independently of elevated blood pressure. MetS can play an important role in identifying healthy subjects who have an increased risk of LA.(C)2007AAN Enterprises, Inc.
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clinicopathologic correlation in pgrn mutations.
(PDF Only) - Davion, S, Johnson, N, Weintraub, S, Mesulam, M-M, Engberg, A, Mishra, M, Baker, M, Adamson, J, BS, MBA, Hutton, M, Rademakers, R, Bigio, E.
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Background: Frontotemporal dementia (FTD) has been linked to the microtubule associated protein tau (MAPT) gene region of chromosome 17. However, many chromosome-17 linked FTLDs do not have MAPT mutations or tau protein deposits, but have ubiquitin positive, tau and alpha-synuclein negative inclusions. Mutations in the progranulin (PGRN) gene, located 1.7 Mb from MAPT at 17q21.31, were recently discovered in some of these individuals. The pathologic phenotype in all cases has thus far included ubiquitinated neuronal intranuclear inclusions (NIIs) and neuronal cytoplasmic inclusions (NCIs).Methods: PGRN mutation analysis was performed in 12 individuals. Informed consent was obtained from next of kin under an IRB-approved protocol. We compared clinical and pathologic findings in those cases with and without PGRN mutations.Results: PGRN mutations were found in four patients, two with clinical FTD and a positive family history, and two with clinical primary progressive aphasia (PPA), one with and one without a family history. All four cases with, and five of eight cases without, PGRN mutations had ubiquitinated NCIs and NIIs. Brains of individuals with PGRN mutations are associated with more frequent frontal NCIs and dystrophic neurites, less frequent dentate gyrus NCIs, and more frequent striatal NIIs than FTLD-U cases without PGRN mutations.Conclusions: PGRN mutations at 17q21 may occur in apparently sporadic frontotemporal lobar dementia with ubiquitinated inclusions cases and in cases presenting with either primary progressive aphasia or the behavioral variant of frontotemporal dementia. Some cases without PGRN mutations also have ubiquitinated neuronal intranuclear inclusions. Clinicopathologic differences are observed among individuals with and without PGRN mutations.(C)2007AAN Enterprises, Inc.
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practice parameter: treatment of nervous system lyme disease (an evidence-based review): report of the quality standards subcommittee of the american academy of neurology.
(PDF Only) - Halperin, J, Shapiro, E, Logigian, E, Belman, A, Dotevall, L, Wormser, G, Krupp, L, Gronseth, G, Bever, C.
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Objective: To provide evidence-based recommendations on the treatment of nervous system Lyme disease and post-Lyme syndrome. Three questions were addressed: 1) Which antimicrobial agents are effective? 2) Are different regimens preferred for different manifestations of nervous system Lyme disease? 3) What duration of therapy is needed?Methods: The authors analyzed published studies (1983-2003) using a structured review process to classify the evidence related to the questions posed.Results: The panel reviewed 353 abstracts which yielded 112 potentially relevant articles that were reviewed, from which 37 articles were identified that were included in the analysis.Conclusions: There are sufficient data to conclude that, in both adults and children, this nervous system infection responds well to penicillin, ceftriaxone, cefotaxime, and doxycycline (Level B recommendation). Although most studies have used parenteral regimens for neuroborreliosis, several European studies support use of oral doxycycline in adults with meningitis, cranial neuritis, and radiculitis (Level B), reserving parenteral regimens for patients with parenchymal CNS involvement, other severe neurologic symptomatology, or failure to respond to oral regimens. The number of children (>=8 years of age) enrolled in rigorous studies of oral vs parenteral regimens has been smaller, making conclusions less statistically compelling. However, all available data indicate results are comparable to those observed in adults. In contrast, there is no compelling evidence that prolonged treatment with antibiotics has any beneficial effect in post-Lyme syndrome (Level A).(C)2007AAN Enterprises, Inc.
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phenotypic clustering of lamin a/c mutations in neuromuscular patients.
(PDF Only) - Benedetti, S, Menditto, I, Degano, M, Rodolico, C, Merlini, L, D'Amico, A, Palmucci, L, Berardinelli, A, Pegoraro, E, Trevisan, C, Morandi, L, Moroni, I, Galluzzi, G, Bertini, E, Toscano, A, Olive, M, Bonne, G, Mari, F, Caldara, R, Fazio, R, Mammi, I, Carrera, P, Toniolo, D, Comi, G, Quattrini, A, Ferrari, M, Previtali, S.
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Background: Mutations in the LMNA gene, encoding human lamin A/C, have been associated with an increasing number of disorders often involving skeletal and cardiac muscle, but no clear genotype/phenotype correlation could be established to date.Methods: We analyzed the LMNA gene in a large cohort of patients mainly affected by neuromuscular or cardiac disease and clustered mutated patients in two groups to unravel possible correlations.Results: We identified 28 variants, 9 of which reported for the first time. The two groups of patients were characterized by clinical and genetic differences: 1) patients with childhood onset displayed skeletal muscle involvement with predominant scapuloperoneal and facial weakness associated with missense mutations; 2) patients with adult onset mainly showed cardiac disorders or myopathy with limb girdle distribution, often associated with frameshift mutations presumably leading to a truncated protein.Conclusions: Our findings, supported by meta-analysis of previous literature, suggest the presence of two different pathogenetic mechanisms: late onset phenotypes may arise through loss of function secondary to haploinsufficiency, while dominant negative or toxic gain of function mechanisms may explain the severity of early phenotypes. This model of patient stratification may help patient management and facilitate future studies aimed at deciphering lamin A/C pathogenesis.(C)2007AAN Enterprises, Inc.
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prednisolone does not reduce withdrawal headache: a randomized, double-blind study.
(PDF Only) - Boe, Magne, Mygland, Ase, MD, PhD, Salvesen, Rolf, MD, PhD.
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Introduction: Medication overuse headache is a condition where abrupt drug withdrawal is considered the treatment of choice.Objective: To study whether prednisolone given orally the first 6 days after medication withdrawal reduces headache intensity during the same period.Methods: From August 2003 through November 2005, we included patients aged 18 to 70 years with probable medication overuse headache. The study was randomized, double-blind, and placebo controlled. The patients were hospitalized for 3 days to start medication withdrawal. They were randomly assigned to receive prednisolone 60 mg on days 1 and 2, 40 mg on days 3 and 4, and 20 mg on days 5 and 6 (Group A) or placebo tablets for 6 days (Group B). Headache intensity was recorded in a diary for a month before withdrawal (baseline) and throughout the study period of 28 days. The primary endpoint was a calculated mean headache (MH), based on number of days with headache and mean intensity the first 6 days after withdrawal.Results: We included 26 men and 74 women. Sixty-five had migraine, 13 had tension-type headache, and 22 had both migraine and tension-type headache. Baseline headache days were 25.4 (CI 24.3 to 26.4). Baseline MH was 1.6 (CI 1.41 to 1.69). Fifty-one received Regimen A, and 49 received Regimen B. Baseline features were similar. During the first 6 days after withdrawal, headache was similar in Groups A and B (MH 1.48 [CI 1.28 to 1.68] vs 1.61 [CI 1.41 to 1.82], p = 0.34).Conclusion: Prednisolone has no effect on withdrawal headache in unselected patients with chronic daily headache and medication overuse.(C)2007AAN Enterprises, Inc.
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psychological or physiological: why are tetraplegic patients content?
(PDF Only) - Abrantes-Pais, Fatima, Friedman, Joyce, Lovallo, William, Ross, Elliott.
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Objective: To assess the effects of spinal cord injury (SCI) on perceived health-related quality of life (QOL).Background: SCI is physically disabling, socially handicapping, and romantically limiting. Nevertheless, little is known about post-SCI neurocognitive and psychosocial life. Better understanding of the cognitive and emotional worlds of SCI patients is essential to better address and meet their needs and expectations.Methods: Twenty subjects with high-cord (T6 and above) complete (American Spinal Injury Association [ASIA] A) SCI (High SCI) were compared with 10 subjects with low-cord (T7 and below) ASIA A SCI (Low SCI) and with 11 Able-Bodied control subjects. Satisfaction with Life and Short Form-36 instruments were used to assess physical and emotional aspects of QOL. Analyses of variance were used to assess potential differences across groups.Results: Overall, satisfaction with life was the same among the groups. Expectedly, High SCI and Low SCI subjects reported lower physical functioning than Able-Bodied subjects (p < 0.0001). But, oddly, there were no differences in perceived physical role, physical health, or social functioning. Furthermore, High SCI subjects reported better perceived mental health than Able-Bodied control subjects (p = 0.004) and a trend over Low SCI subjects (p = 0.06), better perceived emotional role in society (p = 0.02), and greater vitality (p = 0.01) than Low SCI subjects and Able-Bodied subjects.Conclusions: Despite severe physical impairment and disability and frequent medical complications, subjects with complete spinal cord injury at high anatomic levels report better than average quality of life, being overall content. Reasons for these findings are unclear. Psychological adaptive reactions are likely, but the possible role of physiologic and neurocognitive changes needs further exploration.(C)2007AAN Enterprises, Inc.
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apoe [varepsilon]4 allele is associated with cognitive impairment in patients with multiple sclerosis.
(PDF Only) - Shi, J, MD, PhD, Zhao, C, MD, PhD, Vollmer, T, Tyry, T, Kuniyoshi, S, MD, PhD.
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Background: The role of apolipoprotein E (APOE) polymorphism has been well recognized in other cognitive neurodegenerative disorders, such as Alzheimer disease. Its role in multiple sclerosis (MS) is less clear, though studies indicate that 40% to 60% of patients with MS have evidence of cognitive impairment.Objective: To determine whether there is an association between APOE [varepsilon]4 and cognitive deficits in MS.Methods: We performed a standardized battery of neuropsychological tests investigating the four cognitive domains commonly impaired in MS and assessed the association of the presence of APOE [varepsilon]4 with cognition in MS.Results: A strong association was found between the presence of APOE [varepsilon]4 and cognitive deficits in patients with MS, particularly in the domains of learning and memory. This association was strongest in our youngest cohort (age 31 to 40) of patients with MS.Conclusions: APOE [varepsilon]4 is significantly associated with cognitive impairment in patients with multiple sclerosis (MS). However, the modest effects do not justify APOE genotyping of patients with MS in clinical practice.(C)2007AAN Enterprises, Inc.
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als phenotypes with mutations in chmp2b (charged multivesicular body protein 2b).
(PDF Only) - Parkinson, N, Ince, P, Smith, M, Highley, R, Skibinski, G, Andersen, P, Morrison, K, Pall, H, Hardiman, O, Collinge, J, Shaw, P, Fisher, E.
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Mutation in the CHMP2B gene has been implicated in frontotemporal dementia. The authors screened CHMP2B in patients with ALS and several cohorts of control samples. They identified mutations (Q206H; I29V) in two patients with non-SOD1 ALS. Neuropathology of the Q206H case showed lower motor neuron predominant disease with ubiquitylated inclusions in motor neurons. Antibodies to p62 (sequestosome 1) showed novel oligodendroglial inclusions in the motor cortex.(C)2007AAN Enterprises, Inc.
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