Neurology July 2009 Volume 73 Issue 4

Background: Previous modeling studies on treatment of unruptured intracranial aneurysms largely disregarded detailed data on treatment risks and omitted several factors that could influence cost-effectiveness. We performed a cost-effectiveness analysis of surgical and endovascular treatment of unruptured aneurysms for different rupture rates and life expectancies, and assessed the influence of excess mortality risks in these persons, de novo development of aneurysms, and utility of awareness of having an untreated aneurysm, and also identified important factors for which data are lacking.Methods: We used a Markov model to compare surgical, endovascular, and no treatment of unruptured intracranial aneurysms. Inputs for the model were taken mainly from meta-analyses. Direct medical costs were derived from Dutch cost studies and expressed in 2005 Euros. We performed sensitivity analyses to evaluate model robustness.Results: For 50-year-old patients, treatment of unruptured aneurysms is cost-effective for all rupture rate scenarios between 0.3% and 3.5%/year. In 70-year-old patients, treatment is not cost-effective in men with rupture rates <=1%/year and women with rupture rates <=0.5%/year. With lower utility of awareness of an untreated aneurysm, the cost-effectiveness of treatment strongly increased. The effect of excess mortality risks on the incremental cost-effectiveness ratios was modest. The risk of formation of new aneurysms had no relevant impact.Conclusions: Patients' life expectancy, risk of rupture, and utility of awareness of an untreated aneurysm mainly define cost-effectiveness. However, important uncertainties remain on the rupture risk according to size and location of the aneurysm and on the utility of awareness of untreated aneurysm. More data on these factors are needed to define and individualize cost-effectiveness analyses.(C)2009AAN Enterprises, Inc.

Objective: To characterize brain cholinergic deficits in Parkinson disease (PD), PD with dementia (PDD), and dementia with Lewy bodies (DLB).Methods: Participants included 18 patients with PD, 21 patients with PDD/DLB, and 26 healthy controls. The PD group consisted of nine patients with early PD, each with a disease duration of less than 3 years, five of whom were de novo PD patients, and nine patients with advanced PD, each with a disease duration greater than or equal to 3 years. The PDD/DLB group consisted of 10 patients with PDD and 11 patients with DLB. All subjects underwent PET scans with N-[11C]-methyl-4-piperidyl acetate to measure brain acetylcholinesterase (AChE) activity. Brain AChE activity levels were estimated voxel-by-voxel in a three-compartment analysis using the arterial input function, and compared among our subject groups through both voxel-based analysis using the statistical parametric mapping software SPM5 and volume-of-interest analysis.Results: Among patients with PD, AChE activity was significantly decreased in the cerebral cortex and especially in the medial occipital cortex (% reduction compared with the normal mean = -12%) (false discovery rate-corrected p value <0.01). Patients with PDD/DLB, however, had even lower AChE activity in the cerebral cortex (% reduction = -27%) (p < 0.01). There was no significant difference between early PD and advanced PD groups or between DLB and PDD groups in the amount by which regional AChE activity in the brain was reduced.Conclusions: Brain cholinergic dysfunction occurs in the cerebral cortex, especially in the medial occipital cortex. It begins in early Parkinson disease, and is more widespread and profound in both Parkinson disease with dementia and dementia with Lewy bodies.(C)2009AAN Enterprises, Inc.

Objective: To assess the correlations of both MRI and CSF biomarkers with clinical diagnosis and with cognitive performance in cognitively normal (CN) subjects and patients with amnestic mild cognitive impairment (aMCI) and Alzheimer disease (AD).Methods: This is a cross-sectional study with data from the Alzheimer's Disease Neuroimaging Initiative, which consists of CN subjects, subjects with aMCI, and subjects with AD with both CSF and MRI. Baseline CSF (t-tau, A[beta]1-42, and p-tau181P) and MRI scans were obtained in 399 subjects (109 CN, 192 aMCI, 98 AD). Structural Abnormality Index (STAND) scores, which reflect the degree of AD-like anatomic features on MRI, were computed for each subject.Results: We found no significant correlation between CSF biomarkers and cognitive scores in any of the 3 clinical groups individually. Conversely, STAND scores correlated with both Clinical Dementia Rating-sum of boxes and Mini-Mental State Examination in aMCI and AD (p <= 0.01). While STAND and all CSF biomarkers were predictors of clinical group membership (CN, aMCI, or AD) univariately (p < 0.001), STAND was more predictive than CSF both univariately and in combined models.Conclusions: CSF and MRI biomarkers independently contribute to intergroup diagnostic discrimination and the combination of CSF and MRI provides better prediction than either source of data alone. However, MRI provides greater power to effect cross-sectional groupwise discrimination and better correlation with general cognition and functional status cross-sectionally. We therefore conclude that although MRI and CSF provide complementary information, MRI reflects clinically defined disease stage better than the CSF biomarkers tested.(C)2009AAN Enterprises, Inc.

Objective: To evaluate the retinal nerve fiber layer (RNFL) thickness and macular volume in neuromyelitis optica (NMO) spectrum patients using optical coherence tomography (OCT).Background: OCT can quantify damage to retinal ganglion cell axons and can identify abnormalities in multiple sclerosis and optic neuritis (ON) eyes. OCT may also be useful in the evaluation of patients with NMO.Methods: OCT and visual function testing were performed in 26 NMO spectrum patients with a history of ON, 17 patients with isolated longitudinally extensive transverse myelitis (LETM) without ON, 378 patients with relapsing-remitting multiple sclerosis (RRMS), and 77 healthy controls at 2 centers.Results: Substantial RNFL thinning was seen in NMO ON eyes (63.6 [mu]m) relative to both RRMS ON eyes (88.3 [mu]m, p < 0.0001) and control eyes (102.4 [mu]m, p < 0.0001). A first episode of ON was estimated to cause 24 [mu]m more loss of RNFL thickness in NMO than RRMS. Similar results were seen for macular volume. ON also was associated with more severe visual impairment in NMO spectrum patients than in RRMS patients. Eyes in the LETM group and unaffected NMO eyes were not significantly different from controls, though conclusions about these subgroups were limited by small sample sizes.Conclusions: Optical coherence tomography (OCT) shows more severe retinal damage after optic neuritis (ON) episodes in neuromyelitis optica (NMO) than in relapsing-remitting multiple sclerosis. Identification of substantial retinal nerve fiber layer loss (>15 [mu]m) after ON in a non-multiple sclerosis patient should prompt consideration of an NMO spectrum condition. OCT may be a useful tool for the evaluation of patients with NMO.(C)2009AAN Enterprises, Inc.

Objective: Sensory neuropathy is a common problem in HIV-infected patients and is the dose-limiting toxicity of stavudine. Affordable methods of predicting neuropathy risk are needed to guide prescribing in countries where some use of stavudine remains an economic necessity. We therefore aimed to identify factors predictive of neuropathy risk before antiretroviral use.Methods: A total of 294 patients attending clinics in Melbourne, Kuala Lumpur, and Jakarta were enrolled in a cross-sectional neuropathy screening program in 2006. Neuropathy was defined by the presence of symptoms and signs on the AIDS Clinical Trials Group Brief Peripheral Neuropathy Screen. Demographic, laboratory, and treatment details were considered as possible risk factors for neuropathy. The role of patient demographics in predicting stavudine neuropathy were then assessed in 181 patients who reported that they were free of neuropathy symptoms when first prescribed this drug.Results: The prevalence of neuropathy was 42% in Melbourne (n = 100), 19% in Kuala Lumpur (n = 98), and 34% in Jakarta (n = 96). In addition to treatment exposures, increasing age (p = 0.002) and height (p = 0.001) were independently associated with neuropathy. Age and height cutoffs of >=170 cm or >=40 years predicted neuropathy. Among 181 patients who were asymptomatic before stavudine exposure, the risk of neuropathy following stavudine was 20% in younger, shorter patients, compared with 66% in older, taller individuals.Conclusions: Stavudine neuropathy risk increases with patient age and height. Prioritizing older and taller patients for alternative agents would be an inexpensive strategy to reduce neuropathy rates in countries where the burden of HIV disease limits treatment options.(C)2009AAN Enterprises, Inc.