Smoking and risk of multiple sclerosis: evidence of modification by NAT1 variants.

BACKGROUND: Tobacco smoke is an established risk factor for multiple sclerosis (MS). We hypothesized that variation in genes involved in metabolism of tobacco smoke constituents may modify MS risk in smokers. METHODS: A three-stage gene-environment investigation was conducted for NAT1, NAT2, and GSTP1 variants. The discovery analysis was conducted among 1588 white MS cases and controls from the Kaiser Permanente Northern California Region HealthPlan (Kaiser). The replication analysis was carried out in 988 white MS cases and controls from Sweden. RESULTS: Tobacco smoke exposure at the age of 20 years was associated with greater MS risk in both data sets (in Kaiser, odds ratio [OR] = 1.51 [95% confidence interval (CI) = 1.17-1.93]; in Sweden, OR = 1.35 [1.04-1.74]). A total of 42 NAT1 variants showed evidence for interaction with tobacco smoke exposure (P(corrected) < 0.05). Genotypes for 41 NAT1 single nucleotide polymorphisms (SNPs) were studied in the replication data set. A variant (rs7388368C>A) within a dense transcription factor-binding region showed evidence for interaction (Kaiser, OR for interaction = 1.75 [95% CI = 1.19-2.56]; Sweden, OR = 1.62 [1.05-2.49]). Tobacco smoke exposure was associated with MS risk among rs7388368A carriers only; homozygote individuals had the highest risk (A/A, OR = 5.17 [95% CI = 2.17-12.33]). CONCLUSIONS: We conducted a three-stage analysis using two population-based case-control datasets that consisted of a discovery population, a replication population, and a pooled analysis. NAT1 emerged as a genetic effect modifier of tobacco smoke exposure in MS susceptibility.

Standardized discharge orders after stroke: results of the quality improvement in stroke prevention (QUISP) cluster randomized trial.

OBJECTIVE: Proven strategies to reduce risk of stroke recurrence are under-utilized. We sought to evaluate the impact of standardized stroke discharge orders on treatment practices in a cluster-randomized trial. METHODS: The Quality Improvement in Stroke Prevention (QUISP) trial randomized 12 hospitals to continue usual care or to receive assistance in the development and implementation of standardized stroke discharge orders. All patients with ischemic stroke were identified during a 12-month period prior to implementation and for 12 months afterward, and were followed for 6 months after discharge. The primary outcome was optimal treatment at 6 months, defined as taking a statin, having blood pressure <140/90mmHg, and receiving anticoagulation if atrial fibrillation was diagnosed. The primary analysis treated the hospital as the unit of analysis, comparing optimal treatment rates-adjusted for race, age, dementia, atrial fibrillation, and history of bleeding-between intervention and non-intervention hospitals using a paired t test. RESULTS: In the primary analysis with hospital as the unit of analysis, the odds of optimal treatment was not significantly increased at intervention compared to non-intervention hospitals (odds ratio, 1.39; 95% confidence interval, 0.71-2.76; p = 0.27). However, in analyses conducted at the level of the individual patients (N = 3,361), rates of optimal treatment increased from 37% to 45% in the intervention hospitals (p = 0.001) and did not change significantly in the non-intervention hospitals (39% to 40%; p = 0.27). INTERPRETATION: Implementation of standardized discharge orders after stroke was associated with increased rates of optimal secondary prevention; this improvement was not significant in the primary analysis at the hospital level.

Urgent neurology consultation from the ED for transient ischemic attack.

OBJECTIVE: The objective of this study was to evaluate the association between urgent neurology consultation and outcomes for patients with transient ischemic attack (TIA). METHODS: In a secondary analysis of data from 1707 emergency department patients with transient ischemic attack from March 1997 to May 1998, we compared presentation, management, and outcomes by neurology consultation status using generalized estimating equations to adjust for ABCD(2) score and clustering by facility and survival analysis for outcomes. RESULTS: Consultation was obtained f28% of patients. Median ABCD(2) scores were comparable, but consultation was associated with hospital admission (odds ratio, 1.35 [1.02-1.78], P = .04) and use of antithrombotics (odds ratio, 1.88 [1.20-2.93], P = .005). The cumulative stroke risk was significantly lower within 1 week (5.3% versus 7.5%, P = .02) but not at 90 days (9.9% versus 11.0%, P = .21). CONCLUSIONS: Consultation was not targeted to high-risk patients but was associated with some quality of care measures and improved early outcomes; however, improvement in 90-day outcomes was not established.

Familial aggregation of Parkinson's disease in a multiethnic community-based case-control study.

To assess the familial aggregation of Parkinson's disease (PD), we compared the cumulative incidence of PD among first-degree relatives of PD cases and controls. We identified newly diagnosed patients with PD (n = 573) during 1994 to 1995 within Kaiser Permanente Medical Care Program of Northern California and recruited 496 cases (87%) for the case-control study. Of 720 eligible controls matched by birth year and sex to cases, 541 (75%) agreed to participate. Information on family history of PD and other neurodegenerative diseases was obtained by in-person structured interview. We used the reconstructed cohort approach that provides a better estimate of the risk. The cumulative incidence of PD was significantly higher among relatives of PD patients compared with relatives of controls (2.0 vs. 0.7%; relative risk (RR) = 3.4, 95% confidence interval (CI) 1.9-5.9; P = 0.0001). The degree of familial aggregation was higher among first-degree relatives of Hispanic PD cases compared with Hispanic controls (3.7% vs. 0.4%; RR = 8.5, 95% CI 1.0-68.9) than it was among non-Hispanic Caucasian cases and controls (2.0% vs. 0.8%; RR = 2.7, 95% CI 1.5-5.1; P = 0.02). The familial aggregation of PD was stronger among the siblings of PD cases (RR = 5.4, 95% CI 1.8-16.0) than among parents (RR = 2.7, 95% CI 1.3-5.2). The incidence and familial aggregation of PD is highest among Hispanics, warranting further studies of genetic and environmental risk factors in the Hispanic population.

Factors associated with the decision to hospitalize patients after transient ischemic attack before publication of prediction rules.

BACKGROUND AND PURPOSE: One important criterion for hospitalizing patients after transient ischemic attack (TIA) is the short-term risk of stroke. Before publication of prediction rules for stroke after TIA, physician judgment was required to make a decision about hospitalization. We sought to identify factors associated with the decision to admit patients with TIA from the emergency department (ED) and to see whether those at highest risk of stroke were selected for admission. METHODS: All patients diagnosed with TIA in the ED of 16 hospitals in the Kaiser-Permanente Medical Care Plan over a 1-year period before publication of prediction rules were included (n=1707). Risk of subsequent stroke was stratified according to a validated prediction rule (ABCD(2) score), and the decision to admit was correlated with these risk scores. Factors associated with admission in univariate analysis were included in a logistic regression model. RESULTS: Overall, 243 patients with TIA (14%) were admitted. Admission weakly correlated with the ABCD(2) score (rank biserial R(2)=0.036; 10.0% at low 2-day risk of stroke admitted versus 20.3% at high risk). Seven variables were independently associated with a decision to admit after TIA: prior TIA, speech impairment, weakness, gait disturbance, history of atrial fibrillation, symptoms on arrival to ED, and use of ticlopidine. CONCLUSIONS: In this cohort of patients with TIA, the decision to admit was weakly correlated with risk of subsequent stroke as measured by the ABCD(2) score, and several risk factors for stroke were not important for the decision to admit. Before publication of prediction rules for stroke after TIA, physicians were not identifying the majority of patients at highest risk of stroke for admission.

Higher ABCD2 score predicts patients most likely to have true transient ischemic attack.

BACKGROUND AND PURPOSE: Some patients diagnosed with transient ischemic attack (TIA) in the emergency department may actually have alternative diagnoses such as seizure, migraine, or other nonvascular spells. The ABCD2 score has been shown to predict subsequent risk of stroke in patients with TIA diagnosed by emergency physicians, but perhaps high ABCD2 scores simply separate those patients with true TIA from those with alternative diagnoses. We investigated this hypothesis in a cohort of patients with TIA identified in the emergency department whose records were reviewed by an expert neurologist. METHODS: Among patients diagnosed by emergency physicians with TIA in 16 hospitals in the Kaiser-Permanente Medical Care Plan over a 1-year period ending February 1998 (before publication of prediction rules), an expert neurologist reviewed all records for those in which the diagnosis of TIA was considered questionable by a medical records analyst and determined whether the spell was likely to represent a true TIA. Subsequent strokes within 90 days were identified. ABCD2 scores were calculated for all patients and 2-sided Cochrane-Armitage trend tests were used to assess subsequent risk of stroke. RESULTS: Of the 713 patients reviewed by the expert neurologist, 642 (90%) were judged to likely have experienced a true TIA. Ninety-day stroke risk was 24% (95% CI, 20% to 27%) in the group judged to have experienced a true TIA and 1.4% (0% to 7.6%) in the group judged to not have a true TIA (P<0.0001). ABCD(2) scores were higher in those judged to have a true TIA compared with others (P=0.0001). In the group judged to have a true TIA, 90-day stroke risk increased as ABCD2 score increased (P<0.0001); there was no relationship between ABCD2 score and stroke risk in those judged unlikely to have had a TIA (P=0.73). CONCLUSIONS: Among patients diagnosed by emergency department physicians with TIA, higher ABCD2 score was associated with a greater likelihood that the diagnosis was confirmed on expert review. The predictive power of the ABCD2 model is therefore partially explained by identification of those patients likely to have experienced a true TIA, an important aspect of the score when used by nonneurologists. However, higher ABCD2 scores still remained predictive of 90-day stroke rate in the group of patients judged to have a true TIA by an expert neurologist.

Validation and refinement of scores to predict very early stroke risk after transient ischaemic attack.

BACKGROUND: We aimed to validate two similar existing prognostic scores for early risk of stroke after transient ischaemic attack (TIA) and to derive and validate a unified score optimised for prediction of 2-day stroke risk to inform emergency management. METHODS: The California and ABCD scores were validated in four independent groups of patients (n=2893) diagnosed with TIA in emergency departments and clinics in defined populations in the USA and UK. Prognostic value was quantified with c statistics. The two groups used to derive the original scores (n=1916) were used to derive a new unified score based on logistic regression. FINDINGS: The two existing scores predicted the risk of stroke similarly in each of the four validation cohorts, for stroke risks at 2 days, 7 days, and 90 days (c statistics 0.60-0.81). In both derivation groups, c statistics were improved for a unified score based on five factors (age >or=60 years [1 point]; blood pressure >or=140/90 mm Hg [1]; clinical features: unilateral weakness [2], speech impairment without weakness [1]; duration >or=60 min [2] or 10-59 min [1]; and diabetes [1]). This score, ABCD(2), validated well (c statistics 0.62-0.83); overall, 1012 (21%) of patients were classified as high risk (score 6-7, 8.1% 2-day risk), 2169 (45%) as moderate risk (score 4-5, 4.1%), and 1628 (34%) as low risk (score 0-3, 1.0%). IMPLICATIONS: Existing prognostic scores for stroke risk after TIA validate well on multiple independent cohorts, but the unified ABCD(2) score is likely to be most predictive. Patients at high risk need immediate evaluation to optimise stroke prevention.

Vagus nerve stimulation therapy for pharmacoresistant epilepsy: effect on health care utilization.

We retrospectively analyzed the effects of vagus nerve stimulation (VNS) therapy on utilization of medical services by 138 patients in a large staff-model health maintenance organization. We compared average quarterly rates for 12 months before device implantation with quarterly rates during 48 months of follow-up. Wilcoxon matched-pairs signed-ranks tests comparing pre-VNS with post-VNS utilization rates showed statistically significant reductions in numbers of emergency department visits, hospitalizations, and hospital lengths of stay, beginning with the first quarter after implantation (P<0.05 for all post-implantation quarters for these three aspects). For the first two quarters after implantation, the average number of outpatient visits was significantly greater than the pre-implant quarterly average (quarter 1: P<0.0001; quarter 2: P=0.0067), but the average was 12.2% less by the fourth quarter of the first year after implantation and significantly less beginning with the first quarter of the second year (P=0.0017) and continuing through the end of the study (P<0.0001 for all subsequent quarters). A comparison of time spent on epilepsy-related tasks during the year before implantation with the year after implantation also revealed significant decreases in the average number of days on which patients could not work because of health-related concerns, from 3.67 to 1.04 days (P=0.002, paired Student's t test) and the average time spent caring for health problems, from 352.6 to 136.1 minutes per week (P<0.001). VNS therapy had a positive effect on both the utilization of health care services and the time spent on epilepsy-related tasks for these patients with pharmacoresistant epilepsy.

Multiple sclerosis risk loci and disease severity in 7,125 individuals from 10 studies.

OBJECTIVE: We investigated the association between 52 risk variants identified through genome-wide association studies and disease severity in multiple sclerosis (MS). METHODS: Ten unique MS case data sets were analyzed. The Multiple Sclerosis Severity Score (MSSS) was calculated using the Expanded Disability Status Scale at study entry and disease duration. MSSS was considered as a continuous variable and as 2 dichotomous variables (median and extreme ends; MSSS of ≤5 vs >5 and MSSS of <2.5 vs ≥7.5, respectively). Single nucleotide polymorphisms (SNPs) were examined individually and as both combined weighted genetic risk score (wGRS) and unweighted genetic risk score (GRS) for association with disease severity. Random-effects meta-analyses were conducted and adjusted for cohort, sex, age at onset, and HLA-DRB1*15:01. RESULTS: A total of 7,125 MS cases were analyzed. The wGRS and GRS were not strongly associated with disease severity after accounting for cohort, sex, age at onset, and HLA-DRB1*15:01. After restricting analyses to cases with disease duration ≥10 years, associations were null (p value ≥0.05). No SNP was associated with disease severity after adjusting for multiple testing. CONCLUSIONS: The largest meta-analysis of established MS genetic risk variants and disease severity, to date, was performed. Results suggest that the investigated MS genetic risk variants are not associated with MSSS, even after controlling for potential confounders. Further research in large cohorts is needed to identify genetic determinants of disease severity using sensitive clinical and MRI measures, which are critical to understanding disease mechanisms and guiding development of effective treatments.

Exploration of EEG features of Alzheimer's disease using continuous wavelet transform.

We have developed a novel approach to elucidate several discriminating EEG features of Alzheimer's disease. The approach is based on the use of a variety of continuous wavelet transforms, pairwise statistical tests with multiple comparison correction, and several decision tree algorithms, in order to choose the most prominent EEG features from a single sensor. A pilot study was conducted to record EEG signals from Alzheimer's disease (AD) patients and healthy age-matched control (CTL) subjects using a single dry electrode device during several eyes-closed (EC) and eyes-open (EO) resting conditions. We computed the power spectrum distribution properties and wavelet and sample entropy of the wavelet coefficients time series at scale ranges approximately corresponding to the major brain frequency bands. A predictive index was developed using the results from statistical tests and decision tree algorithms to identify the most reliable significant features of the AD patients when compared to healthy controls. The three most dominant features were identified as larger absolute mean power and larger standard deviation of the wavelet scales corresponding to 4-8 Hz (θ) during EO and lower wavelet entropy of the wavelet scales corresponding to 8-12 Hz (α) during EC, respectively. The fourth reliable set of distinguishing features of AD patients was lower relative power of the wavelet scales corresponding to 12-30 Hz (ß) followed by lower skewness of the wavelet scales corresponding to 2-4 Hz (upper δ), both during EO. In general, the results indicate slowing and lower complexity of EEG signal in AD patients using a very easy-to-use and convenient single dry electrode device.

Raloxifene for women with Alzheimer disease: A randomized controlled pilot trial.

OBJECTIVE: To determine whether raloxifene, a selective estrogen receptor modulator, improves cognitive function compared with placebo in women with Alzheimer disease (AD) and to provide an estimate of cognitive effect. METHODS: This pilot study was conducted as a randomized, double-blind, placebo-controlled trial, with a planned treatment of 12 months. Women with late-onset AD of mild to moderate severity were randomly allocated to high-dose (120 mg) oral raloxifene or identical placebo provided once daily. The primary outcome compared between treatment groups at 12 months was change in the Alzheimer's Disease Assessment Scale, cognitive subscale (ADAS-cog). RESULTS: Forty-two women randomized to raloxifene or placebo were included in intent-to-treat analyses (mean age 76 years, range 68-84), and 39 women contributed 12-month outcomes. ADAS-cog change scores at 12 months did not differ significantly between treatment groups (standardized difference 0.03, 95% confidence interval -0.39 to 0.44, 2-tailed p = 0.89). Raloxifene and placebo groups did not differ significantly on secondary analyses of dementia rating, activities of daily living, behavior, or a global cognition composite score. Caregiver burden and caregiver distress were similar in both groups. CONCLUSIONS: Results on the primary outcome showed no cognitive benefits in the raloxifene-treated group. CLASSIFICATION OF EVIDENCE: This study provides Class I evidence that for women with AD, raloxifene does not have a significant cognitive effect. The study lacked the precision to exclude a small effect.

Electrocardiographic findings predict short-term cardiac morbidity after transient ischemic attack.

BACKGROUND: Current guidelines recommend the use of electrocardiography (ECG) in the evaluation of transient ischemic attack (TIA), but the data supporting its value in acute management are sparse. OBJECTIVE: To determine whether ECG findings are useful as independent predictors of short-term cardiac or neurologic complications after TIA. METHODS: We included patients who presented to 1 of 16 emergency departments of a health maintenance organization in northern California and received a diagnosis of TIA from March 1, 1997, through February 28, 1998, for a 90-day follow-up. A cardiac event was defined as a hospitalization or a death due to myocardial infarction, ventricular arrhythmia, heart failure, or unstable angina. RESULTS: Among the 1327 patients with TIA for whom ECG findings were available for diagnostic coding, cardiac events occurred in 2.9%, strokes in 10.9%, recurrent TIAs in 13.7%, and deaths in 2.6% during 90-day follow-up. The ECG findings disclosed a new diagnosis of atrial fibrillation in 28 (2.3%) of the 1200 patients with no history of this condition. The 90-day risk for a cardiac event was greater in those who had any abnormal ECG findings (4.2% vs 0.6%; P<.001). This association remained significant after adjustment for medical history and examination findings (odds ratio, 6.9; 95% confidence interval, 1.6-29.5; P =.009). Left ventricular hypertrophy, atrial fibrillation, and atrioventricular conduction abnormalities were each independently associated with more than doubling of the risk. The ECG abnormalities were not associated with risk for stroke or death. CONCLUSIONS: Short-term cardiac morbidity is substantial after TIA. Electrocardiographic findings disclose new atrial fibrillation in a significant portion of patients with TIA and can identify a group of patients at a substantially higher risk for short-term cardiac events.

A cohort study of systemic and local complications of toe prostheses.

We investigated the role of toe implants in systemic disease and evaluated local complications after foot surgery. Information was obtained from the medical records of Kaiser Permanente (northern California) patients who had undergone toe surgery between 1979 and 1988. Computerized hospitalization records were used to identify patients with toe implants (N=814) and matched controls with foot surgery not involving implants (N=837). Brain cancer and alopecia areata occurred more among implant patients, whereas dysphagia occurred more among nonimplant patients. A larger proportion of implant patients were diagnosed with pain and swelling, tendonitis, and osteomyelitis or periostitis. Nonimplant patients were more often diagnosed with derangement of foot or ankle and delayed postoperative healing. We did not find a general association between implants and connective tissue diseases.

Adverse socioeconomic position during the life course is associated with multiple sclerosis.

BACKGROUND: Adverse socioeconomic position (SEP) in childhood and adulthood is associated with a proinflammatory phenotype, and therefore an important exposure to consider for multiple sclerosis (MS), a complex neuroinflammatory autoimmune disease. The objective was to determine whether SEP over the life course confers increased susceptibility to MS. METHODS: 1643 white, non-Hispanic MS case and control members recruited from the Kaiser Permanente Medical Care Plan, Northern California Region, for which comprehensive genetic, clinical and environmental exposure data have been collected were studied. Logistic regression models investigated measures of childhood and adulthood SEP, and accounted for effects due to established MS risk factors, including HLA-DRB1*15:01 allele carrier status, smoking history, history of infectious mononucleosis, family history of MS and body size. RESULTS: Multiple measures of childhood and adulthood SEP were significantly associated with risk of MS, including parents renting versus owning a home at age 10: OR=1.48, 95% CI 1.09 to 2.02, p=0.013; less than a college education versus at least a college education based on parental household: OR=1.28, 95% CI 1.01 to 1.63, p=0.041; low versus high life course SEP: OR=1.50, 95% CI 1.09 to 2.05, p=0.012; and low versus high social mobility: OR=1.74, 95% CI 1.27 to 2.39, p=5.7×10(-4). CONCLUSIONS: Results derived from a population-representative case-control study provide support for the role of adverse SEP in MS susceptibility and add to the growing evidence linking lower SEP to poorer health outcomes. Both genetic and environmental contributions to chronic conditions are important and must be characterised to fully understand MS aetiology.

Obesity during childhood and adolescence increases susceptibility to multiple sclerosis after accounting for established genetic and environmental risk factors.

OBJECTIVE: To investigate the association between obesity and multiple sclerosis (MS) while accounting for established genetic and environmental risk factors. METHODS: Participants included members of Kaiser Permanente Medical Care Plan, Northern California Region (KPNC) (1235 MS cases and 697 controls). Logistic regression models were used to estimate odds ratios (ORs) with 95% confidence intervals (95% CI). Body mass index (BMI) or body size was the primary predictor of each model. Both incident and prevalent MS cases were studied. RESULTS: In analyses stratified by gender, being overweight at ages 10 and 20 were associated with MS in females (p<0.01). Estimates trended in the same direction for males, but were not significant. BMI in 20s demonstrated a linear relationship with MS (p-trend=9.60×10(-4)), and a twofold risk of MS for females with a BMI≥30kg/m(2) was observed (OR=2.15, 95% CI 1.18, 3.92). Significant associations between BMI in 20s and MS in males were not observed. Multivariate modelling demonstrated that significant associations between BMI or body size with MS in females persisted after adjusting for history of infectious mononucleosis and genetic risk factors, including HLA-DRB1*15:01 and established non-HLA risk alleles. INTERPRETATION: Results show that childhood and adolescence obesity confer increased risk of MS in females beyond established heritable and environmental risk factors. Strong evidence for a dose-effect of BMI in 20s and MS was observed. The magnitude of BMI association with MS is as large as other known MS risk factors.

Seroprevalence of aquaporin-4-IgG in a northern California population representative cohort of multiple sclerosis.

IMPORTANCE: Using an aquaporin-4 (AQP4) M1-isoform-specific enzyme-linked immunosorbent assay (ELISA) and a fixed transfected cell-based assay (CBA), we tested AQP4-IgG in a northern California population representative cohort of 3293 potential cases with multiple sclerosis (MS). Seropositive cases were tested additionally by fluorescence-activated cell sorting, a live transfected cell-based assay. OBSERVATIONS: Sera samples were available in 1040 cases; 7 yielded positive results, 4 by ELISA alone and 3 by both ELISA and CBA. Clinical data (episodes of optic neuritis and longitudinally extensive transverse myelitis [reported on at least 1 magnetic resonance imaging spine]) supported the alternative diagnosis of neuromyelitis optica for 2 patients as seropositive by both ELISA and CBA. These 2 patients alone tested positive by a fluorescence-activated cell-sorting assay. The diagnosis of MS was considered correct in the other 5 patients. Thus, 5 ELISA results and 1 fixed CBA result were false positive. CONCLUSIONS AND RELEVANCE: Sensitive serological evaluation for AQP4-IgG in this large population-representative cohort of predominantly white non-Hispanic patients with MS reveals that neuromyelitis optica spectrum disorder is rarely misdiagnosed as MS in contemporary US neurological practice (0.2%). The frequency of a false-positive result for ELISA and CBA in this MS cohort were 0.5% and 0.1%, respectively. This finding reflects the superior specificity of CBA and justifies caution in interpreting AQP4-IgG results obtained by ELISA.

Identification of resting and active state EEG features of Alzheimer's disease using discrete wavelet transform.

Alzheimer's disease (AD) is associated with deficits in a number of cognitive processes and executive functions. Moreover, abnormalities in the electroencephalogram (EEG) power spectrum develop with the progression of AD. These features have been traditionally characterized with montage recordings and conventional spectral analysis during resting eyes-closed and resting eyes-open (EO) conditions. In this study, we introduce a single lead dry electrode EEG device which was employed on AD and control subjects during resting and activated battery of cognitive and sensory tasks such as Paced Auditory Serial Addition Test (PASAT) and auditory stimulations. EEG signals were recorded over the left prefrontal cortex (Fp1) from each subject. EEG signals were decomposed into sub-bands approximately corresponding to the major brain frequency bands using several different discrete wavelet transforms and developed statistical features for each band. Decision tree algorithms along with univariate and multivariate statistical analysis were used to identify the most predictive features across resting and active states, separately and collectively. During resting state recordings, we found that the AD patients exhibited elevated D4 (~4-8 Hz) mean power in EO state as their most distinctive feature. During the active states, however, the majority of AD patients exhibited larger minimum D3 (~8-12 Hz) values during auditory stimulation (18 Hz) combined with increased kurtosis of D5 (~2-4 Hz) during PASAT with 2 s interval. When analyzed using EEG recording data across all tasks, the most predictive AD patient features were a combination of the first two feature sets. However, the dominant discriminating feature for the majority of AD patients were still the same features as the active state analysis. The results from this small sample size pilot study indicate that although EEG recordings during resting conditions are able to differentiate AD from control subjects, EEG activity recorded during active engagement in cognitive and auditory tasks provide important distinct features, some of which may be among the most predictive discriminating features.

Interdisciplinary treatment for vestibular dysfunction: the effectiveness of mindfulness, cognitive-behavioral techniques, and vestibular rehabilitation.

OBJECTIVE: To investigate whether an interdisciplinary program for vestibular patients improved health outcomes and health care utilization. STUDY DESIGN: Case series with chart review. SETTING: Outpatient neurotology clinic. SUBJECTS AND METHODS: Patients (N = 167) with dizziness attended an interdisciplinary neurotology clinic; 129 were offered group treatment. After an introductory session, group treatment included 5 sessions incorporating mindfulness, cognitive-behavioral techniques, and vestibular rehabilitation. Physical and emotional functioning, depression,anxiety, dizziness, impairment, coping, skill use, and patient satisfaction were measured with rating scales pre- and post-group treatment. Data from 51 patients (male/female = 14/37; age range, 25-82 years) were analyzed with paired t tests or nonparametric tests. Logistic regression analyzed predictors of outcome and utilization for 116 patients (male/female = 81/35; age range, 11-86 years) attending the interdisciplinary clinic, introductory session, and/or group. RESULTS: After group treatment, patients reported better mood (P = .0482); better physical (P = .0006) and mental (P = .0183) health; better functionality, coping, and skill use (Ps< .0001); less impairment (P < .0001); and fewer limitations from dizziness (P < .0001). Higher pretreatment levels of depression (P = .0216), poorer initial mental (P = .0164) or physical (P = .0059) health, and peripheral diagnosis (P = .0220) predicted better outcome. Group treatment decreased utilization more than the interdisciplinary clinic with (P = .0183) or without (P = .0196) the introductory session; 78% of patients with any level of participation showed less utilization. Clinic patients had fewer radiology procedures than group patients (P = .0365). Patients were highly satisfied with the program and found it more effective than previous treatment. CONCLUSION: Interdisciplinary treatment improves patient coping, functionality, and satisfaction and decreases overall health care utilization in vestibular patients.

Reliability and validity of two self-administered questionnaires for screening restless legs syndrome in population-based studies.

BACKGROUND: A reliable and valid questionnaire for screening restless legs syndrome (RLS) is essential for determining accurate estimates of disease frequency. In a 2002 NIH-sponsored workshop, experts suggested three mandatory questions for identifying RLS in epidemiologic studies. We evaluated the reliability and validity of this RLS-NIH questionnaire in a community-based sample and concurrently developed and evaluated the utility of an expanded screening questionnaire, the RLS-EXP. METHODS: The study was conducted at Kaiser Permanente of Northern California and the Stanford University Sleep Clinic. We evaluated test-retest reliability in a random sample of subjects with prior physician-assigned RLS (n=87), subjects with conditions frequently misclassified as RLS (n=31), and healthy subjects (n=9). Validity of both instruments was evaluated in a random sample of 32 subjects, and in-person examination by two RLS specialists was used as the gold standard. RESULTS: For the first three RLS-NIH questions, the kappa statistic for test-retest reliability ranged from 0.5 to 1.0, and sensitivity and specificity was 86% and 45%, respectively. For the subset of five questions on RLS-EXP that encompassed cardinal features for diagnosing RLS, kappas were 0.4-0.8, and sensitivity and specificity were 81% and 73%, respectively. CONCLUSIONS: Sensitivity of RLS-NIH is good; however, the specificity of the instrument is poor when examined in a sample that over-represents subjects with conditions that are commonly misclassified as RLS. Specificity can be improved by including separate questions on cardinal features, as used in the RLS-EXP, and by including a few questions that identify RLS mimics, thereby reducing false positives.

Clinical features in early Parkinson disease and survival.

OBJECTIVE: To examine the association between demographic and clinical features in early Parkinson disease (PD) and length of survival in a multiethnic population. DESIGN: Clinical features within 2 years of diagnosis were determined for an inception cohort established during 1994-1995. Vital status was determined through December 31, 2005. Predictor variables included age at diagnosis, sex, race/ethnicity, as well as clinical subtype (modified tremor dominant, postural instability gait difficulty), symmetry, cognitive impairment, depression, dysphagia, and hallucinations. Cox proportional hazards regression analysis was used to identify factors associated with shorter survival. SETTING: Kaiser Permanente Medical Care Program, northern California. PATIENTS: Five hundred seventy-three men and women with newly diagnosed PD. RESULTS: Three hundred fifty-two participants in the PD cohort (61.4%) had died in the follow-up period. Older age at diagnosis (hazard ratio [HR], 1.1; 95% confidence interval [CI], 1.09-1.12), modified postural instability gait difficulty subtype (HR, 1.8; 95% CI, 1.3-2.7), symmetry of motor signs (HR, 2.0; 95% CI, 1.1-3.7), mild (HR, 1.7; 95% CI, 1.3-2.2) and severe (HR, 2.7; 95% CI, 1.9-3.9) cognitive impairment, dysphagia (HR, 1.4; 95% CI, 1.1-1.9), and hallucinations (HR, 2.1; 95% CI, 1.3-3.2) were associated with increased all-cause mortality, after adjusting for age, sex, and race/ethnicity. None of the other factors altered mortality risk. In an empirical predictive analysis, most previous significant predictors remained associated with shorter survival. CONCLUSIONS: Both motor and nonmotor features in early PD predict increased mortality risk, particularly postural instability gait difficulty, cognitive impairment, and hallucinations. These predictors may be useful in clinical practice and when designing clinical trials.