Associations of Stages of Objective Memory Impairment with Cerebrospinal Fluid and Neuroimaging Biomarkers of Alzheimer's Disease.

OBJECTIVE: To investigate cerebrospinal fluid (CSF) and neuroimaging correlates of Stages of Objective Memory Impairment (SOMI) based on Free and Cued Selective Reminding Test (FCSRT) performance, and to evaluate the effect of APOE ε4 status on this relationship. METHODS: Data from 586 cognitively unimpaired individuals who had FCSRT, CSF, and volumetric magnetic resonance imaging (MRI) measures available was used. We compared CSF measures of ß-amyloid (Aß42/Aß40 ratio), phosphorylated tau (p-Tau181), total tau (t-Tau), hippocampal volume, and PIB-PET mean cortical binding potential with partial volume correction (MCBP) among SOMI groups in the whole sample and in subsamples stratified by APOE ε4 status. RESULTS: Participants had a mean age of 67.4 (SD=9.1) years, had 16.1 (SD=2.6) years of education, 57.0% were female, and 33.8% were APOE ε4 positive. In the entire sample, there was no significant difference between SOMI stages in Aß42/Aß40 ratio, p-Tau181, t-Tau, or PIB-PET MCBP when adjusted for age, sex, and education. However, higher SOMI stages had smaller hippocampal volume (F=3.29, p=0.020). In the stratified sample based on APOE ε4 status, in APOE ε4 positive individuals, higher SOMI stages had higher p-Tau181 (F=2.94, p=0.034) higher t-Tau (F=3.41, p=0.019), and smaller hippocampal volume (F=5.78, p<0.001). There were no significant differences in CSF or imaging biomarkers between SOMI groups in the APOE ε4 negative subsample. CONCLUSION: Cognitively normal older individuals with higher SOMI stages have higher in-vivo tau and neurodegenerative pathology only in APOE ε4 carriers. These original results indicate the potential usefulness of the SOMI staging system in assessing of tau and neurodegenerative pathology.

Parkinson's disease: Evolution of the scientific literature from 1983 to 2017 by countries and journals.

This study charts the evolution of the scientific literature on Parkinson's disease (PD) from 1983 to 2017 to inform communities of scientists, physicians, patients, caregivers and politicians concerned with PD. Articles published in journals indexed in the Science Citation Index-Expanded database of the Web of Science were retrieved and analyzed in seven five-year periods: 1983-1987, 1988-1992, 1993-1997, 1998-2002, 2003-2007, 2008-2012 and 2013-2017. Over 35 years the number of research papers on PD increased 33-fold: 885 papers in 1983-1987 to 29,972 in 2013-2017. At the same time the number of countries contributing to PD research increased from 37 to 131. The USA was the most prolific country throughout, followed by several European (UK, Germany, Italy and France) and English-speaking (Canada and Australia) countries. By 2003, several Asian countries (China, South Korea, India and Turkey) emerged with rapid increases in publications related to PD. By 2013-2017, China surpassed all but the USA to rank 2nd globally in productivity. Despite an increase from 4 to 22 African countries publishing PD research from 1983 to 2017, most were either unproductive or contributed ≤5 papers in each five-year period. There has also been a 12-fold increase in the number of journals (232-2824) containing papers on PD. In 2013-2017 three PD-focused journals (Parkinsonism & Related Disorders, Movement Disorders and Journal of Parkinson's Disease) contained 6.8% of all PD papers while a large majority (82.5%) of journals published ≤ 10 papers. This quantitative study complements the numerous extant qualitative reviews to provide a global perspective on PD research.

The headache under-response to treatment (HURT) questionnaire, an outcome measure to guide follow-up in primary care: development, psychometric evaluation and assessment of utility.

BACKGROUND: Headache disorders are both common and burdensome but, given the many people affected, provision of health care to all is challenging. Structured headache services based in primary care are the most efficient, equitable and cost-effective solution but place responsibility for managing most patients on health-care providers with limited training in headache care. The development of practical management aids for primary care is therefore a purpose of the Global Campaign against Headache. This manuscript presents an outcome measure, the Headache Under-Response to Treatment (HURT) questionnaire, describing its purpose, development, psychometric evaluation and assessment for clinical utility. The objective was a simple-to-use instrument that would both assess outcome and provide guidance to improving outcome, having utility across the range of headache disorders, across clinical settings and across countries and cultures. METHODS: After literature review, an expert consensus group drawn from all six world regions formulated HURT through item development and item reduction using item-response theory. Using the American Migraine Prevalence and Prevention Study's general-population respondent panel, two mailed surveys assessed the psychometric properties of HURT, comparing it with other instruments as external validators. Reliability was assessed in patients in two culturally-contrasting clinical settings: headache specialist centres in Europe (n = 159) and primary-care centres in Saudi Arabia (n = 40). Clinical utility was assessed in similar settings (Europe n = 201; Saudi Arabia n = 342). RESULTS: The final instrument, an 8-item self-administered questionnaire, addressed headache frequency, disability, medication use and effect, patients' perceptions of headache "control" and their understanding of their diagnoses. Psychometric evaluation revealed a two-factor model (headache frequency, disability and medication use; and medication efficacy and headache control), with scale properties apparently stable across disorders and correlating well and in the expected directions with external validators. The literature review found few instruments linking assessment to clinical advice or suggested actions: HURT appeared to fill this gap. In European specialist care, it showed utility as an outcome measure across headache disorders. In Saudi Arabian primary care, HURT (translated into Arabic) was reliable and responsive to clinical change. CONCLUSIONS: With demonstrated validity and clinical utility across disorders, cultures and settings, HURT is available for clinical and research purposes.

The Headache-Attributed Lost Time (HALT) Indices: measures of burden for clinical management and population-based research.

BACKGROUND: The burden attributable to headache disorders has multiple components: a simple measure summarising them all does not exist. The Migraine Disability Assessment (MIDAS) instrument has proved useful, estimating productive time lost in the preceding 3 months due to the disabling effect of headache. We developed adaptations of MIDAS for purposes of the Global Campaign against Headache, embracing epidemiological studies and the provision of clinical management aids. METHODS: We reviewed the structure, content, wording and scoring of MIDAS and made revisions, developing the Headache-Attributed Lost Time (HALT) Indices in three versions. Over 10 years, these were employed in multiple epidemiological and clinical studies in countries worldwide. RESULTS: In the original HALT-90, we made no changes to the structure and scoring of MIDAS, but used wording in questions 1-4 that we believed would be more widely understood and more easily translated into other languages. Of the two alternative versions, HALT-30 kept the same structure, question format and wording except that "3 months" was replaced by "1 month". HALT-7/30 was a variant of HALT-30: focusing only on lost work time for population-based studies of headache-attributed burden, it enquired into lost days in the preceding month (30 days) and week (7 days). CONCLUSIONS: Three versions of the HALT Indices serve different purposes as measures of headache-attributed burden, and offer different means of scoring. In studies using HALT as a population measure, there is no need to reflect the states of individuals, whereas a measure over shorter periods than 3 months is likely to be more reliable through better recall. Assessment of individual patients prior to treatment may best estimate impact if enquiry is made into the preceding 90 days, except in cases where headache is highly frequent. Follow-up in clinical management may be better served by assessments over 30 rather than 90 days.

Increased pain sensitivity in migraine and tension-type headache coexistent with low back pain: A cross-sectional population study.

BACKGROUND: Low back pain is common in the general population and in individuals with primary headaches. We assessed the relative frequency of self-reported back pain in persons with and without primary headaches and examined pain sensitivity. METHOD: A population of 796 individuals completed a headache interview based on ICHD criteria and provided data of interest in a self-administered questionnaire. Headache cases were classified into chronic (≥15) (CH) or episodic (<15 headache days/month) (EH). A total of 495 had a pericranial total tenderness score (TTS), and 494 had cephalic and extracephalic pressure pain thresholds (PPTs) assessed. RESULTS: Adjusted for age, gender, education and poor self-rated health, 1-year relative frequency of back pain was higher in individuals with CH (82.5%) and EH (80.1%) compared to no headache group (65.7%). In persons with back pain, TTS was higher in CH, (26.3 ± 12.1) than in EH, (18.5 ± 10.0; p < 0.001) and higher in both groups than in those with no headache, 10.8 ± 8.5 (p < 0.001 and p < 0.001, respectively). In persons with back pain, temporalis PPT were lower in CH, 169.3 ± 57.8, than in EH, 225.2 ± 98.1, and in no headache group, 244.3 ± 105.4 (p = 0.02 and p = 0.01, respectively). In persons with back pain, finger PPT were lower in CH, 237.1 ± 106.7, than in EH, 291.3 ± 141.3, or in no headache group, 304.3 ± 137.4 (p = 0.02 and p < 0.001, respectively). CONCLUSION: Back pain is highly frequent in individuals with CH, followed by EH and no headache. In persons with CH, back pain is associated with lower cephalic and extracephalic PPTs suggesting central sensitization may be a substrate or consequence of comorbidity. SIGNIFICANCE: We found that back pain has high relative frequency in individuals with CH followed EH and no headache. Back pain is associated with low cephalic and extracephalic PPTs in individuals with CH. Central sensitization may be a substrate or consequence of this comorbidity of back pain and CH.

Neuroticism, depression and pain perception in migraine and tension-type headache.

OBJECTIVES: People with migraine and tension-type headache (TTH) have psychiatric comorbidities. We aimed to test differences in mental health constructs by type and frequency of primary headache and associated pain sensitivity. MATERIALS AND METHODS: Data on headache features, neuroticism (Eysenck Personality Questionnaire) and depression (Major Depression Inventory) were obtained from 547 individuals classified into chronic (≥15) or episodic (<15 headache days/month) and into pure migraine (n=43), pure tension type headache (TTH, n=97), migraine and TTH (n=83) and no headache diagnosis (controls, n=324) groups. A pericranial total tenderness score (TTS) and pressure pain thresholds (PPTs) were measured. Differences in mental health constructs were examined by headache frequency and type using generalized linear mixed models adjusting for sociodemographic covariates. RESULTS: Depression scores were highest among people with chronic headache, lower in those with episodic headache, and lowest in controls. The chronic and episodic headache groups had higher neuroticism scores than controls. Mental health construct scores were highest for the migraine and TTH group and lowest in the control group. TTS and cephalic PPTs were correlated with neuroticism and depression and were higher in the chronic headache group compared to the no headache group even when adjusted for neuroticism and depression. CONCLUSIONS: Neuroticism and depression scores are associated with headache frequency (chronic vs episodic) and are highest for migraine and TTH followed by pure TTH then migraine. Mental health constructs were correlated with but did not influence differences in TTS and PPTs between headache groups.

Validation and calibration of HeadCount, a self-report measure for quantifying heading exposure in soccer players.

The long-term effects of repetitive head impacts due to heading are an area of increasing concern, and exposure must be accurately measured; however, the validity of self-report of cumulative soccer heading is not known. In order to validate HeadCount, a 2-week recall questionnaire, the number of player-reported headers was compared to the number of headers observed by trained raters for a men's and a women's collegiate soccer teams during an entire season of competitive play using Spearman's correlations and intraclass correlation coefficients (ICCs), and calibrated using a generalized estimating equation. The average Spearman's rho was 0.85 for men and 0.79 for women. The average ICC was 0.75 in men and 0.38 in women. The calibration analysis demonstrated that men tend to report heading accurately while women tend to overestimate. HeadCount is a valid instrument for tracking heading behaviour, but may have to be calibrated in women.

Bidirectional Changes in Anisotropy Are Associated with Outcomes in Mild Traumatic Brain Injury.

BACKGROUND AND PURPOSE: Mild traumatic brain injury results in a heterogeneous constellation of deficits and symptoms that persist in a subset of patients. This prospective longitudinal study identifies early diffusion tensor imaging biomarkers of mild traumatic brain injury that significantly relate to outcomes at 1 year following injury. MATERIALS AND METHODS: DTI was performed on 39 subjects with mild traumatic brain injury within 16 days of injury and 40 controls; 26 subjects with mild traumatic brain injury returned for follow-up at 1 year. We identified subject-specific regions of abnormally high and low fractional anisotropy and calculated mean fractional anisotropy, axial diffusivity, radial diffusivity, and mean diffusivity across all white matter voxels brain-wide and each of several white matter regions. Assessment of cognitive performance and symptom burden was performed at 1 year. RESULTS: Significant associations of brain-wide DTI measures and outcomes included the following: mean radial diffusivity and mean diffusivity with memory; and mean fractional anisotropy, radial diffusivity, and mean diffusivity with health-related quality of life. Significant differences in outcomes were found between subjects with and without abnormally high fractional anisotropy for the following white matter regions and outcome measures: left frontal lobe and left temporal lobe with attention at 1 year, left and right cerebelli with somatic postconcussion symptoms at 1 year, and right thalamus with emotional postconcussion symptoms at 1 year. CONCLUSIONS: Individualized assessment of DTI abnormalities significantly relates to long-term outcomes in mild traumatic brain injury. Abnormally high fractional anisotropy is significantly associated with better outcomes and might represent an imaging correlate of postinjury compensatory processes.

The Statistical Modeling of Aging and Risk of Transition Project: Data Collection and Harmonization Across 11 Longitudinal Cohort Studies of Aging, Cognition, and Dementia.

Longitudinal cognitive trajectories and other factors associated with mixed neuropathologies (such as Alzheimer's disease with co-occurring cerebrovascular disease) remain incompletely understood, despite being the rule and not the exception in older populations. The Statistical Modeling of Aging and Risk of Transition study (SMART) is a consortium of 11 different high-quality longitudinal studies of aging and cognition (N=11,541 participants) established for the purpose of characterizing risk and protective factors associated with subtypes of age-associated mixed neuropathologies (N=3,001 autopsies). While brain donation was not required for participation in all SMART cohorts, most achieved substantial autopsy rates (i.e., > 50%). Moreover, the studies comprising SMART have large numbers of participants who were followed from intact cognition and transitioned to cognitive impairment and dementia, as well as participants who remained cognitively intact until death. These data provide an exciting opportunity to apply sophisticated statistical methods, like Markov processes, that require large, well-characterized samples. Thus, SMART will serve as an important resource for the field of mixed dementia epidemiology and neuropathology.

Dipyridamole-induced headache and lower recurrence risk in secondary prevention of ischaemic stroke: a post hoc analysis.

BACKGROUND AND PURPOSE: Our objective was to investigate the association between recurrent stroke risk and headache induced by extended-release dipyridamole (ER-DP) when administered alone or with low-dose aspirin (ASA+ER-DP). METHODS: This was a post hoc analysis of prospectively collected data on recurrent stroke risk and headache as an adverse event or reason for treatment discontinuation from the PRoFESS (N = 20,332) and ESPS2 (N = 6602) trials. Hazard ratios (HRs) for recurrent stroke were calculated using the Cox model. RESULTS: In PRoFESS, the 2.5-year recurrent stroke risk in patients receiving ASA+ER-DP was 8.2% in those with headache within 7 days of starting treatment and 9.4% in those without [HR 0.85, 95% confidence interval (CI) 0.73-0.98; P = 0.03]. Recurrent stroke risk was 5.0% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.2% in those who did not (HR 0.52, 95% CI 0.35-0.77; P = 0.001). No such difference was observed in clopidogrel-treated patients. In ESPS2, risk of recurrent stroke was 6.2% in patients who discontinued ASA+ER-DP due to headache by day 90 versus 9.8% in patients who did not (HR 0.62, 95% CI 0.31-1.27; P = 0.19) and 7.3% in patients who discontinued ER-DP due to headache by day 90 versus 13.2% in those who did not (HR 0.53, 95% CI 0.27-1.04; P = 0.06). CONCLUSIONS: Patients taking ASA+ER-DP in PRoFESS who developed headache had significantly reduced stroke recurrence risk versus those without headache. Similar (non-significant) findings for ASA+ER-DP and ER-DP in ESPS2 suggest that dipyridamole-induced headache may reflect better cerebrovascular function.

OnabotulinumtoxinA for chronic migraine: efficacy, safety, and tolerability in patients who received all five treatment cycles in the PREEMPT clinical program.

OBJECTIVE: Chronic migraine (CM) is a prevalent and disabling neurological disorder. Phase III REsearch Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program assessed efficacy and safety of onabotulinumtoxinA (BOTOX(®)) for prophylaxis of headaches in adults with CM. This secondary analysis assessed patients who received all five treatment cycles and completed the study. MATERIALS AND METHODS: PREEMPT (two phase III studies: 24-week double-blind, placebo-controlled [DBPC], parallel-group phase, followed by 32-week open-label [OL] phase) evaluated the efficacy and safety of onabotulinumtoxinA in CM (≥15 days/month with headache lasting ≥4 h a day). Patients were randomized (1:1) to onabotulinumtoxinA or placebo every 12 weeks for two cycles, followed by onabotulinumtoxinA for three cycles. Multiple headache symptom measures were evaluated. Results for the completer (five cycles) subgroup of patients are reported. RESULTS: Of 1384 total PREEMPT patients, 1005 received all five treatment cycles (513 received onabotulinumtoxinA only [onabotulinumtoxinA/onabotulinumtoxinA (O/O)] and 492 received two cycles of placebo then three cycles of onabotulinumtoxinA [placebo/onabotulinumtoxinA (P/O)]). Demographics were similar between treatment groups. At Week 56, after all patients were treated with onabotulinumtoxinA, there continued to be significant between-group differences favoring the O/O vs P/O group for the following headache symptom measures: LS mean change from baseline in frequencies of headache days (-12.0 O/O, -11.1 P/O; P = 0.035), migraine days (-11.6 O/O, -10.7 P/O; P = 0.038), and moderate/severe headache days (-11.0 O/O, -10.1 P/O; P = 0.042). For other measures (cumulative hours of headache on headache days, frequency of headache episodes, and percentage with severe Headache Impact Test (HIT)-6 score, and total HIT-6 and Migraine-Specific Quality of Life Questionnaire scores), there were also large mean improvements from baseline. The percent of patients with a ≥50% reduction from baseline in frequency of headache days was significantly greater for the onabotulinumtoxinA-only group at Week 56 (69.6% O/O, 62.8% P/O; P = 0.023). The treatment-related adverse event rate was 28.5% for onabotulinumtoxinA vs 12.4% for placebo in the DBPC phase and 34.8% for patients treated with onabotulinumtoxinA for all five cycles throughout the 56-week trials. CONCLUSIONS: This subgroup analysis demonstrated improvements with onabotulinumtoxinA treatment (five cycles) vs placebo (two cycles)/onabotulinumtoxinA (three cycles) for multiple headache symptom measures and suggests that at Week 56, patients treated earlier with onabotulinumtoxinA had better outcomes. These findings demonstrate the continued need and cumulative benefit over time with continued prophylaxis, an important and clinically pragmatic observation for clinicians and patients.

Cost of healthcare for patients with migraine in five European countries: results from the International Burden of Migraine Study (IBMS).

Migraine is a disabling neurological disease that affects 14.7 % of Europeans. Studies evaluating the economic impact of migraine are complex to conduct adequately and with time become outdated as healthcare systems evolve. This study sought to quantify and compare direct medical costs of chronic migraine (CM) and episodic migraine (EM) in five European countries. Cross-sectional data collected via a web-based survey were screened for migraine and classified as CM (≥15 headache days/month) or EM (<15 headache days/month), and included sociodemographics, resource use data and medication use. Unit cost data, gathered using publicly available sources, were analyzed for each type of service, stratified by migraine status. Univariate and multivariate log-normal regression models were used to examine the relationship between various factors and their impact on total healthcare costs. This economic analysis included data from respondents with migraine in the UK, France, Germany, Italy, and Spain. CM participants had higher level of disability and more prevalent psychiatric disorders compared to EM. CM participants had more provider visits, emergency department/hospital visits, and diagnostic tests; the medical costs were three times higher for CM than EM. Per patient annual costs were highest in the UK and Spain and lower in France and Germany. CM was associated with higher medical resource use and total costs compared to EM in all study countries, suggesting that treatments that reduce headache frequency could decrease the clinical and economic burden of migraine in Europe. Comparing patterns of care and outcomes among countries may facilitate the development of more cost-effective care, and bring greater recognition to patients affected by migraine.

Gender differences in the IL6 -174G>C and ESR2 1730G>A polymorphisms and the risk of Parkinson's disease.

The -174G>C (rs1800795) single nucleotide polymorphism (SNP) in the promoter of the interleukin-6 (IL6) gene and the 1730G>A (rs4986938) SNP in the estrogen receptor beta (ESR2) may influence the risk of Parkinson's disease (PD). We investigated these SNPs in 380 unrelated US Caucasian PD cases and 522 controls, including 452 individuals of Ashkenazi Jewish (AJ) origin (260 PD, 192 controls). The G allele of the -174G>C SNP was more common in AJ PD cases (p=0.033) as well as in Non-Jewish (NJ) men with PD (p=0.022). The GG genotype increased the risk of PD by over two fold in NJ men (OR=2.11, 95%CI: 1.14-3.89, p=0.017), and approached significance in the total AJ group with PD (OR=1.42, 95%CI: 0.97-2.06, p=0.067). The A allele of the ESR2 1730G>A SNP was associated with a decreased risk for PD in AJ women, and in this group, having the AA genotype decreased the risk of PD by half (OR=0.45, 95%CI: 0.22-0.92, p=0.029). Our data supports a role for the IL6 -174G>C G allele in AJ individuals overall. In NJ Caucasians, this role appears to be gender mediated. In both groups, the effect is independent from ESR2 1730G>A. A separate association for the ESR2 1730G>A SNP was found exclusively in women of AJ descent. Other polymorphisms in tight linkage disequilibrium with the SNP differentially influencing expression, ethnic differences in allele distribution, and gender differences in genetic load related to PD, may underlie our findings. Larger studies in diverse populations, including analysis of surrounding regions are recommended.

Experiences of female survivors of sexual violence in eastern Democratic Republic of the Congo: a mixed-methods study.

BACKGROUND: The conflict in eastern Democratic Republic of the Congo (DRC) is the deadliest since World War II. Over a decade of fighting amongst an array of armed groups has resulted in extensive human rights abuses, particularly the widespread use of sexual violence against women. METHODS: Using a mixed-methods approach, we surveyed a non-random sample of 255 women attending a referral hospital and two local non-governmental organizations to characterize their experiences of sexual and gender-based violence (SGBV). We then conducted focus groups of 48 women survivors of SGBV to elaborate on survey findings. Quantitative and qualitative data underwent thematic and statistical analysis respectively. FINDINGS: Of the women surveyed, 193 (75.7%) experienced rape. Twenty-nine percent of raped women were rejected by their families and 6% by their communities. Thirteen percent of women had a child from rape. Widowhood, husband abandonment, gang rape, and having a child from rape were significant risk factors for social rejection. Mixed methods findings show rape survivors were seen as "contaminated" with HIV, contributing to their isolation and over 95% could not access prophylactic care in time. Receiving support from their husbands after rape was protective against survivors' feelings of shame and social isolation. INTERPRETATION: Rape results not only in physical and psychological trauma, but can destroy family and community structures. Women face significant obstacles in seeking services after rape. Interventions offering long-term solutions for hyper-vulnerable women are vital, but lacking; reintegration programs on SGBV for women, men, and communities are also needed.

OnabotulinumtoxinA improves quality of life and reduces impact of chronic migraine.

OBJECTIVE: To assess the effects of treatment with onabotulinumtoxinA (Botox, Allergan, Inc., Irvine, CA) on health-related quality of life (HRQoL) and headache impact in adults with chronic migraine (CM). METHODS: The Phase III Research Evaluating Migraine Prophylaxis Therapy (PREEMPT) clinical program (PREEMPT 1 and 2) included a 24-week, double-blind phase (2 12-week cycles) followed by a 32-week, open-label phase (3 cycles). Thirty-one injections of 5U each (155 U of onabotulinumtoxinA or placebo) were administered to fixed sites. An additional 40 U could be administered "following the pain." Prespecified analysis of headache impact (Headache Impact Test [HIT]-6) and HRQoL (Migraine-Specific Quality of Life Questionnaire v2.1 [MSQ]) assessments were performed. Because the studies were similar in design and did not notably differ in outcome, pooled results are presented here. RESULTS: A total of 1,384 subjects were included in the pooled analyses (onabotulinumtoxinA, n = 688; placebo, n = 696). Baseline mean total HIT-6 and MSQ v2.1 scores were comparable between groups; 93.1% were severely impacted based on HIT-6 scores ≥60. At 24 weeks, in comparison with placebo, onabotulinumtoxinA treatment significantly reduced HIT-6 scores and the proportion of patients with HIT-6 scores in the severe range at all timepoints including week 24 (p < 0.001). OnabotulinumtoxinA treatment significantly improved all domains of the MSQ v2.1 at 24 weeks (p < 0.001). CONCLUSIONS: Treatment of CM with onabotulinumtoxinA is associated with significant and clinically meaningful reductions in headache impact and improvements in HRQoL. CLASSIFICATION OF EVIDENCE: This study provides Class 1A evidence that onabotulinumtoxinA treatment reduces headache impact and improves HRQoL.

Olfactory dysfunction in LRRK2 G2019S mutation carriers.

BACKGROUND: Olfactory dysfunction is an established nonmotor feature of idiopathic Parkinson disease (PD), which may precede disease onset. Olfaction is likely disturbed in patients with PD with leucine-rich repeat kinase (LRRK2) G2019S mutations, although the degree of impairment is debated. It is also unclear whether mutation carriers who have not yet manifested with PD have olfactory disturbances. METHODS: Thirty-one subjects with LRRK2 G2019S mutation-related PD (PD-manifesting carriers [PD-MC]), 30 subjects with PD without mutations (PD noncarriers [PD-NC]), 28 mutation carrier family members (nonmanifesting carriers [NMC]), and 46 controls completed the University of Pennsylvania Smell Identification Test (UPSIT). Generalized estimating equations were applied to determine whether olfactory score was associated with PD and LRRK2 mutation status. RESULTS: As expected, having PD was associated with impaired olfaction regardless of LRRK2 mutation status. More importantly, however, impaired olfaction was increased overall in LRRK2 carriers both with and without PD, though the impairment was only present in a subset of NMCs. Compared to controls, the mean score was lower among NMC (difference = -3.518, p = 0.006), MC (difference = -7.677, p < 0.0001), and idiopathic PD (PD-NC) (difference = -13.810, p < 0.0001). Olfaction was better among MC (PD-MC) than non-LRRK2 PD (PD-NC) (difference = 6.13, p = 0.0012). Group differences from the continuous analysis were maintained in dichotomous analysis stratifying at 15th percentile for age and gender. CONCLUSION: Olfaction is impaired in LRRK2 G2019S-mutation related PD, although less overall than other PD. Further, olfaction is impaired in a subset of LRRK2 NMC, suggesting that olfaction may be a marker for development of PD in this group, and that longitudinal studies are warranted.

Chronic migraine: classification and comparisons.

OBJECTIVE: The objective of our study was to field test different chronic migraine (CM) criteria and compare CM epidemiological profiles, which include demographic, personal, and lifestyle characteristics, with high-frequency episodic migraine (HFEM) and low-frequency episodic migraine (LFEM). METHODS: Questionnaires were mailed to a random sample of 18,000 18-65-year-olds in demographically diverse regions of Germany. The epidemiological data for the three classifications of CM, LFEM and HFEM were assessed using descriptive statistics, Pearson Chi-square, and analysis of variance tests. RESULTS: Among 9350 respondents, CM_I was the most restrictive (N = 37, 0.4%), followed by CM_II (N = 45, 0.5%) and CM_III (N = 185, 2.0%). CM groups did not differ in distribution by age, gender, body mass index, education or smoking and alcohol consumption. Compared to those with LFEM and HFEM, those with CM (CM_III) had significantly different epidemiological profiles. CONCLUSIONS: CM prevalence varies by case definition. The epidemiological profiles of the three CM groups are similar but differ significantly from those of HFEM and LFEM. Optimal definitions for clinical practice and epidemiological research require additional field testing.

Rates, predictors, and consequences of remission from chronic migraine to episodic migraine.

OBJECTIVES: This study has 3 objectives: 1) to estimate remission rates in a population-based sample of subjects with chronic migraine (CM); 2) to identify potential predictors of CM remission; and 3) to assess the influence of CM remission on headache-related disability. METHODS: The American Migraine Prevalence and Prevention study is a prospective, population-based, mailed questionnaire survey, which included questions regarding headache frequency, symptomatology, demographics, comorbidities, health care utilization, and headache-related disability. Three years of longitudinal data were analyzed to determine rates of CM remission and assess predictors of remission using logistical regression models. The consequence of remission was measured by changes in disability, as measured by the Migraine Disability Assessment, over time. RESULTS: A total of 383 respondents had CM in 2005 and follow-up data in 2006 and 2007. Over 2 years, among those with CM at baseline, approximately 34% (n = 130) had persistent CM while 26% (n = 100) had remitted CM. In our final multivariate model, predictors of remission included baseline headache frequency (15-19 vs 25-31 headache days/month; odds ratio [OR] 0.29; 95% confidence interval [CI] 0.11 to 0.75) and absence of allodynia (OR 0.45; 95% CI 0.23 to 0.89). Preventive medication use was associated with lower remission rate (OR 0.41; 95% CI 0.23 to 0.75), but this effect lost significance when headache frequency was included. Over 2 years, those with persistent CM demonstrated increased disability while those with remitted CM demonstrated decreased disability. CONCLUSIONS: These findings have clinical practice implications, as it is important to consider that remission rates are variable. However, the benefit of remission goes beyond symptom reduction and may translate to marked decreases in headache-related disability.

Disability, HRQoL and resource use among chronic and episodic migraineurs: results from the International Burden of Migraine Study (IBMS).

BACKGROUND: Migraine imposes significant burden on patients, their families and health care systems. In this study, we compared episodic to chronic migraine sufferers to determine if migraine status predicted headache-related disability, health-related quality of life (HRQoL) and health care resource utilization. METHODS: A Web-based survey was administered to panelists from nine countries. Participants were classified as having chronic migraine (CM), episodic migraine (EM) or neither using a validated questionnaire. Data collected and then analyzed included sociodemographics, clinical characteristics, Migraine Disability Assessment, Migraine-Specific Quality of Life v2.1, Patient Health Questionnaire and health care resource utilization. FINDINGS: Of the respondents, 5.7% had CM and 94.3% had EM, with CM patients reporting significantly more severe disability, lower HRQoL, higher levels of anxiety and depression and greater health care resource utilization compared to those with EM. INTERPRETATION: These results provide evidence that will enhance our understanding of the factors driving health care costs and will contribute to development of cost-effective health care strategies.