Most endovascular innovations have been introduced into clinical care by showing good outcomes in small enthusiastic case series of selected patients. Randomized clinical trials (RCTs) have rarely been performed, except for acute ischemic stroke, but even then most trial designs were too explanatory to inform clinical decisions. In this article, we review 2 × 2 tables and forest plots that summarize RCT results to examine methodological issues in the design and interpretation of clinical studies. Research results can apply in practice when RCTs are all-inclusive, pragmatic trials. Common problems include the following: (i) using restrictive eligibility criteria in explanatory trials, instead of including the diversity of patients in need of care, which hampers future generalizability of results; (ii) ignoring an entire line of the 2 × 2 table and excluding patients who do not meet the proposed criteria of a diagnostic test in its evaluation (perfusion studies) which renders clinical inferences misleading; (iii) ignoring an entire column of the 2 × 2 table and comparing different patients treated using the same treatment instead of different treatments in the same patients (the “wrong axis” comparisons of prognostic studies and clinical experience) which leads to unjustified treatment decisions and actions; or (iv) combining all aforementioned problems (case series and epidemiological studies). The most efficient and reliable way to improve patient outcomes, after as well as long before research results are available, is to change the way we practice: to use care trials to guide care in the presence of uncertainty.

There has been a significant transformation in the treatment of intracranial aneurysms (IAs) over the past century, with the most pivotal changes occurring in the past three decades. To characterize this evolution, we assessed the number of articles published on various procedures for the treatment of IA as a measure of their interest and usage over time. We separated our analysis into two main areas: surgical and endovascular approaches. We further subdivided these two main categories into clipping and bypass for surgery, and coiling, flow diversion, and liquid material embolization for endovascular approaches. We found 5956 publications on open surgical approaches in the 70-year period from 1947 to 2017, with papers on clipping (n = 4204), being the most common. We found 8602 endovascular publications beginning in 1964, with most of the activity taking place in the late 1990s and beyond. Coiling had the most publications of the endovascular approaches (n = 5436). In 1999, the number of annual publications on endovascular treatments surpassed those of open surgery, signaling a crossover point in the IA literature. The same trend continues to this date.

Background: Amyotrophic lateral sclerosis (ALS) is a devastating disease that targets motor neurons. Upper motor neurons degeneration is pathologically characterized by brain iron accumulation. Signal attenuation in the shape of a ribbon at the posterior border of the precentral gyrus can be observed on conventional magnetic resonance imaging (MRI) sequences including T2-weighted sequence. Methods: With the aim to know the qualities of this potential marker of ALS, we conducted a prospective study. Patients with definite ALS in the age range of 40–70 years and healthy controls underwent 3T brain MRI using a standardized sequence. A second MRI was performed 18 months later under the same conditions in the patients with ALS. Results: Most of the patients with ALS (91.66%) exhibited a “black ribbon” (BR) with an average area of 79.98 mm3. Signal attenuation discriminated ALS with a mean value of 63.97 arbitrary units (AU) on the left BR (95% CI: 60.67–67.27), a mean value of 59.15 AU (95% CI: 54.78–63.53) on the right BR, and a significant difference with control subjects presenting a mean value of 107.85 AU (p < 0.001). The optimal cut-off point for differentiating patients with ALS from controls (sensitivity, 0.92; specificity, 0.93) was 83 AU. Forced vital capacity and muscle strength in the contralateral upper extremity were significantly correlated with the ribbon intensity in ALS. Patients who underwent a second study exhibited significant changes in the BR related to the rapid evolution of the disease. Conclusions: This marker represents a valuable tool for the selection of candidates and their follow-up in clinical trials.

Background: Primary Progressive Aphasia (PPA) is a syndrome characterized by an isolated impairment of language function at disease onset. The cholinergic system is implicated in language function and cholinergic deficits are seen in the brains of individuals with PPA. One major source of cholinergic innervation of the cerebral cortex is the nucleus basalis of Meynert (NBM) within which lies the nucleus subputaminalis (NSP). This nucleus is postulated to be involved in language function. We compared the abundance of cholinergic neurons in the NBM and NSP of controls and individuals with PPA. Also explored was whether the individuals presenting with PPA, who subsequently developed different clinical and neuropathological profiles, showed similar cholinergic deficits in the NSP. Methods: Cytoarchitecture of the basal forebrain was studied using Nissl staining in control (n = 5) and PPA (n = 5) brains. Choline acetyltransferase (ChAT) immunohistochemical staining labeled cholinergic neurons were quantified using Neurolucida software. Results: In comparison to matched controls, PPA showed reduction of cholinergic neurons in the NBM (t(8) = 4.04, p = 0.0037; Cohen’s effect size value d = 2.62) and the NSP (t(6) = 4.62, p = 0.0042; Cohen’s d effect size d = 2.92). The average percent of cholinergic neuronal loss was relatively higher in the NSP (64.7%) compared to the NBM (47.7%). Conclusion: Regardless of underlying pathology, all cases presenting with PPA showed a marked loss of cholinergic neurons in the NSP, providing further evidence for the importance of this nucleus in language function.

Objectives: We assessed trends in the incidence, prevalence, and post-diagnosis mortality of parkinsonism in Ontario, Canada over 18 years. We also explored the influence of a range of risk factors for brain health on the trend of incident parkinsonism. Methods: We established an open cohort by linking population-based health administrative databases from 1996 to 2014 in Ontario. The study population comprised residents aged 20–100 years with an incident diagnosis of parkinsonism ascertained using a validated algorithm. We calculated age- and sex-standardized incidence, prevalence, and mortality of parkinsonism, stratified by young onset (20–39 years) and mid/late onset (≥40 years). We assessed trends in incidence using Poisson regression, mortality using negative binomial regression, and prevalence of parkinsonism and pre-existing conditions (e.g., head injury) using the Cochran–Armitage trend test. To better understand trends in the incidence of mid/late-onset parkinsonism, we adjusted for various pre-existing conditions in the Poisson regression model. Results: From 1996 to 2014, we identified 73,129 incident cases of parkinsonism (source population of ∼10.5 million), of whom 56% were male, mean age at diagnosis was 72.6 years, and 99% had mid/late-onset parkinsonism. Over 18 years, the age- and sex-standardized incidence decreased by 13.0% for mid/late-onset parkinsonism but remained unchanged for young-onset parkinsonism. The age- and sex-standardized prevalence increased by 22.8%, while post-diagnosis mortality decreased by 5.5%. Adjustment for pre-existing conditions did not appreciably explain the declining incidence of mid/late-onset parkinsonism. Conclusion: Young-onset and mid/late-onset parkinsonism exhibited differing trends in incidence over 18 years in Ontario. Further research to identify other factors that may appreciably explain trends in incident parkinsonism is warranted.

Background: Essential tremor (ET) is reported to have a bimodal distribution of age at onset (AAO) with phenotypic variability based on the AAO. This study aims to explore the distribution of AAO based on mathematical modeling and ascertain the differences, if any, in the clinical features of groups. Methods: A chart review was conducted for 252 patients with ET diagnosed based on the Consensus statement of the Movement Disorder Society on Tremor. Finite mixture modeling was performed to identify groups of the cohort based on the AAO. Results: Three groups were defined: early onset (EO): AAO ≤ 22 years, n = 63, intermediate onset (IO): 23 ≤ AAO ≤ 35 years, n = 43, and late onset (LO): AAO ≥ 36 years, n = 146. There were no significant differences related to family history or responsiveness to alcohol. The EO group had significantly higher prevalence of upper limb and lower limb tremor. Head tremor and voice tremor was more prevalent in the IO and LO groups. Cerebellar signs showed a significant increase with an increase in AAO. Conclusions: ET shows significant phenotypic variability based on the AAO. Patients with an early AAO are more likely to develop an appendicular tremor, whereas the probability of axial tremor and cerebellar signs increases with increasing AAO.

Background: To assess the prevalence of three nociceptive primitive reflexes (nPR), i.e., glabellar tap, snout reflex, and palmomental reflex, in neurologically and cognitively healthy (NCH) aging subjects. Objective: To investigate whether nPR are cross-sectionally associated with white matter hyperintensities (WMH), lacunes, atrophy of the caudate nuclei, and global brain atrophy. Methods: A total of 1246 NCH subjects aged 45–91 years were included in the study and underwent standard brain MRI. Atrophy of the caudate nuclei and global brain atrophy were assessed through the bicaudate ratio (BCr) and lateral ventricles to brain ratio (LVBr), respectively. WMH were assessed through visual rating scales. Lacunes were also rated. Association of nPR with vascular risk factors/diseases and imaging findings was evaluated using logistic regression analysis. Results: nPR were exhibited by 33.1% of subjects and increased with age. Subjects with nPR performed less than subjects without nPR in tests evaluating global cognition, executive functions, attention, and language. Snout reflex was the most common nPR, followed by glabellar tap and palmomental reflex. Glabellar tap was associated with parieto-temporal WMH, BCr, and LVBr; snout reflex was associated with frontal lacunes, temporal WMH, BCr, and LVBr; palmomental reflex was associated with parieto-occipital WMH, basal ganglia lacunes, BCr, and LVBr. Conclusions: This study demonstrates that in NCH aging individuals, nPR are associated with WMH, lacunes, BCr, and LVBr and are probably a warning sign of incipient cognitive decline. Therefore, NCH subjects presenting nPR should manage their vascular risk factors/vascular diseases rigorously in order to prevent or delay progression of small vessel disease, and future neurological and cognitive disabilities.

Background: We reviewed numerous variables for ischemic stroke patients admitted to a rehabilitation unit to determine those that were statistically associated with discharge destination. Methods: A retrospective chart review of patients with ischemic stroke discharged from the rehabilitation unit between January 1, 2005 and December 31, 2015. Variables were examined for their association with discharge destination (home versus long-term care (LTC)). Univariable relationships with discharge destination were assessed, and a multivariable logistic regression model was built. Results: Univariate predictors of discharge to LTC: advanced age, decreasing admission and discharge functional independence measure (FIM) scores, increasing change in FIM score from admission to discharge, dependency, residence outside of home before the stroke, absence of a caregiver, urinary and bowel incontinence, low Berg balance score at admission and discharge, low Montreal Cognitive Assessment scores, smoking, chronic heart failure, and an inability to transfer. Multivariable logistic regression: five factors remained significant predictors with LTC disposition: advanced age, bowel incontinence, residence outside of the home prior to stroke, right hemisphere site of the stroke, and absence of a caregiver. Conclusions: Several easily measured variables were significantly associated with discharge to LTC versus home following stroke rehabilitation.

Objective: To develop a detailed profile of individuals living with migraine in Canada. Such a profile is important for planning and administration of services. Methods: The 2011–2012 Survey of Living with Neurological Conditions in Canada (SLNCC), a cross-sectional community-based survey, was used to examine a representative sample of migraineurs (N = 949) aged 15 years and older. Several health-related variables were examined (e.g., general health, health utility index (HUI) [a measure of health status and health-related quality of life, where dead = 0.00 and perfect health = 1.00], stigma, depression, and social support). Respondents were further stratified by sex, age, and age of migraine onset. Weighted overall and stratified prevalence estimates and odds ratios, both with 95% CIs, were used to estimate associations. Results: Overall, males had poorer health status compared with females (e.g., mean HUI was 0.67 in males vs. 0.82 in females; men had over two times the odds of their migraine limiting educational and job opportunities compared with females). Poorer health-related variables were seen in the older age groups (35–64 years/≥65 years) compared with the 15–34-year age group. There were no differences between those whose migraine symptoms began before versus after the age of 20 years. Conclusions: In this Canadian sample, migraine was associated with worse health-related variables in men compared with women. However, both men and women were significantly affected by migraine across various health-related variables. Thus, it is important to improve clinical and public health interventions addressing the impact of migraine across individuals of all ages, sexes, and sociodemographic backgrounds.

Objective: To summarize the findings of randomized controlled trials (RCTs) on the efficacy and safety of vitamins and minerals for migraine prophylaxis. Methods: We systematically searched bibliographic databases and relevant websites for parallel and crossover RCTs reporting efficacy and/or safety of vitamins and/or minerals for migraine prophylaxis. Our primary outcomes were migraine frequency (number of attacks) and duration (hours). Secondary outcomes were severity (intensity), days with migraine, and adverse events. Meta-analysis was conducted when analyzable data were available from at least two trials. Results: Eighteen placebo-controlled trials met our eligibility criteria. Only coenzyme Q10 and magnesium contributed to meta-analyses. In adults, compared with placebo, coenzyme Q10 did not significantly decrease migraine frequency (mean difference (MD) −0.44 (−2.14 to 1.26); I2 53%; 2 trials; 97 participants; moderate strength of the evidence), duration (MD −1.97 (−4.82 to 0.87); I2 0%; 2 trials; 97 participants; moderate strength of the evidence), or severity (ratio of means (RoM) −0.05 (−0.20 to 0.11); I2 0%; 2 trials; 97 participants). In adults, compared with placebo, magnesium did not significantly decrease migraine severity (RoM −0.17 (−0.36 to 0.02); I2 48%; 3 trials; 226 participants; low strength of the evidence). Meta-analysis of other vitamins and minerals, and other outcomes were not feasible due to a lack of sufficiently reported data. Conclusions: Based on insufficient evidence, it is unknown if coenzyme Q10 and magnesium are effective for migraine prophylaxis in adults. High-quality, adequately powered RCTs are needed to fully evaluate the efficacy and safety of vitamins and minerals for migraine prophylaxis.

Background: Intensive care unit-acquired weakness (ICU-AW) is associated with poorer outcome of critically ill patients. Microcirculatory changes and altered vascular permeability of skeletal muscles might contribute to the pathogenesis of ICU-AW. Muscular ultrasound (MUS) displays increased muscle echogenicity, although its pathogenesis is uncertain. Objective: We investigated the combined measurement of serum and ultrasound markers to assess ICU-AW and clinical patient outcome. Methods: Fifteen patients and five healthy controls were longitudinally assessed for signs of ICU-AW at study days 3 and 10 using a muscle strength sum score. The definition of ICU-AW was based on decreased muscle strength assessed by the muscular research council-sum score. Ultrasound echogenicity of extremity muscles was assessed using a standardized protocol. Serum markers of inflammation and endothelial damage were measured. The 3-month outcome was assessed on the modified Rankin scale. Results: ICU-AW was present in eight patients, and seven patients and the control subjects did not develop ICU-AW. The global muscle echogenicity score (GME) differed significantly between controls and patients (mean GME, 1.1 ± 0.06 vs. 2.3 ± 0.41; p = 0.001). Mean GME values significantly decreased in patients without ICU-AW from assessment 1 (2.30 ± 0.48) to assessment 2 (2.06 ± 0.45; p = 0.027), which was not observed in patients with ICU-AW. Serum levels of syndecan-1 at day 3 significantly correlated with higher GME values at day 10 (r = 0.63, p = 0.012). Furthermore, the patients’ GME significantly correlated with mRS at day 100 (r = 0.67, p = 0.013). Conclusion: The combined use of muscular ultrasound and inflammatory biomarkers might be helpful to diagnose ICU-AW and to predict long-term outcome in critical illness.

Introduction: Lewis–Sumner syndrome (LSS) is a demyelinating peripheral neuropathy described in 1982. Methods: We reviewed the charts of nine LSS patients in neurological care for their symptoms, response to different treatment regimens, and pattern of nerve involvement. Results: One patient had an Adie’s pupil. Every patient studied had median nerve involvement. Seven of nine patients required intravenous immunoglobulin (IVIg) therapy and all showed improvement with IVIg. Four of nine patients received oral steroid therapy and had some improvement. Two of nine patients received azathioprine to little effect. Two of nine patients experienced significant trauma while receiving neurological follow-up and their symptoms worsened to a clinically significant degree afterward. Discussion: We noticed a possible association between trauma and symptom severity in cases of LSS with preexisting neurological follow-up. We hypothesize that physical trauma exacerbates LSS. To our knowledge, this is an unreported phenomenon.

Measured nerve conduction velocity in the fibular nerve increases across the knee during hip flexion. This is due to stretching of sciatic and fibular nerves. We modeled the additional nerve length required for the sciatic nerve to course around the flexed hip, based upon distance between the hip and the sciatic nerve on magnetic resonance imaging (MRI). The median distance from the femoral head to the sciatic nerve was 41 mm. The model predicted that 64 mm of sciatic nerve is required for hip flexion. This impacts our understanding of lower limb nerve conduction studies and clinical straight leg raising tests.

This study describes the longitudinal changes of resting motor threshold (RMT) and central motor conduction time (CMCT) in 18 patients with Wilson’s disease (WD). The RMT, CMCT, and Global Assessment Scale for Wilson Disease (GAS-WD) were measured at baseline and at follow-up after 12.94 ± 7.23 months. There was a significant decrease in the RMT (72.11 ± 18.62 vs. 63.7 ± 15.52%; p-value = 0.002) and GAS-WD scores (14.38 ± 5.35 vs. 9.77 ± 6.47 ms; p-value = 0.04). CMCT did not improve despite chelation therapy. Hence, RMT may serve as a marker of chelation efficacy in WD.