Brian J. Murray

Living near major roads and the incidence of dementia, Parkinson's disease, and multiple sclerosis: a population-based cohort study

BACKGROUND Emerging evidence suggests that living near major roads might adversely affect cognition. However, little is known about its relationship with the incidence of dementia, Parkinsons disease, and multiple sclerosis. We aimed to investigate the association between residential proximity to major roadways and the incidence of these three neurological diseases in Ontario, Canada. METHODS In this population-based cohort study, we assembled two population-based cohorts including all adults aged 20-50 years (about 4·4 million; multiple sclerosis cohort) and all adults aged 55-85 years (about 2·2 million; dementia or Parkinsons disease cohort) who resided in Ontario, Canada on April 1, 2001. Eligible patients were free of these neurological diseases, Ontario residents for 5 years or longer, and Canadian-born. We ascertained the individuals proximity to major roadways based on their residential postal-code address in 1996, 5 years before cohort inception. Incident diagnoses of dementia, Parkinsons disease, and multiple sclerosis were ascertained from provincial health administrative databases with validated algorithms. We assessed the associations between traffic proximity and incident dementia, Parkinsons disease, and multiple sclerosis using Cox proportional hazards models, adjusting for individual and contextual factors such as diabetes, brain injury, and neighbourhood income. We did various sensitivity analyses, such as adjusting for access to neurologists and exposure to selected air pollutants, and restricting to never movers and urban dwellers. FINDINGS Between 2001, and 2012, we identified 243 611 incident cases of dementia, 31 577 cases of Parkinsons disease, and 9247 cases of multiple sclerosis. The adjusted hazard ratio (HR) of incident dementia was 1·07 for people living less than 50 m from a major traffic road (95% CI 1·06-1·08), 1·04 (1·02-1·05) for 50-100 m, 1·02 (1·01-1·03) for 101-200 m, and 1·00 (0·99-1·01) for 201-300 m versus further than 300 m (p for trend=0·0349). The associations were robust to sensitivity analyses and seemed stronger among urban residents, especially those who lived in major cities (HR 1·12, 95% CI 1·10-1·14 for people living <50 m from a major traffic road), and who never moved (1·12, 1·10-1·14 for people living <50 m from a major traffic road). No association was found with Parkinsons disease or multiple sclerosis. INTERPRETATION In this large population-based cohort, living close to heavy traffic was associated with a higher incidence of dementia, but not with Parkinsons disease or multiple sclerosis. FUNDING Health Canada (MOA-4500314182).

Influence of Continuous Positive Airway Pressure on Outcomes of Rehabilitation in Stroke Patients With Obstructive Sleep Apnea

Background and Purpose— In stroke patients, obstructive sleep apnea (OSA) is associated with poorer functional outcomes than in those without OSA. We hypothesized that treatment of OSA by continuous positive airway pressure (CPAP) in stroke patients would enhance motor, functional, and neurocognitive recovery. Methods— This was a randomized, open label, parallel group trial with blind assessment of outcomes performed in stroke patients with OSA in a stroke rehabilitation unit. Patients were assigned to standard rehabilitation alone (control group) or to CPAP (CPAP group). The primary outcomes were the Canadian Neurological scale, the 6-minute walk test distance, sustained attention response test, and the digit or spatial span-backward. Secondary outcomes included Epworth Sleepiness scale, Stanford Sleepiness scale, Functional Independence measure, Chedoke McMaster Stroke assessment, neurocognitive function, and Beck depression inventory. Tests were performed at baseline and 1 month later. Results— Patients assigned to CPAP (n=22) experienced no adverse events. Regarding primary outcomes, compared to the control group (n=22), the CPAP group experienced improvement in stroke-related impairment (Canadian Neurological scale score, P<0.001) but not in 6-minute walk test distance, sustained attention response test, or digit or spatial span-backward. Regarding secondary outcomes, the CPAP group experienced improvements in the Epworth Sleepiness scale (P<0.001), motor component of the Functional Independence measure (P=0.05), Chedoke-McMaster Stroke assessment of upper and lower limb motor recovery test of the leg (P=0.001), and the affective component of depression (P=0.006), but not neurocognitive function. Conclusions— Treatment of OSA by CPAP in stroke patients undergoing rehabilitation improved functional and motor, but not neurocognitive outcomes. Clinical Trial Registration Information— URL: http://www.clinicaltrials.gov. Unique identifier: NCT00221065.

A Citywide Prehospital Protocol Increases Access to Stroke Thrombolysis in Toronto

Background and Purpose— Intravenous tissue plasminogen activator for ischemic stroke is approved for eligible patients who can be treated within a 3-hour window, but treatment rates remain disappointingly low, often <5%. To improve rapid access to stroke thrombolysis in Toronto, Canada, a citywide prehospital acute stroke activation protocol was implemented by the provincial government to transport acute stroke patients directly to one of 3 regional stroke centers, bypassing local hospitals. This comprised a paramedic screening tool, ambulance destination decision rule, and formal memorandum of understanding of system stakeholders. This report describes the initial impact of the activation protocol at our regional stroke center. Methods— We compared consecutive patients with stroke arriving to our stroke center during the first 4 months of this new triage protocol (February 14 to June 14, 2005) versus the same 4-month period in 2004. Results— The protocol resulted in an immediate doubling in the number of patients with acute stroke arriving to our regional stroke center within 2.5 hours of symptom onset. We observed a 4-fold increase in patients who were eligible for and treated with tissue plasminogen activator. The tissue plasminogen activator treatment rate for ischemic stroke patients increased from 9.5% to 23.4% (P=0.01), and one in 2 patients with ischemic stroke arriving within 2.5 hours received thrombolysis during this period (one in 5 of patients with ischemic stroke overall). The median onset-to-needle time for tissue plasminogen activator-treated patients was significantly reduced. Many implementation challenges were identified and addressed. Conclusions— This prehospital triage was immediately successful in improving tissue plasminogen activator access for patients with ischemic stroke, enabling our center to achieve one of the highest tissue plasminogen activator treatment rates in North America and underscoring the need for coordinated systems of acute stroke care. Sustainability of such an initiative will be dependent on interdisciplinary teamwork, ongoing paramedic training, adequate hospital staffing, bed availability, and repatriation agreements with community hospitals.

Selective enhancement of rapid eye movement sleep by deep brain stimulation of the human pons.

Animal studies suggest that rapid eye movement (REM) sleep is governed by the interaction of REM‐promoting and REM‐inhibiting nuclei in the pontomesencephalic tegmentum. The pedunculopontine nucleus is proposed to be REM promoting. Using polysomnography, we studied sleep in five parkinsonian patients undergoing unilateral pedunculopontine nucleus deep brain stimulation (DBS). We demonstrated a near doubling of nocturnal REM sleep between the DBS “off” and DBS “on” states, without significant changes in other sleep states. This represents the first demonstration that DBS can selectively modulate human sleep, and it supports an important role for the pedunculopontine nucleus region in modulating human REM sleep. Ann Neurol 2009;66:110–114

Exposure to wind turbine noise: Perceptual responses and reported health effects

Health Canada, in collaboration with Statistics Canada, and other external experts, conducted the Community Noise and Health Study to better understand the impacts of wind turbine noise (WTN) on health and well-being. A cross-sectional epidemiological study was carried out between May and September 2013 in southwestern Ontario and Prince Edward Island on 1238 randomly selected participants (606 males, 632 females) aged 18-79 years, living between 0.25 and 11.22 km from operational wind turbines. Calculated outdoor WTN levels at the dwelling reached 46 dBA. Response rate was 78.9% and did not significantly differ across sample strata. Self-reported health effects (e.g., migraines, tinnitus, dizziness, etc.), sleep disturbance, sleep disorders, quality of life, and perceived stress were not related to WTN levels. Visual and auditory perception of wind turbines as reported by respondents increased significantly with increasing WTN levels as did high annoyance toward several wind turbine features, including the following: noise, blinking lights, shadow flicker, visual impacts, and vibrations. Concern for physical safety and closing bedroom windows to reduce WTN during sleep also increased with increasing WTN levels. Other sample characteristics are discussed in relation to WTN levels. Beyond annoyance, results do not support an association between exposure to WTN up to 46 dBA and the evaluated health-related endpoints.

Evaluating the impact of treatment for sleep/wake disorders on recovery of cognition and communication in adults with chronic TBI

Abstract Objective: To longitudinally examine objective and self-reported outcomes for recovery of cognition, communication, mood and participation in adults with traumatic brain injury (TBI) and co-morbid post-traumatic sleep/wake disorders. Design: Prospective, longitudinal, single blind outcome study. Setting: Community-based. Participants: Ten adults with moderate–severe TBI and two adults with mild TBI and persistent symptoms aged 18–58 years. Six males and six females, who were 1–22 years post-injury and presented with self-reported sleep/wake disturbances with onset post-injury. Interventions: Individualized treatments for sleep/wake disorders that included sleep hygiene recommendations, pharmacological interventions and/or treatments for sleep apnea with follow-up. Main outcome measures: Insomnia Severity Index, Beck Depression and Anxiety Inventories, Latrobe Communication Questionnaire, Speed and Capacity of Language Processing, Test of Everyday Attention, Repeatable Battery for the Assessment of Neuropsychological Status, Daily Cognitive-Communication and Sleep Profile. Results: Group analysis revealed positive trends in change for each measure and across sub-tests of all measures. Statistically significant changes were noted in insomnia severity, p = 0.0003; depression severity, p = 0.03; language, p = 0.01; speed of language processing, p = 0.007. Conclusions: These results add to a small but growing body of evidence that sleep/wake disorders associated with TBI exacerbate trauma-related cognitive, communication and mood impairments. Treatment for sleep/wake disorders may optimize recovery and outcomes.

Current Evaluation and Management of Excessive Daytime Sleepiness

Excessive daytime sleepiness has significant impact on neurological function, and has societal implications. Sleepiness is a common feature of many neurological conditions. A careful history will often reveal one of many common causes of excessive daytime sleepiness and suggest appropriate treatment. Neurophysiological testing can provide objective assessment. Behavioural management is an important first step in management. Treatment of common concurrent sleep disorders is also essential. Currently available medications can further symptomatically improve function in many individuals. The strongest evidence base is for the treatment of narcolepsy--a prototype disorder of excessive daytime sleepiness. Currently used medications include modafinil, stimulants, and sodium oxybate amongst others. This review discusses important features in the diagnosis of daytime sleepiness in adults, and outlines a treatment approach. Further evidence-based information about the management of this common problem is essential.

Global Hemispheric CT Hypoperfusion May Differentiate Headache With Associated Neurological Deficits and Lymphocytosis From Acute Stroke

Headache with associated neurological deficits and lymphocytosis (HaNDL) is characterized by temporary recurrent neurological deficits, moderate–severe headache, cerebrospinal fluid lymphocytosis, elevated protein, and increased opening pressure.1 Although CT and MRI should be normal, single photon emission CT may indicate focal hypoperfusion and electroencephalogram may reveal slowing or even epileptiform activity2 resolving once the patient is symptom-free (3 months). Catheter angiography also yields normal results but may trigger an acute neurological episode.3,4 Because HaNDL is a benign, self-limited syndrome, it is important to differentiate it from cerebrovascular disease to avoid unnecessary interventions such as catheter angiography and thrombolysis. We present a case initially thought to be acute stroke in which the patient was considered for thrombolysis. CT perfusion changes atypical for stroke made stroke diagnosis questionable and thrombolysis was withheld. A 31-year-old man with hypertension, dyslipidemia, and sleep apnea (treated with continuous positive airway pressure), but no history of prior migraine, was brought into our emergency department by ambulance with suspected acute ischemic stroke. He had become aphasic at work so his coworkers called 911. On examination, he was globally aphasic without focal weakness or obvious sensory changes aside from questionable mild right facial paresis (National Institutes of Health Stroke Scale score 6). A noncontrast CT and CT angiogram (CTA) were normal, but CT perfusion revealed a striking pattern of …

Seizures during stroke thrombolysis heralding dramatic neurologic recovery

Seizures during thrombolytic therapy for ischemic stroke have not previously been described as a favorable prognostic sign. We report three patients with severe stroke (NIH Stroke Scale [NIHSS] score 15 to 20) who experienced a seizure during tissue plasminogen activator (tPA) infusion. While initially raising alarm about possible hemorrhage, the seizures heralded dramatic recovery (an immediate 15-point NIHSS score improvement after tPA; NIHSS score 0 or 1 at 24 hours). We propose that the seizures during thrombolysis may indicate cortical reperfusion and/or hyperperfusion due to early recanalization of an acutely occluded intracranial artery.

Effects of vagus nerve stimulation on respiration during sleep

To the Editor: Malow et al. recently reported that vagus nerve stimulation (VNS) worsened sleep apnea in four patients with epilepsy.1 Because VNS can induce tachypnea,2 we reviewed polysomnograms of six patients with epilepsy treated with VNS. Patients were referred for evaluation of sleepiness, witnessed apneas, or insomnia. Polysomnograms were reviewed with IRB approval. Most patients had abnormal EEG and sleep architecture, and all had moderate sleep disordered breathing. Two of our patients had frank apneas during VNS (30 and 25 Hz stimulation frequency, 3 mA current). This was not evident in four others (two at 25 Hz, two at 20 Hz). The two patients with VNS-induced apneas did not have more severe VNS-independent sleep apnea. Although Malow et al. suggested that VNS-induced airway narrowing or altered sleep architecture might cause these respiratory events, we doubt these are the main reasons, because VNS-triggered hypopneas were accompanied by immediate tachypnea, without any apparent change in behavioral state. We measured respiratory rate and heart rate in 30-second …