Climate Change and Stroke: A Topical Narrative Review.

The impacts of accumulating atmospheric greenhouse gases on the earth's climate are now well established. As a result, there have been increases in ambient temperatures and resultant higher frequency and duration of temperature extremes and other extreme weather events, which have been linked to a wide range of adverse health outcomes. This topical narrative review provides a summary of published evidence on the links between climate change and stroke. There is consistent evidence of associations between stroke incidence and mortality and increasing ambient temperature and air pollution. Associations have also been shown for changes in barometric pressure, wildfires, and desert dust and sandstorms, but current evidence is limited. Flooding and other extreme weather events appear to primarily cause service disruption, but more direct links to stroke may emerge. Synergies between dietary changes that reduce stroke risk and may also reduce carbon footprint are being explored. We also discuss the impact on vulnerable populations, proposed pathophysiologic mechanisms, mitigation strategies, and current research priorities. In conclusion, climate change increasingly impacts the stroke community, warranting elevated attention.

Decision-making under uncertainty in environmental health policy: new approaches.

Decision-making in environmental health policy is a complex procedure even in well-known conditions. Thus, in the case of uncertainty, decision-making becomes a hurdle race. We address scientific uncertainty, methods to reduce uncertainty, biomedical doubt and science communication, and the role of stakeholders, activists, lobbies and media that together influence policy decisions. We also consider the major responsibility and role of the medico-scientific community in this process. This community can and should teach the principle of scientific uncertainty to all stakeholders, advise policy-makers and underline the ethical issues, considering that our brains are not only the deposit of our humanity but also the route to environmental health and societal harmony.

Air pollution by particulate matter PM10 may trigger multiple sclerosis relapses.

BACKGROUND: Seasonal variation of relapses in multiple sclerosis (MS) suggests that season-dependent factors, such as ambient air pollution, may trigger them. However, only few studies have considered possible role of air pollutants as relapse's risk factor. OBJECTIVE: We investigated the effect of particulate matter of aerodynamic diameter smaller than 10µm (PM10) on MS relapses. METHODS: In total, 536 relapsing MS patients from Strasbourg city (France) were included, accounting for 2052 relapses over 2000-2009 period. A case-crossover design was used with cases defined as the days of relapse and controls being selected in the same patient at plus and minus 35 days. Different lags from 0 to 30 days were considered. Conditional logistic regressions, adjusted on meteorological parameters, school and public holidays, were used and exposure was considered first as a quantitative variable and second, as a binary variable. RESULTS: The natural logarithm of the average PM10 concentration lagged from 1 to 3 days before relapse onset was significantly associated with relapse risk (OR =1.40 [95% confidence interval 1.08-1.81]) in cold season. Consistent results were observed when considering PM10 as a binary variable, even if not significant. CONCLUSION: With an appropriate study design and robust ascertainment of neurological events and exposure, the present study highlights the effect of PM10 on the risk of relapse in MS patients, probably through oxidative stress mechanisms.

Neurological patients confronting climate change: A potential role for the glymphatic system and sleep.

Interest in the health consequences of climate change (global warming, heatwaves) has increased in the neurological community. This review addresses the impact of elevated ambient temperatures and heatwaves on patients with neurological and mental health disorders, including multiple sclerosis, synucleinopathies, dementia, epilepsies, mental health, and stroke. Patients with such conditions are highly vulnerable during heatwaves because of functional disorders affecting sleep, thermoregulation, autonomic system reactivity, mood, and cognitive ability. Several medications may also increase the risk of heatstroke. Special attention is devoted to the involvement of common underlying mechanisms, such as sleep and the glymphatic system. Disease prevention and patient care during heatwaves are major issues for caregivers. Beyond the usual recommendations for individuals, we favor artificially induced acclimation to heat, which provides preventive benefits with proven efficacy for healthy adults.

Sleep and global warming: How will we sleep when the Earth is hotter?

Societal concern about climate change and global warming has grown worldwide along with the concomitant awareness that health will be impacted deeply. Among living beings, humans have quite large capacities for adaptation to varied temperature conditions. Despite their tropical origin, they live under all Earth climates, such as polar, temperate, altitude, arid, and tropical climates, using a wide range of behavioral and physiological adaptive responses. We address the adaptive abilities of human sleep-wake regulation and its interplay with thermoregulation under different natural climates. Sleep represents one-third of our living time and is also a major determinant of morbidity and mortality; shortening sleep duration increases mortality and multimorbidity. In addition, major advances in sleep neurology have occurred in the last decades. Some have been extensively reviewed, notably comparative sleep physiology among animals, allowing one to hypothesize about the functions of the different sleep states, as well as their relation to cognitive neuroscience or body biorhythms. However, the question of the sleep adaptive capacity of humans to global warming has barely been addressed. We examine "normal" sleep and thermoregulation in young adults residing in temperate conditions. We then review the sleep and thermoregulatory reactions under various climatic conditions, demonstrating the role of sleep changes as potent adaptive responses to living under natural hot climatic conditions. As a result, we show that humans are well-equipped to adapt to severe climates.

Heatwaves and human sleep: Stress response versus adaptation.

The World Meteorological Organization considers a heatwave as "a period of statistically unusual hot weather persisting for a number of days and nights". Accompanying the ongoing global climate change, sharp heatwave bouts occur worldwide, growing in frequency and intensity, and beginning earlier in the season. Heatwaves exacerbate the risk of heat-related illnesses, hence human morbidity and mortality, particularly in vulnerable elderly and children. Heat-related illnesses present a continuum from normothermic (prickly heat, heat edema, heat cramps, heat tetany) to hyperthermic syndromes (from heat syncope and heat exhaustion to lethal heat stroke). Heat stroke may occur through passive heating and/or exertional exercise. "Normal sleep", such as observed in temperate conditions, is altered during heatwaves. Brisk excessive heat bouts shorten and fragment human sleep. Particularly, deep N3 sleep (formerly slow-wave sleep) and REM sleep are depleted, such as in other stressful situations. The resultant sleep loss is deleterious to cognitive performance, emotional brain function, behavior, and susceptibility to chronic health conditions and infectious diseases. Our group has previously demonstrated that sleep constitutes an adaptive mechanism during climatic heat acclimatization. In parallel, artificial heat acclimation procedures have been proposed in sports and military activities, and for the elderly. Other preventive actions should be considered, such as education and urban heat island cooling (vegetation, white paint), thus avoiding energy-hungry air conditioning.

Environmental neurology: Concepts and short history of an interdisciplinary approach to etiology, treatment and prevention.

Environmental Neurology (EN), a sub-discipline of Neurology and Neurological Sciences, favors an interdisciplinary collaboration allowing a holistic approach to understanding the impact of environmental factors on the nervous system and their relationship with neurological diseases. Several examples of diseases and conditions show the large scope of subjects addressed by EN. The EN sub-discipline focuses on both individual and population issues thus joining patient care and public health, respectively. Neuropathogenesis is addressed by several major questions: How do the environment and nervous system interact? Which exogenous factors can trigger neurological disease? When, where and how do they act? What are the therapeutic implications, and how can these disorders be controlled or prevented. To answer such questions, we address the incentive for, philosophy of and methods developed by EN, which seeks to safeguard Brain Health and, thus, the quality of life.

Environmental factors and stroke: Risk and prevention.

Stroke is a leading cause of death and adult disability globally. In addition to traditional risk factors, environmental risk factors have emerged over the recent past and are becoming increasingly important. The disproportionate rise of stroke incidence in low- and middle-income countries has been attributed, at least in part, to environmental factors. This narrative review provides details on the interplay between the environment and health generally and stroke specifically, covering topics including air pollution, atmospheric brown clouds, desert dust storms, giant wildfires, chemical contamination, biological aggressors, urbanization, and climate change. It also covers some beneficial environmental effects such as can be harnessed from the exposure to green spaces. It concludes with a summary of pragmatic actions that can be taken to help address some of these challenges at individual, community, and political advocacy levels.

Early-onset, conjugal, twin-discordant, and clusters of sporadic ALS: Pathway to discovery of etiology via lifetime exposome research.

The identity and role of environmental factors in the etiology of sporadic amyotrophic lateral sclerosis (sALS) is poorly understood outside of three former high-incidence foci of Western Pacific ALS and a hotspot of sALS in the French Alps. In both instances, there is a strong association with exposure to DNA-damaging (genotoxic) chemicals years or decades prior to clinical onset of motor neuron disease. In light of this recent understanding, we discuss published geographic clusters of ALS, conjugal cases, single-affected twins, and young-onset cases in relation to their demographic, geographic and environmental associations but also whether, in theory, there was the possibility of exposure to genotoxic chemicals of natural or synthetic origin. Special opportunities to test for such exposures in sALS exist in southeast France, northwest Italy, Finland, the U.S. East North Central States, and in the U.S. Air Force and Space Force. Given the degree and timing of exposure to an environmental trigger of ALS may be related to the age at which the disease is expressed, research should focus on the lifetime exposome (from conception to clinical onset) of young sALS cases. Multidisciplinary research of this type may lead to the identification of ALS causation, mechanism, and primary prevention, as well as to early detection of impending ALS and pre-clinical treatment to slow development of this fatal neurological disease.

Covid-19: Early Cases and Disease Spread.

The emergence and global spread of the Severe Acute Respiratory Syndrome Coronavirus-2 (SARS-CoV-2) is critical to understanding how to prevent or control a future viral pandemic. We review the tools used for this retrospective search, their limits, and results obtained from China, France, Italy and the USA. We examine possible scenarios for the emergence of SARS-CoV-2 in the human population. We consider the Chinese city of Wuhan where the first cases of atypical pneumonia were attributed to SARS-CoV-2 and from where the disease spread worldwide. Possible superspreading events include the Wuhan-based 7th Military World Games on October 18-27, 2019 and the Chinese New Year holidays from January 25 to February 2, 2020. Several clues point to an early regional circulation of SARS-CoV-2 in northern Italy (Lombardi) as soon as September/October 2019 and in France in November/December 2019, if not before. With the goal of preventing future pandemics, we call for additional retrospective studies designed to trace the origin of SARS-CoV-2.

Kampo medicine and Muro disease (Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex): Postscript and Historical Footnote.

Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-dementia Complex (ALS/PDC) is a disappearing neurodegenerative disease in three former high-incidence foci of the U.S. territory of Guam, Papua-Indonesia (New Guinea) and Kii Peninsula, Honshu Island, Japan (Muro disease). We report additional data that associate medicinal use of cycad seed to Muro disease in the southern Kozagawa focus of ALS/PDC. In the other two ALS/PDC-affected populations, cycad seed was used as a traditional topical medicine in New Guinea and Guam and, additionally, for food on Guam.

Kampo medicine and Muro disease (Amyotrophic Lateral Sclerosis and Parkinsonism-Dementia Complex).

Western Pacific Amyotrophic Lateral Sclerosis and Parkinsonism-dementia Complex (ALS/PDC) is a disappearing neurodegenerative disease in three former high-incidence foci of Guam-USA, Papua-Indonesia and Kii Peninsula, Honshu Island, Japan. The latter includes two distinct ALS/PDC-affected regions (Hohara and Kozagawa), where the disorder is known as Muro disease. In Hohara, oral exposure to plant (cycad) neurotoxins used in traditional medical practice has been linked previously to Muro disease. We report new observations that link Kampo medicine to Muro disease in the southern Kozagawa focus. Oral exposure to cycad seed toxins is associated with all three foci of Western Pacific ALS/PDC.

The neurology of COVID-19 revisited: A proposal from the Environmental Neurology Specialty Group of the World Federation of Neurology to implement international neurological registries.

A comprehensive review of the neurological disorders reported during the current COVID-19 pandemic demonstrates that infection with SARS-CoV-2 affects the central nervous system (CNS), the peripheral nervous system (PNS) and the muscle. CNS manifestations include: headache and decreased responsiveness considered initial indicators of potential neurological involvement; anosmia, hyposmia, hypogeusia, and dysgeusia are frequent early symptoms of coronavirus infection. Respiratory failure, the lethal manifestation of COVID-19, responsible for 264,679 deaths worldwide, is probably neurogenic in origin and may result from the viral invasion of cranial nerve I, progressing into rhinencephalon and brainstem respiratory centers. Cerebrovascular disease, in particular large-vessel ischemic strokes, and less frequently cerebral venous thrombosis, intracerebral hemorrhage and subarachnoid hemorrhage, usually occur as part of a thrombotic state induced by viral attachment to ACE2 receptors in endothelium causing widespread endotheliitis, coagulopathy, arterial and venous thromboses. Acute hemorrhagic necrotizing encephalopathy is associated to the cytokine storm. A frontal hypoperfusion syndrome has been identified. There are isolated reports of seizures, encephalopathy, meningitis, encephalitis, and myelitis. The neurological diseases affecting the PNS and muscle in COVID-19 are less frequent and include Guillain-Barré syndrome; Miller Fisher syndrome; polyneuritis cranialis; and rare instances of viral myopathy with rhabdomyolysis. The main conclusion of this review is the pressing need to define the neurology of COVID-19, its frequency, manifestations, neuropathology and pathogenesis. On behalf of the World Federation of Neurology we invite national and regional neurological associations to create local databases to report cases with neurological manifestations observed during the on-going pandemic. International neuroepidemiological collaboration may help define the natural history of this worldwide problem.

Age of onset in concordant twins and other relative pairs with multiple sclerosis.

The ages of onset in multiple sclerosis cases span more than 7 decades. Data are presented for affected relative pairs from a Canadian population base of 30,000 multiple sclerosis index cases (1993-2008). The effects of genetic sharing, parent of origin, intergenerational versus collinear differences, and gender on the ages of onset were evaluated in the following concordant pairs: monozygotic twins (n = 29), dizygotic twins (n = 10), siblings (n = 614), first cousins (n = 405), half siblings (n = 29), parent/child (n = 285), and aunt/uncle/niece/nephew (avunculars) (n = 289). Fisher's z test assessed intraclass correlation (r) for ages of onset. Correlations for monozygotic twins, dizygotic twins, full siblings, and first cousins were 0.60, 0.54, 0.20, and 0.10, respectively. Dizygotic twins resembled monozygotic twins more than siblings. The age-of-onset correlation for maternal half siblings (r = 0.37) was higher than that for paternal half siblings (r = 0.26), consistent with other observations suggesting an intrauterine environmental effect on multiple sclerosis risk. Intergenerational comparisons are complicated by substantial increases of multiple sclerosis incidence over time. Genetic loading (familial vs. sporadic cases) did not generally influence the age of onset, but correlation of age of onset in multiple sclerosis relative pairs was proportional to genetic sharing. A maternal parent-of-origin effect on the age of onset in collinear generations was suggested.

A review of epidemiological research on stroke and dementia and exposure to air pollution.

Background Outdoor air pollution is now a well-known risk factor for morbidity and mortality, and is increasingly being identified as a major risk factor for stroke. Methods A narrative literature review of the effects of short and long-term exposure to air pollution on stroke and dementia risk and cognitive functioning. Results Ten papers on stroke and 17 on dementia were selected. Air pollution, and in particular small particulate matter, contributes to about one-third of the global stroke burden and about one-fifth of the global burden of dementia. It particularly affects vulnerable patients with other vascular risk factors or a prior history of stroke in low- and medium-income countries. New pathophysiological mechanisms of the cause-effect associations are suggested. Conclusion Air pollution should be considered as a new modifiable cerebrovascular and neurodegenerative risk factor. This massive worldwide public health problem requires environmental health policies able to reduce air pollution and thus the stroke and dementia burden.

Environmental neurology: a promising new field of practice and research.

The environment has profound influences on human health. Environment is the combination of natural (physical, chemical, biological) and cultural (sociological) conditions in which living organisms, man in particular, develop. Adaptation is the human physiological response to external factors including mechanisms such as circadian rhythms (sleep and wakefulness), biorhythms, thermoregulation, and others to adjust to changes in natural conditions (night and day, cosmic rhythms, climatic changes). Man remains vulnerable due to a number of factors: genetic, physiological, age, sex, impaired reparative or protective mechanisms, or acquired factors (risky behaviors and lifestyle, nutritional habits). Hazard is the potential of a particular factor to have a negative impact on health. Risk is the probability of that hazard occurring; it defines and measures the predictability of that hazard. A number of environmental factors have a profound influence on the pathogenesis of neurological disorders. Environmental neurology follows the classical diagnostic precepts: from symptom to syndrome in the search for etiology and individualized treatment of the patient. It also utilizes principles of epidemiology and public health, toxicology and occupational medicine; i.e., an approach by "milieu" and by specific factors or "agents." Environmental neurology offers a promising new field of practice and research.

Multiple sclerosis and air pollution exposure: Mechanisms toward brain autoimmunity.

The association between neurodegenerative diseases and environmental exposures, in particular air pollution, has been noticed in the last two decades, but the importance of this environmental factor in multiple sclerosis (MS) pathogenesis has not been considered extensively. However, recent evidence suggests that major mechanisms involved in MS pathogenesis, such as inflammatory factors expression, free radicals overproduction, the blood brain barrier (BBB) breakdown, neuroinflammation, vitamin D deficiency and mitochondrial dysfunction could also occur due to exposure to air pollutants. A prospective hypothesis is suggested here in which exposure to air pollutants may initiate destructive mechanisms inducing inflammatory-oxidative cascades, reduction of immunological self-tolerance and neurodegeneration leading to brain autoimmunity.