Flies as models for circadian clock adaptation to environmental challenges

Life on earth is assumed to have developed in tropical regions that are characterized by regular 24 hr cycles in irradiance and temperature that remain the same throughout the seasons. All organisms developed circadian clocks that predict these environmental cycles and prepare the organisms in advance for them. A central question in chronobiology is how endogenous clocks changed in order to anticipate very different cyclical environmental conditions such as extremely short and long photoperiods existing close to the poles. Flies of the family Drosophilidae can be found all over the world—from the tropics to subarctic regions—making them unprecedented models for studying the evolutionary processes that underlie the adaptation of circadian clocks to different latitudes. This review summarizes our current understanding of these processes. We discuss evolutionary changes in the clock genes and in the clock network in the brain of different Drosophilids that may have caused behavioural adaptations to high latitudes.     

Hemorrhagic stroke in the tropics

With the increasing industrialization of countries in the tropical and subtropical regions, cerebrovascular disease is becoming an increasingly recognized cause of morbidity and mortality. The incidence of hemorrhagic stroke versus ischemic stroke is unclear as data regarding hemorrhagic stroke in developing countries of the tropical and subtropical regions, especially in the English literature, continues to be sparse. As in the developed world, however, the major etiologies for hemorrhagic stroke in developing countries relate to typical vascular risk factors and, to a lesser extent, central nervous system vascular malformations, medications, and infectious etiologies.     

Relevance of neuroimaging in the diagnosis and management of tropical neurologic disorders

The development in neuroimaging techniques has revolutionized the way neurology is practiced, including neurologic disorders in tropics. Some diseases occur exclusively, whereas some are more common in tropical regions. However, some are becoming increasingly prevalent in the developed world too, as a result of patterns of human migration and globalization. It is imperative to learn about the role of imaging in tropical neurology, which might assist early diagnosis and treatment and also add to the existing knowledge. Infections are more common in the tropics and require special attention in view of their potential treatability.     

Is stroke incidence in low- to middle-income countries driven by economics?

The incidence of stroke in low- to middle-income countries now exceeds that in high-income countries. These low- to middle-income countries also have greater case fatality and a younger age of stroke onset, factors that contribute to a high stroke burden. Macroeconomic indicators of socioeconomic status, such as health expenditure, appear to be inversely associated with stroke incidence. However, there are often large socioeconomic gradients between regions such as between urban and rural regions. This article emphasizes that macroeconomic indicators are likely to mask regional disparities in stroke incidence. Public health messages and prevention strategies must therefore be targeted regionally rather than nationwide. Without a comprehensive and multifaceted approach to prevention, the epidemic of stroke will continue.     

Widening gap of stroke between east and west. Eight-year trends in occurrence and risk factors in Russia and Sweden

BACKGROUND AND PURPOSE: Stroke is declining in most of the western and northern European countries, whereas no such decline is seen in eastern Europe. The aim of this study was to investigate trends in stroke attack rates and 28-day case fatality and risk factor levels in Novosibirsk, Siberia, and northern Sweden during 1987-1994. METHODS: Within the World Health Organization Multinational Monitoring of Trends and Determinants in Cardiovascular Disease (MONICA) Project, acute stroke events and 28-day case fatality were registered in a standardized way in men and women aged 35 to 69 years. Cardiovascular risk factors were monitored in randomly selected men and women in the group aged 35 to 64 years in 1985-1986 and 1994-1995. RESULTS: Stroke attack rates increased significantly from 430 per 100 000 to 660 (P=0.005) in men in Novosibirsk and from 298 to 500 (P=0.02) in women. In northern Sweden, stroke attack rates varied between 244 and 303 per 100 000 in men and from 117 to 157 in women, with a small increasing trend in women (P=0.03). The mortality rates were 5 times higher in Novosibirsk, and the case fatality was significantly lower in northern Sweden (P=0.0001). The risk factor surveys showed significantly higher blood pressure, overweight, and more smoking men in Novosibirsk, while northern Sweden had higher cholesterol levels and more smoking women. Most risk factors showed stable or improving patterns over time. CONCLUSIONS: Large differences in both attack rates and case fatality account for the large and widening gap in stroke mortality between Russia and Sweden. A higher prevalence of hypertension in Russia may explain much of the differences in stroke occurrence. In Russia, a marked increase in attack rates has occurred despite stable or improving patterns of conventional cardiovascular risk factors.     

World-wide trends in multiple sclerosis mortality

Mortality attributed to multiple sclerosis (MS) was analyzed for 35 countries around the world using World Health Organization reports from 1965 to 1984. Trends were plotted for the United States and Canada, for various regions of Europe, Israel, South America, Asia, Australia and some Pacific countries. In general, MS mortality has declined steadily in North America and most of western Europe as well as in countries with a western culture but has remained stable or increased in eastern and northern Europe. Although several Mediterranean countries reported a recent increased frequency of MS, it was not (yet?) evident in mortality data. Intensive prospective surveillance of MS frequency trends in selected regions of the world will determine the validity of the trends based on mortality.     

Movement disorders in the tropics

The spectrum of movement disorders in the tropics is different from that seen in the industrialized nations of the west. This is not surprising given the unique combination of environmental and population characteristics in the tropics. Infections seldom encountered in the west such as tuberculous meningitis, typhoid fever, Japanese encephalitis, malaria, trypanosomiasis or cysticercosis are often seen in the tropics and with global patterns of travel and immigration these conditions are becoming more common worldwide. Movement disorders associated with these infections, HIV, slow virus and prion disease are discussed. Taking into account the diverse etiologies of movement disorders in the tropics, movement disorders with a nutritional basis such as the infantile tremor syndrome, seasonal ataxia and tropical ataxic neuropathy, and manganese neurotoxicity are also reviewed. Finally, certain special characteristics of ubiquitous disorders such as Parkinson's disease, and disorders with a genetic basis such as Wilson's disease and spinocerebellar degeneration are described.     

Stroke Epidemiology: Advancing Our Understanding of Disease Mechanism and Therapy

Stroke is the fourth killer and number one cause of adult disability in the United States. The estimated direct and indirect costs of stroke care in this country are $68.9 billion for 2009. The prevalence of stroke and its cost will undoubtedly rise as the aging population increases. In addition, stroke incidence and mortality are increasing in less developed countries in which the lifestyles and population restructuring are rapidly changing. More population-based research to assess incidence, risk factors, and outcomes are needed in these countries. Epidemiologic studies can help identify groups of individuals or regions at higher risk for stroke. They can also help us better understand the natural history of certain conditions and therefore push the direction of therapeutic investigations. Furthermore, the study of trends across different time periods and different populations can help investigators evaluate the effects of stroke care programs and treatment options.     

Photoperiod-independent changes in immunoreactive brain gonadotropin-releasing hormone (GnRH) in a free-living, tropical bird

Timing of seasonal reproduction in high latitude vertebrates is generally regulated by photoperiodic cues. Increasing day length in the spring is associated with changes in the brain that are responsible for mediating reproductive activities. A primary example of this is the increased content of gonadotropin-releasing hormone (GnRH) in the preoptic area of the hypothalamus in birds as they enter the spring breeding season. Increased GnRH activity stimulates the release of luteinizing hormone and follicle-stimulating hormone from the anterior pituitary. These gonadotropins induce growth of the gonads and release of sex steroids which act on the brain to mediate reproductive behaviors. By contrast, seasonal breeding in the tropics can occur in the absence of significant changes in photoperiod. To our knowledge, no studies have investigated whether seasonal breeding in free-living tropical vertebrates is associated with seasonal changes in the GnRH system. We studied two populations of rufous-collared sparrows (Zonotrichia capensis) at the equator, separated by only 25 km, but with asynchronous reproductive phenologies associated with local climate and independent of photoperiodic cues. We collected brains and measured GnRH immunoreactivity (GnRH-ir) during each population's breeding and non-breeding periods. Breeding males had larger, but not more, GnRH-ir cells than non-breeding birds. The plasticity of the GnRH system was associated with local climate, such that the two populations exhibited asynchronous changes in GnRH-ir despite experiencing identical photoperiod conditions. Our results demonstrate that tropical birds can exhibit neural changes similar to those exhibited in higher latitude birds. However, these tropical populations appear to be using supplementary cues (e.g., rainfall, temperature, food availability) in a similar way to higher latitude species using an initial predictive cue (photoperiod). These results raise questions about the evolution of reliance upon photoperiodism and the strength of reproductive responses to other environmental cues in congeners from higher latitudes. The ability to respond to a multitude of environmental cues might be part of the ancestral condition, and the subsequent obligate photoperiodism in high-latitude congeners could reflect a loss of flexibility in response to environmental signals.     

Standardized incidence ratios of stroke: a worldwide review

Comparison of stroke incidence in various parts of the world is difficult because differences in diagnostic criteria, medical facilities and age-sex distributions are often not taken into account. We calculated age-sex standardized incidence ratios (SIR) of stroke in 37 regions based on recent reports. The USA (1976) was taken as the standard population. In western countries SIRs varied from 0.8 to 2.1. In China and Japan, SIRs varied from 0.7 to 3.6. While the lowest and highest SIRs differed by a factor of 5, only 6 of the 37 studies yielded a SIR of more than 2.0 or below 0.75. Of these, 4 were from China and Japan. The highest ratios were based on a very intensive door-to-door survey and probably should not be compared to less intensive studies. We conclude that world-wide variation in age-sex adjusted stroke rates is relatively small.     

Burden of stroke in black populations in sub-Saharan Africa

Sub-Saharan Africa is undergoing epidemiological transition. Stroke and other vascular diseases increasingly contribute to the burden of disease. There are no systematic reviews of stroke mortality, prevalence, incidence, and case fatality. We combined a thorough search and critical assessment of the published research. Stroke mortality is as high, perhaps higher, than in high-income regions and increases with age in sub-Saharan Africa as in high-income countries, but the absolute number of stroke deaths remains low. There are no adequate community-based stroke incidence studies. Hospital-based incidence is lower than in high-income regions, but higher in young people, possibly due to hospital admission bias. There are no community-based data on case fatality, but hospital-based case fatality is higher than elsewhere. The prevalence of stroke is lower than in high-income regions, but disabling stroke is as prevalent. As the region develops economically, the incidence of stroke and other vascular diseases will increase unless interventions are implemented. Only community-based incidence studies will accurately reveal the burden of stroke.     

High incidence rates of stroke in Orebro,Sweden: Further support for regional incidence differences within Scandinavia

BACKGROUND AND PURPOSE: As a basis for comparison of differences in stroke incidence in Scandinavian countries, a community-based stroke register was established in Orebro in the centre of Sweden. METHODS: All first-ever cases of stroke were registered during a 12-month period 1999-2000. The study population was 123,503. The WHO definition of stroke was used. Cases were searched inside as well as outside hospital. Multiple overlapping sources and 'hot pursuit' technique were used in the process of case ascertainment. RESULTS: 388 cases of first-ever stroke were found, corresponding to a crude incidence rate of 314 (95% CI, 283-348) per 100,000 per year, 337 (95% CI, 294-386) for females, and 289 (95% CI, 248-336) for males. Adjusted to the European population, the corresponding rates were 254 (95% CI, 227-284) per 100,000 per year, 273 (95% CI, 238-311) for females and 232 (95% CI, 206-261) for males. The overall 28-day case-fatality rate was 19% (95% CI, 15-23). The case-fatality rates for the different subtypes of stroke were as follows: brain infarction, 10%; intracerebral haemorrhage, 20%; subarachnoidal haemorrhage 45%, and undetermined pathological type 56%. CONCLUSIONS: The present study as well as other studies in northern and middle Scandinavia show significantly higher incidence rates than studies from other regions. The crude incidence rate, reflecting the age distribution of the population, is even higher, indicating a burden to the community that is rather increasing than decreasing.     

Co-infection of HIV and tropical infectious agents that affect the nervous system

Tropical infections refer to a group of diseases usually located in regions with a warm climate, particularly affecting developing countries, partly because of the conditions that allow them to thrive. However, due to the increased international travel, infectious agents that were previously limited to tropical regions pose an increasing threat to populations at risk for opportunistic infection (OI), especially those infected with the HIV. Tropical infections can facilitate HIV transmission and accelerate the progression of asymptomatic HIV infection to AIDS. Some have the potential to alter the epidemiology, natural history, and/or response to treatment of the other. The introduction of highly active antiretroviral therapy has provided a huge benefit for the vast majority of patients infected with the HIV, by allowing the immune system to recover, improving the clinical and radiological results and reducing the number of OI. On the other hand, some patients have developed various disorders of immune reconstitution, resulting in either hyper-immune inflammatory response to an exogenous antigen or autoimmunity. A significant proportion of these cases have been reported in immigrants from tropical countries to high-income countries, therefore awareness of these phenomena is needed since clinical presentations are often atypical and pose diagnostic challenges. This article reviews some of the key diagnostic aspects of tropical infections associated with HIV infection.     

Migraine and risk of cerebral infarction

In this paper we review the evidence that migraine is associated with ischemic stroke, emphasizing potential biases, factors which may influence the association, potential mechanisms, and potential public health impact. Consistency of case-control findings from several countries and supporting evidence from prospective data suggest that the association is not an artifact of study design or execution. However, it is less clear whether migraine without aura is associated with stroke or whether the association is restricted to migraine with aura. Similarly, there are few data examining the magnitude of the association among nonusers of oral contraceptives compared to those who use low estrogen oral contraceptives. Moreover, there is still no convincing evidence on the mechanisms that would be implied and on the groups of migraineurs really at risk of ischemic stroke. Despite the considerable advances in our understanding of the relationship between migraine and stroke, there are many gaps in the data needed for public health recommendations.     

Stroke care during the COVID‐19 pandemic: experience from three large European countries

In order to cope with the exponentially increasing number of patients infected with SARS‐CoV‐2, European countries made enormous efforts to reorganize medical assistance and several diseases, including stroke, were particularly impacted. We report the experience of stroke neurologists from three European countries (Italy, France and Germany) that faced the pandemic at diverse time points and with different approaches, depending on their resources and healthcare system organization. Pre‐hospital and in‐hospital acute stroke pathways were reorganized to prioritize COVID‐19 management and, in severely affected regions of Italy and France, stroke care was centralized to a limited number of centers, whereas the remaining stroke units were dedicated to patients with COVID‐19. Access to acute stroke diagnostics and time‐dependent therapies was limited or delayed because of reduced capacities of emergency services due to the burden of patients with COVID‐19. A marked reduction in the number of patients presenting with transient ischaemic attack and stroke was noted in the emergency departments of all three countries. Although we only have preliminary data, these conditions may have affected stroke outcome. These indirect effects of the COVID‐19 pandemic could negate the efforts of stroke neurologists over the last few years to improve outcome and reduce mortality of stroke patients. Although the SARS‐CoV‐2 infection rate is slowing down in Europe, the effects of ending lockdown in the next months are unpredictable. It is important for the European and world stroke community to share what has been learned so far to be plan strategies to ensure stroke care in the future and upcoming challenging times.     

Standard method for developing stroke registers in low-income and middle-income countries: experiences from a feasibility study of a stepwise approach to stroke surveillance (STEPS Stroke)

BACKGROUND: Stroke is a leading global cause of death, with an estimated 5.8 million fatal events in 2005, two-thirds of which happened in low-income and middle-income countries. In these regions, epidemiological methods to establish hospital-based stroke registers for clinical audit or studies to estimate incidence are scarce. Our aim was to ascertain whether stroke registers could be set up in geographically diverse populations in low-income and middle-income countries, using standardised data-collection manuals and methods, before recommending their wider use. METHODS: WHO's stepwise approach to stroke surveillance (STEPS Stroke) offers an entry point for countries to register stroke patients in health-information systems. The methods proposed in this strategy were tested in a feasibility study, which focused on hospitalised stroke patients in nine different surveillance sites located in five low-income and middle-income countries. Data collection was for a median of 12 months. Observed differences between men and women were adjusted for age and surveillance site with logistic-regression analyses. FINDINGS: A total of 5557 stroke patients were registered; 91 people whose age was missing or younger than 15 years were excluded from the analyses. Mean age was 64.2 years (SD 14.6), and 2484 (45%) participants were women. Ischaemic stroke accounted for about two-thirds of events. Half of all patients were hospitalised the same day. Stroke subtype was verified in 4913 (90%) participants by diagnostic techniques. Women had lower odds of verification of stroke subtype compared with men after adjustment for age and surveillance site (odds ratio 0.69 [95% CI 0.56-0.86]; p=0.0006). INTERPRETATION: STEPS Stroke can be used in diverse populations to provide data in a standardised manner in countries with little or no previous records of stroke. Future studies should concentrate on expansion beyond hospital case series by adding information for stroke patients treated outside the hospital, linked to census data for the source population from which the cases come.     

Stroke epidemiology, prevention, and management strategies at a regional level: Latin America and the Caribbean

Stroke is a major health problem in Latin American and Caribbean countries. In this paper, we review the epidemiology, aetiology, and management of stroke in the region based on a systematic search of articles published in Spanish, Portuguese, and English. Stroke mortality is higher than in developed countries but rates are declining. Population-based studies show variations in incidence of strokes: lower rates of ischaemic stroke and similar rates of intracranial haemorrhages, compared with other regions. A significant proportion of strokes in these populations can be attributed to a few preventable risk factors. Some countries have published national clinical guidelines, although much needs to be done in the organisation of care and rehabilitation. Even though the burden of stroke is high, there is a paucity of information for implementing evidence-based management. The Global Stroke Initiative, the WHO STEPS Stroke surveillance, and WHO-PREMISE projects provide opportunities for surveillance at institutional and community levels.     

Multiple sclerosis in Australia and New Zealand: are the determinants genetic or environmental?

The prevalence of multiple sclerosis (MS) has been recently reported from nine regions of Australia and New Zealand. There is a marked variation of prevalence with latitude. MS is seven times more common in southern New Zealand than in tropical Queensland. On current evidence, it is suggested that in both countries this variation is predominantly due to environmental rather than genetic factors.     

Viral infections of the central nervous system

Viral infections of the central nervous system in the tropical countries of Asia and the Indian subcontinent are different from those of the Western and developed world. Many of the endemic and epidemic encephalitides that are prevalent in these regions, such as Japanese encephalitis, have characteristic findings on imaging, especially on magnetic resonance imaging, allowing a rapid diagnosis and differentiation from clinically similar syndromes. Other emerging viral infections in the region in recent years have posed new challenges. The contribution of neuroimaging to the management of these emerging infections is also discussed.     

Cerebral ischemic stroke: is gender important?

Cerebral stroke continues to be a major cause of death and the leading cause of long-term disability in developed countries. Evidence reviewed here suggests that gender influences various aspects of the clinical spectrum of ischemic stroke, in terms of influencing how a patients present with ischemic stroke through to how they respond to treatment. In addition, this review focuses on discussing the various pathologic mechanisms of ischemic stroke that may differ according to gender and compares how intrinsic and hormonal mechanisms may account for such gender differences. All clinical trials to date investigating putative neuroprotective treatments for ischemic stroke have failed, and it may be that our understanding of the injury cascade initiated after ischemic injury is incomplete. Revealing aspects of the pathophysiological consequences of ischemic stroke that are gender specific may enable gender relevant and effective neuroprotective strategies to be identified. Thus, it is possible to conclude that gender does, in fact, have an important role in ischemic stroke and must be factored into experimental and clinical investigations of ischemic stroke.