Posted in e-learning for strokecarers Resources

Module 3: Stroke warning signs and symptoms

Introduction to the module 3:

Module 3 discusses common stroke warning signs and symptoms, how those relate to the brain basics that we discussed in Module 2. Then, we will delve into the popular F.A.S.T. stroke awareness campaign. I encourage you to re-visit module 2 – brain basics – for a better understanding of how the warning signs occur.

Learning objectives:

3.1. Stroke warning signs and symptoms

3.2. The F.A.S.T. campaign

3.3. The concept of the “golden hour”

3.4. Delays in seeking hospital care

3.5. What should we do in those situations?

3.1. Stroke warning signs and symptoms

According to the National Institute of Neurological Disorders and Stroke1, the following are a list of stroke warning signs and symptoms.

  • Sudden numbness or weakness of one side of the face, an arm, or a leg
  • Sudden confusion
  • Difficulty in understanding or trouble in speech
  • Sudden trouble seeing in one or both eyes
  • Sudden trouble walking, dizziness, loss of balance and coordination
  • Sudden severe headache with no known cause
  • Seeing two images (double vision)
  • Vomiting

If you re-visit Module 2: The brain basics, you can appreciate how these problems occur as a result of interruption to the blood supply routes; anterior, middle, and posterior cerebral arteries.

As soon as the signs and symptoms begin to unfold, no one can be sure whether it is going to be either a stroke or mini-stroke. Hence the safest strategy in this scenario is to suspect a stroke and take the individual to the nearest hospital with a minimum delay. Even if it is a mini-stroke, the patient needs to be assessed as early as possible to prevent a full-blown stroke.

3.2. The F.A.S.T. campaign

F.A.S.T. is an acronym of popular stroke warning signs and symptoms awareness campaign in the world. Each of the first three letters denotes one common sign or a symptom of stroke, which can easily be detected by anyone. The last letter, T, emphasizes the urgency of taking action – call emergency – as soon as possible. Those are;

  • F : face,
  • A :arms,
  • S : speech,
  • T : time.

The following poster (Figure 1) is from such a campaign carried out by the University College London Hospitals in the NHS. It summarises what F.A.S.T. means.

How should we use the F.A.S.T.?

Knowing what these letters represent is not enough. We need to ask its associated specific questions. The following questions assist you in the effective use of the acronym.

How to suspect a stroke

  1. Look at the face

    Ask: can you smile?
    Observe: whether one side of the mouth or an eye is drooping

  2. Compare both arms

    Ask: Raise your both arms
    Observe: Whether the person is having any difficulty of raising one or both arms

  3. Observe the speech

    Observe: whether the person cannot speak or understand as before

  4. Check the time

    Call an ambulance of you observe any one of the above

However, research reveals that the F.A.S.T. campaign, although it raises the awareness of stroke signs and symptoms, may not significantly improve our response to the situation, particularly when the signs and symptoms are not severe such as in the case of mini-stroke2.

3.3. The concept of the “golden hour”

In the event of a stroke, the first hour is the most critical to save brain cells as many as possible. As you already know every passing minute costa about 2 million neurons3. The affected person should be on the bed of a hospital with adequate facilities to manage a stroke emergency. This hour is described as the golden hour4.

However, the elapse of the first hour does not mean that we should lose our hope of salvaging still-alive but affected brain tissues. The Canadian best practice guidelines keep from the “witnessed symptom onset” to hospital arrival time as “four and a half hours”5.

The following video clip from the US CDC summarizes the stroke signs and symptoms except for its reference to the time frame.

Stroke warning signs and symptoms (source: US CDC)

3.4. Delays in seeking hospital care

Saving still-alive brain cells is a race against time. However, delays happen. The delays can be conceptualized as pre-hospital delays and in-hospital delays. This section discusses the reasons for prehospital delays.

3.4.1. The “family member” effect

Interestingly, research shows that if a stroke occurs at home and in front of family members and loved ones, the delaying time to seek hospital care is longer than if it occurs at the workplace or in front of unknown bystanders6.

This is important because the majority of strokes occur at home and they arrive late at the hospital. For example, in the US, 70 percent of stroke events occur at home and 70 percent of patients with a suspected stroke arrive at a hospital six hours after the event6.

3.4.2. Knowledge and perceived seriousness

Lack of knowledge about stroke warning signs and symptoms is a major problem in spite of awareness campaigns. This is especially relevant to low-middle income countries where the majority of strokes occur. Very few studies exist about awareness levels of stroke warning signs and symptoms from those countries.

However, the knowledge of warning signs alone is inadequate to shorten the delay. It is not the knowledge but, research shows, the perceived seriousness of the observed signs and symptoms triggers action8.

3.4.3. Communicating suspected stroke signs and symptoms

The delay also occurs after taking the decision either to call an ambulance or taking to a hospital depending on the services available. This occurs when describing the event via telephone because most of the time people use vague descriptions. Most of the time we tend to use vague terms to describe the events of a stroke9.

3.4.4. Transport

Lack of transport facilities is a major cause for delay in places where community ambulance services either do not exist or not accessible due to geographic and economic reasons, particularly in low-middle income countries.

3.5. What to do when we encounter a suspected patient

  • Decision making is the key; Follow the F.A.S.T.
  • First aid and CPR if necessary
  • Remind the reasons for the delays
  • Act fast; call an ambulance; if that facility does not exist, take the person to the nearest hospital as soon as possible.
References
  1. National Institute of Neurological Disorders and Stroke (NINDS): Basic facts: preventing stroke; NIH; 2020. Accessed on September 16, 2020.
  2. Wolters FJ, Li L, Gutnikov SA, Mehta Z, Rothwell PM. Medical Attention Seeking After Transient Ischemic Attack and Minor Stroke Before and After the UK Face, Arm, Speech, Time (FAST) Public Education Campaign: Results From the Oxford Vascular Study. JAMA Neurol. 2018;75(10):1225–1233. doi:10.1001/jamaneurol.2018.1603
  3. Jeffrey L. Saver (2006): “Time is Brain”: Quantified; Stroke Journal. 2006;37(1): 263-266.
  4. Advani R, Naess H. & Kurz M.W. (2017). The golden hour of acute ischemic stroke.Scand J Trauma Resusc Emerg Med. 2017 May 22;25(1):54. doi: 10.1186/s13049-017-0398-5.
  5. Canadian Stroke Best Practices (2018): Emergency Medical Services Management of Acute Stroke Patients Recommendations.
  6. Dhand, A., Luke, D., Lang, C. et al. Social networks and risk of delayed hospital arrival after acute stroke. Nat Commun 10, 1206 (2019). https://doi.org/10.1038/s41467-019-09073-5.
  7. Eric S. Donkor (2018): Stroke in the 21st Century; Stroke Res Treat.: published online.
  8. Teusch I Y, Brainin M. Stroke Education: Discrepancies among Factors Influencing Prehospital Delay and Stroke Knowledge. International Journal of Stroke. 2010;5(3):187-208. doi:10.1111/j.1747-4949.2010.00428.x
  9. Christopher T. Richards, Baiyang Wang, Eddie Markul, Frank Albarran, Doreen Rottman, Neelum T. Aggarwal, Patricia Lindeman, Leslee Stein-Spencer, Joseph M. Weber, Kenneth S. Pearlman, Katie L. Tataris, Jane L. Holl, Diego Klabjan & Shyam Prabhakaran (2017) Identifying Key Words in 9-1-1 Calls for Stroke: A Mixed Methods Approach, Prehospital Emergency Care, 21:6, 761-766, DOI: 10.1080/10903127.2017.1332124

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brain image
Posted in e-learning for strokecarers Resources

Module 2: Brain Basics for stroke carers

At the end of this module – brain basics for stroke carers – you will be able to describe the brain’s basic anatomy and functions that could be affected by stroke.

In the first module – Stroke basics for stroke carers – we peeped into the definitions of the word, stroke, different stroke types, what happens in a stroke, and who are at risk.

2.1. Brain covers

2.2. Brain surface map

2.2.1. Frontal lobe and Broca’s area

2.2.2. Parietal lobe

2.2.3. The “Homunculus” (“Two Little Humans”)

2.2.4. Temporal lobe

2.2.5. Occipital lobe

2.3. Brain’s blood supply

2.1. Brain covers

Brain basics begin with an introduction to brain covers. Our brain is a very pliable organ. Even a small finger pressure makes a dent over its surface. The bony skull protects it and, as Figure 1 shows, three layers underneath the skull wrap the brain snugly. The outermost cover ( the folded one in Figure 1) is called, “Dura mater” (meaning “tough mother”). As its name implies it is firm and thick. The other two inner covers (“spider mother” and “soft mother”) is thinner, transparent, as well as glistening. Blood vessels traverse through the two layers bathing a colorless “cerebrospinal fluid”. You can also see that the surface is folded into grooves (long convoluted ditches) and bumps (long convoluted surfaces) underneath the inner two covers.

brain covers
Figure 1:Brain covers (source: The University of Utah under the creative commons license

Visual credit: Videos drawn from the NeuroLogic Exam and PediNeuroLogic Exam websites are used by permission of Paul D. Larsen, M.D., University of Nebraska Medical Center and Suzanne S. Stensaas, Ph.D., University of Utah School of Medicine. Additional materials were drawn from resources provided by Alejandro Stern, Stern Foundation, Buenos Aires, Argentina; Kathleen Digre, M.D., University of Utah; and Daniel Jacobson, M.D., Marshfield Clinic, Wisconsin. The movies are licensed under a Creative Commons Attribution-non-commercial-ShareAlike License.

2.2. Surface map

Our brain surface owns a highly advanced map. Let us see how it is organized. An understanding of this map is an essential part of brain basics.

Figure 2 shows the brain sans its covers. It consists of two equal halves – identified as left and right hemispheres. Both communicate with each other via neurons cells who travel through a short thick stalk deep in the middle. We do not see the stalk in this image. 

Frontal lobe
Figure 2: Brain sans its covers (source: the University of Utah under the creative commons license)

Scientists name this densely wrinkled (or densely folded) surface as the “cerebral cortex”; it is a layer with thickness varying from 1mm to 4.5mm averaging about 2.5mm (one inch)1. This layer, grey in color (also called “grey matter”) is made up of tightly packed millions of neurons. Using its grooves and bumps as landmarks, scientists divide it into four large regions, also called “lobes”: Frontal lobe, Parietal lobe, Temporal lobe, and Occipital lobe (Figure 3).

brain lobes (Image source: University of Utah); link: https://library.med.utah.edu/kw/hyperbrain/figures/2a.htm
Figure 3: Brain lobes (source: The University of Utah under the creative commons license)

2.2.1. Frontal lobe (“region”)

Figure 3 depicts the Frontal lobe blue in color. It extends front to back until it meets a groove (or a fissure), scientists name the”Central Sulcus”. This groove separates the Frontal lobe from another two regions (lobes): the Parietal lobe and the Temporal lobe.

Pre-central gyrus (Primary Motor Cortex)

Now, look at Figure 4 and focus on the red-colored strip that lies in front of the Central Sulcus. Scientists name this bump the “Precentral Gyrus” because of its placement. As you can see, this strip ascends parallel to the Central groove from its left side over to the top. It ends after descending about 1cm on its own. We have exactly a similar strip on the right half of the brain too. The nerve cells that populate this strip has a very special job to do; they send commands, with our approval, to muscles of the opposite side of the body to move. Because of this job, scientists call it the “Primary Motor Cortex”.

Figure 4: Pre and postcentral gyrus
(Image courtesy: S Bhimji MD; from Neuroanatomy, Postcentral Gyrus Copyright © 2020, StatPearls Publishing LLC. under the terms of the Creative Commons Attribution 4.0 International License (http://creativecommons.org/licenses/by/4.0/),

The nerve cells in the large grey-colored area that spans towards the front of this “Primary Motor Cortex” become very busy when we think, make decisions, behave in ways whatever we want. Because we, humans, are the only ones who can do these high-end activities, we own the largest Frontal lobe among all animals.

Broca’s area (Figure 5)

This is a special small area in the Frontal lobe that merits our attention. We find it over the left Frontal lobe. The nerve cells in this area specialize in word production both in speech and writing. They process information that receives from another area (Wernicke’s area that situates in the Temporal lobe) and coordinates those with another set of large neural networks2.

Why do we need to know about this? It is because the death of these nerve cells results in a special kind of speech difficulty, called Broca’s aphasia.

Figure 5:The connection between the Broca’s area and the Wernicke’s area
(source: Wikimedia Commons)

2.2.2. Parietal lobe (Figures 3 and 4)

Figure 3 depicts this lobe (“region”) pale white in color. It begins just behind the Central Sulcus (groove), spreads over the top, and descends towards the left side to meet another groove, called the Lateral Sulcus. And the lobe extends behind to meet another groove that separates it from the Occipital lobe.

Post-central Gyrus

Figure 4 depicts this area of strip blue in color. Beginning just behind the Central Sulcus (groove), it runs parallel to its counterpart, the Precentral Gyrus that lies on the opposite bank of the groove. Very much similar to its counterpart, the nerve cells in this area look after the exact same locations of the body’s opposite side. However, there is a marked contrast; unlike its counterpart nerve cells who send commands, these nerve cells receive information about touch, temperature, and pain. Then, they relay the information to the Frontal lobe nerve cells for necessary action. Because of the nature of this job, scientists name this strip the “somatosensory cortex”. For example, when we feel pain in the left arm, the area assigned in this strip receives the information and then relays the information to the Frontal lobe. After processing this information, the nerve cells in the “primary motor cortex” send instructions to move the left arm from the source of the pain.

The other areas of the parietal lobe carry out more complex jobs than the above, however. It includes maintaining balance, recognizing objects, etc.

2.2.3. The two Homunculi (“two little humans”) (Figure 6 and 7)

In Figure 4, we found red-colored and blue-colored strips on either side of the Central Sulcus (groove). While the nerve cells of the former are responsible for sending commands to move muscles, the nerve cells of the latter strip process sensory information from the body.

Researchers have shown that both strips own a unique layout to execute their jobs. If we climb the strip (precentral gyrus) starting from the area closest to the left Lateral Sulcus (groove) (Look at Figure 4) until it ends at the other side, we will find a homunculus; a small replica of the human body. Compare Figures 6 and 7.

The layout is exactly similar to a homunculus: a small replica of a human body. The “Homunculus” refers to a fictional fully formed human being but extremely small in size; it is a miniature replica. Figures 6 and 7 re-create it beautifully. We own two homunculi on each side of the brain: The “motor homunculus – the strip that lies in front of the Central groove, and the “sensory” homunculus that lies just behind the Central groove. Another interesting characteristic is that the assigned area’s sizes are proportional to the complexity of the job to do. For example, the assigned areas for the fingers, tongue, and face are much larger than the rest of the areas.

the little man from Wikimedia Commons
Figure 6: Homunculus (The little man)
(Source: Wikimedia Commons under the CC BY 3.0 license)

Dr. Wilder Penfield and Edwin Boldrey in 1937 “discovered” and wrote a detailed 50-page article with drawings.

We already know what these “little humans” are doing there.

2.2.4. Temporal lobe (Figure 3 and 4)

Figure 3 depicts the left Temporal lobe (region) green in color. It extends from the “Lateral groove” (also called “Lateral Fissure”) back until it reaches the Occipital lobe’s territory. The nerve cells in this region process information about language understanding, hearing, and memory.

Wernicke’s area

The neurons in this special area process information of language understanding and interpretation. Then it relays the information to the Broca’s area’s neurons for word production.

When we hear something, the hearing area receives information from the ear and then send this information to the Wernicke’s area. Similarly, when we see or read something, the visual area receives it and then sends that information to the Wernicke’s area. Neurons in this area work hard to retrieve suitable nouns appropriate to the context from the storeroom, set the language structure, and shoot the processed information to the Broca’s area.

The death of brain cells of the Wernicke’s area will result in a specific language disability called “Wernicke’s aphasia”. We will learn about it in another module.

2.2.5. Occipital lobe (Figure 3)

This lobe appears colored brown in Figure 3 and situates the brain’s back surface. Its neurons interpret images that receive from our eyes. The damage to neurons in this area causes loss of our sight even though the eyes and its nerves are intact.

2.3. Brain’s blood supply

The brain receives oxygen and food for survival via two main supply routes: carotid arteries and vertebral arteries. The carotid arteries climb from the sides of the neck while the vertebral arteries climb through our vertebral column which situates the back of the neck. Inside the brain, they form an inter-connected-circle, called the circle of Willis.

Carotid arteries

Figure 8 still-image taken from a video clip from a demonstration-explanation of the brain’s blood supply by a professor of the University of Utah shows the Left side carotid artery and its divide. This is the main supply route. We own a similar one on our right side too.

Junction of the common carotid artery
Figure 8: Junction of the common carotid artery (Courtesy: University of Utah: under the creative commons license

At the level of the neck, the carotid arteries, both left and right, branch out into two: External and internal. The latter again divides into three smaller ones: anterior (front), middle, and posterior (back).

Figure 9 illustrates their feeding areas in the brain; the first one carries blood to the neurons who manage information related to the lower part of the body including the legs; the second one (the middle branch) nourishes the neurons who manage information related to the upper part of the body including the face, tongue, arm. This also includes areas assigned to language and speech: Broca’s area and Wernicke’s area.

Figure 9: Brain’s surface blood supply
Frank Gaillard. Patrick J. Lynch, medical illustrator (Brain_stem_normal_human.svg) CC BY-SA 3.0

Why should we know about this information? Knowledge is critical to treat and providing care to the affected. For example, if the right middle branch’s blood supply interrupts, the affected person will show difficulties in raising or feeling of the left arm and drooping of the right side of the face, etc. If the left middle branch’s blood supply interrupts, in addition to the above, we can observe speech and understanding difficulties also.

References
  1. Bruce Fischl, Anders M. Dale (2000): Measuring the thickness of the human cerebral cortex from magnetic resonance images bruce Fischl, Anders M. DaleProceedings of the National Academy of Sciences Sep 2000, 97 (20) 11050-11055; DOI: 10.1073/pnas.200033797.
  2. Redefining the role of Broca’s area in speech Adeen Flinker, Anna Korzeniewska, Avgusta Y. Shestyuk, Piotr J. Franaszczuk, Nina F. Dronkers, Robert T. Knight, Nathan E. Crone Proceedings of the National Academy of Sciences Mar 2015, 112 (9) 2871-2875.

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Posted in e-learning for strokecarers Resources

Module 1: Stroke basics for stroke carers

Module 1 for stroke carers introduces what the word – stroke – refers to, what happens in a stroke event, types of stroke, and who are at risk.

Learning objectives:

At the end of this module, you will be able to answer the following questions if someone asks.

1.1. What is a stroke?

1.2. What happens in a stroke?

1.3. How does a stroke occur?: Types of stroke

1.4. What is a “mini-stroke”?

1.5. Who are at risk?

1.1. What is a stroke?

The term, “stroke” is a broad one; a more recent definition from the American Heart Association/ Stroke Association advocates use this term to cover cell death that occurs in the brain, spinal cord, and retina attributable to the interruption to the blood supply. According to this definition, the presence of symptoms or signs of more than 24 hours is not essential to use the term. And, on the other hand, the presence of reversible stroke-like symptoms more than 24 hours due to edema without interruption to the blood supply does not qualify for a stroke.

However, “Stroke” is a disease of the brain, not of the heart. Many believe, incorrectly, that it is a type of heart disease. Since it occurs suddenly, some call it a “brain attack”. Health professionals name the condition as “cerebrovascular disease”.

Stroke is a brain disease,

not a heart disease.

Stroke is the second leading cause of death and the third leading cause of disability in the world. As much as 70 percent of stroke events are thought to occur in low-middle income countries. On average, a stroke occurs 15 years earlier among people living in those countries. During the past four decades, stroke incidence among low-middle income countries has doubled while it has halved in high-income countries1.

A stroke occurs as a result of brain cell death due to an interruption of blood supply to a part/s of the brain. We will discuss this in module 2. 

Stroke warning signs are easy to detect. The common ones are drooping one eyelid, inability or difficulty of raising one or both arms, and slurred speech; there are more. We will discuss these in module 3.

However, a stroke can also occur without any observable changes.

Stroke results in a range of disabilities of the affected person and at least half of these disabilities persist permanently for life, if not treated early. It exerts an enormous burden not only on the person affected but the whole family, and the society. We will discuss various kinds of disabilities in detail and what we can do to rehabilitate those in Part II of this course. 

1.2. What happens in a stroke?

A stroke cuts off blood supply to a part of the brain. (You can learn more about the brain by joining the “journeys to the brain” series). Within minutes, the neuron cells in the affected area begin to die at a rate of 32,000 per each passing second. In terms of minutes, the number amounts to about two million neuron cells per minute2.

Stroke kills about 32,000 neurons in each passing second.

Jeffrey L. Saver (2006): “Time is Brain”: Quantified; Stroke Journal. 2006;37(1): 263-266.(message creator:https://www.strokecarer.com/)

The only way to save the rest of the cells threatened with death is to restore the interrupted blood supply as soon as possible. This can only be done in a hospital with adequate facilities.

1.3. Types of stroke

A stroke usually occurs either due to a block in a supply route or a burst of the supply route’s wall.

Stroke can occur due to a block inside an artery to the brain or a burst of its wall.

1.3.1. Ischemic stroke

Ischemic stroke occurs due to a block by a blood clot inside the supply route. The extent of the damage depends on where the clot clogs the blood supply system inside the brain. If a clot is a bigger one, it clogs a larger artery and blocks the blood supply to a larger area of the brain. If the clot is a smaller one, it may travel as far higher up as possible until it clogs a smaller branch of a smaller artery.

Figure 1: How ischemic stroke occurs (source: National Heart, Lung, and Blood Institute from Wikimedia commons: this work is on the public domain)
How a blood clot forms

A roughened wall of an artery triggers blood clot formation. The roughening begins with fat deposition at one place of the wall. Then, it hardens with calcium and cholesterol deposits. The process continues slowly but surely forming a plaque there. This thickening narrows the lumen and roughens the surface. Plaque build-up can occur anywhere; however, strokes are commonly associated with plaque build-up in the neck vessels – carotid arteries as shown in Figure 1. 

The following video clip from the British Heart Foundation explains simply how arterial thickening occurs and the factors that facilitate the process.

How arterial thickening triggers blood clot formation (source: British Heart Foundation)

A clot can even originate inside the heart particularly among those with heart problems and travel into the brain.

In the US, about 80 percent of all strokes are in this nature according to the National Institute of Neurological Disorders and Stroke3. In low-middle income countries, this percentage is about 66 percent1.

1.3.2. Hemorrhagic stroke

When a stroke occurs due to a burst of the vessel wall, we call it a “hemorrhagic stroke” (Figure 2). As a result, blood seeps out of the vessel, and oxygen and food supply to neurons interrupt. The bleeding exerts pressure on the area causing more damage.

Figure 2: How hemorrhagic stroke occurs (source: Heart Lung and Blood Institute); this work is on the public domain)

However, there is another 5-10 percent of people who develop a stroke due to an unknown reason4.

1.4. What is a “mini-stroke” TIA (Transient Ischemic Attack)?

In this situation, the stroke signs and symptoms last less than 24 hours; most often, less than an hour. Hence, it is also called “Transient Ischemic Attack” (TIA). What happens here is that the clot that blocks the supply route disappears after a brief time.

However, it is a dire warning; it will certainly return as a full-blown stroke, often within the first week after the TIA, if not treated5.

Therefore, a mini-stroke should also be considered as a medical emergency.

In the following video clip, Professor Peter Rothwell explains why we should a mini-stroke also as a medical emergency.

An educational video clip on mini-stroke (source: Stroke Association)

However, if the effects last more than 24 hours, it is considered a stroke. Ideally, anyone who experience a mini-stroke should not drive or operate a machinery for a month. In some countries it is the law.

Do not drive after a mini-stroke at least for a month. In some countries, it is the law.

1.5. Who are at high-risk?

Some are at higher risk for stroke. We can reduce the risk by modifying some risk factors while others are non-modifiable. The source of the following list is the National Institute of Neurological Disorders and Stroke3.

Stroke can strike even the very young; no one is immune.

Non-modifiable risk factors
  • Age: The risk doubles every passing decade from 55 to 85. However, it can also occur in childhood6.
  • Sex: Men are at higher risk in young and middle age. In older ages, however, the risk is equal.
  • Ethnicity: some ethnic groups are at higher risk; for example, African-Americans and Hispanics experience stroke events more than Caucasians.
  • Family history
Modifiable risk factors

There are some risk factors that we can reduce the risk. Those are as follows;

  • High Blood Pressure: This is one of the most potent risk factors we can easily modify.
  • Diabetes
  • High cholesterol
  • Cigarette smoking: This raises the ischemic stroke risk by two-fold and hemorrhagic stroke risk by four-fold.
  • Physical inactivity and obesity
References
  1. Johnson, W., Onuma, O., Owolabi, M. & Sachdev, S. Stroke (2016): a global response is needed. Bulletin of the World Health Organization 94, 634–634A, https://doi.org/10.2471/BLT.16.181636.
  2. Jeffrey L. Saver (2006): “Time is Brain”: Quantified; Stroke Journal. 2006;37(1): 263-266.
  3. National Institute of Neurological Disorders and Stroke (NINDS): Basic facts: preventing stroke; NIH; 2020. Accessed on September 16, 2020.
  4. Donkor E.S. (2018): Stroke in the 21st Century; Stroke Res Treat.: published online.
  5. British Medical Best Practice; accessed on September 20, 2020.
  6. Vrudhula A, Zhao J, Liu RToo Young to Have a Stroke?—a Global Health CrisisStroke and Vascular Neurology 2019;4:doi: 10.1136/svn-2019-00029.

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