A silent stroke (or asymptomatic cerebral infarction) is a

stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...

that does not have any outward symptoms associated with stroke, and the patient is typically unaware they have suffered a stroke. Despite not causing identifiable symptoms, a silent stroke still causes damage to the brain and places the patient at increased risk for both

transient ischemic attack A transient ischemic attack (TIA), commonly known as a mini-stroke, is a minor stroke whose noticeable symptoms usually end in less than an hour. TIA causes the same symptoms associated with strokes, such as weakness or numbness on one side of ...

and major stroke in the future. In a broad study in 1998, more than 11 million people were estimated to have experienced a stroke in the United States. Approximately 770,000 of these strokes were symptomatic and 11 million were first-ever silent MRI infarcts or

hemorrhage Bleeding, hemorrhage, haemorrhage or blood loss, is blood escaping from the circulatory system from damaged blood vessels. Bleeding can occur internally, or externally either through a natural opening such as the mouth, nose, ear, urethra, v ...

s. Silent strokes typically cause

lesion A lesion is any damage or abnormal change in the tissue of an organism, usually caused by disease or trauma. ''Lesion'' is derived from the Latin "injury". Lesions may occur in plants as well as animals. Types There is no designated classif ...

s which are detected via the use of neuroimaging such as MRI. The risk of silent stroke increases with age but may also affect younger adults. Women appear to be at increased risk for silent stroke, with

hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...

and current

cigarette smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...

being amongst the predisposing factors. These types of strokes include lacunar and other ischemic strokes and minor hemorrhages. They may also include leukoaraiosis (changes in the

white matter White matter refers to areas of the central nervous system (CNS) that are mainly made up of myelinated axons, also called tracts. Long thought to be passive tissue, white matter affects learning and brain functions, modulating the distribu ...

of the brain): the white matter is more susceptible to vascular blockage due to reduced amount of blood vessels as compared to the

cerebral cortex The cerebral cortex, also known as the cerebral mantle, is the outer layer of neural tissue of the cerebrum of the brain in humans and other mammals. The cerebral cortex mostly consists of the six-layered neocortex, with just 10% consisting o ...

. These strokes are termed "silent" because they typically affect "silent" regions of the brain that do not cause a noticeable change in an afflicted person’s motor functions such as contralateral paralysis, slurred speech, pain, or an alteration in the sense of touch. A silent stroke typically affects regions of the brain associated with various thought processes, mood regulation and cognitive functions and is a leading cause of vascular cognitive impairment and may also lead to a loss of

urinary bladder The urinary bladder, or simply bladder, is a hollow organ in humans and other vertebrates that stores urine from the kidneys before disposal by urination. In humans the bladder is a distensible organ that sits on the pelvic floor. Urine ente ...

control. In the Cardiovascular Health Study, a population study conducted among 3,660 adults over the age of 65. 31% showed evidence of silent stroke in neuroimaging studies utilizing MRI. These individuals were unaware they had suffered a stroke. It is estimated that silent strokes are five times more common than symptomatic stroke. A silent stroke differs from a transient ischemic attack (TIA). In TIA symptoms of stroke are exhibited which may last from a few minutes to 24 hours before resolving. A TIA is a risk factor for having a major stroke and subsequent silent strokes in the future.

Types

Ischemic stroke A stroke is a medical condition in which poor blood flow to the brain causes cell death. There are two main types of stroke: ischemic, due to lack of blood flow, and hemorrhagic, due to bleeding. Both cause parts of the brain to stop funct ...

: occurs when a blood vessel supplying blood to the brain becomes blocked. This type of stroke accounts for approximately 87 percent of all stroke cases. *

Hemorrhagic stroke A stroke is a disease, medical condition in which poor cerebral circulation, blood flow to the brain causes cell death. There are two main types of stroke: brain ischemia, ischemic, due to lack of blood flow, and intracranial hemorrhage, hemorr ...

: occurs when a blood vessel supplying blood to the brain becomes weakened and ruptures. Typically hemorrhagic stroke is caused by two types of weakened blood vessel:

aneurysm An aneurysm is an outward bulging, likened to a bubble or balloon, caused by a localized, abnormal, weak spot on a blood vessel wall. Aneurysms may be a result of a hereditary condition or an acquired disease. Aneurysms can also be a nidus ( ...

s and

arteriovenous malformation Arteriovenous malformation is an abnormal connection between arteries and veins, bypassing the capillary system. This vascular anomaly is widely known because of its occurrence in the central nervous system (usually cerebral AVM), but can app ...

s (AVMs). *

Lacunar infarcts Lacunar stroke or lacunar cerebral infarct (LACI) is the most common type of ischemic stroke, resulting from the occlusion of small penetrating arteries that provide blood to the brain's deep structures. Patients who present with symptoms of a la ...

(LACI) are small (0.2 to 15 mm in diameter) noncortical (does not affect

) infarcts caused by the occlusion of a single penetrating branch of a larger blood vessel that provides blood to the brain's deep structures including the white matter. LACIs are strongly associated with the development of white matter lesions (WML) which can be detected via the use of computerized tomography (CT scans).

Risk factors

There are various individual risk factors associated with having a silent stroke. Many of these risk factors are the same as those associated with having a major symptomatic stroke. *

Acrolein Acrolein (systematic name: propenal) is the simplest unsaturated aldehyde. It is a colorless liquid with a piercing, acrid smell. The smell of burnt fat (as when cooking oil is heated to its smoke point) is caused by glycerol in the burning fat ...

: elevated levels of acrolein, a toxic

metabolite In biochemistry, a metabolite is an intermediate or end product of metabolism. The term is usually used for small molecules. Metabolites have various functions, including fuel, structure, signaling, stimulatory and inhibitory effects on enzymes, ...

produced from the

polyamines A polyamine is an organic compound having more than two amino groups. Alkyl polyamines occur naturally, but some are synthetic. Alkylpolyamines are colorless, hygroscopic, and water soluble. Near neutral pH, they exist as the ammonium derivatives. ...

spermine Spermine is a polyamine involved in cellular metabolism that is found in all eukaryotic cells. The precursor for synthesis of spermine is the amino acid ornithine. It is an essential growth factor in some bacteria as well. It is found as a ...

spermidine Spermidine is a polyamine compound () found in ribosomes and living tissues and having various metabolic functions within organisms. It was originally isolated from semen. Function Spermidine is an aliphatic polyamine. Spermidine synthase (SPDS ...

and by

amine oxidase An amine oxidase is an enzyme that catalyzes the oxidative cleavage of alkylamines into aldehydes and ammonia Ammonia is an inorganic compound of nitrogen and hydrogen with the formula . A stable binary hydride, and the simplest pnictoge ...

serve as a marker for silent stroke, when elevated in conjunction with C-reactive protein and interleukin 6 the confidence levels in predicting a silent stroke risk increase. *

Adiponectin Adiponectin (also referred to as GBP-28, apM1, AdipoQ and Acrp30) is a protein hormone and adipokine, which is involved in regulating glucose levels as well as fatty acid breakdown. In humans it is encoded by the ''ADIPOQ'' gene and it is produ ...

: is a type of protein secreted by

adipose Adipose tissue, body fat, or simply fat is a loose connective tissue composed mostly of adipocytes. In addition to adipocytes, adipose tissue contains the stromal vascular fraction (SVF) of cells including preadipocytes, fibroblasts, vascular ...

cells that improves insulin sensitivity and possesses antiatherogenic properties. Lower levels of s-adiponectin are associated with ischemic stroke. *

Aging Ageing ( BE) or aging ( AE) is the process of becoming older. The term refers mainly to humans, many other animals, and fungi, whereas for example, bacteria, perennial plants and some simple animals are potentially biologically immortal. In ...

: the prevalence of silent stroke rises with increasing age with a prevalence rate of over twenty percent of the elderly increasing to 30%-40% in those over the age of 70. *

Anemia Anemia or anaemia (British English) is a blood disorder in which the blood has a reduced ability to carry oxygen due to a lower than normal number of red blood cells, or a reduction in the amount of hemoglobin. When anemia comes on slowly, t ...

: children with acute anemia caused by medical conditions other than sickle cell anemia with hemoglobin below 5.5 g/ dL. are at increased risk for having a silent stroke according to a study released at American Stroke Association's International Stroke Conference 2011. The researchers suggested a thorough examination for evidence of silent stroke in all severely anemic children in order to facilitate timely intervention to ameliorate the potential brain damage. **

Sickle cell anemia Sickle cell disease (SCD) is a group of blood disorders typically inherited from a person's parents. The most common type is known as sickle cell anaemia. It results in an abnormality in the oxygen-carrying protein haemoglobin found in red bl ...

: is an

autosomal recessive In genetics, dominance is the phenomenon of one variant ( allele) of a gene on a chromosome masking or overriding the effect of a different variant of the same gene on the other copy of the chromosome. The first variant is termed dominant an ...

genetic blood disorder caused in the gene (HBB gene) which codes for hemoglobin (Hg) and results in lowered levels. The blood cells in sickle cell disease are abnormally shaped (sickle-shaped) and may form clots or block blood vessels. Estimates of children with sickle cell anemia who suffer strokes (with silent strokes predominating in the younger patients) range from 15%-30%. These children are at significant risk of cognitive impairment and poor educational outcomes. **

Thalassemia major Beta thalassemias (β thalassemias) are a group of inherited blood disorders. They are forms of thalassemia caused by reduced or absent synthesis of the beta chains of hemoglobin that result in variable outcomes ranging from severe anemia to cl ...

: is an autosomal recessive genetically inherited form of hemolytic anemia, characterized by red blood cell (hemoglobin) production abnormalities. Children with this disorder are at increased risk for silent stroke. * Atrial fibrillation (AF): atrial fibrillation (irregular heartbeat) is associated with a doubled risk for silent stroke. *

Cigarette smoking Tobacco smoking is the practice of burning tobacco and ingesting the resulting smoke. The smoke may be inhaled, as is done with cigarettes, or simply released from the mouth, as is generally done with pipes and cigars. The practice is believed ...

: The procoagulant and

atherogenic Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually no ...

effects of smoking increase the risk for silent stroke. Smoking also has a deleterious effect on regional

cerebral blood flow Cerebral circulation is the movement of blood through a network of cerebral arteries and veins supplying the brain. The rate of cerebral blood flow in an adult human is typically 750 milliliters per minute, or about 15% of cardiac output. A ...

(rCBF). The chances of having a stroke increase with the amount of cigarettes smoked and the length of time an individual has smoked (pack years). *

C-reactive protein C-reactive protein (CRP) is an annular (ring-shaped) pentameric protein found in blood plasma, whose circulating concentrations rise in response to inflammation. It is an acute-phase protein of hepatic origin that increases following interleukin- ...

(CRP) and

Interleukin 6 Interleukin 6 (IL-6) is an interleukin that acts as both a pro-inflammatory cytokine and an anti-inflammatory myokine. In humans, it is encoded by the ''IL6'' gene. In addition, osteoblasts secrete IL-6 to stimulate osteoclast formation. Smooth ...

(IL6): C-reactive protein is one of the plasma proteins known as

acute phase protein Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the ''acute- ...

s (proteins whose plasma concentrations increase (or decrease) by 25% or more during inflammatory disorders) which is produced by the liver. The level of CRP rises in response to inflammation in various parts of the body including vascular inflammation. The level of CRP can rise as high as 1000-fold in response to inflammation. Other conditions that can cause marked changes in CRP levels include infection, trauma, surgery, burns, inflammatory conditions, and advanced cancer. Moderate changes can also occur after strenuous exercise, heatstroke, and childbirth. Increased levels of CRP as measured by a CRP test or the more sensitive high serum CRP (hsCRP) test have a close correlation to increased risk of silent stroke. Interleukin-6 is an

interleukin Interleukins (ILs) are a group of cytokines (secreted proteins and signal molecules) that are expressed and secreted by white blood cells (leukocytes) as well as some other body cells. The human genome encodes more than 50 interleukins and related ...

(type of protein) produced by

T-cells A T cell is a type of lymphocyte. T cells are one of the important white blood cells of the immune system and play a central role in the adaptive immune response. T cells can be distinguished from other lymphocytes by the presence of a T-cell r ...

(specialized

white blood cells White blood cells, also called leukocytes or leucocytes, are the cells of the immune system that are involved in protecting the body against both infectious disease and foreign invaders. All white blood cells are produced and derived from mult ...

macrophages Macrophages (abbreviated as M φ, MΦ or MP) ( el, large eaters, from Greek ''μακρός'' (') = large, ''φαγεῖν'' (') = to eat) are a type of white blood cell of the immune system that engulfs and digests pathogens, such as cancer ce ...

and

endothelial cell The endothelium is a single layer of squamous endothelial cells that line the interior surface of blood vessels and lymphatic vessels. The endothelium forms an interface between circulating blood or lymph in the lumen and the rest of the vesse ...

s. IL6 is also classified as a

cytokine Cytokines are a broad and loose category of small proteins (~5–25 kDa) important in cell signaling. Cytokines are peptides and cannot cross the lipid bilayer of cells to enter the cytoplasm. Cytokines have been shown to be involved in au ...

(acts in relaying information between cells). IL6 is involved in the regulation of the

acute phase response Acute-phase proteins (APPs) are a class of proteins whose concentrations in blood plasma either increase (positive acute-phase proteins) or decrease (negative acute-phase proteins) in response to inflammation. This response is called the ''acute- ...

to injury and infection may act as both an anti-inflammatory agent and a pro-inflammatory. Increased levels of CRP as measured by a CRP test or the more sensitive high serum CRP (hsCRP) test and elevated levels of I6 as measured by an IL6

ELISA The enzyme-linked immunosorbent assay (ELISA) (, ) is a commonly used analytical biochemistry assay, first described by Eva Engvall and Peter Perlmann in 1971. The assay uses a solid-phase type of enzyme immunoassay (EIA) to detect the presen ...

are markers for the increased risk of silent stroke. *

Diabetes mellitus Diabetes, also known as diabetes mellitus, is a group of metabolic disorders characterized by a high blood sugar level ( hyperglycemia) over a prolonged period of time. Symptoms often include frequent urination, increased thirst and increased ...

: untreated or improperly managed diabetes mellitus is associated with an increased risk for silent stroke. *

Hypertension Hypertension (HTN or HT), also known as high blood pressure (HBP), is a long-term medical condition in which the blood pressure in the arteries is persistently elevated. High blood pressure usually does not cause symptoms. Long-term high b ...

: which affects up to 50 million people in the United States alone is the major treatable risk factor associated with silent strokes. *

Homocysteine Homocysteine is a non-proteinogenic α-amino acid. It is a homologue of the amino acid cysteine, differing by an additional methylene bridge (-CH2-). It is biosynthesized from methionine by the removal of its terminal Cε methyl group. In th ...

: elevated levels of total homocysteine (tHcy) an

amino acid Amino acids are organic compounds that contain both amino and carboxylic acid functional groups. Although hundreds of amino acids exist in nature, by far the most important are the alpha-amino acids, which comprise proteins. Only 22 alpha ...

are an independent risk factor for silent stroke, even in healthy middle-aged adults. *

Metabolic syndrome Metabolic syndrome is a clustering of at least three of the following five medical conditions: abdominal obesity, high blood pressure, high blood sugar, high serum triglycerides, and low serum high-density lipoprotein (HDL). Metabolic syndro ...

(MetS):Metabolic syndrome is a name for a group of risk factors that occur together and increase the risk for coronary artery disease, stroke, and type 2 diabetes. A higher number of these MetS risk factors the greater the chance of having a silent stroke. **

Polycystic ovary syndrome Polycystic ovary syndrome, or PCOS, is the most common endocrine disorder in women of reproductive age. The syndrome is named after the characteristic cysts which may form on the ovaries, though it is important to note that this is a sign and no ...

(PCOS): is associated with double the risk for arterial disease including silent stroke independent of the subjects

Body mass index Body mass index (BMI) is a value derived from the mass ( weight) and height of a person. The BMI is defined as the body mass divided by the square of the body height, and is expressed in units of kg/m2, resulting from mass in kilograms and ...

(BMI). *

Sleep apnea Sleep apnea, also spelled sleep apnoea, is a sleep disorder in which pauses in breathing or periods of shallow breathing during sleep occur more often than normal. Each pause can last for a few seconds to a few minutes and they happen many tim ...

: encompasses a heterogeneous group of sleep-related breathing disorders in which there is repeated intermittent episodes of breathing cessation or

hypopnea Hypopnea is overly shallow breathing or an abnormally low respiratory rate. Hypopnea is defined by some to be less severe than apnea (the complete cessation of breathing), while other researchers have discovered hypopnea to have a "similar if not ...

, when breathing is shallower or slower than normal. Sleep apnea is a common finding in stroke patients but recent research suggests that it is even more prevalent in silent stroke and chronic microvascular changes in the brain. In the study presented at the American Stroke Association's International Stroke Conference 2012 the higher the apnea-hypopnea index, the more likely patients had a silent stroke.

Neuropsychological deficits

Individuals who have had silent strokes often have various neuropsychological deficits and have significant impairment in multiple areas of cognitive performance. One study has shown an association between silent stroke and a history of memory loss and lower scores on tests of cognitive function. In a second study, individuals who have a had a silent stroke scored lower on the

mini–mental state examination The Mini–Mental State Examination (MMSE) or Folstein test is a 30-point questionnaire that is used extensively in clinical and research settings to measure cognitive impairment. It is commonly used in medicine and allied health to screen for de ...

(MMSE) and on Raven's Colored Progressive Matrices—a test designed for children aged 5 through 11 years, mentally and physically impaired individuals, and elderly people.

In children

Children who have suffered silent strokes often have a variety of neuropsychological deficits. These deficits may include lowered I.Q., learning disabilities, and an inability to focus. Silent strokes are the most common form of neurologic injury in children with sickle cell anemia, who may develop subtle neurocognitive deficits in the areas of attention and concentration,

executive function In cognitive science and neuropsychology, executive functions (collectively referred to as executive function and cognitive control) are a set of cognitive processes that are necessary for the cognitive control of behavior: selecting and succe ...

, and visual-motor speed and coordination due to silent strokes which may not have been detected on physical examination.

Link to depression

Major depression is a risk factor and also a consequence of silent brain infarction (SBI). Persons who present with symptoms of presenile and senile major depression showed a markedly higher incidence of SBI (65.9% and 93.7%). Individuals with major depression who have had an SBI present with more marked neurological deficits and more severe depressive symptoms than do those without SBI.

Diagnosis

The diagnosis of a silent stroke is usually made as an

incidental finding Incidental medical findings are previously undiagnosed medical or psychiatric conditions that are discovered unintentionally and during evaluation for a medical or psychiatric condition. Such findings may occur in a variety of settings, including ro ...

(by chance) of various neuroimaging techniques. Silent strokes may be detected by: *

Magnetic resonance imaging Magnetic resonance imaging (MRI) is a medical imaging technique used in radiology to form pictures of the anatomy and the physiological processes of the body. MRI scanners use strong magnetic fields, magnetic field gradients, and radio wave ...

(MRI) * Computed tomography (CT scan) *

Transcranial Doppler Transcranial Doppler (TCD) and transcranial color Doppler (TCCD) are types of Doppler ultrasonography that measure the velocity of blood flow through the brain's blood vessels by measuring the echoes of ultrasound waves moving transcranially ...

ultrasonography (TCD), which measures cerebral blood flow velocity (CBFV) in the large intracranial arteries in the brain, has been shown in various studies to be an effective tool to diagnose children with sickle cell anemia at increased risk of having an initial or recurrent silent stroke. The narrowing of these arteries which is a risk factor for cerebral infarction, is characterized by an increased velocity of blood flow.

Prevention

Preventive measures that can be taken to avoid sustaining a silent stroke are the same as for stroke.

Smoking cessation Smoking cessation, usually called quitting smoking or stopping smoking, is the process of discontinuing tobacco smoking. Tobacco smoke contains nicotine, which is addictive and can cause dependence. As a result, nicotine withdrawal often m ...

is the most immediate step that can be taken, with the effective management of hypertension the major medically treatable factor.

Sickle cell anemia

Transfusion therapy lowers the risk for a new silent stroke in children who have both abnormal

cerebral artery The cerebral arteries describe three main pairs of arteries and their branches, which perfuse the cerebrum of the brain. The three main arteries are the: * ''Anterior cerebral artery'' (ACA) * ''Middle cerebral artery'' (MCA) * ''Posterior cere ...

blood flow velocity, as detected by transcranial Doppler, and previous silent infarct, even when the initial MRI showed no abnormality. A finding of elevated TCD ultrasonographic velocity warrants MRI of the brain, as those with both abnormalities who are not provided transfusion therapy are at higher risk for developing a new silent infarct or stroke than are those whose initial MRI showed no abnormality.

References

External links

{{Medical resources , DiseasesDB = 2247 , ICD10 = {{ICD10, I, 61, , i, 60-{{ICD10, I, 64, , i, 60 , ICD9 = {{ICD9, 434.01-{{ICD9, 434.91 , OMIM = 601367 , MedlinePlus = 000726 , eMedicineSubj = neuro , eMedicineTopic = 9 , eMedicine_mult = {{eMedicine2, emerg, 558 {{eMedicine2, emerg, 557 {{eMedicine2, pmr, 187 , MeshID = D020521
Stanford Stroke Risk Assessment Test

Functional and Cognitive Consequences of Silent Stroke: Discussion

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Stroke