Stroke (Apoplexy): Causes

Pathogenesis (development of disease)

Ischemic apoplexy

In ischemic apoplexy (ischemic insult, cerebral infarction; approximately 80-85% of cases), thrombotic or embolic vascular occlusion occurs. In this case, the apoplexy is usually caused by atherosclerosis (arteriosclerosis, hardening of the arteries). For details on the pathogenesis of atherosclerosis, see below the disease of the same name. The cause of atherosclerosis-related stroke is arterial embolism (occlusion of a blood vessel by material washed in with the blood (embolus)) and unstable plaques as initial sources of arterial embolism in about 50% of cases. Other causes of ischemic apoplexy include cardiac sources of emboli (approximately 20-30% of ischemic insults), thrombophilias (tendency to thrombosis), and nonatherosclerotic vascular disease (e.g., dissection, fibromuscular dysplasia, vasculitis). Pathologists distinguish three forms of ischemic apoplexy:

  1. Atherosclerotic stroke due to occlusion of large arteries (large artery stroke, LAS).
  2. Cardioembolic stroke (CES) due to entrainment of thrombi (blood clots) from the left atrium or, in the case of patent foramen ovale, also from the venous circulation
  3. Stroke as a result of small-vessel disease (SVS).

The TOAST classification of subtypes of acute ischemic stroke also recognizes two other forms:

  • Stroke of another specific etiology.
  • Stroke of undetermined etiology (cryptogenic apoplexy)
    • ≥ 2 causes identified
    • Negative diagnostics
    • Incomplete diagnostics

Cryptogenic apoplexy is usually due to an embolic event (= Embolic Stroke of Undetermined Source, ESUS). The most likely causes include:

  • Thromboembolism due to occult (hidden in plain sight) paroxysmal atrial fibrillation (asymptomatic paroxysmal atrial fibrillation; “atrial fibrillation”, AF). Furthermore, by aortic atheromatosis or other cardiac sources.
  • Paradoxical embolism (transfer of an embolus/vascular plug from the venous to the arterial system of the systemic circulation through a defect in the cardiac septum/septal area) originating in the systemic venous circulation-for example, through a patent foramen ovale (persistent foramen ovale, PFO), atrial septal abnormalities/atrial septal defect, ventricular septal defect (“hole in the cardiac septum”).
  • Unknown thrombophilia (tendency to thrombosis): e.g., hypercoagulability (pathologically increased coagulability of blood with increased tendency of intravascular thrombus formation) associated with malignancy (tumor disease).
  • Zerobrovascular disease associated with stenosis (narrowing) <50% or other vasculopathies (vascular disease: e.g., dissection/tear or a hematoma (hematoma in the wall of the internal carotid artery or vertebral artery, fibromuscular dysplasia/ fibromuscular dysplasia).

Hemorrhagic appoplexy

In contrast, in hemorrhagic apoplexy (intracerebral hemorrhage (ICB); approximately 15-20% of cases), spontaneous vascular rupture (rupture of a blood vessel) occurs. Again, the basic pathomechanism is found in atherosclerosis and concomitant arterial hypertension (high blood pressure). Causes of hemorrhagic apoplexy include subarachnoid hemorrhage (SAB; bleeding between the spider tissue membrane and the soft meninges; 3-5% of all strokes) and intracerebral hemorrhage (ICB, cerebral hemorrhage; 10-12% of all strokes). In both forms of apoplexy, there is decreased perfusion (reduced blood flow) to the affected areas of the brain, resulting in neurologic deficits.

Etiology (causes)

Biographic causes

  • Genetic burden
    • If first-degree relatives are affected, the risk increases by 1.9 times
    • Cardiovascular events in the family.
  • Blood group – blood group AB
  • Ethnic origin – African Americans, Native Americans, and indigenous peoples from the region of what is now Alaska (Inupiaq, Yupik, Aleut, Eyak, Tlingit, Haida, Tsimshian) have a higher risk of apoplexy.
  • Gender
    • Men
      • Men are more often affected than women: The risk for men from age 55 to about age 75 is more than 50% higher than that for women!
      • Men are more likely to be affected if they have a history of erectile dysfunction (+35%)
    • Women
      • Pregnancy aged 12-24 years (relative incidence rate (IRR) of 2.2).
      • Hypertension in pregnancy (+80%).
      • Premature or early menopause: +88% for premature and +40% for early menopause.
      • Late menopause (≥ 55 years): risk of hemorrhagic insult 2.4-fold higher than menopause between 50-54 years.
      • Preterm birth (+60%; stillbirth (approx. +90%).
  • Age
    • Increasing age (after age 55, doubling of risk every 10 years).
    • Pregnancy in women aged 12-24 years (relative incidence rate (IRR) of 2.2)
  • Height – Children who are slightly shorter than average at school age are at increased risk for ischemic stroke as adults:
    • Boys and girls who were 5-8 cm shorter than the age-typical average had an 11% and 10% increased risk of ischemic insult, respectively (hazard ratios = 0.89 and 0.9, respectively)
    • Risk of intracerebral hemorrhage (ICB; brain hemorrhage) increased only in men (HR = 0.89) and not in women (HR = 0.97)
  • Socioeconomic factors – low socioeconomic status.
  • History of apoplexy (past medical history).

Behavioral causes

  • Nutrition
    • Studies show that 10 g salt/day increases the risk of stroke by 23%. This amount corresponds to the usual consumption of table salt in Western countries.
    • Red and processed meat (defined as over 50 g/day), but less whole grains, fruits and vegetables, nuts and seeds, also less cheese and dairy products → ischemic apoplexy.
    • Consumption of eggs: risk of hemorrhagic apoplexy increased by a factor of 1.25 per 20 g/day
    • Increased cholesterol levels due to increased intake of saturated fatty acids (animal fats, contained in sausage, meat, cheese). Instead, mainly polyunsaturated fatty acids from vegetable fats as well as fish should be consumed. Studies show that the predominant use of olive oil and regular consumption of nuts is associated with a low rate of stroke.
    • High intake of highly sugary foods (eg, sweets, sweet drinks) – this increases blood glucose levels in the long term, which is damaging to blood vessels.
    • High intake of sweet drinks, especially if they are mixed with artificial sweeteners.
    • Low intake of whole grain products; fiber intake is inversely associated with apoplexy incidence, i.e., the lower the fiber intake, the higher the risk of stroke
    • Micronutrient deficiency (vital substances) – see prevention with micronutrients.
  • Consumption of stimulants
    • Tobacco (smoking, passive smoking); (1.67-fold risk).
    • Alcohol
      • 1-2 alcoholic drinks/day (day) reduced risk of ischemic stroke; ≥ 3 drinks/day resulted in an increase in intracerebral hemorrhage (ICB; brain hemorrhage) and subarachnoid hemorrhage
        • Maximum of one drink per day: 9% risk reduction for ischemic stroke (relative risk RR 0.90; 95% confidence interval 0.85-0.95)
        • 1-2 drinks/die: 8% risk reduction (RR 0.92; 0.87-0.97).
        • 3-4 drinks/day: 8% increase in risk of ischemic stroke (RR 1.08; 1.01-1.15)
        • >4 drinks/day: 14% increase in risk of ischemic stroke (RR 1.14; 1.02-1.28) and 67% increase in intracerebral hemorrhage (RR 1.67; 1.25-2.23) and 82% increase in subarachnoid hemorrhage (1.82; 1.18-2.82)

        A new evaluation, which included data from 160,000 adults, contradicts this. The evaluation used the method of Mendelian randomization: it measured two genetic variants (rs671 and rs1229984) in the 160,000 adults that significantly reduce alcohol consumption. These genetic variants lead to a 50-fold difference in average alcohol consumption, from nearly 0 to about 4 drinks per day. Similarly, the genetic variants that reduced alcohol consumption also lead to a reduction in blood pressure and stroke risk. As a result, the authors showed that alcohol increases the risk of stroke by about one-third (35%) for every 4 additional drinks per day, with no preventive effect from light or moderate alcohol consumption.

      • linear relationship between the level of alcohol consumption and the risk of apoplexy: for men who consume more than 21 drinks per month, the risk of apoplexy increases by 22% (= every day a glass of wine is already too much).
      • 2.09-fold risk of high or heavy episodic drinking versus never or former drinkers.
  • Drug use
    • Cannabis (hashish and marijuana)
      • There is evidence for a causal relationship between cannabis (hashish and marijuana) and cerebrovascular events.
      • Neither cumulative lifetime marijuana use nor more recent use of marijuana was associated with the occurrence of cardiovascular disease (CVD), apoplexy, or transient ischemic attack (TIA; sudden circulatory disturbance of the brain leading to neurologic dysfunction that resolves within 24 hours) in middle age
      • Taking into account possible cofactors such as tobacco smoking, e-cigarette use, and alcohol consumption, the risk of stroke was shown to be increased with an odds ratio of 1.82 (95% confidence interval 1.08 to 3.10) for cannabis use overall and 2.45 (1.31 to 4.60) for individuals who used cannabis more than 10 days per month.
    • Heroin
    • Cocaine and amphetamines/methamphetamine (“crystal meth”) are a common cause of stroke. Particularly in the 18- to 44-year-old age group, one in seven strokes is caused by drug use. Amphetamines and cocaine can abruptly increase blood pressure. Cocaine can also cause vasospasm, while amphetamines cause cerebral hemorrhage. A U.S. study found that amphetamine users have a 5-fold increased risk of brain hemorrhage, called hemorrhagic stroke. The other form is ischemic stroke, triggered by a sudden disturbance of blood flow in the brain. As a result, brain cells die within a few minutes. According to the US study, cocaine doubled the risk of both ischemic and hemorrhagic stroke.
    • Opiates
  • Physical activity
    • Lack of exercise (physical inactivity)
  • Psycho-social situation (2.2 times the risk).
    • Chronic stress
    • Lonely and socially isolated people (+39%).
    • Hostility
    • Tantrum (trigger; risk increases by a factor of 3 in the first two hours).
    • Work stress (category: high demands, low level of control); women 33%, men 26% higher risk of apoplexy.
    • Long working hours (> 55 h / week).
    • Loneliness and social isolation (32% increased risk (pooled relative risk 1.32; 1.04 to 1.68).
  • Sleep duration
    • Sleep duration 9-10 hours – In a large-scale study, it was observed that people who slept 9-10 hours were 10% more likely to suffer cardiovascular events such as apoplexy (stroke) than those who slept 6-8 hours. If the sleep duration was more than 10 hours, the risk increased to 28%.
  • Overweight (BMI ≥ 25; obesity).
    • Increases the risk for apoplexy
    • Increased risk esp. for cerebral infarction
    • Above-average body mass index at age 7-13 years increases the risk of apoplexy
      • Girls: when the average BMI was exceeded by one standard deviation (corresponding to a weight gain of 6.8 kg), this increased the risk of stroke by 26% by age 55; when the BMI was two standard deviations above the average (16.4 kg of additional weight), the risk increased by 76%
      • Boys: one BMI standard deviation more (5.9 kg weight) = 21% increase in risk of early insult; two standard deviations (14.8 kg) increase of 58

    Note: In biobank studies with so-called Mendelian randomization, no significance was demonstrated for the phenotypically defined cohort “apoplexy” with respect to obesity. Significance for risks associated with increased BMI resulted with full adjustment for arterial hypertension / hypertension (65%) and diabetes mellitus type 2 153%).

  • Android body fat distribution, that is, abdominal/visceral, truncal, central body fat (apple type)-there is a high waist circumference or waist-to-hip ratio (THQ; waist-to-hip ratio (WHR)); 1.44-fold risk When measuring waist circumference according to the International Diabetes Federation guideline (IDF, 2005), the following standard values apply:
    • Men <94 cm
    • Women < 80 cm

    The German Obesity Society published somewhat more moderate figures for waist circumference in 2006: < 102 cm for men and < 88 cm for women.

  • Abdominal obesity is known to be associated with an increased risk of ischemic cerebral infarction. Mendelian randomization was used to examine the effects of waist-hip index (THI)-as an indicator of abdominal obesity-on the mediators systolic blood pressure and fasting glucose. The study showed:
    • 12% of the effect that THI exerted on insult risk was attributable to systolic blood pressure.
    • Fasting glucose and HBA1c levels did not contribute to the THI effect.

    Abdominal obesity increases stroke risk largely independently of systolic blood pressure and glucose levels.CONCLUSION: Abdominal obesity independently triggers pathologic (pathological) processes (eg, inflammatory processes, increased coagulation, and impaired fibrinolysis/dissolution of a fibrin clot by enzyme action) that can cause apoplexy.

Disease-related causes

  • Aneurysm (expansion of the vessel wall of an artery) of the cerebral arteries.
  • Arterial hypertension (high blood pressure).
    • History of hypertension or blood pressure of 140/90 mmHg or higher (2.98-fold risk); was more associated with hemorrhagic than ischemic apoplexy
    • Increase in systolic blood pressure by 10 mmHg increases risk of apoplexy by approximately 10%.
  • Atherosclerosis
  • Carotid stenosis (narrowing of the carotid artery)
  • Chronic kidney disease (CKD; chronic renal failure).
  • Depression (including depressive symptoms)
  • Diabetes mellitus
    • 1.16-fold risk
    • Elderly nursing home residents in France who had type 2 diabetes and regularly took acetaminophen had a more than 3-fold increased risk of having a stroke within the 18-month observation period.
  • Dissection (splitting of the wall layers) of the carotid artery (common cause of stroke in younger people: proportion of 10-25%); common causes: Manipulation of the cervical spine or trauma; clinical symptoms: ischemic strokes (up to 90%), headache or sore throat (30-70%), Horner’s syndrome (15-35%), and pulse-synchronous tinnitus (ringing in the ears) and cranial nerve loss up to 10%.
  • Dyslipidemias/hyperlipoproteinemias (lipid metabolism disorders – see below under laboratory diagnoses).
  • Coagulation disorders (juvenile apoplexy; apoplexy in young people).
  • Hemorrhagic diathesis (increased bleeding tendency).
  • Heart disease (3.17-fold risk).
    • Endocarditis (endocardial inflammation) (juvenile apoplexy; apoplexy in young people).
    • Cardiac arrhythmias, especially atrial fibrillation (VHF):
      • Atrial fibrillation was detected in 23.7% of post-stroke patients in a meta-analysis
      • AF is considered a major cause of cryptogenic stroke (stroke of unknown cause)
      • Patients with VHF taking only acetylsalicylic acid (ASA) were analyzed in terms of apoplexy rate (%/year) according to the type of VHF:
        • Paroxysmal VHF: 2.1%/yr.
        • Persistent VHF: 3.0%/year
        • Permanent VHF: 4.2%/year
    • Congenital vitia (congenital heart defects): e.g., foramen ovale (connection between the atria; prevalence: 25-50%; 30-50% in cryptogenic apoplexy) (juvenile apoplexy; apoplexy in young people).
    • Coronary artery disease (CAD; coronary artery disease).
    • Myocardial infarction (heart attack within the last 4 weeks).
  • Hypercoagulopathies – coagulation disorders associated with increased blood clottability.
  • Infections
    • In children, infections are discussed as a cause: In one study, 18% of children with apoplexy had an infection documented in the week before the insult (control group: 3%). Most commonly, these were upper respiratory infections.
    • Bacterial endocarditis (inflammation of the inner lining of the heart).
    • Herpes zoster (shingles) – ischemic infarction was 2.4 times more common in the first week after the onset of the disease
    • Other infections such as meningitis (meningitis), neurosyphilis, the neuroborreliosis, AIDS, rickettsia and malaria.
  • Insomnia (sleep disorders)
  • Intracerebral hemorrhage (ICB), spontaneous.
  • Head or neck trauma
  • Moyamoya disease (from Jap. moyamoya “mist”); disease of cerebral vessels (especially the internal carotid artery and the middle cerebral artery) in which there is stenosis (narrowing) or obliteration (occlusion) of cerebral arteries; rare cause of juvenile apoplexy in children, adolescents, and young adults)
  • Peripheral arterial occlusive disease (pAVK) – progressive narrowing or occlusion of the arteries supplying the arms/ (more commonly) legs, usually due to atherosclerosis (arteriosclerosis, hardening of the arteries)
  • Polyglobulia (synonym: erythrocytosis); increase in the number of erythrocytes (red blood cells) above the physiological normal value.
  • Preeclampsia (occurrence of hypertension / high blood pressure and proteinuria / increased excretion of protein in the urine during pregnancy) – doubles the risk of subsequent apoplexy (stroke).
  • Transient ischemic attack (TIA), preceding – sudden circulatory disturbance of the brain, which leads to neurological disorders that regress within 24 hours.
  • Sleep-related breathing disorders (SBAS):
    • Obstructive sleep apnea syndrome (OSAS) – characterized by obstruction or complete obstruction of the upper airway during sleep; most common form of sleep apnea (90% of cases).
    • Central sleep apnea syndrome (ZSAS) – characterized by repeated respiratory arrests due to lack of activation of respiratory muscles; 10% of cases.
  • Sinus vein thrombosis (SVT; <1% of cases); oral contraceptive users have an increased risk of sinus thrombosis; this applies esp. to obese women, who were 29.26 times more likely to experience the venous outflow obstruction from the brain
  • Stress cardiomyopathy (synonyms: Broken Heart Syndrome), Tako-Tsubo Cardiomyopathy (Takotsubo Cardiomyopathy), Tako-Tsubo Cardiomyopathy (TTC), Tako-Tsubo Syndrome (Takotsubo Syndrome, TTS), transient left ventricular apical ballooning) – primary cardiomyopathy (myocardial disease) characterized by short-term impairment of myocardial (heart muscle) function in the presence of overall unremarkable coronary arteries; clinical symptoms: Symptoms of acute myocardial infarction (heart attack) with acute chest pain (chest pain), typical ECG changes, and increase in myocardial markers in the blood; in approx. 1-2% of patients with a suspected diagnosis of acute coronary syndrome are found to have TTC on cardiac catheterization instead of a presumed diagnosis of coronary artery disease (CAD); nearly 90% of patients affected by TTC are postmenopausal women; Increased mortality (death rate) in younger patients, especially men, largely due to increased rates of cerebral hemorrhage (brain bleeding) and epileptic seizures; possible triggers include stress, anxiety, heavy physical work, asthma attack, or gastroscopy (gastroscopy);risk factors for sudden cardiac death in TTC include: Male gender, younger age, prolonged QTc interval, apical TTS type, and acute neurological disorders; long-term incidence for apoplexy (stroke) after five years was significantly higher in patients with Takotsubo syndrome at 6.5% than in patients with myocardial infarction (heart attack) at 3.2
  • Subarachnoid hemorrhage (SAB; arterial bleeding into the subarachnoid space/ fluid-filled space between the arachnoid (sensory tissue) and pia mater (connective tissue layer resting directly on the brain and spinal cord; about 5% of all apoplectic episodes; about 85% of these cases are due to aneurysm rupture)
  • Subclinical inflammation (English “silent inflammation”) – permanent systemic inflammation (inflammation that affects the entire organism), which runs without clinical symptoms.
  • Vasculitis (inflammatory diseases of blood vessels) (juvenile apoplexy; apoplexy in young people).
  • Atrial fibrosis → atrial fibrillation (AF) and cryptogenic apoplexy (“Embolic Stroke of Undetermined Source” (ESUS)).
  • Cerebral amyloid angiopathy (ZAA) – degenerative vasculopathy classically associated with spontaneous lobular intracerebral or sulcal hemorrhage; prevalence (disease incidence) is 30% in 60- to 69-year-olds and 50% in 70- to 89-year-oldsNote: platelet aggregration inhibitor or -function inhibition, oral anticoagulation with vitamin K antagonists, and statin therapy increase the risk of intracerebral hemorrhage (ICB; brain hemorrhage)!
  • Cerebral angiopathies (as a cause of ischemic stroke in childhood).

Laboratory diagnoses – laboratory parameters that are considered independent risk factors.

  • Apolipoprotein (Apo)B/ApoA1 quotient (1.84-fold risk).
  • C-reactive protein (CRP)
  • Erythrocytosis – increased number of red blood cells.
  • Glomerular filtration rate ↓ (eGFR: from stage CNI 2: eGFR: 89-60).
  • Hyperhomocysteinemia – Elevated homocysteine levels are associated with an increased risk of ischemic and recurrent apoplexy; however, there is no clear association with hemorrhagic apoplexy.
  • Hyperlipoproteinemias (disorders of lipid metabolism).
    • Hypercholesterolemia:
      • High LDL cholesterol levels (> 115 mg/dl or > 3 mmol/l) (risk increase for ischemic apoplexy).
      • HDL cholesterol: < 40 mg/dl – period 10 years, risk increase 59%.
      • Quotient of total and HDL cholesterol: ≥ 5 – period 10 years, risk increase: 47 %.
      • Total cholesterol
    • Hypocholesterolemia
      • LDL cholesterol < 70 mg/dl vs women with LDL-C levels of 100 to < 130 mg/dl. : 2.17-fold risk of hemorrhagic insult.
    • Hypertriglyceridemia (in men with nonfasting triglyceride levels of 89-176 mg/dl, the risk of apoplexy is already increased by 30%, and even 2.5-fold above 443 mg/dl, compared with men with triglyceride levels below 89 mg/dl. In women, the risk increased even up to 3.8 times at very high triglyceride levels compared to low triglyceride levels).
    • Triglycerides < 74 mg/dl: women with triglyceride levels in the lowest quartile (≤ 74 mg/dl fasting or ≤ 85 mg/dl nonfasting, respectively) compared with women from the highest quartile (> 156 mg/dl or > 188 mg/dl, respectively): 2-fold risk of hemorrhagic apoplexy
  • Hyperuricemia
  • Fasting glucose (fasting blood sugar)
    • Prediabetes as defined by the American Diabetes Association: 100-125 mg/dl (5.6-6.9 mmol/l) (1.06-fold risk)
    • Prediabetes as defined by the WHO: 110-125 mg/dl (6.1-6.9 mmol/l) (1.20-fold risk)

Medication

  • Alpha blockers:
    • In the first 21 days after the first prescription of alfuzosin, doxazosin, tamsulosin, or terazosin, there was a 40% increase in ischemic apoplexy (stroke) events
    • Patients taking another antihypertensive (blood pressure-lowering drug) concomitantly with an alpha blocker had no increased risk of apoplexy in the postexposure 1 period ( ≤ 21 days thereafter), and the incidence in the postexposure 2 period (22-60 days thereafter) decreased even further (IRR 0.67)Conclusion Normotensives may be more sensitive to the first-dose effect of alpha blockers.
    • ALLHAT study:Doxazosin patients had a higher risk of stroke and combined cardiovascular disease than chlorthalidone patients. The risk of CHD was doubled.
  • Nonsteroidal anti-inflammatory drugs (NSAIDs; e.g., ibuprofen, diclofenac) including COX-2 inhibitors (synonyms: COX-2 inhibitors; commonly: coxibs; e.g. Celecoxib, etoricoxib, parecoxib) – increased risk with current use of rofecoxib and diclofenac; increased risk of ischemic infarction with use of diclofenac and aceclofenac up to 30 days before the event.
  • Aceclofenac, similar to diclofenac and the selective COX-2 inhibitors, is associated with an increased risk of arterial thrombotic events.
  • Paracetamol (group of nonacidic analgesics), when used as pain therapy in nursing home residents (N = 5,000; 2,200 subjects took paracetamol daily, mean dose was 2,400 mg), increased the rate of apoplexy a mean of 3-fold.
  • Use of new-generation oral contraceptives (birth control pills) are associated with an increased risk of first-time cerebral infarction.Hormonal contraceptives with lower estrogen concentrations had a lower risk of cerebral infarction compared with those with normal estrogen concentrations.All four generations of progestins were associated with an increased risk of ischemic stroke. The risk of ischemic stroke appeared to be slightly lower among fourth-generation users than among those on the precursor generations of progestins.Note: Transdermal estrogen therapy (patch therapy) does not increase the risk of ischemic cerebrovascular events.
  • Regadenoson (selective coronary vasodilator), which may be used for diagnostic purposes only (stress trigger for myocardial perfusion imaging; myocardial perfusion imaging, MPI), increases the risk of apoplexy; contraindications (contraindications): history of atrial fibrillation or existing risk of severe hypotension (low blood pressure); caveat. Aminophylline is not recommended for termination of regadenoson-related seizures!
  • Recombinant growth hormone (STH) therapy in childhood – in adulthood: factor 3.5 to 7.0 increased incidence rate of hemorrhagic stroke; factor 5.7 to 9.3 increased rate of subarachnoid hemorrhage.

Operations

  • Percutaneous coronary intervention (PCI) → ischemic strokes after PCI/procedure used to dilate stenosed (narrowed) or completely occluded coronaries (arteries that surround the heart in a wreath-like fashion and supply blood to the heart muscle) (= post-PCI strokes) (relatively rare complication)

Environmental stress – intoxications (poisonings).

  • Noise
    • Road noise: compared with road noise <55 db, road noise >60 db increases the risk of apoplexy by a significant 5% in adults and by a significant 9% in those aged 75 years and older
    • Aircraft noise: increase in average noise level by 10 decibels increases stroke risk by 1.3
  • Air pollutants
      • Particulate matter due to environment, household (due to coal stove and stove).
      • Smog (particulate matter, nitrogen dioxide, sulfur dioxide).
  • Weather
    • Temperature drops (risk increase; risk remains elevated for 2 more days; temperature drop of about 3°C each increases risk of apoplexy by 11%)
    • Rapid change in humidity as well as atmospheric pressure.
  • Heavy metals (arsenic, cadmium, lead, copper).

Other causes

  • Vessel wall dissection (tearing of the inner wall of the vessel) – for example, after chiropractic intervention on the cervical spine (the so-called vertebral arteries are affected).
  • Perioperative administration of only one erythrocyte concentrate.
  • Trauma to the cervical spine – occurrence of ischemic apoplexy during hospitalization.
  • Condition after stent implantation for intracranial stenosis – Apoplexy occurred three times more frequently after stent angioplasty (angioplasty in which a stent is implanted in the treated vessel) than during drug-only therapy.

Important note

  • Conjunctival hemorrhages (conjunctival hemorrhage): patients 40 years of age and older with conjunctival hemorrhages have a significant risk of apoplexy within three years of the event (7.3% versus 4.9% of the control group)