ISCHEMIC STROKE / CLASSIFICATION AND ETIOPATHOGENESIS

Stroke in young adults

Created 17/12/2021, last revision 21/12/2022

  • young adults stroke = stroke in persons aged 18 to 55y
    • some authors use an upper age limit of 45 or 49 years
  • young adults comprise 10%–15% of all stroke patients, with a significant increase above the age of 40   [Smajlović, 2015]
  • compared to the older population (where arteriolopathy, atherothrombosis, and cardioembolism due to AFib predominate), the spectrum of risk factors and possible causes is differently distributed and broader in the younger population  [Schöberl, 2017]
    • 25% – cardioembolic stroke (valvular defects, cardiac tumors, PFO)
    • 20% – dissection
    • 10% – rare causes (vasculitis, vasculopathies, thrombophilia, genetic diseases, etc. )
    • 25-50% – cryptogenic stroke (of which 20-30% meet ESUS criteria)
    • ?% – stroke in pregnancy and puerperium
  • approximately from the age of 40, the proportion of vascular risk factors increases, together with the proportion of large and small vessel disease (TOAST 1 and 3)
  • thorough etiologic diagnostic evaluation and individually tailored secondary prevention are essential
  • the acute treatment is the same for patients of all ages ⇒ recanalization therapy if eligible

Etiology and risk factors

  • the identification of rare causes of juvenile stroke requires a significant diagnostic effort
  • the most common etiology of stroke in young adults is a cryptogenic stroke (20-40%) and cardioembolic stroke  Etiology of juvenile strokes (Smajlović, 2015) [Smajlović, 2015]
    • TOAST classification can lead to overestimation of patients with stroke of undetermined etiology (TOAST 5), mainly because patients with two or more potential etiologies fall into this group
  • in young patients with carotid artery occlusion or stenosis, exclude dissection and vasculitis
  • modifiable vascular risk factors are similar for both younger and older patients
    • hypertension, heart disease (including atrial fibrillation), dyslipidemia, and diabetes mellitus are the most common risk factors among the elderly
    • in young stroke patients, the most common vascular risk factors are dyslipidemia, smoking, and hypertension  [Putaala, 2012]
    • patients without documented risk factors have less frequent recurrent ischemic strokes and non-cerebrovascular arterial events

etiologic diagnostic evaluation

DDx in young stroke patients according to TOAST
Large-artery atherosclerosis (TOAST 1)
  • in young adults, most large-artery pathologies are caused by vasculitis or non-inflammatory vasculopathies (which belong to TOAST 4)
  • premature atherosclerosis of large vessels is rare (more likely after the age of 40)
Cardioembolism (TOAST 2)
  • valvular disorders
  • PFO
  • intracardiac tumors (myxoma, fibroelastoma)
  • endocarditis
  • septal defects
  • cardiomyopathy
  • myocarditis
  • atrial fibrillation (rare in younger age)
Small artery disease (TOAST 3)
  • typical arteriolopathy with lacunar syndrome is uncommon in younger patients
  • genetic microangiopathies are included in TOAST 4
Stroke of other determined etiology (TOAST 4)
  • < 5% of stroke patients < 50 years of age   Primary CNS vasculitis
  • mainly PACNS and Takayasu arteritis are present at a younger age

→ see here

  • dissection Dissection in common carotid artery (CCA)
  • vasospasm Vasospasm on DSA
    • primary (idiopathic)
    • secondary (a consequence of complicated migraine, VSP provoked during angiography or by drugs, etc.)
  • reversible vasoconstriction syndrome (RCVS)
  • moya-moya angiopathy Moya-moya disease
    • multiple etiologies (e.g., Grange syndrome, ACTA2 mutations, vasculitis, etc.)
  • metabolic diseases
    • Fabry disease
    • homocystinuria
  • embolization from (pseudo) aneurysm (extra-/intracranial)   Aneurysm with intrasaccular thrombus (CTA)
  • migraine (probably due to vasospasm)
  • genetically linked diseases of the connective tissue
  • Sneddon syndrome

    • non-inflammatory thrombotic angiopathy affecting small to medium-sized arteries, clinically stroke + livedo racemosa
  • carotid artery web  Carotid artery web
  • Grange syndrome
  • dolichoectasia (usually in the basilar artery) Basilar artery dolichoectasia (CTA)
    • more often in older patients
  • CADASIL (Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy)   Cerebral Autosomal Dominant Arteriopathy with Subcortical Infarcts and Leukoencephalopathy (CADASIL)
  • CARASIL
  • CARASAL
  • Fabry
  • MELAS
  • HANAC (Hereditary angiopathy with nephropathy, aneurysms, and muscle cramps)
  • HERNS (Hereditary endotheliopathy with retinopathy, nephropathy, and stroke) → more here
  • Susac syndrome (retino-cochleo-cerebral vasculopathy)
    • rare microangiopathy of the cochlea, retina, and brain of unknown etiology (probably vasculitic in origin)   Susac syndrome - "string of pearls" in internal capsule
  • hypercoagulable states
    • primary – most often antiphospholipid syndrome and APC resistance
    • secondary
      • oncohematological diseases (e.g., leukemia, polycythemia vera)
      • thrombotic thrombocytopenic purpura (TTP)
      • non-specific intestinal inflammation
      • nephrotic syndrome
  • hemoglobinopathies (typically sickle cell disease)
  • hematological malignancies
  • hyperviscosity syndrome (HVS)
  • fat embolism
    • typically occurs after trauma (long bone fractures) and surgery (including plastic surgery with fat removal)
  • air embolism (microscopic x macroscopic) Macroscopic air embolization after endovascular surgery
    • a consequence of the incorrect insertion of a venous catheter into an artery [Riebau, 2004]
    • improper extraction of the central venous catheter (CVC) [Brockmeyer, 2009]
    • repeated IV applications in combination with pulmonary AV shunt or PFO
    • during catheterization
  • embolization of cholesterol particles from plaques should be assessed as TOAST 1 → Cholesterol Embolization Syndrome (CES)
    • spontaneous x iatrogenic
  • diffuse lesions Diffuse cerebral edema due to hypoperfusion during surgery in ECC (Extra Corporeal Circulation)  or border zone (watershed) infarcts Border zone infarcts (BZI)
  • etiology
    • systemic hypotension
      • cardiac failure
      • extracorporeal circulation (ECC) surgery
    • hypoperfusion in carotid occlusion/stenosis (⇒ TOAST 1! )
  • various mechanisms ( e.g., vasospasm, cardioembolism in endocarditis)
  • oral contraceptives (usually in combination with a hypercoagulable state and/or smoking)
  • cocaine, crack, amphetamines, LSD, and heroin (drugs frequently cause IC hemorrhages)
  • sympathomimetics, ergotamine, sumatriptan
Cryptogenic stroke (TOAST 5)  → see here
In addition to the TOAST classification, stroke in pregnancy and puerperium with a wide range of etiopathogenesis should be mentioned.
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Stroke in young adults
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