ISCHEMIC STROKE / CLASSIFICATION AND ETIOPATHOGENESIS

Cancer-related stroke

Created 15/11/2021, last revision 15/02/2022

  • cancer patients are at increased risk of not only venous but also arterial thromboembolism (ATE,  including stroke and MI) [Mulder, 2021] [Babak, 2015]
    • the highest risk of cancer-related stroke is with pancreatic, lung, and colorectal tumors
  • some strokes are directly related to the tumor or metastases, others to diagnostic methods or therapy (early and delayed cardiovascular complications)
  • clinicians should be aware of this risk, which is associated with increased morbidity and mortality

Etiopathogenesis

The cause of a cancer-related stroke is usually complex; multiple mechanisms may contribute:

  • secondary paraneoplastic syndromes
    • nonbacterial endocarditis and hypercoagulable state are common causes
    • vasculitides are rare – only ~5% of vasculitides are paraneoplastic in origin, and only a small percentage of these leads to ischemia [Sánches-Guerrero, 1990]
  • early or delayed complications of therapy   (Anand, 2016)
    • cardiomyopathies (anthracyclines or trastuzumab)
    • systemic hypertension
    • myocardial ischemia
    • pulmonary hypertension
    • radiation-induced vasculopathy
    • chemotherapy-induced vasculopathy
Primary Secondary
  • CNS and cranial nerves
    • encephalomyelitis
    • subacute cerebellar degeneration
    • opsoclonus/myoclonus syndrome
    • limbic encephalitis
    • optic neuritis
    • tumor-associated retinopathy
    • necrotizing myelopathy
    • motor neuron disease
    • stiff person syndrome
    • peripheral nerve lesions
    • polyneuropathy
    • polyradiculoneuritis
  • neuromuscular transmission disorders
    • Lambert-Eaton
    • Myasthenia gravis
  • muscle disorders
    • myotonia
    • myopathy (cachectic, carcinoid)
  • vasculitis
  • hematological disorders
    • thrombocytopenia, thrombocytosis
    • coagulation disorders
    • acquired von Willebrand’s disease (disorder in which the blood does not clot properly)   (Jin, 2014)
  • nonbacterial noncarditis
  • hyperviscosity syndrome
  • metabolic disorders
  • infections
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Clinical presentation

  • similar proportions of ischemic stroke and bleeding, cerebral sinus thrombosis occurs less frequently
    • hemorrhages are frequent in leukemias
    • ischemic strokes typically occur in carcinomas and lymphomas
  • focal neurological deficit corresponds to the affected vascular territory
  • frequent signs of progressive encephalopathy, caused by:
    • multiple embolizations in marantic endocarditis
    • hypercoagulable state with multiple infarcts
    • vasculitis
    • differentiate encephalopathy related to paraneoplastic syndrome (limbic encephalitis, etc.) or therapy-induced encephalopathies

Diagnostic evaluation

  • standard imaging methods (CT+CTA / MR+MRA, neurosonology)
    • often multiple lesions (even in hemorrhages)
    • in DDx distinguish tumorous infiltration from ischemia  Histologically confirmed multiple metastases of lung adenocarcinoma  Histologically proven malignant non-Hodgkin's lymphoma 
  • blood tests
    • complete blood count (CBC) + coagulation tests + erythrocyte sedimentation rate (ESR)
    • basic metabolic panel
    • in suspected vasculitis perform CSF examination
  • look for other vascular manifestations of the tumor (venous thrombosis in legs, venous thrombosis in atypical localisations, migrating thrombophlebitis, etc.)

Management

Acute stroke therapy

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Conservative therapy and stroke prevention

  • cancer treatment + symptomatic treatment of hematological disorders
  • in non-cardioembolic stroke, prescribe aspirin 100 mg/d
  • in atrial fibrillation, prefer DOACs to warfarin (AHA/ASA 2021 2a/B-R)
  • in hypercoagulable states prefer LMWH, but the risk-benefit is uncertain (↑ risk of bleeding)  (AHA/ASA 2021)
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