• cancer patients are at increased risk of not only venous but also arterial thromboembolism (ATE),  including stroke and MI) [Mulder, 2021] [Babak, 2015]
    • stroke is, however, not the most common complication of cancerassociated thrombosis;  HR for stroke is approx.  1.44   [Paterson, 2022]
    • the highest risk of 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)
  • in cryptogenic stroke, cancer survey is suggested ⇒ thromboembolism may be the first manifestation of the disease
    • tremendously increased D-dimers have been found in patients with cryptogenic stroke and occult cancer

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 lead 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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  • hypercoagulable state
    • thrombocytosis
    • hyperviscosity syndrome (tumors with monoclonal Ig production)
    • DIC (mainly acute leukemia)
  • autoimmune disorders
    • paraneoplastic vasculitis
    • antiphospholipid syndrome (APL)
    • acquired von Willebrand syndrome
    • microangiopathic hemolytic anemia
  • non-bacterial (marantic) endocarditis with embolizations
  • angiopathy
    • post-radiation
    • compression of a blood vessel by a tumor
    • tumor invasion into the vessel with its occlusion or embolization of tumor masses peripherally
    • neoplastic vasculitis
  • an adverse effect of chemotherapy
    • microangiopathy
    • cardiac toxicity

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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  • individual assessment of bleeding risk and the potential benefit is necessary; take into account the patient’s prognosis
  • avoid IV thrombolysis in patients with: 
    • ↑ risk of bleeding
    • an infaust prognosis with an expected survival of < 6 months

Conservative therapy and stroke prevention

  • cancer treatment + symptomatic treatment of hematological disorders
  • for non-cardioembolic stroke, prescribe aspirin 100 mg/d
    • the application of anticoagulants in stroke patients with cancerassociated hypercoagulability is controversial;  some authors suggest LMWH or DOACs (Hsu, 2019)
  • in atrial fibrillation or concurrent DVT, prefer DOACs or LMWH to warfarin (AHA/ASA 2021 2a/B-R)
    • in cancer-related thrombosis and thromboembolism, avoid warfarin

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Cancer-related stroke
link: https://www.stroke-manual.com/cancer-related-stroke/