ISCHEMIC STROKE / CLASSIFICATION AND ETIOPATHOGENESIS

Cancer-related stroke

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 cancer–associated 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

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

standard imaging methods (CT+CTA / MR+MRA, neurosonology)
- often multiple lesions (even in hemorrhages)
- in DDx distinguish tumorous infiltration from ischemia
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.)

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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

cancer treatment + symptomatic treatment of hematological disorders
for non-cardioembolic stroke, prescribe aspirin 100 mg/d
- the application of anticoagulants in stroke patients with cancer–associated 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