Paroxysmal Nocturnal Hemoglobinuria in ESUS & ETUS

Inclusion Criteria:

General:

- Participants with embolic ischemic stroke (ESUS), embolic transient ischemic attack (ETUS) or cerebral venous thrombosis (CVTUS) of undetermined source.

For transient ischemic attack (TIA):

One of the following criteria needs to be fulfilled to be considered as embolic TIA:

- Focal symptoms suggesting involvement of de cerebral cortex in the middle cerebral artery (MCA) territory (e.g., aphasia, neglect, apraxia, dystextia, anosognosia, isolated leg, arm or hand weakness). Some of these symptoms have been described as associated with subcortical fibers connecting cortical areas as well but, despite this, they are usually related to cortical localizations. Patients with hemianopia will be included only if hemianopia is not the primary symptom or an isolated symptom.

- Rapidly resolving hemispheric symptoms. This concept comprises two components: (a) sudden onset hemispheric syndrome: sudden onset of symptoms and signs implicating extensive ischemia in the internal carotid artery (ICA) or MCA territories, including hemiparesis, hemianopia, conjugate eye deviation, other cortical signs, or altered consciousness; and (b) spectacular shrinking deficit: improvement within 24 hours (approximately).

- Symptoms involving more than one vascular territory within a single hemisphere (e.g. left sided weakness + left homonymous hemianopia) or both (e.g., left sided weakness and aphasia in a right-handed patient).

- Simultaneous embolization to other organs (e.g., bowel, spleen, liver, kidneys, toes).

- Transient monocular blindness (amaurosis fugax) with no evidence of giant cell arteritis (e.g., normal erythrocyte sedimentation rate).

- No definite cortical symptoms but neuroimaging evidence of prior (chronic) typical infarct (wedge shaped, involving the cerebral cortex).

All of the following criteria must be fulfilled to be considered as TIA of undetermined source:

- No neuroimaging evidence of an acute brain infarct within the brain region(s) responsible for the presenting symptoms.

- Absence of extracranial or intracranial atherosclerosis causing ≥50% luminal stenosis in arteries supplying the area of ischemia.

- No major-risk cardioembolic source of embolism.

- No other specific cause of stroke identified (e.g., arteritis, dissection, migraine, vasospasm, or drug abuse).

- No persistent neurological focal symptoms at the time of neurological examination. The presence of persistent neurological focal symptoms in the absence of a visible brain infarct on DWI MRI will be regarded as a "clinically confirmed stroke with negative DWI MRI".

Exclusion Criteria:

General:

- Inability to provide informed consent

For stroke patients:

- Evidence of >50% stenosis of the internal carotid artery (ICA) or MCA ipsilateral to the qualifying ischemic stroke on neurovascular imaging studies.

- Ischemic stroke involving deep structures and measuring < 15 mm on diffusion-weighted (DWI) magnetic resonance imaging (MRI). Cortical strokes measuring <15 mm will qualify to be included in the study.

- Evidence of a cause explaining the stroke (e.g. hypercoagulable state or any other major source of cardiac embolism).

For TIA patients:

- Patients no fulfilling the criteria for ETUS.

For cerebral venous thrombosis patients:

- Subjects without involvement of the superior sagittal sinus (SSS)

- Subjects with an evident cause explaining the thrombosis (e.g., thrombophilia)