ISCHEMIC STROKE

Neuroimaging in pediatric stroke

Created 09/12/2022, last revision 21/12/2022

pediatric stroke is increasingly being recognized as an important cause of morbidity and mortality
- over 75% of children suffer long-term neurological deficits
- mortality approx. 10%
- 19% recurrence/ 5 years
it has a unique presentation (which may delay correct diagnosis) and etiologies (→ etiology of pediatric stroke)
- the diagnosis of stroke is often tricky in infants and children because nonspecific localizing signs are often overlooked
- according to one study, only 20% of children were diagnosed with stroke within six hours, and stroke was not suspected in over 62% of children at initial presentation (Rafay, 2009)
neuroimaging is an essential component of pediatric stroke management; it helps to:
- confirm the diagnosis and type of stroke (ischemic x hemorrhagic)
- exclude stroke mimics (PRES, epilepsy, CNS infection, complicated migraine, drug toxicity, etc.)
- identify the stroke etiology
- facilitate treatment decisions (acute therapy, prevention)
- provide prognostic information

Overview of neuroimaging modalities

the choice of radiologic study depends on the age of the patient, the clinical scenario, and the hospital resources
non-contrast head CT (NCCT) is often the initial imaging method in a child with stroke symptoms (availability, speed, sensitivity for ICH, etc.)

CT + CT angiography

NCCT has limited sensitivity for the detection of acute pediatric stroke and frequent stroke mimics + requires exposure to ionizing radiation and iodinated contrast dye
if possible, magnetic resonance imaging is preferred
if MRI is contraindicated or unavailable, perform NCCT+CT angiography of the head and neck, with or without CT venography

MRI + MR angiography

MRI + MRA/MRV + MR perfusion are optimal for obtaining the definitive diagnosis of both ischemic and hemorrhagic lesions, as well as to identify underlying arteriopathy, thrombus, or arterial dissection in both neonates and older children
many centers have implemented rapid brain MRI protocols for stroke to shorten examination time; the rapid protocol typically includes:
- diffusion-weighted imaging (DWI) and apparent diffusion coefficient (ADC) maps → DWI in acute stroke diagnosis
- gradient echo (GRE) sequences or susceptibility-weighted imaging (SWI) to detect hemorrhage
- MR angiography
- MR perfusion
  - arterial spin labeling (ASL) – not extensively validated in pediatric stroke
  - contrast-enhanced perfusion imaging is less often used
    - dynamic bolus passage of gadolinium with rapid T2* weighting (dynamic susceptibility contrast, DSC)
    - dynamic bolus passage of gadolinium with T1 weighting (dynamic contrast enhancement, DCE)
- vessel wall imaging (VWI) – to detect inflammatory process or dissection

Digital subtractive angiography

can be considered when the cause of the infarction is unclear from non-invasive imaging studies, and when high clinical suspicion of an arteriopathy remains
it has better sensitivity for aneurysms, vasculopathies involving medium-small vessels, or other structural vascular disorders

Perfusion methods (CTP, MRP, SPECT)

important methods to assess hemodynamic changes when revascularization procedures are considered (bypass or synangiosis in vasculopathies like moyamoya)
strict perfusion parameters are not established in children; physiologic and hemodynamic differences are to be expected

Neuroimaging in different stroke subtypes

Ischemic stroke

→ etiology of pediatric stroke

some disorders are more frequent in pediatric stroke compared to adults:
- focal cerebral arteriopathy (FCA), also known as transient cerebral arteriopathy
- primary and secondary Moyamoya disease
- genetic or syndromic arteriopathies (such as PHACE syndrome, ACTA2 angiopathy, Grange syndrome, etc.)
- vasculitis
- fibromuscular dysplasia
- iatrogenic stroke
- dissection
- hypercoagulable states (thrombophilia)

Computed tomography (CT)

CT is often the first imaging modality performed (if MRI is not available or the child is unstable)
- excludes intracranial hemorrhage but is insensitive to hyperacute or small ischemic infarctions
- infarction has a similar appearance to that in the older child or adult, manifesting as a well-defined, often wedge-shaped region of hypoattenuation in an arterial distribution
CTA is used to detect artery stenosis or occlusion

Magnetic resonance imaging (MRI)

the modality of choice in pediatric stroke; the appearance of infarction is the same as in adults
DWI
- MRI shows reduced diffusivity within minutes, presenting as a high signal on DWI and low computed diffusivity values on ADC maps
- high signal on DWI increases continually in the hyperacute and acute phases, peaking commonly after several days
- a transient pseudo-normalization may be observed for days, with diffusivity then increasing to supranormal levels (the development and evolution of pseudonormalization on ADC will commonly precede that on DWI)
- a pediatric modification of the ASPECTS (pedASPECTS) score was developed using DWI (Mackay, 2020)
  - the score includes two regions of the anterior (A1 and A2), 10 areas of the middle (M1, M2, M3, M4, M5, M6, insula, internal capsule, caudate, and lentiform nucleus), and three regions of the posterior cerebral artery territories (P1, P2, and thalamus) in each hemisphere. One point is allocated to each area affected by infarction; the total pedASPECTS ranges from 0 for normal to 30 for maximal severity (15 per hemisphere)
DWI-FLAIR mismatch
- the mismatch between DWI and FLAIR changes has been proposed for the determination of the time window for recanalization intervention
- in adults, DWI appears to predict the core reliably, and the DWI-perfusion weighted imaging (PWI) mismatch using DSC profiles may then be used to assess penumbra (validation in children is lacking)
- arterial spin labeling (ASL) is correlated with DSC perfusion parameters, but the correlation is imperfect and improved methods are needed
MRA and vessel wall imaging
- MRA helps to identify the site and extent of stenosis or occlusion
- if arteriopathy is suspected, vessel wall imaging (using black-blood, T1-weighted post-contrast imaging) can demonstrate abnormal vessel wall enhancement in the setting of active inflammatory processes, as well as assess for intracranial arterial dissection on pre-contrast T1-weighted imaging
- some genetic arteriopathies have unique imaging appearances, such as ACTA2 mutation, which demonstrates dilation of the proximal internal carotid arteries, occlusion or narrowing of the distal internal carotid arteries, straight “broomstick-like” arteries of the circle of Willis, and absence of lenticulostriate collaterals
MR perfusion
- ASL can identify areas of reduced or increased perfusion, helping to differentiate lesions causing stroke or stroke symptoms from mimics; age-specific labeling protocols should be employed
- perfusion imaging (DSC) is helpful in identifying regions of relative ischemia that are at risk for infarction in moyamoya syndrome
  - benign, compensated oligemic delays cannot be discriminated from regions of severe hemodynamic stress with exhausted cerebrovascular reserve; cerebrovascular reactivity or direct oximetry may be required

Hemorrhagic stroke

pediatric hemorrhagic stroke (intracerebral hemorrhage, ICH) has different causes compared to adults (where hypertensive bleeding prevails)
- rupture of vascular malformations or aneurysms
- hemorrhagic venous infarction (CSVT)
- coagulopathy
- infant intraventricular hemorrhage (IVH)
- genetic arteriopathies associated with hemorrhagic stroke (IVA or JAM3 mutations)
imaging should:
- differentiate hemorrhagic transformation (arterial or venous) from primary hemorrhage
- detect an underlying mass or vascular malformation as a source of bleeding
CT – usually baseline imaging
- excellent sensitivity for the detection of hemorrhage
- CTA can detect underlying vascular pathology
MRI – preferred in stable patients (T1,2, FLAIR, DWI, SWI/GRE, MRA and/or MRV)
DSA – may be considered if no lesion is identified on initial imaging to assess for small vascular malformations
if no malformation is identified on baseline imaging, repeat neuroimaging after the hematoma has resolved (small lesions can be compressed)

Intracranial venous thrombosis

→ clinical presentation and etiology of CSVT
→ diagnosis of CSVT

venous infarcts caused by cerebral sinus venous thrombosis (CSVT) are relatively common (approx. 40% of CSVT cases)
approximately 70% of these infarcts are hemorrhagic
thrombosis should be suspected in any child who has an unexplained hemorrhage or an infarction not fitting an arterial vascular distribution
risk factors include:
- head and neck infections
- chronic diseases such as connective tissue disorders
- coagulation disorders

MRI is the imaging modality of choice
- T1- and T2-weighted images + DWI, GRE/SWI images, and MRV
- acute (<3 days) thrombus exhibits low signal intensity due to the presence of deoxygenated hemoglobin
- in subacute thrombosis (>4-5 days), T1-weighted images show the high signal intensity of the clot
- GRE is helpful in detecting cortical veins thrombosis
CT venography
- sensitive and specific for the diagnosis of dural sinus thrombosis
- disadvantages:
  - radiation and contrast dye exposure
  - a limited diagnostic value for diagnosing cortical vein thrombosis