Evaluation of Ischemic Cerebrovascular Disease in Children

Examination

• Signs and symptoms: Evaluate the patient for signs and symptoms associated with pediatric ischemic stroke (e.g., seizures, lethargy, irritability, weakness, aphasia, dysarthria, vision disturbances, and altered mental status). See Presentation, Symptoms and Signs for more details.
• Neurological exam: Conduct a thorough neurological exam with initial assessment of neurological deficits using the PedNIHSS and the GCS (202-204). Identify a reliable reporter of baseline function; this is important in determining the “clinical penumbra.”
• Last known normal: Determining the last known normal time may inform treatment decisions, including the use of tPA or TNK (61).

Laboratory Tests

• Most important laboratory studies: Obtain CBC, urea and electrolytes; PT/INR and PTT; serum glucose; venous or capillary blood gas; and type and screen (202,203). No particular combination of abnormal results would be expected, but abnormal findings can inform the urgency of intervention, suggest the etiology, and/or determine whether certain actions must be taken (for example, achieving normoglycemia).
• Additional studies: In some patients, additional studies may be indicated early, including lumbar puncture for suspected infectious etiology, toxicology screen, and tests of anticoagulation or antiplatelet therapy effectiveness (202,203).

Radiologic Tests

Regular x-rays, ultrasound, etc

• Cranial ultrasound: Cranial ultrasound may be used at the bedside to rule out intracranial hemorrhage in preterm infants or in infants with a patient anterior fontanelle (199).
• TCD ultrasonography: TCD ultrasonography can be used for stroke risk surveillance in children with sickle cell hemoglobinopathy; a cerebral blood flow velocity greater than 200 cm/sec is associated with an increased risk of stroke (70). Despite this, screening rates remain low in the United States (206). The use of this technique to assess stroke risk is more common in outpatient screening settings than during urgent evaluation.
• Transthoracic echocardiography: Transthoracic echocardiography may be employed to evaluate for cardiac thrombus, vegetations, and right-to-left cardiac shunt; a bubble (saline contrast) study can evaluate for a PFO (203).

CT scans

• Head CT: Despite having less sensitivity for detecting ischemic stroke than MRI, non-contrast head CT may be used as the initial imaging modality for clinically unstable patients, when MRI is not available, or when MRI is contraindicated (199). Findings in patients with ischemic stroke may include loss of grey-white matter differentiation, hyperdense artery sign, and cerebral edema (207). Thrombus in CVST may appear as a hyperdensity within a cortical vein or sinus (199). Non-contrast head CT may also rule out hemorrhage (hyperdense blood collections).

Non-contrast head CT of a 15-year-old male who presented with acute neurological decline: (A) Hyperattenuating clot is present in the left proximal MCA and terminal ICA (yellow arrow). (B) Image shows loss of gray-white matter differentiation and sulcal effacement in the left hemisphere, indicating cytotoxic edema. (Images courtesy of Dr. Fabricio Goncalves and Caroline Davies of the University of Alabama at Birmingham Heersink School of Medicine.)

• CT angiography: CTA performed simultaneously or following non-contrast head CT may reveal thrombus within a vessel (vessel cutoff) and interhemispheric blood flow differences. CT venography may reveal an empty delta sign in CVST (199). In children, the CTA imaging protocol will often acquire images with some incorporation of the venous phase, leading to “venous contamination” of the CTA image. It is important to recognize that the vessel structure contrasted may not reflect the arterial anatomy or may be a mixture of the arterial and venous structures.
• Limit radiation exposure: When employing CT imaging in the pediatric population, consideration must be given to limit exposure to ionizing radiation, especially in younger children.

DSA

• DSA: DSA rarely plays a role in the immediate evaluation of pediatric ischemic stroke, but it can help identify the etiology of ischemic stroke in patients with an equivocal or uninformative initial workup; moreover, DSA is important when endovascular therapy is indicated (208). DSA can reveal arteriopathy and is considered the gold standard for identification and characterization of craniocervical arterial dissection, which may be associated with a double-lumen sign (209).

DSA of an 18-year-old female presenting with cocaine vasospasm: Selective injection of the left ICA demonstrates profound vasospasm of the left MCA (yellow arrow) and its branches. (Left) Image shows a common carotid artery injection with ECA and ICA opacification but abrupt diminished filling at the mid M1 segment in the early arterial phase. (Center) Image later in the arterial phase shows minimal distal M1 or MCA bifurcation filling. The ACA territory provides some leptomeningeal collateralization to supply the MCA-ACA watershed (yellow arrow). (Right) A region of minimal perfusion (yellow arrow) remains during the late arterial phase. (Images courtesy of Dr. Fabricio Goncalves and Caroline Davies of the University of Alabama at Birmingham Heersink School of Medicine.)

MRI

• Brain MRI: As it does not expose patients to ionizing radiation and is highly sensitive for the detection of hyperacute stroke, brain MRI is the preferred imaging modality for diagnosis and evaluation of pediatric ischemic stroke (199). Acute infarction is visible as hyperintensity on DWI and hypointensity on ADC, and PWI can identify penumbra regions (199). SWI and GRE may rule out intracranial hemorrhage, and these sequences can also reveal a hypointense susceptibility vessel sign at the site of thrombus (207). Anatomic delineation and identification of stroke mimics can be achieved by axial T1-weighted and T2-weighted imaging (199,207). Perfusion MRI via arterial spin labeling may be preferable to dynamic susceptibility contrast MR perfusion as it does not require contrast and can characterize causes of intracranial hemorrhage in children (199). There are various techniques to label the arterial flow, so different institutions will have different limitations on interpretation of arterial spin labeling imaging.

MRI of a 15-year-old female presenting with ataxia and dysmetria: (A) T2-weighted MRI shows bilateral cerebellar hyperintensities (yellow arrows). (B) Bilateral cerebellar hyperintensities (yellow arrows) on DWI and (C) corresponding hypointensities (yellow arrows) on ADC are indicative of bilateral cerebellar infarcts. (D) FLAIR MRI shows bilateral cerebellar hyperintensities (yellow arrows). (Images courtesy of Dr. Fabricio Goncalves and Caroline Davies of the University of Alabama at Birmingham Heersink School of Medicine.)

CT and MRI of a 9-year-old female presenting with dizziness: (A) Non-contrast head CT demonstrates a left-sided hypodensity of the cerebellar nodulus (yellow arrow). (B) Coronal and (C) axial FLAIR MRI show a focal hyperintensity of the nodulus (yellow arrows). (D) T2-weighted MRI demonstrates a corresponding hyperintensity (yellow arrow). (E) Corresponding hyperintensity (yellow arrow) demonstrated on DWI and (F) as hypointensity (yellow arrow) on ADC image. (Images courtesy of Dr. Fabricio Goncalves and Caroline Davies of the University of Alabama at Birmingham Heersink School of Medicine.)

• MR angiography: TOF MRA or MRA with contrast of the head and neck can reveal arteriopathy and arterial stenosis or occlusion (207). MR venography, in CVST, may reveal lack of flow in the sinuses (210).

MRI and MRA of a child presenting with right-sided weakness and facial droop: (A) MRA demonstrates occlusion of the proximal left MCA (yellow arrow). (B) FLAIR MRI demonstrates hyperintensities (yellow arrow) of the left internal capsule, basal ganglia, and insular cortex. Note the corresponding (C) hyperintensities on DWI and (D) hypointensities on ADC (yellow arrows). (E) Perfusion-weighted MRI reveals loss of perfusion in the corresponding region (yellow arrow). (F) T2-weighted MRI shows corresponding hyperintensities (yellow arrow). (Images courtesy of Dr. Fabricio Goncalves and Caroline Davies of the University of Alabama at Birmingham Heersink School of Medicine.)

Nuclear Medicine Tests

• Generally not used: Although most centers only infrequently perform nuclear medicine tests in the evaluation of pediatric ischemic stroke, SPECT may be used to elucidate brain perfusion patterns and regions of hypoperfusion (211).

Electrodiagnostic Tests

• ECG may be used to evaluate cardiac function.
• EEG may be used to monitor seizure status.

Neuropsychological Tests

• Neuropsychological testing: Neuropsychological testing can be used in the long-term follow-up of children who suffered ischemic stroke to assess for developmental delay and neuropsychological sequelae (212-214).

Correlation of Tests

The history, physical exam, laboratory tests, and imaging should establish the diagnosis of ischemic stroke versus other diagnoses, including stroke mimics. These sources of information may also indicate the stroke etiology, which can then be used to inform treatment decisions.

• History and observational data: The information obtained in a thorough history, a screen for signs and symptoms, and a neurological exam can suggest the etiology of pediatric ischemic stroke, predict which brain regions are affected, estimate the stroke severity, and indicate whether urgent intervention is needed.
• Laboratory tests: Lab test results can suggest the etiology and inform decisions made in the early stages of evaluation and stabilization.
• Imaging: MRI/MRA or CT/CTA can differentiate between ischemic and hemorrhagic stroke and may reveal the presence of stroke mimics. DSA may be required when the etiology of stroke is unclear despite a thorough workup.