Evaluation of Moyamoya Disease in Children

Examination

History

• Previous neurologic illnesses: Presence of preceding transient ischemic symptoms, cerebral infarction, headache, seizure or cerebral hemorrhage are important clues for diagnosis.  The presence of neurofibromatosis, cranial radiation, sickle cell anemia and other conditions can be associated with cerebrovascular anomalies similar to Moyamoya Disease.
• Family history: The presence of family history can suggest the presence of a genetic mutation associated with increased risk for Moyamoya Disease.
• Daily activities: School performance and emotional stability are valuable information about the functional status of brain.
• Physical Examination: Sometimes systemic hypertension is associated by chronic cerebral ischemia or accompanying renal artery stenosis. Usually carotid pulsation in the neck reveals no diagnostic information. Searching for stigmata of neurofibromatosis type I and other conditions associated with quasi moyamoya may be valuable.
• Neurological Examination: The patient may asymptomatic between the transient ischemic attacks.

Laboratory Tests

• Renal function study: If the patient shows systemic hypertension, renal function should be tested.

Radiologic Tests

MRI

• MRI and MRA best initial screen:  With MR imaging, the thickness of blood columns in distal internal carotid artery and proximal middle, anterior and posterior cerebral arteries can be evaluated.
• Signs of schemic zones: The  Axial flair images can be helpful in identifying areas of slow flow by visualization of high signal in cortical sulci (“ivy sign”).
• Signs of infarction: Presence of cerebral infarction and its staging, identification of moyamoya vessels at the base of brain, leptomeningeal anastomosis, and intracranial hemorrhage should be noted.
• MRA can exaggerate vessel narrowing: It should be born in mind that the MRA may exaggerate the stenosis leading to false positive results, particularly in the setting of anemia.

T2-weighted axial MRI of a patient with Moyamoya Disease: A six-year old boy with transient weakness of both limbs, more prominent in the right side. T2 weighted images show poor visualization of bilateral middle cerebral arteries and multiple small infarcts at the centrum semiovale.

T1-weighted axial MRI of a patient with Moyamoya Disease: T1 weighted images demonstrate multiple collateral channels with flow void at the basal ganglia and multiple small cerebral infarcts at the centrum semiovale.

Gadolinium enhanced T1-weighted axial MRI of a patient with Moyamoya Disease: Enhanced T1 weighted images reveal diffuse leptomeningeal enhancement.

• Perfusion MRI: This is a commonly used tool for the evaluation of cerebral hemodynamics because of its availability, capability of evaluating cerebral vascular reactiveness and cost-effectiveness. A ‘time to peak map of perfusion’ MRI reveals the basal state of cerebral perfusion and a delay in the time to peak means hemodynamic abnormalities with compensation or decompensation. The CBV map can be determined using special T1-weighted, gadolinium enhanced MRI sequences and a map of perfusion generated. This map can show the degree of compensatory vasodilatation and collateral vessel formation present. Increased CBV in an area of delayed TTP perfusion means a compensatory reaction of local cerebrovascular structures is present. The CBV map of perfusion MRI is helpful for prediction of postoperative course.

Perfusion MRI : This patient with transient weakness of the left limbs without cerebral infarction shows increased cerebral blood volume and delayed time to peak in the right cerebral hemisphere and medial aspect of the left hemisphere.

Pre- and postoperative TTP map of perfusion MR : This map shows the same patient as shown in MRI above. Preoperatively perfusion MR shows markedly delayed time to peak in the area of anterior circulation in both sides (upper). At 2 months after indirect revascularization (left STA EDAS and bifrontal EGS), time to peak is much shorter than before surgery at the sites of revascularization (lower).

Cerebral Angiography

• Cerebral angiography: Angiography is still the gold standard for the definitive diagnosis.  Before surgery, cerebral angiography is recommended.  During cerebral angiography, it is recommended to check stenosis of other systemic arteries such as renal arteries. In addition, catheter angiography can help with surgical planning by identifying potential pre-existing spontaneous transdural collaterals, which should be avoided at operation (52).

Cerebral angiography: Cerebral angiography demonstrates bilateral stenosis of internal carotid, anterior and middle cerebral arteries with remarkable enlargement of perforators along the base of brain (left: right internal carotid artery injection, middle: left internal carotid artery injection). Compare with the MR angiography findings (right).

Pre- and postoperative cerebral angiography: Pre- and postoperative cerebral angiography reveals revascularization from the external carotid arterial trees through the scalp and meningeal arteries (upper left: preoperative right external carotid artery (ECA) injection, upper right: preoperative left ECA injection, lower left: postoperative right ECA injection, lower right: postoperative left ECA injection).

Nuclear Medicine Tests

SPECT with an acetazolamide challenge and less commonly PET are commonly used tools for the evaluation of cerebral hemodynamics.

• SPECT with Diamox Challenge: Because of its availability, capability of evaluating cerebral vascular reserve and cost-effectiveness, SPECT with Diamox challenge is more commonly used than PET. SPECT before Diamox challenge indicates the basal state of cerebral perfusion and SPECT after the administration of Diamox (i.e. challenge) demonstrates the reserve of cerebral perfusion. SPECT after Diamox can aid in the management of the expected postoperative course (similar to the information obtained from a CBV map of perfusion MRI).

Brain perfusion MR and Diamox challenge SPECT: Basal SPECT shows mild perfusion decrease at the right anterior frontal and the left posterior frontal areas (middle). SPECT after Diamox infusion reveals markedly decrease of vascular reserve at the right anterior frontal area and mild to moderate decrease at the left frontal area (right). Compare with the perfusion MR finding (left).

Pre- and postoperative brain SPECT and comparison perfusion MR: This patient’s (who experienced a transient weakness without infarction in the right limbs) SPECT scans demonstrate a decrease in vascular reserve for the left hemisphere before revascularization surgery (upper row). At 4 months after the first stage of indirect revascularization surgery (a left STA EDAS), the abnormal findings were improved at the site of surgery even though there is a persisting ischemia in both medial frontal areas (middle row). At 3 months after the second stage of indirect revascularization surgery (a right STA EDAS and bifrontal EGS), SPECT shows normalized vascular reserve (lower row).

• PET: In spite of its limited availability, PET provides useful information on the quantitative value of CBF and associated parameters. However, because of wide availability of MRI with simultaneous evaluation of brain morphology, vessel anatomy and perfusion status, MRI and SPECT are the main tools for evaluation of cerebral hemodynamics in Moyamoya Disease.

Electrodiagnostic Tests

• Diagnostic EEG: EEG is helpful for evaluation of cerebral ischemia in Moyamoya Disease. Electrical dysfunction due to focal cerebral ischemia can be detected with or without hyperventilation. A well-known EEG abnormality in Moyamoya Disease are focal electrical abnormalities caused by cerebral ischemia that disappear just after stopping hyperventilation and soon reappear, but transiently (the so-called “rebuild up” phenomenon). After successful revascularization surgery, this rebuild up phenomenon disappears as the ischemic symptoms are improved.
• Intraoperative protective EEG: Intraoperatively, EEG may help with reduction of perioperative stroke in some cases (60).

Neuropsychological Tests

• Recommended: Neuropsychologic testing is commonly recommended for the assessment of the impact of Moyamoya Disease on neurocognitive function and, when repeated serially, for following any changes that might result from the presence of Moyamoya Disease. While the testing has little localizing value, it will reveal the general functional performance of the brain. For schooling, the results provide useful information and guidance.

Correlation of Tests

• Factors predictive of good prognosis: Patients typically experience good outcomes after revascularization surgery when they have no fixed neurologic deficits, good cognition, normal emotional behavior and development, no infarction on MRI, preserved vascular reactiveness (increased CBV) on perfusion MRI, and less decreased perfusion with relatively preserved vascular reserve on SPECT.
• Factors predictive of poor prognosis: Patients with fixed neurologic deficits, poor intelligence, emotional instability, developmental delay, large infarction on MRI, decreased vascular reactiveness (decreased CBV) on perfusion MRI, and more decreased perfusion and more disturbed vascular reserve on SPECT often show less favorable outcomes after revascularization surgery.