**4. Clinical manifestations in children**

Moyamoya disease presents with ischemic symptoms in children, an incidence of 68% and adults usually present with a hemorrhagic stroke, about 42% [10].

Amongst the ischemic symptoms, completed strokes are more common in children, a possible explanation being their inability to identify and complain about TIAs [15]. They can be transient or fixed. Most commonly occur in the territory of the internal carotid artery and proximal middle and anterior cerebral arteries [10].

Underlying mechanism:

Progressive stenosis of the internal carotid and middle cerebral arteries are responsible for most of the symptoms [10].

Maximally dilated cortical vessels in patients with chronic ischemia, constrict in response to the decreased carbon dioxide due to hyperventilation, resulting in reduced cerebral perfusion and thus exacerbating the symptoms [16].

Precipitating factors: [16].

Crying (In the paediatric population). Hyperventilation (In paediatric population). Exercise. Anaesthesia. Dehydration. Altitude. Eating a hot meal. Focal Symptoms: [10]. Hemiparesis. Dysarthria. Aphasia. Visual deficits. Chorea. Non-focal symptoms: [10].

Headache: Approximately 20% of the paediatric patients under the age of 14 years suffer from headache. Likely explanantion for the headache was the reduction of cerebral blood flow or cerebral blood flow reserve and diffusive cortical inhibition [17]. Dilatation of meningeal and leptomeningeal collateral vessels may stimulate dural nociceptors. Every refractory headache, especially in the paediatric population should be thoroughly worked up for moyamoya disease [17] Headaches can be migraine-like episodes which may respond to revascularization surgery or remain refractory to surgery [17].

Cognitive impairment, learning disability, and attention deficits.

Seizures.

Syncope.

Personality change, mistaken for a psychiatric illness like schizophrenia, acute transient psychosis, and mania [18].

Symptoms and signs which serve as biomarkers in MMD/MMS:

Orthostatic intolerance (also termed "orthostatic dysregulation"): [19] Orthostatic intolerance is defined as" a disturbance in the physiological adjustment mechanism compensating for physical stresses, such as standing, and causes a variety of symptoms associated with hemodynamic or autonomic nervous system compromise". These symptoms can have a potential impact on the quality of life of paediatric MMD patients. In a study done by H. Uchino et al., 59% of children 10–15 years old suffered from orthostatic intolerance. These symptoms usually go unnoticed, and thus a thorough history from the patients and their caretakers become mandatory.

Symptoms which are suggestive of orthostatic intolerance:

Frequent headache.

Susceptibility to vertigo & dizziness on standing.

Fatigue.

Difficulty while getting out of bed.

Motion sickness.

Palpitation &/or dyspnea after mild exercise.

Tendency for fainting in the standing position.

Anorexia.

Occasional umbilical colic (severe abdominal pain).

Nausea on taking a hot bath or encountering unpleasant experiences.

Absent from school due to the above symptoms.

Pallor.

Fundus: Retinovascular anomalies and "morning glory disk" an enlargement of the optic disk should compel the clinician to look for moyamoya vasculopathy [20]. Morning glory syndrome or Morning glory disc anomaly is an unusual

### **Figure 2.**

*Showing morning glory disc [courtesy:Indian J Radiol imaging. 2018 Apr-Jun] [22]. MRI brain CISS sequence of orbit region may further confirm funnel-shaped excavation of the posterior globein morning glory syndrome of Moyamoya disease (Figure 3) [22].*

**Figure 3.** *Showing funnel-shaped excavation of posterior globe [courtesy: Indian J Radiol imaging. 2018 Apr-Jun] [22].*

congenital optic disc anomaly characterised by a funnel-shaped excavation of the posterior globe that incorporates the optic disc [21]. Kindler described it in 1970 because it resembled the morning glory flower. The disc itself is enlarged, and orange or pink in colour within a surrounding area of peripapillary chorioretinal pigmentary changes. Alteration of lamina cribrosa and posterior sclera due to embryonic developmental defect leads to this fundus's flowery appearanace.

Presence of this sign indicates an association with systemic or intracranial vasculopathies such as MMD. Morning glory disc occurs in 50% of patients with the MMD (**Figure 2**).

Sequelae of MMD: [16]. Refractory headaches. Recurrent TIAs. Posterior cerebral artery (PCA) involvement. Recurrent intracranial aneurysms. Unstable MMD.

In children with MMD, recurrent ischemias can result in cerebral atrophy and thus emanate the onset of learning difficulties, cognitive impairment and mental retardation.
