Pediatric Moyamoya disease

Background

Takeuchi and Shimizu [1] (1957) defined Moyamoya disease (MMD) as hypoplasia of bilateral internal carotid arteries. Twelve years later Suzuki and Takaku [2] named it Moyamoya, which means puff of smoke that represents angiographic representation of collaterals. Current definition is progressive internal carotid arteries occlusion with compensatory basal cerebral collaterals development [3]. Its incidence ranges between 0.086 in USA to 0.54 per 100,000 patients globally [4,5]. It accounts for one fifth of the identifiable cerebral arteriopathies in childhood stroke up to most common cerebrovascular disease in children in East Asia [6,7]. In children, unilateral involvement occurs about 18% [8] and progress to bilateral involvement within 2 years [9].

Case Report

A 7-year-old African American girl presented to the pediatric emergency department with acute mental status changes. Her parents reported that she had woken up after a nap agitated and confused. She was observed to stand up from the car seat, was restless and wanted to exit the car. She was able to speak a few words although not in a proper context, and was not able to follow any directions. However, She was able to walk supported. No convulsive movements, head or eye deviation was seen. There was no incontinence or tongue biting.

Review of symptoms was negative except what mentioned previously. There was no observed ingestion of drugs or toxins, although there was potential access to drugs in the house including hydrocodone/acetaminophen, alprazolam, and amitriptyline. There was no history of any past head injury, seizures or central nervous system infections. She was born full-term vaginally with Apgar scores of 8 and 9. There was no history of previous neurological deficit, developmental delay or other significant medical illness. The paramedic staff found persistent confusion and agitation with sluggishly reactive dilated pupils.

Family history was negative for seizure disorder or chronic medical condition including sickle cell disease or trait and neurofibromatosis. There was a paternal history of psychiatric illness, unspecified, treated with multiple medications.

In the emergency department, she was found to be afebrile with following vitals: BP 110/68, HR 123 bpm and RR 24. Her weight was 32.7 kg (75th centile) and her height was 152.4 cm (>97th centile). Child was asleep but arousable, with brief eye contact. Pupils were equal and reactive at 8 mm. She had a normal cranial nerve examination, including sharp disc margins on funduscopy. She moved all 4 extremities well with symmetrical 3+ deep tendon reflexes in the lower limb and 2 + in the upper extremities. Plantar responses were flexor bilaterally, without ankle clonus. Chest, heart and abdomen examination was within normal limits with Tanner stage I pubertal stage. Skin and mucous membrane did not reveal any unusual pigmentation, rash or pallor.

Complete blood picture were WNL as well as comprehensive metabolic panel that showed bicarbonate 18 mmol and anion gap 18 mmol that respond to intravenous saline bolus. Urine drug screen was negative. Acetaminophen and ethanol blood levels were below detectable levels. Hemoglobin electrophoresis showed hemoglobin A1 96.1%, A2 3.2% and F 0.7%. Both electrocardiography and bedside electroencephalography were normal for age. Renal ultrasonography with Doppler flow study showed no evidence of renal artery stenosis.

Non-contrast computerized tomography of brain showed an area of decreased density consistent with encephalomalacia in left parietal cortex (Figure 1). Magnetic resonance imaging (MRI) brain with contrast showed an old ischemic infarct involving left parietal cortex with attenuation and narrowing of cavernous and supra-clinoid internal carotid arteries bilaterally as well as horizontal portion of middle cerebral arteries bilaterally with increased prominence and enhancement of lenticulo-striate and thalamo-perforating arteries bilaterally favoring a diagnosis of MMD (Figure 2).

A trans-femoral four vessel cerebral angiogram showed extra-cranial intracranial collateral anastomoses derived from branches of the external carotid artery to bypass internal carotid obstruction in both sides especially left side. (Figures 3A,B and 4A,B). After this patient had been stabilized and diagnosed, she was discharged on aspirin 1 mg daily and to follow up with pediatric neurosurgeon and neurologist.

Discussion

MOYAMOYA DISEASE:

Reported incidence rate ratios are 4.6 for Asian Americans, 2.2 for blacks and 0.5 for Hispanics as compared with whites [5]. The incidence peaks in two age groups: children who are approximately 5 years of age and adults in their mid 40s [11]. Females are affected nearly twice as often as males [12]. Familial occurrence accounts for about 15% of patients [13]. Pediatric MMD usually presents with cerebral ischemia (80%) rather than hemorrhage (20%) [14]. Immature verbal skills in younger children make it difficult for early diagnosis (transient ischemic attacks versus infarction) [15]. Ischemic events can occur secondary to crying, blowing or hyperventilation. This behavior induces hypocapnic vasoconstriction or vasospasm in an already compromised cerebral circulation [16]. Patients can also present with headaches, seizures, involuntary movements and progressive decline in intellectual ability [17,18].

The typical histopathology of Moyamoya cerebral vasculopathy includes thickened intima with smooth muscle proliferation with tortuous duplicated internal elastic lamina [19]. Abnormalities of vascular growth factor and inflammatory mediators have been reported [20–22].

Ischemic symptoms occur most often during the first 4 years of diagnosis then tend to decline in contrast to intellectual deterioration that increase with time [18,23]. Good prognostic indicators are age greater than 3 years old, TIA on presentation [24], increased cerebral blood volume on perfusion MRI [25], decreased vascular reserve only with normal basal perfusion on SPECT [26] and rebuild phenomenon on EEG [27] in which there is a slowed recovery to baseline after hyperventilation-induced physiologic slowing.

A head CT is typically the first study obtained which shows areas of hypodensity consistent with infarction, and less commonly hemorrhage or atrophy [17]. MRA is very useful for diagnosing MMD with sensitivity of 73% and specificity of 100% [28]. Sensitivity increases to 92% when MRA is combined with MR imaging [29,30]. However, the smaller Moyamoya collaterals are visualized more clearly with conventional cerebral angiography [31] that is still the gold standard for diagnosing and surgical decision making for MMD [5].

Cerebral blood flow techniques are very useful in diagnosis and management of MMD, which include Xe-enhanced CT, PET and SPECT that assess cerebrovascular reserve as well as disease progression [32–34].

Currently there is no definitive medical treatment to reverse or stabilize the course of MMD (except when associated with sickle cell disease with transfusion protocol). Aspirin and calcium channel blockers [35–37] play a supportive role in the medical management of MMD.

At the present time, there is no standardized surgical approach for the treatment of MMD in children and numerous revascularization procedures have been used [38]. They aim to prevent further ischemic injury by increasing collateral flow using external carotid circulation as a donor supply [39–43].

Revascularization procedures can be divided into 3 main groups: indirect (non-anastomotic) bypass techniques, direct (anastomotic) bypass techniques or combined. Indirect procedure group was compared with pooled data from the direct and combined procedure groups, good collateralization was seen more significantly more often in the direct or combined group [38]. Also data proved that addition of bifrontal encephalogaleo-periosteal synangiosis (EGPS) to indirect procedures could improve outcome in pediatric Moyamoya [44].

Conclusions

A high index of suspicion, consideration of wide range of differential diagnosis, complete physical exam and subsequent work up is mandatory to manage pediatric patients with altered mental status. Early diagnosis and intervention will alter the prognosis and life expectancy in pediatric patients with MMD. Conventional cerebral angiography is still the gold standard for diagnosing and surgical decision making for MMD.

There is no definitive medical treatment to reverse or stabilize the course of MMD. At the present time, there is no standardized surgical approach for the treatment of MMD in children and numerous revascularization procedures have been utilized with fairly good results in slowing disease progression.