|Year : 2016 | Volume
| Issue : 3 | Page : 393-396
A rare cause of seizures in children: "Moyamoya disease"
Shoubhi Bhatnagar, Digish Shah
Department of Radio-diagnosis, Padmashree Dr. D. Y. Patil Hospital and Research Centre, Pimpri, Pune, Maharashtra, India
|Date of Web Publication||17-May-2016|
19, Anupam Society, Jetalpur Road, Vadodara - 390 007, Gujarat
Source of Support: None, Conflict of Interest: None
Moyamoya means hazy in Japanese. It is a rare progressive idiopathic condition that affects major intracranial vessels. The disease is characterized by the distinct angiographic appearance of cerebral vessels resembling "puff of cigarette smoke." Although rare, a high index of suspicion in correct clinical setting can be helpful in apt diagnosis. The disease cloaked in common symptoms can lead to a devastating outcome, both in children and adults. Hence, comprehensive knowledge of this peculiar entity is a must.
Keywords: Children, magnetic resonance angiography, moyamoya, seizures
|How to cite this article:|
Bhatnagar S, Shah D. A rare cause of seizures in children: "Moyamoya disease". Med J DY Patil Univ 2016;9:393-6
| Introduction|| |
Moyamoya disease is a rare vasculopathy that affects the main intracranial vessels. The incidence of moyamoya in Asian population is approximately 3/100,000 of pediatric population.  The disease is characterized by progressive stenosis at the apices of the intracranial internal carotid arteries (ICA) including the proximal anterior cerebral arteries and middle cerebral arteries (MCAs). Clinically, a patient can present with epileptic complaints. The finding most diagnostic of moyamoya on magnetic resonance imaging (MRI) is reduced flow voids in cerebral arteries coupled with prominent flow voids through the basal ganglia and thalami representing collaterals. Surgery includes direct anastomoses between the superficial temporal artery and the MCA (STA-MCA anastomosis).
| Case Report|| |
A 12-year-old male child was brought with complaints of seizures (3-4 episodes). The patient had past history of similar complaints 4 months back. No associated history of fever, trauma to head, previous surgery, or any other major illness. Birth history and family history were noncontributory. MRI of the brain was performed on 1.5 Tesla Siemens machine. Scanning was performed in axial, coronal, and sagittal planes. A magnetic resonance (MR) angiogram was performed using three-dimension - time of flight technique and maximum intensity projection images were obtained.
MRI revealed attenuated flow void of the cavernous and supra-clinoid portion of right ICA with nonvisualization of proximal portions of the right anterior cerebral artery (ACA) and MCA. There were multiple flow voids representing small vascular channels in the suprasellar region extending into right sylvian fissure [Figure 1] and [Figure 2].
|Figure 1: Axial T2-weight image magnetic resonance image showing reduced caliber of right internal carotid artery compared to the contralateral side|
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|Figure 2: (a and b) Axial and coronal T2-weight image magnetic resonance images depict numerous small flow voids representing collateral channels in the supra-sellar cistern extending into right sylvian fissure with nonvisualization of proximal segments of right anterior and middle cerebral arteries|
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MR angiography (MRA) demonstrated uniform narrowing of the right ICA (from its origin to intracranial portion) compared to the left ICA with nonvisualization of A1 segment of right ACA and M1 segment of right MCA. The overall paucity of vessels was seen in the right cerebral hemisphere, especially in right MCA territory. Multiple small vascular channels were seen in right sylvian fissure and suprasellar cistern. The rest of the vessels of circle of Willis appeared normal. Left ICA was normal in course and caliber. The vertebro-basillar system was normal [Figure 3].
|Figure 3: (a and b) Maximum intensity projection reconstructions in axial and coronal planes reveal uniform narrowing of the entire right internal carotid artery (from its origin till intracranial portion). Multiple small collateral vascular channels are seen at the apex of right internal carotid arteries with absence of A1 segment of right anterior cerebral artery and M1 segment of right middle cerebral artery. There is paucity of vessels in right cerebral hemisphere. Rest of the vessels of circle of Willis, left internal carotid arteries and vertero-basilar system appear normal in course and caliber|
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| Discussion|| |
Moyamoya means hazy in Japanese. It is a rare vasculopathy that affects the main intracranial vessels. The disease is characterized by the distinct angiographic appearance of cerebral vessels resembling "puff of smoke." Although extensively described in the context of Japanese and Korean population, this characteristic arteriopathy is also found in other Asian countries, in Europe and North America. The reported incidence of moyamoya in Asian population is approximately 3 cases/100,000 of the pediatric population. 
The title of moyamoya disease is reserved for an idiopathic and many times familial condition however numerous systemic disorders can lead to similar appearance, in which case the term moyamoya syndrome or pattern is used. Few of these conditions include neurofibromatosis type I, tuberous sclerosis, connective tissue disorders, grave's disease, fibromuscular dysplasia, meningitis, sickle cell anemia and Down's syndrome. Similar appearance may also be seen as a part of degenerative atherosclerotic changes or due to use of oral contraceptive pills. Although the disease was first described in 1957 as "hypoplasia of the bilateral ICA," characteristic pattern was later described by Kudo in 1960. , The distinctive name of moyamoya was much later applied by Suzuki and Takaku in 1969. 
The disease is characterized by progressive stenosis at the apices of the intracranial ICA including the proximal anterior cerebral arteries and MCAs. Although classically described affecting these vessels, over 50% of patients also have involvement of the posterior cerebral arteries. In the affected cerebral vessels, a pathological examination does not show atherosclerotic or inflammatory lesions. The cause of stenosis is the overgrowth of the smooth muscle layer associated with thrombotic changes.  Due to reduced perfusion in the anterior circulation of the brain; there is the compensatory development of collateral vessels near the carotid apices. Tiny collateral vessels develop on the cortical surface, leptomeninges, dura, and skull base leading to an extensive network of enlarged basal, transcortical, and transdural vessels. On angiography, a combination of widened existing vessels and development of new small, twisting perforating collaterals has been likened to "something hazy, like a puff of cigarette smoke."
Clinically, a patient can present with either ischemic, hemorrhagic or epileptic complaints. Cognitive dysfunction and behavioral disturbances are atypical symptoms. Moyamoya has been associated with approximately 6% of pediatric strokes. ,, There is bimodal age presentation with first peak occurring in the first decade of life and another peak in third to fourth decade of life. Moyamoya disease in children has been suggested to be distinct from that in adults. The childhood disease often presents with cerebral infarction in comparison to adult-onset, which often presents with intracranial hemorrhage, arising from rupture of delicate collateral vessels.
The cause of ischemic symptoms is thrombotic changes occurring within the collateral vessels. On the other hand, an increased blood flow causes stress over the thin vessel walls and leads to formation of microaneurysms, which is the probable cause of intracranial hemorrhages.  It is important to have high suspicion of moyamoya disease, especially in children, when patient presents with unexplained symptoms suggestive of acute neurologic deficits. A delay in diagnosis results in a delay in treatment, increasing the risk of permanent disability from stroke. Although presence of moyamoya can be readily confirmed by radiographic studies, the differential diagnosis for such an appearance is extensive.
The workup of a patient in suspected cases begins with a either a MRI study or computerized tomography (CT) of the brain. CT in a patient with moyamoya disease may show small areas of hypodensity suggestive of ischemic changes in the cortical watershed zones, basal ganglia, deep white matter, or periventricular regions. However, when presenting with transient symptoms, that is, transient ischemic attack, the CT scan can be normal. CT angiography (CTA) can effectively demonstrate intracranial stenosis. The finding most diagnostic of moyamoya on MRI is reduced flow voids in the internal, middle, and anterior cerebral arteries coupled with prominent flow voids through the basal ganglia and thalami representing collaterals.
The advantage of using MRI is not just limited to better resolution but is compounded by various sequences such as diffusion-weighted imaging (DWI), Gradient imaging, and fluid-attenuated inversion recovery (FLAIR) sequences. An acute infarct can be readily identified using DWI, whereas a chronic infarct is more likely to be seen with T1- and T2-weighted imaging. FLAIR sequences show "ivy sign" that is, linear high signal along the fissures and gyri of cerebral hemispheres, resulting most probably from the reduction of the cortical flow.  Although, MRA may be used as primary imaging modality for moyamoya disease instead of conventional cerebral angiography, it frequently overestimates stenosis and is subject to artifacts. Both CTA and MRA are many times unable to demonstrate the characteristic finding of "puff of smoke" due to lower flow and spatial resolution. Furthermore, visualization of basal collateral vessels is better with conventional angiography.
Thus, the definitive diagnosis as with many other diseases is based on conventional angiographic findings. Angiography should consist of a full six-vessel series (both ICA, external carotid arteries and vertebral arteries). External carotid artery imaging is essential to identify preexisting collateral vessels so that surgery, if performed, will not disrupt them. The risk of complications from performing angiography in children with moyamoya disease has been debated time and again. Crying can cause lowering in the partial pressure of carbon dioxide with resultant vasoconstriction and a subsequent increased risk of stroke. However, one of the studies involving 190 patients has clearly suggested that risk of angiography is no higher in patients suffering from moyamoya disease compared to those who are not. The rate of serious complications is <1%.  Preprocedural hydration for children is useful along with aggressive measures to control pain and anxiety.
Disease severity is frequently classified into 1 of 6 progressive stages originally defined by Suzuki and Takaku. Development of an extensive collateral network at the base of the brain along with the classic puff of smoke appearance on angiography is seen during the intermediate stages of the Suzuki grading system. The first stage includes only stenosis of the carotid artery. In the second and third stages, the collateral vasculature develops and becomes prominent. In the fourth and fifth stages, these collaterals start disappearing but extracranial collaterals become prominent, and in the sixth stage there is complete occlusion of ICA with disappearance of collaterals. 
Cerebral blood flow (CBF) studies such as transcranial Doppler ultrasonography, xenon-enhanced CT, positron emission tomography, and single photon emission CT with acetazolamide challenge can be helpful in the diagnostic evaluation of patients with moyamoya syndrome as well as assisting in treatment decisions. Quantitative evaluation of hemodynamic disturbances of the cerebral circulation can be achieved using perfusion CT and MRI.  Perfusion studies have revealed a number of intriguing findings including reduction in bifrontal perfusion with increase or normal occipital blood flow, decrease in cerebrovascular reserve and CBF with increase in cerebral blood volume and oxygen extraction fraction. These changes are much more pronounced in children than in adults explaining higher incidence of ischemic lesions in pediatric population compared to adults. 
Treatment includes medical and surgical options. Medical therapy includes antiplatelet medicines. Anticoagulative therapy is not recommended due to risk of bleeding. Although mild cases can be treated conservatively, severe cases require surgery.  Surgery includes direct anastomoses between the STA-MCA anastomosis as well as indirect procedures involving synangiosis, that is, placement of vascularized tissue in the brain cortex to promote neoangiogenesis. Indirect procedures can use either dura mater (encephaloduroarteriosynangiosis), muscle tissue (encephaloduroarteriomyosynangiosis), or cranial periosteum.  As none of these options can independently prevent recurrence of ischemic episodes; a combined approach is usually preferred. 
The familial incidence of affected first-degree relatives in Japan is 7-12%.  Although there is little evidence to support screening program for the first-degree relatives of patients with moyamoya, devastating presentation of the advanced disease certainly warrants selective screening. It can also be justified in patients with certain systemic disorders such as phakomatoses, Down's syndrome, Graves's disease, and sickle cell disease. Better long-term outcome after treatment, compels toward a more aggressive screening process and earliest intervention.
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[Figure 1], [Figure 2], [Figure 3]