FMD is a non-atherosclerotic non-inflammatory segmental non-inflammatory vascular disease of unknown etiology affecting the medium and small sized arteries of virtually every arterial bed, predominantly the renal and extracranial segment of the ICA [54]. FMD may result in arterial stenosis, occlusion, aneurismal formation, or vessel dissection. While the prevalence of the disease is unknown, FMD is increasingly being diagnosed due to advances in neuroimaging. FMD is more common in young women between the ages of 30 and 50 years, especially in individuals with a history of migraines, thus hormonal factors have been postulated [54]. The disease is uncommon in children. Genetic susceptibility has been suggested in subsets of patients with autosomal mode of inheritance [55–57]. Histologically, medial fibroplasia accounts for 95–99 % of cases. Involvement of the intima and the adventitia is rare (<1 %) [58]. Angiographic characteristics observed in 80–90 % of cases of FMD include multifocal short segment of arterial stenoses with alternating mural dilatations and constriction giving the classic appearance of “string of beads”, predominantly in the mid- and distal portion of the internal carotid and vertebral arteries (medial fibroplasia or type 1) [54, 58] (Fig. 16.5). Less commonly, a unifocal concentric or band-like tubular stenosis may occur due to intimal fibroplasia (type 2). Rarely, adventitial involvement or medial hyperplasia may exit (type 3) [54, 58]. Clinical symptomatology is variable and nonspecific. Majority of cases are asymptomatic incidental findings on neuroangiographic studies. Symptoms may include headaches, pulsatile tinnitus, and blood pressure changes. Arterial dissections and cerebral aneurysms occur in 7–20 % of cases. Although often asymptomatic, these may be responsible for cerebral ischemia or subarachnoid hemorrhage [59, 60].

When arterial dissection occurs, around 20 % of patients may develop transient ischemic symptoms or cerebral infarction [35]. FMD should be suspected in patients with bilateral CCADs, especially when intracranial aneurysms are present. Patients with hypertension, migraine, and history of cigarette smoking are more predisposed to FMD. The condition may coexist with other collagen vascular disorders such as cystic medial necrosis, Ehlers–Danlos syndrome (type IV), Marfan’s syndrome, Alport syndrome, and vasculitic conditions such as Takayasu’s disease [21, 60, 61]. Management of FMD is similar to that of CCAD. There are no randomized controlled trials of revascularization versus medical therapy in patients FMD. Medical management should always be the first choice of therapy, with percutaneous or surgical intervention reverted to patients with recurrent symptoms and cerebral aneurysms [62].

Moyamoya disease is an idiopathic progressive non-inflammatory intracranial occlusive arteriopathy of unknown etiology. It is characterized by vaso-occlusive changes involving the circle of Willis, typically the ICA terminus or proximal anterior cerebral arteries (ACA) and middle cerebral arteries (MCA), resulting in a complex network of collateral net-like tuft of vessels corresponding to the lenticulostriate and thalamoperforate arteries [63, 64]. Moyamoya disease predominantly affects children and young adults in the first or third decades of life with female preponderance. Moyamoya disease was first described by Suzuki and Takaku in 1969 in Japanese patients with abnormal net-like vessels in the base of brain appearing as “something hazy just like a puff of cigarette smoke drifting in the air” (moyamoya in Japanese) [63]. It has since been reported in every ethnic group. Histologically, there is excentric intimal hyperplasia with fibrosis of the cerebral arterial trunks, thinning of the media, and endothelial thickening leading to stenosis or occlusion of the lumen in the internal carotid terminus, ACAs and MCAs, without an obvious underlying inflammatory response [64–66]. The internal elastic lamina of the affected arteries is often tortuous; the adventitia is usually spared. Cerebral aneurysms are common [64]. Immuno-histochemical studies showed aberrant expression of IgG and S100A4 protein in vascular smooth muscle cells of the intracranial vascular wall, suggesting an underlying immune reaction [67, 68].

The pathogenesis of primary moyamoya disease is unclear, with genetic predisposition suggested. Genetic link to telomeric region of 17q25.3 was reported in Japanese family with autosomal dominant pattern [69]. Familial occurrence has also been reported in various ethnic groups in particular among identical twins [68, 70–77].

Clinical manifestations include headaches, cognitive impairment, mental retardation, encephalopathy, seizures, involuntary movements, transient neurological deficits, SAH, and focal neurological impairment secondary to ischemic or hemorrhagic strokes [64, 66, 78–81]. Moyamoya disease should be differentiated from secondary conditions associated with similar intracranial vascular stenotic pattern known as moyamoya syndrome (Table 16.4) [82].

In the absence of hematological, biochemical, and serologic findings, diagnosis is usually based on clinical presentation and neuroradiological and angiographic findings. Cerebral CT and MRI scans may reveal multiple infarctions or hemorrhages, often bilateral, in the distribution of the ACAs, MCAs, and watershed zones. Microbleeds are common. Cerebral atrophy is present in patients with recurrent symptoms due to progressive disease [83–87].

Angiographic findings include multiple mid-sized arterial irregularities and focal arterial stenoses or occlusion (Fig. 16.6) at the terminal portion of the ICAs bilaterally with distinct collateral channels formation at the base of the brain (Fig. 16.7). Except for the occlusion of the posterior cerebral arteries, the vertebrobasilar system is rarely involved. Six angiographic stages have been described: (1) bilateral suprasellar ICA narrowing, (2) collateral channels or moyamoya vessels at the base of the brain, (3) progressive ICA fork stenosis and prominent moyamoya vessels, (4) occlusion of the main arteries of the circle of Willis and extracranial collaterals, (5) further progression of stage 4 with prominent extracranial collaterals and disappearance of moyamoya vessels, and (6) complete absence of moyamoya vessels and major cerebral arteries with predominantly extracranial collaterals [63]. Intracranial aneurysms are common [80, 86]. The optimal treatment of moyamoya disease and timing of neurovascular intervention in symptomatic patients remain unclear. Medical therapy includes antiplatelet agents, vasodilators, and when seizures occur, antiepileptic agents. Patients with symptomatic progressive moyamoya disease are usually referred for neurovascular surgical intervention, with the goal to improve cerebral perfusion thereby halting disease progression, and thus reducing risk of stroke and clinical deterioration [87]. Surgical approaches include direct bypass with extracranial–intracranial anastomosis such as superficial temporal artery to middle cerebral artery (STA-MCA) bypass, indirect bypass such as encephalomyosynangiosis, encephaloduroarteriosynangiosis, encephalomyoarteriosynangiosis, omental pedicle transposition, durapexy, multiple cranial burr holes, multiple cranial burr holes with vessel synangiosis, or combined revascularization approaches [78, 82, 87–94]. Given the rarity of the disorder and of lack evidence-based guidelines, best surgical treatment options remain unknown. Intraoperative video angiography using indocyanine green is a promising technique to assess bypass graft patency in patients undergoing direct bypass with STA-MCA anastomosis [95].

Radiation-induced vasculopathy is a common late complication of cranial radiation therapy. The condition is of particular importance in children treated with intracranial radiation for parasellar brain tumors and craniopharyngiomas [96–99]. Radiation-induced vasculopathy may develop months to years after radiotherapy, a risk persisting until adulthood (Fig. 16.8). The mechanism by which vasculopathy occurs after cranial irradiation remains unclear. Small and medium arteries are primarily affected, with progressive luminal narrowing due to endothelial thickening and medial fibrosis. Radiation injury to the large vessels is rare, usually occurring following radiation therapy for vascular malformations and pituitary tumors (Fig. 16.9). Head and neck radiation for the treatment of epithelial cancers or lymphomas is associated with delayed carotid atherosclerosis. Higher brain radiation with doses exceeding 50 Gy confers increased risk of radiation-induced vasculopathy leading to progressive cerebral arterial occlusive disease mimicking moyamoya syndrome [98, 100].

Clinical manifestations include encephalopathy, seizures, and focal neurological deficits secondary to cerebral ischemia. Hemorrhages from radiation-induced vascular abnormalities are rare, often instead resulting from a chemotherapy effect on hemostatic system [98, 101, 102].

There is no effective treatment for radiation-induced vasculopathy. Physicians should focus on reducing radiation doses. The benefit of antiplatelet agents has not been established. Revascularization surgery may be considered in patients’ progressive arteriopathy (moyamoya syndrome) and recurrent neurological symptoms. In radiation-induced symptomatic carotid artery stenosis, surgical treatment with carotid endarterectomy may be equally effective as in non-irradiated carotid atherosclerosis [101, 102].

Reversible cerebral vasoconstriction syndrome (RCVS) is characterized by thunderclap headaches, usually severe, with or without seizures or other neurologic symptoms, and segmental constriction of cerebral arteries, which resolves spontaneously within 3 months (Table 16.5) [103–105]. RCVS is also known as Call-Fleming syndrome, CNS pseudo-vasculitis, postpartum angiopathy, idiopathic thunderclap headache with reversible vasospasm, isolated benign cerebral vasculitis, and migraine angiitis. RCVS may occur in susceptible patients such as postpartum women, even without preeclampsia or eclampsia, due to transient failure of regulation of cerebral arterial tone with sympathetic overactivity [103, 106, 107]. Migraineurs with aura are more susceptible to the disease, especially when using vasoactive drug such as triptans or ergot-alkaloids. Other precipitants include nasal decongestants containing pseudoephedrine and ephedrine, illicit drugs including cannabis, cocaine, lysergic acid diethylamide, methamphetamine, selective serotonin reuptake inhibitors and selective noradrenaline reuptake inhibitors, catecholamine-secreting tumors, and intravenous immunoglobulin therapy (Table 16.6) [103, 107, 108]. RCVS is more common in women in the mid-40s, although it has been reported in children and in adults in every age group [104]. RCVS is often underdiagnosed with an unknown incidence. While relatively benign, serious ischemic and hemorrhagic events may occur in 5–10 % of patients, thus resulting in permanent neurological deficit [105, 108, 109]. Posterior reversible ischemic encephalopathy syndrome (PRES) may occur [103, 105–107].

The most common presentation includes recurrent severe rapidly escalating thunderclap headache (Table 16.7). Unlike in SAH, the headaches in RCVS are short-lived, lasting minutes to days, often recurrent, and gradually dissipating within 3 weeks of symptom-onset [103, 108, 110]. Patients typically endorse some form of exertional activity as a trigger prior to the onset of headaches. Seizures may occur especially when PRES develops. Transient neurological symptoms in particular visual disturbances mimicking migraine aura are common. When persistent focal deficit lasts beyond 1 h, stroke is suspected. In the absence of cerebral ischemia or ICH, neurological examination is usually normal [103, 108]. A surge in blood pressure may often occur due to the pain intensity.