Multicystic meningioangiomatosis

MA is a rare and benign meningovascular hamartomatous condition that usually involves the cerebral cortex in the frontal or temporal regions, with varying involvement of the overlying leptomeninges. The lesions are often associated with NF2, although the majority of cases are sporadic [8]. Sporadic MA usually occurs as a solitary lesion in young patients and presents with a history of intractable seizures or persistent headaches [9, 10]. In contrast, NF2-associated MA more frequently involves multiple lesions and is asymptomatic [11]. In some patients, MA may be accompanied by tumors such as meningiomas, astrocytomas and oligodendroglioma [12‐14].

All MA lesions share common pathological features, namely, cortical vascular proliferation and perivascular cuffs of proliferative, spindle-shaped, meningothelial-like cells. Although approximately 120 cases of MA have been reported to date worldwide, only six cases of cysts within the MA lesion have been described in the literature (Table 1) [3‐7]. The mean age of these seven patients with cystic MA including our patient was 32 years (range, 12–58 years). Except for one patient for whom insufficient data were available, all patients had intractable seizures or headaches for 2–11 years (mean, 6 years). In two patients, the cysts were visible only on microscopic examination (microcysts); in three patients, the cysts were sufficiently large to be detected on MRI. The diagnosis of MA was confirmed by the pathologist in all seven patients. Wiebe et al. described the histopathological spectrum of MA, which can be broadly classified into predominantly cellular and predominantly vascular types [8]. In our case, the MRI finding of a multicystic structure differentiated the condition from ordinary MA. According to the literature [1, 3, 6], patients with cystic MA are older than patients with non-cystic MA, and the interval between symptom onset and surgery is longer in the former. We therefore consider that cystic/microcystic MA should be classified as a new type of MA in order to better our understanding of this disease and achieve an accurate preoperative diagnosis.

The mechanisms involved in the development of MA have not yet been elucidated. MA was considered a hamartomatous proliferation of meningothelial cells, blood vessels and fibroblasts in variable proportions [4]. However, the observation of abnormal local vascularization in some patients has led several authors to regard MA simply as a vascular malformation with an added meningothelial reaction [15]. Furthermore, it has also been suggested that these tumors do not grow or display malignant features. Some studies have supported the opinion that MA may be related to NF2 gene mutation because of its concomitance with NF2 [16]. In our patient, immunohistochemical examination demonstrated that the perivascular cells had originated from arachnoid cap cells. Considering the histopathological findings, the patient’s age at onset and the location of the lesion, we propose that MA is a hamartoma that results from the trapping of arachnoid and vascular tissue in the cerebral parenchyma during brain development, rather than a true neoplasm. The wide spectrum of immunohistochemical staining patterns observed in the perivascular cells in MA lesions in the cases reported in the literature and in our case suggests that MA originates from pluripotent cells. The exact mechanism underlying cyst development in MA remains controversial. It has been speculated that cysts form due to the accumulation of CSF within the lesion in a manner similar to the mechanism of cyst formation in cystic meningiomas [7]; however, a communication between the cysts and the subarachnoid space has not been confirmed in MA [5]. In our patient, the proliferation of meningothelial-like cells and loose perivascular cells observed on the cortical surface may have been the early stages of the typical cystic lesion in the deep cortex and white matter, and the cystic component was attributable to the enlarged perivascular spaces. The long duration of the illness supports this hypothesis. The fact that the cysts were not connected with the vessels and that the cyst contents were similar to those of the arachnoid cavity demonstrated that the cysts had originated from arachnoid tissue. Furthermore, the same immunoresponse of the perivascular cells, microcystic walls and the arachnoid cavity wall suggests that pluripotent cells differentiate into the various cell types found in MA [17] and that the formation of cysts is an accompanying developmental anomaly. Mechanisms such as increased CSF pulsation, vascular ectasia, small blood vessel obstruction or abnormal arterial wall permeability may be related to the formation of enlarged perivascular spaces, in which CSF gradually accumulates, eventually resulting in the formation of microcysts and cysts. This suggests that MA originates from pluripotent arachnoidal cap cells trapped in the cerebral cortex.

Although many cases of MA have been described, presurgical diagnosis remains difficult because the wide spectrum of clinical, imaging and electrophysiological features often impedes the clinical diagnosis [13, 18, 19]. Surgical resection is important not only for seizure control but also for pathological diagnosis. Wiebe et al. reported that after surgical removal of the tumor, long-term seizures disappeared in 43% of patients, improvement occurred in 30% of patients and antiepileptic drug administration was required in more than 70% of patients [8]. Partial removal of the tumor has been shown to improve symptoms, but total removal still seems to be more effective [8, 20]. In patients in whom postoperative seizure control was not successful, extension of the epileptic foci was found to occur with time [21]. In our patient, ECoG revealed perilesional cortical spikes, and epileptogenic foci were present in not only the right temporal lobe but also the right hippocampus. Therefore, intraoperative or extraoperative ECoG is essential for detecting epileptogenic foci [22], which often exist in the adjacent cortex rather than in the lesion. In the present case, total surgical removal was achieved using intraoperative ECoG assistance, and a favorable outcome was obtained.