Vascular anomaly, lipoma, and polymicrogyria associated with schizencephaly: developmental and diagnostic insights. Illustrative case

Abstract

BACKGROUND

Schizencephaly is an uncommon central nervous system malformation. Intracranial lipomas are also rare, accounting for approximately 0.1% of brain “tumors.” They are believed to be derived from a persistent meninx primitiva, a neural crest–derived mesenchyme that develops into the dura and leptomeninges.

OBSERVATIONS

The authors present a case of heterotopic adipose tissue and a nonshunting arterial vascular malformation arising within a schizencephalic cleft in a 22-year-old male. Imaging showed right frontal gray matter abnormality and an associated suspected arteriovenous malformation with evidence of hemorrhage. Brain magnetic resonance imaging revealed right frontal polymicrogyria lining an open-lip schizencephaly, periventricular heterotopic gray matter, fat within the schizencephalic cleft, and gradient echo hypointensity concerning for prior hemorrhage. Histological assessment demonstrated mature adipose tissue with large-bore, thick-walled, irregular arteries. Mural calcifications and subendothelial cushions suggesting nonlaminar blood flow were observed. There were no arterialized veins or direct transitions from the arteries to veins. Hemosiderin deposition was scant, and hemorrhage was not present. The final diagnosis was consistent with ectopic mature adipose tissue and arteries with meningocerebral cicatrix.

LESSONS

This example of a complex maldevelopment of derivatives of the meninx primitiva in association with cortical maldevelopment highlights the unique challenges from both a radiological and histological perspective during diagnostic workup.

Schizencephaly is an uncommon central nervous system (CNS) malformation with a prevalence of approximately 1.5 cases in 100,000 births^1,2 and is characterized by a gray matter–lined cleft that communicates between the subpial space and the ependymal lining of the lateral ventricle.^3,4 Schizencephaly results from an in utero destructive, often vascular, process^4–9 and frequently has significant clinical implications including intractable epilepsy, motor dysfunction, and cognitive impairment.^4,10 Intracranial lipomas (fat heterotopia) are also rare developmental abnormalities of the CNS^11,12; they are derived from the meninx primitiva, a mesenchymal tissue that gives rise to the three layers of the meninges and the skull.^13–15 These lesions are frequently identified in the midline and in association with other developmental anomalies.¹⁶ In contrast to schizencephaly and intracranial lipomas, vascular malformations are more common lesions with variable risks for life-threatening hemorrhage, stroke, and seizures. Recognizing which malformations require intervention is paramount for appropriate patient care.¹⁷

We report a case of a lipovascular developmental malformation of the meninx primitiva associated with open-lip schizencephaly, a rare example of complex maldevelopment of derivatives of the meninx primitiva in association with underlying cortical maldevelopment. This case proved to be a diagnostic challenge from both radiological and histological perspectives. Moreover, the optimal clinical management strategy remains unclear, although in retrospect, this lesion would likely not have been intervened upon if the vascular component had been recognized as not being high-flow and not demonstrating clear arteriovenous shunting.

Illustrative Case

A 22-year-old man presented after a generalized tonic-clonic seizure. Magnetic resonance imaging (MRI) was interpreted as showing a right frontal gray matter abnormality and an associated suspected arteriovenous malformation (AVM) with evidence of hemorrhage. Antiepileptic therapy was initially beneficial, but after 6 years, he presented with an increased frequency of generalized seizures and auras (characterized by eye fluttering, a sense of doom, and apprehension) prompting evaluation at our institution.

Brain MRI revealed right frontal polymicrogyria lining an open-lip schizencephaly, T1- and fast spin echo T2-hyperintense tissue consistent with fat within the schizencephalic cleft, and gradient echo hypointensity interpreted as concerning for prior hemorrhage. Prominent vessels were present in the cleft, and arterial spin label (ASL) magnetic resonance perfusion demonstrated associated hyperperfusion that was interpreted as arteriovenous shunting; the lesion was thus prospectively interpreted as a suspected AVM within the schizencephalic cleft (Fig. 1). Subsequent digital subtraction angiography was also interpreted as an arteriovenous vascular malformation composed of hypertrophied arteries emanating from the superior division of the right middle cerebral artery, with early venous drainage into several medullary veins (Fig. 1).

FIG. 1.

MRI and cerebral digital subtraction angiography demonstrate heterotopic adipose tissue and abnormal vessels arising within a schizencephalic cleft. A: Sagittal T1-weighted image demonstrates hyperintense fat within a schizencephalic cleft in the right frontal lobe. B: Axial T2-weighted image demonstrates thick, lobulated cortex consistent with polymicrogyria lining the schizencephalic cleft (solid white arrows). Linear serpentine hypointense structures consistent with abnormal flow voids are also seen within the cleft and extending along the brain surface (dashed white arrows). C: An ASL perfusion image demonstrates areas of focal hyperintense signal along the schizencephalic cleft (solid white arrows). This finding raised a concern for arteriovenous shunting, but it may reflect arterial transit abnormality related to dysplastic vessels or possibly hyperperfusion associated with seizure activity. D: Coronal maximum intensity projection (MIP) from a time-of-flight magnetic resonance angiography (MRA) demonstrates a more vertical course of right middle cerebral artery (MCA) vessels compared with the left (solid white arrows) and an increase in vessels corresponding to the location of the schizencephalic cleft (dashed white arrows). E: A lateral view of the late arterial phase following a right internal carotid artery (ICA) injection demonstrates morphologically abnormal arteries within the anterior ascending ramus of the Sylvian fissure (dashed outline). The vessels have an abnormal orientation due to the aberrant sulcal anatomy with an associated increase in arterial caliber and tortuosity. F: A lateral view of the early venous phase following a right ICA injection demonstrates abnormally numerous and maloriented multiple small medullary veins (dashed outline) that drain into a normally sized, although abnormally oriented, cortical vein (arrow). No convincing arteriovenous shunting was demonstrated angiographically.

Due to concern for the risk of future hemorrhage, the patient elected to pursue resection of the suspected AVM. Intraoperatively, large and smaller branches of the right middle cerebral artery were found to supply a vascular malformation with both thick-walled vessels and smaller friable vessels, but no discrete draining vein was identified (Fig. 2). Fat was noted around the numerous blood vessels within the schizencephalic cleft. After resection, intraoperative angiography confirmed complete removal of the vascular malformation.

FIG. 2.

Intraoperative images during resection. A: Large and smaller branches of the right middle cerebral artery were found to supply a vascular malformation with both thick-walled vessels and smaller friable vessels that lacked a discrete draining vein. Fat was noted around the numerous blood vessels within the schizencephalic cleft. B: Gross image of the resected vascular malformation measuring approximately 3.5 cm.

The patient was discharged home on postoperative day 2 with a short steroid taper. He had an episode of multiple seizures on postoperative day 3, which resolved after increasing his levetiracetam and lacosamide dosage. At the initial outpatient follow-up, the patient was seizure free and immediate postoperative upper-extremity weakness, likely secondary to peri-resection cavity edema in the premotor cortex, had resolved. One year later, the patient’s seizures recurred.

Histological assessment of the resected tissue demonstrated mature adipose tissue surrounding large-bore, thick-walled, irregular arteries (Fig. 3A). Some mildly abnormal blood vessels were distributed in the adjacent gliotic, focally calcified gray matter (Fig. 3B). Many vessels showed mural calcifications and subendothelial cushions (Fig. 3C), indicative of nonlaminar blood flow. Elastin van Gieson stain demonstrated some segments of artery with abnormal elastica, but there were no arterialized veins or direct transitions from arteries to veins (Fig. 3D). Prussian blue stain highlighted just scant iron (hemosiderin) deposition, and neither acute nor chronic hemorrhage was present. The diagnosis was reported as “ectopic mature adipose tissue and arteries with meningocerebral cicatrix”; the report noted there was no evidence for AVM. Additionally, no genetic sequencing or profiling of the patient or tissue was performed given that the findings would not influence the final diagnosis or prognosis for the patient.

FIG. 3.

Photomicrographs of resection specimen histology. A hematoxylin and eosin (H&E)–stained section (A) at low magnification showing a heterogeneous collection of large and small blood vessels that have abnormally thick walls (arrows) distributed within abundant adipose tissue, loose fibrous tissue, and foci of calcifications (asterisk). Medium magnification of an H&E-stained section (B, adjacent to the section in panel A) showing an abnormal distribution of blood vessels (arrow) within gliotic brain tissue (asterisk). Although the blood vessel distribution is abnormal, the vessels show no significant abnormality. H&E-stained (C) and elastin van Gieson–stained (D) sections at medium magnification showing an abnormal blood vessel that has an endothelial cushion (asterisk in C) and focal multilayered elastic lamina (arrow in D). Original magnification ×10 (A), ×50 (B), ×20 (C and D).

Discussion

Observations

While the exact timing and sequence of events producing this complex lesion cannot be known, careful analysis of the patterns of normal development provides clues. Schizencephaly arises during fetal brain formation, generally following a destructive, often vascular, insult.^2–4,7 Intracranial lipomas derive from primitive mesenchyme, are typically located in subarachnoid cisterns, and are often associated with developmental abnormalities such as dysgenesis of the corpus callosum.¹⁵ While vasculature within lipomas is often described as abundant, this is generally attributed to native vessels traversing the lesion rather than to a vascular malformation. At least one case of a lipoma within a schizencephalic cleft has been previously reported, although without an associated arterial malformation.¹⁸ The lack of available prenatal and neonatal history to point to a specific prenatal insult makes establishing the etiology of this patient’s anomaly particularly difficult. The absence of hemosiderin on histological analysis renders hemorrhage unlikely as the primary cause of the developmental malformations, although this may have resolved since the intrauterine insult. A shunting or steal phenomenon producing an ischemic event can be considered,¹⁹ but the configuration of the blood vessels makes this unlikely, as a draining venous component should be present. We further note that abnormal vascularity has been described in the setting of schizencephaly¹⁸ and polymicrogyria,²⁰ supporting an embryonic developmental mechanism that links mesenchymal anomalies of adipose and vascular tissue with underlying malformations of cortical development.

This case of schizencephaly associated with fat and an anomalous arrangement of arteries and veins is most simply explained as a complex developmental malformation of both the meninx primitiva and the gray matter underlying it. This case illustrates the importance of distinguishing a likely stable vascular anomaly, where surgical intervention is unnecessary, from a high-flow or shunting malformation that requires treatment. In this case, several misinterpretations of imaging findings contributed to this stable malformation being interpreted as a more concerning pathology. First, the low signal on gradient-echo imaging was interpreted as evidence of prior hemorrhage instead of low signal from fat. Second, the high signal on ASL perfusion was interpreted as shunting, when, in fact, it likely represented an arterial transit artifact in the setting of abnormal vasculature. Perhaps influenced by the indication for the study, the catheter angiogram was interpreted as demonstrating shunting consistent with AVM rather than recognizing the nonshunting nature of the vascular malformation.

Lessons

We present a rare case of a complex developmental malformation of the meninx primitiva arising within a schizencephalic cleft. This case demonstrates the challenge of interpreting abnormal vasculature on imaging in the setting of a developmental malformation. While the initial diagnostic evaluation was interpreted as suggesting AVM, histological evaluation demonstrated a more nuanced picture of abnormal arterial vessels without an identified abnormal venous element and likely carrying a low risk of future hemorrhage. The recognition of the association of developmental malformations of derivatives of the meninx primitiva and the underlying brain parenchyma may assist with more nuanced interpretations in future cases of this rare etiology.

Acknowledgments

We thank Christine Plant for editorial support.

Disclosures

Dr. Heit reported personal fees for consulting from Medtronic and MicroVention, and personal fees for Medical and Scientific Advisory Board membership from iSchemaView outside the submitted work. Dr. Born reported that he is a member of the faculty at Stanford University School of Medicine.

Author Contributions

Conception and design: Steinberg, Kumar, Toland, Born. Acquisition of data: Kumar, Toland, Morrell, Heit, Born. Analysis and interpretation of data: Steinberg, Kumar, Toland, Fischbein, Heit, Born. Drafting of the article: Kumar, Toland, Fischbein, Born. Critically revising the article: Steinberg, Kumar, Toland, Fischbein, Heit, Born. Reviewed submitted version of the manuscript: Steinberg, Kumar, Toland, Fischbein, Heit, Born. Approved the final version of the manuscript on behalf of all authors: Steinberg. Administrative/technical/material support: Steinberg, Born. Study supervision: Steinberg.