Expanding Ventricular Diverticulum Overlying the Cerebral Hemisphere through an Open-Lip Schizencephalic Cleft: A Report of Two Pediatric Cases

Abstract Introduction: Open-lip-type schizencephaly is characterized by trans-cerebral clefts filled with cerebrospinal fluid (CSF) between the subarachnoid space at the hemisphere surface and the lateral ventricles. Disorders related to CSF retention, including hydrocephalus and arachnoid cysts, have reportedly been associated with open-lip schizencephaly and have induced intracranial hypertension in some cases. However, detailed neuroimaging and surgical treatment findings have rarely been described. Case Presentation: We report 2 cases of open-lip schizencephaly with an expanding CSF-filled cavity overlying the ipsilateral cerebral hemisphere that manifested as signs of intracranial hypertension. Detailed three-dimensional heavily T2-weighted imaging revealed thin borders between the CSF-filled cavity and the subarachnoid space, but no separating structures between the cavity and the lateral ventricle, suggesting that the cavity was directly connected to the lateral ventricle through the schizencephalic cleft but not to the subarachnoid space. Neuroendoscopic observation in case 1 confirmed this finding. Endoscopic fenestration of the cavity to the prepontine cistern was ineffective in case 1. Shunting between the lateral ventricle (case 1) or CSF-filled cavity (case 2) and the peritoneal cavity slightly decreased the size of the CSF-filled cavity. Discussion: We speculate that the thin borders along the margin of the CSF-filled cavity are membranes that previously covered the schizencephalic cleft and are now pushed peripherally. In addition, we believe that the cavity is a ventricular diverticulum protruding through the cleft and that shunting operation is effective against such expanding cavity. Detailed magnetic resonance imaging can be useful for evaluating patients with schizencephaly associated with CSF retention disorders. Established Facts Open-lip-type schizencephalic clefts directly connect the lateral ventricles and the subarachnoid spaces. Detailed relationship between the clefts and cerebrospinal fluid retention disorders, including hydrocephalus and arachnoid cysts, remains unknown.


Novel Insights
• Two cases of schizencephaly with an expanding cerebrospinal fluid (CSF)-filled cavity through the cleft overlying the cerebral hemisphere are reported.• High-resolution magnetic resonance imaging (MRI) reveals thin membranes between the subarachnoid space and the cavity but no septum between the lateral ventricle and the cavity.• The CSF-filled cavity may be a ventricular diverticulum protruding through the cleft.
• Shunting operation can be effective against expanding ventricular diverticula associated with schizencephaly.
• Detailed MRI may be recommended in the diagnosis of CSF retention disorders associated with schizencephaly.

Introduction
Schizencephaly is characterized by trans-cerebral clefts that enter from the surface of the hemisphere into the lateral ventricle as a result of a migration disorder [1,2].Schizencephalic clefts are pathologically characterized by an infolding of dysmorphic gray matter along the cleft from the cortex into the ventricles and a fusion of the cortical pia matter and ventricular ependymal layer within the cleft [3].The cleft can be closed (closed-lip type) or separated by a wide communication filled with cerebrospinal fluid (CSF) between the subarachnoid space and the ventricles (open-lip type).
Patients with schizencephaly may present with hemiparesis, developmental deficits, and epilepsy [4,5].Regarding disorders related to CSF retention, studies have reported arachnoid cysts located near open-lip schizencephalic clefts [6][7][8][9][10], and hydrocephalus in some patients with schizencephaly, which require the placement of ventriculoperitoneal (VP) shunts [9,11].However, the detailed relationship between CSF-filled clefts and arachnoid cysts or ventricles has not been fully described, and the association of CSF-filled spaces with schizencephaly remains unknown.
We treated two pediatric cases of open-lip schizencephaly with an expanding CSF-filled cavity overlying the ipsilateral cerebral hemisphere that was directly connected to the lateral ventricle through the cleft but not to the subarachnoid space.Herein, we present the neuroimaging and intraoperative findings of these cases, as well as discuss the possibility that the CSF-filled cavity may be a ventricular diverticulum protruding through the schizencephalic cleft.

Case Report
Case 1 A 1-year-4-month-old boy was admitted to our department for control of a CSF-filled cavity.He was prenatally diagnosed with schizencephaly using MRI at 37 weeks of gestation (Fig. 1a).Postnatal MRI at 5 days of age demonstrated a CSF-filled cavity on the outside of the right cerebral hemisphere extending to the middle cranial fossa, which communicated with the lateral ventricle through a cleft covered with a cortical layer, indicating openlip schizencephaly (Fig. 1b).Septum pellucidum was absent.His fontanel was soft, and he had no apparent motor deficits in his extremities.
At 8 months of age, the patient developed epileptic spasms.Electroencephalographic monitoring revealed ictal discharge that began in the left central and right posterior regions.The seizures were effectively controlled with oral administration of topiramate.MRI revealed enlargement of the outer portion of the CSF-filled cavity, which compressed the cerebral hemisphere, but did not show enlargement of the lateral ventricle (Fig. 1c).Hypoplasty of the optic nerves and hypophyseal stalk was observed, indicating an association with septooptic dysplasia.At this time, his mental development was delayed.The patient was monitored as an outpatient with close follow-up.MRI at 14 months of age revealed a slight enlargement of the CSF-filled cavity.Detailed neuroimaging investigation using three-dimensional heavily T2weighted imaging (3D-hT2WI; Fig. 1d) revealed thin borders Ventricular Diverticulum through an Open-Lip Schizencephalic Cleft Murakami/Kurogi/Shono/Torio/ Shimogawa/Mukae/Morioka/Yoshimoto (green arrows in Fig. 1d) between the CSF-filled cavity and the subarachnoid space at the convex or the cisterns around the internal carotid artery (ICA), but no separating structures between the cavity and the lateral ventricle.No obstruction, including aqueduct stenosis, was observed in the CSF pathways.Bulging and thinning of the right temporal bone were observed using computed tomography (CT).
Because we assumed that the enlargement of the CSF-filled cavity was related to the delay in his mental development, neuroendoscopic fenestration between the cavity and the prepontine cistern was performed at 16 months of age.A burr hole was made in the right temporal region, and a membranous structure was observed just beneath the dural opening.The endoscope was advanced into the outer portion of the cavity and then into the schizencephalic cleft, where no separating structures were found (Fig. 1e).The arachnoid membranes in the vicinity of the right internal carotid artery and the optic nerve were fenestrated to the prepontine cistern using blunt biopsy forceps.Although the membranes to be perforated were tough, to-and-fro motions of the CSF were observed.
The patient remained mostly inactive postoperatively.MRI performed on 8th postoperative day demonstrated no change in size of the CSF-filled cavity and ventricles and the patency of the fenestration of the arachnoid membrane (Fig. 1f-1).The outer membrane of the CSF-filled cavity which was detached from the dura was observed (arrowheads in Fig. 1f-2).At 22nd postoperative day, he developed lethargy, although CT showed no changes in the existing CSF-filled cavity nor presence of subdural hematoma or intra-cavity hemorrhage.A VP shunt was placed in the left anterior horn of the lateral ventricle.The CSF was crystalline.Consequently, his consciousness improved to preoperative levels.The CSF-filled cavity and lateral ventricle showed a slight decrease in size 1 year and 6 months after VP shunt placement (Fig. 1g).His mental development has been progressing gradually.
Case 2 A 10-year-old girl was referred to our hospital for vomiting and control of a CSF-filled cavity.She was diagnosed with bilateral schizencephaly in the neonatal period based on MRI findings, which showed an open-type cleft connecting the lateral ventricle to the CSF-filled cavity on the outside of the left cerebral hemisphere, and a closed-lip on the right peri-Rolandic area (Fig. 2a).Septum pellucidum was absent.She had a mild intellectual delay and right hemiparesis.The CSF-filled cavity slightly increased in size at 6 years of age (Fig. 2b).No obstruction of CSF pathways was observed.Because the patient's general condition was good, the doctor in charge at that time decided to monitor her as an outpatient with close follow-up.At the age of 8 years, she began to develop epileptic spasms, and antiepileptic drugs were ineffective in controlling the seizures.
The patient developed intermittent vomiting a few days before admission to our hospital.MRI taken at that time showed narrowing of the cerebral gyrus and a midline shift, indicating intracranial hypertension (Fig. 2c).She was drowsy but responded when spoken to upon admission.However, she rapidly developed a deep coma with mydriasis after admission.Emergency CSF drainage was performed through a burr hole in the left temporal region and a membranous structure was observed immediately beneath the dural opening.The CSF was crystal-clear, and the intracranial pressure estimated from the drain was within the normal range.One day later, shunting was performed between the outer portion of the CSF-filled cavity and peritoneal cavity instead of the drainage tube.Her consciousness gradually improved to preoperative levels.Her right hemiparesis had worsened.Investigation with 3D-hT2WI was performed after the shunt operation (Fig. 2d), which depicted thin borders (green arrows in Fig. 2d) between the CSF-filled cavity overlying the hemisphere and the subarachnoid space, but no separating structure between the cavity and the lateral ventricle.Scars were observed in the left diencephalon, left medial temporal lobe, and right cerebral peduncle, indicating uncal and central herniations.The surfaces of the clefts were covered with a cortical layer, confirming schizencephaly (Fig. 2e).The CSF-filled cavity and lateral ventricle showed a slight decrease in size 1 year and 5 months after the shunt operation (Fig. 2f).Her hemiparesis showed slight improvement during this period.

Discussion
In the above cases, the CSF-filled cavity had been present in the outer space of the ipsilateral hemisphere since the natal or neonatal period and gradually increased in size.The degree of enlargement was greater than that of the lateral ventricles, which eventually resulted in compressing the hemisphere from the outside.Thin borders were observed along the margin of the CSF-filled cavity that may separate the cavity from the subarachnoid space, while no separating structure was detected between the lateral ventricles and the cavity.This indicated that the CSF-filled cavity directly continued to the lateral ventricles, but not to the subarachnoid spaces.Generally, it is thought that the ventricles and subarachnoid spaces are continuous through an open-lip schizencephalic cleft.This is because the infolding of cerebral cortex is in contact with the ependymal of the lateral ventricle, where the pia lining the cleft contacts the ependyma of the lateral ventricle [1].An arachnoid cyst is thought to be formed by a split of the arachnoid membrane and is filled with CSF; therefore, it is located in a space separated from both the subarachnoid spaces and ventricles [12].Sener speculated that a traction effect and splitting of the leptomeninges attributes the formation of an arachnoid cyst adjacent to the schizencephaly cleft [10].Consequently, the features of the CSF-filled cavity in these disorders do not conform to those observed in the present cases.
Diverticula of the lateral ventricle through congenital cerebral defects have rarely been reported in patients with schizencephaly or porencephaly and were detected by pneumoencephalography or autopsy in the pre-MRI era [13][14][15][16].The formation of the ventricular diverticula has been explained by the presence of thin membranes that Ventricular Diverticulum through an Open-Lip Schizencephalic Cleft form over the clefts in patients with open-lip type schizencephaly, which have been thought to be composed of pia matter or ependymal layers [2,3,15].If such a membrane exists, an open-lip schizencephalic cleft can be a blind-end CSF-filled cavity in which one end is continuous with the ventricles but the other end does not communicate with the subarachnoid space.These cavities can protrude from the cleft and expand over the ipsilateral hemisphere surface, which represents ventricular diverticula, and have a mass effect [14,15].This "roofing membrane" has been reportedly detected by recent neuroimaging studies using MRI [17] and ultrasound imaging [18].The pathogenesis of the CSF-filled cavity in the present case may be explained by this theory if we speculate that the thin borders along the margin of the CSF-filled cavity delineated by 3D-hT2WI consist of the roofing membranes that previously covered the schizencephalic cleft but are now pushed peripherally and protrude into the outer space of the ipsilateral hemisphere (Fig. 3).
In case 1, because we preoperatively failed to rule out the possibility that the outer portion of the CSF-filled cavity was an arachnoid cyst, we performed neuroendoscopic fenestration of the cavity as an initial surgical procedure, considering its minimal invasiveness [19].During the postoperative course, the patient's condition worsened despite the patency of the fenestration.Although it is uncertain why the endoscopic fenestration failed in case 1, a possible explanation is that the CSF dynamics in the cavity were not that of a closed space of arachnoid cyst or that of an obstructive hydrocephalus.A ventricular diverticulum is usually considered to bulge out due to severe obstructive hydrocephalus [20,21].In the present cases, an apparent etiology of obstructive hydrocephalus was not detected, and the pressure gradient between the cavity and the subarachnoid space may have been small.The hydrodynamic pressure and pulsation effect of the CSF may be relevant to the expansion of the cavity.Fenestration of the cavity may have changed the CSF dynamics and exacerbated the intracranial condition.In case 2, shunting procedure was our only choice of treatment because of the emergency situation.Tardieu et al. [16] reported that a VP shunt leads to clinical improvement in patients with congenital porencephaly associated with ventricular diverticulum.We speculate that the patient population in the previous study might have involved some cases of open-lip schizencephaly, considering that the diagnosis was made only by CT and that destructive brain parenchymal lesions can be an etiology common to some schizencephaly and porencephaly [22].The shunting procedure for the CSFfilled cavity slightly decreased the cavity size in the present 2 cases, which may also suggest the effectiveness of the shunt operation against expanding ventricular diverticula associated with schizencephaly.
The aforementioned study using conventional MRI reported that the roofing membrane over the cleft was detected in one of 12 patients with schizencephaly [17].This was assumed to be because the membranes were so thin that conventional MRI could not delineate them.In the present cases, conventional MRI failed to depict the borders between the CSF-filled cavity and subarachnoid spaces, whereas 3D-hT2WI delineated them.3D-hT2WI can depict fine anatomical structures surrounded by the CSF with high contrast and spatial resolution [23,24] and can be useful for detecting thin roofing membranes.Previously, cases of schizencephaly associated with CSF retention disorders such as hydrocephalus, subdural hygroma, and arachnoid cysts have been diagnosed using conventional MRI [9,10,25].Investigations using detailed neuroimaging with high resolution in a larger number of schizencephaly patients with CSF retention disorders may lead to a further understanding of the disease condition.

Conclusion
The present cases demonstrate that ventricular diverticula may occur in patients with open-lip schizencephaly and have a mass effect.Shunting operation can be effective against expanding ventricular diverticula.Detailed MRI examination such as 3D-hT2WI is useful for diagnosis.Ventricular Diverticulum through an Open-Lip Schizencephalic Cleft

Fig. 1 .
Fig. 1. a Prenatal magnetic resonance images (MRI) at 37 weeks and 2 days of gestation.Axial view of half-Fourier acquisition single-shot turbo spin-echo image showing cleft on the right cerebral hemisphere and fluid-filled space on the outside of the hemisphere.b MRI at 5 days of age.Axial T2-weighted images (T2WI) showing a cleft on the right peri-Roland area, and cerebral spinal fluid (CSF)-filled space on the outside of the right cerebral hemisphere extending to the middle cranial fossa.The CSF-filled cavity communicates with the lateral ventricle through the cleft that is covered with the cortical layer.c Axial views of T2WI at 8 months of age reveal enlargement of the outer portion of the CSF-filled cavity which compresses the cerebral hemisphere without enlargement of the lateral ventricle.d Axial (d-1, 2) and coronal (d-3) views of 3D-hT2WI at 14 months of age delineating thin borders (green arrows) between the outer portion of the CSF-filled cavity and the subarachnoid space or the cisterns.No separating structure is delineated between the cavity and the lateral ventricles.e-1 Intraoperative endoscopic view of the lateral ventricle (Vent) through the schizencephalic cleft from the outer space of the right cerebral hemisphere (Hemis).No septa are observed in the cleft.e-2 The arachnoid membrane in the vicinity of the right internal carotid artery where a pathway has been created.Axial (f-1) and coronal (f-2) views of 3D-hT2WI 8 days after endoscopic fenestration revealing the patent path toward the prepontine cistern (arrow in f-1) and the outer membrane of the cavity slackened and attached only to the dura at the burr-hole opening (arrowheads in f-2).g Axial view of computed tomography (CT) 1 year and 6 months after VP shunt placement showing slight shrinkage of the CSF-filled cavity and lateral ventricle.

Fig. 2 .
Fig. 2. a Axial views of T2WI at 1 month of age showing bilateral schizencephaly with an open-lip cleft on the left peri-Rolandic area and CSF-filled space on the outside of the left cerebral hemisphere, and a closed-lip on the right peri-Rolandic area.b Axial views of T2WI at 6 years of age revealing enlargement of the outer portion of the CSF-filled cavity without enlargement of the lateral ventricle.c Axial views of T2WI at the time of admission demonstrating increased size of the outer portion of the CSF-filled cavity associated with narrowing of the cerebral gyrus and midline shift.d Axial (d-1, 2) and coronal (d-3, 4) views of 3D-hT2WI after the shunt operation revealing thin borders (green arrows) between the outer portion of the CSF-filled cavity and the subarachnoid space.No separating structure is delineated between the cavity and the lateral ventricles.Note scar at the left diencephalon (white arrow in d-3), and artifact of the shunt system.e An axial view of T1WI indicating the surface of both clefts covered with the cortical layer.f An axial view of CT 1 year and 6 months after the shunt operation showing slight shrinkage of the CSF-filled cavity and the lateral ventricle.

Fig. 3 .
Fig. 3. Scheme drawn on the edited MRI of case 1 representing the possible formation of ventricular diverticula associated with openlip schizencephaly.a Red line indicates a thin membrane forming over the schizencephalic cleft (SC).Due to this membrane, a blindend CSF-filled cavity is formed (blue) in which one end is continuous with the lateral ventricle (LV) but the other end is not with the subarachnoid space (SAS).b This cavity may protrude from the cleft and expand over the ipsilateral hemisphere surface, representing ventricular diverticula (VD).