Mutations in Chromatin Modifier and Ephrin Signaling Genes in Vein of Galen Malformation.

Normal vascular development includes the formation and specification of arteries, veins, and intervening capillaries. Vein of Galen malformations (VOGMs) are among the most common and severe neonatal brain arterio-venous malformations, shunting arterial blood into the brain's deep venous system through aberrant direct connections. Exome sequencing of 55 VOGM probands, including 52 parent-offspring trios, revealed enrichment of rare damaging de novo mutations in chromatin modifier genes that play essential roles in brain and vascular development. Other VOGM probands harbored rare inherited damaging mutations in Ephrin signaling genes, including a genome-wide significant mutation burden in EPHB4. Inherited mutations showed incomplete penetrance and variable expressivity, with mutation carriers often exhibiting cutaneous vascular abnormalities, suggesting a two-hit mechanism. The identified mutations collectively account for ∼30% of studied VOGM cases. These findings provide insight into disease biology and may have clinical implications for risk assessment.

Recurrent periventricular hemorrhage in cerebral proliferative angiopathy: Case report.

Cerebral proliferative angiopathy (CPA) is a rare vascular lesion. Bleeding from CPA is uncommon, but the risk of rebleeding is high once it bleeds. We describe a case of CPA with multiple intra- and periventricular hemorrhages during 30-year follow-up. Recurrent bleeding in these areas are common in moyamoya disease. These lesions may share the cause of bleeding: proliferation of the periventricular vessels functioning as collateral pathways. Revascularization surgery for CPA may attenuate the vascular proliferation in the vicinity of the ventricle, which may prevent rebleeding.

Transumbilical arterial embolization of a large dural arteriovenous fistula in a low-birth-weight neonate with congestive heart failure.

PURPOSE: The purpose of this study was to report transumbilical arterial embolization of a large dural arteriovenous fistula (AVF) in a low-birth-weight neonate with congestive heart failure (CHF). CASE PRESENTATION: A female neonate was delivered by cesarean section at 31 weeks of gestation. Her birth weight was 1538 g and Apgar scores were 6 at both 1 and 5 min. Because of dyspnea and retracted respiration immediately after birth, she required mechanical ventilation. Ultrasound revealed right cardiac overload and a large cystic mass at the posterior brain. Magnetic resonance imaging on day 1 showed a large dural AVF (dural sinus malformation with arteriovenous (AV) shunts) at the torcular herophili. Umbilical artery and vein catheterization were performed on the same day for neurointervention. CHF prompted emergency embolization on day 8. The transfemoral arterial route could not be used because of its small size and compromised femoral artery blood flow. Transumbilical arterial embolization shrank the AV shunts markedly, resulting in clinical improvement, thus requiring no further intervention. Follow-up angiography at 4 months confirmed no residual AVF. Her growth and development were normal at the last follow-up at age 4 years. CONCLUSION: This patient apparently was the lowest birth weight neonate with a large AVF successfully treated by embolization, which is usually performed through the transfemoral arterial route. The transumbilical arterial route is an alternative for neonates with birth weight <2000 g and very small femoral arteries.

Left internal carotid artery agenesis with trans-sellar collateral and a right aortic arch: Case report.

We present a case of unilateral internal carotid artery (ICA) agenesis with trans-sellar anastomosis associated with a right aortic arch, and discuss the embryonic development and clinical implications of this condition. A 26-year-old woman without significant medical history was referred to our hospital complaining of tinnitus. She denied any other symptoms, and examination did not reveal any other neurological deficits. Radiological examinations showed agenesis of the right ICA with trans-sellar anastomosis, and a right aortic arch. This vascular configuration reflects the anatomical homology with avian vascular structure. Recognition of this anomaly has important implications for clinical situations, such as the planning of carotid or transsphenoidal surgery, the management of thromboembolic disease, and the surveillance and detection of associated cerebral aneurysms.

[A Case of Cervical Spinal Dural Arteriovenous Fistula with Extradural Drainage Presenting with Subarachnoid Hemorrhage due to a Ruptured Anterior Spinal Artery Aneurysm].

We report a rare case of a cervical spinal dural arteriovenous fistula(AVF)at the C2 level presenting with subarachnoid hemorrhage(SAH)due to a ruptured anterior spinal artery aneurysm. A 61-year-old man presented with sudden onset headache. Initial computed tomography revealed SAH around the brainstem. Digital subtraction angiography(DSA)demonstrated a cervical dural AVF that was fed by the left C1 radicular, left C2 radicular, and anterior spinal arteries, and drained into the epidural plexus. An aneurysm in the branch of the cervical anterior spinal artery was considered the bleeding point. A left lateral suboccipital craniotomy and C1 hemilaminectomy were performed on day 43. The feeding arteries were clipped, followed by coagulation of the draining veins. However, the aneurysm was not clipped because we deemed that obliteration of the aneurysm would be difficult without disrupting the blood flow of the parent artery. The patient showed no neurological deterioration after the operation. Postoperative DSA revealed residual dural AVF. Therefore, a second surgery was performed. After the second open surgery, DSA showed that the dural AVF and aneurysm disappeared. The patient also showed no neurological deterioration after the second surgery.

[Spontaneous cerebrospinal fluid rhinorrhea associated with long-standing overt ventriculomegaly in adults (LOVA)].

OBJECTIVE: Spontaneous cerebrospinal fluid rhinorrhea associated with aqueductal stenosis is rare. CSF diversion is reported to be a failure in the majority of cases. The combination of the repair of the skull base and CSF diversion is reported to be successful. We describe a case successfully treated by intradural repair with ventricular drainage followed by endoscopic third ventriculostomy. CLINICAL PRESENTATION: A 28-year-old woman presented with rhinorrhea, and occasional attacks of headache, vomiting, and unconsciousness for two years. She had been diagnosed as arrested hydrocephalus for 10 years. Magnetic resonance imaging revealed triventriculomegaly with ballooning of the floor of the third ventricle, tonsilar herniation, right anterior horn herniation into the cribriform plate, and bilateral temporal lobe herniation into the temporal base. INTERVENTION: A ventricular drain was inserted followed by dissection of the herniated brain and repair of the enlarged cribriform foramen with periosteal flap. Make sure that the bacterial culture negative, endoscopic third ventriculostomy has been performed. There is no recurrence of hydrocephalus and rhinorrhea for two years. CONCLUSION: Direct communication between the lateral ventricle and the nasal/paranasal sinus is a rare complication of aqueductal stenosis and LOVA. Surgical repair of the skull base followed by cerebrospinal fluid diversion with endoscopic third ventriculostomy was a safe and reliable method.

[Experience in the treatment for intracranial arteriovenous shunts in children].

PURPOSE: To report our experiences in the treatment for intracranial arteriovenous shunts (AV shunts) in the pediatric population. MATERIAL AND METHODS: Twelve children with intracranial AV shunts were treated with endovascular embolization between December 1993 and March 2008. These comprised two cases of vein of Galen aneurysmal malformation, three of dural sinus malformation, two of infantile dural AV shunt, five of pial AV fistula including two of vein of Galen aneurysmal dilatation. There were eleven boys and one girl. The age at the first embolization ranged from day 0 to 9 years. We reviewed their clinical features and outcomes. RESULTS: Six patients including four neonates presented with congestive heart failure, one infant with macrocrania and three children with headache, seizure or ataxia. The number of endovascular embolization ranged from one to five per patient. These included eighteen transarterial embolizations and ten transvenous embolizations. All patients except for one who died eventually from pulmonary hemorrhage showed improvement in their symptoms. Although only five patients achieved complete occlusion of AV shunts, six patients including them developed normally. CONCLUSION: Intracranial AV shunts in the pediatric population present characteristic clinical features depending on the age of the presentation. Endovascular embolization is currently the treatment of choice for them. It is more important to obtain normal development than to achieve normal morphological appearance. It is also important to understand the difference of pathophysiological features of these diseases in the pediatric and adult population.

[The usefulness of adjuvant therapy using gamma knife radiosurgery for the recurrent or residual nonfunctioning pituitary adenomas].

We evaluated the treatment results of nonfunctioning pituitary adenomas in the era of radiosurgery. Between January 1994 and December 2003, we operated on 44 patients with nonfunctioning pituitary adenomas. 43 patients were operated on by transsphenoidal surgery and one patient was operated on by the transcranial approach. Total removal was able to be achieved in 13 patients (30%). Gamma knife radiosurgery was performed for residual tumor in 26 patients and for recurrence in 2 patients. The mean tumor diameter at the gamma knife radiosurgery was 18.2 mm (7.9 to 26.3 mm). The treatment dose was a mean of 12.3 Gy (8 to 16 Gy) to the tumor margin. The mean follow-up period after radiosurgery was 36.4 months. Tumor growth control was able to be achieved in 26 patients (93%). Two patients (7%) required adrenal and thyroid hormonal replacement during the follow-up period after radiosurgery due to radiation-induced endocrinopathy. None of the patients suffered from new cranial nerve deficits. This included optic neuropathy. Surgical resection using transsphenoidal surgery and subsequent gamma knife radiosurgery for residual and recurrent tumor proved to have a highly effective tumor growth control rate, and maintained the quality of life in patients with nonfunctioning pituitary adenomas.

A brainstem cavernoma demonstrating a dramatic, spontaneous decrease in size during follow-up: case report and review of the literature.

BACKGROUND: Many reports have demonstrated a worse prognosis for patients whose cavernomas were subtotally removed than for those whose cavernomas were not surgically treated. Therefore, it is better not to touch the cavernoma if a surgeon is not prepared to totally remove it. This report describes a large brainstem cavernoma showing a spontaneous, dramatic reduction in size after removal of only the biopsy specimen of the lesion. CASE DESCRIPTION: A 42-year-old woman experienced facial numbness, diplopia, and ataxia. A magnetic resonance (MR) study revealed a pontine cavernoma with hemorrhage. Two weeks later, recurrence of the patient's symptoms and consciousness disturbance were noted. An MR study revealed massive hemorrhage from the cavernoma with a ventricle dilatation. An operation on the lesion was conducted 3 months after the initial hemorrhage. However, the operation was aborted when an exploration of the lesion showed a tight adhesion between the lesion and the pons. Removal of only a biopsy specimen and evacuation of the suckable hematoma were done. No neurologic recovery and no decrease in the size of the cavernoma were detected postoperatively. Her family did not wish for further treatments. She was in a bedridden state with severe brainstem dysfunction when she was transferred to a local hospital. Sixteen months after the surgery, her consciousness was clear, and MR imaging confirmed a marked reduction in the size of the cavernoma. CONCLUSION: A dramatic, spontaneous decrease in size does occur even in the case of a large brainstem cavernoma showing hemorrhages. Conservative therapy may be one of the treatment options for the symptomatic brainstem cavernoma.

Regrowth and fatal rerupture despite proximal occlusion after coil embolization of a ruptured large basilar bifurcation aneurysm--case report.

A 40-year-old man suffered chronic progressive symptoms of brainstem compression after undergoing endosaccular coil placement in a ruptured large basilar bifurcation aneurysm. Radiographical examinations showed coil compaction and regrowth of the aneurysmal mass with perifocal mesencephalic edema. The symptoms did not resolve even after additional clip occlusion of the upper basilar artery and the patient died of rerupture. At present, direct surgical clipping using a skull base technique with or without hypothermic circulatory arrest or upper basilar artery occlusion with or without bypass surgery may be a better choice as an initial treatment for giant or large basilar bifurcation aneurysm with a wide neck.

[The treatment for asymptomatic meningiomas in the era of radiosurgery].

We evaluated the treatment results in asymptomatic meningiomas in the era of radiosurgery. We encountered 56 patients with asymptomatic meningiomas from January, 1994 to December, 2001. There were 16 male patients and 40 female patients. The most common location was the cerebral convexity. We performed gamma knife radiosurgery for three patients after diagnosis of cavernous sinus meningiomas. The other patients were followed-up after diagnosis for a mean follow-up period of 30.8 months (5 months to 8 years). Tumor growth was verified in 25 patients (43%) and two patients (3.7%) suffered neurological deficits. Among the tumor growth patients, operative resection was performed in six patients (11%) and gamma knife radiosurgery was performed in four patients (7.5%). The other patients were placed under observation. We decided the treatment strategy paying attention to the tumor location, tumor growth speed, tumor size and operative difficulty. The tumor growth rate was 0.1 cm/year among the patients with tumor growth. It was 0.72 cm/year (0.02 to 1.54 cm/year) in the operative group, 0.3 cm/year (0.04 to 0.76 cm/year) in the gamma knife radiosurgery group and 0.08 cm/year (0.01 to 0.76 cm/year) in the observed group. One patient suffered procedure-related deterioration of paresis after operation. The treatment of asymptomatic meningiomas must be decided depending on their natural history and locations. We recommend early radiosurgery for cavernous sinus meningiomas.

[The surgical treatment strategy and results of parasellar meningiomas in the era of radiosurgery].

We evaluated the surgical treatment results of parasellar meningiomas in the era of radiosurgery. We treated 24 patients of parasellar meningiomas surgically. The median age was 60 yrs (ranging from 29 to 82 yrs). The most common tumor location was the sphenoid ridge in 12 patients and the tuberculum sellae in 7 patients. The pterional approach using fronto-temporal craniotomy was performed for all patients. The residual or recurrent tumors were treated by gamma knife radiosurgery (GKS). We are able to follow up these cases for a median of 3.8 yrs (ranging from 1 to 8 yrs) after the operations. The radicality of tumor resection was Simpson grade II in 13 patients (54%), grade III in 3 patients (13%) and grade IV in 7 patients (33%). Clinical improvement was achieved in 81% of the patients. Of the patients who had visual disturbance preoperatively, 8 patients (73%) showed improvement, but 3 patients suffered deterioration postoperatively. None of the patients died. One patient suffered transient memory disturbance and one patient suffered mild facial numbness postoperatively. Boost radiosurgery for the residual tumors was performed for six patients and tumor growth control was able to be achieved in all patients, with a median of 3.1 years follow-up period (ranging from 0.5 to 6 yrs). Five patients with tumor regrowth or recurrence were treated by GKS. We recommend fronto-temporal craniotomy with nonradical resection for parasellar meningiomas and radiosurgery for residual and recurrent tumors. This strategy will achieve good functional outcome with long-term tumor growth control.