Limited dorsal myeloschisis associated with intramedullary infantile hemangioma in the conus medullaris: illustrative case.

BACKGROUND: Limited dorsal myeloschisis (LDM) and intramedullary infantile hemangioma rarely coexist in the spinal cord. OBSERVATIONS: The authors describe the case of a 3-month-old girl who, despite lacking neurological symptoms or signs, had a cigarette burn-like mark at the lumbosacral area and skin dimpling in the gluteal area. Magnetic resonance imaging showed a low-set conus due to a thickened filum and an abnormal subcutaneous stalk connected to the conus medullaris. In combination with the skin lesions, these findings strongly implied nonsaccular-type LDM. An intramedullary mass in the conus medullaris was also shown on magnetic resonance imaging and was homogenously enhanced with isointensity on T1- and T2-weighted images. We prophylactically untethered the spinal cord and partially removed the intramedullary mass, which had no clear borders, for a safe surgical dissection. Histologically, the intramedullary mass was an infantile hemangioma, and the subcutaneous stalk was a lesion associated with LDM. The patient remained neurologically intact after surgery, and then 2 years later, there was spontaneous regression of the residual tumor. LESSONS: Although rare, nonsaccular type LDM may appear concurrently with intramedullary infantile hemangioma at the conus medullaris. The authors present a possible mechanism behind this concurrent presentation in the same area.

Rhabdoid tumor predisposition syndrome with renal tumor 10 years after brain tumor.

We report a case of rhabdoid tumor predisposition syndrome with a renal tumor developing 10 years after a brain tumor, which demonstrated an unexpectedly favorable outcome. A 2-year-old boy underwent gross total resection of a brain tumor located in the fourth ventricle, and received adjuvant chemotherapy and radiotherapy. At the age of 11 years, a renal tumor was found and nephrectomy was performed. He is currently alive without evidence of disease over 2 years without postoperative therapy. Histologically, rhabdoid cells were observed in both brain and renal tumors. Loss of SMARCB1 (also known as INI1) expression was found in the nucleus of both tumor cells. Genetic testing revealed pathogenic variants of SMARCB1 exon 5 in the renal tumor and SMARCB1 exon 9 in the brain tumor. In addition, heterozygous deletion of 22q11.21-q11.23 containing the SMARCB1 locus was shared by both tumors and this deletion was identified in normal peripheral blood. Considering the histopathological and genetic findings, our case was considered to be rhabdoid tumor predisposition syndrome with atypical teratoid/rhabdoid tumor and late-onset rhabdoid tumor of the kidney.

Histological and genetic analysis of anaplastic pleomorphic xanthoastrocytoma suspected of malignant progression over a 12-year clinical course.

We report a case of anaplastic PXA for which histological study and molecular analysis were performed at the time of the first resection and two recurrences. A 15-year-old girl had a temporal lobe tumor that had been followed as a cystic lesion from three years of age without histopathological examination. The first and second surgical specimens exhibited typical histological features of PXA such as nuclear and cytoplasmic pleomorphism. In addition, microvascular proliferation was observed in the second surgical specimen. On the other hand, nuclear pleomorphism was unclear in the third surgical specimen and it was mainly composed of spindle cells. Palisading necrosis was observed. Mitotic figures and the Ki-67 proliferation index gradually increased. BRAF V600E and TERT promoter mutation were detected in the first, second, and third surgical specimens. In addition, PTEN mutation and CDNK2A deletion were detected in the third surgical specimen. Considering the histopathological and genetic changes over time, we concluded that our case of anaplastic PXA underwent malignant progression.

A long-term survivor of pediatric midline glioma with H3F3A K27M and BRAF V600E double mutations.

We report a case of 2-year-old female with lateral ventricular glioma harboring both H3F3A K27M and BRAF V600E mutations. By the methylation analysis, the tumor was classified as a diffuse midline glioma H3 K27M mutant, WHO grade IV. However, the tumor was pathologically low-grade and likely localized rather than diffusely infiltrating. Further, the patient has survived more than 8 years after gross total resection of the tumor. Whereas both H3F3A K27M and BRAF V600E have been reported as poor prognostic markers in pediatric glioma, our case, along with several other reported cases, suggests that the coexistence of these two mutations might not indicate poor prognosis. The case emphasizes the importance of comprehensive assessment based on pathological, genetic and clinical findings and calls for further investigations of non-diffuse glioma with H3F3A K27M and glioma with H3F3A K27M and BRAF V600E.

Successful treatment of metastatic cerebral recurrence of pleuropulmonary blastoma.

Pleuropulmonary blastoma (PPB) is a rare pediatric tumor. The central nervous system (CNS) is the most common site of extrathoracic metastasis. The prognosis of PPB patients with CNS metastases is dismal: most patients die within one year after recurrence. Here, we describe two patients diagnosed with PPB who developed intracranial recurrences shortly after the end of their initial treatment and were successfully treated by gross total resection, radiotherapy, and chemotherapy. Both patients are in complete remission four and three years after recurrence. Although an optimal regimen remains to be determined, these cases demonstrate that PPB with CNS metastases is potentially curable.

Significance of molecular classification of ependymomas: C11orf95-RELA fusion-negative supratentorial ependymomas are a heterogeneous group of tumors.

Extensive molecular analyses of ependymal tumors have revealed that supratentorial and posterior fossa ependymomas have distinct molecular profiles and are likely to be different diseases. The presence of C11orf95-RELA fusion genes in a subset of supratentorial ependymomas (ST-EPN) indicated the existence of molecular subgroups. However, the pathogenesis of RELA fusion-negative ependymomas remains elusive. To investigate the molecular pathogenesis of these tumors and validate the molecular classification of ependymal tumors, we conducted thorough molecular analyses of 113 locally diagnosed ependymal tumors from 107 patients in the Japan Pediatric Molecular Neuro-Oncology Group. All tumors were histopathologically reviewed and 12 tumors were re-classified as non-ependymomas. A combination of RT-PCR, FISH, and RNA sequencing identified RELA fusion in 19 of 29 histologically verified ST-EPN cases, whereas another case was diagnosed as ependymoma RELA fusion-positive via the methylation classifier (68.9%). Among the 9 RELA fusion-negative ST-EPN cases, either the YAP1 fusion, BCOR tandem duplication, EP300-BCORL1 fusion, or FOXO1-STK24 fusion was detected in single cases. Methylation classification did not identify a consistent molecular class within this group. Genome-wide methylation profiling successfully sub-classified posterior fossa ependymoma (PF-EPN) into PF-EPN-A (PFA) and PF-EPN-B (PFB). A multivariate analysis using Cox regression confirmed that PFA was the sole molecular marker which was independently associated with patient survival. A clinically applicable pyrosequencing assay was developed to determine the PFB subgroup with 100% specificity using the methylation status of 3 genes, CRIP1, DRD4 and LBX2. Our results emphasized the significance of molecular classification in the diagnosis of ependymomas. RELA fusion-negative ST-EPN appear to be a heterogeneous group of tumors that do not fall into any of the existing molecular subgroups and are unlikely to form a single category.

Anatomic Understanding of Posterior Quadrant Disconnection from Cadaveric Brain, 3D Reconstruction and Simulation Model, and Intraoperative Photographs.

BACKGROUND: Posterior quadrant disconnection is a surgery for refractory unilateral temporoparieto-occipital epilepsy to limit propagation of epileptic discharges. As incomplete disconnection can lead to residual seizures, detailed procedures are presented using a cadaveric brain, three-dimensional (3D) reconstruction and simulation models, and intraoperative photographs. METHODS: A formalin-fixed adult cadaveric brain was dissected to show each step in posterior quadrant disconnection. Using 3D preoperative planning software, we reconstructed 3D models of operative views from computed tomography and magnetic resonance imaging. Intraoperative photographs were taken from the case of a 7-year-old girl with temporoparieto-occipital epilepsy. RESULTS: Frontotemporoparietal craniotomy was performed. The Sylvian fissure was widely dissected, and the insular cortex was exposed. The temporal stem was disconnected along the inferior peri-insular sulcus. The disconnection was extended from the limen insulae to the atrium of the lateral ventricle. The fibers between the head of the hippocampus and the amygdala were disconnected. The parietal lobe was disconnected along the postcentral sulcus, and the disconnection was connected to the atrium of the lateral ventricle. At the medial surface of the parietal lobe, the disconnection was continued to the corpus callosum. The splenium of the corpus callosum was disconnected via the medial wall of the lateral ventricle. The fornix was divided in the atrium of the lateral ventricle. After these steps, disconnection of the unilateral tempoparieto-occipital lobe was achieved while preserving the arteries and veins. CONCLUSIONS: Inclusion of views from cadaveric brain, 3D reconstruction and simulation models, and intraoperative photographs facilitates a clearer anatomic understanding of posterior quadrant disconnection.

Efficacy and safety of everolimus in patients younger than 12 months with congenital subependymal giant cell astrocytoma.

Tuberous sclerosis complex (TSC) is a multisystem genetic disorder that activates mammalian target of rapamycin and produces tumor growth in several organs. We present five patients younger than 12 months who were diagnosed with TSC and treated with everolimus (EVL), after which congenital subependymal giant astrocytoma (cSEGA) promptly regressed in all patients. All patients achieved at least 50% reduction in the volume of cSEGA within 6 months. The most rapid reduction of cSEGA volume (79.1%) was found during the initial 3 months of EVL treatment. Patients underwent EVL treatment for an average of 27 months (range: 4-55 months). Mean EVL maintenance dose was 1.35 mg per day. EVL blood trough concentrations ranged from 2.0 to 11.7 ng/ml. The cSEGA became larger after discontinuing EVL in two patients. In all four patients who had multiple cardiac rhabdomyomas (CRMs), the CRMs showed accelerated regression after receiving EVL. Adverse events were noted in four patients: infection, stomatitis, and increased triglycerides. Four patients had febrile status epilepticus, which occurred during acute encephalopathy in a patient, and after discontinuing EVL in another. Three patients were still receiving EVL at their latest evaluations. Maintenance therapy with EVL is an effective therapeutic option for patients with cSEGA, and moreover may have additional favorable effects on other complications, even in early infancy; however, adverse effects should be carefully monitored.

Physiological Changes and Clinical Implications of Syndromic Craniosynostosis.

Syndromic craniosynostosis has severe cranial stenosis and deformity, combined with hypoplastic maxillary bone and other developmental skeletal lesions. Among these various lesions, upper air way obstruction by hypoplastic maxillary bone could be the first life-threatening condition after birth. Aggressive cranial vault expansion for severely deformed cranial vaults due to multiple synostoses is necessary even in infancy, to normalize the intracranial pressure. Fronto-orbital advancement (FOA) is recommended for patients with hypoplastic anterior part of cranium induced by bicoronal and/or metopic synostoses, and posterior cranial vault expansion is recommended for those with flattening of the posterior part of the cranium by lambdoid synostosis. Although sufficient spontaneous reshaping of the cranium can be expected by expansive cranioplasty, keeping the cranial bone flap expanded sufficiently is often difficult when the initial expansion is performed during infancy. So far distraction osteogenesis (DO) is the only method to make it possible and to provide low rates of re-expansion of the cranial vault. DO is quite beneficial for both FOA and posterior cranial vault expansion, compared with the conventional methods. Associated hydrocephalus and chronic tonsillar herniation due to lambdoid synostosis can be surgically treatable. Abnormal venous drainages from the intracranial space and air way obstruction should be always considered at any surgical procedures. Neurosurgeons have to know well about the managements not only of the deformed cranial vault and the associated brain lesions but also of other multiple skeletal lesions associated with syndromic craniosynostosis, to improve treatment outcome.

Spinal arteriovenous metameric syndrome in a neonate presenting with congestive heart failure: case report.

BACKGROUND: Spinal arteriovenous metameric syndrome (SAMS) is a combination of more than two separate vascular malformations in the same embryonic metameres. This syndrome, also known as Cobb syndrome, is rare, especially in the neonate. CASE DESCRIPTION: A neonatal girl with a birthmark in the occipital and posterior nuchal regions presented with severe heart failure on the day of birth. The large arteriovenous fistulas in the left hypoglossal canal and in the posterior nuchal region were embolized with detachable coils on the postnatal days 5 and 18, which improved heart failure markedly. The associated intramuscular arteriovenous malformation in the posterior neck was left untreated because large arteriovenous fistulas had been occluded. She grew up without any neurological deficits and developed with normal milestones until the latest follow-up of 8 years old. CONCLUSION: To our knowledge, this is the first case with SAMS in a neonate presenting with congestive heart failure. Presence of a birthmark in a neonate presenting with congestive heart failure may suggest the possible underlying high-flow vascular malformations in the same metamere.

Cranial distraction osteogenesis for syndromic craniosynostosis: long-term follow-up and effect on postoperative cranial growth.

BACKGROUND: Although cranial distraction osteogenesis (CDO) is beneficial, few studies have reported on detailed operative procedures and postoperative cranial growth. Herein, we demonstrated the objective effectiveness of CDO in younger infants. METHODS: The study included infants who underwent primary cranial distraction for craniosynostosis. Infants who had hydrocephalus were excluded and those who underwent additional osteotomy surgeries were analysed before the subsequent procedures. The infants' computed tomography data were analysed using Mimics(®) software (Materialise, Leuven, Belgium) to calculate the cranial volumes and compare them with the Abbott curve for a normal population. We defined cranial growth gap as the difference between the subject data and normal infant data to demonstrate the perioperative effects on cranial growth. RESULTS: CDO was performed in 10 infants. The mean infant age at the time of surgery was 6.4 months (range, 24--61 months) and the mean duration of postoperative follow-up was 38.9 months (range, 24--61 months). Five infants with Crouzon syndrome and five with Apert's syndrome were included. All infants showed postoperative cranial growth, but cranial growth gap showed postoperative declines for a certain period, indicating cranial growth suppression immediately following expansion. At the last follow-up, all cases were within ±2 standard deviation (SD) compared with the normal population. We derived a formula to predict the CDO target volume using the declining cranial growth gap curve. CONCLUSIONS: CDO was applicable and suitable for younger infants requiring aggressive cranial expansion.

[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.

Percutaneous angioplasty of a chronic total occlusion of the intracranial internal carotid artery. Case report.

BACKGROUND: A CTO of the intracranial ICA is usually managed medically and rarely by EC-IC bypass in selected patients. Percutaneous transluminal angioplasty has not been used. CASE DESCRIPTION: A 73-year-old man presented with frequent temporary blindness of the left eye and dizziness due to thrombotic occlusion of the left intracranial ICA, causing hemodynamic compromise. This patient was successfully treated by percutaneous angioplasty (balloon angioplasty and stent placement) under proximal balloon protection at 7 weeks from the ictus. Ischemic symptoms had not recurred during the 6-month follow-up period. CONCLUSION: Percutaneous angioplasty for a CTO of the intracranial ICA is technically feasible and can be an alternative to EC-IC bypass in a selected group of patients with symptomatic hemodynamic compromise, which is refractory to the best medical treatment.

Acute basilar artery dissection treated by emergency stenting in a 13-year-old boy.

We report a 13-year-old boy who presented with acute basilar artery occlusion due to traumatic arterial dissection. Because a grave prognosis was expected if left untreated, and the chance of neurological recovery was believed to be unlikely but not zero, given that emergency stenting for the dissection was performed within 6 h of ictus. Recanalization of the basilar artery with stent placement did not change the poor prognosis in this patient because there was extension of dissection into the posterior cerebral arteries.

[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.