Angiographic features help predict outcome after stereotactic radiosurgery for the treatment of pediatric arteriovenous malformations

Purpose

Arteriovenous malformations (AVMs) are a frequent cause of hemorrhagic stroke in children. Stereotactic radiosurgery (SRS) is an established treatment for these lesions, particularly those that are surgically inaccessible. Because only complete AVM obliteration is believed to protect against the future risk of hemorrhage, identifying lesion characteristics that predict response to therapy is an important objective. The goal of this study is to evaluate the influence of angiographic features of AVMs on the rate of obliteration following treatment with SRS.

Methods

This is a retrospective cohort study of pediatric patients (age ≤18 years) treated with Gamma Knife SRS for cerebral AVMs between 2000 and 2012. Detailed angiographic data at the time of initial angiographic evaluation were prospectively recorded by experienced neurointerventional radiologists. The primary outcome was the rate of obliteration on a 3-year follow-up angiogram.

Results

We identified 42 pediatric patients treated with SRS for cerebral AVMs. Twenty-seven patients completed 3-year angiographic follow-ups. Complete obliteration was seen in 30 %, partial response in 67 %, and no response in 4 %. Higher SRS dose was associated with complete obliteration. Larger AVM diameter, presence of multiple draining veins, and presence of multiple draining veins reaching a sinus were associated with partial response. In this small cohort, diffuse AVM borders, presence of aneurysm, and pre-SRS embolization were not associated with obliteration.

Conclusions

Our study identifies AVMs in the pediatric population with a nidus diameter of <2.5 cm and a solitary draining vein as the most likely to undergo complete obliteration after SRS treatment.     

Gamma Knife radiosurgery for arteriovenous malformations in pediatric patients

Objective

The authors present the results of Gamma Knife stereotactic radiosurgery performed in a series of children with arteriovenous malformations (AVMs).

Methods

Between June 2005 and January 2014, 75 patients 18 years old or younger received Gamma Knife radiosurgery for AVMs. Of these, 58 patients were eligible for further analysis. The median age of the population was 12 years; 41 % presented with hemorrhage, 34 % with neurological insult, and 24 % patients were diagnosed incidentally. The median AVM volume was 3.5 cm³. The median radiosurgery-based AVM score (RSBAVMS) was 0.86. The median follow-up period was 32 months.

Results

Single session Gamma Knife radiosurgery resulted in complete AVM obliteration in 40 (68.9 %) patients. There were 35 (60.3 %) excellent outcome (complete obliteration with no new deficits) in this series. During the follow-up period, nine (15.51 %) patients experienced new deficits and three (5.1 %) patients experienced intracranial hemorrhage. The annual rate of developing new deficits and hemorrhage was calculated as 5.45 and 1.8 %, respectively. Volume, gender, RSBAVMS, and nidus type factor were factors associated with excellent outcome.

Conclusions

Radiosurgery was successful in majority of patients with minimal morbidity. Gamma Knife radiosurgery for AVMs can be a safe and successful method in pediatric patients.     

Retrospective Analysis on 76 Cases of Cerebral Arteriovenous Malformations Treated by Gamma Knife Radiosurgery

Objective

Outcome of gamma knife radiosurgery (GKS) in the consecutive 100 cases with cerebral arteriovenous malformations (AVMs) was analyzed.

Methods

Data from initial 100 patients treated with GKS in the authors'' institute were reviewed retrospectively. Spetzler-Martin grade at diagnosis were I in 18 patients, II in 27, III in 36, IV in 11, and V in 8. Thirty-five patients had experienced previous bleeding, 27 patients presented with seizure, and 31 patients presented with headache. The mean volume of the lesion was 4.3 cm³ (0.1-29.3 cm³). The median radiation dose delivered to the margin was 20.0 Gy (13-32 Gy). Mean follow-up period was 37.5 months (5-63 months).

Results

Angiographic follow-up was performed in 48 patients at least 2 years after GKS. Sixteen patients were lost in follow up following 2 years from GKS. Twenty-eight of 48 patients (58%) showed complete obliteration and 20 patients (42%) showed partial obliteration. Seven patients presented with post-GKS hemorrhage. Adverse radiation effect (ARE) was observed at follow-up MRI in 25 of 76 patients, and it was symptomatic in 5 patients. Complete obliteration was confirmed in 24 of 31 (77%) patients with volume less than 4 cm³, meanwhile only 4 of 17 (24%) patients with volume of 4 cm³ or more showed complete obliteration. Complete obliteration rate was 67% with 20 Gy or higher marginal dose, 63% with 15-20 Gy, and 17% with less than 15 Gy.

Conclusion

GKS can provide high rates of obliteration with acceptable risk of morbidity in a subgroup of small AVMs. However, overall outcome in whole spectrum of AVMs, in which large proportion of cases have unfavorable characteristics for radiosurgery, is much worse. More effective therapeutic strategy needs to be developed for large AVMs that are difficult to be managed with current available treatment modalities.     

Clinical features and endovascular treatment of intracranial arteriovenous malformations in pediatric patients

Purpose

The purpose of this study was to characterize clinical features and evaluate the clinical outcome of endovascular embolization treatment intracranial arteriovenous malformations in pediatric patients.

Methods

A cohort of children (age?≤?18 years) with arteriovenous malformations (AVMs) from 2000 to 2012 was included. Predictors studied included patient gender, age, and angioarchitectural features, including AVM location, nidus morphology and size, venous drainage, and associated aneurysms. Treatment method, complications and outcomes were recorded. The features of AVMs were evaluated before the treatment.

Results

One hundred twenty-seven children (77 males, mean age 13.2 years) were included; 90/127 (70.9 %) children were presented with hemorrhage. AVM size and deep venous drainage were independently associated with hemorrhage; 66/127 patients (52 %) treated with endovascular embolization. Complete obliteration at the end of all endovascular procedures was achieved in 14/66 patients (21.2 %), with an average of 78 % (range, 20–100 %) volume reduction. A mean of 2.9 (range, 1–9) feeding pedicles was embolized per patient. Overall, nine complications occurred in a total of 123 procedures (7.3 %). There was no procedure-related death in this study population. There was no significant difference between patients with and without complications in terms of AVM grade, demographic characteristics, or embolization features.

Conclusions

AVM size and deep venous drainage were independently associated with hemorrhage in pediatric patients. Endovascular procedure is feasible and safe for pediatric AVMs, and complete embolization can be achieved in small AVMs, while large AVMs can be adequately reduced in size for additional microsurgery or stereotactic radiosurgery.     

Radiosurgical Techniques and Clinical Outcomes of Gamma Knife Radiosurgery for Brainstem Arteriovenous Malformations

Objective

Brainstem arteriovenous malformation (AVM) is rare and radiosurgical management is complicated by the sensitivity of the adjacent neurological structures. Complete obliteration of the nidus is not always possible. We describe over 20 years of radiosurgical procedures for brainstem AVMs, focusing on clinical outcomes and radiosurgical techniques.

Methods

Between 1992 and 2011, the authors performed gamma knife radiosurgery (GKRS) in 464 cerebral AVMs. Twenty-nine of the 464 patients (6.3%) reviewed had brainstem AVMs. This series included sixteen males and thirteen females with a mean age of 30.7 years (range : 5-71 years). The symptoms that led to diagnoses were as follows : an altered mentality (5 patients, 17.3%), motor weakness (10 patients, 34.5%), cranial nerve symptoms (3 patients, 10.3%), headache (6 patients, 20.7%), dizziness (3 patients, 10.3%), and seizures (2 patients, 6.9%). Two patients had undergone a previous nidus resection, and three patients had undergone a previous embolization. Twenty-four patients underwent only GKRS. With respect to the nidus type and blood flow, the ratio of compact type to diffuse type and high flow to low flow were 17 : 12 and 16 : 13, respectively. In this series, 24 patients (82.8%) had a prior hemorrhage. The mean target volume was 1.7 cm³ (range 0.1-11.3 cm³). The mean maximal and marginal radiation doses were 38.5 Gy (range 28.6-43.6 Gy) and 23.4 Gy (range 18-27 Gy), and the mean isodose profile was 61.3% (range 50-70%).

Results

Twenty-four patients had brainstem AVMs and were followed for more than 3 years. Obliteration of the AVMs was eventually documented in 17 patients (70.8%) over a mean follow-up period of 77.5 months (range 36-216 months). With respect to nidus type and blood flow, the obliteration rate of compact types (75%) was higher than that of diffuse types (66.7%), and the obliteration rate of low flow AVMs (76.9%) was higher than that of high flow AVMs (63.6%) (p<0.05). Two patients (6.9%) with three hemorrhagic events suffered a hemorrhage during the follow-up period. The annual bleeding rate of AVM after GKRS was 1.95% per year. No adverse radiation effects or delayed cystic formations were found.

Conclusion

GKRS has an important clinical role in treatment of brainstem AVMs, which carry excessive surgical risks. Angiographic features and radiosurgical techniques using a lower maximal dose with higher isodose profiles are important for lesion obliteration and the avoidance of complications.     

Institutional experience of endoscopic suprasellar arachnoid cyst fenestration

Introduction

Suprasellar arachnoid cysts can differ from other arachnoid cysts in several ways, making a separate analysis of these cysts worthwhile. Herein, we present the outcome and perform volumetric analysis of six children with suprasellar arachnoid cysts treated with endoscopic ventriculocystocisternostomy in order to evaluate the long-term outcomes.

Patients and methods

Operative and postoperative data were retrospectively reviewed for six patients harboring suprasellar arachnoid cysts. Imaging was then used to follow success of surgical intervention.

Results

Six patients with suprasellar arachnoid cysts underwent ventriculocystocisternostomy. Presenting symptoms were headaches in three patients, developmental delay in another, and an incidental finding in the remaining patients. All patients had enlarged lateral and third ventricles on initial imaging. Average age at presentation was 145.7 months (65.4–250.2). Follow-up was an average of 46.5 months (3–84). The average cyst size was 153.96 cm³ (42.98–369.20) preoperatively and an average of 39.92 cm³ (3.20–101.47) at follow-up.

Conclusions

Based on our experience, suprasellar arachnoid cyst treatment with ventriculocystocisternostomy is an adequate surgical intervention. Suprasellar and third ventricular size does respond to the surgical intervention at long-term follow-up.     

Diffusion-weighted imaging in Sydenham’s chorea

Purpose

The purpose of this study was to determine of caudate nucleus changes in diffusion-weighted magnetic resonance imaging.

Methods

A total of 13 children (four males and nine females) with history of Sydenham’s chorea and 13 healthy controls were included in to the study. Diffusion cranial magnetic resonance imaging was performed in all subjects before prednisone treatment. Prednisone (2 mg/kg/day, maximum dose 60 mg/day) was used during 4 weeks and then progressively discontinued (20 % of the initial dose was reduced at each 5 days). Two months later, magnetic resonance imaging was repeated.

Results

Before and after 8 weeks of prednisone treatment, apparent diffusion coefficients (ADCs) were calculated for right and left caudate nucleus. The ADC values were significantly different before treatment and 2 months after imaging. For the left caudate nucleus, ADC values before treatment (0.69?±?0.038) were significantly lower than after treatment (0.95?±?0.04). For the right caudate nucleus, ADC values before treatment (0.72?±?0.06?×?10^?3) were significantly lower than after treatment (0.93?±?0.04?×?10^?3).

Conclusions

Although cranial and caudate nucleus magnetic resonance imaging findings were normal, the low ADC value findings in our study support the autoimmune inflammation in basal ganglia of Sydenham’s chorea.     

Rhabdoid meningioma: analysis of one case

Introduction

Rhabdoid meningioma (RM) is rare, and it occurs mainly in children. We report the clinical and pathological features of rhabdoid meningioma in a 9-year-old child.

Material and methods

A 9-year-old child with RM presented to our hospital with headache that had persisted for 3 days. Magnetic resonance imaging of his brain demonstrated supratentorial lesions of the right temporal petrous bone and cisterna magna cyst. He underwent surgery on January 13, 2010. The pathological diagnosis was rhabdoid meningioma (grade III). The patient underwent radiotherapy with 30 Gy/16 fractions delivered to the recurrent tumor after surgery. The patient died in December as a result of complications of recurrent meningioma.

Conclusion

The accumulated data, including this current case, demonstrate the difficulties in reaching the diagnosis and providing treatment for this disease as a consequence of its low incidence, aggressive nature, and poor treatment options for children with rhabdoid meningioma.     

Clinical features and long-term outcomes of intraspinal ependymomas in pediatric patients

Purpose

The aim of this study was to discuss the clinical manifestations, radiological features, treatment, and long-term outcomes of intraspinal ependymomas (Word Health Organization grade II) in pediatric patients.

Methods

The data of 15 pediatric patients who underwent microsurgery for intraspinal grade II ependymomas were retrospectively reviewed. Pre- and postoperative magnetic resonance imaging was performed in all patients. The diagnosis of grade II ependymomas was based on pathology. All the follow-up data were obtained during office visits.

Results

There were ten males and five females, with a mean age of 13.7?±?3.4 years. Four tumors were located in the cervical cord, six in the cervicothoracic cord, four in the thoracic cord, and one in the conus-cauda region, respectively. The most common symptom was motor deficits. Gross total resection (GTR) of the tumor was achieved in 12 cases, and subtotal resection (STR) was achieved in three cases. Regrowth of the residual tumor was observed in two STR cases during a mean follow-up period of 44.8 months. STR was performed again in one case due to clinical progression. At the last follow-up, 12 patients experienced an improvement in the neurological function and three patients maintained their preoperative status.

Conclusions

Pediatric intraspinal grade II ependymomas are amenable to surgical resection before neurological deficits deteriorate. GTR is the best treatment of choice, and the outcome is favorable. Due to uncertain therapeutic efficacy and possible radiation-induced toxicity, postoperative radiotherapy should be considered carefully for cases of STR.     

Pediatric spinal arteriovenous malformations and fistulas: a single institute’s experience

Objective

Pediatric spinal vascular diseases are extremely rare. We aimed to evaluate their clinical characteristics and treatment outcomes in our institute.

Design

A total of 10 patient files were retrospectively reviewed, including 3 cases of intramedullary arteriovenous malformations (AVMs), 6 cases of perimedullary arteriovenous fistulas (AVFs), and 1 case of epidural AVF. Clinical features, radiological findings, treatment results, and clinical outcomes were evaluated. The median durations of the radiologic and clinical follow-ups were 17.7 and 107.9 months, respectively.

Results

The male to female ratio was 1:1, with a median age at diagnosis of 9 years. All AVMs were juvenile type, all perimedullary AVFs were high flow types (three type IVb and three type IVc), and one epidural AVF was associated with intradural venous drainage. Most cases (90 %) were located in the cervical spine and conus medullaris. Acute neurological deterioration was identified in five patients; however, bleeding was identified in only one patient. Two cases were surgically treated, seven cases underwent embolization, and one case underwent radiosurgery. Three cases were completely obliterated, and their clinical states were improved (n = 2; 66.7 %) and stationary (n = 1; 33.3 %). Meanwhile, seven cases were incompletely obliterated, and their clinical states were improved (n = 2; 28.6 %), stationary (n = 3; 42.8 %), and aggravated (n = 2; 28.6 %).

Conclusions

Pediatric spinal AVMs and AVFs were mostly complex and high flow types, and complete obliteration could not be satisfactorily achieved. Incompletely treated lesions should be closely followed up because they may worsen.

     

The role of ventriculoperitoneal shunt placement in patients of tubercular meningitis with hydrocephalus in poor neurological grade: a prospective study in the pediatric population and review of literature

Purpose

There is still no standard protocol for management of patients of tubercular meningitis (TBM) with hydrocephalus in poor neurological grade. In general, a trial of external ventricular drain (EVD) is an accepted method of treatment to decide whether a particular patient will benefit from shunt surgery. However, recent studies suggest that ventriculoperitoneal (VP) shunt may be undertaken without the trial of an EVD. Our study prospectively evaluates the role of direct VP shunt placement in poor grade patients of TBM with hydrocephalus.

Methods

Twenty-six consecutive pediatric patients of TBM with hydrocephalus in Palur grades III and IV underwent direct VP shunt placement, without prior placement of EVD. Outcome was assessed at the end of 3 months using Glasgow Outcome Score.

Results

The mean age of patients was 3.3 years (range, 4 months to 11 years). Twenty-one (80.8 %) patients were in grade III and five (19.2 %) were in grade IV. Good outcome and mortality in grade IV patients was 20 % (1/5) and 60 % (3/5) respectively; whereas in grade III patients, it was 71.4 % (15/21) and 9.5 % (2/21), respectively. Thirteen patients presented with focal neurological deficit at admission, which persisted in only three patients at 3 months follow up. VP shunt-related complications were observed in six (23.5 %) patients

Conclusions

Despite poor grade at admission, 71.4 % patients in grade III and 20 % patients in grade IV had a good outcome at 3 months follow-up. Direct VP shunt placement is a safe and effective option even in poor grade patients of TBM with hydrocephalus, with a low complication rate.     

Long-term tumor-free survival case of congenital embryonal tumor with various pathological components

Purpose

Treatment strategy of malignant congenital brain tumor is controversial. We report a congenital embryonal tumor case with various pathological components.

Methods

A normally delivered male infant had an enlarged head circumference at 1 month after birth. The abnormality of the right side of the head was also noted during the routine 4-month health check. The head circumference was 45.1 cm (+2.25, SD); neurological status, however, was normal, with a pediatric GCS of 9 and body weight of 6,370 g (?0.85, SD). Magnetic resonance imaging (MRI) revealed right brain tumor whose size was 99 × 91 × 86 mm. The tumor was enhanced homogeneously with central necrosis, and the margin of the tumor was well circumscribed.

Results

We performed a subtotal removal of the tumor. The pathological diagnosis was meningioma (MIB-1 index was 2 %). The residual tumor gradually shrank, and we performed monthly MRI follow-up. The tumor abruptly recurred 7 months after the operation. The level of patient consciousness deteriorated, and emergency removal surgery was performed. The histological examination showed various types of embryonal components without meningioma-like parts. The pathological diagnosis was an embryonal tumor. The MIB-1 index was 48 %. One month after the second operation, dissemination of the tumor occurred at the right temporal lobe, cerebellum, and in subcutaneous tissue. Chemotherapy (vincristine, cisplatin, cyclophosphamide, and etoposide) was initiated following radiation therapy (3 Gy/day, 8×). Adjuvant therapies were effective, and no tumor recurrence was detected during 34 months follow-up.

Conclusion

Treatment strategies for malignant indefinite diagnosed tumor need to be discussed.     

Pediatric cranio-vertebral junction tuberculosis: management and outcome

Introduction

Tuberculosis (TB) of the cranio-vertebral junction (CVJ) is a rare condition, accounting for 0.3 % to 1 % of all cases of spinal TB. Early diagnosis and treatment are important in preventing long-term neurological sequelae. Management protocol of this rare site of TB is yet to be conclusively established. This holds particularly true for pediatric age group in which this condition is infrequently encountered.

Materials and methods

A total of 29 consecutive pediatric patients presented to the Department of Neurosurgery at Sanjay Gandhi Post-Graduate Institute of Medical Sciences, Lucknow, from January 1997 to October2011 with clinical and/or radiological features suggestive of CVJ TB. A clinical grading system to evaluate the neurological status was developed, and all patients were evaluated using this scoring system. Patients were radiologically evaluated with computed tomography (CT) of CVJ and magnetic resonance imaging (MRI) with gadolinium enhancement. These cases were managed according to their grade and followed up.

Results

Out of a total of 29 cases, 18 were females and 11 males. Age range was 4 to 18 years with mean age 9?±?3.8 years. The follow-up period ranged from 2 months to 7.5 years with mean follow-up of 2.7 years. Eleven cases were of grades 1 and 2, and 18 cases were of higher grade (grades 3 and 4). Predominantly conservative approach was utilized in cases with better clinical status, and grade (grades 1 and 2) and surgical intervention was needed in the more severe grades. All cases had significant improvement at the last follow-up.

Conclusion

One needs to have a high index of suspicion of CVJ TB if one encounters a case with neck pain, neck restriction, and raised erythrocyte sedimentation rate. CT CVJ and MRI with gadolinium contrast enhancement are the investigations of choice for both establishing a diagnosis and planning the management. For cases with mild neurological deficit, conservative approach would work for majority of cases, and for severe cases, initial conservative approach may be tried, failing which surgical intervention would be needed.     

The assessment of relationship between the skull base development and the severity of frontal plagiocephaly after bilateral fronto-orbital advancement in the early life

Purpose

The deformation of the skull base in patients with unilateral frontal plagiocephaly (UFP) is well known, but the mechanism is not still clear. We analyzed the skull base in the patients with UFP who underwent fronto-orbital advancement (FOA) in the early life during the last decade.

Methods

We assessed the treatment results and outcome of FOA performed in six patients, four girls and two boys younger than 2 years, in the last decade. Also, the basal cranium’s angles were measured by 3D reconstruction images on computed tomography (CT) scan.

Results

The mean patients’ age at FOAs was 11 months. Two cases were classified as grade 2A, two cases as grade 2B, and two cases as grade 3 (the classification of Di Rocco and Velardi). The ethmoidal axis was deviated a mean of 8.2° to the affected side. The mean angle between the petrosal pyramids and the midline (anterior-petrosal-sagittal angle, APSA) was 75.3° on the affected side and 66.2° on the normal side. The mean difference of APSA was 9.2°. On the follow-up CT images 5 years after surgery, the deviations of the ethmoidal axis clearly decreased, 5.7°, but the differences of APSA did not change, 8.8°.

Conclusions

The midline distortion of anterior skull base should be considered to be spontaneously corrected during the follow-up periods in patients with all types of UFP who underwent FOA, unlike posterior skull base in the patients with grades 2B and 3 classification.     

Acute Ischemic Injury on Diffusion-Weighted Magnetic Resonance Imaging after Poor Grade Subarachnoid Hemorrhage

Background

Poor clinical condition is the most important predictor of neurological outcome and mortality after subarachnoid hemorrhage (SAH). Rupture of an intracranial aneurysm was shown to be associated with acute ischemic brain injury in poor grade patients in autopsy studies and small magnetic resonance imaging series.

Methods

We performed diffusion-weighted magnetic resonance imaging (DWI) within 96 h of onset in 21 SAH patients with Hunt–Hess grade 4 or 5 enrolled in the Columbia University SAH Outcomes Project between July 2004 and February 2007. We analyzed demographic, radiological, clinical data, and 3 months outcome.

Results

Of the 21 patients 13 were Hunt–Hess grade 5, and eight were grade 4. Eighteen patients (86%) displayed bilateral and symmetric abnormalities on DWI, but not on computed tomography (CT). Involved regions included both anterior cerebral artery territories (16 patients), and less often the thalamus and basal ganglia (4 patients), middle (6 patients) or posterior cerebral artery territories (2 patients), or cerebellum (2 patients). At 1-year, 15 patients were dead (life support had been withdrawn in 6), 2 were moderately to severely disabled (modified Rankin Scale [mRS] = 4–5), and 4 had moderate-to-no disability (mRS = 1–3).

Conclusions

Admission DWI demonstrates multifocal areas of acute ischemic injury in poor grade SAH patients. These ischemic lesions may be related to transient intracranial circulatory arrest, acute vasoconstriction, microcirculatory disturbances, or decreased cerebral perfusion from neurogenic cardiac dysfunction. Ischemic brain injury in poor grade SAH may be a feasible target for acute resuscitation strategies.     

Response to bevacizumab, irinotecan, and temozolomide in children with relapsed medulloblastoma: a multi-institutional experience

Purpose

Chemotherapy for relapsed medulloblastoma has been inadequate, and most patients succumb to disease.

Methods

We retrospectively reviewed nine cases of relapsed medulloblastoma treated with bevacizumab, irinotecan, ±?temozolomide. Patients received one to three prior therapeutic regimens. Five patients received 10 mg/kg bevacizumab and 125–150 mg/m² irinotecan IV every 2 weeks, with temozolomide, starting at a median dose of 150 mg/m² orally for 5 days monthly. Two patients received bevacizumab and irinotecan, but not temozolomide, due to provider preference. Two of nine patients received 15 mg/kg bevacizumab IV, 90 mg/m² irinotecan orally for five consecutive days, 100 mg/m²/day temozolomide IV for 5 days, and 1.5 mg/m² vincristine IV, each administered every 21 days.

Results

Median time to progression was 11 months. Median overall survival was 13 months. Objective tumor response at 3 months was 67 %, including six patients with partial response (PR) and three patients with stable disease (SD). At 6 months, objective response was 55 %, with two patients with PR and three with complete response. Additionally, one patient had SD and three had PD. Two patients remain alive and progression free at 15 and 55 months; another is alive with disease at 20 months. Toxicities included two patients with grade III neutropenia, two with grade III thrombocytopenia, one with grade III elevation of liver function tests, and one patient with grade III diarrhea.

Conclusions

The combination of bevacizumab and irinotecan, with or without temozolomide, produces objective responses with minimal toxicity in children with recurrent medulloblastoma. Prospective clinical trials are needed to evaluate the efficacy of this strategy.     

Is there relation between COL4A1/A2 mutations and antenatally detected fetal intraventricular hemorrhage?

Background

The aim of the present study is to evaluate the role of COL4A1/A2 mutations in the etiology of intraventricular hemorrhage (IVH) detected in-utero.

Methods

The data of four cases with fetal IVH were analyzed retrospectively. Antenatal risk factors, clinical features, postnatal outcome, and the presence of COL4A1/A2 mutations were evaluated.

Results

Eight cases of fetal IVH were diagnosed between 2005 and 2012 in Erciyes University. Of these, four were eligible for genetic analysis. Mean gestational age at diagnosis was 30 weeks 5 day (min–max: 28–34 weeks); two cases had grade III hemorrhage and two cases had grade IV hemorrhage according to fetal magnetic resonance imaging. Three cases had severe neurodevelopmental delay and one case had mild deficit. In all cases, postnatal evaluation revealed no underlying cause, and no retinal hemorrhagia and hematuria were detected. The mean postnatal follow-up was 19 months, and no recurrent hemorrhages and porencephalic cyst formation were observed. The whole exome sequencing showed no pathological mutations of COL4A1 and COL4A2 in the four patients.

Conclusion

Our data showed that fetal intraventricular hemorrhage is not associated with COL4A1 and COL4A2 mutations in the absence of porencephaly, recurrent hemorrhage, and other organ bleeding.