Multimodality management and outcomes of brain arterio-venous malformations (AVMs) in children: personal experience and review of the literature, with specific emphasis on age at first AVM bleed.

PURPOSE: The purpose of this paper is to study the presentation and analyse the results of multimodality treatment of brain arterio-venous malformations (AVMs) in children at our centre and review age at first AVM rupture in the literature. METHODS: Of 52 patients aged <18 years, 47 with brain AVMs (27 males and 20 females) aged 4-17 years (mean 12.2) were retrospectively reviewed. PubMed search revealed five additional studies including 267 patients where the prevalence of age-related AVMs rupture was analysed. RESULTS: In our study, 37 patients had bled, 9 were symptomatic without haemorrhage and 1 was incidental. Spetzler-Martin score distribution was 5 cases grade I, 18 grade II, 21 grade III and 3 grade IV. Appropriate imaging was performed, either CT/MRI angiogram only (in emergency cases) or catheter angiogram, prior to definitive treatment. There were 40 supratentorial and 7 infratentorial AVMs. Twenty-nine patients had microsurgery alone and 9 patients were treated by radiosurgery only. Three patients were embolised, all followed by radiosurgery, with one requiring surgery too, while 4 patients had combined surgery and radiosurgery. One patient is awaiting radiosurgery while another was not treated. Good outcomes, classified as modified Rankin score (mRS) 0-2 improved significantly after intervention to 89.4% from 38.3% pre-treatment (p value <0.0001). Angiography confirmed 96.6% obliteration after first planned operation. Repeat cerebral angiogram around age 18 was negative in all previously cured patients. Reviewing the literature, 82.0% (95% CI = [77-87]; N = 267) of children diagnosed with brain AVMs (mean age 11.4 ± 0.4) presented with a bleed in the last 22 years. Males significantly outnumbered females (136 vs 84) (p < 0.001). Ninety-five patients underwent surgical intervention alone when compared to other treatment modalities (p < 0.001). CONCLUSIONS: Microsurgical excision of surgically accessible intracranial AVMs remains the primary treatment option with very good outcomes. A significant number of patients' AVMs ruptured around puberty; therefore, understanding the pathophysiology of AVM instability at this age may aid future therapy

Mutations of the DNA repair gene PNKP in a patient with microcephaly, seizures, and developmental delay (MCSZ) presenting with a high-grade brain tumor

Polynucleotide Kinase-Phosphatase (PNKP) is a bifunctional enzyme that possesses both DNA 3'-phosphatase and DNA 5'-kinase activities, which are required for processing termini of single- and double-strand breaks generated by reactive oxygen species (ROS), ionizing radiation and topoisomerase I poisons. Even though PNKP is central to DNA repair, there have been no reports linking PNKP mutations in a Microcephaly, Seizures, and Developmental Delay (MSCZ) patient to cancer. Here, we characterized the biochemical significance of 2 germ-line point mutations in the PNKP gene of a 3-year old male with MSCZ who presented with a high-grade brain tumor (glioblastoma multiforme) within the cerebellum. Functional and biochemical studies demonstrated these PNKP mutations significantly diminished DNA kinase/phosphatase activities, altered its cellular distribution, caused defective repair of DNA single/double stranded breaks, and were associated with a higher propensity for oncogenic transformation. Our findings indicate that specific PNKP mutations may contribute to tumor initiation within susceptible cells in the CNS by limiting DNA damage repair and increasing rates of spontaneous mutations resulting in pediatric glioma associated driver mutations such as ATRX and TP53

International multicentre validation of the arteriovenous malformation-related intracerebral haemorrhage (AVICH) score

OBJECTIVE: The recently published arteriovenous malformation-related intracerebral haemorrhage (AVICH) score showed better outcome prediction for patients with arteriovenous malformation (AVM)-related intracerebral haemorrhage (ICH) than other AVM or ICH scores. Here we present the results of a multicentre, external validation of the AVICH score. METHODS: All participating centres (n=11) provided anonymous data on 325 patients to form the Spetzler-Martin (SM) grade, the supplemented SM (sSM) grade, the ICH score and the AVICH score. Modified Rankin score (mRS) at last follow-up (mean 25.6 months) was dichotomized into favourable (mRS 0-2, n=210) and unfavourable (mRS 3-6;n=115). Univariate and AUROC analyses were performed to validate the AVICH score. RESULTS: Except nidus structure and AVM size, all single parameters forming the SM, sSM, ICH and AVICH score and the scores itself were significantly different between both outcome groups in the univariate analysis. The AVICH score was confirmed to be the highest predictive outcome score with an AUROC of 0.765 compared with 0.705 for the ICH score and 0.682 for the sSM grade. CONCLUSION: The multicentre-validated AVICH score predicts clinical outcome superior to pre-existing scores. We suggest the routine use of this score for future clinical outcome prediction and in clinical research. TRIAL REGISTRATION NUMBER: NCT02920645

Neurointerventional Surgery: An Evidence Based Approach/ by: Park, Min S., Kalani, M. Yashar S., Stiefel, Michael F.

Includes bibliographical references and indexUnique neurointerventional surgery resource analyzes landmark literature to inform optimal patient management The field of neurointerventional surgery is rapidly expanding with an ever-accelerating pace of technological innovations. While industry plays a significant role in designing new technology and defining indications for its use, practitioners need to evaluate and determine the most efficacious treatments for their patients. Neurointerventional Surgery: An Evidence-Based Approach by renowned endovascular neurosurgeons Min Park, M. Yashar S. Kalani, and Michael F. Stiefel examines the mo.1 online resource (250 pages)