Publications by authors named "Kristian Aquilina"

80 Publications

Paediatric neurosurgical implications of a ribosomopathy: illustrative case and literature review.

Childs Nerv Syst 2021 May 21. Epub 2021 May 21.

Department of Neurosurgery, Great Ormond Street Hospital NHS Foundation Trust, London, UK.

Ribosomopathies are rare, recently defined entities. One of these, Labrune syndrome, is recognisable radiologically by its distinctive triad of leukoencephalopathy, intracranial calcifications and cysts (LCC). These cysts may have neurosurgical implications at different ages because of their progressive expansion and local mass effect. The aetiology of LCC is related to a widespread cerebral microangiopathy and is due to a genetic mutation in SNORD118, responsible for stabilisation of the large ribosomal subunit during assembly.
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http://dx.doi.org/10.1007/s00381-021-05208-6DOI Listing
May 2021

Intraventricular haemorrhage and posthaemorrhagic ventricular dilatation: moving beyond CSF diversion.

Childs Nerv Syst 2021 May 15. Epub 2021 May 15.

Department of Neurosurgery, Great Ormond Street Hospital, London, UK.

Advances in medical care have led to more premature babies surviving the neonatal period. In these babies, germinal matrix haemorrhage (GMH), intraventricular haemorrhage (IVH) and posthaemorrhagic ventricular dilatation (PHVD) are the most important determinants of long-term cognitive and developmental outcomes. In this review, we discuss current neurosurgical management of IVH and PHVD, including the importance of early diagnosis of PHVD, thresholds for intervention, options for early management through the use of temporising measures and subsequent definitive CSF diversion. We also discuss treatment options for the evolving paradigm to manage intraventricular blood and its breakdown products. We review the evidence for techniques such as drainage, irrigation, fibrinolytic therapy (DRIFT) and neuroendoscopic lavage in the context of optimising cognitive, neurodevelopmental and quality of life outcomes in these premature infants.
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http://dx.doi.org/10.1007/s00381-021-05206-8DOI Listing
May 2021

MRI-based radiomics for prognosis of pediatric diffuse intrinsic pontine glioma: an international study.

Neurooncol Adv 2021 Jan-Dec;3(1):vdab042. Epub 2021 Mar 5.

Department of Medical Biophysics, Western University, London, Onatrio, Canada.

Background: Diffuse intrinsic pontine gliomas (DIPGs) are lethal pediatric brain tumors. Presently, MRI is the mainstay of disease diagnosis and surveillance. We identify clinically significant computational features from MRI and create a prognostic machine learning model.

Methods: We isolated tumor volumes of T1-post-contrast (T1) and T2-weighted (T2) MRIs from 177 treatment-naïve DIPG patients from an international cohort for model training and testing. The Quantitative Image Feature Pipeline and PyRadiomics was used for feature extraction. Ten-fold cross-validation of least absolute shrinkage and selection operator Cox regression selected optimal features to predict overall survival in the training dataset and tested in the independent testing dataset. We analyzed model performance using clinical variables (age at diagnosis and sex) only, radiomics only, and radiomics plus clinical variables.

Results: All selected features were intensity and texture-based on the wavelet-filtered images (3 T1 gray-level co-occurrence matrix (GLCM) texture features, T2 GLCM texture feature, and T2 first-order mean). This multivariable Cox model demonstrated a concordance of 0.68 (95% CI: 0.61-0.74) in the training dataset, significantly outperforming the clinical-only model ( = 0.57 [95% CI: 0.49-0.64]). Adding clinical features to radiomics slightly improved performance ( = 0.70 [95% CI: 0.64-0.77]). The combined radiomics and clinical model was validated in the independent testing dataset ( = 0.59 [95% CI: 0.51-0.67], Noether's test = .02).

Conclusions: In this international study, we demonstrate the use of radiomic signatures to create a machine learning model for DIPG prognostication. Standardized, quantitative approaches that objectively measure DIPG changes, including computational MRI evaluation, could offer new approaches to assessing tumor phenotype and serve a future role for optimizing clinical trial eligibility and tumor surveillance.
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http://dx.doi.org/10.1093/noajnl/vdab042DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8095337PMC
March 2021

Complications associated with intrathecal drug delivery in a paediatric patient with Niemann-Pick type C.

BMJ Case Rep 2021 May 7;14(5). Epub 2021 May 7.

Neurosurgery, Great Ormond Street Hospital for Children, London, UK.

We report on a male subject with a diagnosis of Niemann-Pick type C (NPC). He received an experimental medicinal product intrathecally initially via lumbar puncture (LP) and eventually via intrathecal drug delivery device. Shortly after implantation, the device catheter migrated outside of the intrathecal space and coiled subcutaneously. The treatment continued via LP after removal of the device. A subdural haematoma developed after repeated LPs. It was surgically evacuated and the patient recovered with sequelae. Surgically implanted drug delivery devices are designed to bypass the blood-brain barrier and deliver a medicinal product directly into the cerebrospinal fluid circulation. Their use has extended into the field of neurodegenerative disorders. Significant adverse events can occur at any given time after implantation including neurological injury, dislodgement or displacement of any of its components, infection and drug-related complications; all can significantly affect the quality of life of patients. Repeated LPs also carry significant risk.
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http://dx.doi.org/10.1136/bcr-2021-241786DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8108650PMC
May 2021

Neurosurgical experience of managing optic pathway gliomas.

Childs Nerv Syst 2021 Jun 3;37(6):1917-1929. Epub 2021 Feb 3.

Department of Neurosurgery, Great Ormond Street Hospital, London, UK.

Background: Optic pathway gliomas (OPGs), also known as visual pathway gliomas, are debilitating tumors that account for 3-5% of all pediatric brain tumors. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of these tumors results in visual loss and blindness, endocrine and hypothalamic dysfunction, hydrocephalus, and premature death. Their involvement of the visual pathways and proximity to other eloquent brain structures typically precludes complete resection or optimal radiation dosing without incurring significant neurological injury. There are various surgical interventions that can be performed in relation to these lesions including biopsy, cerebrospinal fluid diversion, and partial or radical resection, but their role is a source of debate. This study catalogues our surgical experience and patient outcomes in order to support decision-making in this challenging pathology.

Methods: A retrospective review of all cases of OPGs treated in a single center from July 1990 to July 2020. Data was collected on patient demographics, radiographic findings, pathology, and management including surgical interventions. Outcome data included survival, visual function, endocrine, and hypothalamic dysfunction.

Results: One hundred twenty-one patients with OPG were identified, and 50 of these patients underwent a total of 104 surgical procedures. These included biopsy (31), subtotal or gross total resection (20 operations in 17 patients), cyst drainage (17), Ommaya reservoir insertion (9), or cerebrospinal fluid diversion (27). During the study period, there was 6% overall mortality, 18% hypothalamic dysfunction, 20% endocrine dysfunction, and 42% had some cognitive dysfunction. At diagnosis 75% of patients had good or moderate visual function in at least one eye, and overall, this improved to 83% at the end of the study period. In comparison the worst eye had good or moderate visual function in 56%, and this reduced to 53%. Baseline and final visual function were poorer in patients who had a surgical resection, but improvements in vision were still found-particularly in the best eye.

Discussion/conclusion: OPG are debilitating childhood tumor that have lifelong consequences in terms of visual function and endocrinopathies/hypothalamic dysfunction; this can result in substantial patient morbidity. Decisions regarding management and the role of surgery in this condition are challenging and include cerebrospinal fluid diversion, biopsy, and in highly select cases cystic decompression or surgical resection. In this paper, we review our own experience, outcomes, and surgical philosophy.
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http://dx.doi.org/10.1007/s00381-021-05060-8DOI Listing
June 2021

Tractographic and Microstructural Analysis of the Dentato-Rubro-Thalamo-Cortical Tracts in Children Using Diffusion MRI.

Cereb Cortex 2021 Mar;31(5):2595-2609

Developmental Imaging and Biophysics Section, UCL-GOS Institute of Child Health, London WC1N 1EH, UK.

The dentato-rubro-thalamo-cortical tract (DRTC) is the main outflow pathway of the cerebellum, contributing to a finely balanced corticocerebellar loop involved in cognitive and sensorimotor functions. Damage to the DRTC has been implicated in cerebellar mutism syndrome seen in up to 25% of children after cerebellar tumor resection. Multi-shell diffusion MRI (dMRI) combined with quantitative constrained spherical deconvolution tractography and multi-compartment spherical mean technique modeling was used to explore the frontocerebellar connections and microstructural signature of the DRTC in 30 healthy children. The highest density of DRTC connections were to the precentral (M1) and superior frontal gyri (F1), and from cerebellar lobules I-IV and IX. The first evidence of a topographic organization of anterograde projections to the frontal cortex at the level of the superior cerebellar peduncle (SCP) is demonstrated, with streamlines terminating in F1 lying dorsomedially in the SCP compared to those terminating in M1. The orientation dispersion entropy of DRTC regions appears to exhibit greater contrast than that shown by fractional anisotropy. Analysis of a separate reproducibility cohort demonstrates good consistency in the dMRI metrics described. These novel anatomical insights into this well-studied pathway may prove to be of clinical relevance in the surgical resection of cerebellar tumors.
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http://dx.doi.org/10.1093/cercor/bhaa377DOI Listing
March 2021

Neurosurgical applications of tractography in the UK.

Br J Neurosurg 2020 Dec 14:1-6. Epub 2020 Dec 14.

Developmental Imaging and Biophysics Section, UCL GOS Institute of Child Health, London, UK.

Introduction: Tractography derived from diffusion MRI can provide important insights into human brain microstructure . Neurosurgeons were quick to adopt the technique at the turn of the century, but it remains plagued by technical fallibilities. This study aims to describe how tractography is deployed clinically in a modern-day, public healthcare system, serving as a snapshot from the 'shop floor' of British neurosurgical practice.

Methods: An 11-question survey was circulated to the mailing lists of the Society of British Neurological Surgeons and British Neurosurgical Trainees' Association, including questions on frequency, indication, tracts reconstructed, specific details of techniques used and personnel by whom it was performed, and a free-text section on the limitations of tractography.

Results: 58 survey responses were received, covering all 40 neurosurgical units in the UK and Ireland. Overall, responses were received from neurosurgeons at 36 units (90.0%) stating tractography was in use at that unit. 74.1% of the responses were from Consultants. The most common indication for tractography was in tumour resection. It was most commonly performed by neuroradiologists or imaging scientists. 75.9% of respondents stated that the model used to process tractography was the diffusion tensor (DTI). Many respondents were unaware of which algorithm (74.1%) or software tools (65.6%) were used by the operator to produce tractography visualisations. The corticospinal tract was the most commonly reconstructed tract. The most commonly cited limitations of the technique were perceived inaccuracy and brain shift.

Conclusions: In this UK-based survey of practising neurosurgeons, we show that 90% of neurosurgical units in the UK and Ireland use tractography regularly; that predominantly DTI-based reconstructions are used; that tumour resection remains the most frequent use of the technique; and that large tracts such as the corticospinal tract are most frequently identified. Many neurosurgeons remain unfamiliar with the underlying methods used to produce tractography visualisations.
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http://dx.doi.org/10.1080/02688697.2020.1849542DOI Listing
December 2020

Surveillance imaging of grade 1 astrocytomas in children: can duration and frequency of follow-up imaging and the use of contrast agents be reduced?

Neuroradiology 2021 Jun 25;63(6):953-958. Epub 2020 Nov 25.

Radiology Department, Great Ormond Street Hospital, London, UK.

Purpose: The optimum strategy for the surveillance of low-grade gliomas in children has not been established, and there is concern about the use of gadolinium-based contrast agents (GBCAs), particularly in children, due to their deposition in the brain. The number of surveillance scans and the use of GBCAs in surveillance of low-risk tumours should ideally be limited. We aimed to investigate the consistency and utility of our surveillance imaging and also determine to what extent the use of GBCAs contributed to decisions to escalate treatment in children with grade 1 astrocytomas.

Methods: This was a retrospective single-centre study at a tertiary paediatric hospital. All children with a new diagnosis of a non-syndromic World Health Organization (WHO) grade 1 astrocytoma between 2007 and 2013 were included, with surveillance imaging up to December 2018 included in analysis. The intervals of surveillance imaging were recorded, and imaging and electronic health records were examined for decisions related to treatment escalation.

Results: Eighty-eight patients had 690 surveillance scans in the study period. Thirty-one patients had recurrence or progression leading to treatment escalation, 30 of whom were identified on surveillance imaging. The use of GBCAs did not appear to contribute to multidisciplinary team (MDT) decisions in the majority of cases.

Conclusion: Surveillance imaging could be reduced in number and duration for completely resected cerebellar tumours. MDT decisions were rarely made on the basis of post-contrast imaging, and GBCA administration could therefore potentially be restricted in the setting of surveillance of grade 1 astrocytomas in children.
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http://dx.doi.org/10.1007/s00234-020-02609-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7688203PMC
June 2021

Fourth ventricle tumors in children: complications and influence of surgical approach.

J Neurosurg Pediatr 2020 Oct 23:1-10. Epub 2020 Oct 23.

1Department of Neurosurgery, Great Ormond Street Hospital for Children, London.

Objectives: The goal of this study was to characterize the complications and morbidity related to the surgical management of pediatric fourth ventricle tumors.

Methods: All patients referred to the authors' institution with posterior fossa tumors from 2002 to 2018 inclusive were screened to include only true fourth ventricle tumors. Preoperative imaging and clinical notes were reviewed to extract data on presenting symptoms; surgical episodes, techniques, and adjuncts; tumor histology; and postoperative complications.

Results: Three hundred fifty-four children with posterior fossa tumors were treated during the study period; of these, 185 tumors were in the fourth ventricle, and 167 fourth ventricle tumors with full data sets were included in this analysis. One hundred patients were male (mean age ± SD, 5.98 ± 4.12 years). The most common presenting symptom was vomiting (63.5%). The most common tumor types, in order, were medulloblastoma (94 cases) > pilocytic astrocytoma (30 cases) > ependymoma (30 cases) > choroid plexus neoplasms (5 cases) > atypical teratoid/rhabdoid tumor (4 cases), with 4 miscellaneous lesions. Of the 67.1% of patients who presented with hydrocephalus, 45.5% had an external ventricular drain inserted (66.7% of these prior to tumor surgery, 56.9% frontal); these patients were more likely to undergo ventriculoperitoneal shunt (VPS) placement at a later date (p = 0.00673). Twenty-two had an endoscopic third ventriculostomy, of whom 8 later underwent VPS placement. Overall, 19.7% of patients had a VPS sited during treatment.Across the whole series, the transvermian approach was more frequent than the telovelar approach (64.1% vs 33.0%); however, the telovelar approach was significantly more common in the latter half of the series (p < 0.001). Gross-total resection was achieved in 70.7%. The most common postoperative deficit was cerebellar mutism syndrome (CMS; 28.7%), followed by new weakness (24.0%), cranial neuropathy (18.0%), and new gait abnormality/ataxia (12.6%). Use of intraoperative ultrasonography significantly reduced the incidence of CMS (p = 0.0365). There was no significant difference in the rate of CMS between telovelar or transvermian approaches (p = 0.745), and multivariate logistic regression modeling did not reveal any statistically significant relationships between CMS and surgical approach.

Conclusions: Surgical management of pediatric fourth ventricle tumors continues to evolve, and resection is increasingly performed through the telovelar route. CMS is enduringly the major postoperative complication in this patient population.
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http://dx.doi.org/10.3171/2020.6.PEDS2089DOI Listing
October 2020

Ventriculoatrial and ventriculopleural shunts as second-line surgical treatment have equivalent revision, infection, and survival rates in paediatric hydrocephalus.

Childs Nerv Syst 2021 Feb 28;37(2):481-489. Epub 2020 Sep 28.

Department of Neurosurgery, Great Ormond Street Hospital NHS Foundation Trust, London, UK.

Purpose: Ventriculoatrial (VA) and ventriculopleural (VPL) shunts are used as alternatives when CSF diversion to the peritoneal compartment with a ventriculoperitoneal (VP) shunt is not possible. The objective of this study is to compare directly the shunt survival and complications for both procedures in this setting in children.

Methods: A retrospective analysis of 54 consecutive patients who underwent VA (36) or VPL (18) shunt insertion between January 2002 and December 2017 was conducted.

Results: The overall mean follow-up was 4.1 (SD 4.3) years, 2.8 (SD 4.1) for VPL and 4.7 (SD 4.4) for VA shunts, respectively (p = 0.11). Twenty-four (66.7%) patients in the VA group and 9 (50.0%) in the VPL group underwent shunt revision (p = 0.236); mean number of revisions was 2.2 (SD 3.0) and 0.94 (SD 1.4) in the VA and VPL groups (p = 0.079). Median time to failure was 8.5 (IQr 78, range 0-176) months for VA and 5.50 (IQr 36, range 0-60) for VPL shunts (log rank (Mantel-Cox) 0.832). Shunt survival at 3, 6, 12 and 30 months was 60.6, 51.5, 36.4 and 27.3%, respectively, for VA and 56.3, 43.8, 37.5 and 37.5% for VPL shunts (log rank (Mantel-Cox) test value 0.727). The infection rate was 13.8% for VA and 5.6% for VPL shunts (p = 0.358). Four patients with VPL shunts (22.2%) developed pleural effusions. Fourteen deaths (25.9%) were recorded during follow-up, 8 (22.2%) in the VA and 6 (33.3%) in the VPL group (p = 0.380); two of the deaths in the VA group were shunt-related.

Conclusion: This study demonstrates that the outcomes of VA and VPL shunts, when used as second-line surgical treatment in paediatric hydrocephalus, were similar, as were the revision, infection and survival rates. The shorter longevity of these shunts compared with the general shunted population may reflect the complex nature of these children.
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http://dx.doi.org/10.1007/s00381-020-04887-xDOI Listing
February 2021

A persistent craniopharyngeal canal with recurrent bacterial meningitis: case report and literature review.

Childs Nerv Syst 2021 Feb 23;37(2):699-702. Epub 2020 Jul 23.

Department of Paediatric Otorhinolaryngology, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC1N 3JH, UK.

Background: A persistent craniopharyngeal canal (PCC) is a rare but treatable anatomical abnormality that causes recurrent meningitis and should be considered as a differential diagnosis.

Case Report: We report a case of an 8-year-old boy who presented with recurrent meningitis associated to his PCC. Surgical repair was performed, and no further episodes occurred.
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http://dx.doi.org/10.1007/s00381-020-04798-xDOI Listing
February 2021

Spectrum of neuroimaging findings post-proton beam therapy in a large pediatric cohort.

Childs Nerv Syst 2021 Feb 23;37(2):435-446. Epub 2020 Jul 23.

Great Ormond Street Hospital, London, UK.

Purpose: Proton beam therapy (PBT) is now well established for the treatment of certain pediatric brain tumors. The intrinsic properties of PBT are known to reduce long-term negative effects of photon radiotherapy (PRT). To better understand the intracranial effects of PBT, we analyzed the longitudinal imaging changes in a cohort of children with brain tumors treated by PBT with clinical and radiotherapy dose correlations.

Materials And Methods: Retrospective imaging review of 46 patients from our hospital with brain tumors treated by PBT. The imaging findings were correlated with clinical and dose parameters.

Results: Imaging changes were assessed by reviewing serial magnetic resonance imaging (MRI) scans following PBT over a follow-up period ranging from 1 month to 7 years. Imaging changes were observed in 23 patients undergoing PBT and categorized as pseudoprogression (10 patients, 43%), white matter changes (6 patients, 23%), parenchymal atrophy (6 patients, 23%), and cerebral large vessel arteriopathy (5 patients, 25%). Three patients had more than one type of imaging change. Clinical symptoms attributable to PBT were observed in 13 (28%) patients.

Conclusion: In accordance with published literature, we found evidence of varied intracranial imaging changes in pediatric brain tumor patients treated with PBT. There was a higher incidence (10%) of large vessel cerebral arteriopathy in our cohort than previously described in the literature. Twenty-eight percent of patients had clinical sequelae as a result of these changes, particularly in the large vessel arteriopathy subgroup, arguing the need for angiographic and perfusion surveillance to pre-empt any morbidities and offer potential neuro-protection.
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http://dx.doi.org/10.1007/s00381-020-04819-9DOI Listing
February 2021

Drainage, irrigation and fibrinolytic therapy (DRIFT) for posthaemorrhagic ventricular dilatation: 10-year follow-up of a randomised controlled trial.

Arch Dis Child Fetal Neonatal Ed 2020 Sep 4;105(5):466-473. Epub 2020 Jul 4.

Neonatal Neurology, Bristol Medical School, Faculty of Health Sciences, University of Bristol, Bristol, UK.

Background: Progressive ventricular dilatation after intraventricular haemorrhage (IVH) in preterm infants has a very high risk of severe disability and death. Drainage, irrigation and fibrinolytic therapy (DRIFT), in a randomised controlled trial (RCT), reduced severe cognitive impairment at 2 years.

Objective: To assess if the cognitive advantage of DRIFT seen at 2 years persisted until school age.

Participants: The RCT conducted in four centres recruited 77 preterm infants with IVH and progressive ventricular enlargement over specified measurements. Follow-up was at 10 years of age.

Intervention: Intraventricular injection of a fibrinolytic followed by continuous lavage, until the drainage was clear, and standard care consisting of control of expansion by lumbar punctures and if expansion persisted via a ventricular access device.

Primary Outcome: Cognitive quotient (CQ), derived from the British Ability Scales and Bayley III Scales, and survival without severe cognitive disability.

Results: Of the 77 children randomised, 12 died, 2 could not be traced, 10 did not respond and 1 declined at 10-year follow-up. 28 in the DRIFT group and 24 in the standard treatment group were assessed by examiners blinded to the intervention. The mean CQ score was 69.3 (SD=30.1) in the DRIFT group and 53.7 (SD=35.7) in the standard treatment group (unadjusted p=0.1; adjusted p=0.01, after adjustment for the prespecified variables sex, birth weight and IVH grade). Survival without severe cognitive disability was 66% in the DRIFT group and 35% in the standard treatment group (unadjusted p=0.019; adjusted p=0.003).

Conclusion: DRIFT is the first intervention for posthaemorrhagic ventricular dilatation to objectively demonstrate sustained cognitive improvement.

Trial Registration Number: ISRCTN80286058.
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http://dx.doi.org/10.1136/archdischild-2019-318231DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7547901PMC
September 2020

The utility of brain biopsy in pediatric cryptogenic neurological disease.

J Neurosurg Pediatr 2020 Jul 3:1-8. Epub 2020 Jul 3.

Departments of1Neurosurgery.

Objective: The authors' aim was to characterize a single-center experience of brain biopsy in pediatric cryptogenic neurological disease.

Methods: The authors performed a retrospective review of consecutive brain biopsies at a tertiary pediatric neurosciences unit between 1997 and 2017. Children < 18 years undergoing biopsy for neurological pathology were included. Those with presumed neoplasms and biopsy performed in the context of epilepsy surgery were excluded.

Results: Forty-nine biopsies in 47 patients (25 females, mean age ± SD 9.0 ± 5.3 years) were performed during the study period. The most common presenting symptoms were focal neurological deficit (28.6%) and focal seizure (26.5%). Histopathological, microbiological, and genetic analyses of biopsy material were contributory to the diagnosis in 34 cases (69.4%). Children presenting with focal seizures or with diffuse (> 3 lesions) brain involvement on MRI were more likely to yield a diagnosis at biopsy (OR 3.07 and 2.4, respectively). Twelve patients were immunocompromised and were more likely to yield a diagnosis at biopsy (OR 6.7). Surgery was accompanied by severe complications in 1 patient. The most common final diagnoses were infective (16/49, 32.7%), followed by chronic inflammatory processes (10/49, 20.4%) and occult neoplastic disease (9/49, 18.4%). In 38 cases (77.6%), biopsy was considered to have altered clinical management.

Conclusions: Brain biopsy for cryptogenic neurological disease in children was contributory to the diagnosis in 69.4% of cases and changed clinical management in 77.6%. Biopsy most commonly revealed underlying infective processes, chronic inflammatory changes, or occult neoplastic disease. Although generally safe, the risk of severe complications may be higher in immunocompromised and myelosuppressed children.
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http://dx.doi.org/10.3171/2020.4.PEDS19783DOI Listing
July 2020

A systematic review of ongoing clinical trials in optic pathway gliomas.

Childs Nerv Syst 2020 09 18;36(9):1869-1886. Epub 2020 Jun 18.

Department of Neurosurgery, Great Ormond Street Hospital, London, UK.

Introduction: Optic pathway gliomas (OPGs), also known as Visual Pathway Gliomas, are insidious, debilitating tumours. They are most commonly WHO grade 1 pilocytic astrocytomas and frequently occur in patients with neurofibromatosis type 1. The location of OPGs within the optic pathway typically precludes complete resection or optimal radiation dosing, hence outcomes remain poor compared to many other low-grade gliomas. The aim of this systematic review was to formulate a comprehensive list of all current ongoing clinical trials that are specifically looking at clinical care of OPGs in order to identify trends in current research and provide an overview to guide future research efforts.

Methods: This systematic review was conducted in line with the Preferred Reporting Items for Systematic Reviews and Meta-Analysis (PRISMA) guidelines. The Cochrane Controlled Register of Trials (CENTRAL) and ClinicalTrials.gov were searched. Inclusion and exclusion criteria were applied and final results were reviewed.

Results: 501 clinical trials were identified with the search strategy. All were screened and eligible studies extracted and reviewed. This yielded 36 ongoing clinical trials, 27 of which were pharmacological agents in phase I-III. The remaining trials were a mixture of biological agents, radiation optimisation, diagnostic imaging, surgical intervention, and a social function analysis.

Conclusion: OPG is a complex multifaceted disease, and advances in care require ongoing research efforts across a spectrum of different research fields. This review provides an update on the current state of research in OPG and summarises ongoing trials.
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http://dx.doi.org/10.1007/s00381-020-04724-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7434789PMC
September 2020

Infant High-Grade Gliomas Comprise Multiple Subgroups Characterized by Novel Targetable Gene Fusions and Favorable Outcomes.

Cancer Discov 2020 07 1;10(7):942-963. Epub 2020 Apr 1.

Department of Neuropathology, University Hospital Hamburg-Eppendorf, and Research Institute Children's Cancer Center, Hamburg, Germany.

Infant high-grade gliomas appear clinically distinct from their counterparts in older children, indicating that histopathologic grading may not accurately reflect the biology of these tumors. We have collected 241 cases under 4 years of age, and carried out histologic review, methylation profiling, and custom panel, genome, or exome sequencing. After excluding tumors representing other established entities or subgroups, we identified 130 cases to be part of an "intrinsic" spectrum of disease specific to the infant population. These included those with targetable MAPK alterations, and a large proportion of remaining cases harboring gene fusions targeting ( = 31), ( = 21), ( = 9), and ( = 4) as their driving alterations, with evidence of efficacy of targeted agents in the clinic. These data strongly support the concept that infant gliomas require a change in diagnostic practice and management. SIGNIFICANCE: Infant high-grade gliomas in the cerebral hemispheres comprise novel subgroups, with a prevalence of , or gene fusions. Kinase fusion-positive tumors have better outcome and respond to targeted therapy clinically. Other subgroups have poor outcome, with fusion-negative cases possibly representing an epigenetically driven pluripotent stem cell phenotype...
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http://dx.doi.org/10.1158/2159-8290.CD-19-1030DOI Listing
July 2020

Intraoperative electrophysiology during single-level selective dorsal rhizotomy: technique, stimulation threshold, and response data in a series of 145 patients.

J Neurosurg Pediatr 2020 Feb 28:1-10. Epub 2020 Feb 28.

Departments of1Neurosurgery.

Objective: Selective dorsal rhizotomy (SDR) is effective at permanently reducing spasticity in children with spastic cerebral palsy. The value of intraoperative neurophysiological monitoring in this procedure remains controversial, and its robustness has been questioned. This study describes the authors' institutional electrophysiological technique (based on the technique of Park et al.), intraoperative findings, robustness, value to the procedure, and occurrence of new motor or sphincter deficits.

Methods: The authors analyzed electrophysiological data of all children who underwent SDR at their center between September 2013 and February 2019. All patients underwent bilateral SDR through a single-level laminotomy at the conus and with transection of about 60% of the L2-S2 afferent rootlets (guided by intraoperative electrophysiology) and about 50% of L1 afferent roots (nonselectively).

Results: One hundred forty-five patients underwent SDR (64% male, mean age 6 years and 7 months, range 2 years and 9 months to 14 years and 10 months). Dorsal roots were distinguished from ventral roots anatomically and electrophysiologically, by assessing responses on free-running electromyography (EMG) and determining stimulation thresholds (≥ 0.2 mA in all dorsal rootlets). Root level was determined anatomically and electrophysiologically by assessing electromyographic response to stimulation. Median stimulation threshold was lower in sacral compared to lumbar roots (p < 0.001), and 16% higher on the first operated (right) side (p = 0.023), but unrelated to age, sex, or functional status. Similarly, responses to tetanic stimulation were consistent: 87% were graded 3+ or 4+, with similar distributions between sides. This was also unrelated to age, sex, and functional status. The L2-S2 rootlets were divided (median 60%, range 50%-67%), guided by response to tetanic stimulation at threshold amplitude. No new motor or sphincter deficits were observed, suggesting sparing of ventral roots and sphincteric innervation, respectively.

Conclusions: This electrophysiological technique appears robust and reproducible, allowing reliable identification of afferent nerve roots, definition of root levels, and guidance for rootlet division. Only a direct comparative study will establish whether intraoperative electrophysiology during SDR minimizes risk of new motor or sphincter worsening and/or maximizes functional outcome.
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http://dx.doi.org/10.3171/2019.12.PEDS19372DOI Listing
February 2020

Biopsy in diffuse pontine gliomas: expert neurosurgeon opinion-a survey from the SIOPE brain tumor group.

Childs Nerv Syst 2020 04 4;36(4):705-711. Epub 2020 Feb 4.

Department of Pediatric Neurosurgery, Charité Universitätsmedizin, Berlin, Germany.

Introduction: The prognosis of diffuse intrinsic pontine glioma (DIPG) is poor. The role of biopsy in DIPG remains controversial since the diagnosis may be established with imaging alone. Recent advances in understanding molecular biology and targeting of brain tumors have created a renewed interest in biopsy for DIPG. The Neurosurgery Working Group (NWG) of the SIOP-Europe Brain Tumor Group (BTG) undertook a survey among international pediatric neurosurgeons to define their current perceptions and practice regarding DIPG biopsy.

Methods: The NWG developed a 20-question survey which was emailed to neurosurgeons in the International Society for Pediatric Neurosurgery (ISPN). The questionnaire included questions on diagnosis, indications, and techniques for biopsy, clinical trials, and healthcare infrastructure.

Results: The survey was sent to 202 neurosurgeons and 73 (36%) responded. Consensus of > 75% agreement was reached for 12/20 questions, which included (1) radiological diagnosis of DIPG is sufficient outside a trial, (2) clinical trial-based DIPG biopsy is justified if molecular targets are investigated and may be used for treatment, and (3) morbidity/mortality data must be collected to define the risk:benefit ratio. The remaining 8/20 questions proved controversial and failed to reach consensus.

Conclusions: Routine DIPG biopsy continues to be debated. Most neurosurgeons agreed that DIPG biopsy within a clinical trial should be supported, with the aims of defining the procedure risks, improving understanding of tumor biology, and evaluating new treatment targets. Careful family counseling and consent remain important.
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http://dx.doi.org/10.1007/s00381-020-04523-8DOI Listing
April 2020

Surgical approaches in pediatric neuro-oncology.

Cancer Metastasis Rev 2019 12;38(4):723-747

Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, England, WC1N 3JH, UK.

Tumors of the central nervous system comprise nearly a quarter of all childhood cancers and are the most frequent solid tumor in the pediatric population. The most common location is in the posterior fossa, but tumors can occur anywhere intracranially. The spectrum of lesions encountered varies, from being completely benign and requiring surveillance alone to being highly malignant and requiring aggressive treatment in the form of surgery and adjuvant therapy. The extent of resection plays a crucial role in the oncological outcome of many of these tumors. A variety of surgical approaches are available for the spectrum of lesions encountered. This review focuses on summarizing the location, types, and neurosurgical management strategies for pediatric brain intracranial brain tumors. Here, we discuss neurosurgical approaches for a variety of brain tumors and regions, including the management of tumors of the posterior fossa, brainstem, pineal region, intraventricular region, sellar and suprasellar regions, optic pathway and hypothalamus, and supratentorial hemispheres.
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http://dx.doi.org/10.1007/s10555-019-09832-2DOI Listing
December 2019

Craniopharyngioma in children: trends from a third consecutive single-center cohort study.

J Neurosurg Pediatr 2019 Dec 20:1-9. Epub 2019 Dec 20.

3Great Ormond Street Hospital, London; and.

Objective: The management of children with craniopharyngioma has evolved over time, with a trend toward less invasive neurosurgical approaches as surgeons have sought to balance oncological control and treatment-related morbidity. To this end, the aim of this study was to evaluate the safety and effectiveness of the current management of children with craniopharyngioma compared to the previous management methods used at the authors' treatment center.

Methods: A prospectively maintained database was searched over a 14-year period between January 1, 2005, and December 31, 2018, to identify all children 17 years of age or younger with a new diagnosis of craniopharyngioma. A retrospective case note review was performed for each child to extract data on the presentation, investigation, treatment, and outcome of their illness. Morbidity was assessed in the same fashion as in previous cohorts, according to the following categories: visual loss, pituitary dysfunction, hypothalamic dysfunction, neurological deficits, and cognitive impairment.

Results: In total, 59 children were identified with craniopharyngioma during the study period. A total of 92 operations were performed, including cyst drainage (35/92; 38.0%), craniotomy and resection (30/92; 32.6%), and transsphenoidal resection (16/92; 17.4%). Approximately two-thirds of all operations were performed using image guidance (66/92; 71.7%) and one-third were performed using endoscopy (27/92; 29.3%). The majority of children had adjuvant therapy comprising proton beam therapy (18/59; 30.5%) or conventional radiotherapy (16/59; 27.1%). The median follow-up duration was 44 months (range 1-142 months), and approximately one-half of the children had no evidence of residual disease on MRI studies (28/59; 47.5%). Of the remaining 31 children, there was a reduction in the volume of residual disease in 8 patients (8/59; 13.6%), stable residual disease in 18 (18/59; 30.5%), and tumor growth in 5 patients (5/59; 8.5%). There was significantly reduced morbidity (p < 0.05) in all categories in the current cohort compared with our last cohort (1996-2004).

Conclusions: The authors' institutional experience of pediatric craniopharyngioma confirms a trend toward less invasive neurosurgical procedures, most of which are now performed with the benefit of image guidance or endoscopy. Moreover, the authors have identified an expanding role for more targeted radiotherapy for children with residual disease. These advances have allowed for tumor control comparable to that achieved in previous cohorts, but with significantly reduced morbidity and mortality.
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http://dx.doi.org/10.3171/2019.10.PEDS19147DOI Listing
December 2019

Childhood medulloblastoma-a single institution's historical perspective on survival and functional morbidity.

Childs Nerv Syst 2019 12 4;35(12):2327-2338. Epub 2019 Nov 4.

Department of Neurosurgery, Great Ormond Street Hospital for Children NHS Foundation Trust, Great Ormond Street, London, WC2N 3JH, UK.

Purpose: To compare results from a third (1995-2010) cohort of children with medulloblastoma with two previous series (J Neurosurg 86:13-21, 1997; Arch Dis Child 54:200-203, 1979) to analyse the effects of management changes aimed at improving both overall and event-free survivals (OS and EFS) and functional outcomes.

Methods: Review of neuro-oncology and imaging databases and previously published results.

Results: There was no statistically significant improvement in the 5-year OS for 104 children diagnosed 1995-2010, 61.5% (95% CI, 52.9, 71.6), compared with 50% of the 80 children presenting 1980-1990 (J Neurosurg 86:13-21, 1997) (difference 11.5%; 95% CI, 2.8, 25.4). Five-year OS for 96 children suitable for risk-stratification was overall 66% (95% CI, 57.9, 75.8); standard risk 77.8% (95% CI, 67.4, 89.7); high risk < 3 years 50.0% (95% CI, 32.3, 77.5); high risk ≥ 3 years 54.5% (95% CI, 37.2, 79.9); 5-year EFS were standard risk 68.5% (95% CI, 57.2, 82.1); high risk < 3 years 40.0% (95% CI, 23.4, 68.4); and high risk ≥ 3 years 36.4% (95% CI, 20.9, 63.2); overall 55.2% (95% CI, 46.1, 66.1). Of 62/63 ≥ 5-year survivor, 9 died later from tumour relapse and 4 from second malignancy. Functional outcomes of 62 of the 63 ≥ 5-year survivors: 67.7% had educational issues requiring remedial input; 18% restricted mobility indoors and outdoors; 59.7% hearing impairment (42% prescribed aids).

Conclusions: 1. Comparison of this single-institution series with its predecessor found that revised chemotherapy and RT protocols and greater accuracy of risk stratification did not result in statistically significant improvements in either survival or treatment-related functional disability. 2. Extended (> 5-year) follow-up is essential if 20% of late deaths from relapse and second malignancies are not to be overlooked.
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http://dx.doi.org/10.1007/s00381-019-04402-xDOI Listing
December 2019

Recurrent Langerhans cell histiocytosis at the site of prior craniotomy: case report.

J Neurosurg Pediatr 2019 Sep 27:1-5. Epub 2019 Sep 27.

Departments of1Neurosurgery and.

Tumors of the CNS represent the largest group of solid tumors found in the pediatric patient population. Langerhans cell histiocytosis (LCH) is an inflammatory lesion that may present in bone and/or soft tissue, including the CNS. Management depends on the extent of multisystem involvement, which determines resection with or without systemic chemotherapy. The authors report on the case of a child who underwent an open craniotomy for biopsy of a pituitary stalk lesion followed by neuropathological assessment, procedures used to diagnose LCH. The patient then underwent 12 months of systemic chemotherapy with subsequent resolution of the pituitary stalk lesion. Two years following pathological diagnosis, the patient presented with frontal orbital pain at the site of the prior craniotomy. Advanced imaging revealed MRI enhancement and radiotracer uptake of a soft-tissue growth at the frontal burr-hole site and MRI enhancement at a posterior burr-hole site without soft-tissue growth. The patient then underwent open biopsy and curettage that revealed LCH recurrence at the site of prior craniotomy. This case demonstrates that LCH may represent an abnormal reactive clonal proliferation of dendritic cells, rather than a de novo malignant neoplasm that can occur at sites of prior craniotomy despite systemic chemotherapy. The authors advocate close follow-up with contrast-enhanced imaging. Special attention should be given to sites of prior surgical manipulation to avoid missing distant sites of recurrence.
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http://dx.doi.org/10.3171/2019.6.PEDS19286DOI Listing
September 2019

Molecular correlates of cerebellar mutism syndrome in medulloblastoma.

Neuro Oncol 2020 02;22(2):290-297

Division of Haematology/Oncology, The Hospital for Sick Children, Toronto, Ontario, Canada.

Background: Cerebellar mutism syndrome (CMS) is a common complication following resection of posterior fossa tumors, most commonly after surgery for medulloblastoma. Medulloblastoma subgroups have historically been treated as a single entity when assessing CMS risk; however, recent studies highlighting their clinical heterogeneity suggest the need for subgroup-specific analysis. Here, we examine a large international multicenter cohort of molecularly characterized medulloblastoma patients to assess predictors of CMS.

Methods: We assembled a cohort of 370 molecularly characterized medulloblastoma subjects with available neuroimaging from 5 sites globally, including Great Ormond Street Hospital, Christian Medical College and Hospital, the Hospital for Sick Children, King Hussein Cancer Center, and Lucile Packard Children's Hospital. Age at diagnosis, sex, tumor volume, and CMS development were assessed in addition to molecular subgroup.

Results: Overall, 23.8% of patients developed CMS. CMS patients were younger (mean difference -2.05 years ± 0.50, P = 0.0218) and had larger tumors (mean difference 10.25 cm3 ± 4.60, P = 0.0010) that were more often midline (odds ratio [OR] = 5.72, P < 0.0001). In a multivariable analysis adjusting for age, sex, midline location, and tumor volume, Wingless (adjusted OR = 4.91, P = 0.0063), Group 3 (adjusted OR = 5.56, P = 0.0022), and Group 4 (adjusted OR = 8.57 P = 9.1 × 10-5) tumors were found to be independently associated with higher risk of CMS compared with sonic hedgehog tumors.

Conclusions: Medulloblastoma subgroup is a very strong predictor of CMS development, independent of tumor volume and midline location. These findings have significant implications for management of both the tumor and CMS.
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http://dx.doi.org/10.1093/neuonc/noz158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7442348PMC
February 2020

Current and Emerging Methods of Management of Ependymoma.

Curr Oncol Rep 2019 07 29;21(9):78. Epub 2019 Jul 29.

Department of Neurosurgery, Great Ormond Street Hospital for Children, London, WC1N 3JH, UK.

Purpose Of Review: This review discusses the evidence base behind current and emerging strategies of management of intracranial and spinal ependymomas in children, with a particular focus on aspects of surgical techniques, challenges and complications.

Recent Findings: The cornerstone of management remains maximal safe resective surgery, which has repeatedly been shown to correlate with improved survival. This is followed by focal conformal radiotherapy, although good results using proton beam therapy, with the potential for diminished side effects, are emerging. The role of chemotherapy remains largely unproven for paediatric ependymoma. Despite optimal management strategies, many children with ependymoma suffer from tumour recurrence. The standard of care for paediatric ependymoma comprises surgery and radiotherapy. Results of ongoing clinical trials will help shape its management in order to leverage our increasingly sophisticated understanding of the genetic drivers behind these tumours into survival benefit for this challenging group of patients.
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http://dx.doi.org/10.1007/s11912-019-0826-yDOI Listing
July 2019

Challenges in the Diagnosis of Medulloblastoma Recurrence at an Unusual Site in a Patient With Prader-Willi Syndrome.

J Pediatr Hematol Oncol 2020 07;42(5):e381-e384

Departments of Paediatric Oncology.

Medulloblastoma is the most common malignant pediatric brain tumor. Survival rates range between 50% and 80% depending on histology and other biologic features, metastases, and treatment approach. Prader-Willi syndrome (PWS) is a genetically inherited disorder characterized by dysmorphic features, mental retardation, obesity, and hypogonadism among other features. We describe a 10.5-year-old girl with PWS and previous standard-risk medulloblastoma that relapsed in the pons 3 years after the end of treatment. Diagnosis of relapse was delayed by a preceding varicella infection, an initial clinical/radiologic response to steroids and the unusual location, and was confirmed with a stereotactic biopsy. Second-line therapy was commenced, however, the patient rapidly deteriorated and died. This is the first report of medulloblastoma in a patient with PWS.
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http://dx.doi.org/10.1097/MPH.0000000000001555DOI Listing
July 2020

A congenital pseudotail in a neonate.

Arch Dis Child Fetal Neonatal Ed 2019 Jul 1;104(4):F371. Epub 2019 Feb 1.

Barnet Hospital, Starlight Neonatal Unit, Royal Free London NHS Trust, Barnet, UK.

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http://dx.doi.org/10.1136/archdischild-2018-316001DOI Listing
July 2019

Selective dorsal rhizotomy in ambulant children with cerebral palsy: an observational cohort study.

Lancet Child Adolesc Health 2019 07 30;3(7):455-462. Epub 2019 Apr 30.

School of Population Health and Environmental Sciences, King's College London, London, UK.

Background: Selective dorsal rhizotomy (SDR) is an irreversible surgical procedure involving the division of selected sensory nerve roots, followed by intensive physiotherapy. The aim is to improve function and quality of life in children with cerebral palsy and a Gross Motor Function Classification System (GMFCS) level of II or III (walks with or without assistive devices, respectively). We assessed gross motor function before and after SDR and postoperative quality of life in a study commissioned by NHS England.

Methods: We did a prospective observational study in five hospitals in England who were commissioned to perform SDR on children aged 3-9 years with spastic diplegic cerebral palsy. The primary outcome was score changes in the 66-item Gross Motor Function Measure (GMFM-66) and seven domains of the Cerebral Palsy Quality of Life Questionnaire ([CP-QoL] social wellbeing and acceptance, feelings about functioning, participation and physical health, emotional wellbeing and self-esteem, access to services, family health, and pain and impact of disability) from before to 24 months after SDR.

Findings: From Sept 4, 2014, to March 21, 2016, 137 children underwent SDR. The mean age was 6·0 years (SD 1·8). The mean GMFM-66 score increased after SDR with an annual change of 3·2 units (95% CI 2·9 to 3·5, n=137). Of the seven CP-QoL domains, five showed significant improvements over time: feelings about functioning mean annual change 3·0 units (95% CI 2·0 to 4·0, n=133), participation and physical health 3·9 units (2·5 to 5·3, n=133), emotional wellbeing and self-esteem 1·3 units (0·2 to 2·3, n=133), family health 2·0 units (0·7 to 3·3, n=132), and pain and impact of disability -2·5 units (-3·9 to -1·2, n=133). 17 adverse events were reported in 15 children, of which none were severe and 15 (88%) resolved.

Interpretation: SDR improved function and quality of life in the 24 months after surgery in children with cerebral palsy classified as GMFCS levels II and III. On the basis of these findings, an interim national policy decision was made that SDR would be funded for eligible children in England from 2018.

Funding: National Institute for Health and Care Excellence, National Institute for Health Research Biomedical Research Centre, NHS England.
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http://dx.doi.org/10.1016/S2352-4642(19)30119-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7153769PMC
July 2019

Ten-year follow-up of a randomised trial of drainage, irrigation and fibrinolytic therapy (DRIFT) in infants with post-haemorrhagic ventricular dilatation.

Health Technol Assess 2019 02;23(4):1-116

Neonatal Neurology, University of Bristol, Bristol, UK.

Background: The drainage, irrigation and fibrinolytic therapy (DRIFT) trial, conducted in 2003-6, showed a reduced rate of death or severe disability at 2 years in the DRIFT compared with the standard treatment group, among preterm infants with intraventricular haemorrhage (IVH) and post-haemorrhagic ventricular dilatation.

Objectives: To compare cognitive function, visual and sensorimotor ability, emotional well-being, use of specialist health/rehabilitative and educational services, neuroimaging, and economic costs and benefits at school age.

Design: Ten-year follow-up of a randomised controlled trial.

Setting: Neonatal intensive care units (Bristol, Katowice, Glasgow and Bergen).

Participants: Fifty-two of the original 77 infants randomised.

Interventions: DRIFT or standard therapy (cerebrospinal fluid tapping).

Main Outcome Measures: Primary - cognitive disability. Secondary - vision; sensorimotor disability; emotional/behavioural function; education; neurosurgical sequelae on magnetic resonance imaging; preference-based measures of health-related quality of life; costs of neonatal treatment and of subsequent health care in childhood; health and social care costs and impact on family at age 10 years; and a decision analysis model to estimate the cost-effectiveness of DRIFT compared with standard treatment up to the age of 18 years.

Results: By 10 years of age, 12 children had died and 13 were either lost to follow-up or had declined to participate. A total of 52 children were assessed at 10 years of age (DRIFT,  = 28; standard treatment,  = 24). Imbalances in gender and birthweight favoured the standard treatment group. The unadjusted mean cognitive quotient (CQ) score was 69.3 points [standard deviation (SD) 30.1 points] in the DRIFT group compared with 53.7 points (SD 35.7 points) in the standard treatment group, a difference of 15.7 points, 95% confidence interval (CI) -2.9 to 34.2 points;  = 0.096. After adjusting for the prespecified covariates (gender, birthweight and grade of IVH), this evidence strengthened: children who received DRIFT had a CQ advantage of 23.5 points ( = 0.009). The binary outcome, alive without severe cognitive disability, gave strong evidence that DRIFT improved cognition [unadjusted odds ratio (OR) 3.6 (95% CI 1.2 to 11.0;  = 0.026) and adjusted OR 10.0 (95% CI 2.1 to 46.7;  = 0.004)]; the number needed to treat was three. No significant differences were found in any secondary outcomes. There was weak evidence that DRIFT reduced special school attendance (adjusted OR 0.27, 95% CI 0.07 to 1.05;  = 0.059). The neonatal stay (unadjusted mean difference £6556, 95% CI -£11,161 to £24,273) and subsequent hospital care (£3413, 95% CI -£12,408 to £19,234) costs were higher in the DRIFT arm, but the wide CIs included zero. The decision analysis model indicated that DRIFT has the potential to be cost-effective at 18 years of age. The incremental cost-effectiveness ratio (£15,621 per quality-adjusted life-year) was below the National Institute for Health and Care Excellence threshold. The cost-effectiveness results were sensitive to adjustment for birthweight and gender.

Limitations: The main limitations are the sample size of the trial and that important characteristics were unbalanced at baseline and at the 10-year follow-up. Although the analyses conducted here were prespecified in the analysis plan, they had not been prespecified in the original trial registration.

Conclusions: DRIFT improves cognitive function when taking into account birthweight, grade of IVH and gender. DRIFT is probably effective and, given the reduction in the need for special education, has the potential to be cost-effective as well. A future UK multicentre trial is required to assess efficacy and safety of DRIFT when delivered across multiple sites.

Trial Registration: Current Controlled Trials ISRCTN80286058.

Funding: This project was funded by the NIHR Health Technology Assessment programme and will be published in full in ; Vol. 23, No. 4. See the NIHR Journals Library website for further project information. The DRIFT trial and 2-year follow-up was funded by Cerebra and the James and Grace Anderson Trust.
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http://dx.doi.org/10.3310/hta23040DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6398084PMC
February 2019

Surgical Outcomes of Single-Level Bilateral Selective Dorsal Rhizotomy for Spastic Diplegia in 150 Consecutive Patients.

World Neurosurg 2019 05 16;125:e60-e66. Epub 2019 Jan 16.

Department of Neurosurgery, Bristol Royal Hospital for Children, University Hospitals Bristol NHS Foundation Trust, Bristol, United Kingdom; Department of Neurosurgery, North Bristol NHS Trust, Bristol, United Kingdom; School of Clinical Sciences, University of Bristol, Bristol, United Kingdom. Electronic address:

Objectives: Selective dorsal rhizotomy (SDR) is used to improve spasticity, gait, and pain in children with spastic diplegia. There is growing evidence supporting its long-term benefits in terms of functional outcomes, independence, and quality of life. There is, however, little contemporary work describing the surgical morbidity of this irreversible procedure. The purpose of this study is to evaluate the surgical outcomes and complications of SDR at a single United Kingdom center.

Methods: Demographics, surgical, postoperative, and follow-up data for all patients undergoing SDR between 2011 and 2016 were collected from medical records.

Results: Preoperative Gross Motor Function Classification System levels in 150 consecutive patients were II (35%), III (65%), and IV (1%). Median age was 6 years and 58% were male patients. There were no deaths, cerebrospinal fluid leaks, returns to theater, or readmissions within 30 days. There were no new motor or sphincter deficits. Postoperative neuropathic pain was reported by 5.3% and sensory symptoms by 8.7%. Other complications included: postoperative nausea and vomiting (19.3%), superficial wound infection (3.3%), urinary retention (1.3%), headache (6.7%), and urine or chest infection (4.7%). Follow-up data were available for all patients (93% to 12 months, 72% to 24 months). Persistent neuropathic symptoms were reported in 6.5% at 24 months.

Conclusions: SDR using a single-level approach is a safe procedure with low surgical morbidity. This study complements the growing evidence base in support of SDR for spastic diplegia and should help inform decisions when considering treatment options.
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http://dx.doi.org/10.1016/j.wneu.2018.12.187DOI Listing
May 2019

Robot-assisted stereotactic brainstem biopsy in children: prospective cohort study.

J Robot Surg 2019 Aug 6;13(4):575-579. Epub 2018 Dec 6.

Department of Neurosurgery, Great Ormond Street Hospital, London, UK.

Tumours located within the brainstem comprise approximately a tenth of all paediatric brain tumours. Surgical biopsy of these tumours is technically challenging and has historically been associated with considerable risk. To this end, robot-assisted surgery theoretically allows for increased accuracy and precision. In this study we report our experience using the Neuromate robot (Renishaw, Gloucestershire, UK) to perform robot-assisted stereotactic biopsy in children with tumours located within the brainstem. An uncontrolled prospective cohort study was performed (phase II) according to the IDEAL model for safe surgical innovation. All cases were recorded on a prospectively maintained database. The database was searched over a 2-year period between the 1st December 2015 and the 31st November 2017 to identify all children with brainstem tumours that underwent robot-assisted stereotactic brain biopsy. When accessible, the post-operative MRI scans and pre-operative plans were compared to assess the target point localisation error (TPLE). Adverse events were recorded prospectively according to whether they resulted in increased hospital stay, caused neurological injury, or lead to death. In all, 11 consecutive children were identified with brain tumours located within the brainstem. In 10/11 cases specimens were diagnostic; in the remaining case a further biopsy was successful. The most frequent pathology was DIPG (7/15). Seven patients underwent an early post-operative volumetric MRI; the calculated median TPLE was 2.7 mm (range 0.5-4.2 mm). There were no surgical complications noted. Robot-assisted stereotactic biopsy in children appears to be feasible and safe. Research databases and comparative studies are warranted to further assess the technique.
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http://dx.doi.org/10.1007/s11701-018-0899-xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6647535PMC
August 2019