Motor seizures confer overall survival benefit in who grade 2 glioma.

OBJECTIVE: The prevalence of epilepsy in World Health Organization (WHO) grade 2 glioma is high, with seizures being the presenting symptom in 60%-90%. We explore the epidemiology of seizures in this patient population in a regional neurosurgical center. METHODS: Electronic health records of patients with histologically-proven WHO grade 2 glioma (n = 228) were reviewed between 1997 and 2021, with data collected including patient demographics, epilepsy prevalence, and seizure semiology. The influence of seizure type on overall survival was calculated using a Cox proportional hazards model. RESULTS: Overall, 197 of 228 patients (86.4%) were diagnosed with epilepsy-either at presentation or during the course of their disease. Male patients were more likely than female patients to be diagnosed with epilepsy (91.1% vs 77.1%, p = .003) and, in those with epilepsy, more likely to experience at least one focal to bilateral tonic-clonic seizure (69.4% vs 54.1%, p = .05). Patients with left-sided tumors were twice as likely to have experienced a focal to bilateral tonic-clonic seizure (p = .02, odds ratio [OR] = .47). Predominantly experiencing seizures with motor activity appeared to confer better overall survival, with a 65% decrease in the risk of death 10 years post diagnosis (hazard ratio [HR] = .35, p = .02). This is despite accounting for previously described prognostic markers including tumor histology/genetics, time from diagnosis to surgery, and the extent of tumor resection. SIGNIFICANCE: Motor seizure activity is a frequent feature in WHO grade 2 glioma and appears to confer a survival benefit regardless of histology or surgical factors. Seizures due to dominant hemisphere tumors may be more likely to propagate and cause bilateral tonic-clonic activity.

Refractory status epilepticus arrested by vagus nerve stimulation.

A 54-year-old man developed altered mental state and generalised tonic-clonic seizures after 1 week of upper respiratory tract symptoms and diarrhoea, having been previously well. His MR scan of brain showed multifocal progressive T2 cortical signal changes. He was diagnosed with new-onset refractory status epilepticus (NORSE), initially treated as being secondary to autoimmune/paraneoplastic limbic encephalitis, although subsequent investigations were negative. His seizures and electrographic epileptiform activity continued despite escalating doses of antiseizure medications, immunosuppression with corticosteroids, immunoglobulins, plasma exchange and rituximab, and thereafter anaesthetic agents. A vagus nerve stimulator (VNS) was implanted 6 weeks after admission and its voltage rapidly increased over 4 days; his seizure activity resolved in the third week after VNS implantation. This case highlights the role of VNS in the early management of NORSE.

Levetiracetam as a first-line antiseizure medication in WHO grade 2 glioma: Time to seizure freedom and rates of treatment failure.

OBJECTIVE: The high seizure burden seen in World Health Association (WHO) grade 2 gliomas is well documented. This study aims to identify factors that influence the probability of seizure freedom (12 months of seizure remission) and treatment failure (antiseizure medication [ASM] cessation or introduction of an alternative) in patients with WHO grade 2 glioma. METHODS: This is a retrospective observational analysis of patients from a regional UK neurosurgical center with histologically proven (n = 146) WHO grade 2 glioma and brain tumor related epilepsy. Statistical analyses using both Kaplan-Meier and Cox proportional hazards models were undertaken, with a particular focus on treatment outcomes when the commonly prescribed ASM levetiracetam (n = 101) is used as first line. RESULTS: Treatment with levetiracetam as a first-line ASM resulted in a significant increase in the probability of seizure freedom (p < .05) at 2 years compared with treatment with an alternative ASM. Individuals presenting with focal seizures without bilateral tonic-clonic progression were between 39% and 42% significantly less likely to reach seizure freedom within 10 years (p < .05) and 132% more likely to fail treatment by 5 years (p < .01) when compared to individuals who had seizures with progression to bilateral tonic-clonic activity. ASM choice did not significantly affect treatment failure rates. SIGNIFICANCE: More than two-thirds of patients with WHO grade 2 glioma related epilepsy treated with levetiracetam first line achieve seizure freedom within 2 years and it is a reasonable first-choice agent. Experiencing mainly focal seizures without progression infers a significant long-term reduction in the chance of seizure freedom. Further studies are needed to inform ASM selection.

Feasibility and safety of a non-operative clinical strategy for radiologically diagnosed low grade anterior mesial temporal tumours in the absence of a histological diagnosis.

BACKGROUND: Although resection of mesial temporal lobe lesions can be achieved with relatively low morbidity, resective surgery is not without risk. Whilst many lesions found in the anterior mesiotemporal lobe are low-grade entities, transforming and high-grade lesions have also been demonstrated. We investigate the feasibility of utilising serial quantitative volumetric imaging, to determine if a strategy of imaging surveillance can be safely employed for the management of radiologically diagnosed anterior mesial temporal low-grade tumours without a confirmed histological diagnosis. METHODS: A retrospective case-note and radiology review design were utilised. The primary presenting symptomatology was recorded together with the efficacy of symptomatic control. Volumetric analysis of MRI images was performed using Brainlab software. Pre- and post-operative neuropsychological data were analysed. RESULTS: 35 patients were identified with a radiological diagnosis of a low-grade anterior mesial temporal lobe tumour. Of these, 29% (n = 10) underwent surgical resection. For the whole cohort, the mean tumour volume at diagnosis was 6.5cm3, with a mean volumetric expansion of 1.4% per month. A significant difference was found between the volumetric expansion rate of those that underwent surgical treatment and those that did not (4.9% per month vs 0.06% per month, p < .01). Of those cases that did not undergo surgical resection, no significant difference was seen between the initial diagnostic volume and the volume at the time of their most recent interval surveillance scan (p = .97). New onset epilepsy was significantly associated with a requirement for eventual surgical tumour resection; relative risk = 6.25, 95% CI = 1.5-25.9, p = .0114. CONCLUSION: Where medical seizure control is adequate, we suggest that conservative management is feasible even in the absence of a confirmed histological diagnosis. However, in patients aged over 50 years with new onset epilepsy, a lower threshold for intervention should be considered.

'Possible shunt malfunction' pathway for paediatric hydrocephalus-a study of clinical outcomes and cost implications.

BACKGROUND: Shunt insertion for hydrocephalus is a common paediatric neurosurgery procedure. Shunt complications are frequent with an estimated 20-40% failure rate within the first year, and 4.5% per year subsequently. We have an open-door 'possible shunt malfunction' pathway for children treated with a shunt or endoscopic third ventriculostomy, providing direct ward access to ensure rapid assessment and timely management of children. OBJECTIVE: To audit the 'possible shunt malfunction' pathway in terms of clinical outcomes (percentage-confirmed shunt dysfunction and number of re-attendances) and costs. METHODS: Clinical data for patients attending the triage service were prospectively recorded over 7 months-including the number of attendances, previous shunt revisions, shunt type, investigations performed (CT, x-rays), and outcome. Costings (e.g. costs of physician, inpatient stay, investigations) were obtained from the hospital's procurement department. RESULTS: In the study period, there were 81 attendances by 62 patients and only 16% of attendances resulted in surgical management (either shunt revision or ETV). Approximately 17% of patients re-attended at least once. The average cost per attendance in our pathway was £765.57 ($969.63; €858.73). The total expenditure for the pathway over 7 months was £62,011.03 ($78,540.07; €69,556.81), with inpatient stay making up the biggest percentage of cost (49.2%). CONCLUSION: Only 16% (13 attendances) of those attending through our pathway required neurosurgical intervention. Investigations for possible blocked shunt come at significant health, social, and financial cost. High rates of shunt failure, re-attendance, investigations, and inpatient stays incur a sizable financial burden to the healthcare system.

Augmented reality for the virtual dissection of white matter pathways.

BACKGROUND: The human white matter pathway network is complex and of critical importance for functionality. Thus, learning and understanding white matter tract anatomy is important for the training of neuroscientists and neurosurgeons. The study aims to test and evaluate a new method for fiber dissection using augmented reality (AR) in a group which is experienced in cadaver white matter dissection courses and in vivo tractography. METHODS: Fifteen neurosurgeons, neurolinguists, and neuroscientists participated in this questionnaire-based study. We presented five cases of patients with left-sided perisylvian gliomas who underwent awake craniotomy. Diffusion tensor imaging fiber tracking (DTI FT) was performed and the language-related networks were visualized separated in different tracts by color. Participants were able to virtually dissect the prepared DTI FTs using a spatial computer and AR goggles. The application was evaluated through a questionnaire with answers from 0 (minimum) to 10 (maximum). RESULTS: Participants rated the overall experience of AR fiber dissection with a median of 8 points (mean ± standard deviation 8.5 ± 1.4). Usefulness for fiber dissection courses and education in general was rated with 8 (8.3 ± 1.4) and 8 (8.1 ± 1.5) points, respectively. Educational value was expected to be high for several target audiences (student: median 9, 8.6 ± 1.4; resident: 9, 8.5 ± 1.8; surgeon: 9, 8.2 ± 2.4; scientist: 8.5, 8.0 ± 2.4). Even clinical application of AR fiber dissection was expected to be of value with a median of 7 points (7.0 ± 2.5). CONCLUSION: The present evaluation of this first application of AR for fiber dissection shows a throughout positive evaluation for educational purposes.

A comparison of the extent of resection in pineal region tumours via the occipital transtentorial and supracerebellar infratentorial approaches.

PURPOSE: To perform a single unit review of surgical approaches to the pineal region, looking to ascertain if trends were identifiable regarding the extent of resection and the rate of post-operative complications between approaches. We hypothesised that each approach would offer different exposure of the pineal region which may result in poor access to certain areas of the tumour. This may lead to residual tumour in reliable and predictable locations, and an awareness of these regions could help with pre-operative planning and lead to higher levels of suspicion when inspecting these regions intraoperatively. MATERIALS AND METHODS: We performed a single centre, retrospective review of all adult and paediatric patients who underwent surgical debulking of pineal region tumours between 2008 and 2019. Patient demographics, pre- and post- operative radiological tumour volume data, histology and complication rates were compared between the two groups. RESULTS AND CONCLUSIONS: The occipital transtentorial approach resulted in a significantly lower extent of resection when compared to the supracerebellar infratentorial approach (p = 0.04), even after multivariate analysis (p = 0.006). There was no significant difference between the location of residual tumour relative to the superior colliculi between the two approaches (p = 1.00). There was a significant incidence of radiological occipital lobe ischaemia from the occipital transtentorial approach (p = 0.04). Within our series, we did not demonstrate a consistent location of residual tumour relative to the surgical approach chosen. Whilst there was a significant difference with regards to the extent of resection between approaches, in the context of small comparative groups this is difficult to draw far-reaching conclusions from.

Quality of life after selective dorsal rhizotomy: an assessment of family-reported outcomes using the CPQoL questionnaire.

BACKGROUND: Selective dorsal rhizotomy (SDR) is widely accepted as an effective procedure for management of lower limb spasticity in children with cerebral palsy. However, effects of the procedure on quality of life are not widely reported and less so using a structured and validated quality of life tool such as Cerebral Palsy Quality of Life Questionnaire (CPQoL). Here, we present complete data for CPQoL outcomes for SDR patients operated in a single institution at 2 years follow-up. METHODS: Patients were operated over a 5-year period by the same surgeon using the same technique in a single institution. CPQoL questionnaires were completed by patients and families pre-operatively and at 6 months, 1 year and 2 years post-operatively. Data was collected prospectively. RESULTS: A total of 78 patients (58 male, 20 female), age range 2.6-13.8 years (median 6.33) were included whom underwent SDR between October 2012-November 2017. All had complete follow-up up to 2 years post-procedure (most recent November 2019). Four patients were excluded due to incomplete follow-up data. Statistically significant improvement was seen across five out of seven CPQoL domains and this was sustained to 2 years post-SDR. CONCLUSIONS: We demonstrate using a validated Quality of Life Tool that SDR has a beneficial effect on the quality of life for patients with cerebral palsy at this length of follow-up.

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

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.

Anesthesia management for low-grade glioma awake surgery: a European Low-Grade Glioma Network survey.

BACKGROUND: Awake surgery has become a key treatment of diffuse low-grade gliomas (DLGG) and is divided in three main phases: opening, tumor resection - during which the patient needs to be fully awake - and closure. The anesthetic management of awake neurosurgery is a challenge, and there are currently no guidelines. OBJECTIVE: The objective of the survey was to explore differences and commonalities regarding the anesthetic management of awake DLGG surgery within the European Low-Grade Glioma Network (ELGGN) centers. METHODS: A form that contained 14 questions about the anesthetic management was sent to 28 centers in May 2015. RESULTS: Twenty centers responded. During the opening and closing non-awake periods, 56% of teams chose general anesthesia with mechanical ventilation for at least one period (asleep-awake-asleep, SAS protocol), and 44% monitored anesthesia care including sedation without mechanical ventilation (MAC protocol). In case of SAS, all the teams chose intravenous anesthesia, 82% used laryngeal mask instead of endotracheal intubation during the opening sequence, and 71% during closure. Local and regional anesthesia was practiced by all the teams. The most frequently reported cause of pain was dural and cerebral vessels manipulation (77%). Pain management was mostly based on paracetamol (70%) and remifentanil (55%). CONCLUSION: Our survey showed that there was an equivalent proportion of centers using SAS or MAC protocols in the anesthetic management of awake surgery in ELGGN centers. The advantages and disadvantages of each anesthesia protocol were reviewed.

Children's Cancer and Leukaemia Group (CCLG): review and guidelines for the management of meningioma in children, teenagers and young adults.

Primary tumours of the meninges are rare accounting for only 0.4-4.6% of all paediatric tumours of the central nervous system. Due to the rarity of these tumours in children, and the consequent absence of collaborative prospective trials, there is no clear consensus on how the unique characteristics of paediatric meningiomas impact clinical status, management approach, and survival. Much of the evidence and treatment recommendations for paediatric meningiomas are extrapolated from adult data. Translating and adapting adult treatment recommendations into paediatric practice can be challenging and might inadvertently lead to inappropriate management. In 2009, Traunecker et al. published guidelines for the management of intracranial meningioma in children and young people on behalf of UK Children's Cancer and Leukaemia Group (CCLG). Ten years later we have developed the updated guidelines following a comprehensive appraisal of the literature. Complete surgical resection is the treatment of choice for symptomatic meningiomas, while radiotherapy remains the only available adjuvant therapy and may be necessary for those tumours that cannot be completely removed. However, significant advances have been made in the identification of the genetic and molecular alterations of meningioma, which has not only a potential value in the development of therapeutic agents but also in surveillance of childhood meningioma survivors. This guideline builds upon the CCLG 2009 guideline. We summarise recommendations for the diagnosis, treatment, surveillance and long-term follow-up of children and adolescents with meningioma.

Recovery of major cognitive deficits following awake surgery for insular glioma: a case report.

BACKGROUND: Resection of insular tumours utilising modern neurosurgical techniques has become commonplace since its safety and reduced morbidity was first established. Interest has grown in the cognitive consequences of insula neurosurgery and studies have largely shown postoperative stability or minor decline. Major or widespread improvements in cognitive functioning following resection of insular tumours have not previously been reported. CASE DESCRIPTION: A 34-year-old, left-handed man with a right insular low-grade glioma (LGG) presented with seizures, nausea, altered sensation, poor balance and extensive cognitive decline. Comprehensive neuropsychological assessment highlighted a striking left hemispatial neglect and impairments in attention, working memory, verbal learning and fluency. During an awake craniotomy with functional cortical mapping, he reported intraoperative improvements in hand function and processing speed. Resolution of the neglect and significant improvements in cognition, mood and functioning were observed at follow-up and sustained over several years. CONCLUSIONS: This case highlights that right insular LGGs can cause significant cognitive and functional deficits and that neurosurgery has the potential to alleviate these difficulties to an extent beyond those documented in the extant literature.

Chiari I malformation and altered cerebrospinal fluid dynamics-the highs and the lows.

PURPOSE: This paper reviews the altered cerebrospinal fluid dynamics that can be associated with paediatric Chiari I malformation and we present our own institutional experience. METHODS: We conducted a thorough review of the literature and retrospectively analyzed all cases of operatively managed paediatric Chiari 1 malformation at our institution between February 2006 and February 2019. RESULTS: Acquired Chiari malformation (ACM) can radiologically mimic Chiari I and has been associated with both intracranial hypotension (either secondary to lumboperitoneal shunting or spontaneous CSF hypotension) and idiopathic intracranial hypertension (IIH). At our institution, 61 paediatric cases (range, 2-15 years) underwent foramen magnum decompression (FMD) for Chiari I malformation. Whilst 80% (50/61) of cases underwent FMD with no preceding or post-operative problems of CSF dynamics, 8% (5/61) of cases had hydrocephalus at initial presentation requiring CSF diversion followed by FMD for persistent Chiari, and 10% (6/61) developed hydrocephalus following FMD and required long-term CSF diversion. CONCLUSIONS: In paediatric ACM, the management of intracranial hypotension involves thorough radiological assessment and inclusion/adjustment of a valve in the case of lumboperitoneal shunting or epidural blood patch or interventional techniques in the case of spontaneous CSF leak. Thereby, unwarranted posterior fossa decompression surgery is avoided. In the case of IIH and Chiari I malformation, children who have recurrent symptoms despite adequate posterior fossa decompression surgery (failed Chiari), there is a strong role for intracranial pressure monitoring as raised intracranial pressure may indicate long-term CSF diversion.

SIOP-E-BTG and GPOH Guidelines for Diagnosis and Treatment of Children and Adolescents with Low Grade Glioma.

Low grade gliomas (LGGs) constitute the largest, yet clinically and (molecular-) histologically heterogeneous group of pediatric brain tumors of WHO grades I and II occurring throughout all pediatric age groups and at all central nervous system (CNS) sites. The tumors are characterized by a slow growth rate and may show periods of growth arrest. Around 40% of all LGG patients can be cured by complete neurosurgical resection and are followed by close observation. In case of relapse, second resection often is possible. Following incomplete resection observation is recommended, as long as there is no radiologic tumor growth and the patient does not suffer from significant, tumor-related symptoms. This also applies to patients with a diagnosis of LGG on the basis of radiological criteria. By contrast, clinical worsening and / or radiologic progression are an indication to treatment with either chemo- or radiotherapy. Overall survival is around 90%, and many patients survive with residual tumor, i. e. they suffer from chronic disease. All patients need comprehensive neuro-oncological care, the principles and details of which are summarized in the current guidelines. These represent standard of care for diagnostic work-up (including neuroimaging and neuropathology), and for therapeutic decisions (including the indications to non-surgical treatment) as well as concepts for neurosurgical intervention, chemotherapy and radiotherapy as well as surveillance and rehabilitation. The current treatment algorithm was compiled by members of the LGG working group of the SIOP-E brain tumor group (SIOP-E-BTG) and is based upon the results of previous European LGG studies and international reports.

Imaging practice in low-grade gliomas among European specialized centers and proposal for a minimum core of imaging.

OBJECTIVE: Imaging studies in diffuse low-grade gliomas (DLGG) vary across centers. In order to establish a minimal core of imaging necessary for further investigations and clinical trials in the field of DLGG, we aimed to establish the status quo within specialized European centers. METHODS: An online survey composed of 46 items was sent out to members of the European Low-Grade Glioma Network, the European Association of Neurosurgical Societies, the German Society of Neurosurgery and the Austrian Society of Neurosurgery. RESULTS: A total of 128 fully completed surveys were received and analyzed. Most centers (n = 96, 75%) were academic and half of the centers (n = 64, 50%) adhered to a dedicated treatment program for DLGG. There were national differences regarding the sequences enclosed in MRI imaging and use of PET, however most included T1 (without and with contrast, 100%), T2 (100%) and TIRM or FLAIR (20, 98%). DWI is performed by 80% of centers and 61% of centers regularly performed PWI. CONCLUSION: A minimal core of imaging composed of T1 (w/wo contrast), T2, TIRM/FLAIR, PWI and DWI could be identified. All morphologic images should be obtained in a slice thickness of ≤ 3 mm. No common standard could be obtained regarding advanced MRI protocols and PET. IMPORTANCE OF THE STUDY: We believe that our study makes a significant contribution to the literature because we were able to determine similarities in numerous aspects of LGG imaging. Using the proposed "minimal core of imaging" in clinical routine will facilitate future cooperative studies.

Monitoring the changing pattern of delivery of paediatric epilepsy surgery in England--an audit of a regional service and examination of national trends.

PURPOSE: The demand for paediatric epilepsy surgery in the UK greatly exceeds the number of operations performed. Hence, Children's Epilepsy Surgery Service (CESS) was commenced in 2012. This study is aimed to characterise the changes in service delivery in the North East of England Paediatric Neuroscience Network and nationally. METHODS: A retrospective cohort study of paediatric epilepsy surgery in Leeds between 2005 and 2012 is presented followed by analysis of British Paediatric Neurosurgical Group (BPNG) data before and after CESS commissioning. RESULTS: During the study period, 42 children underwent epilepsy surgery in Leeds. The commonest aetiologies were neoplasm (33%), focal cortical dysplasia (19%) and mesial temporal sclerosis (19%). Seizure outcome was 71 % EngelI and 83% EngelI+II. Complications included one infection (2%), two temporary (5%) and one permanent (2%) motor deficits, three new/worsened visual field deficits (7%). There were six re-craniotomies (14%). The BPNG data show a 48% increase in paediatric epilepsy surgery in England between 2009 (90 cases) and 2012 (133 cases), and a 20% fall in 2013 (106 cases)--the first calendar year for CESS. On average, 64% of all operations were performed in London. CONCLUSIONS: The number of children receiving surgery for epilepsy in England had increased annually up to, and declined after, the establishment of CESS centres. The yearly caseload in neurosurgical units outside of London is small. The outcomes from Leeds are comparable to those published elsewhere. Other UK units are encouraged to publish outcomes to facilitate patient, commissioner and provider decision making.

Fingerprint changes in CSF composition associated with different aetiologies in human neonatal hydrocephalus: inflammatory cytokines.

PURPOSE: Hydrocephalus (HC) has a multifactorial and complex picture of pathophysiology due to aetiology, age at and duration since onset. We have previously identified distinctions in markers of cell death associated with different aetiologies. Here, we examined cerebrospinal fluid (CSF) from human HC neonates for cytokines to identify further distinguishing features of different aetiologies. METHODS: CSF was collected during routine lumbar puncture or ventricular tap from neonates with hydrocephalus, or with no neurological condition (normal controls). Total protein, Fas receptor, Fas ligand, stem cell factor (SCF), hepatocyte growth factor (HGF), vascular endothelial growth factor (VEGF), insulin growth factor-1 (IGF-1), tumour necrosis factor alpha (TNF-α) and interleukin 6 (IL-6) were measured and compared between 8 unaffected and 28 HC neonatal CSF samples. RESULTS: Total protein was significantly (P < 0.05) raised in late-onset hydrocephalus (LOH). Fas receptor was raised (P < 0.05) in post-haemorrhagic hydrocephalus (PHH) and spina bifida with hydrocephalus (SB/HC), but no difference in Fas ligand was found. SCF was raised (P < 0.05) in SB/HC. HGF was found in all HC and was increased (P < 0.01) in PHH. Increased VEGF was found in PHH (P < 0.01) and SB/HC (P < 0.05). Variable levels of IL-6, TNF-α and IGF-1 were found in all HC groups compared with none in normal. CONCLUSIONS: LOH was unusual with significantly raised total protein indicating an inflammatory state. Increased Fas receptor, VEGF, IGF-1 and HGF suggest anti-apoptotic and repair mechanism activation. By contrast, elevated TNF-α and IL-6 indicate inflammatory processes in these neonatal brains. Taken with our previous study, these data indicate that different pathophysiology, inflammation and repair are occurring in HC of different aetiologies and that additional treatment strategies may benefit these infants in addition to fluid diversion.

Preliminary results on validity and reliability from two prospective cohort studies on a new Neonatal Coma Score.

OBJECTIVE: To collect data on content/face validity and interobserver agreement for a Neonatal Coma Score (NCS) in well full-term neonates and on construct validity in unwell and preterm babies, specifically how the NCS changed with gestational age and illness. DESIGN: Prospective cohort studies. SETTING: Two UK tertiary neonatal units (Sheffield and Leeds). PATIENTS: 151 well full-term (≥37 weeks gestational age) newborn babies recruited between January and February 2020 in Sheffield and April and May 2021 in Leeds; 101 sick preterm and full-term babies admitted to Sheffield neonatal unit between January 2021 and May 2022. INTERVENTION: A new NCS. MAIN OUTCOME MEASURES: Determination of normal values in well babies born ≥37 weeks gestational age; data on how the NCS changes with gestational age and illness. RESULTS: Face validity was demonstrated during development of the NCS. The median NCS of well, full-term newborn babies was 15 and the intraclass correlation coefficient was 0.78 (95% CI 0.70 to 0.84). In the 'well' preterm population, 95% <28 weeks had a score ≥11; 28-31 weeks ≥11; 32-36 weeks ≥13 and 37-44 weeks 14-15. The NCS dropped during periods of deterioration, demonstrating evidence of construct validity. Criterion validity was not assessed. CONCLUSIONS: The NCS has good intraobserver agreement in well full-term babies, with a normal NCS 14-15. The NCS in preterm neonates depended on gestational age, and deterioration from baseline was associated with illness. Further work is needed to determine normal scores each gestational age, reliability at lower levels, how early the NCS identifies deterioration and comparison with other assessment tools to demonstrate criterion validity.