Postoperative de novo epilepsy after craniotomy: a nationwide register-based cohort study

Background and objectivesThe risks of postoperative risk of epilepsy after a craniotomy is widely believed to be raised. A study is warranted to quantify the risks for any neurosurgical indication. In this unselected register-based nationwide cohort study with virtually complete follow-up, the short-term and long-term cumulative risks of postoperative de novo epilepsy for all major neurosurgical indications were estimated.MethodsThe study was based on 8948 first-time craniotomy patients in Denmark 1 January 2005 to 31 December 2015 with follow-up until 31 December 2016. The patients were classified according to their underlying neurosurgical pathology. Patients with preoperative epilepsy were excluded. The postcraniotomy risks of de novo epilepsy were estimated using the Aalen-Johansen estimator in a multistate model.ResultsThe overall cumulative 1-year risk of postcraniotomy de novo epilepsy was 13.9% (95% CI 13.2 to 14.6). For patients with intracranial tumour the cumulative 1-year risk was 15.4% (95% CI 14.4 to 16.5), for spontaneous intracranial haemorrhage 11.3% (95% CI 10.1 to 12.6), for traumatic intracranial haemorrhage 11.1% (95% CI 9.6 to 12.9), for cerebral abscess 27.6% (95% CI 22.8 to 33.5) and for congenital malformations 3.8% (95% CI 1.3 to 11.7). The 6-month, 1-year and 5-year risks for all major indications by specific subtypes are provided.ConclusionsThe cumulative risk of de novo epilepsy following craniotomy is high for patients with any indication for craniotomy, as compared with the background population. The results provide comprehensive data to support future recommendations regarding prophylactic antiepileptic treatment and driving restrictions.

DIAGNOSTIC ACCURACY OF SQUASH CYTOLOGY OF ASTROCYTOMA

BACKGROUND: Primary Central nervous system tumours occupies less than 2% of overall human cancers in adults. The accurate diagnosis of intracranial tumour is necessary for therapeutic and prognostic purpose. Intraoperative smear cytology provides a rapid diagnosis which helps the neurosurgeon for immediate decision regarding the extent of surgery. To Objectives: determine the accuracy of squash preparation, by comparing it with histopathological sections and analysing the cytomorphological features of astrocytoma This was both retrospective and prospective study. We receive Methods: d nineteen radiologically and clinically suspected Astrocytoma in saline with xatives. Crush smear were made and stained with rapid Haematoxylin and Eosin. The corresponding biopsy materials were xed in 10% neutral buffered formalin and submitted for tissue processing. Staining was done with routine Haematoxylin and Eosin stain. The cytomorphologicalfeatures of these tumours were correlated with histopathological sections. In our study, we received Results: nineteen radiologically and clinically suspected Astrocytoma , tissue of all the tumours were soft and easy to smear . Glioblastomamultiforme was the most commonly encounterd tumor amomgneuroepithelial tumor constituting about 42.1% followed by diffuse astrocytoma (36.8%), WHOgrade II and IV tumors of astrocytoma were commonly encountered in ourstudy. Astrocytoma was common in males than females with majority of them fall in 5 th decade. we got 94.7% correlation between squash cytology and histopathology. Squash cytology is Conclusion: simple,rapid, accurate and cost effective diagnostic tool for Astrocytoma

Estimating population-based incidence of brain metastases – a comprehensive incident cohort study

Aims Brain metastases are the most common intracranial tumour and affect approximately 20% of adult cancer patients, most commonly from lung, breast, melanoma, and kidney cancer. However, the true incidence of brain metastasis is unknown. England’s cancer registration system only reliably captures brain metastases present at diagnosis (rather than those that develop later), and the same is true for US-based data. Although it is relatively easy to identify patients receiving some treatments for brain metastases (surgery, stereotactic radiosurgery (SRS) and whole-brain radiation therapy (WBRT)), identifying those receiving chemotherapy or no treatment is much harder. As a result, the existing literature is heavily biased towards reporting treated populations. This study attempts to find an unbiased estimate of the true number of patients developing brain metastases, based on data from a single centre. Method Cases of brain metastasis were retrospectively identified from the radiology information system database (SolitonTM). We performed a Boolean search for specific keywords in the radiology reports of all CT and MRI head scans performed at the trust between 1st January 2018 and 31st December 2019. The following keywords were searched for “metastases”, “metastatic“, “metastasis”, “mets”, “deposit”, “deposits”, “secondaries”, “secondary” and “disseminated”. Duplicate cases were then removed and the subsequent list was manually reviewed We identified all patients who received any treatment for brain metastases who were diagnosed at our centre. We only included patients with newly diagnosed brain metastases (included: leptomeningeal; excluded: skull-based metastases). We excluded patients who were diagnosed in other centres and treated here or diagnosed outside the study period. We then extracted data on primary diagnosis, admissions, and survival. Results 1192 patients had a CT or MRI of the head with a mention of “brain metastases” in the report; of these 305 were newly diagnosed with brain metastases during the study period (432 had metastases; 127 diagnosed earlier). Of these 305 patients, 217 (71.1%) were treated locally (SRS = 88; WBRT = 74; surgery = 88; systemic therapy = 16; multiple treatments = 45) and 10 (3.3%) were referred elsewhere. 78 (25.6%) patients received no treatment. Of the 217 treated patients, 124 were female, and the median age was 61. Of the 78 untreated patients, 38 were females, and the median age was 70 years old. The commonest primary diagnoses in both groups were lung (39%) and breast (21%) cancer. 16 (21%) of the untreated patients had an unbiopsied primary tumour. Median survival for patients having (any) treatment was 52 weeks compared to 5 weeks for those not having treatment. Conclusion We have presented an unbiased single-centre estimate of brain metastases occurrence. Unlike previous work, we manually reviewed all imaging reports that suggested metastasis, and included all patients diagnosed with brain metastases at any timepoint. We reduced the bias associated with being a tertiary centre by only including patients who were diagnosed here, rather than referred from other centres. 25% of our cohort received no treatment, and survival in this group is poor. This is broadly in line with the only other study on this topic (Bentley, 2019) that reported a large minority (39%) of untreated patients. Our key conclusions are: When assessing the incidence of brain metastases, studies that do not account for untreated patients are likely to significantly underestimate incidence, and over-estimate survival. Improving outcomes in patients with brain metastases might be best achieved by addressing earlier identification and intervention in those who currently receive no treatment

Proteomic analysis of genetically stratified low-grade meningioma

Aims Meningioma is the most common primary intracranial tumour. Although ~80% are benign WHO grade I and show high rates of recurrence. Surgery is the main therapeutic approach, yet location can hamper complete resection and chemotherapies are ineffective. Moreover, accurate biomarkers for clinical management are lacking. Approximately 60% sporadic meningiomas harbour mutations in the NF2gene, while mutations in genes including TRAF7, KLF4, AKT1, SMO and PIK3CAhave been identified majority in the NF2-positive low grade-tumours. Moreover, mutations in TRAF7 mostly co-occur with a KLF4K409Q or with AKT1E17K mutation. The mutations and their molecular manifestations consequently affect the signalling pathways at the protein level. The molecular mechanisms behind meningioma tumourigenesis are still obscure and the identification of specific biomarker is necessary to enable their implementation in routine diagnostics and therapeutics. Therefore, we aim to identify novel biomarkers and therapeutic targets of genetically stratified low-grade meningioma by characterising the proteomic landscape. Method Frozen tumour samples have already been analysed for NF2-/- by next generation sequencing and genotyped for common mutational hotspots in non-NF2 meningioma such as TRAF7, KLF4 and AKT1 and grouped in to three different mutational groups: AKT1E17K/TRAF7, KLF4K409Q/TRAF7and NF2-/- and all these mutations will be compared to normal healthy meninges. For global proteomics, proteins were separated by SDS-PAGE followed by in-gel tryptic digestion and sample preparation for LC-MS/MS analysis. Raw mass spectrometry data files were processed by MaxQuant (1.6.2.10) and Perseus software (1.6.1.3). Quantitative phospho-proteomics was performed using TMT 10plex labelling approach followed by motif analysis using motif-X algorithm. GO enrichment analyses were performed using (DAVID) v6.8 against all human proteins. Potential candidates from expression data analysis will be validated via Western Blot and immunohistochemistry. Results We have quantified 4162 proteins across all mutational meningioma subgroups and normal meninges (n=31). Hierarchical clustering analysis showed distinct proteomic profiles of mutational subgroups revealing clusters of differentially expressed proteins. Comparative analysis showed 10 proteins were commonly significantly upregulated (log2 fold-change≥1; p<0.05) among all mutational subtypes vs. normal meninges, indicating proteomic landscapes of mutational subtypes to be highly variable. In contrast, 257 proteins were commonly significantly downregulated (log2 fold-change≤-1; p<0.05) and enriched with molecular functions including aldehyde dehydrogenase and oxido-reductase. Mutational subtype-specific analysis identified 162 proteins significantly upregulated in AKT1E17K/TRAF7 vs. remaining sample groups to be enriched in the oxidative phosphorylation pathway. However, only 14 and 7 proteins were commonly significantly upregulated in KLF4K409Q/TRAF7 and NF2-/- mutant meningioma subtypes respectively. Several of these up-regulated proteins including ANNEXIN-3, CRABP2, CLIC3 and Endoglin were already verified via WB. Lastly, analyses of 6600 phospho-sites (n=8) predicted regulatory kinases including CHEK1, CHEK2 and LCK. Conclusion Global proteomic and phos-phoproteomics analysis has led to the identification of proteins differentially expressed in mutant subtypes. Results of this study to date suggest that a proteomic approach is an effective tool to identify distinct patterns in genetically distinct meningioma subgroups. Further validation and functional verification (with inhibitory or knockdown approaches) of potential candidates will allow us to identify potential drug targets/biomarkers for meningiomas.

Selection of headache cases for expedited scanning to assist prompt diagnosis of brain tumour

Aims Patients with brain tumours and headache commonly have poorer cognitive skills, either overtly or covertly, when cognitively tested. Cognitive changes reflect, tumour mass, fronto-temporal location or hydrocephalus, Previous work has demonstrated that the “semantic Verbal Fluency Test (SVFT) -“How many animals can you think of in a minute?” is a useful fast screening test for cognitive issues. Median SVFT in patients with brain tumour on admission is 10 animals. Most GPs can now order “direct access cerebral imaging (DACI)” in patients with headache suspicious of cancer. The waiting times for scanning can be many weeks. The aim of this study was to determine whether low SVFT scores: might be useful to help stratify or expedite DACI. We present data from referrals through and electronic Protocol Based Referral (PBR) pathway for CT scanning over 3 years, to determine whether SVFT might be a useful adjunct to history and examination. Method From 2017, in Edinburgh/Lothians, Scotland, an electronic PBR was developed with involvement of Primary Care Cancer Lead, PBR lead, Neurology, Neurosurgery and Neuro-Imaging for outpatient imaging of patients in the community with Headache Suspicious of Cancer, to expedite their scans. The PBR sat alongside the routine outpatient DACI system. If the forms were correctly filled in Neuro-Radiology prioritised their appointments. The referrer (GP) was asked to complete the ePBR form and SVFT at the time of referral. Other data were also gathered, including: Past Medical History of cancer; other symptoms/signs; and co-morbid conditions and medications filled automatically from the GP system. This formed the dataset. We also retrospectively assessed a) whether English was first language b) past history of Pain Clinic Attendance or Functional Illness and subsequent final diagnosis of headache/condition, through evaluation of electronic GP referral letters through SCI Gateway system of those cases where SVFT was recorded. Results Between March 2017 - November 2019, 669 scans through PBR pathway. (62% females; Mean age 53 years: 60% cases <60 years). SVFT was completed in only 381/669 (57%). Median SVFT was 17. Eleven of 381 cases had cancer (2.9%). 10 cases with cancer had SVFT <17 animals (median 10) (5.32%). One case had SVFT >=17 (35 animals) (0.5%) - CT scan showed small multiple intra-cerebral calcified and non-calcified lesions, consistent with metastases. 12% with PMH cancer had a tumour. Other possible reasons for low SVFT were: co-existing presumed dementia/mild cognitive impairment (19); non native English speakers (12); headache after traumatic brain injury (5); significant small vessel disease/vascular(5); intracranial cysts (4)(pineal / arachnoid, Giant Cell Arteritis (4) (all new - symptomatic); Chiari 1 malformations (2), PMH – encephalitis (1). Interestingly, there were 53 cases with known psychiatric/pain conditions on drugs (e.g. codeine/antidepressants/antipsychotics) with SVFT < 17 words/min. Conclusion People with Headache "Suspicious of Cancer" + SVFT <17 words in a minute are more likely to have a tumour (5.32% vs 0.5%) or other secondary cause for poor cognition. Other probable causes /associations, with SVFT <17 are age, poor English skills, co-existing dementia. SVFT score may be a useful adjunct or “red flag,” to consider, to expedite DACI scan in patients with “Headache Suspicious of Cancer”. A SVFT >=17 in those with Headache Suspicious of Cancer, does not exclude the possibility of an intracranial tumour. Excluding cases with recognised causes for low SVFT e.g. dementia and those with existing chronic pain/psychiatric disease further increases the likelihood of a secondary cause for headache. SVFT should be tested in the persons native language. A larger prospective study is required to establish whether these pilot study data and to examine whether chronic pain, functional neurology are negative predictive factors for secondary headache.

Prevalence of Hyponatremia in Neurosurgical Patients in South India – An Institution-Based Observational Study

BACKGROUND Hyponatremia is the most frequently encountered electrolyte abnormality in hospitalized patients, especially those with neurological injury. Acute onset hyponatremia is common in patients with any type of cerebral insult including traumatic brain injury (TBI), subarachnoid haemorrhage (SAH) and brain tumours. Also seen as a complication of intracranial procedures, contributing to increased morbidity and mortality. Early diagnosis and effective management can reduce mortality associated with this condition. This study was done to estimate the prevalence of hyponatremia in neurosurgical patients in our institution. METHODS This is an observational study that analysed the adult patients admitted to the neuro intensive care unit (ICU) after having undergone the neurosurgical procedure from January 2019 to July 2019. A structured questionnaire was used for data collection. The prevalence of hyponatremia was calculated with preoperative serum sodium levels in the study population. RESULTS In this study with 61 patients undergoing neurosurgical procedures, the prevalence of hyponatremia was 34.4 %. The majority of patients for surgery comes between 41 to 50 years. 57.4 % cases were with traumatic brain injury, 11.5 % cases were with sub arachnoid haemorrhage and 31.1 % were with intracranial tumour. 26 % of hyponatremia patients belonged to mild grade while 8 % to moderate grade. 62.5 % of patients above 70 years, 44.4 % of patients between 51 to 60 years and 40 % of patients between 61 and 70 years presented with mild hyponatremia. 37.5 % of patients above 70 years and 10 % of patients between 61 and 70 years presented with moderate hyponatremia. CONCLUSIONS Our study showed an increased prevalence of hyponatremia in neurosurgical patients which demand effective approaches for an accurate and timely diagnosis of this electrolyte disorder. Hyponatremia frequently occurs in patients with TBI, SAH and intracranial tumours. It is also essential to differentiate between syndrome of inappropriate antidiuretic hormone (SIADH) and cerebral salt wasting syndrome (CSW) as the treatment modalities are entirely different for these two entities. Early detection, close monitoring, etiological evaluation and prompt treatment based on aetiology can reduce the complications and improve patient’s outcomes. KEYWORDS Electrolyte Abnormality; Brain Injury, Morbidity

OPTC-1. Proteomic analysis of genetically stratified low-grade meningioma

Introduction Meningioma are the most common primary intracranial tumour. According to WHO, ~80% tumours are benign grade I. Although, some grade I tumour clinically show aggressive behaviour. Radio-surgery are the main therapeutic approaches, chemotherapies are ineffective. Accurate biomarkers for clinical management are lacking. The mutational profile of low-grade meningioma is well-defined, with non-NF2 mutated tumours harbouring recurrent mutations in genes including TRAF7, KLF4, AKT1 and SMO. Here, we aim to identify novel biomarkers and therapeutic targets of genetically stratified low-grade meningioma by characterising the proteomic landscape. Materials and methods Meningioma specimens were stratified according to mutational background: AKT1E17K/TRAF7, KLF4K409Q/TRAF7 and NF2-/-. Proteins were separated by SDS-PAGE followed by in-gel tryptic digestion and sample preparation for LC-MS/MS analysis. Raw mass spectrometry data files were processed by MaxQuant and Perseus software. Quantitative phospho-proteomics was performed using TMT-10plex labelling approach followed by motif analysis using motif-X algorithm. GO enrichment analyses were performed using DAVID against all human proteins. Results and Conclusions We have quantified 4162 proteins across all mutational meningioma subgroups and normal meninges (n=31). Hierarchical clustering analysis showed distinct proteomic profiles of mutational subgroups revealing clusters of differentially expressed proteins (DEPs). Comparative analysis showed 10 proteins were commonly significantly upregulated (log2 fold-change≥1; p<0.05) among all mutational subtypes vs. normal meninges, indicating proteomic landscapes of mutational subtypes to be highly variable. In contrast, 257 proteins were commonly significantly downregulated (log2 fold-change≤-1; p<0.05) and enriched with molecular functions including aldehyde dehydrogenase and oxido-reductase. Mutational subtype-specific analysis identified 162 proteins significantly upregulated in AKT1E17K/TRAF7 vs. remaining sample groups to be enriched in the oxidative phosphorylation pathway. Lastly, analyses of 6600 phospho-sites (n=8) predicted regulatory kinases including EGFR and PKCα. Several of these up-regulated proteins and kinases already verified via WB. Further validation and functional verification will allow us to identify potential drug targets/biomarkers for meningioma.

Concurrent chemoradiation in the management of newly diagnosed glioblastoma multiforme: Retrospective review of single center experience over a period of 10 years.

e14028 Background: Glioblastoma Multiforme (GBM) is the most common primary intracranial tumour of the brain. The standard of care first line management is maximum safe debulking followed by concurrent chemo radiation (Stupp et al, 2005). In spite of further recent advances, median survival still remains poor and ranges between 14 to 21 months, especially in the MGMT unmethylated group. There are no randomised trials investigating less than 6 cycles of adjuvant temozolomide (TMZ). In our study we retrospectively analyse the impact on overall survival (OS) and progression free survival (PFS) in cases where adjuvant treatment has been discontinued due to toxicity or patient’s fitness Methods: We collected data from 2007 to 2016 for a cohort of patients who underwent adjuvant treatment for GBM following histological diagnosis. The final analyses included patient’s who completed concurrent chemoradiotherapy to a dose of 60 Gray in 30 fractions and had at least one cycle of adjuvant TMZ chemotherapy Results: Of 110 patient cohorts, 57% of patients completed adjuvant chemo radiotherapy followed by 4-6 cycles of adjuvant TMZ, 43% received 3 or less cycles of TMZ. Overall PFS was 11.9 months. Those that completed 4 or more cycles of adjuvant TMZ had an improved PFS (Log rank test P-value 0.001) versus those that completed 3 or less cycles. On cox analysis the number of adjuvant cycles of TMZ significantly affects OS, P-value 0.0003. Median overall survival was 16 months for the whole group, but was 10 vs. 20 months for the two groups. On cox analysis we also identified second line chemotherapy had a significant impact on OS (cox model P-value 0.002) Conclusions: We identified patients receiving three or fewer cycles of adjuvant TMZ had poorer outcomes. Second-line chemotherapy improved outcomes at relapse regardless of redo surgery.

Central Neurocytoma in the Fourth Ventricle: Case Report and Literature Review

Background: Central neurocytoma is a rare primary intracranial tumour that usually occurs in young people. Central neurocytoma is more common in the lateral ventricle, but it is rare in the fourth ventricle. Herein, we report a case of central neurocytoma in the fourth ventricle. To improve our understanding, diagnosis, and treatment of this disease, we reviewed the literature to analyse the age, gender, clinical manifestations, imaging characteristics, and surgical prognosis of CNC in the fourth ventricle.Case presentation: A 44-year-old Chinese women presented with headache and dizziness for 8 years, walking instability for 2 years, and aggravation for 1 month. MRI revealed a 3.0 cm × 3.6 cm ×3.4 cm lesion located in the fourth ventricle. The tumour was completely resected. Pathological results were consistent with central neurocytoma. The patient could not walk or speak fluently during post-operative period, and no recurrence was found during the seventh month of follow-up.Conclusions: Central neurocytoma in the fourth ventricle is a rare intracranial tumour that is difficult to diagnose preoperatively. However, it can be considered when cystic and solid lesions are present in the fourth ventricle, especially when the morphology is like a soap bubble. Surgery is the main treatment for CNC. Adjuvant radiotherapy can be considered for partial or subtotal resection cases, and the prognosis is good. No recurrence of central neurocytoma in the fourth ventricle has been reported thus far.