Endovascular treatment of cerebral aneurysm: early experience in a Malaysian tertiary centre

Universiti Kebangsaan Malaysia Medical Center (UKMMC) started neurointerventional service in August 2008. In this study, we aimed to evaluate the immediate and short term outcome of endovascular treatment (EVT) of cerebral aneurysm during early period of the services. A retrospective study for cerebral aneurysm treated by endovascular technique, from the Neurosurgical and Radiology Department from September 2008 till February 2010 was performed. Patient's demographic data, initial clinical presentation and assessment of the aneurysm were performed. The immediate results and short term assessment post EVT were evaluated based on standard criteria. Recurrence and complications during and following EVT procedures, were recorded. Twenty one patients with total of 22 aneurysms were treated. The mean age was 54.52 years with 57 being males and 43 females. The majority (81) had single aneurysm. The most common site was anterior communicating artery (28 ). Mean aneurysm sac size was 6.19 mm and 2.55 mm for aneurysm neck. At follow-up, 3 (27.2) had a small residual neck. Four patients (37.2) had residual aneurysm filling, but three of them were treated with stent aiming to achieve flow diversion effect instead of complete occlusion during initial treatment. There was no rebleed or rupture from the immediate to follow-up. Significant complications up to 30-days was observed in 4 patients (20) whereby 2 patients showed improvement and 2 patients died (10 mortality rate). Endovascular treatment of cerebral aneurysms performed in our centre had early outcome, morbidity and mortality compared to other higher volume centres. Longer term follow up is needed to evaluate the long termoutcome/occlusion rate, morbidity and mortality

Identification of missense mutations in genes related to cancer pathways in glioma

Glioma is the most common primary brain tumour of the central nervous system. Many genetic alterations and mutations have been identified in glioma using various approaches. We performed DNA sequencing on the tumours of 16 patients with Grade I, II, III and IV glioma. The AmpliSeq Cancer Primers Pool was used to generate the amplicons. The targeted-ion sphere particles were prepared using the Ion One Touch and Ion Enrichment systems. DNA sequencing was performed on the Ion Torrent Personal Genome Machine (PGM) and the data were analysed using the Torrent Suite Software. In total, 14 mutations were identified in the following genes: KDR (Q472H), MLH1 (V384D), MET (N375S), PTPN11 (E69K), BRAF (V600E), TP53 (D149E, E154K, V157F), IDH1 (R132H), PIK3CA (H1047R), CSF1R (c1061_1061 ins A), KIT (M541L), PTEN (c1373_1373 del A) and PDGFRA (E556V). In addition, there were four novel mutations identified; TP53 (E154K, and D149E), CSF1R (c1061_1061 ins A) and PDGFRA (E556V). The pathogenicity prediction showed that only three mutations were pathogenic: PTPN11 (E69K), BRAF (V600E) and Tp53 (E154K). These mutations result in changes of the proteins’ structure and could affect their functions. Pathway analyses suggested that these genes are closely related to the pathogenesis of GBM through several pathways such as proliferation and invasion, metabolism and angiogenesis. In conclusion, PGM in combination with the AmpliSeq Cancer Panel could be utilised as a potential molecular diagnostic tool not only for glioma but also for other cancers

Tranexamic acid to improve functional status in adults with spontaneous intracerebral haemorrhage: the TICH-2 RCT

BACKGROUND: Tranexamic acid reduces death due to bleeding after trauma and postpartum haemorrhage. OBJECTIVE: The aim of the study was to assess if tranexamic acid is safe, reduces haematoma expansion and improves outcomes in adults with spontaneous intracerebral haemorrhage (ICH). DESIGN: The TICH-2 (Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage) study was a pragmatic, Phase III, prospective, double-blind, randomised placebo-controlled trial. SETTING: Acute stroke services at 124 hospitals in 12 countries (Denmark, Georgia, Hungary, Ireland, Italy, Malaysia, Poland, Spain, Sweden, Switzerland, Turkey and the UK). PARTICIPANTS: Adult patients (aged ≥ 18 years) with ICH within 8 hours of onset. EXCLUSION CRITERIA: Exclusion criteria were ICH secondary to anticoagulation, thrombolysis, trauma or a known underlying structural abnormality; patients for whom tranexamic acid was thought to be contraindicated; prestroke dependence (i.e. patients with a modified Rankin Scale [mRS] score > 4); life expectancy  4.5 hours after stroke onset. Pragmatic inclusion criteria led to a heterogeneous population of participants, some of whom had very large strokes. Although 12 countries enrolled participants, the majority (82.1%) were from the UK. CONCLUSIONS: Tranexamic acid did not affect a patient's functional status at 90 days after ICH, despite there being significant modest reductions in early death (by 7 days), haematoma expansion and SAEs, which is consistent with an antifibrinolytic effect. Tranexamic acid was safe, with no increase in thromboembolic events. FUTURE WORK: Future work should focus on enrolling and treating patients early after stroke and identify which participants are most likely to benefit from haemostatic therapy. Large randomised trials are needed. TRIAL REGISTRATION: Current Controlled Trials ISRCTN93732214. FUNDING: This project was funded by the National Institute for Health Research Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 23, No. 35. See the NIHR Journals Library website for further project information. The project was also funded by the Pragmatic Trials, UK, funding call and the Swiss Heart Foundation in Switzerland

Tranexamic acid for hyperacute primary IntraCerebral Haemorrhage (TICH-2): an international randomised, placebo-controlled, phase 3 superiority trial

BackgroundTranexamic acid (TXA) reduces death due to bleeding after trauma and post-partum haemorrhage. The aim was to assess if tranexamic acid reduces haematoma expansion and improves outcome in adults with stroke due to intracerebral 6 haemorrhage (ICH). MethodsWe undertook an international, randomised placebo-controlled trial in adults with intracerebral haemorrhage. Participants received 1g intravenous tranexamic acid bolus followed by an 8 hour 1g infusion, or matching placebo, within 8 hours of symptom onset. The primary outcome was functional status at day 90, measured by shift in the modified Rankin Scale (mRS), using ordinal logistic regression, with adjustment for stratification and minimisation criteria. All analyses were performed on an intention to treat basis. This trial is registered as ISRCTN93732214.FindingsWe recruited 2,325 participants (TXA 1161, placebo 1164) from 124 hospitals in 12 countries between 2013 and 2017. Treatment groups were well balanced at baseline. The primary outcome was determined for 2307 (99·2%) participants. There was no statistically significant difference between the groups for the primary outcome of functional status at day 90 (adjusted odds ratio [aOR] 0·88, 95% CI 0·76-1·03, p=0·11). Although there were fewer deaths by day 7 in the TXA group (aOR 0·73, 95% CI 0·53-0·99, p=0·0406), there was no difference in case fatality at 90 days (adjusted hazard ratio 0·92, 95% CI 0·77 to 1·10, p =0·37). There were fewer serious adverse events after TXA vs. placebo by days 2 (p=0·0272), 7 (p=0·0200) and 90 (p=0·0393).InterpretationThere was no significant difference in functional status 90 days after intracerebral haemorrhage with tranexamic acid, despite a reduction in early deaths and serious adverse events. Larger randomised trials are needed to confirm or refute a clinically significant treatment effect

What Lurks Beneath: Lacrimal Gland Adenocarcinoma Dedifferentiation to Sarcomatoid Carcinoma

This was a case of a young lady presenting with 10 year history of a mass in the right eye. It was found to be an adenocarcinoma of the lacrimal gland from histopathological biopsy. She underwent wide excision, orbital exenteration and reconstruction with a free rectus abdominis flap. Unfortunately, she had a tumour recurrence which was not controlled by radiotherapy and a second excision. The behavior of the tumour was aggressive, resulting in widespread metastases. She passed away within a year of her presentation. Of note, the histopathology report from the second excision turned out to be sarcomatoid carcinoma. This is described in the literature as dedifferentiation, or high grade transformation (HGT). Occurrence of dedifferentiation in salivary gland tumours is well-established, but not as well-described in lacrimal gland tumours. In this case, there was a severely delayed presentation of a lacrimal gland adenocarcinoma in a young person, which underwent dedifferentiation into a sarcomatoid carcinoma. This phenomena is associated with aggressive tumour biology behavior and poor prognosis, despite surgery and radiotherapy

Olfactory and gustatory outcomes following endoscopic transsphenoidal hypophysectomy

Abstract Objective The aim of this study was to evaluate olfactory, gustatory, and quality-of-life outcomes in patients who underwent endonasal transsphenoidal hypophysectomy. Methods In this prospective study, the patients were assessed subjectively using the Malay version of sQOD-NS (short questionnaire of olfactory disorders in a negative statement) and objectively using the culturally adapted Sniffin’ Sticks smell test and taste test preoperatively and 3 months postoperatively. The Sniffin’ Sticks smell test consists of odor identification, odor discrimination, and odor threshold tests. The taste test consists of different sweet, salt, sour, and bitter concentrations. Results Twenty patients were enrolled in the study. The study comprises 45% female and 55% male. On average patients’ ages were 49.5 years. In this study we found a significantly reduced in odor identification score (p = 0.049) post-surgery; however, there was no statistically significant difference in odor threshold, odor discrimination, and taste. The olfactory quality of life outcome based on the Malay version of sQOD-NS (p = 0.001) was significantly reduced after surgery. There was no significant difference in the Sniffin’ Sticks smell test (p < 0.178) and taste test (p < 0.425) pre-surgery and post-surgery. The tumor’s location, either sellar or suprasellar, did not influence the smell outcome of patients postoperatively (p = 0.056). Conclusion The study showed that the endoscopic transsphenoidal technique for pituitary surgery does not pose permanent olfactory disability

Isolated Intrasellar Pituitary Mucocele

Mucous cyst or mucocele are epithelial lined cavities containing mucous that occurs mainly in the frontal and ethmoid sinuses. Intracranial mucocele is a rare occurrence. We are presenting an interesting case of a young lady, presented with fainting spells, syncopal attack, recurrent frontal headache and blurring of vision for at least 2 months prior to presentation to us. CT scan showed shows a hyperdense mass arising from the tuberculum sellae with no foci of calcification within and no erosion of the adjacent bony structures. The intrasellar mucocele was diagnosed following surgery via trans-sphenoidal approach and biopsy with confirmatory histopathology

Safety and Use of MLC601/MLC901 (NeuroAiDTM) in Primary Intracerebral Hemorrhage: A Cohort Study from the NeuroAiD Safe Treatment Registry

Background: MLC601/MLC901 (NeuroAiD&trade;) is a combination of natural products shown to be safe and to aid neurological recovery after brain injuries, especially ischemic stroke. Few studies have investigated NeuroAiD in primary intracerebral hemorrhage (ICH). The NeuroAiD Safe Treatment (NeST) Registry explores NeuroAiD use in the real-world setting. This cohort study aimed to assess its use and safety in ICH. Methods: The online NeST Registry of subjects with ICH given NeuroAiD prospectively collected clinical data at baseline and monthly visits (V) 1 to 3. Outcome measures included compliance, side effects, Glasgow Coma Scale (GCS), National Institutes of Health Stroke Scale (NIHSS), modified Rankin Scale (mRS), and Short Orientation-Memory-Concentration Test (SOMCT). Results: Sixty-six subjects were included. NeuroAiD was well-tolerated with fair compliance over three months. Two non-serious side effects were reported. Mean scores significantly improved on all outcome scales. The proportion of subjects with favorable outcomes significantly improved from baseline to V3: NIHSS 0&ndash;4, from 12% to 59% (p &lt; 0.0001); GCS 13&ndash;15, from 64% to 88% (p = 0.007); mRS 0&ndash;1, from 9% to 37% (p = 0.004); and SOMCT score 0&ndash;8, from 44% to 68% (p = 0.029). Conclusions: NeuroAiD in the real-world setting was safe and showed potential for a sustained positive effect on neurological recovery after ICH

Effects of Different Scan Duration on Brain Effective Connectivity among Default Mode Network Nodes

Background: Resting-state functional magnetic resonance imaging (rs-fMRI) can evaluate brain functional connectivity without requiring subjects to perform a specific task. This rs-fMRI is very useful in patients with cognitive decline or unable to respond to tasks. However, long scan durations have been suggested to measure connectivity between brain areas to produce more reliable results, which are not clinically optimal. Therefore, this study aims to evaluate a shorter scan duration and compare the scan duration of 10 and 15 min using the rs-fMRI approach. Methods: Twenty-one healthy male and female participants (seventeen right-handed and four left-handed), with ages ranging between 21 and 60 years, were recruited. All participants underwent both 10 and 15 min of rs-fMRI scans. The present study evaluated the default mode network (DMN) areas for both scan durations. The areas involved were the posterior cingulate cortex (PCC), medial prefrontal cortex (mPFC), left inferior parietal cortex (LIPC), and right inferior parietal cortex (RIPC). Fifteen causal models were constructed and inverted using spectral dynamic causal modelling (spDCM). The models were compared using Bayesian Model Selection (BMS) for group studies. Result: The BMS results indicated that the fully connected model was the winning model among 15 competing models for both 10 and 15 min scan durations. However, there was no significant difference in effective connectivity among the regions of interest between the 10 and 15 min scans. Conclusion: Scan duration in the range of 10 to 15 min is sufficient to evaluate the effective connectivity within the DMN region. In frail subjects, a shorter scan duration is more favourable

Mitochondrial DNA Mutations in Grade II and III Glioma Cell Lines Are Associated with Significant Mitochondrial Dysfunction and Higher Oxidative Stress

The role of mitochondria in tumorigenesis has regained much attention as it could dysregulate cellular energetics, oxidative stress and apoptosis. However, the role of mitochondria in different grade gliomasis still unknown. This study aimed to identify mitochondrial DNA (mtDNA) sequence variations that could possibly affect the mitochondrial functions and also the oxidative stress status. Three different grades of human glioma cell lines and a normal human astrocyte cell line were cultured in-vitro and tested for oxidative stress biomarkers. Relative oxidative stress level, mitochondria activity, and mitochondrial mass were determined by live cell imaging with confocal laser scanning microscope using CM-H2DCFDA, MitoTracker Green, and MitoTracker Orange stains. The entire mitochondrial genome was sequenced using the AffymetrixGeneChip Human Mitochondrial Resequencing Array 2.0. The mitochondrial sequence variations were subjected to phylogenetic haplogroup assessment and pathogenicity of the mutations were predicted using pMUT and PolyPhen2. The Grade II astrocytoma cells showed increased oxidative stress wherea high level of 8-OHdG and oxidative stress indicator were observed. Simultaneously, Grade II and III glioma cells showed relatively poor mitochondria functions and increased number of mutations in the coding region of the mtDNA which could be due to high levels of oxidative stress in these cells. These non-synonymous mtDNA sequence variations were predicted to be pathogenic and could possibly lead to protein dysfunction, leading to oxidative phosphorylation (OXPHOS) impairment, mitochondria dysfunction and could create a vicious cycle of oxidative stress. The Grade IV cells had no missense mutation but preserved intact mitochondria and excellent antioxidant defense mechanisms thus ensuring better survival. In conclusion, Grade II and III glioma cells demonstrated coding region mtDNA mutations, leading to mitochondrial dysfunction and higher oxidative stress