Papers by Vasileios Apostolopoulos

Journal of Clinical Neuroscience, Sep 1, 2012
We report a rare occurrence of intracranial Rosai-Dorfman disease (RDD), in a young patient with ... more We report a rare occurrence of intracranial Rosai-Dorfman disease (RDD), in a young patient with multiple bilateral intracerebral lesions, and discuss her management. RDD is an histiocytic proliferative disorder, which seldom presents with intracranial pathology. Intraparenchymal RDD without concurrent systemic features is rare. This 31-year old woman presented with two focal seizures, but no peripheral lymphadenopathy, and no significant systemic abnormalities. Preoperative imaging showed intrinsic space-occupying lesions in the left frontal lobe, and right parietal and right inferior frontal white matter. She underwent excision of the peripherally located left frontal lesion, and aside from a five-day course of postoperative dexamethasone, received no further active treatment. Histopathological analysis revealed the characteristic features of RDD. Postoperative imaging, taken at 10 weeks and 12 months, demonstrated resolution of all three lesions. This patient had a rare multifocal, bilateral, intracerebral RDD, illustrating that although a histological diagnosis is necessary, further treatment may not be required.

Clinical Neurology and Neurosurgery, Apr 1, 2009
We present the case of an unexpected response by the cerebral vasculature to bypass surgery. A 66... more We present the case of an unexpected response by the cerebral vasculature to bypass surgery. A 66year-old man sustained a subarachnoid haemorrhage and cerebral angiography showed a large fusiform anterior communicating artery (ACoA) aneurysm and an anomalous anterior circulation. The right A1 segment was hypoplastic and blood supply to the entire right A2 was from the left anterior circulation via the ACoA. The aneurysm was therefore not amenable to endovascular coiling or surgical clipping alone. An extracranial-intracranial bypass was performed to revascularize the territory of the right A2 independently of the ACoA to allow the latter vessel to be clipped. Although the bypass graft was patent on post-operative cerebral angiography, it was in fact only perfusing a limited, peripheral anterior cerebral artery territory. The bulk of the right anterior circulation was derived retrogradely by latent collaterals from the internal carotid and ophthalmic arteries via small dural vessels which were not apparent prior to surgery.

BMJ Open
IntroductionSurgery remains the mainstay for treatment of primary glioblastoma, followed by radio... more IntroductionSurgery remains the mainstay for treatment of primary glioblastoma, followed by radiotherapy and chemotherapy. Current standard of care during surgery involves the intraoperative use of image-guidance and 5-aminolevulinic acid (5-ALA). There are multiple other surgical adjuncts available to the neuro-oncology surgeon. However, access to, and usage of these varies widely in UK practice, with limited evidence of their use. The aim of this trial is to investigate whether the addition of diffusion tensor imaging (DTI) and intraoperative ultrasound (iUS) to the standard of care surgery (intraoperative neuronavigation and 5-ALA) impacts on deterioration free survival (DFS).Methods and analysisThis is a two-stage, randomised control trial (RCT) consisting of an initial non-randomised cohort study based on the principles of the IDEAL (Idea, Development, Exploration, Assessment and Long-term follow-up) stage-IIb format, followed by a statistically powered randomised trial compari...

Neuro-Oncology
AIMS Despite evidence of correspondence with intraoperative stimulation, there remains limited da... more AIMS Despite evidence of correspondence with intraoperative stimulation, there remains limited data on MRI diffusion tractography (DT)’s sensitivity to predict morbidity after brain tumour resection. Our aims were: (1) evaluate DT against subcortical stimulation mapping and performance changes during and following awake surgery; (2) evaluate the use of early post-operative DT to predict recovery from post-surgical deficits. METHOD We performed a retrospective review our first 100 awake neurosurgery procedures using DTneuronavigation. Intra-operative stimulation and performance outcomes were assessed to classify DT predictions for sensitivity and specificity calculations. RESULTS Between 2014 and 2019 a total of 91 adult brain tumour patients (mean age 49.2 years) underwent 100 awake surgeries with subcortical stimulation. The sensitivity and specificity of pre-operative DT predictions were 92.2% and 69.2%, varying among tracts. Post-operative deficits occurred after 41 procedures (3...

Oxford Textbook of Neurological Surgery
Intraventricular tumours are relatively rare, histologically diverse, and commonly low grade. The... more Intraventricular tumours are relatively rare, histologically diverse, and commonly low grade. The location of the tumour, MRI features, associated conditions, and the age of the patient help to narrow the radiological differential diagnosis. The management of intraventricular tumours needs to be tailored to the presumed nature of the tumour, its location, size, and the general state of the patient. The management of hydrocephalus is often the first priority. Radical excision of intraventricular tumours is usually favoured for younger patients, whereas subtotal excisions or even just cerebrospinal fluid (CSF) diversion is favoured for older patients with tumours which are less accessible. Excision of tumours, usually ependymomas originating from the floor of the fourth ventricle may be associated with significantly disabling postoperative deficit with can frequently but not always improve over a period of time. As always in brain tumour surgery, balancing radical excision and overall...

Spine, Sep 1, 2009
Case Report. To share our experience about the unique histological appearances of a calcified int... more Case Report. To share our experience about the unique histological appearances of a calcified intradural, extramedullary lesion involving a nerve root. A 53-year-old man presented with a long history of low back pain and a few months of occasional left groin pain with no neurological deficit. Imaging of the spine revealed a calcified intradural extramedullary lesion at L1, separate from vertebrae. Intraoperatively, the lesion was found to involve closely one of the roots and was heavily calcified but relatively easy to excise. The histology revealed calcifying fibroblastic proliferation associated with a nerve root. This is an unusual pathological entity, which appears distinct from the rare but occasionally reported reactive process known, as heterotopic bone formation in a nerve or "neuritis ossificans," and it is important to distinguish it from other calcified intradural neoplasms. The histology of an excised calcified intradural extramedullary lesion was initially reviewed by our local neuropathologist. A second opinion was requested from Prof. Malcolm, who is a histopathologist and bone specialist. The unique histological features of the lesion were confirmed. The literature (no date limitations) was reviewed. A calcified intradural extramedullary lesion, closely related to nerve root was found to have unique histological features, not reported in the literature so far. The histological features of the calcified lesion that we report here have not been described before. It is highly likely they represent a reactive process. We think these features are useful to be added to the differential diagnosis of a calcified intradural extramedullary lesion involving a nerve root.

Neuro-Oncology Advances, 2022
Background Elderly patients with glioblastoma are perceived to face a poor prognosis with percept... more Background Elderly patients with glioblastoma are perceived to face a poor prognosis with perceptions surrounding older age and a relative lack of randomized data contributing. This study evaluated survival prognosticators in elderly glioblastoma patients to more accurately guide their treatment. Materials and methods The records of 169 elderly (≥70 years) patients with a new diagnosis of glioblastoma who had undergone neurosurgical intervention were retrospectively examined for patient sex, age, performance status, comorbidities, MGMT promoter methylation, surgical intervention and chemoradiation regime. The adjusted survival impact of these factors was determined using Cox proportional hazards model and used to devise a two-stage scoring system to estimate patient survival at the stage of surgical (Elderly Glioblastoma Surgical Score, EGSS) and oncological management (Elderly Glioblastoma Oncological Score, EGOS). Results The median overall survival (mOS) of the cohort was 28.8 we...

Journal of Clinical Neuroscience, 2012
We report a rare occurrence of intracranial Rosai-Dorfman disease (RDD), in a young patient with ... more We report a rare occurrence of intracranial Rosai-Dorfman disease (RDD), in a young patient with multiple bilateral intracerebral lesions, and discuss her management. RDD is an histiocytic proliferative disorder, which seldom presents with intracranial pathology. Intraparenchymal RDD without concurrent systemic features is rare. This 31-year old woman presented with two focal seizures, but no peripheral lymphadenopathy, and no significant systemic abnormalities. Preoperative imaging showed intrinsic space-occupying lesions in the left frontal lobe, and right parietal and right inferior frontal white matter. She underwent excision of the peripherally located left frontal lesion, and aside from a five-day course of postoperative dexamethasone, received no further active treatment. Histopathological analysis revealed the characteristic features of RDD. Postoperative imaging, taken at 10 weeks and 12 months, demonstrated resolution of all three lesions. This patient had a rare multifocal, bilateral, intracerebral RDD, illustrating that although a histological diagnosis is necessary, further treatment may not be required.

Journal of Clinical Neuroscience, 2012
We report a rare occurrence of intracranial Rosai-Dorfman disease (RDD), in a young patient with ... more We report a rare occurrence of intracranial Rosai-Dorfman disease (RDD), in a young patient with multiple bilateral intracerebral lesions, and discuss her management. RDD is an histiocytic proliferative disorder, which seldom presents with intracranial pathology. Intraparenchymal RDD without concurrent systemic features is rare. This 31-year old woman presented with two focal seizures, but no peripheral lymphadenopathy, and no significant systemic abnormalities. Preoperative imaging showed intrinsic space-occupying lesions in the left frontal lobe, and right parietal and right inferior frontal white matter. She underwent excision of the peripherally located left frontal lesion, and aside from a five-day course of postoperative dexamethasone, received no further active treatment. Histopathological analysis revealed the characteristic features of RDD. Postoperative imaging, taken at 10 weeks and 12 months, demonstrated resolution of all three lesions. This patient had a rare multifocal, bilateral, intracerebral RDD, illustrating that although a histological diagnosis is necessary, further treatment may not be required.

Journal of Neuro-Oncology
Introduction Despite evidence of correspondence with intraoperative stimulation, there remains li... more Introduction Despite evidence of correspondence with intraoperative stimulation, there remains limited data on MRI diffusion tractography (DT)’s sensitivity to predict morbidity after neurosurgical oncology treatment. Our aims were: (1) evaluate DT against subcortical stimulation mapping and performance changes during and after awake neurosurgery; (2) evaluate utility of early post-operative DT to predict recovery from post-surgical deficits. Methods We retrospectively reviewed our first 100 awake neurosurgery procedures using DT- neuronavigation. Intra-operative stimulation and performance outcomes were assessed to classify DT predictions for sensitivity and specificity calculations. Post-operative DT data, available in 51 patients, were inspected for tract damage. Results 91 adult brain tumor patients (mean 49.2 years, 43 women) underwent 100 awake surgeries with subcortical stimulation between 2014 and 2019. Sensitivity and specificity of pre-operative DT predictions were 92.2% a...

Experience in the management of COVID-19 vaccine induced thrombosis and thrombocytopenia is curre... more Experience in the management of COVID-19 vaccine induced thrombosis and thrombocytopenia is currently lacking. In this case series we report the presentation and our experience in the management of cerebral venous sinus thrombosis and thrombocytopenia post ChAdOx1 nCoV-19 vaccination. Two of the three cases had confirmed anti-platelet factor 4 antibodies and extracranial thrombosis. In all the cases, plasma exchange, intravenous immunoglobulins and steroids normalised the platelet count and intravenous argatroban was used for initial anticoagulation. Two cases received a platelet transfusion and required decompressive hemicraniectomy due to raised intracranial pressure, secondary to cerebral oedema and haemorrhage. Prompt assessment of a new persistent headache occurring between 5 and 28 days of receiving the ChAdOx1 nCoV-19 vaccine is warranted irrespective of age. In cases with venous thrombosis on imaging or abnormal laboratory findings (thrombocytopenia, abnormal clotting or ele...

American Journal of Respiratory and Critical Care Medicine
Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown d... more Rationale: Although early antimicrobial discontinuation guided by procalcitonin (PCT) has shown decreased antibiotic consumption in lower respiratory tract infections, the outcomes in long-term sepsis sequelae remain unclear. Objectives: To investigate if PCT guidance may reduce the incidence of long-term infection-associated adverse events in sepsis. Methods: In this multicenter trial, 266 patients with sepsis (by Sepsis-3 definitions) with lower respiratory tract infections, acute pyelonephritis, or primary bloodstream infection were randomized (1:1) to receive either PCT-guided discontinuation of antimicrobials or standard of care. The discontinuation criterion was ≥80% reduction in PCT levels or any PCT ≤0.5 μg/L at Day 5 or later. The primary outcome was the rate of infection-associated adverse events at Day 180, a composite of the incidence of any new infection by Clostridioides difficile or multidrug-resistant organisms, or any death attributed to baseline C. difficile or multidrug-resistant organism infection. Secondary outcomes included 28-day mortality, length of antibiotic therapy, and cost of hospitalization. Measurements and Main Results: The rate of infection-associated adverse events was 7.2% (95% confidence interval [CI], 3.8–13.1%; 9/125) versus 15.3% (95% CI, 10.1–22.4%; 20/131) (hazard ratio, 0.45; 95% CI, 0.20–0.98; P = 0.045); 28-day mortality 15.2% (95% CI, 10–22.5%; 19/125) versus 28.2% (95% CI, 21.2–36.5%; 37/131) (hazard ratio, 0.51; 95% CI, 0.29–0.89; P = 0.02); and median length of antibiotic therapy 5 (range, 5–7) versus 10 (range, 7–15) days (P < 0.001) in the PCT and standard-of-care arms, respectively. The cost of hospitalization was also reduced in the PCT arm. Conclusions: In sepsis, PCT guidance was effective in reducing infection-associated adverse events, 28-day mortality, and cost of hospitalization. Clinical trial registered with www.clinicaltrials.gov (NCT03333304).
DECLARATION OF ORIGINALITY 'I Vasileios Apostolopoulos confirm that the work presented in this th... more DECLARATION OF ORIGINALITY 'I Vasileios Apostolopoulos confirm that the work presented in this thesis is my own. Where information has been derived from other sources, I confirm that this has been indicated in the thesis'.

NeuroImage: Clinical
The occurrence of wide-scale neuroplasticity in the injured human brain raises hopes for biomarke... more The occurrence of wide-scale neuroplasticity in the injured human brain raises hopes for biomarkers to guide personalised treatment. At the individual level, functional reorganisation has proven challenging to quantify using current techniques that are optimised for population-based analyses. In this cross-sectional study, we acquired functional MRI scans in 44 patients (22 men, 22 women, mean age: 39.4 ± 14 years) with a language-dominant hemisphere brain tumour prior to surgery and 23 healthy volunteers (11 men, 12 women, mean age: 36.3 ± 10.9 years) during performance of a verbal fluency task. We applied a recently developed approach to characterise the normal range of functional connectivity patterns during task performance in healthy controls. Next, we statistically quantified differences from the normal in individual patients and evaluated factors driving these differences. We show that the functional connectivity of brain regions involved in language fluency identifies &quot;fingerprints&quot; of brain plasticity in individual patients, not detected using standard task-evoked analyses. In contrast to healthy controls, patients with a tumour in their language dominant hemisphere showed highly variable fingerprints that uniquely distinguished individuals. Atypical fingerprints were influenced by tumour grade and tumour location relative to the typical fluency-activated network. Our findings show how alterations in brain networks can be visualised and statistically quantified from connectivity fingerprints in individual brains. We propose that connectivity fingerprints offer a statistical metric of individually-specific network organisation through which behaviourally-relevant adaptations could be formally quantified and monitored across individuals, treatments and time.
Quantitative Imaging in Medicine and Surgery
Ganau et al. Real-time intraoperative ultrasound in brain surgery qims.amegroups.com Ganau et al.... more Ganau et al. Real-time intraoperative ultrasound in brain surgery qims.amegroups.com Ganau et al. Real-time intraoperative ultrasound in brain surgery
Frontiers in Cellular Neuroscience
Neuro-Oncology
PCA/LDA was performed. Most easily identified tumors include meningiomas and metastases. Low grad... more PCA/LDA was performed. Most easily identified tumors include meningiomas and metastases. Low grade and high grade gliomas were also identified with high accuracy. CONCLUSIONS: Raman spectroscopy represents a new modality for in-vivo tissue characterisation with high accuracy. Our study demonstrates it can correctly characterise a range of different types of brain tumors rapidly during surgery. Current challenges to more widespread adoption include the modifications necessary for it to work in the OR and patient-patient and machine-machine variability.

Journal of Therapeutic Ultrasound
Background: There is growing evidence that maximal surgical resection of primary intrinsic brain ... more Background: There is growing evidence that maximal surgical resection of primary intrinsic brain tumours is beneficial, both by improving progression free and overall survival and also by facilitating postoperative chemotherapy and radiotherapy. Hence, there has been an increase in the popularity of real-time intraoperative imaging in brain tumour surgery. The complex theatre arrangements, prohibitive cost and prolonged theatre time of intraoperative MRI have restricted its application. By comparison, intraoperative three-dimensional ultrasound (i3DUS) is user friendly, cost-effective and portable and adds little to surgical time. However, operator-dependent image quality and image interpretation remain limiting factors to the wider application of this technique. The aim of this study was to explore objective i3DUS image analysis and its potential therapeutic role in brain tumour surgery. Methods: A prospective, observational study was undertaken (approved by the local Research and Ethics Committee prior to recruitment). Biopsies were taken from the solid, necrotic, periphery and brain/tumour interface of intrinsic primary brain tumours. Digital i3DUS images were analysed to extract quantitative parameters from these regions of interest (ROI) in the i3DUS images. These were then correlated with the histology of the relevant specimens. The histopathologist was blinded to the imaging findings. Results: Ninety-seven patients (62 males; mean 54 years) with varying gliomas (84 high grade) were included. Two hundred and ninety regions of interest were analysed. Mean pixel brightness (MPB) and standard deviation (SD) were correlated with histological features. Close correlations were noted between MPB and cellularity, and SD and intrinsic cellular diversity. Conclusions: MPB and SD are objective measures reflecting the sensitivity of i3DUS in detecting the presence and extent of intrinsic brain tumours. They indirectly suggest heterogeneity, cellularity and invasiveness, providing information of the nature of the tumour, and also reflect the sensitivity of intraoperative US to detect the presence of residual intrinsic brain tumours. Development of this paradigm will enhance i3DUS use as an adjunct in brain tumour surgery. Optimizing its intraoperative application will impact surgical resection and, hence, patient outcome.
Uploads
Papers by Vasileios Apostolopoulos