Evaluating the utility of quantitative pupillometry in a neuro-critical care setting for the monitoring of intracranial pressure: A prospective cohort study.

INTRODUCTION: Assessment of the pupillary light reflex (PLR) is key in intensive care monitoring of neurosurgical patients, particularly for monitoring intracranial pressure (ICP). Quantitative pupillometry using a handheld pupillometer is a reliable method for PLR assessment. However, many variables are derived from such devices. We therefore aimed to assess the performance of these variables at monitoring ICP. METHODS: Sedated patients admitted to neurocritical care in a tertiary neurosurgical centre with invasive ICP monitoring were included. Hourly measurement of ICP, subjective pupillometry (SP) using a pen torch device, and quantitative pupillometry (QP) using a handheld pupillometer were performed. RESULTS: 561 paired ICP, SP and QP pupillary observations from nine patients were obtained (1122 total pupillary observations). SP and QP had a moderate concordance for pupillary size (κ=0.62). SP performed poorly at detecting pupillary size changes (sensitivity=24%). In 40 (3.6%) observations, SP failed to detect a pupillary response whereas QP did. Moderate correlations with ICP were detected for maximum constriction velocity (MCV), dilation velocity (DV), and percentage change in pupillary diameter (%C). Discriminatory ability at an ICP threshold of >22 mmHg was moderate for MCV (AUC=0.631), DV (AUC=0.616), %C (AUC=0.602), and pupillary maximum size (AUC=0.625). CONCLUSION: QP is superior to SP at monitoring pupillary reactivity and changes to pupillary size. Although effect sizes were moderate to weak across assessed variables, our data indicates MCV and %C as the most sensitive variables for monitoring ICP. Further study is required to validate these findings and to establish normal range cut-offs for clinical use.

Tumour treating fields in glioblastoma: is the treatment tolerable, effective, and practical in UK patients?

BACKGROUND: Tumour Treating Fields (TTF) in combination with standard therapy, prolongs survival in patients with glioblastoma (GBM). The aim of the current study was to assess the feasibility of integrating TTF into a standard UK neuro-oncology service with a focus on patient tolerability, compliance, and treatment delivery. METHODS: A prospective study was performed of UK patients with IDH 1 Wild Type, MGMT Unmethylated GBM treated with TTF, in conjunction with conventional therapy. Patient compliance data, device-specific tolerability questions, and an evaluation of disease progression and survival were collected. Monthly quality of life (QoL) questionnaires (EORTC QLQ-C30 with BN-20) examined the trend of global health, psychosocial function, and symptom progression. RESULTS: Nine patients were enrolled with a median age of 47 (seven males; two females). Overall, compliance with TTF was 89% (range 16-97%). Only one patient failed to comply with treatment. Patients tolerated the device with minimal side effects. Eight patients described mild to moderate skin irritation, whilst all patients were keen to recommend the device to other patients (100%). Most patients found the weight and size of the device to be its biggest drawback (72%). Progression-free survival was 5.5 months and median overall survival was 14.9 months. CONCLUSIONS: TTF was well-tolerated amongst a small cohort of UK patients, who were able to comply with treatment without any significant complication. QoL questionnaires showed no sustained deterioration in global health, physical and emotional function until the final months of life when the disease burden was greatest.

Vascular Ehlers-Danlos Syndrome: Literature review and surgical management of intracranial vascular complications.

Vascular Ehlers-Danlos (vEDS) is a rare form of the Ehlers-Danlos Syndrome (EDS) where arterial fragility results from mutations in the gene that encodes type III collagen. The disease can lead to major neurological complications including carotico-cavernous fistulae (CCF), aneurysms of the Circle of Willis and endovascular procedures have an increased risk profile due to the delicate vasculature. Management of intracranial disease in vEDS requires an intricate understanding of the syndrome but is still associated with significant complications that lead to morbidity and mortality. As well as providing an approach to the management of neurovascular complications in vEDS, the relevant literature regarding nosology, aetiology and genetics of the condition is summarised here. Particular emphasis is placed on the two most common intracranial complications, namely carotico-cavernous fistulas and and cerebral aneurysms. Pros and cons of surgical and endovascular interventions are discussed and a technical discussion is concentrated on the surgical aspects of management.

Spontaneous haemorrhage into a large abducens nerve schwannoma: a case report.

Purpose: Abducens schwannomas are rare tumors that are not known to present with acute haemorrhage. We present a case of a 59 year-old female on warfarin who presented acutely with a sudden onset headache, nausea and photophobia. Neuroimaging revealed an acute haemorrhage into a lesion that entered Dorello's canal and was consistent with an abducens nerve schwannoma.Materials and methods: The patient's case notes, imaging, histology and operative recording were reviewed retrospectively to compile this case report.Results: The tumor was resected via a retro-mastoid approach with sacrifice of the abducens nerve. Removal of the haematoma intra-operatively provided more space in the surgical corridor to facilitate resection. Final histological examination confirmed the diagnosis of schwannoma and the patient made a good post-operative recovery.Conclusion: We conclude that accurate pre-operative radiological diagnosis can facilitate surgical planning and removal of haematoma at an early stage during the operation can create space and facilitate resection. Furthermore, abducens schwannoma should be considered in the differential diagnosis of any heamorrhagic cerebello-pontine angle lesion.

Development of a Microfluidic Culture Paradigm for Ex Vivo Maintenance of Human Glioblastoma Tissue: A New Glioblastoma Model?

BACKGROUND: One way to overcome the genetic and molecular variations within glioblastoma is to treat each tumour on an individual basis. To facilitate this, we have developed a microfluidic culture paradigm that maintains human glioblastoma tissue ex vivo. METHODS: The assembled device, fabricated using a photolithographic process, is composed of two layers of glass bonded together to contain a tissue chamber and a network of microchannels that allow continued tissue perfusion. RESULTS: A total of 128 tissue biopsies (from 33 patients) were maintained in microfluidic devices for an average of 72 hours. Tissue viability (measured with Annexin V and propidium iodide) was 61.1% in tissue maintained on chip compared with 68.9% for fresh tissue analysed at commencement of the experiments. Other biomarkers, including lactate dehydrogenase absorbance and trypan blue exclusion, supported the viability of the tissue maintained on chip. Histological appearances remained unchanged during the tissue maintenance period, and immunohistochemical analysis of Ki67 and caspase 3 showed no significant differences when compared with fresh tissues. A trend showed that tumours associated with poorer outcomes (recurrent tumours and Isocitrate Dehydrogenase - IDH wildtype) displayed higher viability on chip than tumours linked with improved outcomes (low-grade gliomas, IDH mutants and primary tumours). CONCLUSIONS: This work has demonstrated for the first time that human glioblastoma tissue can be successfully maintained within a microfluidic device and has the potential to be developed as a new platform for studying the biology of brain tumours, with the long-term aim of replacing current preclinical GBM models and facilitating personalised treatments.

Cranial subarachnoid and subdural haemorrhage caused by spinal melanoma metastasis.

A 73-year-old female with a history of metastatic melanoma presented with extensive intracranial subarachnoid haemorrhage. Cranial imaging failed to reveal any vascular anomaly or tumour. MRI of the neuroaxis revealed a melanoma metastasis at T10 with associated subarachnoid haemorrhage. We review the literature on this rare presentation of subarachnoid haemorrhage.

Concomitant idiopathic hypertrophic spinal pachymeningitis and Guillain-Barré syndrome in a patient: coincidence or a triggering mechanism?

Idiopathic hypertrophic spinal pachymeningitis (IHSP), a rare diffuse inflammatory thickening of the dura mater, and Guillain-Barré syndrome (GBS) are known entities but they have never been reported as concomitant diagnoses. To their knowledge, the authors present the first reported case in the international literature with supportive evidence for both IHSP (based on MRI, intraoperative, and histological findings) and GBS (based on history, clinical examination, and electrophysiological findings). They review the literature on IHSP and the diagnostic criteria for GBS, with the view of identifying a possible causative connection.