The utility of plasma circulating cell-free messenger RNA as a biomarker of glioma: a pilot study.

BACKGROUND: Research into the potential utility of plasma-derived circulating cell-free nucleic acids as non-invasive adjuncts to radiological imaging have been occasioned by the invasive nature of brain tumour biopsy. The objective of this study was to determine whether significant differences exist in the plasma transcriptomic profile of glioma patients relative to differences in their tumour characteristics, and also whether any observed differences were representative of synchronously obtained glioma samples and TCGA glioma-derived RNA. METHODS: Blood samples were collected from twenty glioma patients prior to tumour resection. Plasma ccfmRNAs and glioma-derived RNA were extracted and profiled. RESULTS: BCL2L1, GZMB, HLA-A, IRF1, MYD88, TLR2, and TP53 genes were significantly over-expressed in glioma patients (p < 0.001, versus control). GZMB and HLA-A genes were significantly over-expressed in high-grade glioma patients (p < 0.001, versus low-grade glioma patients). Moreover, the fold change of the BCL2L1 gene was observed to be higher in patients with high-grade glioma (p = 0.022, versus low-grade glioma patients). There was positive correlation between the magnitude of fold change of differentially expressed genes in plasma- and glioma-derived RNA (Spearman r = 0.6344, n = 14, p = 0.017), and with the mean FPKM in TCGA glioma-derived RNA samples (Spearman r = 0.4614, n = 19, p < 0.05). There was positive correlation between glioma radiographic tumour burden and the magnitude of fold change of the CSF3 gene (r = 0.9813, n = 20, p < 0.001). CONCLUSION: We identified significant differential expression of genes involved in cancer inflammation and immunity crosstalk among patients with different glioma grades, and there was positive correlation between their transcriptomic profile in plasma and tumour samples, and with TCGA glioma-derived RNA.

Plasma circulating cell free messenger RNA as a potential biomarker of melanoma.

BACKGROUND: Blood borne cell free nucleic acids are increasingly emerging as significant non-invasive adjuncts to current methods of disease status evaluation in cancer patients. In this study, we sought to examine whether significant differences exist in the plasma transcriptomic profile of advanced melanoma patients with a high disease burden compared to patients with a low disease burden or therapeutic response. METHODS: Pathway focussed gene expression analysis was performed using cDNA derived from the plasma circulating cell free messenger ribonucleic acid (ccfmRNA) samples of twenty-two patients with advanced melanoma. Patients were assessed with paired blood sample collection and CT scan assessments at baseline and at 3 months follow up. RESULTS: We identified several genes which were significantly over-expressed in patients with a low disease burden or therapeutic response; BCL2L1, CXCL9, IDO1, IL13, MIF, MYD88 and TLR4 (p ≤ 0.001, versus high disease burden). There was an increase in the magnitude of fold change (2^ (-dd CT)) of BCL2L1 (p = 0.031), CCL4 (p = 0.001), CCL5 (p = 0.043), CXCL9 (p = 0.012), GZMB (p = 0.023) and TNFSF10 (p = 0.039) genes in patients with therapeutic response at 3 months follow up assessment relative to baseline assessment. Moreover, in stage IV melanoma patients with brain metastases, CCL18, CCR1, CCR4, CD274, CSF2, EGF, and PTGS2 genes were significantly over-expressed (p < 0.001, versus patients without melanoma brain metastasis). CONCLUSION: Significant differences were observed in the plasma transcriptomic profile between the various melanoma patient groups, and we postulate that these differences may be exploited to identify novel therapeutic targets or biomarkers relevant to melanoma.

Biopsychosocial variations in quality of life outcome following microdiscectomy.

BACKGROUND: Lumbar microdiscectomy is one of the most frequently performed neurosurgical procedures. In this review, we ask why patients' outcomes vary so widely even within the same unit, with the same surgeon performing the procedure and utilizing the technique? METHODS: In a cohort of 87 patients, we investigated how/whether multiple patient variables impacted outcomes following single-level lumbar microdiscectomy. We studied whether early surgical intervention improved the patients' quality of life (QOL) versus late intervention. Furthermore, we assessed other variables that could influence patient-perceived improvement. Preoperatively and postoperatively, we additionally utilized the following internationally standardized questionnaires (EQ-5D, Oswestry, and Core Outcome Measures Index [COMI]). RESULTS: A generalized substantial improvement in QOL was identified throughout the cohort population (<0.05). There was no difference in health measurement scores for those undergoing early versus late surgery. However, there was a statistically significant improvement in all QOL scores for privately insured patients versus publicly insured patients (e.g., on COMI, EQ-5D, and ODI Scores). CONCLUSION: There was no objective statistically significant difference in QOL health scores between patients undergoing early versus late surgical lumbar microdiscectomy. This would suggest that the length of time patients is symptomatic before surgery did not significantly impact postoperative outcome. Of interest, however, was the difference in QOL health scores for private versus public patients suggesting that there are more subjective, complex, and psychosocial issues that influence outcome.

Octreotide use for rescue of vision in a pregnant patient with acromegaly.

Pregnancy in acromegaly is rare and generally safe, but tumour expansion may occur. Managing tumour expansion during pregnancy is complex, due to the potential complications of surgery and side effects of anti-tumoural medication. A 32-year-old woman was diagnosed with acromegaly at 11-week gestation. She had a large macroadenoma invading the suprasellar cistern. She developed bitemporal hemianopia at 20-week gestation. She declined surgery and was commenced on 100 µg subcutaneous octreotide tds, with normalisation of her visual fields after 2 weeks of therapy. She had a further deterioration in her visual fields at 24-week gestation, which responded to an increase in subcutaneous octreotide to 150 µg tds. Her vision remained stable for the remainder of the pregnancy. She was diagnosed with gestational diabetes at 14/40 and was commenced on basal bolus insulin regimen at 22/40 gestation. She otherwise had no obstetric complications. Foetal growth continued along the 50th centile throughout pregnancy. She underwent an elective caesarean section at 34/40, foetal weight was 3.2 kg at birth with an APGAR score of 9. The neonate was examined by an experienced neonatologist and there were no congenital abnormalities identified. She opted not to breastfeed and she is menstruating regularly post-partum. She was commenced on octreotide LAR 40 mg and referred for surgery. At last follow-up, 2 years post-partum, the infant has been developing normally. In conclusion, our case describes a first presentation of acromegaly in pregnancy and rescue of visual field loss with somatostatin analogue therapy. Learning points: Tumour expansion may occur in acromegaly during pregnancy. Treatment options for tumour expansion in pregnancy include both medical and surgical options. Somatostatin analogues may be a viable medical alternative to surgery in patients with tumour expansion during pregnancy.

Intra-operative imaging for spinal level localisation in lumbar surgery.

Study Design: Retrospective review of the practice of 3 surgeons in a single centre during a 1-year period. Objective: We aimed to investigate our adherence to the Society of British Neurological Surgeons (SBNS) guidelines regarding intra-operative imaging during lumbar surgery and to determine if this has any impact on length of surgery or complications rates, in particular rates of wrong-level surgery. Background: The SBNS recommends three x-rays for intra-operative spinal localisation - one prior to incision, the second after exposure of the laminae and before the commencement of decompression, and the third at the end of the operation to confirm the adequacy of decompression. At our centre, surgeon A performs x-rays 1 and 3 routinely, and x-ray 2 in cases where the anatomy is uncertain, surgeon B performs x-ray 2 only, and the practice of surgeon C varies depending on the complexity of cases. Method: We reviewed the surgical logbooks of 3 consultant neurosurgeons in our centre for the 1-year period between October 2015 and October 2016. Our study included 301 patients who had undergone lumbar decompression or lumbar discectomy during this period. Results: There were no cases of wrong-level surgery. The incorrect spinal level was initially exposed in 13 cases (4.3%). 10 of these had x-ray 2 only, 1 had x-ray 1, 1 had x-rays 1 and 2, and 1 had all 3 x-rays. Surgeon B performed 8 of these cases, four were performed by surgeon C, and 1 by surgeon A. The median duration of surgery was 80 minutes for lumbar decompression and 67.5 minutes for lumbar discectomy. The median duration of surgery in patients in whom the wrong level was initially exposed was 85 minutes for lumbar decompression and 80 minutes for lumbar discectomy. Conclusion: Performance of the 3 recommended x-rays may increase the identification of wrong-level exposures before the commencement of decompression and may reduce the length of surgery.

Spontaneous Fractures in the Setting of Extensive Craniocervical Pneumatization: Case Report and Literature Review.

BACKGROUND: Cranial pneumatization in humans is normally confined to the paranasal sinuses and the petrous and mastoid parts of the temporal bones. CASE DESCRIPTION: We present a case of left-sided fractures of the occipital condyle and lateral mass of the atlas in the setting of extensive craniocervical pneumatization but in the absence of trauma, with a resulting unilateral hypoglossal nerve palsy. CONCLUSIONS: We discussed the possible etiology of this rare disease, its management, and prognosis.

Interdural Spinal Cyst: A Rare Clinical Entity.

BACKGROUND: For more than 2 decades, dural spinal cysts have been broadly classified as extradural and intradural. CASE DESCRIPTION: A 40-year-old woman presented with radicular thoracic pain. Intraoperative findings showed the cyst to be present within the dura itself. CONCLUSIONS: We suggest a revised classification of spinal dural cysts. This case highlights that, during surgery for spinal meningeal cysts, surgeons should bear in mind the possibility of an interdural cyst. This may help avoid inadvertent tears in the deep layers of such cysts, thus maintaining dural patency.

Extradural haematoma--to evacuate or not? Revisiting treatment guidelines.

BACKGROUND: We describe three cases of extradural haematomas (EDHs) and their management, focusing on operative and non-operative treatment. We also review the available literature from the past three decades as well as the guidelines for the management of EDH. An algorithm is formulated based on different factors, including the clinical course of the patients and their CT findings. METHODS: The first patient presented to us after sustaining a fall with a GCS of 15/15 and a large parieto-occipital EDH with a volume of 90 cm3. He was treated non-operatively. Follow-up CT showed good resolution of the haematoma. The second patient presented with a GCS of 7/15, a posterior fossa EDH with a volume of 30 cm3, and obstructive hydrocephalus. Emergency ventriculostomy was performed, which was converted to a VP shunt. The third case was a patient presenting with a large hemispheric EDH, which was 130 cm3 in volume. The GCS at presentation was 14/15 but dropped to 6/15, following which he underwent craniotomy and evacuation of the EDH. RESULTS: The Glasgow Outcome Scale (GOS) at three months was five for the first two cases and three for the third case with a dense right hemiplegia. CONCLUSION: EDH, both supratentorial and in the posterior fossa, can be managed non-operatively. A large volume EDH (>30 cm3) can be managed non-operatively provided the GCS at presentation and follow up remains the same with symptomatic improvement. Prompt treatment of a large volume EDH may still result in a poor outcome.

Brain dead or not? CT angiogram yielding false-negative result on brain death confirmation.

We describe a case of severe traumatic brain injury with multiple facial and skull fractures where CT angiogram (CTA) failed to yield a definite result of brain death as an ancillary test. A 28-year-old man was admitted following a road traffic accident with a Glasgow Coma Score (GCS) of 3/15 and fixed pupils. CT brain revealed uncal herniation and diffuse cerebral oedema with associated multiple facial and skull fractures. 72 h later, his clinical condition remained the same with high intracranial pressure refractory to medical management. Clinical confirmation on brain death was not feasible owing to facial injuries. A CTA, performed to determine brain perfusion, yielded a 'false-negative' result. Skull fractures have possibly led to venous prominence in the cortical and deep venous drainage system. This point needs to be borne in mind while considering CTA as an ancillary test to confirm brain death.

Does surgical technique affect the incidence of spondylodiscitis post-lumbar microdiscectomy? A retrospective analysis of 3063 patients.

STUDY DESIGN: Retrospective audit in a single center during a period of 7 years operated by 3 groups of surgeons after 3 different surgical techniques. OBJECTIVE: Our study aimed to determine whether surgical technique had any influence on the incidence of spondylodiscitis in patients undergoing lumbar microdiscectomy and to compare this with published rate of incidence of spondylodiscitis. SUMMARY OF BACKGROUND DATA: The incidence of spondylodiscitis post-lumbar microdiscectomy ranges from 0.2% to 15%. There is limited evidence to compare different techniques and the incidence of spondylodiscitis. METHODS: A total of 3063 patients were analyzed from 2005 to 2011 for discitis postoperatively. The first group followed a standard microdiscectomy technique, the second group used antiseptic (Savlon; Novartis Consumer Health UK Limited, Surrey, UK) irrigation at the end of the procedure to irrigate the disc space, and the third group followed standard microdiscectomy along with usage of a separate disc instruments when discectomy was performed. The number of patients operated in the individual groups was 559, 1122, and 1382. RESULTS: The total number of patients who had postoperative discitis was 3 (0.10%), with a range of 0.07% to 0.18%. There was 1 case of discitis in each group. The incidence of spondylodiscitis in groups A, B, and C were 0.18%, 0.09%, and 0.07%, respectively. CONCLUSION: This study concluded that different techniques used for lumbar microdiscectomy revealed that standard microsurgical technique with usage of antiseptic irrigation for the disc space and usage of separate disc instruments had lesser incidence of spondylodiscitis in comparison with standard microdiscectomy. The overall incidence of postoperative discitis remains less in our series. So far, to our knowledge, this report involves the largest number of patients studied to determine the incidence of discitis in patients undergoing lumbar microdiscectomy. LEVEL OF EVIDENCE: 3.

Dyskalaemia following diffuse axonal injury: case report and review of the literature.

Traumatic brain injury, and its management, commonly causes derangements in potassium balance. There are a number of recognised causative factors including head trauma, hypothermia and iatrogenic factors such as pharmacological agents and permissive cooling. We describe a case of a 19-year-old man with a severe traumatic brain injury. In a 36-h period, his intracranial pressure increased despite maximal medical therapy and he developed refractory hypokalaemia. Immediately following a decompressive craniectomy, the patient was noted to be profoundly hyperkalaemic; this led to the development of ventricular tachycardia and cardiac arrest, from which the patient did not recover. The effects of brain injury on potassium balance are not well appreciated; the effect of decompressive craniectomy on potassium (K(+)) balance has not been described previously. We would like to emphasise the potential effect of diffuse axonal injury, a severe form of brain injury and decompressive craniectomy on potassium balance.

A prospective randomised study to compare the utility and outcomes of subdural and subperiosteal drains for the treatment of chronic subdural haematoma.

BACKGROUND: The usage of a drain following evacuation of a chronic subdural haematoma (CSDH) is known to reduce recurrence. In this study we aim to compare the clinical outcomes and recurrence rate of utilising two different types of drains (subperiosteal and subdural drain) following drainage of a CSDH. METHODS: Prospective randomised single-centre study analysing 50 patients who underwent CSDH treatment. Two types of drains, subperiosteal (SPD) and subdural (SDD), were utilised on consecutive alternate patients following burr-hole craniostomy, with a total of 25 patients in each group. The drains were left in for 48-h duration and then removed. The modified Rankin Scale (mRS) was used for outcome measurement at 3 and 6 months. RESULTS: Data analysis was performed by unpaired t test with Welch's correction. It was observed that none of the patients in either group had haematoma recurrence during a 6-month follow-up, and a significant difference in outcome was noted at 6 months (p = 0.0118) more than at 3 months (p = 0.0493) according to the statistical analysis. Postoperative seizure and inadvertent placement of the subdural drain into the brain parenchyma were the two complications noted in this study. Anticoagulant use prior to the surgery did not affect the outcome in either group. CONCLUSIONS: We conclude there was no recurrence of CSDH utilising the SDD and SPD following burr-hole craniostomy. The mRS measurement at the 6-month follow-up was found to be statistically significant, with better outcomes with utilisation of the SPD. The SPD may thus prove to be more beneficial than the SDD in the treatment of CSDH. A multi-centre study with a larger group of patients is recommended to reinforce the results from our study.

'Miracle baby': an outcome of multidisciplinary approach to neurotrauma in pregnancy.

Traumatic brain injury (TBI) warranting neurosurgical intervention in the pregnant population is a rarity. We describe a case of a 27-year-old woman who at 13 weeks of gestation presented with multiple traumas having been involved in a near fatal road traffic accident. Glasgow Coma Scale was 6/15. CT brain showed extensive haemorrhagic contusions, diffuse brain swelling and multiple skull and facial fractures. Decompressive craniectomy was performed to control her intracranial pressure during her management in the intensive care. A viable intrauterine pregnancy was confirmed and progressed as maternal stabilisation and rehabilitation continued. At 35+3 weeks a 2770 g male child was delivered via emergency caesarean section after spontaneous onset of labour. The child had no detectable abnormalities and is clinically well. Eight months post-TBI the patient continues to make gradual improvements but is left with severe cognitive impairment and currently undergoing rehabilitation. A multidisciplinary approach was adopted in the management of this patient.

Superior cerebellar aneurysm causing subarachnoid haemorrhage in a 17-year-old with alagille syndrome.

Alagille syndrome is a rare autosomal dominant condition characterised by mutation in Jagged1 gene. Intracranial aneurysms may be seen in this condition and may present as subarachnoid hemorrhage. We describe the first case of superior cerebellar aneurysm rupture causing WFNS grade 1 subarachnoid haemorrhage in a 17-year-old girl. The clinical condition and management of this rare occurrence is discussed with a review of literature.

A neurosurgical presentation of patent foramen ovale with atrial septal aneurysm.

We describe a case of cerebral abscess in a 53-year-old lady with a background of congenital heart defect. She has an atrial septal defect with atrial septal aneurysm, which remained undiagnosed until this clinical presentation. She presented with a short history of right-sided hemiplaegia and neuroimaging revealed a heterogeneous lesion in the left frontoparietal region. Neuronavigation-guided left frontoparietal craniotomy was performed to debulk the lesion and preoperatively frank pus was drained, which grew Streptococcus constellatus. She was successfully treated with antibiotics for 6 weeks and her clinical condition improved. We believe that the patients' previous dental extraction has possibly resulted in a paradoxical embolism through the atrial septal defect bypassing the pulmonary circulation. The MRI scan picture was misleading, as it was initially thought to be a high-grade brain tumour.

Osteogenesis imperfecta presenting as aneurysmal subarachnoid haemorrhage in a 53-year-old man.

The authors describe a case of aneurysmal subarachnoid haemorrhage in a 53-year-old man with background of osteogenesis imperfecta (OI). CT brain revealed diffuse subarachnoid haemorrhage (SAH) and cerebral angiogram subsequently confirmed vertebral artery aneurysm rupture leading to SAH. To the authors knowledge this is the first case of vertebral artery aneurysmal SAH described in OI. A previously undiagnosed OI was confirmed by genetic analysis (COL1A1 gene mutation). This aneurysm was successfully treated by endovascular route. Post interventional treatment patient developed stroke secondary to vasospasm. Communicating hydrocephalus, which developed in the process of management, was successfully treated with ventriculo-peritoneal shunt. The aetio-pathogenesis and management of this condition is described. The authors have reviewed the literature and genetic basis of this disease.

Sciatica as a presenting feature of thyroid follicular adenocarcinoma in a 79-year-old woman.

The authors describe an unusual case of metastatic thyroid follicular adenocarcinoma presenting with sciatica in a 79-year-old woman. The primary thyroid tumour was undiagnosed until this clinical presentation. The patient gave a short history of back pain and right-sided sciatica, which was progressive and nocturnal in nature. Neuroimaging revealed an enhancing intradural mass lesion, which was completely excised through a right L1-L3 hemilaminectomy. Histopathological examination of the excised tissue revealed a follicular thyroid carcinoma. Subsequent metastatic investigation revealed a heterogeneously attenuating mixed solid cystic mass in a retrosternal thyroid gland, with multiple solid pulmonary nodules suggestive of metastatic disease. She opted for palliative radiotherapy for the primary thyroid cancer and made remarkable postoperative improvement. The authors conclude that surgical treatment of solitary metastatic lesion may produce good symptomatic relief irrespective of patient's age and primary pathology, while emphasising the need for detailed clinical evaluation of patients with 'red flag' symptoms.

Use of a simple intraoperative hydrostatic pressure test to assess the relationship between mobility of the ventricular stoma and success of third ventriculostomy.

OBJECT: Neuroendoscopists often note pulsatility or flabbiness of the floor of the third ventricle during endoscopic third ventriculostomy (ETV) and believe that either is a good indication of the procedure's success. Note, however, that this belief has never been objectively measured or proven in a prospective study. The authors report on a simple test-the hydrostatic test-to assess the mobility of the floor of the third ventricle and confirm adequate ventricular flow. They also analyzed the relationship between a mobile floor (a positive hydrostatic test) and prospective success of ETV. METHODS: During a period of 3 years between July 2001 and July 2004, 30 ETVs for obstructive hydrocephalus were performed in 22 male and eight female patients. Once the stoma had been created, the irrigating Ringer lactate solution was set at a 30-cm height from the external auditory meatus, and the irrigation valve was opened while the other ports on the endoscope were closed. The ventricular floor ballooned downward and stabilized. The irrigation valve was then closed and ports of the endoscope were opened. The magnitude of the upward displacement of the floor was then assessed. Funneling of the stoma was deemed to be a good indicator of floor mobility, adequate flow, and a positive hydrostatic test. All endoscopic procedures were recorded using digital video and recordings were subsequently assessed separately by two blinded experienced neuroendoscopists. Patients underwent prospective clinical follow up during a mean period of 11.2 months (range 1 month-3 years), computerized tomography and/or magnetic resonance imaging studies of the brain, and measurements of cerebrospinal fluid pressure through a ventricular reservoir when present. Failure of ETV was defined as the subsequent need for shunt implantation. The overall success rate of the ETV was 70% and varied from 86.9% in patients with a mobile stoma and a positive hydrostatic test to only 14.2% in patients with a poorly mobile floor and a negative test (p < 0.05). The positive predictive value of the hydrostatic test was 86.9%, negative predictive value 85.7%, sensitivity 95.2%, and specificity 66.6%. CONCLUSIONS: The authors concluded that the hydrostatic test is an easy, brief test. A positive test result confirms a mobile ventricular floor and adequate flow through the created ventriculostomy. Mobility of the stoma is an important predictor of ETV success provided that there is no obstruction at the level of the arachnoid granulations or venous outflow. A thin, redundant, mobile third ventricle floor indicates a longstanding pressure differential between the third ventricle and the basal cisterns, which is a crucial factor for ETV success. A positive hydrostatic test may avert the need to insert a ventricular reservoir, thus avoiding associated risks of infection.

Intracranial metastasis from a sacrococcygeal chordoma. Case report.

Chordoma is a locally invasive tumor of low metastatic potential. Only six cases of chordoma that metastasized to the brain are found in the English literature. Most of these lesions were clinically silent and all were associated with extraneural metastases. The authors report a case of symptomatic brain metastasis from a sacrococcygeal chordoma in the absence of other metastases. The incidence, sites, and factors predictive of chordoma metastasis are discussed.