Endovascular and microsurgical management of blister aneurysms: a multi-centre review.

Blister aneurysms (BA) are high-risk cerebrovascular lesions accounting for 1% of intracranial aneurysms. The defective vessel wall and broad-based neck make this clinical entity difficult to treat, with high rates of re-rupture and mortality in patients presenting with acute subarachnoid haemorrhage. Blister aneurysms pose substantial challenges for both endovascular and microsurgical management. The objective of this study is to evaluate endovascular and microsurgical outcomes in intracranial blister aneurysm management across two tertiary hospitals. A review of two tertiary hospitals with a systematic imaging database search for term of "blister" in modalities from January 2010 to October 2022 was conducted. Operation reports were screened for the 5-year period since cerebral angiogram reports transitioned to surgical database. Identified reports were screened and reviewed for confirmed diagnosis by consultant neuroradiologist. A total of 21 cases of blister aneurysms managed at respective facilities were included. Sixteen cases (76%) were managed endovascularly. Four cases (19%) were managed surgically-2 with primary clipping, and 2 wrap and clipping. One case was managed conservatively (5%). Clinical outcomes were discharge disposition, aneurysm exclusion and post-operative complications. BAs have challenging considerations with high mortality and morbidity. Endovascular treatment offers a less invasive modality with lower rates of intraoperative rupture and morbidity. Mortality rates and patients discharged home were comparable. Commencement of dual anti-platelet therapy was safe in patients with flow diversion stents despite sub-arachnoid blood volume. Management of blister aneurysms is complex. Endovascular treatment shows promise for acute management but careful collaborative consideration of antithrombotic regime and requirement for further surgery should be considered.

Aneurysmal Bone Cyst of the Orbit With USP6 Gene Rearrangement.

PURPOSE: Aneurysmal bone cyst (ABC) of the orbit is a very rare tumor, occurring mostly in the pediatric population, and can result in sight threatening complications and disfigurement. This review discusses previously reported cases with a focus on evolving treatment options and molecular genetics. METHODS: We report the youngest case of an orbital ABC with a confirmed gene fusion: a 17-month-old girl, with confirmed FGFR-UPS6 (Fibroblast Growth Factor Receptor 1-ubiquitin specific peptidase 6/tre-2). A literature search for relevant publications on the topic was performed via Medline and PubMed, with the appropriate data extracted. RESULTS: Thirty-two cases of orbital aneurysmal bone cyst were identified in the literature. Presentations are varied and can include pain, proptosis, decreased vision, and extraocular motility disturbance. Typical imaging and histopathology findings are discussed, in particular the usefulness of identifying USP6 gene arrangements. Treatment modalities are reviewed including surgery, embolization, and receptor activator of nuclear factor kappa-B ligand (RANKL) inhibitors. Recurrences can occur, usually within 2 years. CONCLUSIONS: Orbital ABC is a neoplasm that presents unique diagnostic and treatment challenges. Gene rearrangements can confirm primary ABC and rule out other underlying pathology. Disfigurement and sight threatening complications can occur due to both the disease process and with treatment. Outcomes may be improved with the use of systemic therapy.

Giant aneurysms of the distal posterior inferior cerebellar artery - systematic review.

BACKGROUND: Posterior inferior cerebellar artery (PICA) aneurysms are uncommon and are typically found at the origin or proximal segments of the vessel. Giant aneurysms are uncommon and present unique treatment challenges. Giant distal PICA aneurysms are exceedingly rare and have traditionally been managed via open surgical approaches. METHODS: A total of 207 studies were assessed, identifying 26 cases of giant distal PICA aneurysms from 26 separate publications. One additional case is described followed by a review of presentation, anatomical characteristics, treatment and outcome. RESULTS: Presentation was due to local mass effect in 19 (70%), hydrocephalus in 4 (15%) and acute haemorrhage in 5 (19%). All reported cases were partially (86%) or completely (14%) thrombosed. The telovelotonsillar segment was involved in 18/24 (75%) cases. Two cases (7%) were associated with an arteriovenous malformation. Twenty-two (81%) were managed surgically and 5 (19%) managed endovascularly. Outcome was good in 22 (85%) and poor in one (4%). CONCLUSIONS: Giant distal PICA aneurysms can be managed effectively through a variety of open surgical and endovascular techniques.

Reduced complications from intracranial grid insertion by using a small grid size and a precise protocol during monitoring.

BACKGROUND: A study of the risk factors associated with complications during intracranial EEG monitoring led to a change in protocol for monitoring and implantation at our centres. We conducted a study to identify any reduction in complications following the changed protocols involving the use of smaller subdural electrode arrays, continuous ICP monitoring, use of a central line, and intake of prophylactic antibiotics and dexamethasone. METHODS: We prospectively collected data on patient outcomes between 2005 and 2012 (group B) compared with patients between 1988 and 2004 (group A) before the protocol changes. RESULTS: Seventy-one patients in group A and 58 patients in group B underwent intracranial electrode implantation. Complications directly related to grids occurred in 25 % of group A vs. 8.6 % in group B (p < 0.05) and those indirectly related to grids were 11.2 % in group A vs. none in group B. The rate of transient complications requiring no treatment was 12.5 % in group A versus 1.7 % in group B. The rate of transient complications requiring treatment was 10 % in group A and 6.9 % in group B. There were two deaths in group A. The infection rate was higher in group B than group A (5.2 % vs. 2.8 %; p = 0.90). Since 2008 there have been no infective complications. Complications directly related to intracranial EEG monitoring were significantly reduced using the revised protocol (p < 0.05). Regression analysis identifying only the size of the grids (≤4 × 8 grid arrays) implanted was an independent predictor of more complications in group A (P < 0.05). CONCLUSIONS: Complication rates following intracranial implantation decreased following the use of a small grid size and adherence to a stringent protocol.

Institution of sustained endovascular treatment prior to clinical deterioration in patients with severe angiographic vasospasm: A retrospective observational study of clinico-radiological outcomes.

UNLABELLED: Severe angiographic vasospasm (aVSP) is a risk factor for infarction following subarachnoid haemorrhage and infarction is strongly associated with poor outcome. We present the clinico-radiological results of cohort with severe aVSP who underwent a program of angiographic surveillance and sustained endovascular treatment using multiple verapamil infusions and/or transluminal balloon angioplasty (TBA). METHODS: This was a dual-centre retrospective observational study. Angiographic screening for vasospasm was undertaken at days 5-7 post-ictus. Treatment was instituted principally on the basis of radiographic findings. The rate of infarction was evaluated on follow-up CT. Clinical outcome was assessed using the modified Rankin Scale (mRS). RESULTS: Fifty-seven WFNS grades 1-5 patients were studied. The mean number of procedures/patient was 6, range 2-13. Mean verapamil dose administered to the ICA was 14 mg and VA was 12 mg. Thirty-one patients underwent TBA (52.6%). The rate of proximal vessel infarction was 3/45 (6.7%) for patients presenting <72 hours. Rates of favourable outcome (mRS 0-2) were 16/19 (84.2%) for WFNS grades 1-2, 12/19 (63.2%) for grades 3-4 and 5/19 (26.3%) for grade 5 patients. Delayed presentation >72 hours was the only factor on multivariate analysis to significantly predict aVSP-infarction [OR19.3 (3.2-116.6) P=0.0012]. Large aVSP-infarction [OR19.0 (1.7-216.4) 0.0179] and poor WFNS grade [OR 6.6 (1.3-33.9) P = 0.0233] were significant predictors of poor outcome on multivariate analysis. CONCLUSION: This approach may result in low rates of aVSP-infarction and encouraging rates of favourable outcome when compared to literature benchmarks. Delayed presentation, however, predicts infarction and large infarct and poor initial grade significantly influence functional outcome.

Somatostatin receptor expression and clinical outcome of multilineage pituitary tumours expressing PIT1 and SF1.

The application of transcription factor immunohistochemistry to pituitary neuroendocrine tumour (PitNET) assessment has allowed identification of tumours that do not conform to a single lineage. Multilineage pituitary transcription factor 1 (PIT1) and steroidogenic factor 1 (SF1) PitNETs are a rare and relatively newly described tumour subtype. These tumours express both transcription factors and may also express combinations of hormones corresponding to both lineages. Histological and clinical characteristics can vary, and overall clinical behaviour and prognosis is not known. We describe the clinical outcomes and somatostatin receptor status (SSTR) of a series of nine cases identified from our cohort of pituitary tumours at Westmead Hospital. Eight PitNETs (88.9%) expressed growth hormone and caused acromegaly at presentation. Of the seven macrotumours that caused acromegaly, one had cavernous sinus invasion. The Ki-67 labeling index score ranged from 0.6% to 3.6%. About 88% of tumours that secreted excess growth hormone exhibited strong immunostaining for SSTR 2 and all tumours displayed weak immunoreactivity for SSTR5. In 62.5% of patients with acromegaly, cure was achieved after surgical resection. Somatostatin receptor ligands resulted in clinical remission in cases where medical treatment was initiated. There was no new tumour recurrence or regrowth over an overall mean follow-up period of 62.5 months.

Successful stereoelectroencephalography re-evaluation in epilepsy patients after failed initial subdural grid evaluation.

OBJECTIVE: Epilepsy surgery success is dependent on accurate localization of the epileptogenic zone. Despite the use of invasive EEG using subdural grids and strips, surgical failures can occur. In this series, we explore the utility of a second evaluation with stereoelectroencephalography in patients whose initial invasive evaluation with subdural grid electrodes was unsuccessful in localizing seizure origin. METHODS: We conducted a retrospective review of patients who underwent subdural grid evaluation (SDE) at our center and identified patients who underwent a re-evaluation with stereoelectroencephalography (SEEG). RESULTS: We identified three patients who had both subdural and SEEG electrodes in the region of the identified epileptogenic zone in whom the initial SDE evaluation failed to make the patients seizure-free. Two of these patients underwent a second resection and became seizure-free. SIGNIFICANCE: Stereoelectroencephalography can be useful in the re-evaluation and re-operation of patients who previously had surgical failure using SDE.

From Pediatric to Adult Brain Cancer: Exploring Histone H3 Mutations in Australian Brain Cancer Patients.

Genetic histone variants have been implicated in cancer development and progression. Mutations affecting the histone 3 (H3) family, H3.1 (encoded by HIST1H3B and HIST1H3C) and H3.3 (encoded by H3F3A), are mainly associated with pediatric brain cancers. While considered poor prognostic brain cancer biomarkers in children, more recent studies have reported H3 alterations in adult brain cancer as well. Here, we established reliable droplet digital PCR based assays to detect three histone mutations (H3.3-K27M, H3.3-G34R, and H3.1-K27M) primarily linked to childhood brain cancer. We demonstrate the utility of our assays for sensitively detecting these mutations in cell-free DNA released from cultured diffuse intrinsic pontine glioma (DIPG) cells and in the cerebral spinal fluid of a pediatric patient with DIPG. We further screened tumor tissue DNA from 89 adult patients with glioma and 1 with diffuse hemispheric glioma from Southwestern Sydney, Australia, an ethnically diverse region, for these three mutations. No histone mutations were detected in adult glioma tissue, while H3.3-G34R presence was confirmed in the diffuse hemispheric glioma patient.

Diagnostic pitfall in the diagnosis of mesenchymal chondrosarcoma arising in the central nervous system.

Mesenchymal chondrosarcoma is a rare aggressive neoplasm typically affecting the bones of young adults. It may also arise in somatic soft tissue, the CNS and other organs. It has a characteristic biphasic histological pattern composed of highly undifferentiated small round cells and islands of well-differentiated hyaline cartilage. We report a case of mesenchymal chondrosarcoma arising from the right tentorium cerebelli in a 21-year-old woman with symptoms relating to mass effect. Histological examination demonstrated a purely small round cell appearance in a specimen obtained during partial resection at an outside institution, leading to an erroneous diagnosis of Ewing sarcoma/primitive neuroectodermal tumor (PNET). The diagnosis of mesenchymal chondrosarcoma was made only after tissue obtained during a definitive complete macroscopic removal involving the regional tentorium cerebelli, transverse and sigmoid dural venous sinuses which showed a prominent cartilaginous component. We discuss the features of mesenchymal chondrosarcoma arising in the CNS, the important differential diagnoses of small round-cell tumors within the CNS, and the differentiating features of mesenchymal chondrosarcoma from Ewing sarcoma/PNET, medulloblastoma, hemangiopericytoma, monophasic synovial sarcoma and atypical teratoid/rhabdoid tumour.

Epidural abscess in a neonate.

We report the case of a 16-day-old neonate who presented with fever and irritability. Blood and cerebrospinal fluid (CSF) samples collected on his admission grew methicillin sensitive Staphylococcus aureus on culture, prompting an urgent search for parameningeal collections or an occult sinus involving the central nervous system. Magnetic resonance imaging revealed a pyogenic collection within the epidural space extending from the upper cervical to lumbosacral level and multiple other deep tissue collections that required repeated surgical drainage. Central nervous system infections due to S. aureus are uncommon, particularly in the absence of an anatomical defect or prior neurosurgical instrumentation. This case demonstrates the importance of a timely and thorough search for parameningeal foci when CSF cultures are positive for unusual organisms such as S. aureus.

Localisation and stimulation of the parietal eye field.

Localisation of the human parietal eye fields (PEF) has not been as well studied as the human frontal eye fields (FEF). Stimulation studies in rhesus monkeys have suggested the localisation of the PEF to be within the intraparietal sulcus. Functional MRI studies have demonstrated this region to be highly active and potentially connected in saccadic and gaze shifting tasks. Here, we present a case of a patient with left versive seizures evaluated with SEEG, in whom electrical stimulation within the right intraparietal sulcus resulted in horizontal and downward conjugate eye movements contralateral to stimulation. We illustrate clinical differences between the FEF and PEF on cortical stimulation. In addition to the frontal eye field, it is important to recognise other cortical regions involved in eye movement which can cause conjugate contralateral eye movement.

Predictors of longitudinal seizure outcomes after epilepsy surgery in childhood.

There is a paucity of data on longitudinal seizure outcome of children undergoing epilepsy surgery. All children (n = 132) who underwent resective epilepsy surgery from January 1998 to December 2015 were identified. Relevant clinical, neurophysiological, imaging, surgical and seizure outcome data were extracted. Multivariable logistic regression analysis and Kaplan-Meier survival with Cox proportional hazard modelling were performed. The mean age at surgery was 7.8 years (range 0.2-17.9). 71% were seizure-free at a mean follow up of 5.3 ± 2.7 years. Of those who were seizure-free, 65 patients were able to completely wean off anti- seizure medications successfully. Using survival analysis, the probability of Engel Class I outcome at one year after surgery was 81% (95% confidence interval [CI] 87%-75%). This dropped to 73% at two years (95% CI 81%-65%), 58% at five years (95% CI 67.8%-48%), and 47% at ten years. Proportional hazard modelling showed that the presence of moderate to severe developmental disability (HR 6.5; p = 0.02) and lack of complete resection (HR 0.4; p = 0.02) maintain association as negative predictors of seizure-free outcome. Our study demonstrates favorable long-term seizure control following pediatric epilepsy surgery and highlights important predictors of seizure outcome guiding case selection and counseling of expectations prior to surgery.

Investigating the Precise Localization of the Grasping Action in the Mid-Cingulate Cortex and Future Directions.

Objective: To prospectively study the cingulate cortex for the localization and role of the grasping action in humans during electrical stimulation of depth electrodes. Methods: All the patients (n = 23) with intractable focal epilepsy and a depth electrode stereotactically placed in the cingulate cortex, as part of their pre-surgical epilepsy evaluation from 2015 to 2017, were included. Cortical stimulation was performed and examined for grasping actions. Post-implantation volumetric T1 MRIs were co-registered to determine the exact electrode position. Results: Five patients (male: female 4:1; median age 31) exhibited contralateral grasping actions during electrical stimulation. All patients had electrodes implanted in the ventral bank of the right cingulate sulcus adjacent to the vertical anterior commissure (VAC) line. Stimulation of other electrodes in adjacent regions did not elicit grasping. Conclusion: Grasping action elicited from a localized region in the mid-cingulate cortex (MCC) directly supports the concept of the cingulate cortex being crucially involved in the grasping network. This opens an opportunity to explore this region with deep brain stimulation as a motor neuromodulation target for treatment in specific movement disorders or neurorehabilitation.

FISH analysis of brain smears obtained at intraoperative diagnosis - An accurate and fast method to detect 1p/19q-codeletion in gliomas.

The importance of molecular testing of gliomas is highlighted in the 2016 revised 4th edition of the WHO Classification of Tumours of the Central Nervous System, which applies an integrated diagnosis of histological and molecular features. In this classification system, oligodendrogliomas (ODG) are defined as IDH-mutant and 1p/19q-codeleted. Fluorescence in situ hybridization (FISH) analysis of formalin-fixed paraffin-embedded (FFPE) tissue is a standard method of determining 1p/19q-codeletion. However, it has several disadvantages, including requiring lengthy pretreatment, truncation artefact and lack of on-site access in many centers. In an effort to address these issues, we analysed FISH performed on smears obtained at intraoperative frozen section on 51 gliomas and compared this to FISH performed on subsequent FFPE sections. Four cases were excluded due to uninterpretable FISH results. Of the remaining 47 cases, 17 were concordant for 1p/19q-codeletion, 29 were concordant for lack of 1p/19q-codeletion, and 1 was discordant with 1p/19q-codeletion found on FFPE tissue but not on intraoperative smears. The discordant case was most likely due to sampling error, as the frozen section had not shown definite tumor. The FISH results on intraoperative smears were received within 24-48 h after the sample was collected, compared with 3-4 days for FFPE tissue. FISH on smears obtained at intraoperative frozen section is an accurate and fast method for determining 1p/19q-codeletion.

Failure of platelet function analyser 200 to demonstrate clinical clopidogrel resistance in a patient undergoing intracranial vascular stenting.

A patient undergoes intracranial stent insertion for stent-assisted coiling of a basilar tip aneurysm and left middle cerebral artery aneurysm. A flow diverting stent is also placed across an anterior communicating artery aneurysm. Prior to the procedure, the patient takes dual antiplatelet medications, being aspirin and clopidogrel. Because of the concern regarding in-stent thrombus and thromboembolic complications related to intracranial stenting and the high rate of clopidogrel resistance, preoperative platelet function testing (PFT) was undertaken to ensure platelet inhibition. In this case, PFT was performed on a platelet function analyser which demonstrated platelet inhibition. Ten days following the procedure, the patient represented with thromboembolic stroke. Repeat PFT performed with whole blood impedance aggregometry and despite full medication compliance demonstrated clopidogrel resistance. Clopidogrel was then ceased and prasugrel commenced. This case demonstrates the importance of appropriate platelet inhibition in patients with intracranial stents and the controversy surrounding PFT.

Successful epilepsy surgery for tuberous sclerosis complex evaluated by stereoelectroencephalography.

Evaluating the candidacy for epilepsy surgery in patients with tuberous sclerosis can be challenging, particularly when non-invasive investigations do not show a clear epileptogenic zone. Stereoencephalography may be useful in such cases. We present a case in which the primary epileptogenic tuber was successfully identified by stereoencephalography, which resulted in seizure freedom following epilepsy surgery. [Published with video sequences].

Usefulness of smears in intra-operative diagnosis of newly described entities of CNS.

The recent edition of World Health Organisation (WHO) Classification of Tumours of the Central Nervous System has incorporated a substantial number of important changes. It has recognised several new entities, many of which are rare. Intra-operative diagnosis of these tumours can be difficult with the freezing artefact that often cripples brain frozen sections. In many instances intra-operative smears are extremely useful adjuvants in neuropathological diagnosis. In this article, we describe intra-operative smear findings of three of the newly described tumours. Their characteristic cytologic features are illustrated along with differentiating features from the common mimics, together with a general approach to brain smears. The entities we discuss here are papillary glioneuronal tumour, papillary tumour of the pineal region and angiocentric glioma. All three tumours share at least focal pseudo-papillary/vasculocentric architecture. Smears from papillary glioneuronal tumour demonstrated dual population of cells in a neuropil background, whereas papillary tumour of the pineal region and angiocentric glioma comprise a single population of cells. These two tumours can further be differentiated based on their cell morphology and background.

Continuous intrathecal baclofen for children with spasticity and/or dystonia: Goal attainment and complications associated with treatment.

AIM: To describe complications and outcomes of intrathecal baclofen (ITB) therapy in children with spasticity and/or dystonia. METHODS: A prospective study of goal attainment after ITB therapy and a retrospective review of medical records for complications. The children were described as dystonia-predominant or spasticity-predominant and the subgroups were compared. Goals were assessed at baseline and goal attainment at 6 months post-implant. Data were analysed using Wilcoxon signed-rank test. The patients' goals were measured with the Canadian Occupational Performance Measure (COPM) and goal attainment scaling (GAS). Complication rates were calculated by dividing the number of complications by the duration of pump implantation. RESULTS: Twenty-five children were included, 16 with complete goal attainment data. The mean age was 10 years and 3 months. Eighty-eight percent had a diagnosis of cerebral palsy. The most common goals were improved positioning and transfers. A statistically significant increase (P < 0.001) in both domains of the COPM was demonstrated. The mean GAS T-score was significantly higher at 6 months post implant (P < 0.001). Seventy percent of the subjects achieved their goals at 6 months. The complication rate was 0.38 per year of pump operation, higher in subjects with dystonia (0.71) compared with those with spasticity (0.25). CONCLUSIONS: ITB results in statistically significant levels of satisfaction and goal attainment in children with spasticity and/or dystonia. GAS was a useful measure of goal attainment. While, ITB is effective for children with spasticity and dystonia, those with dystonia have a higher rate of complications.