Tumour infiltrating lymphocyte density differs by meningioma type and is associated with prognosis in atypical meningioma.

Tumour infiltrating lymphocyte (TIL) density is prognostically significant in various tumours, but few studies have investigated its significance in meningioma. This study aimed to investigate how TIL density differs by meningioma histology and whether it is a predictor of meningioma recurrence. We studied CD3, CD8, CD4, FOXP3 and PD-1 positive (+) TIL density in a continuous cohort of 476 meningiomas resected at Auckland Hospital between 2002 and 2011 using tissue microarrays and computer assisted image analysis. TILs were identified in all meningiomas except one (median CD3+ TIL density across entire cohort 53.0 cells/mm2). Most TILs were CD8+ (median 33.6 cells/mm2) with smaller numbers of CD4+ TILs (median 2.9 cells/mm2). PD-1+ (median 0.32 cells/mm2) and FOXP3+ (median 0.0 cells/mm2) TILs were scarce. Reduced CD3+ (p=0.0066), CD8+ (p=0.0029) and PD-1+ (p=0.0375) TIL density was seen in WHO grade II/III meningioma compared with WHO grade I. Pairwise comparison confirmed statistically significant differences in TIL density existed between meningioma types (CD3, CD8, CD4, p<0.0001; FOXP3, p=0.0096; PD-1, p=0.0090) with chordoid meningioma having the lowest overall CD3+ TIL density (median 12.5 cells/mm2). Despite its low TIL density, chordoid meningioma had a higher FOXP3:CD8 ratio than several meningioma types. Atypical meningioma had a higher FOXP3:CD8 ratio than transitional meningioma (p=0.0045). No association between TIL density and recurrence was seen across the entire cohort or by WHO grade. However, CD3+ and CD8+ TIL density was associated with recurrence in atypical meningioma on multivariable analysis (CD3, p=0.0012; CD8, p=0.0071). A higher CD3+ and CD8+ TIL density was associated with improved recurrence free survival. Our findings suggest CD3+ and CD8+ TIL density is prognostically significant in atypical meningioma. Further investigation of this observation and its biological basis is warranted. The differences in TIL density by meningioma histology may be of relevance in studies of therapeutic immune checkpoint inhibition.

A long-term follow-up of safety and clinical efficacy of NTCELL® [Immunoprotected (Alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease.

INTRODUCTION: In 2019, we published the results of a Phase IIb randomized controlled trial of putaminal encapsulated porcine choroid plexus cell (termed NTCELL®) administration in patients with Parkinson's disease. This study failed to meet its primary efficacy end-point of a change in UPDRS part III score in the 'off' state at 26-weeks post-implant. However, a number of secondary end-points reached statistical significance. We questioned whether with longer follow-up, clinically significant improvements would be observed. For this reason, we decided to follow-up all patients periodically to week 104. Herein, we report the results of this long-term follow-up. METHODS: All 18 patients included in the original study were periodically re-assessed at weeks 52, 78 and 104 post-implant. At each time-point, motor and non-motor function, quality of life and levodopa equivalent daily dose was assessed using a standardized testing battery. RESULTS: At week 104, no significant differences in UPDRS part III scores in the 'off' state were observed in any of the treatment groups compared to baseline. Only a single serious adverse event - hospitalisation due to Parkinson's disease rigidity not responding to changes in medications - was considered potentially related to the implant procedure. There was no evidence of xenogeneic viral transmission. CONCLUSION: Un-blinded, long-duration follow-up to week 104 post-implantation showed no evidence that putaminal NTCELL® administration produces significant clinical benefit in patients with moderately advanced Parkinson's disease.

Dural venous sinus thrombosis after cerebellopontine angle surgery: Should it be treated?

INTRODUCTION: Dural venous sinus thrombosis is an uncommon, but significant sequela that may occur after resection of a cerebellopontine angle lesion. The natural history and management of this pathology has not been sufficiently studied. METHODS: All operative cases for cerebellopontine angle lesions performed in our local institution dating from 1 January 2005 to 30 June 2018 were retrospectively reviewed to identify patients who developed new post-operative dural venous sinus thrombosis. Patients who developed a significantly narrowed sinus without intrinsic thrombus were also identified. Progression of sinus thrombosis through time was followed, with comparisons made between complications amongst patients with and without a compromised sinus. RESULTS: Of the 126 patients, 20 were found to have new sinus thrombosis, with another 16 developing a critically narrowed sinus without intrinsic thrombus. These cases are significantly associated with translabyrinthine resection of acoustic schwannoma. 4 patients amongst the thrombosed group were commenced on additional therapeutic anticoagulation or antiplatelets, whilst the rest were observed. Based on available follow up imaging, 10/17 patients had significantly improved sinus thrombosis on serial imaging, including 8/14 amongst those not given additional anticoagulation. Patients with a compromised sinus demonstrated a higher rate of cerebrospinal fluid leak requiring blindsac procedures. When involving a dominant sinus, there is also an association of an increased requirement for permanent CSF diversion. CONCLUSION: Therapeutic anticoagulation should be considered for symptomatic post-operative dural venous sinus thrombosis or if it involves a dominant sinus. Further prospective studies are warranted to better elucidate the risk-benefit justification of treatment for postoperative sinus thrombosis.

The epidemiology of patients undergoing meningioma resection in Auckland, New Zealand, 2002 to 2011.

The incidence of meningioma is known to vary by gender and ethnicity. This study aimed to describe the epidemiological characteristics of a 10-year cohort of patients undergoing meningioma resection at Auckland City Hospital, Auckland, New Zealand. Of particular interest was whether there was any difference in meningioma incidence and recurrence rates between New Zealand Maori and Pacific Island patients compared with other ethnic groups. The study was a retrospective analysis of 493 patients with pathologically confirmed meningioma over the period 1 January 2002 to 31 December 2011. Based on this neurosurgical cohort, the minimum incidence of meningioma in the Auckland region was 3.39 per 100,000 population per year (95% C.I. 3.02-3.80) for the study period. Meningioma was significantly more common in women than men by a ratio of 4.2:1. New Zealand Maori and Pacific Island patients had a significantly higher incidence of meningioma than other ethnic groups. New Zealand Maori had a meningioma incidence 2.74 times that of Europeans (95% C.I. 2.01-3.73, p < 0.001). Pacific Island patients had 2.03 times higher incidence of meningioma than Europeans (95% C.I. 1.42 - 2.89, p < 0.001). The overall meningioma recurrence rate was 21.6% with a mean follow-up of 77 months. Recurrence rates for meningioma among Pacific Island patients were significantly higher than for other ethnic groups (hazard ratio 1.73, p = 0.008). Multivariate analysis of clinical variables confirmed the significance of traditional prognostic factors such as WHO tumour grade and Simpson grade of surgical excision in predicting meningioma recurrence.

A phase IIb, randomised, double-blind, placebo-controlled, dose-ranging investigation of the safety and efficacy of NTCELL® [immunoprotected (alginate-encapsulated) porcine choroid plexus cells for xenotransplantation] in patients with Parkinson's disease.

INTRODUCTION: Regenerative therapies in Parkinson's disease aim to slow neurodegeneration and re-establish damaged neuronal circuitry. Neurotrophins are potent endogenous regulators of neuronal survival, development and regeneration. They represent an attractive regenerative treatment option in Parkinson's disease. Porcine choroid plexus produces a number of neurotrophins, and can be safely delivered to the striatum in an encapsulated formulation (termed NTCELL®) to protect them from immune attack. NTCELL® has shown regenerative potential in animal models of stroke, Huntington's disease and Parkinson's disease. Following promising results from an initial open label safety study of intra-striatal delivery of NTCELL® in human subjects, we sought to specifically investigate the safety and efficacy of NTCELL® for the treatment of Parkinson's disease. METHODS: 18 patients aged 56-65 years with idiopathic Parkinson's disease of at least 5 years duration were randomised to receive either sham surgery (general anaesthesia and partial thickness burr holes) or intra-striatal delivery of NTCELL® (the 3 groups in the treatment arm receiving incremental NTCELL® doses). RESULTS: At 26 weeks, we found no significant difference in total UPDRS scores ('on' and 'off'), UPDRS motor scores ('on' and 'off'), PDQ-39, UDysRS, timed walk or modified Hoehn and Yahr stage between patients implanted with NTCELL® and patients undergoing sham procedure. There were no serious adverse events or xenogeneic viral transmission during the study. CONCLUSION: The study did not meet its primary efficacy end-point of a change in UPDRS at 26 weeks post-intervention compared with baseline. Stereotactic NTCELL® implantation was safe and well tolerated.

Patients' Perioperative Experience of Awake Deep-Brain Stimulation for Parkinson Disease.

BACKGROUND: Awake craniotomy for tumor resection and epilepsy surgery is a well-tolerated procedure. Qualitative data on patients' experience of awake deep-brain stimulation (DBS) are, however, lacking. We collected qualitative data on patients' experience of awake DBS with a view to identifying areas for improvement. METHODS: Forty-one patients undergoing DBS for Parkinson disease between 2009 and 2015 were surveyed with a structured questionnaire designed to receive patient feedback regarding perioperative management of the awake stage of the procedure. RESULTS: More than 90% of patients felt well-informed. Most remembered the procedure, and almost all were happy that they did. One half of the patients experienced pain, often significant, during the procedure. This mainly occurred during burr-hole drilling and stereotactic frame placement. CONCLUSIONS: Although awake DBS is well-tolerated, pain and off-period symptoms are an issue for a significant number of patients. Efforts should be made to minimize these unpleasant aspects of awake DBS.

Successful conservative operative management of pineal apoplexy.

A 71-year-old woman presented with obstructive hydrocephalus caused by a haemorrhagic pineal mass. A right ventriculo-peritoneal shunt was inserted with successful treatment of the hydrocephalus and resolution of symptoms and signs. Post-operative MRI both as an inpatient and at 5 and 18 months showed no contrast enhancement of the lesion and there was resolution of the radiographic abnormality. She remains symptom-free at 18 months. Previous reports have advocated resection of the pineal lesion, but this patient has done well with CSF shunting and MRI surveillance.

Peritumoral Citrobacter koseri abscess associated with parasagittal meningioma.

OBJECTIVE AND IMPORTANCE: This is the second report of a Citrobacter-associated brain abscess in an adult and the first report of its association with an intradural tumor. Excluding those associated with trauma, neurosurgical procedures, and proximity to the skull base, only seven other cases of abscesses associated with intracranial tumors have been published. Five of seven tumor-associated abscesses with a microbiological diagnosis involved gram-negative bacteria, a finding that may indicate a predilection of these microorganisms for intracranial tumors. CLINICAL PRESENTATION: A 78-year-old female patient presented with a 6-month history of confusion and personality changes. Her medical history included paroxysmal atrial fibrillation and a 10-day course of high-dose dexamethasone but no other predisposing conditions for sepsis. She was afebrile, had no focal neurological deficits, and had no systemic abnormalities on examination. Computed tomographic imaging revealed a noncalcified, homogeneously enhancing, 3-cm-diameter, extra-axial tumor associated with the right anterior falx cerebri. The tumor did not extend to the skull base. INTERVENTION: At craniotomy, 10 to 20 ml of thick pus was found around the posteroinferior surface of the tumor. On extended culture, this material demonstrated Citrobacter koseri growth, which was effectively treated with ceftriaxone followed by meropenem and one repeated abscess aspiration. No systemic source of the infection was found. CONCLUSION: The characteristic endothelial invasiveness of Citrobacter and related gram-negative bacteria may predispose to the formation of abscesses in association with intracranial tumors.