Access to MRI in Patients With Cardiac Implantable Electronic Devices is Variable and an Issue in Australia.

AIMS: This study aimed to characterise the level of access to magnetic resonance imaging (MRI) in Australian hospitals for patients with MR-conditional and non-MR-conditional cardiac implantable electronic devices (CIED), and to identify any barriers impeding this access. METHODS: All Australian Tertiary Referral Public Hospitals (n=38) were surveyed with a mixed qualitative and quantitative questionnaire. Provision of MRI to patients with MR-conditional and non-MR-conditional CIEDs; patient monitoring strategies during scan and personnel in attendance; barriers impeding MRI access. RESULTS: Of the 35 (92%) hospitals that completed the survey, a majority (85.7%) scan MR-conditional CIEDs, while a minority (8.6%) scan non-MR-conditional CIEDs. MR-conditional device scanning is often limited to non-pacing dependent patients, excluding implantable cardioverter-defibrillators. In total, 21% of sites exclude thoracic MR scans for CIED patients. Although most centres scan on 1.5 Tesla (T) machines (59%), 10% scan at 3T and 31% scan at both strengths. Sites vary in patient monitoring strategies and personnel in attendance; 80% require staff with Advanced Cardiac Life Support to be present. Barriers to service expansion include an absence of national guidelines, formal training, and logistical device support. CONCLUSIONS: Most surveyed Australian hospitals offer MRI for patients with MR-conditional CIEDs, however many still have exclusions for particular patient groups or scan requests. Only three surveyed sites offer MRI for patients with non-MR-conditional CIEDs in Australia. A national effort is needed to address the identified barriers including the development of national guidelines, formal training, and logistical support.

Role of Optic Nerve Sheath Fenestration in Inflammatory Pachymeningitis Causing Visual Impairment.

Eye disease due to pachymeningitis caused by immunoglobulin G4-related disease (IgG4-RD) is a rare occurrence. Here, the authors report a unique case of a patient presenting with visual loss from raised intracerebral pressure from pachymeningitis most likely related to IgG4-RD. The patient was treated with acetazolamide and steroids, and an optic nerve sheath fenestration was performed to successfully save the patients vision.

Diagnostic and management considerations in incidental common peroneal intraneural haemangioma.

Intraneural haemangiomas are rare tumours that can affect peripheral nerves. We describe a case of a 10-year-old female with an incidental finding of a common peroneal nerve lesion following knee injury. MRI demonstrated avid heterogeneous enhancement and peri-lesional oedema, and an open biopsy was performed revealing haemangioma on histopathological analysis. The patient was managed with observation and remains intact at 24-month follow-up.

Influence of molecular classification in anaplastic glioma for determining outcome and future approach to management.

INTRODUCTION: Assess survival of patients with anaplastic glioma (AG) and the relationship to molecular subtype. METHODS: Patients with AG managed with IMRT between 2008 and 2014 were entered into a prospective database assessing relapse-free survival (RFS) and overall survival (OS). Isocitrate dehydrogenase (IDH) mutations were assessed prospectively from 2011, and subsequent testing of historical patients allowing categorisation under WHO 2016 classification as anaplastic astrocytoma IDH wild type (AAwt), anaplastic astrocytoma IDH mutated (AAmut), anaplastic oligodendroglioma (AOD) or other glial tumour (OTH). Kaplan-Meier estimates of survival distribution were calculated for the primary endpoint of overall survival and Log-rank test used to determine associated factors. RESULTS: One hundred and fifty-six patients were included with median follow-up for survivors of 4.7 years. Fifty-six per cent were managed after initial diagnosis, whilst 18% received IMRT at second or later relapse. Seventy-three per cent had temozolomide as part of initial therapy. A total of 118 or 75% of patients had IDH mutated glioma, of which 61 were AOD and 57 AAmut. There were 68 relapses and 52 deaths for a 6yrRFS of 51.2% and 6yrOS of 62.5%. AAwt was associated with worse survival (P < 0.001); and delay of RT until second or later relapse (P = 0.03). Within the 118 patients with IDH mutated tumours, 6yrOS for AOD and AAmut were 90.0% and 62.5%, respectively (P = 0.003). Also two or more craniotomies (P < 0.001), delayed RT (P = 0.006) and age <40 years (P = 0.022) were associated with worse survival on univariate analysis but only AAmut subtype and number of craniotomies on multivariate analysis. CONCLUSION: Within AG, molecular classification predicts for survival, and should influence current decision-making.

Tumour volume reduction following PET guided intensity modulated radiation therapy and temozolomide in IDH mutated anaplastic glioma.

The role of maximal surgical debulking in isocitrate dehydrogenase (IDH) mutated anaplastic glioma prior to adjuvant radiation therapy remains uncertain. This study assessed the reduction in tumour volume following intensity modulated radiation therapy (IMRT) and temozolomide in this favourable and more responsive tumour pathology. 56 patients were managed from 2011 to 2014 and 53 had residual disease. To assess radiological response, tumour volumes were created on representative T1/T2Flair MRI sequences using identical slice-levels in three planes for pre-IMRT, month + 3 and month + 12 post-IMRT scans. Change in volumes was assessed between time periods. Progression-free survival (PFS) was calculated from start of radiotherapy. Median follow-up for survivors is 48.2 months. Pathology was anaplastic oligodendroglioma (AOD) and anaplastic astrocytoma IDH-mutated (AAmut) in 32 and 21 patients respectively. 93% received sequential chemotherapy. The median residual disease on T1 and T2Flair imaging was 9.7 cm3 and 20.6 cm3. 17 patients relapsed for projected 5 year PFS of 74.9%; with 8 isolated relapses within initial surgical site. On MRI at month + 3, the median volume for T1 and T2Flair reduced by 69.4% and 67.3% respectively; which further decreased to 82.4% and 81.3% at month + 12. By month + 12, 69.2% and 62.2% of patients had >75% volume reduction. Patients with AOD had superior reduction at month + 3 compared with AAmut (p = 0.02); but equivalent reduction at month + 12 (p = 0.14). Thus, in patients with anaplastic glioma harbouring an IDH mutation, where an attempt at near-total resection may be associated with unacceptable morbidity, this data suggests that the radiation therapy may provide effective cytoreduction of residual disease.

Predicting patterns of failure in temporal lobe GBMs: possible implications on radiotherapy treatment portals.

BACKGROUND: Characterise patterns of failure of Temporal Lobe (TL) Glioblastoma (GBM) following treatment with relation to normal temporal lobe anatomy and neural pathways. METHODS: 335 GBM patients received radiotherapy between 03/2007 and 07/2014, 100 were located in TL. Site of initial tumour and subsequent relapse were subdivided into 5 local TL sites (anterior, lateral, medial, posterior and superior); 5 adjacent regional sites (occipital lobe, inferior frontal lobe, caudate/thalamus/internal/external capsules, fornix/ventricular trigone), and 5 distant failure sites (ventricles, contralateral hemisphere, brainstem, leptomeninges and spine). Extension along major neuroanatomical pathways at initial presentation and at first documented Magnetic Resonance Imaging (MRI) failure were categorised into anterior, superior, medial and posterior pathways. RESULTS: Of the 100 patients, 86 had radiological progress with a median survival of 17.3 months. At initial diagnosis, 74% of tumours were linked to one TL site and 94% were confined to the TL. 19% had neural pathway disease at initial pre-treatment MRI. At first recurrence locoregional site failure was 74%. 26% failed within distant sites and 53% patients were noted to have neural pathway involvement. Initial tumour location predicted for local site recurrence (p < 0.0001), regional site recurrence (p = 0.004) and neural pathway recurrence pattern (p = 0.005), but not for distant sites (p = 0.081). CONCLUSION: Most GBMs fail at local or adjacent regional sites. Many of the recurrences occurred in a predictable pattern within a local or regional site, unique to initial TL site with more than half involving neural pathways. Knowledge of tumour infiltration and failure may improve target definition and radiotherapy.

Survival improvements with adjuvant therapy in patients with glioblastoma.

BACKGROUND: Evaluate survival of patients diagnosed with glioblastoma multiforme (GBM) managed with adjuvant intensity modulated radiation therapy and temozolomide since the introduction of the European Organisation for Research and Treatment of Cancer and National Cancer Institute of Canada Clinical Trials Group (EORTC-NCIC) protocol. METHODS: All patients with GBM managed between May 2007 and December 2014 with EORTC-NCIC protocol were entered into a prospective database. The primary endpoint was the median survival. Univariate predictors of survival were evaluated with respect to tumour resection, age and Eastern Cooperative Oncology Group (ECOG) performance status using log-rank comparisons. RESULTS: Two hundred and thirty-three patients were managed under the protocol and analysed for outcome. The median age was 57 years; the rate of gross total resection, subtotal resection and biopsy were 47.2%, 35.2% and 17.6%, respectively. At progression, 49 patients had re-resection, and in addition to second-line chemotherapy, 86 patients had Bevacizumab including 26 with re-irradiation. Median survival was 17.0 months (95% CI: 15.4-18.6). On univariate evaluation, extent of resection (P = 0.001), age, ECOG performance status and recursive partitioning analysis class III were shown to significantly improve survival (P < 0.0001). The median survival for gross total resection, age <50 years, ECOG 0-1 and recursive partitioning analysis class III were 21, 27, 20 and 47 months, respectively. CONCLUSION: This study confirms the significant improvement in median survival in GBM that has occurred in recent years since introduction of the EORTC-NCIC protocol. Further improvements have occurred presumably related to subspecialized care, improved resection rates, sophisticated radiotherapy targeting and early systemic salvage therapies. However, the burden of the disease within the community remains high and the median survival improvements over time have plateaued.

Utilizing 18F-fluoroethyl-l-tyrosine positron emission tomography in high grade glioma for radiation treatment planning in patients with contraindications to MRI.

INTRODUCTION: Patients with high grade glioma (HGG) and contraindications to magnetic resonance imaging (MRI) are dependent on contrast-enhanced computerized tomography (CT) scan imaging for radiation therapy (RT) target volume delineation. This study reviews the experience with the utilization of 18F-fluoroethyl-l-tyrosine positron emission tomography (FET-PET) to define residual disease post craniotomy and optimize RT planning. METHODS: Patients with HGG and a contraindication to MRI managed with radiation therapy between 2007 and 2015 were identified. RT target volumes including gross tumour volume (GTV) defined by CT-alone and the biological target volume (BTV) defined by PET-CT were recorded. Clinical target volumes (CTV) were created from the GTV and BTV respectively using standard protocol volume expansion. The expanded BTV was termed clinical target volume biological (CTV-B). Union and intersection between CTV and CTV-B, conformity index, volumetric parameters and individual patient outcomes were analysed. RESULTS: Six patients fit study criteria. There was a mean increase in CTV-B from CTV by 31.6% with a conformity index of 0.78. Two out of six patients had FET-PET avid disease outside the constructed PTV when delineated by CT-alone. One patient with CT-only planning had a new contrast-enhancing mass within 1 month of completing RT, suggesting potential geographical miss. CONCLUSION: Patients with contraindication to MRI the addition of FET-PET can improve target volume delineation for RT Planning.

Pharmacokinetics of Cromolyn and Ibuprofen in Healthy Elderly Volunteers.

BACKGROUND AND OBJECTIVES: The combination of cromolyn and ibuprofen is being investigated as a treatment for early Alzheimer's disease (AD). This study investigated the pharmacokinetics, safety, and tolerability of cromolyn and ibuprofen co-administration in healthy elderly adult volunteers. METHODS: In this open-labeled study, 26 subjects, aged 55-75 years, received co-administration of inhaled cromolyn (single dose 17.1 mg; double dose 34.2 mg total) and oral ibuprofen (single dose 10 mg; double dose 20 mg total). Blood sampling was performed for 6 h after co-administration in all subjects; cerebrospinal fluid (CSF) was collected in three to four subjects per cohort for 4 h following co-administration. Safety parameters, including adverse events (AEs), were monitored throughout the study. RESULTS: For cromolyn, the mean (±SD) maximum observed concentration (C max) in plasma was 46.69 ± 32.97 and 96.75 ± 46.22 ng/ml after single- and double-dose inhalation, respectively [time to C max (t max) ~22 min for each; terminal elimination half-life (t ½) ~1.8 h for each]. For ibuprofen, the plasma C max was 1090.98 ± 474.64 ng/ml and 2062.96 ± 655.13 ng/ml after single- and double-dose oral administration, respectively (t max ~1.6-1.8 h; t ½ ~1.9 h for each). For cromolyn, the CSF C max was 0.24 ± 0.08 ng/ml at 3.72 ± 0.70 h after single-dose administration and 0.34 ± 0.17 ng/ml at 3.45 ± 0.95 h after double-dose administration, and for ibuprofen, the CSF C max was 3.94 ± 1.29 ng/ml at 2.55 ± 0.96 h after single-dose administration and 8.93 ± 3.29 ng/ml at 3.15 ± 1.05 h after double-dose administration. Three (12%) subjects reported mild or moderate AEs which were unlikely to be related to study drug. CONCLUSIONS: The combination of cromolyn and ibuprofen was safe and well tolerated. The concentrations of cromolyn and ibuprofen observed in the CSF are considered sufficient to titrate the estimated daily amyloid production and the associated inflammatory response in patients with AD.

Survival Outcomes of Elderly Patients With Glioblastoma Multiforme in Their 75th Year or Older Treated With Adjuvant Therapy.

PURPOSE: To assess the outcomes of the most elderly cohort of patients with a diagnosis of glioblastoma multiforme (GBM) after intensity modulated radiation therapy (IMRT). METHODS AND MATERIALS: The data of patients with GBM who had underwent IMRT from May 2007 to December 2015 were entered into a prospective database. Analysis was performed on the data from patients diagnosed during or after 75 years of age. The primary endpoint was the median survival. Univariate and multivariate analyses were performed with respect to survival for patients aged 74 to 80 versus >80 years, Eastern Cooperative Oncology Group performance status of 0 to 1 versus 2 to 3, extent of resection, a high radiation dose (60 Gy) versus any hypofractionated schedule, MGMT methylation status, planning target volume, and the use of temozolomide (TMZ) versus no TMZ. RESULTS: Of the 108 patients, 35 received best supportive care, 1 received TMZ alone, 40 received RT alone, and 32 received combined RT and TMZ. IMRT was delivered with a hypofractionated technique (40 Gy) in 58 patients or long-course RT (60 Gy) in 11 patients. The median age was 79 years, with 61.6% of patients aged 74 to 80 years and 38.4% aged >80 years. Of the 108 patients, 64 died during the follow-up period, with a median survival of 10 months (95% confidence interval 7.1-11.9), projected 12-month survival rate of 35.6%, and 24-month survival rate of 7.9%. On univariate analysis, the independent predictors of survival included younger age (P=.02), better performance status (P=.014), greater resection extent (P=.002), and TMZ use (P<.001). MGMT methylation status, RT dose, and planning target volume showed no significant differences between the groups. Only chemotherapy use remained statistically significant (P=.035) on multivariate analysis. CONCLUSION: The current data underrepresent elderly patients aged >75 years with GBM. Despite elderly patients having a worse prognosis, the results of the present study suggest the presence of survival benefits with IMRT for selected patients that can be further extended with addition of TMZ. Further study of this cohort and an understanding of the appropriate selection criteria are warranted.

Femoroacetabular impingement.

Femoroacetabular impingement (FAI) of the hip is a well-recognized entity that can cause hip pain and limit range of motion. Although there are 2 types of FAI (cam and pincer), these 2 entities most commonly coexist. Plain radiographs and magnetic resonance imaging are commonly used to assess FAI, and play an integral role in diagnosis in conjunction with patient symptoms and clinical examination. Treatment of FAI is also evolving, with arthroscopic management becoming increasingly more popular. This review provides an overview of the proposed etiology, mechanisms, clinical history, imaging, and treatment of FAI.

Computed tomographic analysis of outer calvarial thickness for osseointegrated bone-anchored hearing system insertion.

INTRODUCTION: Osseointegrated bone-anchored hearing systems (BAHSs) are a useful tool in auditory rehabilitation for single-sided deafness and conductive/mixed hearing loss. They rely on adequate osseointegration of titanium implants, which can be limited by calvarial thickness. This study examines adult computed tomographic (CT) temporal bone normative data for calvarial thickness in the areas commonly recommended for BAHS insertion and identifies hazards that may compromise the osseointegration process. METHODS: Prospective analysis of 100 consecutive adult helical CT scans. Calvarial thickness was measured in axial and coronal planes 5.5 cm posterior to the superior external auditory canal at 6 vertical points (EAC, +1 cm, +2 cm, +3 cm, +4 cm, and +5 cm). Other parameters measured include temporal bone pneumatization and the presence of suture lines, bone marrow, and vascular structures. RESULTS: A total of 195 temporal bones were examined in 100 patients. Mean patient age was 60.9 years, of whom 54.4% were men and 45.6% were women. Mean calvarial thickness was greatest at +1 cm above the EAC level (6.3 mm) and thinnest at +4 cm (5.1 mm). Of temporal bones, 55% had at least 1 site thinner than 4 mm and 21% had at least 1 site thinner than 3 mm. Air cells and suture lines were more likely to be encountered within 2 cm above the EAC level, and marrow space is more likely to be encountered 3 to 4 cm above the EAC level. DISCUSSION: Selecting a position 3 to 4 cm above the level of the EAC is more likely to result in dural exposure for a 3-mm BAHS abutment, especially in men. Selecting a position near the level of the EAC provides thicker bone, but the surgeon is more likely to encounter suture line or enter mastoid air cells. Preoperative CT imaging may be a useful tool in evaluating calvarial thickness and hazards when planning BAHS insertion in the adult population.

Intrathecal catheter granuloma associated with isolated baclofen infusion.

Intrathecal (IT) baclofen is an effective management strategy for controlling spasticity in patients unresponsive to maximal oral therapy. We present the case of a 57-yr-old woman who was rendered quadriplegic after a complete spinal cord transection at the C6 level. Her course was complicated by severe spasms, which were uncontrolled despite titrating orally administered baclofen to 80 mg/d. IT baclofen testing was performed with good response, and administration was commenced via an implanted intrathecal pump 6 mo after the injury at an initial dose of 200 microg/d. Catheter revision was required 2 wk later as a result of catheter displacement. The initial IT baclofen dose was gradually increased to achieve good control at a level of 400 microg/d. After a period of stability lasting 38 mo, her lower limb spasms dramatically increased in severity and remained poorly controlled despite repeated dose increases. Contrast pumpogram and computed tomography myelogram were performed to exclude a mechanical cause for this apparent increase in baclofen requirement. These investigations revealed neither catheter displacement nor fracture as suspected but, rather, displayed the presence of a catheter tip-associated mass. Catheter tip granuloma has not previously been described in a patient receiving IT baclofen alone. This suggests that although uncommon, the possibility of catheter-associated granuloma must be considered in all patients receiving IT baclofen presenting with altered neurological function or significant increase in drug requirement.

Intracranial hypotension caused by cervical cerebrospinal fluid leak: treatment with epidural blood patch.

UNLABELLED: This report describes treatment with cervical epidural blood patch of low cerebrospinal fluid (CSF) pressure headache resulting from spontaneous CSF leak via a tear in a cervical dural cuff. The leak was diagnosed by a dynamic computed tomography (CT)-myelography study followed by gadolinium enhanced magnetic resonance imaging(MRI)-scan. The epidural needle was inserted with the aid of image intensifier and CT-scan to guide the needle to the precise site of the CSF leak. Blood mixed with gadolinium was injected, and subsequent MRI scanning provided the first description of spread of blood after cervical epidural blood patch. IMPLICATIONS: Low cerebrospinal fluid (CSF) pressure may cause severe posturally-related headache. In the patient, a vertebral disc protrusion in the neck seems to have contributed to a CSF leak. An injection of blood into the epidural space at the precise site of the CSF leak was followed by complete and lasting resolution of the headache.

Daptomycin pharmacokinetics and safety following administration of escalating doses once daily to healthy subjects.

The purpose of this paper is to establish the pharmacokinetics and safety of escalating, once-daily doses of daptomycin, a novel lipopeptide antibiotic active against gram-positive pathogens, including those resistant to methicillin and vancomycin. This phase 1, multiple-dose, double-blind study involved 24 healthy subjects in three dose cohorts (4, 6, and 8 mg/kg of body weight) who were randomized to receive daptomycin or the control at a 3:1 ratio and administered the study medication by a 30-min intravenous infusion every 24 h for 7 to 14 days. Daptomycin pharmacokinetics was assessed by blood and urine sampling. Safety and tolerability were evaluated by monitoring adverse events (AEs) and laboratory parameters. Daptomycin pharmacokinetics was linear through 6 mg/kg, with a slight ( approximately 20%) nonlinearity in the area under the curve and trough concentration at the highest dose studied (8 mg/kg). The pharmacokinetic parameters measured on the median day of the study period, (day 7) were half-life ( approximately 9 h), volume of distribution ( approximately 0.1 liters/kg), systemic clearance ( approximately 8.2 ml/h/kg), and percentage of the drug excreted intact in urine from 0 to 24 h ( approximately 54%). Daptomycin protein binding (mean amount bound, 91.7%) was independent of the drug concentration. No gender effect was observed. All subjects who received daptomycin completed the study. The frequencies and distributions of treatment-emergent AEs were similar for the subjects who received daptomycin and the control subjects. There were no serious AEs and no pattern of dose-related events. The pharmacokinetics of once-daily administration of daptomycin was linear through 6 mg/kg. For all three doses, plasma daptomycin concentrations were consistent and predictable throughout the dosing interval. Daptomycin was well tolerated when it was administered once daily at a dose as high as 8 mg/kg for 14 days.

CT perfusion scanning with deconvolution analysis: pilot study in patients with acute middle cerebral artery stroke.

PURPOSE: To measure mean cerebral blood flow (CBF) in ischemic and nonischemic territories and in low-attenuation regions in patients with acute stroke by using deconvolution-derived hemodynamic imaging. MATERIALS AND METHODS: Twelve patients with acute middle cerebral artery stroke and 12 control patients were examined by using single-section computed tomography (CT) perfusion scanning. Analysis was performed with a deconvolution-based algorithm. Comparisons of mean CBF, cerebral blood volume (CBV), and mean transit time (MTT) were determined between hemispheres in all patients and between low- and normal-attenuation regions in patients with acute stroke. Two independent readers examined the images for extent of visually apparent regional perfusion abnormalities. The data were compared with extent of final infarct in seven patients with acute stroke who underwent follow-up CT or magnetic resonance imaging. RESULTS: Significant decreases in CBF (-50%, P =.001) were found in the affected hemispheres of patients with acute stroke. Significant changes in CBV (-26%, P =.03) and MTT (+111%, P =.004) were also seen. Significant alterations in perfusion were also seen in low- compared with normal-attenuation areas. Pearson correlation between readers for extent of CBF abnormality was 0.94 (P =.001). Intraobserver variation was 8.9% for CBF abnormalities. CONCLUSION: Deconvolution analysis of CT perfusion data is a promising method for evaluation of cerebral hemodynamics in patients with acute stroke.