Pretreatment findings on magnetic resonance imaging in primary central nervous system lymphoma may predict overall survival duration.

BACKGROUND: and purpose: Primary central nervous system lymphoma (PCNSL) lesions often show avid contrast enhancement on T1-weighted contrast-enhanced MRI sequences. However, several case reports and a clinical study have described PCNSL in patients with no contrast enhancement on MRI. We assessed whether overall survival (OS) time was related to any tumor characteristics (lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; and edema) on MRI in patients with PCNSL. MATERIALS AND METHODS: We retrospectively reviewed records (MRI features, pathology, and survival data) of all patients at our institution with PCNSL who had been seen from, 2007 through 2017, and had undergone pretreatment MRI. RESULTS: We identified 79 patients (42 men, 37 women) with a mean age at diagnosis of 61.7 ± 10.4 years. The mean OS duration was 44.6 ± 41.7 months. The most common pathological diagnosis (74 patients) was diffuse large B-cell lymphoma. No associations were found between OS time and lesion location, volume, and number; contrast enhancement; necrosis; proximity to the subarachnoid space; or edema. However, a sole patient with non-enhancing PCNSL on MRI was found to have low-grade disease, with prolonged survival (>83 months). Several other patients with leptomeningeal disease had a mean OS time of 80 months. Patients with hemorrhagic lesions had a mean OS of 25.5 months. CONCLUSIONS: The survival time for patients with PCNSL may be longer than previously thought, especially for patients with leptomeningeal seeding and lesions with hemorrhagic components Also, non-enhancing tumors may be less aggressive than enhancing tumors.

Early phase clinical studies of AR-42, a histone deacetylase inhibitor, for neurofibromatosis type 2-associated vestibular schwannomas and meningiomas.

OBJECTIVES: Two pilot studies of AR-42, a pan-histone deacetylase inhibitor, in human neurofibromatosis type 2 (NF2), vestibular schwannomas (VS), and meningiomas are presented. Primary endpoints included safety, and intra-tumoral pharmacokinetics (PK) and pharmacodynamics (PD). METHODS: Pilot 1 is a subset analysis of a phase 1 study of AR-42 in solid tumors, which included NF2 or sporadic meningiomas. Tumor volumes and treatment-related adverse events (TRAEs) are reported (NCT01129193).Pilot 2 is a phase 0 surgical study of AR-42 assessing intra-tumoral PK and PD. AR-42 was administered for 3 weeks pre-operatively. Plasma and tumor drug concentrations and p-AKT expression were measured (NCT02282917). RESULTS: Pilot 1: Five patients with NF2 and two with sporadic meningiomas experienced a similar incidence of TRAEs to the overall phase I trial. The six evaluable patients had 15 tumors (8 VS, 7 meningiomas). On AR-42, tumor volume increased in six, remained stable in eight, and decreased in one tumor. The annual percent growth rate decreased in eight, remained stable in three, and increased in four tumors. Pilot 2: Four patients with sporadic VS and one patient with meningioma experienced no grade 3/4 toxicities. Expression of p-AKT decreased in three of four VS. All tumors had higher AR-42 concentrations than plasma. CONCLUSIONS: AR-42 is safe. Tumor volumes showed a mixed response, but most slowed growth. On a 40-mg regimen, drug concentrated in tumors and growth pathways were suppressed in most tumors, suggesting this may be a well-tolerated and effective dose. A phase 2 study of AR-42 for NF2-associated tumors appears warranted. LEVEL OF EVIDENCE: 1b, 4.

Meningioangiomatosis: Clinical, Imaging, and Histopathologic Characteristics.

Meningioangiomatosis is a rare benign lesion involving the central nervous system. Radiographic appearance can be highly variable which makes pre-operative diagnosis difficult. In this report, we describe meningioangiomatosis in a previously healthy 17-year-old woman who presented with seizures and continued headache and dizziness. This patient presented with a predominately calcified lesion on imaging and eventually underwent near total resection. Meningioangiomatosis is difficult to preoperatively identify, but is an important consideration as prognosis with surgical resection is typically good.

Impact of Ketorolac on Opioid Consumption after Knee Arthroscopy.

PURPOSE: The objective of this study was to examine postoperative opioid consumption in outpatients undergoing knee arthroscopy after a single dose of intravenous ketorolac. METHODS: Patients ages 18-65 years old, weighing over 50kg and scheduled for knee arthroscopy were randomized to one of the four groups of preoperative ketorolac (0mg, 7.5mg, 15mg, 30mg). The primary outcome measured was postoperative opioid consumption. Secondary outcomes included visual analog scale pain scores, patient satisfaction scores, side effects and total postoperative anesthesia care unit time. Equivalency between ketorolac groups in opioid reduction relative to placebo was evaluated for each dose pair (7.5 vs. 15mg, 7.5 vs. 30mg, and 15 vs. 30mg). Linear regression models were used to examine associations between ketorolac dose with postoperative length of stay and patient satisfaction. A linear mixed model was used to evalaute the association between ketorolac dose and pain scores over time. RESULTS: A total of 112 patients with comparable patient and procedural characteristics were enrolled. Equivalency in opioid reduction relative to placebo was not demonstrated between any examined ketorlac doses (7.5 vs. 15mg, P = 0.167; 7.5 vs. 30mg, P = 0.451; 15 vs. 30mg, P = 0.515). Compared to placebo, all ketorlac doses decreased postoperative pain scores (global P=0.012). Patient satisfaction and postoperative duration did not vary with ketorolac dose. CONCLUSIONS: Although all ketorolac doses decreased PACU pain scores, equivalency in PACU opioid reduction between ketorolac doses was not demonstrated.

MRI with Magnetic Resonance Spectroscopy of multiple brain abscesses secondary to Scedosporium apiospermum in two immunocompromised patients.

Scedosporium apiospermum is a deadly fungal infection that can infect the central nervous system, particularly in immunocompromised patients. We present two cases of Scedosporium brain abscesses. The first case was fatal and relevant conventional MRI and MR spectroscopy findings are discussed. To our knowledge, this is the first reported case of MR spectroscopy in Scedosporium apiospermum abscesses. In the second case, the patient recovered and conventional MR findings are followed over several months. In the appropriate clinical setting, conventional MR imaging and MR spectroscopy may facilitate diagnosis, earlier initiation of antifungal pharmacotherapy and surgical intervention in this frequently fatal infection.

Hemorrhage rates and outcomes when using up to 100 mg intra-arterial t-PA for thrombolysis in acute ischemic stroke.

This work presents a unique single center experience with intra-arterial delivery of tissue plasminogen activator (t-PA) doses as high as 100mg for thrombolysis. Hemorrhage volumes, hemorrhage rates, clinical outcomes and radiographic outcomes were assessed. Prospectively collected angiographic, clinical and laboratory information on 67 consecutive patients with acute ischemic stroke involving either the m1 segment of the middle cerebral artery, the intracranial internal carotid artery or the basilar artery were retrospectively analyzed. Patients who received more than 50 mg t-PA were compared with those patients receiving 50 mg or less. Outcome measures included: symptomatic hemorrhage, significant hemorrhage volume (greater than 25 ml), hemorrhage rate, change in National Institutes of Health stroke scale score at 24 hours and at hospital discharge, modified Rankin score at 90 days, in-hospital deaths, death within 90 days, reperfusion rate, and infarct volume. Multivariate logistic regression analysis demonstrated that t-PA dose over 50 mg was associated with higher rates of hemorrhage and larger hemorrhages. Poor pial collateral formation, poor reperfusion (less than 50% of the territory involved), and platelet count below 200 K/µL influenced hemorrhage. Limiting t-PA dose to 100mg rather than 50mg improved documented reperfusion rates from 37% to 61%. Restricting intra-arterial t-PA administration to 100mg rather than 50mg, is associated with higher overall reperfusion rates and improves overall outcomes, however, the hemorrhage rate is also elevated. Poor pial collateral formation and platelet count less than 200 K/µL may be reasons to curtail the use of higher t-PA dose to reduce hemorrhage rate.

Intra-arterial thrombolysis within three hours of stroke onset in middle cerebral artery strokes.

BACKGROUND AND PURPOSE: The Prolyse in Acute Cerebral Thromboembolism II (PROACT II) trial showed improved outcomes in patients with proximal middle cerebral artery (MCA) occlusions treated with intra-arterial (IA) thrombolysis within 6 h of stroke onset. We analyzed outcomes of patients with proximal MCA occlusions treated within 3 h of stroke onset in order to determine the influence of time-to-treatment on clinical and angiographic outcomes in patients receiving IA thrombolysis. METHODS: Thirty-five patients from three academic institutions with angiographically demonstrated proximal MCA occlusions were treated with IA thrombolytics within 3 h of stroke onset. Outcome measures included outcomes at 30-90 day follow-up, recanalization rates, incidence of symptomatic intracranial hemorrhage, and mortality in the first 90 days. The endpoints were compared to the IA treated and control groups of the PROACT II trial. RESULTS: The median admission National Institutes of Health Stroke Scale (NIHSS) score was 16 (range 4-24). The mean time to initiation of treatment was 106 min (range 10-180 min). Sixty-six percent of patients treated, had a modified Rankin Scale (mRS) score of 2 or less at 1-3 month follow-up compared to 40% in the PROACT II trial. The recanalization rate was 77% (versus 66% in PROACT II). The symptomatic intracranial hemorrhage rate was 11% (versus 10% in PROACT II) and the mortality rate was 23% (versus 25% in PROACT II). CONCLUSION: Time-to-treatment is just as important in IA thrombolysis as it is in IV thrombolysis, both for improving clinical outcomes and recanalization rates as well.

Primary meningeal CNS lymphoma treated with intra-arterial chemotherapy and blood-brain barrier disruption.

Diffuse large B-cell lymphoma of the meninges is a particularly rare form of primary CNS lymphoma. We report a case of a 63-year-old woman found to have primary meningeal lymphoma (PML) with dural and leptomeningeal involvement whom we treated with multiple cycles of intra-arterial (IA) methotrexate, intravenous (IV) etoposide phosphate, and IV cyclophosphamide after reversible osmotic blood-brain barrier disruption (BBBD). Improvement was evident on gadolinium-enhanced brain MRI one month into therapy. At 67 months post-diagnosis there is no evidence of CNS disease. After completing her therapy regimen, she remained disease-free for 34 months, when stage IV diffuse large B-cell lymphoma was discovered in her left adrenal gland and right thigh. Following six cycles of rituximab and CHOP treatment, she is presently in complete remission. IA methotrexate and reversible osmotic BBBD without radiation therapy may be an effective therapy for treating PML.

Spinal myxopapillary ependymoma metastatic to bilateral internal auditory canals.

OBJECTIVES: We report a rare case of spinal myxopapillary ependymoma metastatic to both internal auditory canals (IACs) and its implications for diagnosing neurofibromatosis type 2 (NF2). METHODS: We present a detailed clinical history, magnetic resonance imaging (MRI), intraoperative photographs, and histopathologic findings from a patient with bilateral IAC lesions, and review the diagnostic criteria for NF2. RESULTS: An 11-year-old boy with surgically resected spinal myxopapillary ependymoma, treated with total spine irradiation for recurrence, later showed bilaterally enhancing IAC lesions on T1-weighted MRI with contrast. The diagnosis of NF2 with bilateral vestibular schwannomas was entertained. Close examination of T2-weighted MRI, however, demonstrated the masses to be isointense to cerebrospinal fluid. This finding raised the possibility of other, more unusual IAC lesions. The patient underwent sequential suboccipital craniotomies for tissue diagnosis, and both IAC lesions were found to be myxopapillary ependymomas. CONCLUSIONS: This is the youngest reported patient with metastatic myxopapillary ependymoma. Although vestibular schwannomas account for the majority of contrast-enhancing T1-weighted IAC lesions, other uncommon lesions may present in a similar manner. A T2 fast-spin echo screening MRI would have missed this patient's lesions. Therefore, both T1-weighted MRI with or without contrast and T2-weighted MRI may be necessary to distinguish vestibular schwannoma from other, more unusual IAC lesions.

Extradural dermoid tumor of the petrous apex. Case report.

Dermoid cysts are rare, benign, congenital tumors. Most case series thus far have featured intradural tumors. The authors report on a case of an extradural dermoid tumor of the middle cranial fossa with osseous invasion, successfully removed using a left subtemporal extradural approach. The clinical presentation, histological features, radiological findings, and management of this unique case are described.

Incidence of infusion plan alterations after angiography in patients undergoing intra-arterial chemotherapy for brain tumors.

During intra-arterial (IA) chemotherapy of brain tumors, the initial vessels chosen for infusion are based on the vascular distribution of the tumor as revealed by CT or MR imaging. However, angiography may reveal details of vascular anatomy that require an alteration of the vessel infusion plan. The incidence of infusional alterations and the underlying vascular anatomy involved remains unknown in patients with brain tumors undergoing IA chemotherapy. To evaluate this question, we performed a chart, CT/MRI, and angiography review of brain tumor patients receiving IA chemotherapy. Seventy-eight patients were identified with primary (39) and metastatic (39) brain tumors. The cohort consisted of 40 males and 38 females, with a mean age of 47.8 years. During the course of IA treatment, angiographic review identified 5 patients (6.4%) that required an alteration of the vessel infusion plan. In three cases, angiography demonstrated more substantial perfusion of the tumor from a different arterial supply. In two cases, angiography revealed variations in normal anatomy associated with unexpected tumor perfusion. Careful interpretation of angiography at the initiation of each cycle of IA chemotherapy is very important to verify that the appropriate vessels have been chosen for drug infusion, in order to maximize regional dose intensity. In our series, the angiography results necessitated an alteration of the infusion plan in 6.4% of the patient cohort.

Prevalence and rupture rate of cerebral aneurysms discovered during intra-arterial chemotherapy of brain tumors.

BACKGROUND: During the administration of intra-arterial (IA) chemotherapy for the treatment of brain tumors (BTs), angiography may demonstrate asymptomatic, incidental cerebral aneurysms. The prevalence and complication rate of incidental aneurysms in patients undergoing IA chemotherapy remains unknown. It remains unclear whether the presence of an aneurysm represents an increased risk or a contraindication to this form of treatment. METHODS: We performed a chart and angiography review of BT patients receiving IA chemotherapy over the previous 16 months. Seventy-eight patients were identified with primary (39) and metastatic (39) BTs. RESULTS: The cohort consisted of 40 men and 38 women, with a mean age of 47.8 years (range, 22-80 years). During initial angiography, 8 patients (10.3%) were identified with incidental cerebral aneurysms. The aneurysms were saccular and varied in size from 2-4 mm (mean, 3 mm). Seven of the 8 patients continued IA chemotherapy after detection of the aneurysm, for a total of 35 IA procedures. Of these 7 patients, 5 expired from nonaneurysmal complications (mean survival, 5.4 months; range, 2-10 months); 4 from the primary tumor, and one from an infected craniotomy site. Two patients continue to survive; one remains in treatment, and the other has completed 12 months of IA therapy. There were no aneurysmal complications during or after IA treatment in any of the BT patients. CONCLUSION: Incidental aneurysms may be more common in patients with BTs than the general population. In our patient population, there was no indication that an incidental aneurysm was reason to preclude or delay the use of IA chemotherapy.

Assessment of the lingual nerve in the third molar region using magnetic resonance imaging.

PURPOSE: The purpose of this study was to determine the precise in situ location of the lingual nerve in the third molar region using high-resolution magnetic resonance imaging. PATIENTS AND METHODS: Ten healthy volunteers (20 sides) with mandibular third molars underwent bilateral axial and coronal high-resolution magnetic resonance imaging (MRI) examinations of the posterior mandible and floor of the mouth from the lingula to the mental foramen. Three trained individuals made measurements of each image to determine the vertical and horizontal position of the lingual nerve in the third molar region. RESULTS: The mean vertical (2.75 +/- 0.97 mm [range, 1.52-4.61]) and horizontal (2.53 +/- 0.67 mm [range, 0.00-4.35]) distances to the lingual crest and lingual plate of the mandible were determined. In the third molar region, there were only 2 of 20 cases (10%) in which the nerve was above the lingual crest, and there were 5 of 20 instances (25%) in which the nerve was in direct contact with the lingual plate. CONCLUSIONS: This study precisely documents the in situ location of the lingual nerve in the third molar region, and reconfirms the relative vulnerable position of this structure during third molar surgery.

The effect of hemicholinium-3 and physostigmine on choline in rat brain.

Physostigmine and hemicholinium-3 were examined for their effects on rat brain choline levels after microwave irradiation and after postmortem incubation. Hemicholinium-3 and physostigmine increased choline levels in the cerebellum and striatum when measured after microwave irradiation, but decreased the level of choline produced after postmortem incubation of the brain areas. Addition of the drugs in vitro to whole brain homogenates also decreased postmortem choline production. The data shows that the effect of hemicholinium-3 and physostigmine on in vivo choline levels can be differentiated from their effects on the postmortem production of choline, suggesting that the drugs are affecting at least two of the regulatory processes for choline in the brain.