Matthias Reitz

Intranasal Delivery of Neural Stem/Progenitor Cells: A Noninvasive Passage to Target Intracerebral Glioma

Stem cell‐based therapies for neurological disorders, including brain tumors, advance continuously toward clinical trials. Optimized cell delivery to the central nervous system remains a challenge since direct intracerebral injection is an invasive method with low transplantation efficiency. We investigated the feasibility of intranasal administration of neural stem/progenitor cells (NSPCs) as an alternative, noninvasive, and direct passage for the delivery of stem cells to target malignant gliomas. Tumor‐targeting and migratory pathways of murine and human NSPCs were investigated by intravital magnetic resonance imaging and in histological time course analyses in the intracerebral U87, NCE‐G55T2, and syngenic Gl261 glioblastoma models. Intranasally administered NSPCs displayed a rapid, targeted tumor tropism with significant numbers of NSPCs accumulating specifically at the intracerebral glioma site within 6 hours after intranasal delivery. Histological time series analysis revealed that NSPCs migrated within the first 24 hours mainly via olfactory pathways but also by systemic distribution via the microvasculature of the nasal mucosa. Intranasal application of NSPCs leads to a rapid, targeted migration of cells toward intracerebral gliomas. The directional distribution of cells accumulating intra‐ and peritumorally makes the intranasal delivery of NSPCs a promising noninvasive and convenient alternative delivery method for the treatment of malignant gliomas with the possibility of multiple dosing regimens.

Clinical relevance of associated aneurysms with arteriovenous malformations of the posterior fossa.

The aim of this study was to determine the frequency of aneurysms associated with arteriovenous malformations (AVMs) of the posterior fossa and their relation to hemorrhagic presentation in comparison to supratentorial AVMs. We performed a retrospective analysis of 474 patients with intracranial AVMs treated in our center from 1990 to 2010. Patients were analyzed for AVM size, drainage type and their clinical course with focus on vessel anomalies including AVM-associated aneurysms. Seventeen (30%) of 57 posterior fossa AVMs versus 46 (11%) of 417 supratentorial AVMs were associated with aneurysms. In six (10.5%) versus seven (1.7%) patients, respectively, flow-associated aneurysms were the source of hemorrhage. Infratentorial location of an AVM was a significant risk factor for the incidence (p < 0.001) and rupture (p < 0.001) of AVM-associated aneurysms. Feeding artery aneurysms in particular represented a risk factor for hemorrhage in the overall group of AVM patients, independently of the location (p < 0.001). The majority of patients with a posterior fossa AVM were treated by combined embolization and surgical removal within one procedure (n = 33, 58%). Feeding artery aneurysms were excluded by endovascular coiling or surgical clipping whenever feasible. Overall treatment-associated permanent morbidity in the subgroup of posterior fossa AVMs was 11% (n = 6) and mortality 4% (n = 2). Posterior fossa AVMs display a significantly higher frequency of associated aneurysms of the adjacent vessels that are correlated to the high bleeding rate compared to AVMs of the supratentorial compartment. We therefore recommend aggressive AVM treatment including the exclusion of associated aneurysms as a minimal therapeutic goal whenever possible.

Intramedullary spinal cavernoma: clinical presentation, microsurgical approach, and long-term outcome in a cohort of 48 patients

OBJECT Intramedullary spinal cavernoma (ISC) is a rare entity and accounts for approximately 5%-12% of all spinal vascular pathologies. The purpose of the present study was to examine the influence of clinical presentation, localization, and different surgical approaches on long-term outcome in patients treated for ISC. METHODS The authors performed a retrospective single-center study of 48 cases of ISC treated microsurgically over the past 28 years. Analyzed factors included preoperative clinical history, microsurgical strategies, neurological outcome (American Spinal Injury Association [ASIA] grade, Epstein and Cooper grade), and the occurrence of postoperative spinal ataxia. Univariate analysis was performed to identify factors influencing long-term outcome. RESULTS Preoperatively, 18.8% of all patients experienced a slow, progressive decline in neurological function and 33.3% suffered repetitive episodes of acute neurological deterioration over a time frame of months to years. Moreover, 16.7% noted the sudden onset of a severe neurological deficit, whereas 25% experienced the sudden onset of symptoms with a subsequent gradually progressive decline in neurological function. On long-term follow-up after treatment (mean ± SD, 79.3 ± 35.2 months), 70.8% of patients showed no change in neurological function, 6.3% suffered from a decline, and 22.9% improved neurologically. Thoracolumbar localization (p = 0.043), low preoperative Epstein and Cooper grade for the lower extremities (p < 0.001), and a low preoperative ASIA grade (p < 0.001) were identified as factors associated with an unfavorable outcome (ASIA Grade A-C). The rate of spinal ataxia related to surgical approach was 16.7%. CONCLUSION Postoperative neurological function in ISC patients is determined by the preoperative neurological status. On long-term follow-up after microsurgical treatment, 93.7% of patients presented with a stable or improved condition (ASIA grade); thus, definite microsurgical treatment should be considered as long as patients present with only mild symptoms after the diagnosis of symptomatic ISC.

56‐YEAR OLD WOMAN WITH SPHENOID WING TUMOR

Cranial Chondromyxoid Fibroma (CMF) is an extremely rare diagnosis. We report a case of a 56-year old female patient who presented with a left-sided chronic headache. The neuroradiological examination revealed an osteolytic lesion in the left sphenoid bone. Following a gross total resection pathological evaluation revealed the lesion to be a CMF. To the best of our knowledge, this is the first case of an intracranial CMF localized within the lateral sphenoid wing. Microsurgical, total resection with tumor-free boundaries is the therapy of choice. Correspondence 228 Brain Pathology 21 (2011) 225–228