Unruptured aneurysmal clipping complicated by delayed and refractory vasospasm: case report.

BACKGROUND: Delayed symptomatic vasospasm is a rare complication following clipping of an unruptured intracranial saccular aneurysm. There have been ten reported cases of delayed symptomatic vasospasm and only two of these occurred after 2 weeks from initial intervention. Our case is the first to document the refractory nature of such vasospasm despite aggressive first line therapy. CASE PRESENTATION: Here, we present a 67-year-old female who had surgical clipping of a 10x7mm right middle cerebral artery (MCA) bifurcation aneurysm. Her surgery and initial postoperative course were uncomplicated, but she presented with acute left hemiparesis, dysarthria, headache and vomiting on post-op day 29 secondary to vasospasm of M2. She was initially stabilized with intra-arterial verapamil then managed with volume expansion, permissive hypertension, and nimodipine. She developed recurrent vasospasm of M2 the following day and was again treated with intra-arterial verapamil. Magnetic resonance imaging (MRI) brain showed an infarction involving the right basal ganglia, frontal lobe, and parietal lobe and her hospital course was complicated by super-refractory status epilepticus. At her follow up appointment she displayed continued left lower extremity weakness, left visual field defect, and left-sided neglect. CONCLUSIONS: Overall, cerebral vasospasms associated with unruptured aneurysms remain rare complications and are not often monitored for after initial recovery. Reviewing the documented cases highlights the unpredictability of when these events occur with our current knowledge. Current hypotheses for the mechanisms responsible for delayed and refractory vasospasms include: blood-derived breakdown products, mechanically induced vasospastic responses, and delayed reactions from the trigemino-cerebrovascular system (TCVS). The uncertainly of these events warrants further research and supports a strong argument for monitoring patients with initial surgical clipping up to a month out from their initial procedure.

"Doctor, what would you do if you were me?" - A survey of physician perspectives toward glioblastoma resection.

OBJECTIVE: How maximal safe resection (MSR) of glioblastoma is implemented in the clinical setting remains understudied. Here, we utilized a survey-based approach to understand physician perspectives on this matter. METHODS: Scenarios involving glioblastomas were presented to physicians who were asked to select from planned sub-total resection (STR), gross total resection (GTR), medical therapy only, or palliative care. Demographic, experience, and Likert scales of value assessment were collected. RESULTS: In the scenario involving a corpus callosum glioblastoma, 2.33% opted for GTR. For a right frontal glioblastoma, 91.7% opted for GTR. In contrast, only 30.8% chose GTR of a right motor strip glioblastoma (p< 0.001). When presented with a left motor strip glioblastoma, fewer respondents (12.7%,p < 0.001) opted for GTR. Physicians who placed a high value on preserving physical independence were more likely to forgo GTR for right motor glioblastomas (HR=0.068,95% CI:0.47-0.97,p=0.035), and physicians who placed a high value on their faith were more likely to opt for surgical treatments that differ from the general consensus, for instance opting for GTR of the corpus callosum glioblastoma (HR=4.18,95%CI:1.63-10.74,p=0.003). No other associations were found between the choice for GTR and other variables collected. INTERPRETATION: Our results suggest that while maximal safe resection remains a guiding principle for glioblastoma resection, physician preference in terms of the extent of resection varies significantly as a function of tumor location and personal values.

Proteopathic tau primes and activates interleukin-1ß via myeloid-cell-specific MyD88- and NLRP3-ASC-inflammasome pathway.

Pathological hyperphosphorylation and aggregation of tau (pTau) and neuroinflammation, driven by interleukin-1ß (IL-1ß), are the major hallmarks of tauopathies. Here, we show that pTau primes and activates IL-1ß. First, RNA-sequence analysis suggests paired-helical filaments (PHFs) from human tauopathy brain primes nuclear factor κB (NF-κB), chemokine, and IL-1ß signaling clusters in human primary microglia. Treating microglia with pTau-containing neuronal media, exosomes, or PHFs causes IL-1ß activation, which is NLRP3, ASC, and caspase-1 dependent. Suppression of pTau or ASC reduces tau pathology and inflammasome activation in rTg4510 and hTau mice, respectively. Although the deletion of MyD88 prevents both IL-1ß expression and activation in the hTau mouse model of tauopathy, ASC deficiency in myeloid cells reduces pTau-induced IL-1ß activation and improves cognitive function in hTau mice. Finally, pTau burden co-exists with elevated IL-1ß and ASC in autopsy brains of human tauopathies. Together, our results suggest pTau activates IL-1ß via MyD88- and NLRP3-ASC-dependent pathways in myeloid cells, including microglia.