Glioblastoma (GBM) is a rapidly fatal malignancy typically treated with radiation and temozolomide (TMZ), an alkylating chemotherapeutic. These cytotoxic therapies cause oxidative stress and DNA damage, yielding a senescent-like state of replicative arrest in surviving tumor cells. Unfortunately, recurrence is inevitable and may be driven by surviving tumor cells eventually escaping senescence. A growing number of so-called “senolytic” drugs have been recently identified that are defined by their ability to selectively eliminate senescent cells. A growing inventory of senolytic drugs is under consideration for several diseases associated with aging, inflammation, DNA damage, as well as cancer. Ablation of senescent tumor cells after radiation and chemotherapy could help mitigate recurrence by decreasing the burden of residual tumor cells at risk of recurrence. This strategy has not been previously explored for GBM. We evaluated a panel of 10 previously described senolytic drugs to determine whether any could exhibit selective activity against human GBM persisting after exposure to radiation or TMZ. Three of the 10 drugs have known activity against BCL-XL and preferentially induced apoptosis in radiated or TMZ-treated glioma. This senolytic activity was observed in 12 of 12 human GBM cell lines. Efficacy could not be replicated with BCL-2 inhibition or senolytic agents acting against other putative senolytic targets. Knockdown of BCL-XL decreased survival of radiated GBM cells, whereas knockdown of BCL-2 or BCL-W yielded no senolytic effect. Implications: These findings imply that molecularly heterogeneous GBM lines share selective senescence-induced BCL-XL dependency increase the significance and translational relevance of the senolytic therapy for latent glioma.

The artery of Percheron (AOP) represents a rare anatomic variant of the posterior circulation. It is a solitary trunk that provides bilateral arterial supply to the rostral midbrain and paramedian thalamus. AOP infarction presentation varies, most often presents with altered mental status, memory impairment, and supranuclear vertical gaze palsy. Diagnosis of the AOP infarct is most often missed in the initial CT scan. A majority of these diagnoses are made outside the window of thrombolytic treatment for ischemic stroke. We report a case of a 67-year old male with a history of well-managed diabetes mellitus type 2 and hypertension, presented in the ER sudden onset severe drowsiness. On a physical exam, we found left pupil dilation and left eye deviation. Initial CT scan showed no pathological changes. The diagnosis was made on the third day of hospitalization via an MRI. Our case highlights the unusual presentation and that an absence of evidence of AOP infarction in CT scan does not exclude its diagnosis. The artery of the Percheron infarct requires a comprehensive clinical and radiological examination.

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Cholesterol granulomas are chronic inflammatory lesions located primarily in the apex of the petrous part of the temporal bone. They are benign, tumor-like lesions, consisting of a cystic cavity filled with a chocolate-brown fluid and present as hyperintense masses on T1 and T2 sequences on MRI. The most common causes of cholesterol granulomas are chronic middle ear infections and traumas, explaining their prevalence in young to middle aged patients. Due to their progressively expanding nature, clinical presentation include vertigo, diplopia, tinnitus, hearing loss and seizures. Treatment of cholesterol granulomas consists of two different approaches: watch and wait or radical surgery to remove the granulomatous tissue. We present the case of a 38-year-old male patient who was admitted to the Neurology Clinic with complaints of loss of consciousness, headache, pain on the left side of the face and tinnitus in the left ear. These symptoms had been present for some time and gradually worsened in intensity and frequency. Initially after an EEG was performed, the patient showed signs of focal epilepsy and began treatment accordingly. Subsequently, a CT and an MRI of the head and neck were performed, which showed a large, well demarcated expansile mass within the left petrous apex, which was hyperintense on T1 and T2. Based on his clinical presentation and radiologic findings, a diagnosis of cholesterol granuloma was established. Through this case report we hope to emphasize the role imaging modalities play in the diagnosis and appropriate management of cholesterol granulomas.