Pierre Giglio

Syncope and head CT scans in the emergency department

ContextPatients presenting with syncope to the emergency department (ED) of a community hospital were evaluated.AimThe objective of this study is to examine the use and results of head computerized tomography (CT) scans in patients presenting with syncope to the ED of a community hospital.Settings and designA retrospective chart review of patients presenting with syncope to the emergency room was conducted.Methods and materialsWe reviewed the charts of patients who presented to the ED over a 6-month period with syncope. When performed, head CT scan findings were noted, and their relationship to the clinical presentation was examined.ResultsOne hundred twenty-eight patients were identified. Forty-four patients had their head CT scans performed. In 1 patient, the CT scan showed evidence of infarction in the posterior circulation. In 19 patients, the head CT scan was normal. Twenty-four patients had abnormal findings unrelated to the ED presentation.ConclusionsHead CT scans were commonly used in our series of syncope patients. Abnormal findings pertinent to the syncope were observed in only 1 patient. A prospective study examining yield in a larger series of patients may help define the utility of this neuroimaging modality in syncope.

Diffuse magnetic resonance imaging white-matter changes in a 15-year-old boy with mitochondrial encephalomyopathy.

We report a 15-year-old boy who presented with recurrent headaches associated with numbness, confusion, and speech difficulty. Brain magnetic resonance imaging (MRI) revealed diffuse bilateral white-matter hyperintensity on fluid-attenuated inversion-recovery and T2-weighted images in the internal capsule, periventricular and subcortical white matter, base of the pons, and middle cerebellar peduncles. Lesions were isointense on T1weighted images and nonenhancing. Muscle biopsy showed changes consistent with a mitochondrial myopathy. Mitochondrial respiratory chain enzyme activity analysis revealed a significant reduction in complex II activity. Genetic testing was negative. We conclude that mitochondrial encephalomyopathy may present with unusual diffuse supratentorial and infratentorial white-matter changes on MRI. (J Child Neurol 2002;17:47-49).

Synergistic Effects of Crizotinib and Temozolomide in Experimental FIG-ROS1 Fusion-Positive Glioblastoma

Glioblastoma (GB) is the most common malignant brain tumor. Drug resistance frequently develops in these tumors during chemotherapy. Therefore, predicting drug response in these patients remains a major challenge in the clinic. Thus, to improve the clinical outcome, more effective and tolerable combination treatment strategies are needed. Robust experimental evidence has shown that the main reason for failure of treatments is signal redundancy due to coactivation of several functionally linked receptor tyrosine kinases (RTKs), including anaplastic lymphoma kinase (ALK), c-Met (hepatocyte growth factor receptor), and oncogenic c-ros oncogene1 (ROS1: RTK class orphan) fusion kinase FIG (fused in GB)-ROS1. As such, these could be attractive targets for GB therapy. The study subjects consisted of 19 patients who underwent neurosurgical resection of GB tissues. Our in vitro and ex vivo models promisingly demonstrated that treatments with crizotinib (PF-02341066: dual ALK/c-Met inhibitor) and temozolomide in combination induced synergistic antitumor activity on FIG-ROS1-positive GB cells. Our results also showed that ex vivo FIG-ROS1+ slices (obtained from GB patients) when cultured were able to preserve tissue architecture, cell viability, and global gene-expression profiles for up to 14 days. Both in vitro and ex vivo studies indicated that combination blockade of FIG, p-ROS1, p-ALK, and p-Met augmented apoptosis, which mechanistically involves activation of Bim and inhibition of survivin, p-Akt, and Mcl-1 expression. However, it is important to note that we did not see any significant synergistic effect of crizotinib and temozolomide on FIG-ROS1-negative GB cells. Thus, these ex vivo culture results will have a significant impact on patient selection for clinical trials and in predicting response to crizotinib and temozolomide therapy. Further studies in different animal models of FIG-ROS1-positive GB cells are warranted to determine useful therapies for the management of human GBs.

Primary central nervous system lymphoma masquerading as herpes encephalitis: clinical, magnetic resonance imaging and pathologic findings

An 84-year-old man presented with acute confusion, global aphasia, and fever. Magnetic resonance imaging (MRI) showed hyperintense lesions on T2-weighted and fluid-attenuated inversion recovery (FLAIR) images predominantly affecting the cortical gray matter of the left mesial temporal and inferior frontal lobes, and insula. Acyclovir was prescribed for presumed viral encephalitis. Clinical and MRI worsening prompted a left temporal lobe biopsy that revealed primary central nervous system lymphoma (PCNSL). This case adds to the MRI spectrum of PCNSL and illustrates that it may mimic the clinical and MRI presentation of herpes simplex encephalitis.

Paradoxical Brain Embolism From Thrombus Associated With Vena Caval Filter in a Patient With Cancer

A 71‐year‐old man experienced sudden onset of hemiparesis and aphasia. He had a 4‐month history of gallbladder cholangiocarcinoma, complicated with a postoperative deep‐vein thrombosis (DVT) that necessitated a vena caval filter placement. Diffusion‐weighted magnetic resonance imaging of the brain showed multiple hyperintense foci. Magnetic resonance spectroscopy was compatible with cerebral infarction. Abdominal computed tomography showed a thrombus in the inferior vena cava extending through the filters. A transcranial Doppler bubble study revealed the presence of a right‐to‐left shunt. Paradoxical cerebral embolism must be considered in patients with DVT who have new onset neurologic deficits even in the presence of a caval filter.