Chronicles of EGFR Tyrosine Kinase Inhibitors: Targeting EGFR C797S Containing Triple Mutations

Epidermal growth factor receptor (EGFR) is a receptor tyrosine kinase widely expressed in many cancers such as non-small cell lung cancer (NSCLC), pancreatic cancer, breast cancer, and head and neck cancer. Mutations such as L858R in exon 21, exon 19 truncation (Del19), exon 20 insertions, and others are responsible for aberrant activation of EGFR in NSCLC. First-generation EGFR tyrosine kinase inhibitors (TKIs) such as gefitinib and erlotinib have clinical benefits for EGFR-sensitive (L858R and Del19) NSCLC patients. However, after 10-12 months of treatment with these inhibitors, a secondary T790M mutation at the gatekeeper position in the kinase domain of EGFR was identified, which limited the clinical benefits. Second-generation EGFR irreversible inhibitors (afatinib and dacomitinib) were developed to overcome this T790M mutation. However, their lack of selectivity toward wild-type EGFR compromised their clinical benefits due to serious adverse events. Recently developed third-generation irreversible EGFR TKIs (osimertinib and lazertinib) are selective toward driving mutations and the T790M mutation, while sparing wildtype EGFR activity. The latest studies have concluded that their efficacy was also compromised by additional acquired mutations, including C797S, the key residue cysteine that forms covalent bonds with irreversible inhibitors. Because second- and thirdgeneration EGFR TKIs are irreversible inhibitors, they are not effective against C797S containing EGFR triple mutations (Del19/ T790M/C797S and L858R/T790M/C797S). Therefore, there is an urgent unmet medical need to develop next-generation EGFR TKIs that selectively inhibit EGFR triple mutations via a non-irreversible mechanism.

Comparison of Conventional Surgical Tracheostomy and Percutaneous Dilatational Tracheostomy in the Neurosurgical Intensive Care Unit / 대한신경손상학회지

Objective@#Tracheostomy is a necessary procedure for patients admitted to the neurosurgery intensive care unit (ICU) with severe brain injury, because mechanical ventilation must be maintained for a long time following neurologic failure. The purpose of this study was to compare conventional surgical tracheostomy (CST) and percutaneous dilatational tracheostomy (PDT) performed at the bedside in critically ill neurosurgery patients requiring tracheostomy to determine which procedure has comparative advantages. @*Methods@#This retprospective study was conducted between January 2019 and December 2020. PDT was performed on 52 patients and CST was performed on 44 patients. The baseline characteristics, procedural characteristics, and clinical outcomes were recorded. @*Results@#The mean operative time in the CST group was 25.5±6.5 minutes and that in the PDT group was 15.1±2.5 minutes; the difference was statistically significant (p<0.01). Four patients in the CST group and none in the PDT group experienced bleeding requiring transfusion. However, there was no significant difference in total ICU mortality or length of hospital stay. There were no statistical differences in the individual complication categories between the 2 study groups. @*Conclusion@#There were fewer procedure-induced complications among patients receiving PDT than among those receiving CST. In addition, the treatment time for PDT was shorter than that for CST treatment.

Posterior Inferior Cerebellar Artery Infarction Originating at C1-2 after C1-2 Fusion / 대한신경손상학회지

Vertebral artery injuries associated with C1 lateral mass screw insertion rarely occur during C1-2 fusion. The posterior inferior cerebellar artery (PICA) is uncommonly located at the C1 lateral mass insertion position. A 71-year-old woman with atlanto-axial subluxation and cord compression underwent C1-2 fusion. Sixth nerve palsy and diplopia were detected postoperatively, and decreased consciousness occurred on postoperative day 4. Brain magnetic resonance image (MRI) and computed tomography (CT) revealed PICA infarction. In the preoperative CT angiography, the PICA originated between the C1 and C2 level. In the postoperative CT scan, the PICA was not visible. The patient was treated conservatively for two weeks and recovered. PICA originating between the C1 and C2 level comprises 1.1–1.3% of cases. Therefore, vertebral artery anomalies should be evaluated prior to C1-2 fusion to prevent vessel injuries.

Solitary intraventricular hemorrhage without subarachnoid hemorrhage due to aneurysmal rupture: a case report

The presence of primary intraventricular hemorrhage (IVH) without vascular lesion is very rare. We experienced solitary IVH without subarachnoid hemorrhage due to aneurysmal rupture in a 58-year-old man treated with coil embolization, which contributed to his good prognosis. After 33 days of hospitalization, he had mild right hemiplegic symptoms remaining, and he was transferred to a rehabilitation institute for further treatment. In cases of primary IVH, computed tomography angiography seems worthwhile for making a differential diagnosis, although the possibility of IVH due to cerebral aneurysmal rupture is very low. Endovascular intervention is a good option for diagnosis and treatment.

Cystic Meningiomas: Correlation between Radiologic and Histopathologic Features

BACKGROUND: Tumors with cysts often correlate with gliomas, metastatic tumors, or hemangioblastomas, which require differentiation. METHODS: Thirty-eight cases of cyst associated-meningioma based on preoperative radiologic studies and histologic confirmations were reviewed from November 1998 to July 2017. RESULTS: A total of 395 cases of meningioma were observed in the 20 years, and surgical treatment of intracranial meningioma was performed in 120 cases. Thirty-eight (9.6%) cases of cyst associated meningiomas were analyzed. Nauta type I was the most common type of cyst (39.5%) and the most frequent histopathological subtype was meningothelial type (36.8%). CONCLUSION: Statistically there were no significant associations between meningioma histopathological type and associated cysts; however, the rate of World Health Organization grade II was higher in cyst associated meningiomas than in unrelated meningiomas. This correlation was weak, in accordance with the meningioma grade.

Stent-Assisted Coil Embolization Using Only a Glycoprotein IIb/IIIa Inhibitor (Tirofiban) for Ruptured Wide-Necked Aneurysm Repair

OBJECTIVE: The aim of this study was to evaluate the safety and efficacy of stent-assisted coil embolization using only a glycoprotein IIb/IIIa inhibitor (tirofiban). MATERIALS AND METHODS: We retrospectively reviewed patients with a subarachnoid hemorrhage due to ruptured wide-necked intracranial aneurysms who were treated by stent-assisted coil embolization. In all patients, the glycoprotein IIb/IIIa inhibitor tirofiban was administered just before stent deployment. Electronic medical records for these patients were reviewed for peri-procedural complications and extra-ventricular drainage catheter related hemorrhage, as well as Glasgow outcome scale (GOS) at discharge, 3 months, and 6 months follow-up were recorded. RESULTS: Fifty-one aneurysms in 50 patients were treated. The mean patient age was 64.9 years. Eighteen patients (36%) received a World Federation of Neurosurgical Societies grade of 4 or 5. The mean aneurysm size was 9.48 mm and mean dome-to-neck ratio was 1.06. No intraoperative aneurysm ruptures occurred, although five (10%) episodes of asymptomatic stent thrombosis did occur. Three patients experienced a delayed thrombo-embolic event and two a delayed hemorrhagic event. Immediate radiologic assessment indicated a complete occlusion in 29 patients, a residual neck in 19, and a residual sac in 3. Four patients (8%) died. Sixteen patients (32%) experienced a poor GOS (< 4). Two aneurysms were recanalized during the follow-up period (mean, 19 months for clinical and 18 months for angiographic follow-up). CONCLUSION: Treatment of ruptured wide-necked intracranial aneurysms via stent-assisted coil embolization with a glycoprotein IIb/IIIa inhibitor alone was found to be relatively safe and efficient.

Y-configuration Stent-assisted Coil Embolization for Wide-necked Intracranial Bifurcation Aneurysms

OBJECTIVE: The objective of this study was to determine the efficiency and safety of Y configuration stent-assisted coiling with double-closed stents for wide-necked intracranial aneurysms located at arterial bifurcations thorough analysis of a multicenter case series. MATERIALS AND METHODS: A retrospective chart review was done on 10 patients who underwent endovascular treatment of wide-necked intracranial aneurysms with Y-configuration stent-assisted coil embolization in three centers from August 2011 to March 2014. The degree of aneurysmal occlusion was assessed using the Raymond scale. Clinical outcomes were assessed before operation, at discharge, and at the last follow-up visit using the Glasgow outcome scale. RESULTS: The 10 patients included 6 females and 4 males with a mean age of 58.6 years. Indications for treatment included 6 unruptured intracranial aneurysms and 4 ruptured intracranial aneurysms. Five aneurysms were located at the basilar artery bifurcation, four aneurysms were located in an anterior communicating artery, and one aneurysm was in the pericallosal artery. The mean size of the 10 aneurysms was 9.7 mm. All aneurysms had a dome-to-neck ratio of < 1.5 (mean, 0.89). Immediate complications included one thromboembolic event out of the 10 cases. Immediate posttreatment angiograms showed complete occlusion in 1 aneurysm and residual necks in 9 aneurysms. Follow-up results showed 8 complete occlusions and 2 residual necks. No delayed complications were observed during the follow-up period (mean: 20 months). CONCLUSION: Y configuration using double-closed cell stents is feasible and safe in selected patients. This method is an acceptable option for managing complex wide-necked bifurcations.

Persistent Primitive Trigeminal Artery That Mimics Persistent Primitive Otic Artery on Cerebral Angiography

Persistent primitive trigeminal artery (PPTA) is the most common carotid-basilar anastomosis; on the other hand, persistent primitive otic artery (PPOA) is extremely rare. PPTA is often misdiagnosed as PPOA on cerebral angiography. We present a case of PPTA that mimicked PPOA on cerebral angiography. We further describe the utility of brain computed tomography angiography for differential diagnosis of PPTA from PPOA, together with a review of previous literature.

Electrodiagnostic Studies in Neurological Complications of Acute Hemorrhagic Conjunctivitis

Electrodiagnostic studies were carried out in 31 patients with neurological complications of AHC, who were seen at Seoul National University Hospital from August 1981 to February 1982. Age of the patients ranged from 14 to 62 years. Both velocity and distal latency of motor and sensory conduction were normal in the nerves innervating the affected muscles. During the acute phase of motor paralysis, there was an absence of electrical activity in completely paralysed muscles. In partially denervated muscles, there were polyphasic motor unit potentials of normal duration and amplitrde on weak contraction and reduced interference on maximal effort. From the third or fourth week onwards, fibrillation potentials and positive sharp waves at rest were observed in paraspinal muscles in most cases. All the above findings were supporting the view that the principal site of involvement for the paralytic phenomena is at the level of the anterior horn cells or anterior roots.