Ha Son Nguyen

Progressing Bevacizumab-Induced Diffusion Restriction Is Associated with Coagulative Necrosis Surrounded by Viable Tumor and Decreased Overall Survival in Patients with Recurrent Glioblastoma

The authors explored regions of diffusion restriction following bevacizumab therapy in patients with glioblastoma by 1) analyzing tissue samples from patients at postmortem to pathologically confirm tumor cellularity or coagulative necrosis and 2) assessing the patient populationto determine the effect that these lesions have on overall survival. The postmortem examinations were performed on 6 patients with recurrent glioblastoma on bevacizumab withprogressively growing regions of diffusion restriction. ADC values were extracted from regions of both hypercellular tumor and necrosis. They conclude that progressive diffusion-restricted lesions were pathologically confirmed to be coagulative necrosis surrounded by viable tumor and associated with decreased overall survival. BACKGROUND AND PURPOSE: Patients with recurrent glioblastoma often exhibit regions of diffusion restriction following the initiation of bevacizumab therapy. Studies suggest that these regions represent either diffusion-restricted necrosis or hypercellular tumor. This study explored postmortem brain specimens and a population analysis of overall survival to determine the identity and implications of such lesions. MATERIALS AND METHODS: Postmortem examinations were performed on 6 patients with recurrent glioblastoma on bevacizumab with progressively growing regions of diffusion restriction. ADC values were extracted from regions of both hypercellular tumor and necrosis. A receiver operating characteristic analysis was performed to define optimal ADC thresholds for differentiating tissue types. A retrospective population study was also performed comparing the overall survival of 64 patients with recurrent glioblastoma treated with bevacizumab. Patients were separated into 3 groups: no diffusion restriction, diffusion restriction that appeared and progressed within 5 months of bevacizumab initiation, and delayed or stable diffusion restriction. An additional analysis was performed assessing tumor O6-methylguanine-DNA-methyltransferase methylation. RESULTS: The optimal ADC threshold for differentiation of hypercellularity and necrosis was 0.736 × 10−3mm2/s. Progressively expanding diffusion restriction was pathologically confirmed to be coagulative necrosis surrounded by viable tumor. Progressive lesions were associated with the worst overall survival, while stable lesions showed the greatest overall survival (P < .05). Of the 40% of patients with O6-methylguanine-DNA-methyltransferase methylated tumors, none developed diffusion-restricted lesions. CONCLUSIONS: Progressive diffusion-restricted lesions were pathologically confirmed to be coagulative necrosis surrounded by viable tumor and associated with decreased overall survival. Stable lesions were, however, associated with increased overall survival. All lesions were associated with O6-methylguanine-DNA-methyltransferase unmethylated tumors.

Coincidence of an anterior cerebral artery aneurysm and a glioblastoma: case report and review of literature.

Background The association between glioblastoma and intracranial aneurysm is rare. Treatment guidelines do not exist, and operative mortality and morbidity are significantly high. To our knowledge, no prior cases have employed endovascular therapy for the treatment of these intra-tumor intracranial aneurysms followed by tumor resection. Case presentation A 74-year-old male, history of a left A2 aneurysm, presented after a motor vehicle accident at low speeds. Imaging was concerning for a possible traumatic brain contusion, an aneurysmal hemorrhage given history of left A2 aneurysm, or a hemorrhage from an underlying tumor given profound edema. The patient was discussed at the brain tumor board, where the plan was to address the aneurysm followed by resection of the mass versus close monitoring with subsequent imaging. The high risk of rehemorrhage, given the real possibility of an aneurysmal hemorrhage, motivated prompt treatment of the aneurysm. The patient was taken to the angiography suite; an anterosuperiorly projecting azygous A2 aneurysm, measuring 4.5 mm × 5.5 mm with a neck width at 3.5 mm and a small daughter sac, was completely obliterated with primary coiling. The following day, he underwent a left craniotomy along a forehead skin crease for mass excision. Final pathology revealed glioblastoma. The patient recovered well from both procedures, with a baseline neurological exam. The patient subsequently underwent hypofractionated radiation and temodar. Conclusion To our knowledge, no prior cases have employed endovascular therapy for the treatment of these intracranial aneurysms. We emphasize that efforts to introduce less invasive elements may improve the overall outcomes in this rare patient population.

Lumbar spine endplate fractures: Biomechanical evaluation and clinical considerations through experimental induction of injury.

Lumbar endplate fractures were investigated in different experimental scenarios, however the biomechanical effect of segmental alignment was not outlined. The objectives of this study were to quantify effects of spinal orientation on lumbar spine injuries during single‐cycle compressive loads and understand lumbar spine endplate injury tolerance. Twenty lumbar motion segments were compressed to failure. Two methods were used in the preparation of the lumbar motion segments. Group 1 (n = 7) preparation maintained pre‐test sagittal lordosis, whereas Group 2 (n = 13) specimens had a free‐rotational end condition for the cranial vertebra, allowing sagittal rotation of the cranial vertebra to create parallel endplates. Five Group 1 specimens experienced posterior vertebral body fracture prior to endplate fracture, whereas two sustained endplate fracture only. Group 2 specimens sustained isolated endplate fractures. Group 2 fractures occurred at approximately 41% of the axial force required for Group 1 fracture (p < 0.05). Imaging and specimen dissection indicate endplate injury consistently took place within the confines of the endplate boundaries, away from the vertebral periphery. These findings indicate that spinal alignment during compressive loading influences the resulting injury pattern. This investigation identified the specific mechanical conditions under which an endplate breach will take place. Development of endplate injuries has significant clinical implication as previous research identified internal disc disruption (IDD) and degenerative disc disease (DDD) as long‐term consequences of the axial load‐shift that occurs following a breach of the endplate.

Upright magnetic resonance imaging of the lumbar spine: Back pain and radiculopathy

Background: Lumbar back pain and radiculopathy are common diagnoses. Unfortunately, conventional magnetic resonance imaging (MRI) findings and clinical symptoms do not necessarily correlate in the lumbar spine. With upright imaging, disc pathologies or foraminal stenosis may become more salient, leading to improvements in diagnosis. Materials and Methods: Seventeen adults (10 asymptomatic and 7 symptomatic volunteers) provided their informed consent and participated in the study. A 0.6T upright MRI scan was performed on each adult in the seated position. Parameters were obtained from the L2/3 level to the L5/S1 level including those pertaining to the foramen [cross-sectional area (CSA), height, mid-disc width, width, thickness of ligamentum flavum], disc (bulge, height, width), vertebral body (height and width), and alignment (lordosis angle, wedge angle, lumbosacral angle). Each parameter was compared based on the spinal level and volunteer group using two-factor analysis of variance (ANOVA). Bonferroni post hoc analysis was used to assess the differences between individual spinal levels. Results: Mid-disc width accounted for 56% of maximum foramen width in symptomatic volunteers and over 63% in asymptomatic volunteers. Disc bulge was 48% greater in symptomatic volunteers compared to asymptomatic volunteers. CSA was generally smaller in symptomatic volunteers compared to asymptomatic volunteers, particularly at the L4-L5 and L5-S1 spinal levels. Thickness of ligamentum flavum (TLF) generally increased from the cranial to caudal spinal levels where the L4-L5 and L5-S1 spinal levels were significantly thicker than the L1-L2 spinal level. Conclusions: The data implied that upright MRI could be a useful diagnostic option, as it can delineate pertinent differences between symptomatic volunteers and asymptomatic volunteers, especially with respect to foraminal geometry.

Granulomatous amebic encephalitis following hematopoietic stem cell transplantation.

Background: Granulomatous amebic encephalitis (GAE) is rare, but often fatal. The infection has been documented predominantly among the immunocompromised population or among those with chronic disease. To date, however, there have only been eight cases regarding the infection following hematopoietic stem cell transplantation (HSCT). Case Description: A 62-year-old female with a history of relapsed diffuse large B-cell lymphoma, recently underwent peripheral blood autologous stem cell transplant after BEAM conditioning (day 0). On day +15, she began to exhibit worsening fatigue, generalized weakness, and fever. Symptoms progressed to nausea, emesis, somnolence, confusion, and frontal headaches over the next few days. Imaging demonstrated multifocal ill-defined vasogenic edema with patchy enhancement. The patient was started on broad antibiotics, antifungals, and seizure prophylaxis. Evaluation for bacterial, fungal, mycobacterial, and viral etiologies was fruitless. Her mental status progressively deteriorated. On day +22, she exhibited severe lethargy and went into pulseless electrical activity arrest, requiring chest compressions. The episode lasted <2 min and her pulse was restored. She was taken to the operating room for a brain biopsy. Postoperatively, her right pupil began to dilate compared to the left; she demonstrated extensor posturing in her upper extremities and withdrawal in her lower extremities. Repeat computed tomography demonstrated progressive edema. Given poor prognosis and poor neurological examination, the family opted for withdrawal of care. Final pathology was consistent with Acanthamoeba GAE. Conclusion: The authors report the third case of GAE after autologous stem cell transplant, and the ninth case overall after HSCT. This case is unusual due to its rapid clinical presentation after HSCT compared to prior literature. The case highlights the need for high suspicion of Acanthamoeba infection in this patient population.

Surgical decompression coupled with diagnostic dynamic intraoperative angiography for bow hunter's syndrome.

Background: Bow hunters syndrome, also known as rotational vertebrobasilar insufficiency, arises from mechanical compression of the vertebral artery during the neck rotation. Surgical options have been the mainstay treatment of choice. Postoperative imaging is typically used to assess adequate decompression. On the other hand, intraoperative assessment of decompression has been rarely reported. Case Description: A 52-year-old male began to see “black spots,” and experienced presyncope whenever he rotated his head toward the right. The patient ultimately underwent a dynamic diagnostic cerebral angiogram, which revealed a dominant right vertebral artery and complete proximal occlusion of the right vertebral artery with the head rotated toward the right. Subsequently, the patient underwent an anterior transcervical approach to the right C6/C7 transverse process. The bone removal occurred along with the anterior wall of the C6 foramen transversarium, followed by the upper portion of the anterior C6 body medially, and the transverse process of C6 laterally. An oblique osseofibrous band was noted to extend across the vertebral artery; it was dissected and severed. An intraoperative cerebral angiogram confirmed no existing compression of the vertebral artery with the head rotated toward the right. The patient recovered from surgery without issues; he denied recurrence of preoperative symptoms at follow-up. Conclusions: The authors report the third instance where intraoperative dynamic angiography was employed with good outcomes. Although intraoperative cerebral angiography is an invasive procedure, which prompts additional risks, the authors believe the modality affords better, real-time visualization of the vertebral artery, allowing for assessment of the adequacy of the decompression. This advantage may reduce the probability for a second procedure, which has its own set of risks, and may counteract the risks involved with intraoperative dynamic angiography.

Case Report and Review of Literature of Delayed Acute Subdural Hematoma

BACKGROUND The authors present a case of delayed acute subdural hematoma and review all reported cases in the literature. The focus of this paper is to identify the subset of the population who are at risk, and determine whether they should be admitted for observation in the setting of mild traumatic brain injury. CASE DESCRIPTION A 75-year-old woman taking daily aspirin (81 mg) had a fall with loss of consciousness. Her Glasgow Coma Scale (GCS) score was 15 at the time of presentation to the emergency department. However, because of her postconcussive symptoms, computed tomography (CT) of the head was obtained, and the results were negative for any intracranial hemorrhage or fractures. She was admitted for workup. The next day, she neurologically deteriorated to a GCS score of 6. CT of the head was reobtained and showed acute, left-sided subdural hematoma with shift and herniation. She was taken to operating room for emergent decompressive craniotomy. Postoperatively, she developed left-sided temporal and occipital intraparenchymal hemorrhage. She died after being placed on comfort care. CONCLUSION Delayed acute subdural hematoma occurs mainly in the middle-aged or older population who are taking anticoagulation or antiplatelet therapy. Most patients have a GCS score of 15 with no loss of consciousness. Neurological deterioration occurs within the first 24 hours for 70% of the patients. Therefore, we recommend admission and observation of these selected group of patients. Due to small reported population of patients, we could not determine whether the patients taking anticoagulant, antiplatelet, or both anticoagulant and antiplatelet medication are at higher risk. In addition, the role of delayed CT of the head without change in the examination result needs to be explored further.

Density measurements with computed tomography in patients with extra-axial hematoma can quantitatively estimate a degree of brain compression.

Background Extra-axial hematoma can cause significant brain compression. Guidelines for surgical evacuation include imaging findings (midline shift and hematoma thickness/volume) in conjunction with Glasgow Coma Scale (GCS) scores and/or intracranial pressure (ICP) monitoring. Physiologically, overall brain density should also change with compression. In our observational study, we explored whether overall brain density, defined using computed tomography Hounsfield Units (CT HU), changes after surgical evacuation of extra-axial hematoma. Methods and materials Only patients with a surgical acute epidural hematoma or subacute/chronic subdural hematoma were considered. Other exclusion criteria were concurrent intraparenchymal pathology, bilateral pathology, or incomplete follow-up imaging. Between fall 2012 and spring 2015, 22 patients were included in the study. CT head imaging (preoperative, postoperative, and at ∼1- to 2-month clinic visit) were loaded into OsiriX (Pixmeo, Switzerland). All the intracranial regions were selected and all extra-axial features were removed; subsequently, software was used to calculate a global CT HU value. Results A repeated-measures ANOVA found significant time effect, p < 0.01, with significance between preoperative versus postoperative CT (p = 0.03) and preoperative versus clinic visit CT (p < 0.01). Conclusion The results from this study suggest that extra-axial hematomas, which deform the brain, can cause an elevation in global CT HU value; moreover, surgical decompression is associated with lower global CT HU values. The use of global CT HU values in selected populations may serve as an adjunct for the evaluation of surgical lesions.

Posterolateral lumbar fusion: Relationship between computed tomography Hounsfield units and symptomatic pseudoarthrosis.

Background: Assessment of bone quality can guide spinal surgery. However, surgeons infrequently evaluate bone quality in a quantitative manner. Recent literature suggests a role for computed tomography (CT) Hounsfield units (HUs) as a marker for bone quality. Limited data exist regarding its utility with respect to posterolateral lumbar fusion (PLF). Methods: From fall 2010 to winter 2012, 10 patients underwent revision surgery for symptomatic pseudoarthrosis (defined as intractable pain associated with either radiographic evidence of nonunion or intraoperative evidence of nonunion) after a prior L4–S1 PLF. These patients were age-matched (±5 years) to 10 patients who underwent L4–S1 PLF with no clinical signs of pseudoarthrosis at 1-year follow-up. Available CT imaging (with or without instrumentation) was evaluated from L1 to L5 for the averaged HU. Data were pooled among L1–L3 values and between L4 and L5 values. Results: Within the pseudoarthrosis group, the pooled L1–L3 HU value was similar to the pooled L4–L5 HU value (168.39 ± 22.84 HU vs. 166.98 ± 23.20 HU respectively, P = 0.89). The same pattern was observed for the control group (190.24 ± 37.13 HU vs. 201.89 ± 36.59 HU respectively, P = 0.44). On the other hand, the pooled L1–L3 and L4–L5 HU values were larger for the control group compared to the pseudoarthrosis group, with the pooled L4–L5 HU demonstrating statistical significance, P = 0.01. Conclusion: Currently, CT imaging is typically not obtained prior to lumbar fusion. Results demonstrated that CT HU values were significantly larger for patients who did not exhibit symptomatic pseudoarthrosis at 1-year follow-up compared to those who required revision surgery. As such, CT HU values may serve as a predictor for bony fusion to guide surgical management of patients under consideration for PLF.

Dysembryoplastic Neuroectodermal Tumor: An Analysis from the Surveillance, Epidemiology, and End Results Program, 2004–2013

BACKGROUND Dysembryoplastic neuroectodermal tumor (DNT) is a rare neoplasm. Though the pathology is commonly considered benign, there have been various reports documenting rapid growth, recurrence/progression, sudden death, and malignant transformation. Most studies have addressed outcomes regarding seizure control, but limited data exist regarding incidence and survival. Consequently, we explore the Surveillance, Epidemiology, and End Results (SEER) database to explore the epidemiology of DNT. METHODS From the SEER-18 registry database, information from all patients diagnosed with intracranial DNT between 2004 and 2013 was extracted, including age, sex, race, marital status, tumor location, tumor size, receipt of surgery, extent of primary surgery, receipt of radiation, and follow-up data. Age-adjusted incidence rates and overall survival (OS) were calculated. A Cox proportional hazards model was used to assess relationships between various demographic/treatment variables and OS. RESULTS A total of 381 cases were identified in the SEER-18 database. The incidence of DNT within the large subset of the United States population represented by SEER was 0.033 per 100,000 person-years (95% confidence interval [CI], 0.030-0.037). The median duration of follow-up was 50 months. The median OS was not attained. The 3-, 5-, and 9-year OS was 99.363% (95% CI, 97.428%-99.844%), 97.993% (95% CI, 95.168%-99.174%), and 96.296% (95% CI, 91.834%-98.341%), respectively. Seven of the 381 patients passed at their last follow up. Of all demographic/treatment factors, only receipt of radiation demonstrated a significant relationship with OS (hazard ratio, 0.051; 95% CI, 0.01-0.267; P < 0.01). CONCLUSIONS Although the prognosis for DNT is generally favorable, the pathology can lead to poor outcomes in rare cases. Common demographic factors, treatment with surgery, and the extent of surgical resection did not show significant associations with OS. In contrast, treatment with radiation was associated with poorer OS.