Frank P.K. Hsu

Hyperperfusion Syndrome: Toward a Stricter Definition

OBJECTIVEHyperperfusion syndrome is a rare and potentially devastating complication of carotid endarterectomy or carotid artery angioplasty and stenting. With the advent of new imaging techniques, we reviewed our experience with this phenomenon. METHODSThis report is a retrospective review of 129 consecutive cases of carotid endarterectomy performed between June 1, 2000, and May 31, 2002, and 44 consecutive cases of carotid artery angioplasty and stenting performed between January 1, 1997, and May 31, 2002. We specifically searched for examples of patients who developed postprocedural nonthrombotic neurological deficits that typified the hyperperfusion syndrome. RESULTSSeven cases of hyperperfusion syndrome occurred, four after endarterectomy (3.1% of carotid endarterectomy cases) and three after stenting (6.8% of stenting cases). The cases of hyperperfusion were classified as presenting with 1) acute focal edema (two cases with stroke-like presentation, attributable to edema immediately after revascularization), 2) acute hemorrhage (two cases of intracerebral hemorrhage immediately after stenting and one case immediately after endarterectomy), or 3) delayed classic presentation (two cases with seizures, focal motor weakness, and/or late intracerebral hemorrhage at least 24 hours after endarterectomy). CONCLUSIONHyperperfusion syndrome may be more common and more variable in clinical presentation than previously appreciated.

Extracting kinetic information from human motor cortical signals

Brain machine interfaces (BMIs) have the potential to provide intuitive control of neuroprostheses to restore grasp to patients with paralyzed or amputated upper limbs. For these neuroprostheses to function, the ability to accurately control grasp force is critical. Grasp force can be decoded from neuronal spikes in monkeys, and hand kinematics can be decoded using electrocorticogram (ECoG) signals recorded from the surface of the human motor cortex. We hypothesized that kinetic information about grasping could also be extracted from ECoG, and sought to decode continuously-graded grasp force. In this study, we decoded isometric pinch force with high accuracy from ECoG in 10 human subjects. The predicted signals explained from 22% to 88% (60 ± 6%, mean ± SE) of the variance in the actual force generated. We also decoded muscle activity in the finger flexors, with similar accuracy to force decoding. We found that high gamma band and time domain features of the ECoG signal were most informative about kinetics, similar to our previous findings with intracortical LFPs. In addition, we found that peak cortical representations of force applied by the index and little fingers were separated by only about 4mm. Thus, ECoG can be used to decode not only kinematics, but also kinetics of movement. This is an important step toward restoring intuitively-controlled grasp to impaired patients.

Amygdala-hippocampal dynamics during salient information processing

Recognizing motivationally salient information is critical to guiding behaviour. The amygdala and hippocampus are thought to support this operation, but the circuit-level mechanism of this interaction is unclear. We used direct recordings in the amygdala and hippocampus from human epilepsy patients to examine oscillatory activity during processing of fearful faces compared with neutral landscapes. We report high gamma (70–180 Hz) activation for fearful faces with earlier stimulus evoked onset in the amygdala compared with the hippocampus. Attending to fearful faces compared with neutral landscape stimuli enhances low-frequency coupling between the amygdala and the hippocampus. The interaction between the amygdala and hippocampus is largely unidirectional, with theta/alpha oscillations in the amygdala modulating hippocampal gamma activity. Granger prediction, phase slope index and phase lag analysis corroborate this directional coupling. These results demonstrate that processing emotionally salient events in humans engages an amygdala-hippocampal network, with the amygdala influencing hippocampal dynamics during fear processing.

The evolution of the EGFRvIII (rindopepimut) immunotherapy for glioblastoma multiforme patients

Glioblastoma Multiforme (GBM) is the most common type of brain tumor and it is uniformly fatal. The community standard of treatment for this disease is gross or subtotal resection of the tumor, followed by radiation and temozolomide. At recurrence bevacizumab can be added for increased progression free survival. Many challenges are encountered while trying to devise new drugs to treat GBM, such as the presence of the blood brain barrier which is impermeable to most drugs. Therefore in the past few years attention was turned to immunological means for the treatment of this devastating disease. EGFRvIII targeting has proven a good way to attack glioblastoma cells by using the immune system. Although in still in development, this approach holds the promise as a great first step toward immune-tailored drugs for the treatment of brain cancers.

Stereotactic robot-assisted MRI-guided laser thermal ablation of radiation necrosis in the posterior cranial fossa: technical note

Laser interstitial thermal therapy (LITT) is a minimally invasive procedure used to treat a variety of intracranial lesions. Utilization of robotic assistance with stereotactic procedures has gained attention due to potential for advantages over conventional techniques. The authors report the first case in which robot-assisted MRI-guided LITT was used to treat radiation necrosis in the posterior fossa, specifically within the cerebellar peduncle. The use of a stereotactic robot allowed the surgeon to perform LITT using a trajectory that would be extremely difficult with conventional arc-based techniques. A 60-year-old man presented with facial weakness and brainstem symptoms consistent with radiation necrosis. He had a history of anaplastic astrocytoma that was treated with CyberKnife radiosurgery 1 year prior to presentation, and he did well for 11 months until his symptoms recurred. The location and form of the lesion precluded excision but made the patient a suitable candidate for LITT. The location and configuration of the lesion required a trajectory for LITT that was too low for arc-based stereotactic navigation, and thus the ROSA robot (Medtech) was used. Using preoperative MRI acquisitions, the lesion in the posterior fossa was targeted. Bone fiducials were used to improve accuracy in registration, and the authors obtained an intraoperative CT image that was then fused with the MR image by the ROSA robot. They placed the laser applicator and then ablated the lesion under real-time MR thermometry. There were no complications, and the patient tolerated the procedure well. Postoperative 2-month MRI showed complete resolution of the lesion, and the patient had some improvement in symptoms.

State and trajectory decoding of upper extremity movements from electrocorticogram

Electrocorticography has been widely explored as a long-term signal acquisition platform for brain-computer interface (BCI) control of upper extremity prostheses. However, a comprehensive study of elementary upper extremity movements and their relationship to electrocorticogram (ECoG) signals has yet to be performed. This study examines whether kinematic parameters of 6 elementary upper extremity movements can be decoded from ECoG signals in 3 subjects undergoing subdural electrode placement for epilepsy surgery evaluation. To this end, we propose a 2-stage decoding approach that consists of a state decoder to determine idle/move states, followed by a Kalman filter-based trajectory decoder. This proposed decoder successfully classified idle/move states with an average accuracy of 91%, and the correlation between decoded and measured trajectory averaged 0.70 for position and 0.68 for velocity. These performances represent an improvement over a simple regression-based approach.

Electrocorticogram encoding of upper extremity movement trajectories

Electrocorticogram (ECoG)-based brain computer interfaces (BCI) can potentially control upper extremity pros-theses to restore independent function to paralyzed individuals. However, current research is mostly restricted to the offline decoding of finger or 2D arm movement trajectories, and these results are modest. This study seeks to improve the fundamental understanding of the ECoG signal features underlying upper extremity movements to guide better BCI design. Subjects undergoing ECoG electrode implantation performed a series of elementary upper extremity movements in an intermittent flexion and extension manner. It was found that movement velocity, θ̇, had a high positive (negative) correlation with the instantaneous power of the ECoG high-γ band (80-160 Hz) during flexion (extension). Also, the correlation was low during idling epochs. Visual inspection of the ECoG high-γ band revealed power bursts during flexion/extension events that had a waveform that strongly resembled the corresponding flexion/extension event as seen on θ̇. These high-γ bursts were present in all elementary movements, and were spatially distributed in a somatotopic fashion. Thus, it can be concluded that the high-γ power of ECoG strongly encodes for movement trajectories, and can be used as an input feature in future BCIs.

Sensitivity and specificity of upper extremity movements decoded from electrocorticogram

Electrocorticogram (ECoG)-based brain computer interfaces (BCI) can potentially be used for control of arm prostheses. Restoring independent function to BCI users with such a system will likely require control of many degrees-of-freedom (DOF). However, our ability to decode many-DOF arm movements from ECoG signals has not been thoroughly tested. To this end, we conducted a comprehensive study of the ECoG signals underlying 6 elementary upper extremity movements. Two subjects undergoing ECoG electrode grid implantation for epilepsy surgery evaluation participated in the study. For each task, their data were analyzed to design a decoding model to classify ECoG as idling or movement. The decoding models were found to be highly sensitive in detecting movement, but not specific in distinguishing between different movement types. Since sensitivity and specificity must be traded-off, these results imply that conventional ECoG grids may not provide sufficient resolution for decoding many-DOF upper extremity movements.

Therapeutic targeting of malignant glioma.

Glioblastoma Multiforme (GMB) is the most aggressive primary brain tumor with poor survival rates and universal recurrence despite aggressive treatments. Recent research suggested that GBM has multiple glioma cell populations, some of which are organized in a stem cell hierarchical order with different stages of differention. Evidence indicated that recurrence is due to a development or persistance of a subpopulation of these tumor cells which are inherently resistant to treatment and these were defined as the glioma stem-like cells (GSC). It is hypothesized that GSC become highly malignant by accumulating mutations in oncogenic pathways. These cells present with specific surface markers which helps identify them. Targeting the surface markers as well as the signaling pathways of GSCs has been an ongoing research effort. This review focuses on summarizing the current treatment modalities used to glioblastoma treatments, evaluating their efficacy in controlling and eradicatig the GSCs, discussing the machanisms involved in GSC tumor proliferation and resistance to treatments in addition to proposing potential avenues to target GSCs in order to provide a potential cure for this cancer.

Antivascular Endothelial Growth Factor Antibody for Treatment of Glioblastoma Multiforme

Despite aggressive investigation, glioblastoma multiforme (GBM) remains one of the deadliest cancers, with low progression-free survival and high one-year mortality. Current first-line therapy includes surgery with adjuvant radiation therapy and cytotoxic chemotherapy, but virtually all tumors recur. Given the highly vascular nature of GBM and its high expression of vascular endothelial growth factor and other angiogenic factors, recent investigation has turned to bevacizumab, an antivascular endothelial growth factor monoclonal antibody, for treatment of recurrent GBM. Phase 2 studies demonstrated the efficacy and safety of bevacizumab therapy for recurrent GBM, which led to its approval by the US Food and Drug Administration in 2009 for use in recurrent GBM. Since then, several new Phase 2 studies and retrospective series have demonstrated that bevacizumab significantly increased six-month progression-free survival in patients with recurrent GBM and may do so in new-onset GBM. The objective of this review is to provide a collective resource for these materials, highlighting the efficacy and safety of bevacizumab and calling for increased investigation toward its optimal application in the management of high-grade glioma.