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Sunil Manjila, Timothy W. Vogel, Yunwei Chen, Mark S. Rodgers and Alan R. Cohen

Hypothalamic hamartomas (HHs) are rare developmental lesions arising from the inferior hypothalamus that may cause gelastic seizures and central precocious puberty. Cystic changes in HHs are rare, usually occurring in giant lesions. The authors describe an unusual case of cystic HH masquerading as a suprasellar arachnoid cyst in an 18-month-old girl presenting with precocious puberty. Microsurgical removal of the lesion led to complete resolution of the precocious puberty on long-term follow-up. This case is the first reported HH with pathological demonstration of corticotropin-releasing hormone immunostaining in the solid tumor and glial cells in the cyst wall of the lesion. The clinical and radiological characteristics of HHs are reviewed, along with the unique surgical strategies used to manage cystic lesions in the suprasellar region.

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Jodi L. Smith, Jon Hobbs, Aonan Tang, David Jackson, Wei Chen, Hema Patel, Anita Prieto, Alexander Sher, Alan Litke and John M. Beggs

Introduction

Epileptogenicity of neuronal tissues requires both altered excitability and altered synchronization of neurons. However, the network-level mechanisms responsible for neuronal hyperexcitability and synchronization remain unknown, and there is much to learn regarding how even small networks of neurons interact. The present study examines local and network properties of cortical neurons from epileptogenic human and excited (“epileptic”) rat cortex.

Methods

Epileptogenic cortex was harvested from pediatric patients with medically refractory seizures undergoing resective surgery. Local field potential signals (LFPs) were recorded continuously for up to several hours with a 60-channel microelectrode array. We also recorded LFPs from slices and organotypic and dissociated cultures of rat cortex bathed in high K+ and low Mg++. We then compared the human and rat data, applied a second-order maximum entropy model (MEM) to the data, and explored how well the MEM predicted sequences of correlated states over time.

Results

Both human and rat cortex produced LFP signals in the form of interictal spikes on almost all electrodes. However, only human cortex demonstrated spontaneous activity in normal cerebrospinal fluid, and the LFPs from human cortex showed greater synchrony across electrodes than the rat LFPs. Moreover, when a second-order MEM was applied to human and rat data, the model accounted for roughly 88% of network correlations. However, in 8/13 preparations the observed sequences of correlated states were significantly longer than predicted by independently concatenating states from the model, suggesting that temporal dependencies are a common feature of cortical network activity.

Conclusion

Excited slices of rat cortex fail to capture some important features of network activity found in epileptogenic human cortex. Furthermore, a second-order MEM successfully predicts correlated states in cortical networks, but not their evolution over time. Thus, higher-order MEMs are necessary to account for temporal correlations observed between states.

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Michael Y. Chen, Alan Hoffer, Paul F. Morrison, John F. Hamilton, Jeffrey Hughes, Kurt S. Schlageter, Jeongwu Lee, Brandon R. Kelly and Edward H. Oldfield

Object. Achieving distribution of gene-carrying vectors is a major barrier to the clinical application of gene therapy. Because of the blood—brain barrier, the distribution of genetic vectors to the central nervous system (CNS) is even more challenging than delivery to other tissues. Direct intraparenchymal microinfusion, a minimally invasive technique, uses bulk flow (convection) to distribute suspensions of macromolecules widely through the extracellular space (convection-enhanced delivery [CED]). Although acute injection into solid tissue is often used for delivery of oligonucleotides, viruses, and liposomes, and there is preliminary evidence that certain of these large particles can spread through the interstitial space of the brain by the use of convection, the use of CED for distribution of viruses in the brain has not been systematically examined. That is the goal of this study.

Methods. Investigators used a rodent model to examine the influence of size, osmolarity of buffering solutions, and surface coating on the volumetric distribution of virus-sized nanoparticles and viruses (adeno-associated viruses and adenoviruses) in the gray matter of the brain. The results demonstrate that channels in the extracellular space of gray matter in the brain are large enough to accommodate virus-sized particles and that the surface characteristics are critical determinants for distribution of viruses in the brain by convection.

Conclusions. These results indicate that convective distribution can be used to distribute therapeutic viral vectors in the CNS.

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Alan M. Chen, Kunal B. Karani, J. Michael Taylor, Bin Zhang, Andrew Furthmiller, Gabriel De Vela, James L. Leach, Sudhakar Vadivelu and Todd A. Abruzzo

OBJECTIVE

Although intracranial arterial aneurysms (IAAs) of childhood are usually idiopathic, it is possible that underlying arteriopathy escapes detection when using conventional diagnostic tools. Quantitative arterial tortuosity (QAT) has been studied as a biomarker of arteriopathy. The authors analyzed cervicocerebral QAT in children with idiopathic IAAs to assess the possibility of arteriopathy.

METHODS

Cases were identified by text-string searches of imaging reports spanning the period January 1993 through June 2017. QAT of cervicocerebral arterial segments was measured from cross-sectional studies using image-processing software. Other imaging and clinical data were confirmed by retrospective electronic record review. Children with idiopathic IAAs and positive case controls, with congenital arteriopathy differentiated according to aneurysm status (with and without an aneurysm), were compared to each other and to healthy controls without vascular risk factors.

RESULTS

Cervicocerebral QAT was measured in 314 children: 24 with idiopathic IAAs, 163 with congenital arteriopathy (including 14 arteriopathic IAAs), and 127 healthy controls. QAT of all vertebrobasilar segments was larger in children with IAAs (idiopathic and arteriopathic forms) (p < 0.05). In children with congenital arteriopathy without an aneurysm, QAT was decreased for the distal cervical vertebral arteries and increased for the supraspinal vertebral artery relative to healthy children. QAT of specific cervicocerebral segments correlated with IAA size and rupture status.

CONCLUSIONS

Cervicocerebral QAT is a biomarker of arteriopathy in children with IAA, even in the absence of other disease markers. Additional findings suggest a correlation of cervicocerebral QAT with IAA size and rupture status and with the presence of IAA in children with congenital arteriopathy.