David Barba

Stereotactic radiosurgery for recurrent gliomas

Background. The treatment of recurrent gliomas is palliative; however, the local pattern of tumor recurrence permits retreatment with single fraction, high dose stereotactic radiotherapy or radiosurgery (RS).

Nerve Growth Factor Gene Therapy: Activation of Neuronal Responses in Alzheimer Disease

IMPORTANCEnAlzheimer disease (AD) is the most common neurodegenerative disorder and lacks effective disease-modifying therapies. In 2001, we initiated a clinical trial of nerve growth factor (NGF) gene therapy in AD, the first effort at gene delivery in an adult neurodegenerative disorder. This program aimed to determine whether a nervous system growth factor prevents or reduces cholinergic neuronal degeneration in patients with AD. We present postmortem findings in 10 patients with survival times ranging from 1 to 10 years after treatment.nnnOBJECTIVEnTo determine whether degenerating neurons in AD retain an ability to respond to a nervous system growth factor delivered after disease onset.nnnDESIGN, SETTING, AND PARTICIPANTSnPatients in this anatomicopathological study were enrolled in clinical trials from March 2001 to October 2012 at the University of California, San Diego, Medical Center in La Jolla. Ten patients with early AD underwent NGF gene therapy using ex vivo or in vivo gene transfer. The brains of all 8 patients in the first phase 1 ex vivo trial and of 2 patients in a subsequent phase 1 in vivo trial were examined.nnnMAIN OUTCOMES AND MEASURESnBrains were immunolabeled to evaluate in vivo gene expression, cholinergic neuronal responses to NGF, and activation of NGF-related cell signaling. In 2 patients, NGF protein levels were measured by enzyme-linked immunosorbent assay.nnnRESULTSnAmong 10 patients, degenerating neurons in the AD brain responded to NGF. All patients exhibited a trophic response to NGF in the form of axonal sprouting toward the NGF source. Comparing treated and nontreated sides of the brain in 3 patients who underwent unilateral gene transfer, cholinergic neuronal hypertrophy occurred on the NGF-treated side (Pu2009<u2009.05). Activation of cellular signaling and functional markers was present in 2 patients who underwent adeno-associated viral vectors (serotype 2)-mediated NGF gene transfer. Neurons exhibiting tau pathology and neurons free of tau expressed NGF, indicating that degenerating cells can be infected with therapeutic genes, with resultant activation of cell signaling. No adverse pathological effects related to NGF were observed.nnnCONCLUSIONS AND RELEVANCEnThese findings indicate that neurons of the degenerating brain retain the ability to respond to growth factors with axonal sprouting, cell hypertrophy, and activation of functional markers. Sprouting induced by NGF persists for 10 years after gene transfer. Growth factor therapy appears safe over extended periods and merits continued testing as a means of treating neurodegenerative disorders.

A phase1 study of stereotactic gene delivery of AAV2-NGF for Alzheimer's disease

Nerve growth factor (NGF) is an endogenous neurotrophic‐factor protein with the potential to restore function and to protect degenerating cholinergic neurons in Alzheimers disease (AD), but safe and effective delivery has proved unsuccessful.

Multiple plasma cell granulomas of the central nervous system: case report.

Plasma cell granulomas of the central nervous system are exceedingly rare. Of the six well-documented cases that have been published to date, five plasma cell granulomas were intracranial and one was located in the spinal meninges. Multiple plasma cell granulomas of the central nervous system have not previously been reported. We now report a patient who had two plasma cell granulomas in the spinal meninges and one in the anterior cerebral falx. The histological findings that differentiate this rare lesion from other central nervous system lesions, such as plasmacytoma and meningioma, are discussed with a review of the literature.

Intranasal schwannoma with extension into the intracranial compartment: case report

The authors present a case of intranasal schwannoma with extension into the intracranial compartment. Computed tomographic findings are presented, and a combined intranasal and subfrontal operative approach is described. The pathology, origin, and clinical characteristics of intranasal schwannomas are reviewed.

Changes in fiber tract integrity and visual fields after anterior temporal lobectomy

Objective: To investigate postoperative changes in fiber tract integrity in patients with temporal lobe epilepsy (TLE) following anterior temporal lobectomy (ATL) and to determine whether postoperative changes are 1) stable vs progressive and 2) related to visual field defects. Methods: Diffusion tensor imaging (DTI) was obtained in 7 patients with TLE before, 2 months after, and 1 year after ATL. Changes in fractional anisotropy (FA) were evaluated in a whole-brain voxel-wise analysis, as well within specific fiber tracts. Repeated-measures analysis of variance was performed to examine the time course of FA changes within ipsilateral and contralateral fiber tracts. Quantitative visual field analysis was performed to determine whether decreases in regional FA were related to the extent or location of visual field defects. Results: Patients showed decreased FA 2 months post-ATL in ipsilateral fiber tracts transected during surgery (parahippocampal cingulum, uncinate fasciculus, inferior longitudinal fasciculus, and fornix), as well as in fiber tracts not directly transected (inferior fronto-occipital fasciculus and corpus callosum). Additional decreases in FA were not observed from 2 months to 1 year post-ATL. Visual field defects in most patients were characterized by incomplete quadrantanopsias. However, FA reductions in one patient extended into temporo-occipital cortex and the splenium of the corpus callosum and were associated with a complete hemianopia. Conclusions: Wallerian degeneration is apparent 2 months following unilateral ATLs in ipsilateral fibers directly and indirectly affected during surgery. These changes do not appear to progress over the course of a year, but may correlate with the nature and extent of postoperative visual field defects.

Deep Brain Stimulation of the Subthalamic Nucleus Facilitates Coordination of Hand Preshaping in Parkinson's Disease

Several studies have found that Parkinsons disease (PD) disrupts the organization of complex motor sequences regardless of the influence of parkinsonian medications. A clear candidate for the neural bases of such deficits, which we term “coordinative,” is the failure to integrate propioceptive and visual information by cortico-striatal circuits in a timed fashion. Recent reports, however, have indicated that deep-brain stimulation of the subthalamic nucleus (STN DBS) may result in an improvement in coordinative deficits beyond the amelioration of “intensive deficits” such as bradykinesia and scaling errors. The present study examined the spatio-temporal organization underlying the shaping of the hand during reaching to grasp objects differing in shape. Six PD patients ON and OFF their STN DBS when OFF their concomitant medications and six age-matched controls participated in this study. STN DBS improved the coordination involved in preshaping the hand while grasping. We discuss these results in light of our earlier work with PD patients on and off dopamine replacement therapy.

Developmental and extracellular matrix-remodeling processes in rosiglitazone-exposed neonatal rat cardiomyocytes

OBJECTIVEnThe objective of this study was to investigate the effects of rosiglitazone (Avandia(®)) on gene expression in neonatal rat ventricular myocytes.nnnMATERIALS & METHODSnMyocytes were exposed to rosiglitazone ex vivo. The two factors examined in the experiment were drug exposure (rosiglitazone and dimethyl sulfoxide vs dimethyl sulfoxide), and length of exposure to drug (½ h, 1 h, 2 h, 4 h, 6 h, 8 h, 12 h, 18 h, 24 h, 36 h and 48 h).nnnRESULTSnTranscripts that were consistently expressed in response to the drug were identified. Cardiovascular system development, extracellular matrix and immune response are represented prominently among the significantly modified gene ontology terms.nnnCONCLUSIONnHmgcs2, Angptl4, Cpt1a, Cyp1b1, Ech1 and Nqo1 mRNAs were strongly upregulated in cells exposed to rosiglitazone. Enrichment of transcripts involved in cardiac muscle cell differentiation and the extracellular matrix provides a panel of biomarkers for further analysis in the context of adverse cardiac outcomes in humans. Original submitted 15 November 2013; Revision submitted 14 February 2014.

Novel High-Frequency Peripheral Nerve Stimulator Treatment of Refractory Postherpetic Neuralgia: A Brief Technical Note

The study aims to describe an ultrasound (US)‐guided peripheral nerve stimulation implant technique and describe the effect of high‐frequency peripheral nerve stimulation on refractory postherpetic neuralgia.

A clinic compatible, open source electrophysiology system

Open source electrophysiology (ephys) recording systems have several advantages over commercial systems such as customization and affordability enabling more researchers to conduct ephys experiments. Notable open source ephys systems include Open-Ephys, NeuroRighter and more recently Willow, all of which have high channel count (64+), scalability, and advanced software to develop on top of. However, little work has been done to build an open source ephys system that is clinic compatible, particularly in the operating room where acute human electrocorticography (ECoG) research is performed. We developed an affordable (<;