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Biomedical subjects

Nicholas M Barbaro

Publications and source records attributed to Nicholas M Barbaro.

At least 19 recordsLinked to original sources
PubMed2006

MMP-9 expression is associated with leukocytic but not endothelial markers in brain arteriovenous malformations.

Brain arteriovenous malformations (BAVM) have high matrix metalloproteinase-9 (MMP-9) expression, the source of which is unclear. We hypothesized MMP-9 production might be due to inflammation in BAVM. Compared to control brain tissues (n = 5), BAVM tissue (n = 139) had a higher expression (by ELISA) of myeloperoxidase (MPO) (193 +/- 189 vs. 6 +/- 3, ng/mg, P < .001), MMP-9 (28 +/- 32 vs. 0.7 +/- 0.6, ng/mg, P < .001), and IL-6 (102 +/- 218 vs. 0.1 +/- 0.1, pg/mg, P < .001), but not eNOS (114 +/- 87 vs. 65 +/- 9, pg/mg, P = .09). MMP-9 expression in BAVM highly correlated with myeloperoxidase (R2 = .76, P < .001), as well as with IL-6 (R2 = .32, P < .001). In contrast, MMP-9 in BAVM poorly correlated with the endothelial marker, eNOS (R2 = .03, P = .05), and CD31 (R2 = .004, P = .57). Compared to non-embolized patients (n = 46), patients with pre-operative embolization (n = 93) had higher levels of myeloperoxidase (236 +/- 205 vs. 106 +/- 108, ng/mg, P < .001) and MMP-9 (33 +/- 35 vs. 16 +/- 20, ng/mg, P < .001), however the correlation between MMP-9 and myeloperoxidase was equally strong for both groups (R2 = .69, n = 93, P < .001, for both). MMP-9 expression correlated with the lipocalin-MMP-9 complex, suggesting neutrophils as the MMP-9 source. MPO co-localized with majority of MMP-9 signal by immunohistochemistry. Our data suggest that inflammation is a prominent feature of BAVM lesional phenotype, and neutrophils appear to be a major source of MMP-9 in these lesions.

Adult↗
PubMed2006

Interleukin-6 upregulates expression of KDR and stimulates proliferation of human cerebrovascular smooth muscle cells.

Interleukin-6 (IL-6) may play multiple roles in angiogenesis and vascular remodeling. Our previous study showed that a promoter polymorphism (174G>C) in IL-6 is associated with brain arteriovenous malformation hemorrhage; tissue expression is related to genotype. In this study, we investigated the effects of IL-6 on human cerebral smooth muscle cells (HCSMCs) and smooth muscle cells isolated from brain arteriovenous malformation surgical specimens (AVM SMCs) and surgical controls (control HCSMCs--from structurally normal temporal lobe taken during surgical treatment of epilepsy patients). We found that IL-6 (1.1+/-0.27 versus 0.37+/-0.04 pg/mL, n=5, P<0.05) and endogenous vascular endothelial growth factor (VEGF) receptor II (kinase domain-containing receptor (KDR), 15+/-3 versus 1.5+/-3 pg/mL, n=5, P<0.05) were increased in brain AVM SMCs compared with control HCSMCs. Further research revealed that IL-6 could stimulate SMC proliferation, VEGF release, and KDR activation in control HCSMCs. It could also stimulate KDR phosphorylation in control HCSMCs, further confirming a unique role of IL-6 in the triggering of KDR. Interleukin-6 could increase matrix metalloproteinase-9 (MMP-9) secretion through activating KDR in control HCSMCs (P<0.05 versus control). Inhibiting IL-6-induced KDR could reduce MMP-9 activity at least 50% compared with the control group (P<0.05). Increased MMP-9 activity was accompanied by increased control HCSMC proliferation, and blocking MMP-9 activity significantly reduced IL-6-induced control HCSMC proliferation (P<0.05). Collectively, our results show that IL-6 could activate, amplify, and maintain the angiogenic cascade in HCSMCs. A novel role of IL-6 during HCSMC proliferation is upregulating KDR expression and phosphorylation. The results may contribute to the angiogenic phenotype of human brain vascular diseases, such as brain AVM.

Adult↗
PubMed2006

Focal cortical dysplasia: a review of pathological features, genetics, and surgical outcome.

Focal cortical dysplasia (FCD) is found in approximately one-half of patients with medically refractory epilepsy. These lesions may involve only mild disorganization of the cortex, but they may also contain abnormal neuronal elements such as balloon cells. Advances in neuroimaging have allowed better identification of these lesions, and thus more patients have become surgical candidates. Molecular biology techniques have been used to explore the genetics and pathophysiological characteristics of FCD. Data from surgical series have shown that surgery often results in significant reduction or cessation of seizures, especially if the entire lesion is resected.

Brain Diseases↗
PubMed2006

Magnetic resonance neurography in extraspinal sciatica.

BACKGROUND: Sciatica without evidence of lumbosacral root compression is often attributed to piriformis syndrome. However, specific diagnostic tools have not been available to demonstrate sciatic nerve entrapment by the piriformis muscle. OBJECTIVE: To evaluate the use of magnetic resonance (MR) neurography in identifying abnormalities of the sciatic nerve in patients with unexplained sciatica. DESIGN: Case series from a retrospective medical record review. PATIENTS: Fourteen patients with sciatic distribution pain and normal results on MR imaging for lumbosacral radiculopathy were referred for MR neurography of the lumbosacral plexus and sciatic nerves. RESULTS: In 12 patients, MR neurography demonstrated increased fluid-attenuated inversion recovery signal in the ipsilateral sciatic nerve. In most patients, this abnormal signal was seen at the sciatic notch, at or just inferior to the level of the piriformis muscle. To date, 4 patients have undergone surgical decompression, with excellent relief of symptoms in 3 of them. CONCLUSION: Magnetic resonance neurography often identifies an abnormal increased signal in the proximal sciatic nerve in patients with extraspinal sciatica and allows more accurate diagnosis of sciatic nerve entrapment in suspected cases.

Adult↗
PubMed2006

Aberrant seizure-induced neurogenesis in experimental temporal lobe epilepsy.

Neurogenesis in the hippocampal dentate gyrus persists throughout life and is increased by seizures. The dentate granule cell (DGC) layer is often abnormal in human and experimental temporal lobe epilepsy, with dispersion of the layer and the appearance of ectopic granule neurons in the hilus. We tested the hypothesis that these abnormalities result from aberrant DGC neurogenesis after seizure-induced injury. Bromodeoxyuridine labeling, in situ hybridization, and immunohistochemistry were used to identify proliferating progenitors and mature DGCs in the adult rat pilocarpine temporal lobe epilepsy model. We also examined dentate gyri from epileptic human hippocampal surgical specimens. Prox-1 immunohistochemistry and pulse-chase bromodeoxyuridine labeling showed that progenitors migrate aberrantly to the hilus and molecular layer after prolonged seizures and differentiate into ectopic DGCs in rat. Neuroblast marker expression indicated the delayed appearance of chainlike progenitor cell formations extending into the hilus and molecular layer, suggesting that seizures alter migratory behavior of DGC precursors. Ectopic putative DGCs also were found in the hilus and molecular layer of epileptic human dentate gyrus. These findings indicate that seizure-induced abnormalities of neuroblast migration lead to abnormal integration of newborn DGCs in the epileptic adult hippocampus, and implicate aberrant neurogenesis in the development or progression of recurrent seizures.

Adult↗
PubMed2006

Speech preservation during language-dominant, left temporal lobe seizures: report of a rare, potentially misleading finding.

PURPOSE: To evaluate the prevalence and mechanism of ictal speech in patients with language-dominant, left temporal lobe seizures. METHODS: We retrospectively reviewed the video-EEG telemetry records for the presence of ictal speech in 96 patients with surgically proven left temporal lobe epilepsy and studied the seizure-propagation patterns in three patients who required intracranial EEG recordings for seizure localization. RESULTS: Ictal speech preservation was observed in five patients. One patient's seizures demonstrated rapid propagation of the ictal discharges to the contralateral temporal area where the seizure evolved, resembling a nondominant temporal lobe seizure. The other two patients had ictal discharges that remained confined to the inferomesial temporal areas, sparing language cortex. CONCLUSIONS: Preservation of speech in complex partial seizures of language-dominant, left temporal lobe origin is rare. Based on intracranial EEG recordings, the likely mechanism underlying this potentially misleading clinical finding is the preservation of language areas due to limited seizure-propagation patterns.

Adult↗
PubMed2005

Dysfunction of synaptic inhibition in epilepsy associated with focal cortical dysplasia.

Focal cortical dysplasia (FCD) is a common and important cause of medically intractable epilepsy. In patients with temporal lobe epilepsy and in several animal models, compromised neuronal inhibition, mediated by GABA, contributes to seizure genesis. Although reduction in GABAergic interneuron density has been reported in FCD tissue samples, there is little available information on the resulting physiological changes in synaptic inhibition and the potential contribution of these changes to epileptogenesis in the dysplastic human brain. Using visualized whole-cell patch-clamp recordings from identified neurons in tissue slices obtained from patients with FCD, we demonstrate that GABAA-receptor-mediated inhibition is substantially altered in regions of dysplasia. These alterations include a significant reduction in IPSC frequency and a potentially compensatory decrease in transporter-mediated GABA reuptake function; the latter is marked by a significant increase in the decay-time constant for evoked and spontaneous IPSCs and a lack of effect of the GABA transport-inhibitor 1-[2([(diphenylmethylene)imino]oxy)ethyl]-1,2,5,6-tetrahydro-3-pyridinecarboxylic acid hydrochloride on IPSC kinetics. Immunohistochemical staining revealed a scattering of GABAergic interneurons across dysplastic cortex and striking reductions in GABA transporter expression. Together, these results suggest that profound alterations in GABA-mediated synaptic inhibition play an essential role in the process of epileptogenesis in patients with FCD.

Adolescent↗
PubMed2005

Recurrent or refractory trigeminal neuralgia after microvascular decompression, radiofrequency ablation, or radiosurgery.

OBJECT: Trigeminal neuralgia (TN) is characterized by paroxysmal lancinating pain in the trigeminal nerve distribution. When TN is refractory to medical management, patients are referred for microvascular decompression (MVD), radiofrequency ablation, or radiosurgery. After the initial treatment, patients may have refractory or recurrent symptoms requiring retreatment. The purpose of this study was to determine what factors are associated with the need for retreatment and which modality is most effective. METHODS: To define this population further, the authors evaluated a cohort of patients who required retreatment for TN. The mean follow-up periods were 51 months from the first treatment and 23 months from the last one, and these were comparable among treatment groups. CONCLUSIONS: Trigeminal neuralgia can recur after neurosurgical treatment. In this study the authors demonstrate that the number of patients requiring retreatment is not negligible. Lower retreatment rates were seen in patients who initially underwent radiosurgery, compared with those in whom MVD or radiofrequency ablation were performed. Radiosurgery was more likely to be the final treatment for recurrent TN regardless of the initial treatment. After retreatment, the majority of patients attained complete or very good pain relief. Pain relief after retreatment correlates with postoperative facial numbness.

Aged↗
PubMed2005

Management of medically refractory trigeminal neuralgia in patients with multiple sclerosis.

OBJECT: Trigeminal neuralgia (TN) is a painful disorder that frequently causes lancinating, electrical shock-like pain in the trigeminal distribution. Common surgical treatments include microvascular decompression (MVD), radiosurgery, and radiofrequency ablation, and complete pain relief is generally achieved with a single treatment in 70 to 85% of cases for all modalities. In a subset of patients with multiple sclerosis (MS), however, the rates of surgical treatment failure and the need for additional procedures are significantly increased compared with those in patients without MS. In this study the authors report their experience with a cohort of 11 patients with TN who also had MS, and assess the efficacy of MVD, gamma knife surgery (GKS), and radiofrequency ablation in achieving complete or partial long-term pain relief. METHODS: Eleven patients with TN and MS who were treated by the senior author (N.B.) at the University of California, San Francisco were included in this study. All patients underwent GKS and/or radiofrequency ablation, and four received MVD. A detailed clinical history and intraoperative findings were recorded for each patient and frequent follow-up evaluations were performed, with a mean follow-up duration of 40.6 months (range 1-96 months). Pain was assessed for each patient by using the Barrow Neurological Institute scale (Scores I-V). CONCLUSIONS: Achieving complete pain relief in patients with TN and MS required significantly more treatments compared with all other patients with TN who did not have MS (p = 0.004). Even when compared with a group of 32 patients who had highly refractory TN, the cohort with MS required significantly more treatments (p = 0.05). Radiosurgery proved to be an effective procedure and resulted in fewer retreatments and longer pain-free intervals compared with MVD or radiofrequency ablation.

Aged↗
PubMed2005

Frame-based stereotactic biopsy remains an important diagnostic tool with distinct advantages over frameless stereotactic biopsy.

OBJECT: As the availability of image-guided surgical navigation systems has increased, the application of frame-based biopsy has declined at our institution, despite equivalent accuracy and safety. There are several cost issues separating the use of surgical navigation systems and stereotactic frames for simple biopsy which may have implications in this era of health care cost control. We retrospectively reviewed the UCSF experience with stereotactic brain biopsy from a 9 year period. METHODS: Data were collected for 213 consecutive stereotactic brain biopsies performed at UCSF (139 frame-based and 74 frameless). There were no significant differences between the frame-based and frameless biopsy groups with regard to patient demographics, overall histopathology, proportion of nondiagnostic biopsies, or incidence of complications. General anesthesia was used for 9 (6%) and 70 (95%) of the frame-based and frameless biopsy cases, respectively. Frame-based biopsies required a mean of 114+/-3 min of operating room time, while frameless biopsies required 185+/-6 min (P<0.0001). For patients admitted to our neurosurgery service who underwent frame-based (n=110) or frameless (n=52) biopsy within 24 h of admission, the mean lengths of hospital stay were 1.8+/-0.2 and 3.2+/-0.6 days, respectively (P=0.007). CONCLUSION: Frame-based and frameless stereotactic biopsy approaches were equally effective at providing a tissue diagnosis with minimum morbidity and mortality. The frame-based approach, however, required significantly less anesthesia resources, less operating room time and shorter hospital stays, and thus should still be considered a first-line approach for stereotactic brain biopsy.

Adolescent↗
PubMed2005

Significance of source and size in the mechanical response of human cerebral blood vessels.

Cerebral blood vessels are frequently damaged in traumatic brain injury. Mechanical properties of fresh human cerebral vessels obtained through surgeries have been reported. Because surgical sources of human specimens are rare and produce a limited amount of material, we sought to compare the properties of more readily available cerebral arteries and veins obtained from cadavers to fresh vessel data. Additionally, because the previous study was limited to small vessels available in surgery, it was unknown how generally applicable the results were to larger cerebral arteries and veins. In the current study, large and small cerebral vessels from autopsy were stretched axially. Data from these and similar tests on fresh vessels were combined to determine the significance of source and size on mechanical properties. Structural comparisons of histological samples were additionally utilized to characterize differences. Results indicate that specimens from autopsy and surgery behave similarly except that vessels from autopsy tend to be less extensible. While tests on large vessels were limited, small arteries obtained from autopsy tended to be slightly stiffer than large arteries. In contrast, bridging veins from cadavers were typically stiffer and stretched less before structural failure than cortical veins from the same source. These effects are, however, secondary to differences identified between arteries and veins in the previous study.

Adult↗
PubMed2005

Coexpression of angiogenic factors in brain arteriovenous malformations.

OBJECTIVE: Brain arteriovenous malformations (BAVMs) are structurally unstable blood vessels that display an angiogenic phenotype, possibly maintained by concerted effects of key angiogenic factors. Therefore, we hypothesized that there are close correlations among key angiogenic factors in BAVMs and that levels of key angiogenic factors are associated with BAVM clinical characteristics that are linked with vascular instability. METHODS: We measured the expression of angiopoietin-2 (Ang-2), matrix metalloproteinase-9, vascular endothelial growth factor (VEGF), and platelet-derived growth factor-AA and -BB by use of enzyme-linked immunosorbent assay in 27 BAVM surgical specimens. Tissues were also collected from 14 structurally normal brain specimens obtained during epilepsy surgery. RESULTS: Ang-2, VEGF, and matrix metalloproteinase-9 were highly expressed in BAVM samples (11.9 +/- 15.5 ng/mg protein, 137 +/- 102 pg/mg protein, and 379 +/- 455 pg/mg protein, respectively). Platelet-derived growth factor-BB was detectable in 7 of 21 BAVM samples. There were close correlations between Ang-2 and VEGF (R2 = 0.79). Higher Ang-2 and VEGF levels seemed to be associated with draining vein characteristics linked with BAVM hemorrhage but not with feeding artery pressure or BAVM size. In the structurally normal brain specimens, levels of Ang-2, VEGF, and matrix metalloproteinase-9 were low (0.8 +/- 2.3 ng/mg protein, 38 +/- 25 pg/mg protein, and 52 +/- 43 pg/mg protein, respectively). CONCLUSION: There were close correlations among angiogenic factors in BAVMs. Concerted effects of angiogenic factors may maintain the angiogenic phenotype in BAVMs and thereby determine the clinical course of BAVMs.

Angiopoietin-2↗
PubMed2004

Primary brachial plexus tumors: imaging, surgical, and pathological findings in 25 patients.

OBJECT: The authors report on the treatment of primary brachial plexus tumors in 25 patients at the University of California, San Francisco. They compare their findings with those obtained in similar series. METHODS: The authors reviewed the electronic and medical records, radiological images, operative reports, and pathological findings in 25 consecutive cases of primary brachial plexus tumors. Cases of metastatic lesions or adjacent neoplasms extending into and involving the brachial plexus were excluded. At presentation patients ranged in age from 19 to 71 years (mean 47-15 years), and neurofibromatosis was present in eight patients (32%). Presenting signs and symptoms included palpable mass (60%), numbness/paresthesias (44%), radiating pain (44%), local pain (16%), and weakness (12%). Duration of symptoms ranged from 2 months to 10 years. Neuroimaging revealed lesions ranging widely in size (volume approximately 1 to 100 ml). Pathological diagnoses included schwannoma (15 [60%]), neurofibroma (five [20%]), malignant peripheral nerve sheath tumor (four [16%]), and desmoid tumor (one [4%]). CONCLUSIONS: Primary tumors arising in the brachial plexus are rare. Careful workup, surgical technique, and attention to pathological diagnosis optimize management.

Adult↗
PubMed2004

Unique astrocyte ribbon in adult human brain contains neural stem cells but lacks chain migration.

The subventricular zone (SVZ) is a principal source of adult neural stem cells in the rodent brain, generating thousands of olfactory bulb neurons every day. If the adult human brain contains a comparable germinal region, this could have considerable implications for future neuroregenerative therapy. Stem cells have been isolated from the human brain, but the identity, organization and function of adult neural stem cells in the human SVZ are unknown. Here we describe a ribbon of SVZ astrocytes lining the lateral ventricles of the adult human brain that proliferate in vivo and behave as multipotent progenitor cells in vitro. This astrocytic ribbon has not been observed in other vertebrates studied. Unexpectedly, we find no evidence of chains of migrating neuroblasts in the SVZ or in the pathway to the olfactory bulb. Our work identifies SVZ astrocytes as neural stem cells in a niche of unique organization in the adult human brain.

Adult↗
PubMed2004

Magnetoencephalography source localization and surgical outcome in temporal lobe epilepsy.

OBJECTIVE: We prospectively investigated the role of magnetoencephalography (MEG) in localizing the seizure focus and in predicting outcome to surgical resections for intractable temporal lobe epilepsy (TLE). METHODS: We performed simultaneous interictal EEG and MEG recording (two 37-channel system) in 26 TLE patients followed by MEG source localization. We correlated early modeling dipoles with intracranial EEG, temporal surgical resection and surgical outcome. RESULTS: There were 12 patients who had anterior temporal horizontal or tangential dipoles to the anterior infero-lateral temporal tip cortex. Two patients underwent selective amygdalo-hippocampectomy (SAH) and nine patients had antero-medial temporal lobectomy (AMTL). All patients had successful outcome except for one patient who initially failed SAH, but became seizure-free after AMTL. There were 11 patients who demonstrated anterior temporal vertical or tangential oblique dipoles. Five patients had AMTL and three had SAH; all became seizure free. Five of above 23 patients had invasive EEG and demonstrated mesial seizure onset. Three TLE patients had lateral vertical dipoles that were concordant with intracranial EEG and these became seizure free after temporal neocortical resections. CONCLUSIONS: MEG source analysis produces distinct source patterns that provide useful localizing information, predict surgical outcome, and may aid in planning limited surgical resection in TLE.

Electroencephalography↗