Intrathecal Baclofen and Opioid Therapy: Cerebrospinal Fluid Leak and Infection Incidence, Risk Factors, and Outcomes.

Background: Intrathecal drug therapy treats medically refractory spasticity and pain. cerebrospinal fluid (CSF) leak or infection can limit efficacy and increase morbidity. We aim to evaluate risk factors and outcomes after CSF leaks and infections requiring reoperation.

Preoperative Embolization With Fused CT Angiography and Tractography Facilitates Safe Resection of a Spetzler-Martin Grade IV Arteriovenous Malformation.

Brain arteriovenous malformations (BAVMs) are high-flow vascular lesions that have a propensity to rupture resulting in high rates of morbidity and mortality. Microsurgical resection of BAVMs is the standard of care for high-risk, resectable lesions. Multiple imaging modalities aid in the surgical planning and resection of high-grade BAVMs, but all have hidden variables that would prove useful if available.

Thromboelastography-Guided Therapy of Hemorrhagic Complications after Craniopharyngioma Resection: Case-Based Update.

Purpose: Thromboelastography (TEG) is a point-of-care test that evaluates the entire hemostatic process. The use of TEG is expanding in multiple pediatric surgical disciplines. However, there is very little literature regarding its application in pediatric neurosurgical patients.

Simultaneous explantation and implantation of intrathecal pumps: a case series.

Objective: Intrathecal drug delivery devices (IDDDs) are a mainstay in the treatment of spasticity and refractory pain. While these devices have been shown to greatly improve the quality of life for patients, they also have a high perioperative complication and failure rate. A major complication of IDDD implantation is infection.

Subarachnoid-to-Subarachnoid Shunt for Correction of Nonfunctioning Baclofen Pump in a Severe Case of Chronic Debilitating Post-Spinal Cord Injury Spasticity.

Background: Perhaps the most disabling condition seen in patients with spinal cord injury (SCI) is spasticity. Spasticity is characterized as hyperreflexia and hypertonicity as a result of damage to the supraspinal tracts in the aftermath of SCI. Intrathecal baclofen (ITB) is the mainstay therapy for spasticity unresponsive to oral baclofen.

Delay Differential Analysis of Seizures in Multichannel Electrocorticography Data.

High-density electrocorticogram (ECoG) electrodes are capable of recording neurophysiological data with high temporal resolution with wide spatial coverage. These recordings are a window to understanding how the human brain processes information and subsequently behaves in healthy and pathologic states. Here, we describe and implement delay differential analysis (DDA) for the characterization of ECoG data obtained from human patients with intractable epilepsy.

Effects of distance and transport method on intervention and mortality in aneurysmal subarachnoid hemorrhage.

OBJECTIVE Most patients suffering from aneurysmal subarachnoid hemorrhage (aSAH) initially present to a hospital that lacks a neurosurgical unit. These patients require interhospital transfer (IHT) to tertiary facilities capable of multidisciplinary neurosurgical intervention. Yet, little is known about the effects of IHT on the outcomes of patients suffering from aSAH.

Effect of short-term ε-aminocaproic acid treatment on patients undergoing endovascular coil embolization following aneurysmal subarachnoid hemorrhage.

OBJECTIVE Aneurysmal rebleeding before definitive obliteration of the aneurysm is a cause of mortality and morbidity. There are limited data on the role of short-term antifibrinolytic therapy among patients undergoing endovascular intervention. METHODS All consecutive patients receiving endovascular therapy for their ruptured saccular aneurysm at the authors' institution between 2000 and 2011 were included in this study.

Discovering independent parameters in complex dynamical systems.

The transformation of a nonlinear dynamical system into a standard form by using one of its variables and its successive derivatives can be used to identify the relationships that may exist between the parameters of the original system such as the subset of the parameter space over which the dynamics is left invariant. We show how the size of the attractor or the time scale (the pseudo-period) can be varied without affecting the underlying dynamics. This is demonstrated for the Rössler and the Lorenz systems.

Muscle artifacts in single trial EEG data distinguish patients with Parkinson's disease from healthy individuals.

Parkinson's disease (PD) is known to lead to marked alterations in cortical-basal ganglia activity that may be amenable to serve as a biomarker for PD diagnosis. Using non-linear delay differential equations (DDE) for classification of PD patients on and off dopaminergic therapy (PD-on, PD-off, respectively) from healthy age-matched controls (CO), we show that 1 second of quasi-resting state clean and raw electroencephalogram (EEG) data can be used to classify CO from PD-on/off based on the area under the receiver operating characteristic curve (AROC). Raw EEG is shown to classify more robustly (AROC=0.

Non-linear dynamical classification of short time series of the rössler system in high noise regimes.

Time series analysis with delay differential equations (DDEs) reveals non-linear properties of the underlying dynamical system and can serve as a non-linear time-domain classification tool. Here global DDE models were used to analyze short segments of simulated time series from a known dynamical system, the Rössler system, in high noise regimes. In a companion paper, we apply the DDE model developed here to classify short segments of encephalographic (EEG) data recorded from patients with Parkinson's disease and healthy subjects.

Non-linear dynamical analysis of EEG time series distinguishes patients with Parkinson's disease from healthy individuals.

The pathophysiology of Parkinson's disease (PD) is known to involve altered patterns of neuronal firing and synchronization in cortical-basal ganglia circuits. One window into the nature of the aberrant temporal dynamics in the cerebral cortex of PD patients can come from analysis of the patients electroencephalography (EEG). Rather than using spectral-based methods, we used data models based on delay differential equations (DDE) as non-linear time-domain classification tools to analyze EEG recordings from PD patients on and off dopaminergic therapy and healthy individuals.

Biochemical sensor tubing for point-of-care monitoring of intravenous drugs and metabolites.

In medical facilities, there is strong motivation to develop detection systems that can provide continuous analysis of fluids in medical tubing used to either deliver or remove fluids from a patient's body. Possible applications include systems that increase the safety of intravenous (IV) drug injection and point-of-care health monitoring. In this work, we incorporated a surface-enhanced Raman scattering (SERS) sensor comprised of an array of closely spaced metal nanodomes into flexible tubing commonly used for IV drug delivery and urinary catheters.

Angiotensin type 1 receptor antagonist losartan, reduces MPTP-induced degeneration of dopaminergic neurons in substantia nigra.

Background: Recent attention has focused on understanding the role of the brain-renin-angiotensin-system (RAS) in stroke and neurodegenerative diseases. Direct evidence of a role for the brain-RAS in Parkinson's disease (PD) comes from studies demonstrating the neuroprotective effect of RAS inhibitors in several neurotoxin based PD models. In this study, we show that an antagonist of the angiotensin II (Ang II) type 1 (AT1) receptor, losartan, protects dopaminergic (DA) neurons against 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) toxicity both in primary ventral mesencephalic (VM) cultures as well as in the substantia nigra pars compacta (SNpc) of C57BL/6 mice (Fig.

Angiotensin II protects cultured midbrain dopaminergic neurons against rotenone-induced cell death.

In this study, we demonstrate that angiotensin II (Ang II) protects dopamine (DA) neurons from rotenone toxicity in vitro. Primary ventral mesencephalic (VM) cultures from E15 rats were grown for 5 days and then cultured in the presence of the mitochondrial complex I inhibitor, rotenone. Acute exposure (20 h) to 20 nM rotenone reduced the number of tyrosine hydroxylase-positive (TH+) neurons by 50 +/- 6% when compared to untreated cultures.

Angiotensin type 2 receptor neuroprotection against chemical hypoxia is dependent on the delayed rectifier K+ channel, Na+/Ca2+ exchanger and Na+/K+ ATPase in primary cortical cultures.

We have previously reported that angiotensin II (Ang II) protects cortical neurons from chemical-induced hypoxia through activation of the angiotensin type 2 (AT(2)) receptor. Here, we show in mouse primary neuronal cultures that the AT(2) receptor neuroprotection results from the activation of the delayed rectifier K(+) channel as well as the involvement of the Na(+)/Ca(2+) exchanger (NCX) and Na(+)/K(+) ATPase (ATPase). Roles of the K(+) channel, NCX and ATPase were determined using the specific blockers alpha-dendrotoxin, KB-R7943 and ouabain, respectively.

Glutamate mediates cell death and increases the Bax to Bcl-2 ratio in a differentiated neuronal cell line.

Excessive stimulation of the NMDA receptor by glutamate induces cell death and has been implicated in the development of several neurodegenerative diseases. While apoptosis plays a role in glutamate-mediated toxicity, the mechanisms underlying this process have yet to be completely determined. Recent evidence has shown that exposure to excitatory amino acids regulates the expression of the antiapoptotic protein, Bcl-2, and the proapoptotic protein, Bax, in neurons.

Angiotensin II attenuates NMDA receptor-mediated neuronal cell death and prevents the associated reduction in Bcl-2 expression.

While angiotensin II (Ang II) plays a major role in the regulation of blood pressure, fluid homeostasis and neuroendocrine function, recent studies have also implicated the peptide hormone in cell growth, differentiation and apoptosis. In support of this, we have previously demonstrated that Ang II attenuates N-methyl-D-aspartate (NMDA) receptor signaling [Molec. Brain Res.

Inhibitory effects of angiotensin on NMDA-induced cytotoxicity in primary neuronal cultures.

Primary cultures from the hypothalamus/thalamus/septum/midbrain (HTSM) region of 1-day-old mice were used to investigate the effects of angiotensin on NMDA excitotoxicity. Cell viability was determined following exposure to 1-10 mM glutamate or 0.01-10 mM NMDA.

Human angiotensin II type-2 receptor inhibition of insulin-mediated ERK-2 activity via a G-protein coupled signaling pathway.

While it has been shown that the angiotensin type-2 (AT(2)) receptor plays an important role in the development and differentiation of many tissues, the second messengers involved in its signaling pathways are just beginning to be understood. To further determine the signaling pathways for the AT(2) receptor, we have investigated whether human angiotensin type-2 receptor transfected into Chinese hamster ovary (CHO) cells can modulate insulin-induced extracellular signal-related protein kinase (ERK-2) phosphorylation via a G-protein coupled mechanism. Our results indicate that the human AT(2) receptor decreases insulin-induced ERK-2 phosphorylation through a G-protein mediated pathway since inhibition was attenuated by pertussis toxin (a G(i)/G(0) inhibitor).

Angiotensin II attenuates chemical hypoxia-induced caspase-3 activation in primary cortical neuronal cultures.

In this study we determined whether caspase-3 is required in mouse cortical neurons for sodium azide-mediated apoptosis. Primary cortical neuronal cultures were treated with a cell permeable caspase-3 inhibitor, DEVD (1 nM-100 fM), prior to sodium azide-induced hypoxia. Treatment with the caspase-3 inhibitor resulted in a dose-dependent decrease in apoptosis, suggesting that sodium azide-induced apoptosis is mediated through a caspase-3 dependent pathway.

Effects of mutations in the highly conserved DRY motif on binding affinity, expression, and G-protein recruitment of the human angiotensin II type-2 receptor.

The signaling pathways for the seven transmembrane G-protein coupled angiotensin II receptors (AT(1) and AT(2)) are just beginning to be understood. While these receptors play an important role in the development and differentiation of many tissues, including the cardiovascular and central nervous systems, information about amino acid motifs involved in angiotensin II-mediated signaling is only available for the AT(1) receptor subtype. In the present study, we mutated the conserved DRY(141-143) motif in the AT(2) receptor, which is thought to be involved in G-protein recruitment.

Angiotensin protects cortical neurons from hypoxic-induced apoptosis via the angiotensin type 2 receptor.

The effects of angiotensin on mouse cortical neuronal cultures exposed to chemical-induced hypoxia was investigated. Cultures exposed to 10 mM sodium azide for 5 min showed a 17% increase in apoptosis when assayed 24 h postinsult. The N-methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocked sodium azide-induced cell death suggesting that the NMDA receptor contributes to the mediated cell death.

Expression of the 75 kDA TNF receptor and its role in contact-mediated neuronal cell death.

We previously demonstrated TNF toxicity, at high TNF doses or in the presence of actinomycin D, in the N1E-115 neuronal cell line (N1Es), which expresses only the 55 kDa TNF receptor (TNFR). To determine whether presence of the 75 kDa TNFR increases N1E sensitivity to TNF toxicity, cells were transfected with a 75 kDa TNFR expression construct. However, 75 kDa TNFR protein expression was undetectable in stably transfected N1Es.