Joaquin Azpiroz

Effects of Noninvasive Facial Nerve Stimulation in the Dog Middle Cerebral Artery Occlusion Model of Ischemic Stroke

Background and Purpose— Facial nerve stimulation has been proposed as a new treatment of ischemic stroke because autonomic components of the nerve dilate cerebral arteries and increase cerebral blood flow when activated. A noninvasive facial nerve stimulator device based on pulsed magnetic stimulation was tested in a dog middle cerebral artery occlusion model. Methods— We used an ischemic stroke dog model involving injection of autologous blood clot into the internal carotid artery that reliably embolizes to the middle cerebral artery. Thirty minutes after middle cerebral artery occlusion, the geniculate ganglion region of the facial nerve was stimulated for 5 minutes. Brain perfusion was measured using gadolinium-enhanced contrast MRI, and ATP and total phosphate levels were measured using 31P spectroscopy. Separately, a dog model of brain hemorrhage involving puncture of the intracranial internal carotid artery served as an initial examination of facial nerve stimulation safety. Results— Facial nerve stimulation caused a significant improvement in perfusion in the hemisphere affected by ischemic stroke and a reduction in ischemic core volume in comparison to sham stimulation control. The ATP/total phosphate ratio showed a large decrease poststroke in the control group versus a normal level in the stimulation group. The same stimulation administered to dogs with brain hemorrhage did not cause hematoma enlargement. Conclusions— These results support the development and evaluation of a noninvasive facial nerve stimulator device as a treatment of ischemic stroke.

Game Motivated and Constraint Induced Therapy in Late Stroke with fMRI Studies Pre and Post Therapy

20 patients with stroke more than one year earlier were evaluated, admitted to a novel therapy including constraint-induced and computer game-motivated therapy. Statistically significant improvements after 4 weeks of late therapy were seen in all 20 patients on nine out of eleven quantified clinical evaluation scales. The patients looked forward to and enjoyed the therapy. These same late stroke patients were studied via fMRI BOLD immediately before therapy and post therapy. fMRI BOLD studies confirm brain functional reorganization; 3 of the 20 fMRI cases are presented here. We propose that fMRI can help in the process of designing effective stroke therapy programs based on biological principles of brain plasticity

Effect of pulsed magnetic stimulation of the facial nerve on cerebral blood flow

In these experiments we define an effective means of pulsed magnetic stimulation of the facial nerve for the purpose of increasing cerebral blood flow (CBF). In normal anesthetized dog and sheep, a focal magnetic field was directed toward the facial nerve within the temporal bone by placing a 6.5 cm figure-8 stimulation coil over the ear. In an initial set of experiments, CBF was measured by laser Doppler flowmetry and the cerebral vasculature was visualized by angiography. The effect of facial nerve stimulation was found to be dependent on stimulation power, frequency, and the precise positioning of the stimulation coil. Furthermore, an increase in CBF was not observed after direct electrical stimulation in the middle ear space, indicating that non-specific stimulation of the tympanic plexus, an intervening neural structure with vasoactive effects, was not responsible for the increase in CBF after pulsed magnetic stimulation. Subsequent experiments using perfusion MRI demonstrated reproducible increases in CBF throughout the forebrain that manifested bilaterally, albeit with an ipsilateral predominance. These experiments support the development of a non-invasive pulsed magnetic facial nerve stimulator that will increase CBF as a treatment of ischemic stroke.

Restored brain perfusion after non-invasive stimulation of the facial nerve in a canine stroke model

Ischemic stroke affects over 15 million patients per year and is a leading cause of death worldwide. Currently available treatments are indicated for less than 5% of patients. Stimulation of the facial nerve has been proposed as a possible new treatment of ischemic stroke that acts by increasing blood flow to the brain and thereby restoring perfusion through collateral vessels. The objective of this project was to evaluate the changes in brain perfusion, following facial nerve stimulation in an animal stroke model using MRI measures of cerebral blood flow. Autologous blood clot was injected in the internal carotid artery to occlude the middle cerebral artery (MCA) in 17 mongrel dogs. Occlusion in the MCA was verified using fluoroscopy and MRI angiography. Following baseline and post-stroke MRI images, the facial nerve at the site of the geniculate ganglion was located and then stimulated using a transcranial magnetic stimulator and a neuro-navigation system in 11 animals. Six animals followed the same procedure but were not stimulated (control group). The perfusion index of both sides of the brain was measured using gadolinium contrast MRI before and after stroke, and at 30 minute intervals after stimulation. Results show a significant and persistent increase in perfusion in the stroke side of the brain relative to the non-stroke / contralateral side, after stimulation, when compared to the control group. These results strongly support the future development and evaluation of a non-invasive facial nerve stimulator device for the early treatment of ischemic stroke.

Best Parameters for Magnetic Stimulation of the Facial Nerve to Improve Cerebral Blood Flow

Magnetic stimulation of the vasomotor component of the facial nerve has been shown to be effective in significantly increasing cerebral blood flow (CBF) in various animal models. With the intention of eventually developing a clinical, non-invasive, magnetic stimulation device to increase cerebral blood flow as a treatment for ischemic stroke (IS), we first need to understand the relationship between stimulation power, duration and the resulting physiological response. The ideal stimulation parameters are those that maximize the effect on CBF in both magnitude and duration, while minimizing the applied power needed, thereby minimizing patient risk, discomfort, and equipment requirements. We performed experiments in Yorkshire pigs, modifying the power and the stimulation time, and measuring the corresponding effect on brain perfusion as measured by gadolinium contrast-enhanced MRI. We also looked at the effect of repeated stimulation. Perfusion scans were obtained before stimulation, and at 30 minute intervals after stimulation. We observed the perfusion index with 2, 3.5 and 5 minutes of stimulation duration (rapid pulse trains of 10 pulses per second), and at 65%, 80% and 95% of stimulation power. We found that we obtained an average increase of about 70% in perfusion index over baseline after a single stimulation train, lasting more than two hours and returning to normal after four hours. We observed no significant difference in response with any of the stimulation parameters tested, confirming that we get a very effective response at 65 power and 2 minutes, but suggesting the minimum power and duration needed is even lower than the parameters tested. Repeated stimulation caused the same effect as the first stimulation in every pig tested.

Active metabolic weight estimation using bioimpedance, indirect calorimetry and the clino-ortho maneuver

The resting energy expenditure (REE) and substrate utilization are computed by indirect calorimetry technique (ICT). The REE represents 80-85% of the total energy expenditure (TEE) but only accounts for the 7% of the actual body weight (ABW). The TEE is produced by the organs plus muscles, whereas the REE accounts only for the main organs. An important problem comes up when the REE is computed throughout the fat free mass (FFM) computation or anthropometric measurements because they do not explain the tremendous catabolic variability by ICT when subjects show the same body composition. Therefore, the aim of this work is to develop a method to compute the metabolic active weight (MAW) as a new form that may help to understand the catabolic activity of the body composition. The premise was the clino-ortho maneuver can split the ABW in two parts: one in which the MAW reflects the FFM catabolism while the second part was not considered since there is not energy requirement in it. The experiment design studied 37 young volunteers undergoing the clino-ortho maneuver during fast and postprandial conditions. The results showed REE increments of 21% during phase I (fast), while in phase II (postprandial) only 14% was achieved in ortho-postprandial. Therefore, the computed MAWs were 65.5Kg and 58Kg, respectively, when the ABW average was 70 Kg and the FFM was 50 Kg. One first conclusion was that the 15.5 Kg of the MAW above the FFM could explain a catabolic equivalence which can be exclusively related to the fast-ortho position which can help to classify exclusively the dynamic over activity of the FFM.

A Simple Model Implementation to Measure Breath by Breath the VO2 and VCO2 by the Indirect Calorimetry Technique

This paper proposes a discrete random time series modeling for the VO2 and VCO2 measurement in the indirect calorimetry technique (ICT). Mathematical equations are developed in order to establish clear differences between the breath-by-breath and mixing chamber measurement based calorimeters. This simple model offers not only a physiological ICT definition approach but also defines the idea of VO2 and VCO2 short-term variability information for research. The preliminary results show a new physiological information when a computer oriented algorithm model implementation was applied to a data acquisition system in order to obtain the power spectrum analysis from a typical observation subject submitted to the clino-ortho maneuver

Negative effects of obesity analyzed through bioimpedance, indirect calorimetry, the sympathovagal index and the orthoclinostatic test

Early analysis of the negative effects of obesity is important to prevent the development of chronic diseases related to this condition. There is a need to monitor these effects through simple instrumentation that measures fat-free mass (FFM) catabolism. Obesity leads to a decrease in the FFM energy expenditure and to an increase in the autonomic nervous system (ANS) activity. Thus, the measurement of FFM dynamic catabolism can provide information regarding the effects of obesity. The hypothesis is that this increased ANS activity produces an increase of energy expenditure of carbohydrates and fats when the subjects are under stress; in this case after an 8-hour fast and while they are undergoing an orthoclinostatic test. A pilot study was conducted on 29 volunteers, 16 women and 13 men. The results show significant statistical differences (p0.1) in fat and carbohydrate utilization during the orthoclinostatic tests: A move from the clinostatic to the orthostatic positions produced the following: Fat metabolism varied from 97.2 to 105.9 gr/day of fat for women and 24.9 to 35.7 gr/day of fat for men; carbohydrate metabolism changed from 38 to 39 gr/day for women and 239 to 277 gr/day for men; FFM averages were 47 Kg for women and 57.6 Kg for men; changes in the sympathovagal index (SVI) averages were 0.4 to 1.8 for women and 0.8 to 2.7 for men. The conclusions show that the methodologys sensitivity is such that gender differences can be used as a model to prove FFM metabolic differences. We believe that further studies will lead to the development of a robust methodology for the early detection of the negative effects of obesity.

Metabolic Variability Analysis Using a Mixing Chamber-Breath by Breath based Indirect Calorimeter and the Clino-Ortho Maneuver

This work proposes the clino-ortho maneuver to analyze the metabolic energy expenditure variability by Indirect Calorimetry (IC). This analysis uses a hybrid calorimeter which includes simultaneously the mixing- chamber (MC) and the breath by breath (BbB) IC techniques. VO2 and VCO2 short-term variability was characterized as metabolic variability in the MC technique by intra-group standard deviation averages. When the BbB technique was used the metabolic variability characterization was done by VO2 and VCO2 discrete time series power spectrum analysis in the 0-0.5 Hz band. Thus a statistical population of 17 young healthy volunteers was studied using a clino-ortho maneuver with 30-30 minutes in each position after 8 hours of fasting. The results showed an energy expenditure change of 40% in Kcal/day (p<0.01). The metabolic variability was partially significant using the MC technique while BbB total power spectrum changed from 35 to 60 for the VO2 and from 24 to 37 for the VCO2 (ml/bth)2, (p<0.05) in the region from 0 to 0.04 Hz. It was concluded that using this new measurement technique and the clino-ortho maneuver metabolic variability information not yet studied was revealed.