Proceedings of 17th International Conference of the Engineering in Medicine and Biology Society, 1995
Abstract Ten Holter records were analyzed, corresponding to four chagasic patients who suffered s... more Abstract Ten Holter records were analyzed, corresponding to four chagasic patients who suffered sudden death during Holter recording, three chagasic patients that survived and three normal subjects. HRV signals were obtained from Holter tapes. Power spectral analysis was performed on each series by AR modeling. Compressed spectral arrays (CSA) were plotted for each series, where a tendency was observed to maintain frequency peak positions along time in sudden death series, as opposite to control series, where the ...
Proceedings of 16th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Abstract-A methodology based on heart rate variability (HRV) analysis, is proposed to study ambul... more Abstract-A methodology based on heart rate variability (HRV) analysis, is proposed to study ambulatory sudden death in Chagas patients who died while wearing a Holter monitor. The HRV evolution over time before death is carefully reviewed and a Compressed Spectral Array ( ...
Publisher Summary This chapter describes the results of a multicenter study of a closed-loop neur... more Publisher Summary This chapter describes the results of a multicenter study of a closed-loop neurostimulation system called the responsive neurostimulator (RNS) system undertaken by the NeuroPace, Inc. The institution performed nine implants and all cases involved more than one year follow-up. One of these nine (the only case without preoperative invasive monitoring) cases was an insulin dependent juvenile diabetic who was subsequently found to have anti-GAD antibody. This patient never responded to the neurostimulator system and her initial IPG was not replaced when the battery depleted. Follow-up on the other eight cases ranged from 19 to 32 months. All of these eight cases underwent preimplant invasive monitoring with discrete seizure focus localization. The median seizure frequency reduction was 56% and the mean reduction was 65%. The range in seizure frequency reduction was 43–100%. Seven cases required replacement of IPGs due to battery depletion and the time to IPG replacement ranged from 12 to 26 months with a median of 22 months and a mean of 21 months. There has been only one infection requiring explantation of the system. This infection occurred 16 months after implantation of a new IPG and 28 months after the original implantation. No adverse neurological events were reported in these cases. Observation of this study also support the ability of this automated seizure detection/therapeutic stimulation device to positively influence electrographic seizure activity. However, the study is still in a preliminary phase and more data is required to define optimal stimulation parameters as well as patient candidacy for seizure control.
Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammat... more Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammation regulates the resolution of pain by producing specialized pro-resolving mediators (SPMs), such as resolvin D1 (RvD1). However, it remains unclear how SPMs are induced in the central nervous system and whether these mechanisms can be reconciled with outcomes of neuromodulation therapies for pain, such as spinal cord stimulation. Here, we show that in a male rat model of neuropathic pain produced by spared nerve injury (SNI), 1 kHz spinal cord stimulation (1 kHz SCS) alone was sufficient to reduce mechanical allodynia and increase RvD1 in the cerebrospinal fluid (CSF). SNI resulted in robust and persistent mechanical allodynia and cold allodynia. Spinal cord electrode implantation was conducted at the T11-T13 vertebral level 1 week after SNI. The spinal locations of the implanted electrodes were validated by X-Ray radiography. 1 kHz SCS was applied for 6 h at 0.1 ms pulse-width, and th...
Enhancing the efficacy of spinal cord stimulation (SCS) is needed to alleviate the burden of chro... more Enhancing the efficacy of spinal cord stimulation (SCS) is needed to alleviate the burden of chronic pain and dependence on opioids. Present SCS therapies are characterized by the delivery of constant stimulation in the form of trains of tonic pulses (TPs). We tested the hypothesis that modulated SCS using novel time-dynamic pulses (TDPs) leads to improved analgesia and compared the effects of SCS using conventional TPs and a collection of TDPs in a rat model of neuropathic pain according to a longitudinal, double-blind, and crossover design. We tested the effects of the following SCS patterns on paw withdrawal threshold and resting state EEG theta power as a biomarker of spontaneous pain: Tonic (conventional), amplitude modulation, pulse width modulation, sinusoidal rate modulation, and stochastic rate modulation. Results demonstrated that under the parameter settings tested in this study, all tested patterns except pulse width modulation, significantly reversed mechanical hypersen...
Kilohertz-frequency electric field stimulation (kEFS) applied to the spinal cord can reduce chron... more Kilohertz-frequency electric field stimulation (kEFS) applied to the spinal cord can reduce chronic pain without causing the buzzing sensation (paresthesia) associated with activation of dorsal column fibers. This suggests that high-rate spinal cord stimulation (SCS) has a mode of action distinct from conventional, parasthesia-based SCS. A recent study reported that kEFS hyperpolarizes spinal neurons, yet this potentially transformative mode of action contradicts previous evidence that kEFS induces depolarization and was based on patch clamp recordings whose accuracy in the presence of kEFS has not been verified. We sought to elucidate the basis for kEFS-induced hyperpolarization and to validate the effects of kEFS observed in patch clamp recordings by comparing with independent optical methods. Using patch clamp electrophysiology and voltage-sensitive dye (VSD) imaging, we measured the response to kEFS applied in vitro to hippocampal and spinal neurons. The kEFS-induced hyperpolari...
Focal seizures can arise from coordinated activity across large-scale epileptic networks and prop... more Focal seizures can arise from coordinated activity across large-scale epileptic networks and propagate to regions that are not functionally altered but are recruited by epileptiform discharges. In preclinical models of focal epilepsy, the thalamus is recruited by cortical onset seizures, but it remains to be demonstrated in clinical studies. In this pilot study, the authors investigate whether seizures with onset within and outside the mesial temporal structures are detected in the anterior thalamus (ATN). After written consent, three subjects with suspected temporal lobe epilepsy undergoing stereotactic electrode implantation were recruited prospectively for thalamocortical depth EEG recordings. Three seizure detection metrics (line length-LL, Laplace operator-Lap; Teager energy-TE) were studied within the seizure onset zone and ATN. The LL, Lap, and TE metrics detected 40 (95%) seizures each in the ATN before the behavioral manifestation. Rates of detection in the seizure onset zo...
Proceedings of 17th International Conference of the Engineering in Medicine and Biology Society, 1995
Abstract Ten Holter records were analyzed, corresponding to four chagasic patients who suffered s... more Abstract Ten Holter records were analyzed, corresponding to four chagasic patients who suffered sudden death during Holter recording, three chagasic patients that survived and three normal subjects. HRV signals were obtained from Holter tapes. Power spectral analysis was performed on each series by AR modeling. Compressed spectral arrays (CSA) were plotted for each series, where a tendency was observed to maintain frequency peak positions along time in sudden death series, as opposite to control series, where the ...
Proceedings of 16th Annual International Conference of the IEEE Engineering in Medicine and Biology Society
Abstract-A methodology based on heart rate variability (HRV) analysis, is proposed to study ambul... more Abstract-A methodology based on heart rate variability (HRV) analysis, is proposed to study ambulatory sudden death in Chagas patients who died while wearing a Holter monitor. The HRV evolution over time before death is carefully reviewed and a Compressed Spectral Array ( ...
Publisher Summary This chapter describes the results of a multicenter study of a closed-loop neur... more Publisher Summary This chapter describes the results of a multicenter study of a closed-loop neurostimulation system called the responsive neurostimulator (RNS) system undertaken by the NeuroPace, Inc. The institution performed nine implants and all cases involved more than one year follow-up. One of these nine (the only case without preoperative invasive monitoring) cases was an insulin dependent juvenile diabetic who was subsequently found to have anti-GAD antibody. This patient never responded to the neurostimulator system and her initial IPG was not replaced when the battery depleted. Follow-up on the other eight cases ranged from 19 to 32 months. All of these eight cases underwent preimplant invasive monitoring with discrete seizure focus localization. The median seizure frequency reduction was 56% and the mean reduction was 65%. The range in seizure frequency reduction was 43–100%. Seven cases required replacement of IPGs due to battery depletion and the time to IPG replacement ranged from 12 to 26 months with a median of 22 months and a mean of 21 months. There has been only one infection requiring explantation of the system. This infection occurred 16 months after implantation of a new IPG and 28 months after the original implantation. No adverse neurological events were reported in these cases. Observation of this study also support the ability of this automated seizure detection/therapeutic stimulation device to positively influence electrographic seizure activity. However, the study is still in a preliminary phase and more data is required to define optimal stimulation parameters as well as patient candidacy for seizure control.
Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammat... more Mounting evidence from animal models of inflammatory and neuropathic pain suggests that inflammation regulates the resolution of pain by producing specialized pro-resolving mediators (SPMs), such as resolvin D1 (RvD1). However, it remains unclear how SPMs are induced in the central nervous system and whether these mechanisms can be reconciled with outcomes of neuromodulation therapies for pain, such as spinal cord stimulation. Here, we show that in a male rat model of neuropathic pain produced by spared nerve injury (SNI), 1 kHz spinal cord stimulation (1 kHz SCS) alone was sufficient to reduce mechanical allodynia and increase RvD1 in the cerebrospinal fluid (CSF). SNI resulted in robust and persistent mechanical allodynia and cold allodynia. Spinal cord electrode implantation was conducted at the T11-T13 vertebral level 1 week after SNI. The spinal locations of the implanted electrodes were validated by X-Ray radiography. 1 kHz SCS was applied for 6 h at 0.1 ms pulse-width, and th...
Enhancing the efficacy of spinal cord stimulation (SCS) is needed to alleviate the burden of chro... more Enhancing the efficacy of spinal cord stimulation (SCS) is needed to alleviate the burden of chronic pain and dependence on opioids. Present SCS therapies are characterized by the delivery of constant stimulation in the form of trains of tonic pulses (TPs). We tested the hypothesis that modulated SCS using novel time-dynamic pulses (TDPs) leads to improved analgesia and compared the effects of SCS using conventional TPs and a collection of TDPs in a rat model of neuropathic pain according to a longitudinal, double-blind, and crossover design. We tested the effects of the following SCS patterns on paw withdrawal threshold and resting state EEG theta power as a biomarker of spontaneous pain: Tonic (conventional), amplitude modulation, pulse width modulation, sinusoidal rate modulation, and stochastic rate modulation. Results demonstrated that under the parameter settings tested in this study, all tested patterns except pulse width modulation, significantly reversed mechanical hypersen...
Kilohertz-frequency electric field stimulation (kEFS) applied to the spinal cord can reduce chron... more Kilohertz-frequency electric field stimulation (kEFS) applied to the spinal cord can reduce chronic pain without causing the buzzing sensation (paresthesia) associated with activation of dorsal column fibers. This suggests that high-rate spinal cord stimulation (SCS) has a mode of action distinct from conventional, parasthesia-based SCS. A recent study reported that kEFS hyperpolarizes spinal neurons, yet this potentially transformative mode of action contradicts previous evidence that kEFS induces depolarization and was based on patch clamp recordings whose accuracy in the presence of kEFS has not been verified. We sought to elucidate the basis for kEFS-induced hyperpolarization and to validate the effects of kEFS observed in patch clamp recordings by comparing with independent optical methods. Using patch clamp electrophysiology and voltage-sensitive dye (VSD) imaging, we measured the response to kEFS applied in vitro to hippocampal and spinal neurons. The kEFS-induced hyperpolari...
Focal seizures can arise from coordinated activity across large-scale epileptic networks and prop... more Focal seizures can arise from coordinated activity across large-scale epileptic networks and propagate to regions that are not functionally altered but are recruited by epileptiform discharges. In preclinical models of focal epilepsy, the thalamus is recruited by cortical onset seizures, but it remains to be demonstrated in clinical studies. In this pilot study, the authors investigate whether seizures with onset within and outside the mesial temporal structures are detected in the anterior thalamus (ATN). After written consent, three subjects with suspected temporal lobe epilepsy undergoing stereotactic electrode implantation were recruited prospectively for thalamocortical depth EEG recordings. Three seizure detection metrics (line length-LL, Laplace operator-Lap; Teager energy-TE) were studied within the seizure onset zone and ATN. The LL, Lap, and TE metrics detected 40 (95%) seizures each in the ATN before the behavioral manifestation. Rates of detection in the seizure onset zo...
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Papers by Rosana Esteller