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Applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.

ABSTRACT: Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. The cynomolgus macaque (Macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or therapeutics can mitigate CNS infection or disease in this model. The documentation of alphavirus encephalitis in animals relies on traditional physiological biomarkers and behavioral/neurological observations by veterinary staff; quantitative measurements such as electroencephalography (EEG) and intracranial pressure (ICP) can recapitulate underlying encephalitic processes. We detail a telemetry implantation method suitable for continuous monitoring of both EEG and ICP in awake macaques, as well as methods for collection and analysis of such data. We sought to evaluate whether changes in EEG/ICP suggestive of CNS penetration by virus would be seen after aerosol exposure of naïve macaques to VEEV IC INH9813 or EEEV V105 strains compared to mock-infection in a cohort of twelve adult cynomolgus macaques. Data collection ran continuously from at least four days preceding aerosol exposure and up to 50 days thereafter. EEG signals were processed into frequency spectrum bands (delta: [0.4 - 4Hz); theta: [4 - 8Hz); alpha: [8-12Hz); beta: [12-30] Hz) and assessed for viral encephalitis-associated changes against robust background circadian variation while ICP data was assessed for signal fidelity, circadian variability, and for meaningful differences during encephalitis. Results indicated differences in delta, alpha, and beta band magnitude in infected macaques, disrupted circadian rhythm, and proportional increases in ICP in response to alphavirus infection. This novel enhancement of the cynomolgus macaque model offers utility for timely determination of onset, severity, and resolution of encephalitic disease and for the evaluation of vaccine and therapeutic candidates.

SUBMITTER: Ma H

PROVIDER: S-EPMC7316240 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.

Ma Henry H Lundy Jeneveve D JD Cottle Emily L EL O'Malley Katherine J KJ Trichel Anita M AM Klimstra William B WB Hartman Amy L AL Reed Douglas S DS Teichert Tobias T

PloS one 20200625 6

Alphaviruses such as Venezuelan equine encephalitis virus (VEEV) and Eastern equine encephalitis virus (EEEV) are arboviruses that can cause severe zoonotic disease in humans. Both VEEV and EEEV are highly infectious when aerosolized and can be used as biological weapons. Vaccines and therapeutics are urgently needed, but efficacy determination requires animal models. The cynomolgus macaque (Macaca fascicularis) provides a relevant model of human disease, but questions remain whether vaccines or ...[more]

PMID: 32584818

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Project description:BACKGROUND:Although placement of an intra-cerebral catheter remains the gold standard method for measuring intracranial pressure (ICP), several non-invasive techniques can provide useful estimates. The aim of this study was to compare the accuracy of four non-invasive methods to assess intracranial hypertension. METHODS:We reviewed prospectively collected data on adult intensive care unit (ICU) patients with traumatic brain injury (TBI), subarachnoid hemorrhage (SAH), or intracerebral hemorrhage (ICH) in whom invasive ICP monitoring had been initiated and estimates had been simultaneously collected from the following non-invasive indices: optic nerve sheath diameter (ONSD), pulsatility index (PI), estimated ICP (eICP) using transcranial Doppler, and the neurological pupil index (NPI) measured using automated pupillometry. Intracranial hypertension was defined as an invasively measured ICP >?20?mmHg. RESULTS:We studied 100 patients (TBI?=?30; SAH?=?47; ICH?=?23) with a median age of 52?years. The median invasively measured ICP was 17 [12-25] mmHg and intracranial hypertension was present in 37 patients. Median values from the non-invasive techniques were ONSD 5.2 [4.8-5.8] mm, PI 1.1 [0.9-1.4], eICP 21 [14-29] mmHg, and NPI 4.2 [3.8-4.6]. There was a significant correlation between all the non-invasive techniques and invasive ICP (ONSD, r?=?0.54; PI, r?=?0.50; eICP, r?=?0.61; NPI, r?=?-?0.41-p?<?0.001 for all). The area under the curve (AUC) to estimate intracranial hypertension was 0.78 [CIs?=?0.68-0.88] for ONSD, 0.85 [95% CIs 0.77-0.93] for PI, 0.86 [95% CIs 0.77-0.93] for eICP, and 0.71 [95% CIs 0.60-0.82] for NPI. When the various techniques were combined, the highest AUC (0.91 [0.84-0.97]) was obtained with the combination of ONSD with eICP. CONCLUSIONS:Non-invasive techniques are correlated with ICP and have an acceptable accuracy to estimate intracranial hypertension. The multimodal combination of ONSD and eICP may increase the accuracy to estimate the occurrence of intracranial hypertension.

Project description:Introduction: We investigated the effect of hematoma volume reduction with minimally invasive surgery (MIS) on intracranial pressure (ICP) and cerebral perfusion pressure (CPP) in patients with large spontaneous intracerebral hemorrhage (ICH). Methods: Post-hoc analysis of the Minimally Invasive Surgery Plus Alteplase for Intracerebral Hemorrhage Evacuation (MISTIE III) study, a clinical trial with blinded outcome assessments. The primary outcome was the proportion of ICP readings ≥20 and 30 mmHg, and CPP readings <70 and 60 mm Hg. Secondary outcomes included major disability (modified Rankin scale >3) and mortality at 30 and 365 days. We assessed the relationship between proportion of high ICP and low CPP events and MIS using binomial generalized linear models, and outcomes using multiple logistic regression. Results: Of 499 patients enrolled in MISTIE III, 72 patients had guideline based ICP monitors placed, 34 in the MIS group and 38 in control (no surgery) group. Threshold ICP and CPP events ≥20/ <70 mmHg occurred in 31 (43.1%) and 52 (72.2%) patients respectively. On adjusted analyses, proportion of ICP readings ≥20 and 30 mmHg were significantly lower in the MIS group vs. control group [Odds Ratio (OR) 0.27, 95% Confidence Interval [CI] 0.11-0.63 (p = 0.002); OR = 0.18, 0.04-0.75, p = 0.02], respectively. Proportion of CPP readings <70 and 60 mm Hg were also significantly lower in MIS patients [OR 0.31, 95% CI 0.15-0.63 (p = 0.001); OR 0.30, 95% CI 0.11-0.83 (p = 0.02)], respectively. Higher proportions of CPP readings <70 and 60 mm were significantly associated with short term mortality (p = 0.04), and (p = 0.006), respectively. Long term mortality was significantly associated with higher proportion of time with ICP ≥ 20 (p = 0.04), ICP ≥ 30 (p = 0.04), and CPP <70 mmHg (p = 0.01). Conclusion: Our results are consistent with the hypothesis that surgical reduction of ICH volume decreases proportion of high ICP and low CPP events and that these variables are associated with short- and long-term mortality.

Project description:OBJECTIVE:Cerebrovascular reactivity (CR) is a mechanism that maintains stable blood flow supply to the brain. Pressure reactivity index (PRx), the correlation coefficient between slow waves of invasive arterial blood pressure (ABP) and intracranial pressure (ICP) has been validated for CR assessment. However, in clinical ward, not every subarachnoid hemorrhage (SAH) patient has invasive ABP monitoring. Pulse transit time (PTT), the propagation time of a pulse wave travelling from the heart to peripheral arteries, has been suggested as a surrogate measure of ABP. In this study, we proposed to use PTT instead of invasive ABP to monitor CR. APPROACH:Forty-five SAH patients with simultaneous recordings of invasive ABP, ICP, oxygen saturation level (SpO2) and electrocardiograph (ECG) were included. PTT was calculated as the time from the ECG R-wave peak to the onset of SpO2. PTT based pressure reactivity index (tPRx) was calculated as the correlation coefficient between slow waves of PTT and ICP. Wavelet tPRx (wtRx) was calculated as the cosine of wavelet phase shift between PTT and ICP. Meanwhile, PRx and wPRx were also calculated using invasive ABP and ICP as input. MAIN RESULTS:The result showed a negative relationship between PTT and ABP (r??=??-0.58, p???<??0.001). tPRx negatively correlated with PRx (r??=??-0.51, p???=??0.003). Wavelet method correlated well with correlation method demonstrated through positive relationship between wPRx and PRx (r??=??0.82, p???<??0.001) as well as wtPRx and tPRx (r??=??0.84, p???<??0.001). SIGNIFICANCE:PTT demonstrates great potential as a useful tool for CR assessment when invasive ABP is unavailable. Key points • Pulse transit time (PTT), defined as the propagation time of a pulse wave travelling from the heart to the peripheral arteries, has been proposed as a surrogate measure of ABP. The relationship between PTT and ABP in SAH patients remains unknown. • Cerebrovascular reactivity (CR) assessment through PTT has advantages over invasive ABP, as it avoids bleeding and infection risk, and can be used outside of the ICU. • We introduced a new method to assess CR using PTT and ICP through correlation based method and wavelet based method. • We found that beat-to-beat PTT was negatively related with invasive ABP in SAH patients. A significant linear relationship exists between PTT-based CR parameter and a well validated method, PRx. PTT demonstrates great potential as a useful tool for CR assessment when invasive ABP is unavailable in SAH patients.

Dataset Information

Applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.

Publications

Applications of minimally invasive multimodal telemetry for continuous monitoring of brain function and intracranial pressure in macaques with acute viral encephalitis.

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