Combined counter-maneuvers accelerate recovery from orthostatic hypotension in familial dysautonomia

May 2012

M J Hilz
E C Ehmann
E Pauli
F B Axelrod
Philip A. DeFina
…and others.

ABSTRACT: In patients with familial dysautonomia (FD), prominent orthostatic hypotension (OH) endangers cerebral perfusion. Supine repositioning or abdominal compression improves systolic and diastolic blood pressure (BPsys and BPdia). To determine whether OH recovers faster with combined supine repositioning and abdominal compression than with supine repositioning alone. In 9 patients with FD (17.8 ± 3.9 years) and 10 healthy controls (18.8 ± 5 years), we assessed 2-min averages of BPsys, BPdia, and heart rate (HR) during supine rest, standing, supine repositioning, another supine rest, second standing, and supine repositioning with abdominal compression by leg elevation and flexion. We determined BPsys- and BPdia-recovery-times as intervals from return to supine until BP reached values equivalent to each participant’s 2-min average at supine rest minus two standard deviations. Differences in signal values and BP-recovery-times between groups and positions were assessed by ANOVA and post hoc testing (significance: P < 0.05). Patients with FD had pronounced OH that improved with supine repositioning. However, BP only reached supine rest values with additional abdominal compression. In controls, BP was stable during positional changes. Without abdominal compression, BP-recovery-times were longer in patients with FD than those in controls, but similar to control values with compression (BPsys: 83.7 ± 64.1 vs 36.6 ± 49.5 s; P = 0.013; BPdia: 84.6 ± 65.2 vs 35.3 ± 48.9 s; P = 0.009). Combining supine repositioning with abdominal compression significantly accelerates recovery from OH and thus lowers the risk of hypotension-induced cerebral hypoperfusion.

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Frequency Analysis Unveils Cardiac Autonomic Dysfunction after Mild Traumatic Brain Injury

March 2011

Max J Hilz
Philip A Defina
Stefan Anders
Harald Marthol
…and others.

ABSTRACT: Long-term mortality is increased after mild traumatic brain injury (mTBI). Central cardiovascular-autonomic dysregulation resulting from subtle, trauma-induced brain lesions might contribute to cardiovascular events and fatalities. We investigated whether there is cardiovascular-autonomic dysregulation after mTBI. In 20 mTBI patients (37±13 years, 5-43 months post-injury) and 20 healthy persons (26±9 years), we monitored respiration, RR intervals (RRI), blood pressures (BP), while supine and upon standing. We calculated the root mean square successive RRI differences (RMSSD) reflecting cardiovagal modulation, the ratio of maximal and minimal RRIs around the 30th and 15th RRI upon standing (30:15 ratio) reflecting baroreflex sensitivity (BRS), spectral powers of parasympathetic high-frequency (HF: 0.15-0.5 Hz) RRI oscillations, of mainly sympathetic low-frequency (LF: 0.04-0.15 Hz) RRI oscillations, of sympathetic LF-BP oscillations, RRI-LF/HF-ratios reflecting sympathovagal balance, and the gain between BP and RRI oscillations as additional BRS index (BRS(gain)). We compared supine and standing parameters of patients and controls (repeated measures analysis of variance; significance: p<0.05). While supine, patients had lower RRIs (874.2±157.8 vs. 1024.3±165.4 ms), RMSSDs (30.1±23.6 vs. 56.3±31.4 ms), RRI-HF powers (298.1±309.8 vs. 1507.2±1591.4 ms(2)), and BRS(gain) (8.1±4.4 vs. 12.5±8.1 ms·mmHg(-1)), but higher RRI-LF/HF-ratios (3.0±1.9 vs. 1.2±0.7) than controls. Upon standing, RMSSDs and RRI-HF-powers decreased significantly in controls, but not in patients; patients had lower RRI-30:15-ratios (1.3±0.3 vs. 1.6±0.3) and RRI-LF-powers (2450.0±2110.3 vs. 4805.9±3453.5 ms(2)) than controls. While supine, mTBI patients had reduced cardiovagal modulation and BRS. Upon standing, their BRS was still reduced, and patients did not withdraw parasympathetic or augment sympathetic modulation adequately. Impaired autonomic modulation probably contributes to cardiovascular irregularities post-mTBI.

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Neuroplasticity and Neuromarker Driven Neuromodulation: The Future Path to Normalizing Brain Function

January 2016

Philip A Defina
James P Halper
Jonathan Fellus
Charles J Prestigiacomo
…and others.

ABSTRACT: The purpose of this paper is to present a novel approach to promoting brain neuroplasticity through the application of neuromarker driven neuro- modulation. A tripartite model utilizing structural, electromagnetic, and neurochemical modalities to identify and localize neuromarkers and then to create personalized, tailored interventions are described. It is proposed that neuromarker-guided neuromodulation of brain pathways can promote neuroplasticity for healing, repair and improved neuroconnectivity. A clinical application of this model has already been utilized and reported in preliminary retrospective research in the treatment of severe disorders of consciousness. This model serves as a template for future use of neuromarker driven procedures and complex interventions for brain repair.

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Disrupted Axonal Fiber Connectivity As a Marker of Impaired Consciousness States

June 2013

Project: PVS / MCS
Philip A. Defina
Rafael Rodriguez-RojasRafael
Batista García-Ramó
Yasser Iturria
Maylen Carballo-Barreda
…and others.

ABSTRACT: Background: Persistent vegetative states (PVS) and locked-in syndrome (LIS) are well differentiated disorders of consciousness that can be reached after a localized brain injury in the brainstem. The relations of the lesion topography with the impairment in the whole-brain architecture and functional disconnections are poorly understood. Methods: Two patients (PVS and LIS) and 20 age-matched healthy volunteers were evaluated using diffusion tensor imaging (DTI). Anatomical network was modeled as a graph whose nodes are represented by 71 brain regions. Inter-region connections were quantified through Anatomical Connection Strength (ACS) and Density (ACD). Complex networks properties such as local and global efficiency and vulnerability were studied. Mass univariate testing was performed at every connection using network based statistic approach. Results: LIS patients’ network showed significant differences from controls in the brainstem-thalamus-frontal cortex circuitry, while PVS patients showed a widespread disruption of anatomical connectivity in both hemispheres. Both patients showed a reorganization of network attributes, with decreased global and local efficiency, significantly more pronounced in PVS. Conclusions: Our results suggest that DTI-based network connectivity combined with graph theory is useful to study the long-range effect of confined injuries and the relationship to the degree of consciousness impairment, underlying PVS and LIS.

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