Unusual Brainstem Twisting Revealed by MRI Tractography in a Patient Who Survived a Severe Traumatic Upper Spinal Dislocation

June 2013

Calixto Machado
Jesús Pérez Néllar
Rafael Rodriguez-Rojas
Mauricio Chinchilla
Philip A. DeFina
…and others.

ABSTRACT: We report unusual twisting of the brainstem in MRI tractography in a patient who survived a traumatic brain injury with upper spinal dislocation. A 39-year-old male patient involved in a high-speed car accident was admitted in coma on February 2003. He had a Glasgow Coma Scale of 4, respiratory arrhythmia and tetraplegia. Four weeks later he was diagnosed as being in a persistent vegetative state (PVS). Our group evaluated him for first time in 2010. The patient was then in a minimally conscious state (MCS), with a limited but clear evidence of awareness of the environment, based on a reproducible gestural response following simple commands and visual pursuit of relatives and other persons in his room. He maintained a severe tetraplegia, hyperreflexia, and bilateral Babinski sign. Neuroimaging studies (Figure 1) performed according to our protocol for the assessment of PVS/MCS,1,2 demonstrated a severe atrophic and twisted brainstem. There was an MRI-T2 hyperintensity in the lower part of the medulla oblongata that suggested the presence of an old infarct, probably due to an ischemic and/or hemorrhagic insult because of the compression of the brainstem. MRI-Tractography revealed brainstem long tracts twisting. In order to have a better visualization of bone abnormalities, CT with 3D reconstruction was performed demonstrating a rotatory deformity of the upper spine. In our patient hypoxic encephalopathy secondary to acute respiratory insufficiency was surely the cause of his chronic consciousness disorder.1,2 Probably his critical condition, and the needs of life support protocols upon arrival to the intensive care, hampered the with upper spinal dislocation diagnosis,3-5 leading to a lack of radiological evidence, or due to the presence of additional injuries where a clinical examination is impossible. The demonstration of brainstem twisting instead of section in MRI-Tractography has is an unusual neuroimaging finding, and scientifically highlights the neuroimaging findings in this patient who survived severe upper spinal dislocation.

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Dextromethorphan/Quinidine alleviates pseudobulbar affect and rapidly eliminates suicidal ideation in individuals with traumatic brain injury

January 2014

Philip A Defina
Jonathan Fellu
Christine Carson
Mauricio Chinchilla
…and others.

ABSTRACT: Recent prevalence estimates of pseudobulbar affect (PBA) symptomatology secondary to traumatic brain injury (TBI) exceed 55%. Treatment with dextromethorphan/quinidine (DMQ) has been shown to robustly diminish the frequency and severity of PBA episodes associated with different neurological conditions. Objective. This retrospective case study aims to demonstrate the efficacy of DMQ to minimize PBA symptoms in a series of patients with traumatic brain injury (TBI) and describe unforeseen evidence of its additional therapeutic potential to mitigate diverse neuropsychiatric sequelae. Methods. The case histories of five patients were reviewed according to the clinical observations of their neurologist (JLF). Five patients sustained TBI an average of nine years prior, presenting with a stable history of PBA and frequent suicidal ideation. DMQ therapy was indicated for all five patients to ameliorate paroxysmal episodes of laughter, crying or both. Results. The results of this clinical case study confirm DMQ as a potent treatment for PBA and reveal its potential to ameliorate additional neuropsychiatric behaviors associated with TBI. Surprisingly, concomitant suicidal ideation and associated impulsivity were discovered to rapidly resolve following treatment with DMQ. Conclusions. The rapid onset and sustained tolerability of DMQ suggest it deserves consideration as an alternative to conventional pharma-cotherapies for managing PBA, suicidal ideation and associated impulsivity. DMQ therapy holds promise to significantly reduce morbidity and mortality, profoundly enhance quality of life and fundamentally improve longterm outcome for TBI survivors.

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Zolpidem induces paradoxical metabolic and vascular changes in a patient with PVS

August 2013

Rafael Rodriguez-Rojas
Calixto Machado
Lazaro M Alvarez
Philip A Defina
…and others.

ABSTRACT: Introduction: Zolpidem is a non-benzodiazepine drug used for the therapy of insomnia, which has selectivity for stimulating the effect of GABA-A receptors. Recently, a paradoxical arousing effect of zolpidem in patients with severe brain damage has been repeatedly reported. Methods: A placebo-controlled magnetic resonance study was conducted to evaluate its effect on BOLD and metabolites spectral signals in a patient with severe brain injuries and an age-matched healthy volunteer. A multi-modal analysis was used to assess aspects in the pharmacologically-induced changes in the resting-state brain metabolism. Results: A significantly increased BOLD signal was transiently localized in the left frontal cortices, bilateral anterior cingulated areas, left thalamus and right head of the caudate nucleus. The healthy subject showed a deactivation of the frontal, parietal and temporal cortices. BOLD signal changes were found to significantly correlate with concentrations of extravascular metabolites in the left frontal cortex. It is discussed that, when zolpidem attaches to modified GABA receptors of neurodormant brain cells, brain activation is induced. This might explain the significant correlations of BOLD signal changes and proton-MRS metabolites in this patient after zolpidem. Conclusion: It was concluded that proton-MRS and BOLD signal assessment could be used to study zolpidem-induced metabolic modulation in a resting state.

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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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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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