Alzheimer’s Disease Clinical and Research Update for Health Care Practitioners

September 2013

Philip A Defina
Rosemarie Scolaro Moser
Megan Glenn
Jonathan Fellus
…and others.

ABSTRACT: Of the approximately 6.8 million Americans who have been diagnosed with dementia, over 5 million have been diagnosed with Alzheimer’s Disease (AD). Due to the rise in the aging population, these figures are expected to double by 2050. The following paper provides an up-to-date review of clinical issues and relevant research. Research related to the methods of the earliest possible detection of AD is ongoing. Health care professionals should play a critical role in differentially diagnosing AD patients, as well as supporting their families. Novel interventions, including medications, natural supplements, and behavioral techniques, are constantly appearing in the literature. It is necessary for the health practitioner to remain current, regarding AD, as such information will facilitate better care for patients and their families.

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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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Heart rate variability for assessing comatose patients with different Glasgow Coma Scale scores

October 2012

Yazmina Machado-Ferrer
Mario Estévez
Calixto Machado
Yanín Machado
Philip A. DeFina
…and others.

ABSTRACT: OBJECTIVE: To assess the autonomic nervous system (ANS) in coma by heart rate variability (HRV). METHODS: Sixteen comatose patients and 22 normal subjects with comparable ages and genders were studied. Patients were classified in two subgroups according to the Glasgow Coma Scale (GCS). Time, frequency, and informational HRV domain indices were calculated. RESULTS: A notable reduction of HRV was found in patients. Regarding the time domain indices, the triangular index, and the Delta_RRs, were significantly reduced in the subgroup with GCS=3. Absolute power for the whole frequency spectrum decreased whenever GCS scores were lower. A significant decrement was found for absolute power of the VLF and LF bands in the subgroup of GCS=3, and although it was lower for the HF band in these patients, those changes were not statistically significantly different. The LF/HF ratio and the Shannon´s entropy indices were significantly reduced in the subgroup with GCS=3. Our results are discussed regarding the progressive dysfunction the ANS networks when coma deepens. CONCLUSIONS: The HRV procedure is a powerful tool to assess the ANS in comatose patients. SIGNIFICANCE: HRV is a minimally invasive, low-cost methodology, suitable for assessing the ANS in coma.

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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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