Faculty Bibliography

BACKGROUND:Few data exist on the rate of clinical progression for Parkinson's disease (PD) patients who have entered a late stage of the disease. OBJECTIVE:Study the clinical progression of a late-stage PD (LSPD) population over one year follow-up. METHODS:50 LSPD patients (Schwab and England ADL Scale <50 or Hoehn Yahr Stage >3 in MED ON) underwent an extensive clinical assessment at baseline and after one year and an acute levodopa test at baseline. RESULTS:Mean age of LSPD patients (female 46%) was 77.5 ± 5.9 years and mean disease duration was 15.5 ± 6.5 years. At baseline, 76% had levodopa-induced motor complications (MC), usually non-troublesome, 68% were demented, 54% had psychosis and 68% depression. Caregiver distress was high. l-dopa responsiveness was mild (18% ± 12 of improvement on MDS-UPDRS-III). After one-year, 20% of the patients were dead, institutionalized or HY 5. MDS-UPDRS-motor mean score worsened 7.2 ± 10.3 points although there was heterogeneity between patients, and there was a global worsening of non-motor symptoms, mostly in cognition/mood, urinary and gastrointestinal domains. Nevertheless, MC improved despite similar levodopa equivalent dose. Functional independence and quality of life worsened. Dysphagia severity at baseline predicted a poor outcome (death, institutionalization or HY 5) (Hazard ratio 2.3, 95% CI 1.12-4.4; p = 0.01), whereas magnitude of l-dopa response of LSPD patients did not. CONCLUSIONS:LSPD patients still present a significant, although heterogeneous, motor and non-motor progression over 1 year. Dysphagia severity predicts the occurrence of additional disease severity milestones and its management must be prioritized.

Visuospatial attention is asymmetrically distributed with a leftward bias (i.e. pseudoneglect), while evidence for asymmetries in auditory spatial attention is still controversial. In the present study, we investigated putative asymmetries in the distribution of auditory spatial attention and the influence that visual information might have on its deployment. A modified version of the Posner task (i.e. the visuo-audio spatial task [VAST]) was used to investigate spatial processing of auditory targets when endogenous orientation of spatial attention was mediated by visual cues in healthy adults. A line bisection task (LBT) was also administered to assess the presence of a leftward bias in deployment of visuospatial attention. Overall, participants showed rightward and leftward biases in the VAST and the LBT, respectively. In the VAST, sound localization was enhanced by visual cues. Altogether, these findings support the existence of a facilitation effect for auditory targets originating from the right side of space and provide new evidence for crossmodal links in endogenous spatial attention between vision and audition.

OBJECTIVE:The laryngeal adductor reflex (LAR) is an airway-protective response triggered by sensory laryngeal receptors and resulting in bilateral vocal fold adduction. The normal morphology of the early R1 response resembles that of the compound muscle action potential (CMAP). However, in a small subset of patients, the morphology is dyssynchronous with multiple peaks. This study investigates whether preoperative LAR dyssynchrony predicts intraoperative nerve behavior during thyroid surgeries. STUDY DESIGN/METHODS:Retrospective case-control study. SETTING/METHODS:US academic health center. SUBJECTS AND METHODS/METHODS:Opening and closing LAR waveforms from 200 patients with normal preoperative laryngeal examinations monitored continuously during thyroid surgeries using the LAR were analyzed. Area under the curve (AUC) and number of "events" during surgery (defined as any transient decline in AUC >50% baseline) were determined for patients who demonstrated opening dyssynchronous LAR traces compared to demographically matched controls. RESULTS:= .007). Upon thyroid removal, 1 patient converted from a dyssynchronous to synchronous trace. CONCLUSIONS:intraoperative nerve monitoring, frequent tissue relaxation, and saline irrigation as means to minimize nerve stress intraoperatively.

Background: Alzheimer's disease (AD) is thought to involve a cerebrovascular component and AD shares many risk factors with cardiovascular diseases. Amyloid beta (Abeta) is neurotoxic and damages brain microcirculation. Abeta production is up-regulated by hypoxia. Oxygen availability and extraction not only depends on the increase in cerebral blood flow (CBF) but also on the decrease of capillary transit-time heterogeneity (CTH). Structural or functional damage caused to the brain microcirculation will reduce the oxygen availability by a reduction in CBF and increased CTH (capillary dysfunction). Carbonic anhydrase inhibitors (CAIs) have shown to reduce the Abeta neurovascular mitochondrial toxicity, but the effect of this treatment in brain hemodynamics has not been evaluated. The present work aims to investigate the effect of long-term treatment with carbonic anhydrase inhibitors (CAIs) on the neurovascular response in Tg-SweDI mice.
Method(s): All experiments were approved by the Danish Animal Inspectorate. Tg-SwDI mice (4 months old) were fed for 140 - 150 days with a diet supplemented with acetazolamide (G1), methazolamide (G2) or no medication (G3). The groups were randomized and researchers were blind during the data acquisition. A control group of wild-type (WT; G4) mice was included. We performed imaging in awake head-restrained TgSwDI and WT mice through a cranial window placed onto the somatosensory area of the barrel cortex. We estimated relative changes in brain hemodynamics during whiskers stimulation (10 s). We estimated CBF and cerebral blood volume (rCBV) using laser Doppler flowmetry and optical intrinsic signal imaging, respectively. Two-photon imaging was employed to estimate intravascular oxygen partial pressure (ptO2), mean transit-time (MTT), CTH and capillary hemodynamics.
Result(s): Our preliminary analysis in awake WT mice (G4; N = 7) shows that functional activation produced an increase in regional CBF and CBV of 9.41 +/-3.7% and 1.49+/-0.35%, respectively. During activation, MTT and CTH respectively decreased 14.06 +/-5.92% and 23.28 +/- 9.60%. Arterial and venous ptO2 increased by 1.33 +/- 0.33% and 2.60 +/-0.56%. The estimated OEF showed a decrease of 12.4% +/-2.9%. A blinded analysis is currently assessed to evaluate the effect of CAIs on the brain hemodynamic response to functional activation.
Conclusion(s): Our work describes the signature of capillary dysfunction in an AD mouse model. Our results also enable us to elucidate the effect of the carbonic anhydrase inhibitors in capillary dysfunction in AD

Neuropsychological assessment is critical for understanding the impact of seizures on cognition and informing treatment decisions. While focus is often placed on examining groups based on seizure type/epilepsy syndrome, an alternate approach emphasizes empirically derived groups based solely on cognitive performance. This approach has been used to identify cognitive phenotypes in temporal lobe epilepsy (TLE). The current study sought to replicate prior work by Hermann and colleagues (2007) and identify cognitive phenotypes in a separate, larger cohort of 185 patients with TLE (92 left TLE, 93 right TLE). Cluster analysis revealed 3- and 4-cluster solutions, with clusters differentiated primarily by overall level of performance in the 3-cluster solution (Low, Middle, and High performance) and by more varying cognitive phenotypes in the 4-cluster solution (Globally Low, Low Executive Functioning/Speed, Low Language/Memory, and Globally High). Differences in cognitive performance as well as demographic and clinical seizure variables are presented. A greater proportion of the patients with left TLE were captured by Cluster 3 (Low Language/Memory) than by the other 3 clusters, though this cluster captured only approximately one-third of the overall group with left TLE. Consistent with prior findings, executive functioning and speed emerged as additional domains of interest in this sample of patients with TLE. The current results extend prior work examining cognitive phenotypes in TLE and highlight the importance of identifying the comprehensive range of potential cognitive profiles in TLE.

BACKGROUND:Pisa syndrome is a lateral deviation of the trunk described in Parkinson's disease (PD). Its etiology is still unknown; advanced muscular signal analysis techniques, such as inter-muscular coherence, could help clarifying its pathophysiology and suggest therapeutic strategies. METHODS:Fourteen idiopathic PD subjects with a lateral deviation of the trunk of at least 10° were included. Electromyographic (EMG) signal was recorded from bilateral thoracic, and lumbar para-spinal and obliqui externi muscles. The synchronization between EMG right and left side signals was quantified using the magnitude-squared coherence function. RESULTS:In our sample, coherence (range 0-1) did not exceed 0.3, which indicates a lack of intra-muscular coherence. CONCLUSION/CONCLUSIONS:This finding is suggestive of a defective muscular fine-tuning, which has been associated with bradykinesia. These data support the hypothesis of PS as a clinical sign of bradykinesia, impacting on therapeutic and rehabilitative options.

Objectives: To demonstrate the development and use of an acute imaging protocol for the metabolic assessment of tissue viability during acute stroke.
Method(s): The DAWN and DEFUSE 3 trials (1,2) have demonstrated that there is much to gain from the use of physiologically based guidelines to extend the use of mechanical recanalization. Literature reports provide strong data supporting the use of brain tissue sodium concentration (TSC) as a biomarker for identifying physiologically non-viable tissue during evolving brain ischemia (3,4). Testing this hypothesis in vivo, in humans, have been previously hampered by acquisition times that were long for routine clinical use. Recent developments in MRI data acquisition and hardware make it possible to acquire the data to provide the aforementioned assessment in under 5 minutes at a level of signal-to-noise ratio (SNR) and spatial resolution compatible with physiologically driven MRI scans such as diffusion weighted imaging and perfusion imaging. This was achieved using an Ultra-Short-Echo Time sequence with optimal acquisition throughput (TPI, TE/TR 0.3/100 ms, p 0.2). Signal excitation/reception was performed using a patient-friendly double-tuned (¹H/²³Na) birdcage coil (Quality Electrodynamics Inc., Mayfield Heights, Ohio). The protocol was implemented on a MAGNETOM Skyra 3 Tesla scanner at NYU's Tisch hospital. The scanner is located adjacent (20 feet) to the neuro interventional suite where patients are recanalized. Subject's anesthesia was maintained (FabiusMRI, DraegerInc., Telford, PA) and physiological status continuously monitored using MRI-compatible equipment (Expression MR400, Phillips Healthcare, Andover, MA).
Result(s): After phantom validation and healthy volunteer studies to determine the quantitative performance of the data acquisition techniques the protocol was used on post-endovascular thrombectomy subjects (n 3), immediately upon procedure completion and under its own IRB approved protocol. During these studies, the use of the proposed methodology was found to be compatible with the clinical care of the subjects. Specifically, performing the required scans was not found to interfere with the subject's post-recanalization care. Tissue sodium concentration data were, likewise, found to meet the required levels of SNR to provide the quantitative assessment mentioned above. A representative data set from one of these sessions is shown in figure 1. This mechanically-recanalized patient had an area of non-salvaged tissue in the left parietal lobe that is clearly depicted on the ²³Na MRI scan. The TSC in this area was 76 mM at the time of the scan. (Figure presented)
Conclusion(s): This work demonstrates that state-of-the-art MRI methodology can be used to provide a clinically viable imaging protocol for evaluating the use of sodium MRI as a quantitative biomarker for identifying physiologically viable tissue during evolving brain ischemia

Amiodarone (Cordarone^®, Pfizer Inc) is an antiarrhythmic medication with a well-known toxicity profile, including rare cases of hyponatremia as a result of syndrome of inappropriate antidiuretic hormone (SIADH). We report on such a case in which a patient was found to be hyponatremic after evaluation. An 88-year-old male who presented to the emergency department was found to be hyponatremic secondary to amiodarone-induced SIADH following a fall, with possible seizure and traumatic brain injury. He had a history of hypertension, paroxysmal atrial fibrillation, emphysema, myocardial infarction, benign prostatic hyperplasia, chronic kidney disease, Meniere's disease, anemia, and gastroesophageal reflux. Upon admission, his urine sodium level was elevated, and his serum sodium, urine osmolality, and anion gap were below normal. In the setting of hyponatremia, the patient's amiodarone was held: he had been taking amiodarone 200 mg once daily for nine months prior to admission. He was treated with intravenous (IV) normal saline over four days. He was fluid-restricted and his sodium levels were closely monitored every two hours. Within 19 hours, his serum sodium levels had improved. Amiodarone was restarted approximately three days later. Upon follow-up after discharge, the patient remained on amiodarone for the next two months. His serum sodium level ranged from 126 mEq/L to 131 mEq/L over a two-week period. He was supplemented with sodium chloride tablets and has been otherwise stable. Amiodarone may cause acute or chronic SIADH, with a wide range of symptoms. Seizures have not been reported in the literature but our patient had a witnessed seizure, although his electroencephalogram (EEG) was negative. Syndrome of inappropriate antidiuretic hormone can occur with any formulation of amiodarone in a dose-dependent fashion. Our patient's sodium levels stabilized within two weeks after amiodarone was resumed. The mechanism of amiodarone-induced SIADH remains unclear.

BACKGROUND:Little data exists regarding reversal and resumption of antithrombotics following left ventricular assist device (LVAD)-associated intracranial hemorrhage (ICH). METHODS:Prospectively collected data of LVAD patients with ICH was reviewed. Coagulopathy reversal agents, antithrombotic regimens and thrombotic (venous thromboembolism, ischemic stroke, myocardial infarction) and hemorrhagic (recurrent ICH, gastrointestinal bleed, anemia requiring transfusion) complications were recorded. RESULTS:Of 405 patients, intracranial hemorrhage occurred in 39 (10%): 23 intracerebral hemorrhages, 10 subarachnoid hemorrhages, and 6 subdural hematomas. Of 27 patients who received antithrombotic reversal, 8 (30%) had inadequate coagulopathy reversal and 3 of these had hemorrhage expansion or died before repeat imaging. One (4%) had a thrombotic complication (deep vein thrombosis). Antithrombotic therapy was resumed in 17(100%) survivors in a median time 8 days for antiplatelet agents, and 14 days for warfarin. Recurrent intracranial hemorrhage occurred within a median of 7 days of antithrombotic resumption, while ischemic stroke occurred in a median of 428 days. Patients who resumed antiplatelets alone (N=4) had a trend toward more thrombotic events (1.37 vs. 0.14 events-per-patient-year [EPPY],P=0.08), including more fatal thrombotic events (0.34 EPPY vs. 0.08, P=0.89) compared to those resuming warfarin±antiplatelet (N=14). Non-fatal hemorrhage event rates were 0.34 EPPY in the warfarin±antiplatelet vs. 0 EPPY in the antiplatelet alone group (P=0.16). No fatal hemorrhagic events occurred. CONCLUSIONS:Reversal of anticoagulation appears safe following LVAD-associated intracranial hemorrhage, though inadequate reversal was common. Resumption of warfarin±antiplatelet was associated with fewer fatal and non-fatal thrombotic events compared to antiplatelets alone, though more non-fatal hemorrhage events occurred.