Delayed Signs and Symptoms of Extended Release Guanfacine Overdose in Two Adolescent Patients: Implications of Monitoring on the Psychiatry Unit.

Guanfacine is a selective alpha-2a adrenoreceptor agonist that with overdose can cause symptoms ranging from mild sedation to coma, respiratory depression, hyporeflexia, hypotonia, bradycardia, and hypotension. Despite a well-defined and predictable toxidrome, variations can be seen based on multiple factors including age, quantity ingested, organ functions, coingestions, time since ingestion, and specific dosage form. Here, we describe two cases of delayed presentation of extended release guanfacine toxicity and highlight the variations encountered in the toxidrome presentation. These cases bring to attention the importance of maintaining a high suspicion for such atypical presentations, keeping in mind the limitations of managing these complications on an inpatient psychiatric unit.

Intracranial Hemorrhage in COVID-19 Patients.

OBJECTIVE: To describe the clinical, laboratory, temporal, radiographic, and outcome features of acute Intracranial Hemorrhage (ICH) in COVID-19 patients. METHODS: Retrospective, observational, consecutive case series of patients admitted with ICH to Maimonides Medical Center from March 1 through July 31, 2020, who had confirmed or highly suspected COVID-19. Demographic, clinical, laboratory, imaging, and outcome data were analyzed. ICH rates among all strokes were compared to the same time period in 2019 in two-week time intervals. Correlation of systolic blood pressure variability (SBPV) and neutrophil-to-lymphocyte ratio (NLR) to clinical outcomes were performed. RESULTS: Of 324 patients who presented with stroke, 65 (20%) were diagnosed with non-traumatic ICH: 8 had confirmed and 3 had highly suspected COVID-19. Nine (82%) had at least one associated risk factor for ICH. Three ICHs occurred during inpatient anticoagulation. More than half (6) suffered either deep or cerebellar hemorrhages; only 2 were lobar hemorrhages. Two of 8 patients with severe pneumonia survived. During the NYC COVID-19 peak period in April, ICH comprised the highest percentage of all strokes (40%), and then steadily decreased week-after-week (p = 0.02). SBPV and NLR were moderately and weakly positively correlated to discharge modified Rankin Scale, respectively. CONCLUSIONS: COVID-19 associated ICH is often associated with at least one known ICH risk factor and severe pneumonia. There was a suggestive relative surge in ICH among all stroke types during the first peak of the NYC pandemic. It is important to be vigilant of ICH as a possible and important manifestation of COVID-19.

Brain correlates of stress-induced peripheral vasoconstriction in patients with cardiovascular disease.

The influence of acute psychological stress on cardiovascular disease is an emerging public health concern. Identification of brain mechanisms underlying this may aid in the discovery of possible treatments. Acute psychological stress may induce arteriolar vasoconstriction and reduce blood flow to vital organs. We hypothesized that functional changes in brain regions involved with memory and autonomic/emotional regulation are implicated in the vasoconstrictive stress response, including the medial prefrontal cortex (anterior cingulate), insula, and dorsolateral prefrontal cortex. Subjects with a history of coronary artery disease (N = 59) underwent measurement of microvascular vasomotor tone with the EndoPAT device and O-15 positron emission tomography (PET) imaging of the brain during exposure to mental stress and control conditions. The peripheral arterial tonometry (PAT) ratio was calculated as the mean peripheral vasomotor tone during stress divided by the mean tone during rest. Whole brain contrasts were performed between groups above and below the median PAT ratio, and significant contrasts were defined with cutoff p < 0.005. Stress-induced peripheral vasoconstriction (below median PAT ratio) was associated with increased stress activation in insula and parietal cortex, and decreased activation in the medial prefrontal cortex with stress tasks compared to control tasks. These findings demonstrate that stress-induced vasoreactivity is associated with changes in brain responses to stress in areas involved in emotion and autonomic regulation. These findings have important implications on possible treatments for mental stress-induced vascular toxicity.

Brain mechanisms of stress and depression in coronary artery disease.

INTRODUCTION: Major depression is associated with an increased risk for and mortality from coronary artery disease (CAD), however the mechanisms by which this occurs are not clear. Depression, which is linked to stress, is associated with changes in brain areas involved in memory and the stress response, and it is likely that these regions play an important role in this increased risk. This study assessed the effects of stress on brain and cardiac function in patients with CAD with and without depression. METHODS: CAD patients with (N = 17) and without (N = 21) major depression based on the Structured Clinical Interview for DSM-IV (DSM-IV) and/or a Hamilton Depression Scale score of nine or greater underwent imaging of the brain with high resolution positron emission tomography (HR-PET) and [O-15] water and imaging of the heart with single photon emission tomography (SPECT) and [Tc-99 m] sestamibi during mental stress (mental arithmetic) and control conditions. RESULTS: Patients with CAD and major depression showed increased parietal cortex activation and a relative failure of medial prefrontal/anterior cingulate activation during mental stress compared to CAD patients without depression. Depressed CAD patients with stress-induced myocardial ischemia, however, when compared to depressed CAD patients without showed increased activation in rostral portions of the anterior cingulate. CONCLUSIONS: These findings are consistent with a role for brain areas implicated in stress and depression in the mechanism of increased risk for CAD morbidity and mortality in CAD patients with the diagnosis of major depression.

A Pilot Study of the Effects of Mindfulness-Based Stress Reduction on Post-traumatic Stress Disorder Symptoms and Brain Response to Traumatic Reminders of Combat in Operation Enduring Freedom/Operation Iraqi Freedom Combat Veterans with Post-traumatic Stress Disorder.

OBJECTIVE: Brain imaging studies in patients with post-traumatic stress disorder (PTSD) have implicated a circuitry of brain regions including the medial prefrontal cortex, amygdala, hippocampus, parietal cortex, and insula. Pharmacological treatment studies have shown a reversal of medial prefrontal deficits in response to traumatic reminders. Mindfulness-based stress reduction (MBSR) is a promising non-pharmacologic approach to the treatment of anxiety and pain disorders. The purpose of this study was to assess the effects of MBSR on PTSD symptoms and brain response to traumatic reminders measured with positron-emission tomography (PET) in Operation Enduring Freedom/Operation Iraqi Freedom (OEF/OIF) combat veterans with PTSD. We hypothesized that MBSR would show increased prefrontal response to stress and improved PTSD symptoms in veterans with PTSD. METHOD: Twenty-six OEF/OIF combat veterans with PTSD who had recently returned from a combat zone were block randomized to receive eight sessions of MBSR or present-centered group therapy (PCGT). PTSD patients underwent assessment of PTSD symptoms with the Clinician-Administered PTSD Scale (CAPS), mindfulness with the Five Factor Mindfulness Questionnaire (FFMQ) and brain imaging using PET in conjunction with exposure to neutral and Iraq combat-related slides and sound before and after treatment. Nine patients in the MBSR group and 8 in the PCGT group completed all study procedures. RESULTS: Post-traumatic stress disorder patients treated with MBSR (but not PCGT) had an improvement in PTSD symptoms measured with the CAPS that persisted for 6 months after treatment. MBSR also resulted in an increase in mindfulness measured with the FFMQ. MBSR-treated patients had increased anterior cingulate and inferior parietal lobule and decreased insula and precuneus function in response to traumatic reminders compared to the PCGT group. CONCLUSION: This study shows that MBSR is a safe and effective treatment for PTSD. Furthermore, MBSR treatment is associated with changes in brain regions that have been implicated in PTSD and are involved in extinction of fear responses to traumatic memories as well as regulation of the stress response.

Recurrent Stroke due to Patent Foramen Ovale Closure Device Thrombus Eight Years after Implantation.

Patent foramen ovale (PFO) is a common heart defect and is found in about 25% of the general population. Although randomized trials have failed to show the superiority of percutaneous closure of PFO over medical management, the number of patients with closure device placement has grown over the years. Delayed complications from PFO closure are rare. We present a case of cardioembolic stroke secondary to a mobile thrombus on a PFO closure device 8 years after implantation.

Bilateral Vein of Trolard Thrombosis.

Isolated cortical vein thrombosis without dural sinus involvement is not common. The vein of Trolard is an important cortical vein as it drains eloquent cortex. We report 2 cases of bilateral vein of Trolard thrombosis; one with and the other without dural sinus involvement. To our knowledge, there have been no cases of bilateral vein of Trolard thrombosis reported in literature. The clinical presentation of cerebral venous thrombosis is variable; patients can present with isolated intracranial hypertension, focal neurological abnormalities, seizures, or encephalopathy.