Delayed Toxic-Hypoxic Leukoencephalopathy As Sequela of Opioid Overdose and Cerebral Hypoxia-Ischemia.

Delayed leukoencephalopathy in the aftermath of toxic exposure and cerebral hypoxia-ischemia is known as "delayed post-hypoxic leukoencephalopathy" (DPHL) but the name "delayed toxic-hypoxic leukoencephalopathy" (DTHL) may be more accurate if toxic and hypoxic mechanisms are both involved in the pathogenesis of delayed leukoencephalopathy. DTHL is characterized by initial recovery from toxic exposure and cerebral hypoxia-ischemia, clinical stability over a few weeks, and subsequent neurological deterioration with the sudden emergence of diffuse white matter disease. A 46-year-old man suffered respiratory failure and hypotension as a result of opioid overdose. Brain MRI showed watershed infarcts and EEG showed diffuse theta-delta slowing consistent with global cerebral hypoperfusion. He recovered fully and was discharged with intact cognitive function. Three weeks later, he presented with abulia and psychomotor retardation. MRI revealed extensive white matter hyperintensity and EEG showed diffuse polymorphic delta activity. DTHL was diagnosed based on classic MRI features, history of opioid overdose and hypoxic brain injury, and negative test results for etiology of white matter disease. He developed akinetic mutism prompting administration of methylprednisolone 1000-mg IV q24h for five days. He also received amantadine 100-mg PO q12h. His cognition, motivation, and psychomotor function slowly improved and returned to baseline about two months after the overdose. Clinic reassessment two and a half months after the overdose revealed normal cognitive function, slight residual MRI hyperintensity, and mild EEG slowing anteriorly. Toxic-metabolic myelinopathy causing diffuse demyelination in the deep white matter is a perfect explanation for the patient's neurological symptoms, MRI changes, EEG findings, and time course of recovery.

Altered mental status predicts length of stay but not death in a community-based cohort of hospitalized COVID-19 patients.

INTRODUCTION: Altered Mental Status (AMS) is a common neurological complication in patients hospitalized with the diagnosis of COVID-19 (Umapathi et al., 2020; Liotta et al., 2020). Studies show that AMS is associated with death and prolonged hospital stay. In addition to respiratory insufficiency, COVID-19 causes multi-organ failure and multiple metabolic derangements, which can cause AMS, and the multi-system involvement could account for the prolonged hospital stay and increased mortality. In this study, we built on our previous publication (Chachkhiani et al., 2020) using a new, larger cohort to investigate whether we could reproduce our previous findings while addressing some of the prior study's limitations. Most notably, we sought to determine whether AMS still predicted prolonged hospital stay and increased mortality after controlling for systemic complications such as sepsis, liver failure, kidney failure, and electrolyte abnormalities. OBJECTIVES: The primary purpose was to document the frequency of AMS in patients with COVID-19 at the time of presentation to the emergency room. Secondary aims were to determine: 1) if AMS at presentation was associated with worse outcomes as measured by prolonged hospitalization and death; and 2) if AMS remained a predictor of worse outcome after adjusting for concomitant organ failure and metabolic derangements. RESULTS: Out of 367 patients, 95 (26%) had AMS as a main or one of the presenting symptoms. Our sample has a higher representation of African Americans (53%) than the US average and a high frequency of comorbidities, such as obesity (average BMI 29.1), hypertension (53%), and diabetes (30%). Similar to our previous report, AMS was the most frequent neurological chief complaint. At their admission, out of 95 patients with AMS, 83 (88%) had organ failure or one of the systemic problems that could have caused AMS. However, a similar proportion (86%) of patients without AMS had one or more of these same problems. Age, race, and ethnicity were the main demographic predictors. African Americans had shorter hospital stay [HR1.3(1.0,1.7),p = 0.02] than Caucasians. Hispanics also had shorter hospital stay than non-Hispanics [HR1.6(1.2,2.1), p = 0.001]. Hypoxia, liver failure, hypernatremia, and kidney failure were also predictors of prolonged hospital stay. In the multivariate model, hypoxia, liver failure, and acute kidney injury were the remaining predictors of longer hospital stay, as well as people with AMS at baseline [HR0.7(0.6,0.9), p < 0.02] after adjusting for the demographic characteristics and clinical predictors. AMS at baseline predicted death, but not after adjusting for demographics and clinical variables in the multivariate model. Hypoxia and hyperglycemia at baseline were the strongest predictors of death. CONCLUSION: Altered mental status is an independent predictor of prolonged hospital stay, but not death. Further studies are needed to evaluate the causes of AMS in patients with COVID-19.

Neurological complications of COVID19 during March 2020 at LCMC health university medical center: Dataset.

We reviewed the electronic medical records (EMR) of patients hospitalized during the peak of the pandemic, March 1st through March 31st, to document the type and frequency of neurological problems seen in patients with COVID-19 at presentation to the emergency room. Secondary aims were to determine: 1) the frequency of neurological complaints during the hospital stay; 2) whether the presence of any neurological complaint at presentation or any of the individual types of neurological complaints at admission predicted three separate outcomes: death, length of hospital stay, or the need for intubation; and 3) if the presence of any neurological complaint or any of the individual types of neurological complaints developed during hospital stay predicted the previous three outcomes. SETTING: The Louisiana Health Sciences Center - New Orleans Institutional Review Board and the University Medical Center Clinical Research Review Committee approved the study protocol. DATA ACQUISITION: We reviewed the electronic medical records (EMR) of patients hospitalized during March (March 1st through March 31st) 2020 at the University Medical Center New Orleans (UMCNO), who tested positive for SARS-CoV-2 during the same hospitalization. The EMR team generated a list of 257 patients admitted for COVID-19. We excluded seven patients because of a negative COVID-19 test result or incomplete medical record documentation. Three neurology residents (DC, MS, DB) reviewed the EMR in detail to capture the relevant medical history, clinical course, and laboratory test results and abstracted data into an electronic data collection spreadsheet.We recorded the presentation or development of the following neurological complaints: headache, syncope, altered mental status, seizure, status epilepticus, and ischemic or hemorrhagic stroke. STATISTICAL ANALYSIS: We used "R" (statistics software) and Microsoft Excel to generate summary tables. To analyze hospital length of stay or death, we fitted a competing risks proportional hazards model for time to discharge or death using the crr() function in R version 4.0.0. The competing risks model allowed the analysis of hospital stay, taking into account that the censoring of cases due to death was not random. To predict the likelihood of intubation, we used the glm() function in R to fit a logistic regression model. For each model, we determined baseline demographic variables predictive of the outcomes and generated adjusted models. For variables with less than five cases per cell, we reported the p-values for Fisher's Exact Test.The analyses and results are published in:Chachkhiani, David et al. "Neurological complications in a predominantly African American population of COVID-19 predict worse outcomes during hospitalization." Clinical Neurology and Neurosurgery (in press).These data will be useful for researchers trying to build larger datasets regarding COVID19 neurological complications for metanalysis or to answer other questions requiring larger sample sizes.

Neurological complications in a predominantly African American sample of COVID-19 predict worse outcomes during hospitalization.

People with Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infection, COVID-19, can have neurological problems including headache, anosmia, dysgeusia, altered mental status (AMS), ischemic stroke with or without large vessel occlusion, and Guillen-Barre Syndrome. Louisiana was one of the states hit hardest by the pandemic with just over 57,000 laboratory-confirmed cases of COVID-19 by the end of June 2020. We reviewed the electronic medical records (EMR) of patients hospitalized during the peak of the pandemic, March 1st through March 31st, to document the type and frequency of neurological problems seen in patients with COVID-19 at presentation to the emergency room. Secondary aims were to determine: 1) the frequency of neurological complaints during the hospital stay; 2) whether the presence of any neurological complaint at presentation or any of the individual types of neurological complaints at admission predicted three separate outcomes: death, length of hospital stay, or the need for intubation; and 3) if the presence of any neurological complaint or any of the individual types of neurological complaints developed during hospital stay predicted the previous three outcomes. A large proportion of our sample (80 %) was African American and had hypertension (79 %). Out of 250 patients, 56 (22 %) patients died, and 72 (29 %) patients required intubation. Thirty-four (14 %) had a neurological chief complaint at presentation; the most common neurological chief complaints in the entire sample were altered mental status (AMS) (8 %), headache (2 %), and syncope (2 %). We used a competing risk model to determine whether neurological symptoms at presentation or during hospital stay were predictors of prolonged hospital stay and death. To establish whether neurological symptoms were associated with higher odds of intubation, we used logistic regression. Age was the only significant demographic predictor of death and hospital stay. The HR (95 %CI) for remaining in the hospital for a ten-year increase in age was 1.2, (1.1, 1.3, p < 0.0001), and for death was 1.3, (1.1, 1.5, p < 0.01). There were no demographic characteristics, including age or comorbidities predictive of intubation. Adjusting for age, patients who at presentation had neurological issues as their chief complaint were at significantly increased risk for remaining in the hospital, HR = 1.7, (1.1,2.5, p = 0.0001), and dying, HR = 2.1(1.1,3.8, p = 0.02), compared to patients without any neurological complaint. Of the individual admission complaints, AMS was associated with a significantly prolonged hospital stay, HR = 1.8, (1.0-3.3, p = 0.05). Patients that required dialysis or intubation or had AMS during hospitalization had more extended hospital stays. After adjusting for age, dialysis, and intubation, patients with AMS during hospital stay had a HR of 1.6, (1.1, 2.5, p = 0.01) for remaining in the hospital. Patients who had statistically significant higher odds of requiring intubation were those who presented with any neurological chief complaint, OR = 2.8 (1.3,5.8, p = 0.01), or with headaches OR = 13.3 (2.1,257.0, p = 0.008). Patients with AMS during the hospital stay, as well as those who had seizures, were more likely to need intubation. In the multivariate model, dialysis, OR = 4.9 (2.6,9.4, p < 0.0001), and AMS, OR = 8.8 (3.9,21.2, p < 0.0001), were the only independent predictors of intubation. Neurological complaints at presentation and during the hospital stay are associated with a higher risk of death, prolonged hospital stay, and intubation. More work is needed to determine whether the cause of the neurological complaints was direct CNS involvement by the virus or the other systemic complications of the virus.

Sitagliptin for prevention of stress hyperglycemia in patients without diabetes undergoing general surgery: A pilot randomized study.

AIM: We investigated if a dipeptidyl peptidase-4 inhibitor, sitagliptin, can prevent perioperative stress hyperglycemia in patients without prior history of diabetes mellitus undergoing general surgery. METHODS: This double-blind pilot trial randomized general surgery patients to receive sitagliptin (n = 44) or placebo (n = 36) once daily, starting one day prior to surgery and continued during the hospital stay. The primary outcome was occurrence of stress hyperglycemia, defined by blood glucose (BG) >140 mg/dL and >180 mg/dL after surgery. Secondary outcomes included: length-of-stay, ICU transfers, hypoglycemia, and hospital complications. RESULTS: BG >140 mg/dL was present in 44 (55%) of subjects following surgery. There were no differences in hyperglycemia between placebo and sitagliptin (56% vs. 55%, p = 0.93). BG >180 mg/dL was observed in 19% and 11% of patients treated with placebo and sitagliptin, respectively, p = 0.36. Both treatment groups had resulted in similar postoperative BG (148.9 ±â€¯29.4 mg/dL vs. 146.9 ±â€¯35.2 mg/dL, p = 0.73). There were no differences in length-of-stay (4 vs. 3 days, p = 0.84), ICU transfer (3% vs. 5%, p = 1.00), hypoglycemia <70 mg/dL (6% vs. 11%, p = 0.45), and complications (14% vs. 18%, p = 0.76). CONCLUSION: Preoperative treatment with sitagliptin did not prevent stress hyperglycemia or complications in individuals without diabetes undergoing surgery.

A Randomized Controlled Study Comparing a DPP4 Inhibitor (Linagliptin) and Basal Insulin (Glargine) in Patients With Type 2 Diabetes in Long-term Care and Skilled Nursing Facilities: Linagliptin-LTC Trial.

OBJECTIVES: Safe and easily implemented treatment regimens are needed for the management of patients with type 2 diabetes mellitus (T2DM) in long-term care (LTC) and skilled nursing facilities. DESIGN: This 6-month open-label randomized controlled trial compared the efficacy and safety of a DPP4 inhibitor (linagliptin) and basal insulin (glargine) in LTC residents with T2DM. SETTINGS: Three LTC institutions affiliated with a community safety-net hospital, US Department of Veterans Affairs and Emory Healthcare System in Atlanta, Georgia. PARTICIPANTS: A total of 140 residents with T2DM treated with oral antidiabetic agents or low-dose insulin (≤0.1 U/kg/d), with fasting or premeal blood glucose (BG) > 180 mg/dL and/or HbA1c >7.5%. INTERVENTION: Baseline antidiabetic therapy, except metformin, was discontinued on trial entry. Residents were treated with linagliptin 5 mg/d (n = 67) or glargine at a starting dose of 0.1 U/kg/d (n = 73). Both groups received supplemental rapid-acting insulin before meals for BG > 200 mg/dL. MEASUREMENTS: Primary outcome was mean difference in daily BG between groups. Main secondary endpoints included differences in frequency of hypoglycemia, glycosylated hemoglobin (HbA1c), complications, emergency department visits, and hospital transfers. RESULTS: Treatment with linagliptin resulted in no significant differences in mean daily BG (146 ± 34 mg/dL vs. 157 ± 36 mg/dL, P = .07) compared to glargine. Linagliptin treatment resulted in fewer mild hypoglycemic events <70 mg/dL (3% vs. 37%, P < .001), but there were no differences in BG < 54 mg/dL (P = .06) or <40 mg/dL (P = .05) compared to glargine. There were no significant between-group differences in HbA1c, length of stay, complications, emergency department visits, or hospitalizations. CONCLUSION: Treatment with linagliptin resulted in noninferior glycemic control and in significantly lower risk of hypoglycemia compared to insulin glargine in long-term care and skilled nursing facility residents with type 2 diabetes.