Delirium in Critically Ill Cancer Patients With COVID-19.

BACKGROUND: COVID-19 has been a devastating pandemic with little known of its neuropsychiatric complications. Delirium is one of the most common neuropsychiatric syndromes among hospitalized cancer patients with incidence ranging from 25% to 40% and rates of up to 85% in the terminally ill. Data on the incidence, risk factors, duration, and outcomes of delirium in critically ill cancer patients with COVID-19 are lacking. OBJECTIVE: To report the incidence, risks and outcomes of critically ill cancer patients who developed COVID-19. METHODS: This is a retrospective single-center study evaluating delirium frequency and outcomes in all critically ill cancer patients with COVID-19 admitted between March 1 and July 10, 2020. Delirium was assessed by Confusion Assessment Method for Intensive Care Unit, performed twice daily by trained intensive care unit (ICU) nursing staff. Patients were considered to have a delirium-positive day if Confusion Assessment Method for Intensive Care Unit was positive at least once per day. RESULTS: A total of 70 patients were evaluated. Of those 70, 53 (75.7%) were found to be positive for delirium. Patients with delirium were significantly older than patients without delirium (median age 67.5 vs 60.3 y, P = 0.013). There were no significant differences in demographic characteristics, chronic medical conditions, neuropsychiatric history, cancer type, or application of prone positioning between the 2 groups. Delirium patients were less likely to receive cancer-directed therapies (58.5% vs 88.2%, P = 0.038) but more likely to receive antipsychotics (81.1% vs 41.2%, P = 0.004), dexmedetomidine (79.3% vs 11.8%, P < 0.001), steroids (84.9% vs 58.8%, P = 0.039), and vasopressors (90.6% vs 58.8%, P = 0.006). Delirium patients were more likely to be intubated (86.8% vs 41.2%, P < 0.001), and all tracheostomies (35.9%) occurred in patients with delirium. ICU length of stay (19 vs 8 d, P < 0.001) and hospital length of stay (37 vs 12 d, P < 0.001) were significantly longer in delirium patients, but there was no statistically significant difference in hospital mortality (43.4% vs 58.8%, P = 0.403) or ICU mortality (34.0% vs 58.8%, P = 0.090). CONCLUSIONS: Delirium in critically ill cancer patients with COVID-19 was associated with less cancer-directed therapies and increased hospital and ICU length of stay. However, the presence of delirium was not associated with an increase in hospital or ICU mortality.

Incidence of Seizure and Associated Risk Factors in Patients in the Medical Intensive Care Unit (ICU) at Memorial Sloan Kettering Cancer Center (MSK) from 2016-2017.

Background: Seizures and status epilepticus are common neurologic complications in the intensive care unit (ICU) but the incidence in a cancer ICU is unknown. It is important to understand seizure risk factors in cancer patients to properly diagnose the seizure type to ensure appropriate therapy. Methods: We identified patients admitted to the medical ICU at Memorial Sloan Kettering Cancer Center (MSK) from January 2016 to December 2017 who had continuous or routine electroencephalography (EEG) and identified clinical and electrographic seizures by chart review. Results: Of the 1059 patients admitted to the ICU between 2016 and 2017, 50 patients had clinical and/or electrographic seizures (incidence of 4.7%, 95% CI: 3.4-6.0). The incidences of clinical and electrographic seizure were 4.1% and 1.1%, respectively. In a multivariable stepwise regression model, history of seizure (OR: 2.9, 95% CI: 1.1-7.8, P: .03), brain metastasis (OR: 2.5, 95% CI: 1.1-5.8, P: .03), vasopressor requirement (OR: 2.2, 95% CI: 1.0-4.9, P: .05), and age < 65 (2.4, 95% CI: 1.2-5.0, P: .02) were associated with increased risk of seizure (either clinical or electrographic). Obtaining continuous EEG instead of routine EEG increased the yield of seizure detection significantly (OR: 3.9, 95% CI: 1.3-11.1, P: .01). No chemotherapy in the past 30 days, no antibiotic use, vasopressor requirement, and having a brain tumor increased risk of electrographic seizure. Length of continuous EEG > 24 h significantly increased the chances of both clinical and electrographic seizure detection, (OR: 2.6 [95% CI: 1.2-5.7] and 15.0 [95% CI: 2.7-82.5], respectively). Conclusions: We identified known and cancer-related risk factors which can aid clinicians in diagnosing seizures in cancer ICUs. Long-term video EEG monitoring should be considered, particularly given the treatable and reversible nature of seizures.

Critically ill patients with severe immune checkpoint inhibitor related neurotoxicity: A multi-center case series.

PURPOSE: Serious immune checkpoint inhibitor (ICI)-related neurotoxicity is rare. There is limited data on the specifics of care and outcomes of patients with severe neurological immune related adverse events (NirAEs) admitted to the Intensive Care Unit (ICU). MATERIALS AND METHODS: Retrospective study of patients with severe NirAEs admitted to the ICU at 3 academic centers between January 2016 and December 2018. Clinical data collected included ICI exposure, type of NirAE (central [CNS] or peripheral nervous system [PNS) disorders), and patient outcomes including neurological recovery and mortality. RESULTS: Seventeen patients developed severe NirAEs. Eight patients presented with PNS disorders; 6 with myasthenia gravis (MG), 1 had a combination of MG and polyneuropathy and 1 had Guillain-Barre syndrome. Nine patients had CNS disorders (6 seizures and 5 had concomitant encephalopathy. During ICU admission, 65% of patients required mechanical ventilation, 35% vasopressors, and 18% renal replacement therapy. The median ICU and hospital length of stay were 7 (2-36) and 18 (4-80) days, respectively. Hospital mortality was 29%. At hospital discharge, 18% of patients made a full neurologic recovery, 41% partial recovery, and 12% did not recover. CONCLUSION: Severe NirAEs while uncommon, can be serious or even life-threatening if not diagnosed and treated early.

Inflammatory Leptomeningeal Cytokines Mediate COVID-19 Neurologic Symptoms in Cancer Patients.

SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction that emerges weeks after the acute respiratory infection. To better understand this pathology, we prospectively analyzed of a cohort of cancer patients with neurologic manifestations of COVID-19, including a targeted proteomics analysis of the cerebrospinal fluid. We find that cancer patients with neurologic sequelae of COVID-19 harbor leptomeningeal inflammatory cytokines in the absence of viral neuroinvasion. The majority of these inflammatory mediators are driven by type II interferon and are known to induce neuronal injury in other disease states. In these patients, levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks after convalescence from acute respiratory infection. These prolonged neurologic sequelae following systemic cytokine release syndrome lead to long-term neurocognitive dysfunction. Our findings suggest a role for anti-inflammatory treatment(s) in the management of neurologic complications of COVID-19 infection.

Inflammatory leptomeningeal cytokines mediate delayed COVID-19 encephalopathy.

SARS-CoV-2 infection induces a wide spectrum of neurologic dysfunction. Here we show that a particularly vulnerable population with neurologic manifestations of COVID-19 harbor an influx of inflammatory cytokines within the cerebrospinal fluid in the absence of viral neuro-invasion. The majority of these inflammatory mediators are driven by type 2 interferon and are known to induce neuronal injury in other disease models. Levels of matrix metalloproteinase-10 within the spinal fluid correlate with the degree of neurologic dysfunction. Furthermore, this neuroinflammatory process persists weeks following convalescence from the acute respiratory infection. These prolonged neurologic sequelae following a systemic cytokine release syndrome lead to long-term neurocognitive dysfunction with a wide range of phenotypes.

Neurointensive care biophysiological monitoring.

Monitoring various physiological parameters and their derangements provides a valuable tool for management of severely brain injured patients. The various parameters and their monitoring tools include but are not all inclusive are cerebral blood flow and oxygen monitoring, jugular bulb oximetry, intracerebral microdialysis and continuous electroencephalography. It needs to be seen how these devices are applied to improve patient outcomes.

Acute localized exanthematous pustulosis (ALEP) caused by Ibuprofen. A case report.

Acute generalized exanthematic pustulosis (AGEP) is characterized by a generalized rash and sterile disseminated, sometimes coalescing subcorneal pustules. It occurs in body flexures such as the inguinal folds and intertriginous areas. The acute onset of disease is accompanied by malaise, fever >38 degrees C and peripheral granulocytosis. We report on a female patient who according to the criteria of AGEP was diagnosed as having acute localized exanthematic pustulosis (ALEP) on the face.