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Guidelines for Seizure Prophylaxis in Adults Hospitalized with Moderate-Severe Traumatic Brain Injury: A Clinical Practice Guideline for Health Care Professionals from the Neurocritical Care Society

Frontera, Jennifer A; Gilmore, Emily J; Johnson, Emily L; Olson, DaiWai; Rayi, Appaji; Tesoro, Eljim; Ullman, Jamie; Yuan, Yuhong; Zafar, Sahar F; Rowe, Shaun
BACKGROUND:There is practice heterogeneity in the use, type, and duration of prophylactic antiseizure medications (ASMs) in patients with moderate-severe traumatic brain injury (TBI). METHODS:We conducted a systematic review and meta-analysis of articles assessing ASM prophylaxis in adults with moderate-severe TBI (acute radiographic findings and requiring hospitalization). The population, intervention, comparator, and outcome (PICO) questions were as follows: (1) Should ASM versus no ASM be used in patients with moderate-severe TBI and no history of clinical or electrographic seizures? (2) If an ASM is used, should levetiracetam (LEV) or phenytoin/fosphenytoin (PHT/fPHT) be preferentially used? (3) If an ASM is used, should a long versus short (> 7 vs. ≤ 7 days) duration of prophylaxis be used? The main outcomes were early seizure, late seizure, adverse events, mortality, and functional outcomes. We used Grading of Recommendations Assessment, Development, and Evaluation (GRADE) methodology to generate recommendations. RESULTS:The initial literature search yielded 1998 articles, of which 33 formed the basis of the recommendations: PICO 1: We did not detect any significant positive or negative effect of ASM compared to no ASM on the outcomes of early seizure, late seizure, adverse events, or mortality. PICO 2: We did not detect any significant positive or negative effect of PHT/fPHT compared to LEV for early seizures or mortality, though point estimates suggest fewer late seizures and fewer adverse events with LEV. PICO 3: There were no significant differences in early or late seizures with longer versus shorter ASM use, though cognitive outcomes and adverse events appear worse with protracted use. CONCLUSIONS:Based on GRADE criteria, we suggest that ASM or no ASM may be used in patients hospitalized with moderate-severe TBI (weak recommendation, low quality of evidence). If used, we suggest LEV over PHT/fPHT (weak recommendation, very low quality of evidence) for a short duration (≤ 7 days, weak recommendation, low quality of evidence).
PMID: 38316735
ISSN: 1556-0961
CID: 5632812

Trajectories of Inflammatory Markers and Post-COVID-19 Cognitive Symptoms: A Secondary Analysis of the CONTAIN COVID-19 Randomized Trial

Frontera, Jennifer A; Betensky, Rebecca A; Pirofski, Liise-Anne; Wisniewski, Thomas; Yoon, Hyunah; Ortigoza, Mila B
BACKGROUND AND OBJECTIVES/OBJECTIVE:Chronic systemic inflammation has been hypothesized to be a mechanistic factor leading to post-acute cognitive dysfunction after COVID-19. However, little data exist evaluating longitudinal inflammatory markers. METHODS:We conducted a secondary analysis of data collected from the CONTAIN randomized trial of convalescent plasma in patients hospitalized for COVID-19, including patients who completed an 18-month assessment of cognitive symptoms and PROMIS Global Health questionnaires. Patients with pre-COVID-19 dementia/cognitive abnormalities were excluded. Trajectories of serum cytokine panels, D-dimer, fibrinogen, C-reactive peptide (CRP), ferritin, lactate dehydrogenase (LDH), and absolute neutrophil counts (ANCs) were evaluated over 18 months using repeated measures and Friedman nonparametric tests. The relationships between the area under the curve (AUC) for each inflammatory marker and 18-month cognitive and global health outcomes were assessed. RESULTS:< 0.05), with the exception of IL-1β, which remained stable over time. There were no significant associations between the AUC for any inflammatory marker and 18-month cognitive symptoms, any neurologic symptom, or PROMIS Global Physical or Mental health T-scores. Receipt of convalescent plasma was not associated with any outcome measure. DISCUSSION/CONCLUSIONS:At 18 months posthospitalization for COVID-19, cognitive abnormalities were reported in 27% of patients, and below average PROMIS Global Mental and Physical Health scores occurred in 24% and 51%, respectively. However, there were no associations with measured inflammatory markers, which decreased over time.
PMCID:11087048
PMID: 38626359
ISSN: 2332-7812
CID: 5655822

The authors reply [Comment]

Frontera, Jennifer A
PMID: 38483229
ISSN: 1530-0293
CID: 5692212

Antithrombotic Treatment for Stroke Prevention in Cervical Artery Dissection: The STOP-CAD Study

Yaghi, Shadi; Shu, Liqi; Mandel, Daniel M; Leon Guerrero, Christopher R; Henninger, Nils; Muppa, Jayachandra; Affan, Muhammad; Ul Haq Lodhi, Omair; Heldner, Mirjam R; Antonenko, Kateryna; Seiffge, David J; Arnold, Marcel; Salehi Omran, Setareh; Crandall, Ross Curtiss; Lester, Evan; Lopez Mena, Diego; Arauz, Antonio; Nehme, Ahmad; Boulanger, Marion; Touzé, Emmanuel; Sousa, João André; Sargento-Freitas, Joao; Barata, Vasco; Castro-Chaves, Paulo; Brito, Maria Teresa Álvares Pereira; Khan, Muhib; Mallick, Dania; Rothstein, Aaron; Khazaal, Ossama; Kaufmann, Josefin; Engelter, Stefan T; Traenka, Christopher; Aguiar de Sousa, Diana; Soares, Mafalda; Rosa, Sara Db; Zhou, Lily W; Gandhi, Preet; Field, Thalia S; Mancini, Steven; Metanis, Issa; Leker, Ronen R; Pan, Kelly; Dantu, Vishnu; Baumgartner, Karl Viktor; Burton, Tina M; Freiin von Rennenberg, Regina; Nolte, Christian H; Choi, Richard K; MacDonald, Jason A; Bavarsad Shahripour, Reza; Guo, Xiaofan; Ghannam, Malik; AlMajali, Mohammad; Samaniego, Edgar A; Sanchez, Sebastian; Rioux, Bastien; Zine-Eddine, Faycal; Poppe, Alexandre Y; Fonseca, Ana Catarina; Baptista, Maria; Cruz, Diana; Romoli, Michele; De Marco, Giovanna; Longoni, Marco; Keser, Zafer; Griffin, Kim J; Kuohn, Lindsey; Frontera, Jennifer A; Amar, Jordan; Giles, James A; Zedde, Marialuisa; Pascarella, Rosario; Grisendi, Ilaria; Nzwalo, Hipólito; Liebeskind, David S; Molaie, Amir M; Cavalier, Annie; Kam, Wayneho; Mac Grory, Brian; Al Kasab, Sami; Anadani, Mohammad; Kicielinski, Kimberly P; Eltatawy, Ali Rada; Chervak, Lina M; Chulluncuy-Rivas, Roberto; Aziz, Yasmin Ninette; Bakradze, Ekaterina; Tran, Thanh Lam; Rodrigo-Gisbert, Marc; Requena, Manuel; Saleh Velez, Faddi Ghassan; Ortiz Garcia, Jorge G; Muddasani, Varsha; de Havenon, Adam; Vishnu, Venugopalan Y; Yaddanapudi, Sridhara S; Adams, Latasha; Browngoehl, Abigail; Ranasinghe, Tamra; Dunston, Randy; Lynch, Zachary; Penckofer, Mary; Siegler, James E; Mayer, Silvia V; Willey, Joshua Z; Zubair, Adeel S; Cheng, Yee Kuang; Sharma, Richa; Marto, João Pedro; Mendes Ferreira, Vitor; Klein, Piers; Nguyen, Thanh N; Asad, Syed Daniyal; Sarwat, Zoha; Balabhadra, Anvesh; Patel, Shivam; Secchi, Thais Leite; Martins, Sheila Co; Mantovani, Gabriel Paulo; Kim, Young Dae; Krishnaiah, Balaji; Elangovan, Cheran; Lingam, Sivani; Qureshi, Abid Y; Fridman, Sebastian; Alvarado-Bolaños, Alonso; Khasiyev, Farid; Linares, Guillermo; Mannino, Marina; Terruso, Valeria; Vassilopoulou, Sofia; Tentolouris-Piperas, Vasileios; Martínez-Marino, Manuel; Carrasco Wall, Víctor A; Indraswari, Fransisca; El Jamal, Sleiman; Liu, Shilin; Alvi, Muhammad; Ali, Farman; Sarvath, Mohammed Madani; Morsi, Rami Z; Kass-Hout, Tareq; Shi, Feina; Zhang, Jinhua; Sokhi, Dilraj; Said, Jamil; Simpkins, Alexis N; Gomez, Roberto; Sen, Shayak; Ghani, Mohammad Ravi; Elnazeir, Marwa; Xiao, Han; Kala, Narendra Sharma; Khan, Farhan; Stretz, Christoph; Mohammadzadeh, Nahid; Goldstein, Eric D; Furie, Karen L
PMID: 38335240
ISSN: 1524-4628
CID: 5632012

Association of Neighborhood Socioeconomic Status With Withdrawal of Life-Sustaining Therapies After Intracerebral Hemorrhage

Melmed, Kara R; Lewis, Ariane; Kuohn, Lindsey; Marmo, Joanna; Rossan-Raghunath, Nirmala; Torres, Jose; Muralidharan, Rajanandini; Lord, Aaron S; Ishida, Koto; Frontera, Jennifer A
BACKGROUND AND OBJECTIVES/OBJECTIVE:Mortality after intracerebral hemorrhage (ICH) is common. Neighborhood socioeconomic status (nSES) is an important social determinant of health (SDoH) that can affect clinical outcome. We hypothesize that SDoH, including nSES, contribute to differences in withdrawal of life-sustaining therapies (WLSTs) and mortality in patients with ICH. METHODS:tests. We performed multivariable analysis using backward stepwise logistic regression. RESULTS:≤ 0.01 for both). In multivariable analysis adjusting for age and clinical severity scores, patients who lived in zip codes with high-income levels were more likely to have WLST (adjusted odds ratio [aOR] 1.88; 95% CI 1.29-2.74) and mortality before discharge (aOR 1.5; 95% CI 1.06-2.13). DISCUSSION/CONCLUSIONS:SDoH, including nSES, are associated with WLST after ICH. This has important implications for the care and management of patients with ICH.
PMID: 38237088
ISSN: 1526-632x
CID: 5624412

The American Society of Transplant Surgeons Consensus Statement on Normothermic Regional Perfusion

Wall, Anji E; Adams, Bradley L; Brubaker, Aleah; Chang, Cherylee W J; Croome, Kristopher P; Frontera, Jennifer; Gordon, Elisa; Hoffman, Jordan; Kaplan, Lewis J; Kumar, Deepali; Levisky, Josh; Miñambres, Eduardo; Parent, Brendan; Watson, Christopher; Zemmar, Ajmal; Pomfret, Elizabeth A
On June 3, 2023, the American Society of Transplant Surgeons convened a meeting in San Diego, California to (1) develop a consensus statement with supporting data on the ethical tenets of thoracoabdominal normothermic regional perfusion (NRP) and abdominal NRP; (2) provide guidelines for the standards of practice that should govern thoracoabdominal NRP and abdominal NRP; and (3) develop and implement a central database for the collection of NRP donor and recipient data in the United States. National and international leaders in the fields of neuroscience, transplantation, critical care, NRP, Organ Procurement Organizations, transplant centers, and donor families participated. The conference was designed to focus on the controversial issues of neurological flow and function in donation after circulatory death donors during NRP and propose technical standards necessary to ensure that this procedure is performed safely and effectively. This article discusses major topics and conclusions addressed at the meeting.
PMID: 38254280
ISSN: 1534-6080
CID: 5624742

Code ICH: A Call to Action

Li, Qi; Yakhkind, Aleksandra; Alexandrov, Anne W; Alexandrov, Andrei V; Anderson, Craig S; Dowlatshahi, Dar; Frontera, Jennifer A; Hemphill, J Claude; Ganti, Latha; Kellner, Chris; May, Casey; Morotti, Andrea; Parry-Jones, Adrian; Sheth, Kevin N; Steiner, Thorsten; Ziai, Wendy; Goldstein, Joshua N; Mayer, Stephan A
Intracerebral hemorrhage is the most serious type of stroke, leading to high rates of severe disability and mortality. Hematoma expansion is an independent predictor of poor functional outcome and is a compelling target for intervention. For decades, randomized trials aimed at decreasing hematoma expansion through single interventions have failed to meet their primary outcomes of statistically significant improvement in neurological outcomes. A wide range of evidence suggests that ultra-early bundled care, with multiple simultaneous interventions in the acute phase, offers the best hope of limiting hematoma expansion and improving functional recovery. Patients with intracerebral hemorrhage who fail to receive early aggressive care have worse outcomes, suggesting that an important treatment opportunity exists. This consensus statement puts forth a call to action to establish a protocol for Code ICH, similar to current strategies used for the management of acute ischemic stroke, through which early intervention, bundled care, and time-based metrics have substantially improved neurological outcomes. Based on current evidence, we advocate for the widespread adoption of an early bundle of care for patients with intracerebral hemorrhage focused on time-based metrics for blood pressure control and emergency reversal of anticoagulation, with the goal of optimizing the benefit of these already widely used interventions. We hope Code ICH will endure as a structural platform for continued innovation, standardization of best practices, and ongoing quality improvement for years to come.
PMID: 38099439
ISSN: 1524-4628
CID: 5588962

Optimal Dosing of Levetiracetam for Seizure Prophylaxis in Critically Ill Patients: A Prospective Observational Study

Valdes, Eduard; Fang, Taolin; Boffa, Michael; Frontera, Jennifer A
OBJECTIVES/OBJECTIVE:Critically ill patients eliminate levetiracetam (LEV) more rapidly than healthy controls, yet low doses are commonly used for seizure prophylaxis in the ICU setting. We compared the rates of achievement of target serum levels and new onset seizure (clinical and/or electrographic) among patients who received low (500 mg bid) versus high (750-1,000 mg bid) dose LEV. DESIGN/METHODS:Prospective, observational study. SETTING/METHODS:Tertiary care, academic center. PATIENTS/METHODS:We included patients who received prophylactic LEV following traumatic brain injury, intracerebral hemorrhage, spontaneous subarachnoid hemorrhage, or supratentorial neurosurgery between 2019 and 2021. Patients with a history of seizure, antiseizure medication use, or renal failure requiring dialysis were excluded. INTERVENTIONS/METHODS:None. MEASUREMENTS/METHODS:LEV levels were obtained at steady state. The impact of low-dose versus high-dose LEV on the primary outcome of target LEV levels (12-46 μg/mL), and the secondary outcome of clinical and/or electrographic seizure, were assessed using multivariable logistic regression analyses adjusting for age, LEV loading dose, BMI, primary diagnosis and creatinine clearance (CrCl). MAIN RESULTS/RESULTS:Of the 205 subjects included in analyses, n = 106 (52%) received LEV 500 mg bid (median 13 mg/kg/d), and n = 99 (48%) received LEV 750-1,000 mg bid (median 25 mg/kg/d). Overall, 111 of 205 patients (54%) achieved target levels: 48 (45%) from the low-dose group versus 63 (64%) from the high-dose group (odds ratio [OR] 2.1; 95% CI, 1.1-3.7; p = 0.009). In multivariable analyses, high-dose LEV predicted target levels (adjusted OR [aOR] 2.23; 95% CI, 1.16-4.27; p = 0.016), and was associated with lower seizure odds (aOR 0.32; 95% CI, 0.13-0.82; p = 0.018) after adjusting for age, loading dose, BMI, diagnosis, and CrCl. CONCLUSIONS:Underdosing of LEV was common, with only 54% of patients achieving target serum levels. Higher doses (750-1,000 mg bid) were more than twice as likely to lead to optimal drug levels and reduced the odds of seizure by 68% compared with low-dose regimens (500 mg bid).
PMID: 37734033
ISSN: 1530-0293
CID: 5613032

Prevalence and Trajectories of Post-COVID-19 Neurological Manifestations: A Systematic Review and Meta-Analysis

Giussani, Giorgia; Westenberg, Erica; Garcia-Azorin, David; Bianchi, Elisa; Yusof Khan, Abdul Hanif Khan; Allegri, Ricardo Francisco; Atalar, Arife Çimen; Baykan, Betul; Crivelli, Lucia; Fornari, Arianna; Frontera, Jennifer A; Guekht, Alla; Helbok, Raimund; Hoo, Fan Kee; Kivipelto, Miia; Leonardi, Matilde; Lopez Rocha, Ana Sabsil; Mangialasche, Francesca; Marcassoli, Alessia; Özdag Acarli, Ayse Nur; Ozge, Aynur; Prasad, Kameshwar; Prasad, Manya; Sviatskaia, Ekaterina; Thakur, Kiran; Vogrig, Alberto; Leone, Maurizio; Winkler, Andrea Sylvia; ,
INTRODUCTION/BACKGROUND:The aim of this systematic review and meta-analysis was to evaluate the prevalence of thirteen neurological manifestations in people affected by COVID-19 during the acute phase and at 3, 6, 9 and 12-month follow-up time points. METHODS:The study protocol was registered with PROSPERO (CRD42022325505). MEDLINE (PubMed), Embase, and the Cochrane Library were used as information sources. Eligible studies included original articles of cohort studies, case-control studies, cross-sectional studies, and case series with ≥5 subjects that reported the prevalence and type of neurological manifestations, with a minimum follow-up of 3 months after the acute phase of COVID-19 disease. Two independent reviewers screened studies from January 1, 2020, to June 16, 2022. The following manifestations were assessed: neuromuscular disorders, encephalopathy/altered mental status/delirium, movement disorders, dysautonomia, cerebrovascular disorders, cognitive impairment/dementia, sleep disorders, seizures, syncope/transient loss of consciousness, fatigue, gait disturbances, anosmia/hyposmia, and headache. The pooled prevalence and their 95% confidence intervals were calculated at the six pre-specified times. RESULTS:126 of 6,565 screened studies fulfilled the eligibility criteria, accounting for 1,542,300 subjects with COVID-19 disease. Of these, four studies only reported data on neurological conditions other than the 13 selected. The neurological disorders with the highest pooled prevalence estimates (per 100 subjects) during the acute phase of COVID-19 were anosmia/hyposmia, fatigue, headache, encephalopathy, cognitive impairment, and cerebrovascular disease. At 3-month follow-up, the pooled prevalence of fatigue, cognitive impairment, and sleep disorders was still 20% and higher. At six- and 9-month follow-up, there was a tendency for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache to further increase in prevalence. At 12-month follow-up, prevalence estimates decreased but remained high for some disorders, such as fatigue and anosmia/hyposmia. Other neurological disorders had a more fluctuating occurrence. DISCUSSION/CONCLUSIONS:Neurological manifestations were prevalent during the acute phase of COVID-19 and over the 1-year follow-up period, with the highest overall prevalence estimates for fatigue, cognitive impairment, sleep disorders, anosmia/hyposmia, and headache. There was a downward trend over time, suggesting that neurological manifestations in the early post-COVID-19 phase may be long-lasting but not permanent. However, especially for the 12-month follow-up time point, more robust data are needed to confirm this trend.
PMID: 38272015
ISSN: 1423-0208
CID: 5728892

Relationship Between Hemorrhage Type and Development of Emotional and Behavioral Dyscontrol After Hemorrhagic Stroke

Talmasov, Daniel; Kelly, Sean; Ecker, Sarah; Olivera, Anlys; Lord, Aaron; Gurin, Lindsey; Ishida, Koto; Melmed, Kara; Torres, Jose; Zhang, Cen; Frontera, Jennifer; Lewis, Ariane
OBJECTIVE/UNASSIGNED:Emotional and behavioral dyscontrol (EBD), a neuropsychiatric complication of stroke, leads to patient and caregiver distress and challenges to rehabilitation. Studies of neuropsychiatric sequelae in stroke are heavily weighted toward ischemic stroke. This study was designed to compare risk of EBD following intracerebral hemorrhage (ICH) and subarachnoid hemorrhage (SAH) and to identify risk factors for EBD following hemorrhagic stroke. METHODS/UNASSIGNED:The authors conducted a prospective cohort study of patients hospitalized for nontraumatic hemorrhagic stroke between 2015 and 2021. Patients or legally authorized representatives completed the Quality of Life in Neurological Disorders (Neuro-QOL) EBD short-form inventory 3 months after hospitalization. Univariable and multivariable analyses identified risk factors for EBD after hemorrhagic stroke. RESULTS/UNASSIGNED:The incidence of EBD was 21% (N=15 of 72 patients) at 3 months after hemorrhagic stroke. Patients with ICH were more likely to develop EBD; 93% of patients with EBD (N=14 of 15) had ICH compared with 56% of patients without EBD (N=32 of 57). The median Glasgow Coma Scale (GCS) score at hospital admission was lower among patients who developed EBD (13 vs. 15 among those without EBD). Similarly, admission scores on the National Institutes of Health Stroke Scale (NIHSS) and the Acute Physiology and Chronic Health Evaluation II (APACHE II) were higher among patients with EBD (median NIHSS score: 7 vs. 2; median APACHE II score: 17 vs. 11). Multivariable analyses identified hemorrhage type (ICH) and poor admission GCS score as predictors of EBD 3 months after hemorrhagic stroke. CONCLUSIONS/UNASSIGNED:Patients with ICH and a low GCS score at admission are at increased risk of developing EBD 3 months after hemorrhagic stroke and may benefit from early intervention.
PMID: 38650464
ISSN: 1545-7222
CID: 5711292