Monkeypox-Associated Central Nervous System Disease: A Case Series and Review.

OBJECTIVE: Monkeypox virus (MPXV) disease has been declared a public health emergency by the World Health Organization, creating an urgent need for neurologists to be able to recognize, diagnosis, and treat MPXV-associated neurologic disease. METHODS: Three cases of MPXV-associated central nervous system (CNS) disease occurring during the 2022 outbreak, and their associated imaging findings are presented, with 2 cases previously published in a limited capacity in a public health bulletin. RESULTS: Three previously healthy immunocompetent gay men in their 30s developed a febrile illness followed by progressive neurologic symptoms with presence of a vesiculopustular rash. MPXV nucleic acid was detected by polymerase chain reaction (PCR) from skin lesions of 2 patients, with the third patient having indeterminate testing but an epidemiologic link to a confirmed MPXV disease case. Cerebrospinal fluid demonstrated a lymphocytic pleocytosis, elevated protein, and negative MPXV-specific PCR. In 2 patients, magnetic resonance imaging of the brain and spine demonstrated partially enhancing, longitudinally extensive central spinal cord lesions with multifocal subcortical, basal ganglia, thalamic, cerebellar, and/or brainstem lesions. The third patient had thalamic and basal ganglia lesions. All patients received 14 days of tecovirimat, and 2 patients also received multiple forms of immunotherapy, including intravenous immunoglobulin, pulsed high-dose steroids, plasmapheresis, and/or rituximab. Good neurologic recovery was observed in all cases. INTERPRETATION: MPXV can be associated with CNS disease. It is unclear whether this is from a parainfectious immune-mediated injury or direct CNS viral invasion. ANN NEUROL 2023;93:893-905.

Intracranial Hemorrhage in Hospitalized SARS-CoV-2 Patients: A Case Series.

The SARS-CoV-2 virus causing Coronavirus Disease 2019 (COVID-19) is a global pandemic with almost 30 million confirmed worldwide cases. Prothrombotic complications arising from those affected with severe symptoms have been reported in various medical journals. Currently, clinical trials are underway to address the questions regarding anticoagulation dosing strategies to prevent thrombosis for these critically ill patients. However, given the increasing use of therapeutic anticoagulation in patients admitted with COVID-19 to curtail this prothrombotic state, our institution has witnessed six cases of devastating intracranial hemorrhage as well as thrombosis leading to five fatalities and we examine their hospital course and anticoagulation used.

Early vs. Late Anticoagulation in Acute Ischemic Stroke for Non-Atrial Fibrillation Indications.

Background/Objective: In persons whose sole indication for anticoagulation is atrial fibrillation (AF), early therapeutic anticoagulation after acute ischemic stroke (AIS) may decrease ischemic risk without increasing hemorrhagic risk. However, literature to guide anticoagulation timing in patients with a non-AF indication remains extremely limited. Methods : This retrospective cohort study compared outcomes of early (within ≤4 days of AIS) versus late anticoagulation (5-14 days) for persons with AIS and non-AF indications for anticoagulation. The primary outcome was a composite of intracranial hemorrhage or major extracranial bleeding while on therapeutic anticoagulation, within 30 days of the index event. The main secondary outcome was a composite of major bleeding events while on therapeutic anticoagulation, recurrent AIS, systemic embolism, and all-cause mortality, within 30 days of the index event. Results : Eighty-one patients were included for analysis, with 65 patients in the early cohort and 16 patients in the late cohort; median time to anticoagulation was 1 day and 7 days, respectively. The most common indication for anticoagulation was deep vein thrombosis. The primary composite outcome occurred in 3 patients (4.6%) in the early cohort and 2 patients (12.5%) in the late cohort (p = 0.255). The secondary composite outcome occurred in 10 patients (15.4%) in the early cohort and 7 patients (43.8%) in the late cohort (p = 0.034). There were no statistical differences in any individual components of the composite outcomes, although recurrent AIS and mortality had numerically higher incidence in the late cohort. Conclusions : In this retrospective study, early anticoagulation was not associated with increased major bleeding risk, but late anticoagulation was associated with an increased composite risk of major bleeding, thrombotic events, and all-cause mortality, driven by increases in recurrent AIS and mortality. Further studies are warranted to expound on the optimal timing of anticoagulation in this patient population.

Centriolin interacts with HectD1 in a cell cycle dependent manner.

OBJECTIVE: The centrosome is universally recognized as the microtubule organizing center of animal cells, but emerging evidence suggests that it has other important functions including primary cilia formation, DNA damage checkpoints, and cell cycle progression. Despite this, the role of individual components of the centrosome remains unclear. Previous studies suggest that one component, centriolin, has an important function in cytokinesis and cell cycle progression, although its exact role in these processes is not known. To determine how centriolin influences the progression through the cell cycle, we sought to identify interacting partners that may be involved in regulating its function. RESULTS: This study provides evidence that the ubiquitin E3 ligase HectD1 binds to centriolin and that this association likely accounts for our observation that HectD1 co-localizes with centriolin at the centrosome during mitosis. In addition to its centrosomal localization, we also show that the expression of HectD1 fluctuates throughout the cell cycle, with the highest levels during mitosis, coinciding with a marked reduction in centriolin expression. We propose that the interaction between HectD1 and centriolin may be necessary for normal cell cycle progression and we speculate that this function may involve HectD1-mediated degradation of centriolin.