Case Report: Papilledema Secondary to Cerebral Venous Sinus Thrombosis after Severe COVID-19 Infection.

SIGNIFICANCE: This case highlights ocular adverse effects of a rare, potentially life-threatening complication from coronavirus disease 2019 (COVID-19). Papilledema can occur because of increased intracranial pressure caused by cerebral venous sinus thrombosis, the incidence of which may be more likely in patients with a history of COVID-19 because of an induced hypercoagulable state. PURPOSE: This case report presents a case of papilledema secondary to cerebral venous sinus thrombosis in a patient with a recent history of severe coronavirus disease (COVID-19). CASE REPORT: A 29-year-old man hospitalized with a complicated course of coronavirus disease (COVID-19) was referred to the ophthalmology department for episodic blurry vision of both eyes and intermittent binocular diplopia. Clinical examination revealed diffuse bilateral optic disc edema. Magnetic resonance venography of the brain during his admission revealed subtotal occlusion of the right transverse sinus by thrombosis. At the time of diagnosis, the patient was already taking systemic anticoagulation therapy for treatment of a recent pulmonary embolism also thought to be induced by COVID-19. After additional treatment with acetazolamide, there was improvement in his optic nerve edema. CONCLUSIONS: Cerebral venous sinus thrombosis, a serious and potentially life-threatening condition, can occur as a rare complication of COVID-19. In such cases, patients may develop increased intracranial pressure, papilledema, and subsequent vision loss. Magnetic resonance venography should be ordered in patients with suspected papilledema to help rule out the presence of cerebral venous sinus thrombosis.

Clinical Significance and Cut-Off Scores for the Pre-Sleep Arousal Scale in Chronic Insomnia Disorder: A Replication in a Clinical Sample.

Background: In contrast to pre-sleep cognitive arousal, self-reported pre-sleep somatic arousal is a rather elusive construct for which little validity has been provided. Thus, the clinical significance of somatic symptoms during the pre-sleep period remains unknown. Participants: 248 patients (45.0 ± 16.7 years old, 65.3% female) with a diagnosis of chronic insomnia disorder, out of 388 consecutive patients evaluated at the Behavioral Sleep Medicine (BSM) program of Penn State Hershey Sleep Research & Treatment Center. Methods: Participants completed the Pre-sleep Arousal Scale assessing cognitive (PSAS-C) and somatic (PSAS-S) arousal as well as the Insomnia Severity Index (ISI), Ford Insomnia Response to Stress Test (FIRST), Arousal Predisposition Scale (APS), and Depression Anxiety Stress Scale (DASS). Multivariable stepwise regression assessed which clinical factors were independently associated with greater PSAS-C and PSAS-S scores. Receiver operating characteristic analysis determined the predictive value for identifying sleep reactivity (FIRST≥18) and clinical anxiety (DASS-A ≥ 10) and clinically useful cutoff scores. Results: The strongest correlates of PSAS-S were DASS-A (ß = 0.64) and chronic pain (ß = 0.11), while those of PSAS-C were FIRST (ß = 0.29) and a history of stroke (ß = 0.10). A PSAS-S score of 14.8 (AUC = 0.87, 95%CI = 0.83-0.91) and a PSAS-C score of 24.5 (AUC = 0.82, 95%CI = 0.76-0.88) showed the best balance in specificity and sensitivity to identify clinical anxiety and sleep reactivity, respectively. Conclusions: Self-reported pre-sleep somatic symptoms are a marker of comorbid anxiety and, potentially chronic pain, impacting nighttime sleep. The optimal cutoff scores of 14 and 20 proposed herein can help clinicians with case formulation, with tailoring BSM treatments and their targets.

Integrated Drug Mining Reveals Actionable Strategies Inhibiting Plexiform Neurofibromas.

Neurofibromatosis Type 1 (NF1) is one of the most common genetic tumor predisposition syndromes, affecting up to 1 in 2500 individuals. Up to half of patients with NF1 develop benign nerve sheath tumors called plexiform neurofibromas (PNs), characterized by biallelic NF1 loss. PNs can grow to immense sizes, cause extensive morbidity, and harbor a 15% lifetime risk of malignant transformation. Increasingly, molecular sequencing and drug screening data from various preclinical murine and human PN cell lines, murine models, and human PN tissues are available to help identify salient treatments for PNs. Despite this, Selumetinib, a MEK inhibitor, is the only currently FDA-approved pharmacotherapy for symptomatic and inoperable PNs in pediatric NF1 patients. The discovery of alternative and additional treatments has been hampered by the rarity of the disease, which makes prioritizing drugs to be tested in future clinical trials immensely important. Here, we propose a gene regulatory network-based integrated analysis to mine high-throughput cell line-based drug data combined with transcriptomes from resected human PN tumors. Conserved network modules were characterized and served as drug fingerprints reflecting the biological connections among drug effects and the inherent properties of PN cell lines and tissue. Drug candidates were ranked, and the therapeutic potential of drug combinations was evaluated via computational predication. Auspicious therapeutic agents and drug combinations were proposed for further investigation in preclinical and clinical trials.