Faculty Bibliography

Comprehensive understanding of venous anatomy is a key factor in the approach to a multitude of conditions. Moreover, the venous system has become the center of attention as a new frontier for treatment of diseases such as idiopathic intracranial hypertension (IIH), arteriovenous malformation (AVM), pulsatile tinnitus, hydrocephalus, and cerebrospinal fluid (CSF) venous fistulas. Its knowledge is ever more an essential requirement of the modern brain physician. In this article, the authors explore the descriptive and functional anatomy of the venous system of the CNS in 5 subsections: embryology, dural sinuses, cortical veins, deep veins, and spinal veins.

OBJECTIVE:This study was undertaken to estimate incidence of rare epilepsies and compare with literature. METHODS:We used electronic health record text search to identify children with 28 rare epilepsies in New York City (2010-2014). We estimated cumulative incidence and compared with literature. RESULTS:Eight of 28 rare epilepsies had five or more prior estimates, and our measurements were within the published range for all. The most common were infantile epileptic spasms syndrome (1 in 2920 live births), Lennox-Gastaut syndrome (1 in 9690), and seizures associated with tuberous sclerosis complex (1 in 14 300). Fifteen of 28 had fewer than five prior estimates, and of these, we provided additional estimates for early infantile developmental and epileptic encephalopathy (1 in 32 700), epilepsy with myoclonic-atonic seizures (1 in 34 100), Sturge-Weber syndrome plus seizures/epilepsy (1 in 40 900), epilepsy in infancy with migrating focal seizures (1 in 54 500), Aicardi syndrome plus seizures/epilepsy (1 in 71 600), hypothalamic hamartoma with seizures (1 in 225 000), and Rasmussen syndrome (1 in 450 000). Five of 28 rare epilepsies had no prior estimates, and of these, we provided a new estimate for developmental/epileptic encephalopathy with spike-and-wave activation in sleep and/or continuous spikes and waves during sleep (1 in 34 100). Data were limited for the remaining 12 rare epilepsies, which were all genetic epilepsies, including PCDH19, CDKL5, Alpers disease, SCN8A, KCNQ2, SCN2A, GLUT1 deficiency, Phelan-McDermid syndrome, myoclonic epilepsy with ragged-red fibers, dup15q syndrome, ring chromosome 14, and ring chromosome 20. SIGNIFICANCE/CONCLUSIONS:We estimated the incidence of rare epilepsies using population-based electronic health record data and literature review. More research is needed to better estimate the incidence of genetic epilepsies with nonspecific clinical features. Electronic health records may be a valuable data source for studying rare epilepsies and other rare diseases, particularly as genetic testing becomes more widely adopted.

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.

PURPOSE OF REVIEW/OBJECTIVE:Myoclonus, a common hyperkinetic movement disorder, can be disabling for patients. It is important to identify and classify myoclonus correctly to ensure appropriate workup and treatment. While the clinical history, examination, and process of classifying myoclonus remain largely unchanged, new causes and triggers for myoclonus are being elucidated, and new genetic causes have been found. Treatment can be challenging, though preliminary data about new options has been promising. RECENT FINDINGS/RESULTS:In this article, we will briefly outline the process of classifying and treating myoclonus. We will then discuss three specific scenarios where myoclonus has been identified: myoclonus associated with SARS-CoV-2 infections, spinal myoclonus following surgery or anesthesia of the spine, and auricular myoclonus. We will also discuss new genetic findings associated with myoclonus-dystonia, and promising results regarding the use of perampanel in treating myoclonus. SUMMARY/CONCLUSIONS:The process of describing unique scenarios associated with myoclonus has helped us build our understanding of the causes, genetic background, expected prognosis, and effective treatment of specific types of myoclonus. We hope that further studies on this topic will help tailor treatment.

BACKGROUND AND OBJECTIVES/OBJECTIVE:Many adolescents with undiagnosed focal epilepsy seek evaluation in emergency departments (EDs). Accurate history-taking is essential to prompt diagnosis and treatment. In this study, we investigated ED recognition of motor vs nonmotor seizures and its effect on management and treatment of focal epilepsy in adolescents. METHODS:This was a retrospective analysis of enrollment data from the Human Epilepsy Project (HEP), an international multi-institutional study that collected data from 34 sites between 2012 and 2017. Participants were 12 years or older, neurotypical, and within 4 months of treatment initiation for focal epilepsy. We used HEP enrollment medical records to review participants' initial diagnosis and management. RESULTS:= 0.03) and occurred in both pediatric and nonpediatric ED settings. DISCUSSION/CONCLUSIONS:Our study supports growing evidence that nonmotor seizures are often undiagnosed, with many individuals coming to attention only after conversion to motor seizures. We found this treatment gap is exacerbated in the adolescent population. Our study highlights a critical need for physicians to inquire about the symptoms of nonmotor seizures, even when the presenting seizure is motor. Future interventions should focus on improving nonmotor seizure recognition for this population in EDs.

Although mismatch repair (MMR) is essential for correcting DNA replication errors, it can also recognize other lesions, such as oxidized bases. In G0 and G1, MMR is kept in check through unknown mechanisms as it is error-prone during these cell cycle phases. We show that in mammalian cells, D-type cyclins are recruited to sites of oxidative DNA damage in a PCNA- and p21-dependent manner. D-type cyclins inhibit the proteasomal degradation of p21, which competes with MMR proteins for binding to PCNA, thereby inhibiting MMR. The ability of D-type cyclins to limit MMR is CDK4- and CDK6-independent and is conserved in G0 and G1. At the G1/S transition, the timely, cullin-RING ubiquitin ligase (CRL)-dependent degradation of D-type cyclins and p21 enables MMR activity to efficiently repair DNA replication errors. Persistent expression of D-type cyclins during S-phase inhibits the binding of MMR proteins to PCNA, increases the mutational burden, and promotes microsatellite instability.

BACKGROUND AND PURPOSE/OBJECTIVE:Non-O blood types are known to be associated with thromboembolic complications (TECs) in population-based studies. TECs are known drivers of morbidity and mortality in intracerebral hemorrhage (ICH) patients, yet the relationships of blood type on TECs in this patient population are unknown. We sought to explore the relationships between ABO blood type and TECs in ICH patients. METHODS:Consecutive adult ICH patients enrolled into a prospective observational cohort study with available ABO blood type data were analyzed. Patients with cancer history, prior thromboembolism, and baseline laboratory evidence of coagulopathy were excluded. The primary exposure variable was blood type (non-O versus O). The primary outcome was composite TEC, defined as pulmonary embolism, deep venous thrombosis, ischemic stroke or myocardial infarction, during the hospital stay. Relationships between blood type, TECs and clinical outcomes were separately assessed using logistic regression models after adjusting for sex, ethnicity and ICH score. RESULTS:Of 301 ICH patients included for analysis, 44% were non-O blood type. Non-O blood type was associated with higher admission GCS and lower ICH score on baseline comparisons. We identified TECs in 11.6% of our overall patient cohort. . Although TECs were identified in 9.9% of non-O blood type patients compared to 13.0% in O blood type patients, we did not identify a significant relationship of non-O blood type with TECs (adjusted OR=0.776, 95%CI: 0.348-1.733, p=0.537). The prevalence of specific TECs were also comparable in unadjusted and adjusted analyses between the two cohorts. In additional analyses, we identified that TECs were associated with poor 90-day mRS (adjusted OR=3.452, 95% CI: 1.001-11.903, p=0.050). We did not identify relationships between ABO blood type and poor 90-day mRS (adjusted OR=0.994, 95% CI:0.465-2.128, p=0.988). CONCLUSIONS:We identified that TECs were associated with worse ICH outcomes. However, we did not identify relationships in ABO blood type and TECs. Further work is required to assess best diagnostic and prophylactic and treatment strategies for TECs to improve ICH outcomes.