Faculty Bibliography

Burst suppression is an electroencephalogram pattern of globally symmetric alternating high amplitude activity and isoelectricity that can be induced by general anaesthetics. There is scattered evidence that burst suppression may become spatially non-uniform in the setting of underlying pathology. Here, we induced burst suppression with isoflurane in rodents and then created a neocortical acute seizure focus with injection of 4-aminopyridine (4-AP) in somatosensory cortex. Burst suppression events were recorded before and after creation of the focus using bihemispheric wide-field calcium imaging and multielectrode arrays. We find that the seizure focus elicits a rapid alteration in triggering, initiation, and propagation of burst suppression events. Compared with the non-seizing brain, bursts are triggered from the thalamus, initiate in regions uniquely outside the epileptic focus, elicit marked increases of multiunit activity and propagate towards the seizure focus. These findings support the rapid, widespread impact of focal epilepsy on the extended brain network.

BACKGROUND:The treatment of selected wide-neck and fusiform posterior circulation aneurysms is challenging for clipping as well as for endovascular route. OBJECTIVE:To describe an endovascular approach for vertebral artery aneurysm treatment using transradial access (TRA) instead of the conventional transfemoral access. METHODS:We collected cases from two institutions in which TRA was used for posterior circulation Pipeline Embolization Device (Medtronic, Dublin, Ireland) deployment. RESULTS:A total of four patients were treated. TRA was useful in the setting of extreme vessel tortuosity. We utilized 5F Terumo Glidesheath (Terumo Medical, Somerset, New Jersey), intermediate catheter, and a 027 microcatheter for Pipeline deployment. TRA was not associated with any access or deployment difficulties. CONCLUSIONS:Early experience suggests that TRA for Pipeline Embolization Device placement for posterior circulation aneurysm is a safe and efficient alternative to standard transfemoral access. While this approach was initially applied to patients with vascular anatomy that may not allow for safe femoral access or navigation, experience so far argues for considering a radial approach towards some posterior circulation aneurysm treatment.

The histone methyltransferase activity of PRC2 is central to the formation of H3K27me3-decorated facultative heterochromatin and gene silencing. In addition, PRC2 has been shown to automethylate its core subunits, EZH1/EZH2 and SUZ12. Here, we identify the lysine residues at which EZH1/EZH2 are automethylated with EZH2-K510 and EZH2-K514 being the major such sites in vivo. Automethylated EZH2/PRC2 exhibits a higher level of histone methyltransferase activity and is required for attaining proper cellular levels of H3K27me3. While occurring independently of PRC2 recruitment to chromatin, automethylation promotes PRC2 accessibility to the histone H3 tail. Intriguingly, EZH2 automethylation is significantly reduced in diffuse intrinsic pontine glioma (DIPG) cells that carry a lysine-to-methionine substitution in histone H3 (H3K27M), but not in cells that carry either EZH2 or EED mutants that abrogate PRC2 allosteric activation, indicating that H3K27M impairs the intrinsic activity of PRC2. Our study demonstrates a PRC2 self-regulatory mechanism through its EZH1/2-mediated automethylation activity.

Background: Quantitative measurement of serum markers play an important role in the diagnosis and treatment monitoring of hepatitis b virus (HBV) infection. In the present study, we analyzed the data from Abbott Architect i2000 immunoassay analyzer and investigate the relationship between HBeAg and anti-HBe.
Method(s): Quantitative data of HBV serum markers between January first 2013 and March twentyeight 2016, which are measured by Abbott Architect i2000, were exported from laboratory information system. Data cleaning and analysis were performed by R language. Records contain unprecise value were omitted and the rest were divided into groups according to the HBeAg state. The relationship between HBeAg and anti-HBe was explored by plotting and linear regression.
Result(s): Anti-HBe was correlated with HBeAg and linear regression showed R² equal to 0.92. Only in HBeAg positive data could this correlation be observed, whereas no pattern was observed from HBeAg negative ones. HBeAg and anti-HBe double positive can onley be seen in low HBeAg samples.
Conclusion(s): This study suggests that HBeAg partly interfere with the measurement of anti-HBe, which could lead to unprecise results of the patients who are HBeAg and anti-HBe double positive

Objective: To study the efficacy of Middle Meningeal Artery (MMA) embolization for treatment of chronic subdural hematoma (SDH) and characterize its post-embolization volumetric resolution.
Background(s): Chronic subdural hematoma (cSDH) can be associated with slow neurological deterioration and increased mortality. Open surgical treatment may not always be feasible or successful. Recurrence has been estimated in among 10-20% of cases. MMA embolization has become a new approach used for both initial treatment and for recalcitrant lesions.
Method(s): 10 patients diagnosed with 13 cSDH underwent MMA embolization. SDH volume were measured from time of initial discovery on imaging to pre-operative, post-operative, short-term and long-term follow-up. Time between procedure to obliteration was also measured. Volumetric analysis was done using the 'Coniglobus' formula and recurrence rate as well as resolution timeline was defined using best-fit models.
Result(s): Out of 10 patients; 5 were recurrent lesions, 3 were bilateral and 7 unilateral cSDH. Average and median preoperative volumes were 105.3 cc and 97.4 cc, respectively. Embolization on average was performed 21 days after discovery. 60 percent of patients had concurrent use of antiplatelets or anticoagulation. 40% patients had embolization treatment as a primary modality. Recurrence was not seen in any patients treated with embolization. There was no peri- or post-operative complication. 5 patients reported complete or near-complete obliteration while those with partial resolution showed a composite average of 75% volumetric reduction in 45 days. Postembolization the volumetric resolution followed an exponential decay curve over time and was independent of initial volume.
Conclusion(s): MMA embolization is assosciated with a marked reduction in SDH volume post-operatively and can be used as a curative therapy for primary or recurrent SDH

BACKGROUND:H3 K27M-mutant diffuse midline glioma is a fatal malignancy with no proven medical therapies. The entity predominantly occurs in children and young adults. ONC201 is a small molecule selective antagonist of dopamine receptor D2/3 (DRD2/3) with an exceptional safety profile. Following up on a durable response in the first H3 K27M-mutant diffuse midline glioma patient who received ONC201 (NCT02525692), an expanded access program was initiated. METHODS:Patients with H3 K27M-mutant gliomas who received at least prior radiation were eligible. Patients with leptomeningeal spread were excluded. All patients received open-label ONC201 orally once every week. Safety, radiographic assessments, and overall survival were regularly assessed at least every 8 weeks by investigators. As of August 2018, a total of 18 patients with H3 K27M-mutant diffuse midline glioma or DIPG were enrolled to single patient expanded access ONC201 protocols. Among the 18 patients: seven adult (> 20 years old) and seven pediatric (< 20 years old) patients initiated ONC201 with recurrent disease and four pediatric patients initiated ONC201 following radiation, but prior to disease recurrence. FINDINGS/RESULTS:Among the 14 patients with recurrent disease prior to initiation of ONC201, median progression-free survival is 14 weeks and median overall survival is 17 weeks. Three adults among the 14 recurrent patients remain on treatment progression-free with a median follow up of 49.6 (range 41-76.1) weeks. Among the 4 pediatric patients who initiated adjuvant ONC201 following radiation, two DIPG patients remain progression-free for at least 53 and 81 weeks. Radiographic regressions, including a complete response, were reported by investigators in a subset of patients with thalamic and pontine gliomas, along with improvements in disease-associated neurological symptoms. INTERPRETATION/CONCLUSIONS:The clinical outcomes and radiographic responses in these patients provide the preliminary, and initial clinical proof-of-concept for targeting H3 K27M-mutant diffuse midline glioma with ONC201, regardless of age or location, providing rationale for robust clinical testing of the agent.

BACKGROUND:Fear of falling may be significantly associated with falls in Parkinson's disease (PD) and may have a negative impact on quality of life. Nevertheless, there are no valid and reliable tools to examine this condition in PD. The objective of this study was to design and determine the psychometric attributes of an instrument to assess fear of falling in PD. METHODS:A prospective 1-year, 2-phase study was conducted to validate the Fear of Falling Scale, a self-assessed instrument for assessing fear of falling in PD. During phase 1, we designed a scale to measure the severity of fear of falling and determine its baseline psychometric characteristics, whereas phase 2 was a 1-year follow-up study to assess the frequency of falls and other clinical factors linked to fear of falling. Convergent and discriminant validity were assessed against the Fear of Falling Measure and the Starkstein Apathy Scale, respectively. RESULTS:The Fear of Falling Scale showed high internal consistency, test-retest reliability, and strong convergent and discriminant validity. There was a significant association between fear of falling score and the presence of both generalized anxiety disorder and major depression, poor balance-related motor ability, increased nonmotor symptoms of PD, more severe impairments in activities of daily living, and increased motor fluctuations. Finally, generalized anxiety disorder was a significant predictor of number of falls during a 12-month follow-up period. CONCLUSIONS:The Fear of Falling Scale is a valid and reliable instrument to assess fear of falling in PD. Fear of falling in PD is associated with specific psychiatric and motor disorders and is significantly related to the performance of balance-related motor functions. © 2019 International Parkinson and Movement Disorder Society.