Faculty Bibliography

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.

PURPOSE/OBJECTIVE:To evaluate the results of the randomized, double-blind, placebo-controlled phase II clinical trial of ICT-107 in patients with newly diagnosed glioblastoma. PATIENTS AND METHODS/METHODS:received radiotherapy and concurrent temozolomide. Following completion of radiotherapy, 124 patients, randomized 2:1, received ICT-107 [autologous dendritic cells (DC) pulsed with six synthetic peptide epitopes targeting GBM tumor/stem cell-associated antigens MAGE-1, HER-2, AIM-2, TRP-2, gp100, and IL13Rα2] or matching control (unpulsed DC). Patients received induction ICT-107 or control weekly × 4 followed by 12 months of adjuvant temozolomide. Maintenance vaccinations occurred at 1, 3, and 6 months and every 6 months thereafter. RESULTS:= 0.011). The frequency of HLA-A2 primary tumor antigen expression was higher than that for HLA-A1 patients, and HLA-A2 patients had higher immune response (via Elispot). HLA-A2 patients achieved a meaningful therapeutic benefit with ICT-107, in both the MGMT methylated and unmethylated prespecified subgroups, whereas only HLA-A1 methylated patients had an OS benefit. CONCLUSIONS:PFS was significantly improved in ICT-107-treated patients with maintenance of QoL. Patients in the HLA-A2 subgroup showed increased ICT-107 activity clinically and immunologically.

Background. CRAb is a major cause of healthcare-associated infections and is associated with high mortality due to the lack of reliable treatment options. We aimed to elucidate the contemporary population structure of CRAb isolates circulating in US hospitals using whole-genome sequencing (WGS). Methods. A total of 131 CRAb isolates were identified at four tertiary care medical centers located in Ohio, Pennsylvania, Texas and North Carolina between 2017 and 2018. The genomes were sequenced with Illumina NextSeq and De novo assembled. Sequence types (STs) were identified using the Pasteur Institute MLST scheme. beta-Lactamase genes were identified by ResFinder and manually curated. Results. The 131 isolates belonged to 10 different ST types, including 8 known and 2 novel ones. In this collection, 101 isolates (77.1%) belonged to ST2, the dominant drug-resistant clone in the United States and Europe; 20 isolates belonged to ST499, a less common, but also globally distributed clone. Two isolates each belonged to ST46 and ST79, both common in South America. For the chromosomally encoded blaOXA-51-group genes, 11 variants were identified with blaOXA-66, blaOXA-82, and blaOXA-95 being predominant. For the chromosomally encoded blaADC-group genes, 26 variants were identified, with blaADC-161, blaADC-181, and blaADC-30 being the most common. The most frequent acquired carbapenemase gene was blaOXA-23, which was present in 89 isolates (67.9%). Other acquired blaOXA carbapenemase genes were identified much less frequently and included blaOXA-24, blaOXA-72, blaOXA-207, and blaOXA-237. 17 isolates (13.0%) did not contain any known acquired carbapenemase genes despite resistance to carbapenems. Conclusion. ST2 is the most prevalent ST type among contemporary CRAb isolates identified in US hospitals, however, new STs are emerging, most notably ST499. Significant diversity was seen among chromosomal blaOXA-51-group carbapenemase, intrinsic blaADC-group cephalosporinase and plasmid-mediated blaOXA-group carbapenemase genes, which likely represented diversification within the STs. Correlations between clinical presentation and outcomes and the genomic features of the infecting isolates are being investigated

OBJECTIVE:The current Phase 2b study aimed to evaluate the efficacy of mindfulness-based cognitive therapy for migraine (MBCT-M) to reduce migraine-related disability in people with migraine. BACKGROUND:Mindfulness-based interventions represent a promising avenue to investigate effects in people with migraine. MBCT teaches mindfulness meditation and cognitive-behavioral skills and directly applies these skills to address disease-related cognitions. METHODS:Participants with migraine (6-30 headache days/month) were recruited from neurology office referrals and local and online advertisements in the broader New York City area. During the 30-day baseline period, all participants completed a daily headache diary. Participants who met inclusion and exclusion criteria were randomized in a parallel design, stratified by chronic migraine status, to receive either 8 weekly individual MBCT-M sessions or 8 weeks of waitlist/treatment as usual (WL/TAU). All participants completed surveys including primary outcome evaluations at Months 0, 1, 2, and 4. All participants completed a headache diary during the 30-day posttreatment evaluation period. Primary outcomes were the change from Month 0 to Month 4 in the headache disability inventory (HDI) and the Migraine Disability Assessment (MIDAS) (total score ≥ 21 indicating severe disability); secondary outcomes (headache days/30 days, average headache attack pain intensity, and attack-level migraine-related disability [Migraine Disability Index (MIDI)]) were derived from the daily headache diary. RESULTS:Sixty participants were randomized to receive MBCT-M (n = 31) or WL/TAU (n = 29). Participants (M age = 40.1, SD = 11.7) were predominantly White (n = 49/60; 81.7%) and Non-Hispanic (N = 50/60; 83.3%) women (n = 55/60; 91.7%) with a graduate degree (n = 35/60; 55.0%) who were working full-time (n = 38/60; 63.3%). At baseline, the average HDI score (51.4, SD = 19.0) indicated a moderate level of disability and the majority of participants (50/60, 83.3%) fell in the "Severe Disability" range in the MIDAS. Participants recorded an average of 16.0 (SD = 5.9) headache days/30 days, with an average headache attack pain intensity of 1.7 on a 4-point scale (SD = 0.3), indicating moderate intensity. Average levels of daily disability reported on the MIDI were 3.1/10 (SD = 1.8). For the HDI, mean scores decreased more from Month 0 to Month 4 in the MBCT-M group (-14.3) than the waitlist/treatment as an usual group (-0.2; P < .001). For the MIDAS, the group*month interaction was not significant when accounting for the divided alpha, P = .027; across all participants in both groups, the estimated proportion of participants falling in the "Severe Disability" category fell significantly from 88.3% at Month 0 to 66.7% at Month 4, P < .001. For diary-reported headache days/30 days an average headache attack pain intensity, neither the group*month interaction (Ps = .773 and .888, respectively) nor the time effect (Ps = .059 and .428, respectively) was significant. Mean MIDI scores decreased in the MBCT-M group (-0.6/10), whereas they increased in the waitlist/treatment as an usual group (+0.3/10), P = .007. CONCLUSIONS:MBCT-M demonstrated efficacy to reduce headache-related disability and attack-level migraine-related disability. MBCT-M is a promising emerging treatment for addressing migraine-related disability.

Many studies have reported that heavy substance use is associated with impaired response inhibition. Studies typically focused on associations with a single substance, while polysubstance use is common. Further, most studies compared heavy users with light/non-users, though substance use occurs along a continuum. The current mega-analysis accounted for these issues by aggregating individual data from 43 studies (3610 adult participants) that used the Go/No-Go (GNG) or Stop-signal task (SST) to assess inhibition among mostly "recreational" substance users (i.e., the rate of substance use disorders was low). Main and interaction effects of substance use, demographics, and task-characteristics were entered in a linear mixed model. Contrary to many studies and reviews in the field, we found that only lifetime cannabis use was associated with impaired response inhibition in the SST. An interaction effect was also observed: the relationship between tobacco use and response inhibition (in the SST) differed between cannabis users and non-users, with a negative association between tobacco use and inhibition in the cannabis non-users. In addition, participants' age, education level, and some task characteristics influenced inhibition outcomes. Overall, we found limited support for impaired inhibition among substance users when controlling for demographics and task-characteristics.

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:Deep brain stimulation (DBS) can be an effective therapy for tics and comorbidities in select cases of severe, treatment-refractory Tourette syndrome (TS). Clinical responses remain variable across patients, which may be attributed to differences in the location of the neuroanatomical regions being stimulated. We evaluated active contact locations and regions of stimulation across a large cohort of patients with TS in an effort to guide future targeting. METHODS:We collected retrospective clinical data and imaging from 13 international sites on 123 patients. We assessed the effects of DBS over time in 110 patients who were implanted in the centromedial (CM) thalamus (n=51), globus pallidus internus (GPi) (n=47), nucleus accumbens/anterior limb of the internal capsule (n=4) or a combination of targets (n=8). Contact locations (n=70 patients) and volumes of tissue activated (n=63 patients) were coregistered to create probabilistic stimulation atlases. RESULTS:Tics and obsessive-compulsive behaviour (OCB) significantly improved over time (p<0.01), and there were no significant differences across brain targets (p>0.05). The median time was 13 months to reach a 40% improvement in tics, and there were no significant differences across targets (p=0.84), presence of OCB (p=0.09) or age at implantation (p=0.08). Active contacts were generally clustered near the target nuclei, with some variability that may reflect differences in targeting protocols, lead models and contact configurations. There were regions within and surrounding GPi and CM thalamus that improved tics for some patients but were ineffective for others. Regions within, superior or medial to GPi were associated with a greater improvement in OCB than regions inferior to GPi. CONCLUSION/CONCLUSIONS:The results collectively indicate that DBS may improve tics and OCB, the effects may develop over several months, and stimulation locations relative to structural anatomy alone may not predict response. This study was the first to visualise and evaluate the regions of stimulation across a large cohort of patients with TS to generate new hypotheses about potential targets for improving tics and comorbidities.

The current planned secondary analysis of a randomized clinical trial aimed to evaluate whether the efficacy of Mindfulness-Based Cognitive Therapy for Migraine (MBCTM) to reduce headache-related disability differs among people with episodic migraine (EM) and chronic migraine (CM). After a 30-day monitoring period, participants were stratified by EM (6-14 days/month) and CM (15-30 days/month) and randomized to receive MBCT-M (8 weekly individual sessions) or 8 weeks of wait list/treatment as usual (WL/TAU). Surveys were completed at Months 0, 1, 2, and 4; daily diary was also completed during the 30-day post-treatment evaluation period. Primary outcomes were the Headache Disability Inventory (HDI; Range 0-100) and the Migraine Disability Assessment (MIDAS >= 21 indicating Severe Disability); secondary outcomes (headache days/30 days, average headache attack pain intensity) were derived from daily headache diary. Intent-to-treat mixed models for repeated measures tested formal moderation (time*treatment*CM) in the full sample. Planned subgroup analyses evaluated treatment*time effects EM and CM separately. Sixty participants were randomized to receive MBCT-M (n = 31) or WL/TAU (n = 29). Participants (M age = 40.1, SD = 11.7) were predominantly White (n = 49/60; 81.7%), Non-Hispanic (N = 50/60; 83.3%) women (n = 55/60; 91.7%). At baseline, 29 participants (48.3%) met criteria for EM and 31 (51.7%) met criteria for CM. At baseline, people with CM reporter higher HDI [M(SD) = 57.6 (16.7) vs. 45.5 (19.4), p = .015] and greater headache days/30 days [M(SD) = 20.5 (3.0) vs 11.2 (4.2), p < .001]; no other variable differed by CM status (ps > .30). For the MIDAS, CM status moderated the effect of MBCTM on the MIDAS; MBCT-M reduced the proportion of people reporting severe disability in EM only, p = .013. For the HDI, subgroup analysis revealed that MBCT-M (vs WL/TAU) significantly reduced HDI for EM (p = .011) but not for CM (p = .268). Subgroup analysis found no significant effect of MBCT-M on headache days/30 days or average headache attack pain intensity in either EM or CM. MBCT-M is a promising treatment for reducing disability. Surprisingly, MBCT-M produced larger changes on both primary outcomes in the EM, rather than CM, subgroup