Faculty Bibliography

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.

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

Hypocretin 1 and hypocretin 2 (orexin A and B) regulate sleep, wakefulness and emotion. Tumour necrosis factor alpha (TNF-α) is an important neuroinflammation mediator. Here, we examined the effects of TNF-α treatment on hypocretin expression in vivo and behaviour in mice. TNF-α decreased hypocretin 1 and hypocretin 2 expression in a dose-dependent manner in cultured hypothalamic neurons. TNF-α decreased mRNA stability of prepro-hypocretin, the single precursor of hypocretin 1 and hypocretin 2. Mice challenged with TNF-α demonstrated decreased expression of prepro-hypocretin, hypocretin 1 and hypocretin 2 in hypothalamus. In response to TNF-α, prepro-hypocretin mRNA decay was increased in hypothalamus. TNF-α neutralizing antibody restored the expression of prepro-hypocretin, hypocretin 1 and hypocretin 2 in vivo in TNF-α challenged mice, supporting hypocretin system can be impaired by increased TNF-α through decreasing hypocretin expression. Repeated TNF-α challenge induced muscle activity during rapid eye movement sleep and sleep fragmentation, but decreased learning, cognition and memory in mice. TNF-α neutralizing antibody blocked the effects of TNF-α; in contrast, hypocretin receptor antagonist enhanced the effects of TNF-α. The data support that TNF-α is involved in the regulation of hypocretin expression, sleep and cognition. The findings shed some lights on the role of neuroinflammation in neurodegenerative diseases including Alzheimer's disease and Parkinson's disease.

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

Diabetes mellitus is becoming increasingly common worldwide. As this occurs, there will be an increase in the prevalence of known comorbidities from this disorder of glucose metabolism. One of the most disabling adverse comorbidities is diabetic neuropathy. The most common neuropathic manifestation is distal symmetric polyneuropathy, which can lead to sensory disturbances, including diminished protective sense, making patients prone to foot injuries. However, focal, multifocal, and autonomic neuropathies are also common. Diabetic nerve pain and Charcot osteoarthropathy are advanced neuropathic conditions that portend a severe deterioration in quality of life. To combat these symptoms, along with glycemic control and establishment of health care systems to educate and support patients with the complexities of diabetes, there are pharmacologic remedies to ameliorate the neurologic symptoms. Several guidelines and review boards generally recommend the use of tricyclic antidepressants, serotonin/norepinephrine-reuptake inhibitors, α-2-delta ligands, and anticonvulsants as medications to improve painful diabetic neuropathy and quality of life.

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.

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.