Faculty Bibliography

PURPOSE OF REVIEW/OBJECTIVE:This article provides an overview of nystagmus and saccadic intrusions with the goal of facilitating recognition and differentiation of abnormal eye movements to assist with accurate diagnosis of neurologic disease and evidence-based specific treatment of oscillopsia. Myriad advances have been made in the understanding of several types of nystagmus and saccadic intrusions, even in the past 5 to 10 years, especially regarding underlying pathophysiology, leading to pharmacologic advances rooted in physiologic principles. RECENT FINDINGS/RESULTS:Specific recent advances in the study of nystagmus and saccadic intrusions include (1) improved understanding of the underlying etiologies and mechanisms of nystagmus enhanced or unmasked by provocative maneuvers such as supine position or head shaking; (2) recognition of the differences in behavior and treatment responsivity of acquired pendular nystagmus in demyelinating disease versus oculopalatal myoclonus; (3) recognition that oculopalatal myoclonus results from a dual mechanism of abnormal inferior olivary gap junction connection formation and maladaptive cerebellar learning; and (4) well-controlled clinical trials to evaluate the efficacy of pharmacologic interventions, such as memantine for acquired pendular nystagmus and 4-aminopyridine for downbeat nystagmus. SUMMARY/CONCLUSIONS:Accurate recognition of nystagmus and saccadic intrusions, including familiarity with the subtleties of examination techniques that allow such eye movements to be unmasked, is critical to proper diagnosis and ultimate alleviation of the visual impairment these patients experience.

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.

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.

Aneurysm size correlates with rupture risk and is important for treatment planning. User annotation of aneurysm size is slow and tedious, particularly for large data sets. Geometric shortcuts to compute size have been shown to be inaccurate, particularly for nonstandard aneurysm geometries. To develop and train a convolutional neural network (CNN) to detect and measure cerebral aneurysms from magnetic resonance angiography (MRA) automatically and without geometric shortcuts. In step 1, a CNN based on the U-net architecture was trained on 250 MRA maximum intensity projection (MIP) images, then applied to a testing set. In step 2, the trained CNN was applied to a separate set of 14 basilar tip aneurysms for size prediction. Step 1-the CNN successfully identified aneurysms in 85/86 (98.8% of) testing set cases, with a receiver operating characteristic (ROC) area-under-the-curve of 0.87. Step 2-automated basilar tip aneurysm linear size differed from radiologist-traced aneurysm size on average by 2.01 mm, or 30%. The CNN aneurysm area differed from radiologist-derived area on average by 8.1 mm² or 27%. CNN correctly predicted the area trend for the set of aneurysms. This approach is to our knowledge the first using CNNs to derive aneurysm size. In particular, we demonstrate the clinically pertinent application of computing maximal aneurysm one-dimensional size and two-dimensional area. We propose that future work can apply this to facilitate pre-treatment planning and possibly identify previously missed aneurysms in retrospective assessment.

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

INTRODUCTION: Familial dysautonomia (FD) is a progressive neurogenetic disease with carrier rate as high as 1 in 18 persons in European Jews of Polish origin. Clinical hallmarks include cardiovascular instability, spinal deformities, renal dysfunction, alacrima, ataxia, and impaired nociception. Physical or emotional stress may elicit autonomic crises characterized by hypertension and vomiting. Despite profound sensory deficits, GI perturbations are frequently reported by FD patients. While the incidence of inflammatory bowel disease (IBD) and FD is unknown, concurrence is underreported given increased frequency of both diseases in Ashkenazi Jews. CASE DESCRIPTION/METHODS: We report a 33-year-old female with FD and ulcerative colitis who presented with one week of abdominal pain and bloody diarrhea. She had been maintained on balsalazide. Colonoscopy one year prior revealed endoscopic and histologic remission. On physical examination, her abdomen was tender in the lower quadrants. A CT scan revealed pancolitis. Stool studies resulted negative. Her CRP was 58.4 mg/L and albumin was 2.4 g/dL. A flexible sigmoidoscopy noted Mayo endoscopic score 3 in the rectum and CMV staining was negative. The patient was started on IV steroids. Her hospital course was complicated by ileus, parainfluenza infection, and MSSA bacteremia with a pacemaker lead vegetation, requiring extraction. Lack of optimal clinical response to treatment on hospital day five led to consideration of alternative treatments with careful attention to her underlying FD. A subtotal colectomy with end ileostomy was unfavorable due to concern for volume loss. Infliximab and cyclosporine were opposed due to infection risk and later exhibiting possible nephrotoxicity. During this discussion the patient improved enough to be transitioned to oral steroids with a plan to initiate vedolizumab as an outpatient. On recent colonoscopy she had achieved mucosal healing. DISCUSSION: This is the first case of UC in a FD patient reported. Given myriad GI symptoms in the later diagnosis it can be hard to distinguish disease-related from treatment-related events. Due to the gut-specificity of vedolizumab, infection risk is considerably reduced compared to that of other biologics and is the most favorable option in the setting of underlying FD. This case highlights the difficulty encountered when treating IBD in the setting of systemic illness and underscores the need to carefully consider management options to enhance patient outcomes. (Figure Presented)

OBJECTIVE:(1) Determine the pervasiveness of the belief that brain death/death by neurologic criteria (BD/DNC) is not death among rabbis. (2) Examine rabbinic beliefs about management after BD/DNC. METHODS:An electronic anonymous survey about BD/DNC determination and management after BD/DNC was created and distributed to members of the Central Conference of American Rabbis (the Reform Rabbinic leadership organization), the Rabbinic Council of America (an Orthodox organization), the Rabbinic Assembly (a Conservative organization), and the Reconstructionist Rabbinic Association. RESULTS:Ninety-nine rabbis (40 Reform, 32 Orthodox, 22 Conservative, and 5 Reconstructionist) completed the survey. Awareness of the requirements for BD/DNC was poor (median of 33% of the requirements correctly identified [interquartile range of 22-66%]), but 81% of rabbis knew that absence of heartbeat is not required for BD/DNC. Although only 5% of all rabbis believed a person who is brain dead could recover, 22% did not believe BD/DNC is death, and 18% believed mechanical ventilation should be continued after BD/DNC. There was a significant relationship between denomination and belief that: (1) a person who is brain dead can recover (p = 0.04); (2) a person who is brain dead is dead (p < 0.001); (3) mechanical ventilation should be continued after BD/DNC (p < 0.001); (4) hydration should be continued after BD/DNC (p = 0.002); (5) nutrition should be continued after BD/DNC (p < 0.001); (6) medications to support blood pressure should be continued after BD/DNC (p < 0.001); and (7) cardiopulmonary resuscitation should be performed when a brain dead person's heart stops (p = 0.006). CONCLUSIONS:Rabbinic knowledge about the intricacies of BD determination is poor. Rabbinic perspectives on management after BD/DNC vary. These empirical data on rabbinic perspectives about BD/DNC may be helpful when considering accommodation of religious objections to BD/DNC.

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.