Faculty Bibliography

DSA is the standard imaging technique for evaluation of cerebrovascular conditions. However, One drawback is its limitation in depicting a single angiographic phase at a time. We describe a new 3D-DSA algorithm, which we call arterial and venous-3D-DSA, which allows the concurrent yet distinct display of the arterial and venous structures, which may be useful for different clinical and educational purposes.

BACKGROUND:Clinical research indicates that successful posttraumatic stress disorder (PTSD) treatment does not lead to improvements in alcohol use outcomes in comorbid PTSD and alcohol use disorder (AUD). Emerging theory suggests that treating PTSD may not disrupt an association between negative affect and alcohol craving, which underlies negative reinforcement drinking. The goal of the current study was to determine the respective influences of PTSD symptoms, coping motives, and negative affect on trauma and alcohol cue reactivity to inform theoretical models of co-occurring PTSD and AUD. METHODS:The sample consisted of 189 young adults (50.3% women; 49.2% current PTSD; 84.0% current AUD) who endorsed interpersonal trauma (e.g., sexual/physical assault) and current weekly alcohol use. Participants completed a trauma and alcohol cue reactivity assessment, in which subjective (e.g., craving, affect) and physiological (i.e., salivation) measures were recorded in response to 4 narrative (i.e., personalized trauma or standard neutral) and in vivo beverage (i.e., personalized alcohol or water) cue combinations. RESULTS:Forward-fitted linear mixed-effects (LME) models confirmed that trauma cue-elicited craving was elevated among those high but not low in PTSD symptoms, consistent with prior research and theory. Trauma cue-elicited craving was fully explained by increases in negative affect, with no evidence of a direct effect of trauma cue on craving. PTSD symptoms moderated an association between trauma cue and negative affect (but not negative affect and craving), and coping motives for alcohol moderated an association between negative affect and craving (but not trauma cue and negative affect). CONCLUSIONS:This study provides novel laboratory evidence for the respective contributions of negative affect, PTSD symptoms, and coping motives on alcohol craving in trauma-exposed drinkers. It offers a methodological framework in which to evaluate novel strategies that aim to disrupt negative reinforcement drinking in individuals with co-occurring PTSD and AUD.

BACKGROUND:H3K27M-mutant midline lesions were recently reclassified by the World Health Organization (WHO) as "diffuse midline glioma" (DMG) based entirely on their molecular signature. DMG is one of the most common and most lethal pediatric brain tumors; terminal progression is typically caused by local midbrain or brainstem progression, or secondary leptomeningeal dissemination. H3K27M mutations have also been infrequently associated with a histologically and prognostically diverse set of lesions, particularly spinal masses with early leptomeningeal spread. CASE PRESENTATION/METHODS:A 15-year-old girl after 1 week of symptoms was found to have a T2/FLAIR-hyperintense and contrast-enhancing thalamic mass accompanied by leptomeningeal enhancement along the entire neuraxis. Initial infectious workup was negative, and intracranial biopsy was inconclusive. Spinal arachnoid biopsy revealed an H3K27M-mutant lesion with glioneuronal features, classified thereafter as DMG. She received craniospinal irradiation with a boost to the thalamic lesion. Imaging 1-month post-radiation demonstrated significant treatment response with residual enhancement at the conus. CONCLUSIONS:This case report describes the unique presentation of an H3K27M-mutant midline lesion with significant craniospinal leptomeningeal spread on admission and atypical glioneuronal histopathological markers. With such florid leptomeningeal disease, spinal dural biopsy should be considered earlier given its diagnostic yield in classifying the lesion as DMG. Consistent with similar prior reports, this lesion additionally demonstrated synaptophysin positivity-also potentially consistent with a diagnosis of diffuse leptomeningeal glioneuronal tumor (DLGNT). In atypical DMG cases, particularly with leptomeningeal spread, further consideration of clinical and histopathological context is necessary for accurate diagnosis and prognostication.

PURPOSE/OBJECTIVE:To describe the temporal association of specific acute neurological symptoms in pediatric patients with confirmed SARS-CoV-2 infection between May and August 2020. METHODS:We performed a recollection of all the clinical and laboratory data of patients having acute neurological symptoms temporally associated with SARS-CoV-2 infection at a third-level referral hospital in Mexico City (Instituto Nacional de Pediatría). Patients in an age group of 0-17 years with acute neurological signs (including ascending weakness with areflexia, diminished visual acuity, encephalopathy, ataxia, stroke, or weakness with plasma creatinine kinase (CK) elevation) were evaluated. RESULTS:Out of 23 patients with neurological manifestations, 10 (43%) had a confirmed SARS-CoV-2 infection. Among the infected patients, 5 (50%) were males aged 2-16 years old (median age 11.8 years old). Four (40%) patients confirmed a close contact with a relative positive for SARS-CoV-2, while 6 (60%) cases had a history of SARS-CoV-2-related symptoms over the previous 2 weeks. The following diagnoses were established: 3 cases of GBS, 2 of ON, 2 of AIS, one of myositis with rhabdomyolysis, one ACA, and one of anti-NMDA-R encephalitis. CONCLUSIONS:Neurological manifestations temporally associated with SARS-CoV-2 infection were noticed in the pediatric population even without respiratory symptoms. In this study, 2 of 6 symptomatic patients had mild respiratory symptoms and 4 had unspecific symptoms. During this pandemic, SARS-CoV-2 infection should be considered as etiology in patients with acute neurological symptoms, with or without previous respiratory manifestations, particularly in teenagers.

OBJECTIVE:To assess telehealth practice for headache visits in the United States. BACKGROUND:The rapid roll out of telehealth during the COVID-19 pandemic impacted headache specialists. METHODS:American Headache Society (AHS) members were emailed an anonymous survey (9/9/20-10/12/20) to complete if they had logged ≥2 months or 50+ headache visits via telehealth. RESULTS:Out of 1348 members, 225 (16.7%) responded. Most were female (59.8%; 113/189). Median age was 47 (interquartile range [IQR] 37-57) (N = 154). The majority were MD/DOs (83.7%; 159/190) or NP/PAs (14.7%; 28/190), and most (65.1%; 123/189) were in academia. Years in practice were 0-3: 28; 4-10: 58; 11-20: 42; 20+: 61. Median number of telehealth visits was 120 (IQR 77.5-250) in the prior 3 months. Respondents were "comfortable/very comfortable" treating via telehealth (a) new patient with a chief complaint of headache (median, IQR 4 [3-5]); (b) follow-up for migraine (median, IQR 5 [5-5]); (c) follow-up for secondary headache (median, IQR 4 [3-4]). About half (51.1%; 97/190) offer urgent telehealth. Beyond being unable to perform procedures, top barriers were conducting parts of the neurologic exam (157/189), absence of vital signs (117/189), and socioeconomic/technologic barriers (91/189). Top positive attributes were patient convenience (185/190), reducing patient travel stress (172/190), patient cost reduction (151/190), flexibility with personal matters (128/190), patient comfort at home (114/190), and patient medications nearby (103/190). Only 21.3% (33/155) of providers said telehealth visit length differed from in-person visits, and 55.3% (105/190) believe that the no-show rate improved. On a 1-5 Likert scale, providers were "interested"/"very interested" in digitally prescribing headache apps (median 4, IQR 3-5) and "interested"/"very interested" in remotely monitoring patient symptoms (median 4, IQR 3-5). CONCLUSIONS:Respondents were comfortable treating patients with migraine via telehealth. They note positive attributes for patients and how access may be improved. Technology innovations (remote vital signs, digitally prescribing headache apps) and remote symptom monitoring are areas of interest and warrant future research.

Extensive work on movement-related beta oscillations (~13-30 Hz) over the sensorimotor areas in both humans and animals has demonstrated that sensorimotor beta power decreases during movement and transiently increases after movement. This beta power modulation has been interpreted as reflecting interactions between sensory and motor cortical areas with attenuation of sensory afferents during movement and their subsequent re-activation for internal models updating. More recent studies in neurologically normal subjects have demonstrated that this movement-related modulation as well as mean beta power at rest increase with practice and that previous motor learning enhances such increases. Conversely, patients with Parkinson's disease (PD) do not show such practice-related increases. Interestingly, a 2-h inactivity period without sleep can restore beta power values to baseline in normal subjects. Based on these results and on those of biochemical and electrophysiological studies in animals, we expand the current interpretation of beta activity and propose that the practice-related increases of beta power over sensorimotor areas are local indices of energy used for engaging plasticity-related activity. This paper provides some preliminary evidence in this respect linking findings of biochemical and electrophysiological studies in both humans and animals. This novel interpretation may explain the high level of beta power at rest, the deficient modulation during movement as well as the decreased skill formation in PD as resulting from deficiency in energy consumption, availability and regulation that are altered in this disease.

PURPOSE/OBJECTIVE:The purpose of this study is to evaluate the effectiveness of Extracellular Matrix Cartilage Allograft (EMCA) as an adjuvant to bone marrow stimulation (BMS) compared to BMS alone in the treatment of osteochondral lesions of the talus (OLT). METHODS:or Fisher exact test for categorical variables. RESULTS:Twenty-four patients underwent BMS with EMCA (BMS-EMCA group) and 24 patients underwent BMS alone (BMS group). The mean age was 40.8 years (range, 19 to 60 years) in BMS-EMCA group and 47.8 years (range, 24 to 60 years) in BMS group (p=0.060). The mean follow-up time was 20.0 months (range, 12-36 months) in BMS-EMCA group and 26.9 months (range, 12 to 55 months) in BMS group (p=0.031). Both groups showed significant improvements in all FAOS subscales. No significant differences between groups were found in all postoperative FAOS. The mean MOCART score in BMS-EMCA group was higher (76.3 vs 66.3), but not statistically significant (p=0.176). The MRI analysis showed that 87.5% of BMS-EMCA group had complete infill of the defect with repair tissue, however less than half (46.5%) of BMS group had complete infill (p=0.015). CONCLUSION/CONCLUSIONS:BMS with EMCA is an effective treatment strategy for the treatment of OLT and provides better cartilage infill in the defect on MRI. However, this did not translate to improved functional outcomes compared with BMS alone in the short-term. Additionally, according to the minimal clinically important difference (MCID) analysis, there was no significant difference in clinical function scoring between either group postoperatively. LEVEL OF EVIDENCE/METHODS:Level III retrospective comparative study.

CDKL5 deficiency disorder (CDD) is an X-linked pharmacoresistant neurogenetic disorder characterized by global developmental delays and uncontrolled seizures. Fenfluramine (FFA), an antiseizure medication (ASM) indicated for treating convulsive seizures in Dravet syndrome, was assessed in six patients (five female; 83%) with CDD whose seizures had failed 5-12 ASMs or therapies. Median age at enrollment was 6.5 years (range: 2-26 years). Mean FFA treatment duration was 5.3 months (range: 2-9 months) at 0.4 mg/kg/day (n = 2) or 0.7 mg/kg/day (n = 4; maximum: 26 mg/day). One patient had valproate added for myoclonic seizures. The ASM regimens of all other patients were stable. Among five patients with tonic-clonic seizures, FFA treatment resulted in a median 90% reduction in frequency (range: 86%-100%). Tonic seizure frequency was reduced by 50%-60% in two patients with this seizure type. One patient experienced fewer myoclonic seizures; one patient first developed myoclonic seizures on FFA, which were controlled with valproate. Adverse events were reported in two patients. The patient with added valproate experienced lethargy; one patient had decreased appetite and flatus. No patient developed valvular heart disease or pulmonary arterial hypertension. Our preliminary results suggest that FFA may be a promising ASM for CDD. Randomized clinical trials are warranted.

Background/UNASSIGNED: Objectives/UNASSIGNED:To explore the clinical contribution of myocardial scintigraphy in discriminating different forms of parkinsonisms, especially when atypical features are present. Methods/UNASSIGNED:I-MIBG myocardial scintigraphy in our Movement Disorders Center. Disease evolution was reviewed by applying the latest disease criteria for PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS), as appropriate. Three diagnostic times were defined: T1 (before scintigraphy execution), T2 (immediately after the exam) and T3 (two years later). Early and delayed heart/mediastinum (H/M) ratios and washout rate (WR) were analyzed. Results/UNASSIGNED:I-MIBG myocardial scintigraphy (T2), in 9 patients (22%) an improvement of diagnostic accuracy was reached. Conclusions/UNASSIGNED:I-MIBG myocardial scintigraphy for the discrimination of PD from atypical parkinsonism, especially when dysautonomic symptoms are present.

BACKGROUND:Inhibition of vascular endothelial growth factor receptor (VEGFR) has shown antitumour activity in advanced hepatocellular carcinoma, but few studies of VEGFR inhibitors have been done in populations with a high prevalence of hepatitis B virus infection. The aim of this study was to evaluate the efficacy and safety of apatinib in patients with pretreated advanced hepatocellular carcinoma. METHODS:AHELP was a randomised, double-blind, placebo-controlled, phase 3 trial done at 31 hospitals in China, in patients (aged ≥18 years) with advanced hepatocellular carcinoma who had previously been refractory or intolerant to at least one line of systemic chemotherapy or targeted therapy. Patients were randomly assigned (2:1) to receive apatinib 750 mg or placebo orally once daily in 28-day treatment cycles. Group allocation was done with a central randomisation system, with a block size of six, and was stratified by Eastern Cooperative Oncology Group performance status, previous sorafenib treatment, and presence of vascular invasion or extrahepatic metastasis. The primary endpoint was overall survival, which was defined as time from randomisation to death from any cause, and was analysed in patients who were randomly assigned and received at least one dose of the study drug. Safety analyses were done in patients who received at least one dose of the study treatment and had post-dose safety assessments. This trial is registered with ClinicalTrials.gov, NCT02329860. FINDINGS/RESULTS:Between April 1, 2014, and May 3, 2017, 400 eligible patients were randomly assigned to receive apatinib (n=267) or placebo (n=133). Seven patients (six in the apatinib group and one in the placebo group) did not receive study treatment and were excluded from efficacy analyses. Overall survival was significantly improved in the apatinib group compared with the placebo group (median 8·7 months [95% CI 7·5‒9·8] vs 6·8 months [5·7‒9·1]; hazard ratio 0·785 [95% CI 0·617‒0·998], p=0·048). 387 patients (257 in the apatinib group and 130 in the placebo group) had a safety assessment after study treatment and were included in safety analyses. The most common treatment-related adverse events of grade 3 or 4 were hypertension (71 [28%] patients in the apatinib group vs three [2%] in the placebo group), hand-foot syndrome (46 [18%] vs none), and decreased platelet count (34 [13%] vs one [1%]). 24 (9%) patients in the apatinib group and 13 (10%) in the placebo group died due to adverse events, but none of these deaths were deemed to be related to treatment by investigators. INTERPRETATION/CONCLUSIONS:Apatinib significantly improved overall survival in patients with pretreated advanced hepatocellular carcinoma compared with placebo, with a manageable safety profile. FUNDING/BACKGROUND:Jiangsu Hengrui Medicine.