Faculty Bibliography
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school:SOM
Department/Unit:Neurology
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23143
Medication utilization among vascular dementia population
BACKGROUND:It is estimated that up to 40% of Alzheimer's Disease and Related Dementias cases can be prevented or delayed by addressing modifiable factors including those that influence vascular risk (hypertension, obesity, smoking, physical activity, diabetes). Prevention may be particularly important in the vascular dementia subtypes. Despite the supporting evidence, the rates of medical therapy to reduce vascular risk are not well described. METHOD/METHODS:We assessed the utilization of statins, aspirin, and blood pressure (BP) medications in adults age ≥65 years cared for at NYU Langone Health, as recorded in the electronic health record. We included two cohorts: cohort 1 included patients who were diagnosed with vascular dementia (VaD) at NYU Langone Barlow Center for Memory Evaluation between January 1, 2015 and June 24, 2019. Cohort 2 extended the inclusion to seniors with VD diagnosis by any NYU Langone physician. Definitions for vascular dementia, the covariates assessed, and medications that we included in each category are shown in Tables 1-3. RESULT/RESULTS:We included 419 and 3745 patients in cohort 1 and cohort 2, respectively. Table 4 shows the characteristics and medication adherence in cohorts 1 and 2. In cohort 1, the prescription rates for statins, aspirin, and BP medications were 66%, 66%, 70%. In cohort 2, the rates for statin, aspirin, and BP medications were 56%, 46%, and 65%, respectively. The differences between prescription rates in cohort 1 and 2 for the three medication groups were statistically significant (p<0.05). CONCLUSION/CONCLUSIONS:Our analysis of the utilization of cardiovascular medications among patients with vascular dementia illuminates potential gaps both among patients who receive care at specialty clinics, as well as the overall population with vascular dementia. The rates of medication utilization are higher for patients under the care of cognitive neurologists. Electronic health records can help identify large cohorts of patients who may benefit from improved access to preventative measures including cardiovascular medications.
PMID: 34971267
ISSN: 1552-5279
CID: 5108332
Decline in subarachnoid haemorrhage volumes associated with the first wave of the COVID-19 pandemic
BACKGROUND:During the COVID-19 pandemic, decreased volumes of stroke admissions and mechanical thrombectomy were reported. The study's objective was to examine whether subarachnoid haemorrhage (SAH) hospitalisations and ruptured aneurysm coiling interventions demonstrated similar declines. METHODS:We conducted a cross-sectional, retrospective, observational study across 6 continents, 37 countries and 140 comprehensive stroke centres. Patients with the diagnosis of SAH, aneurysmal SAH, ruptured aneurysm coiling interventions and COVID-19 were identified by prospective aneurysm databases or by International Classification of Diseases, 10th Revision, codes. The 3-month cumulative volume, monthly volumes for SAH hospitalisations and ruptured aneurysm coiling procedures were compared for the period before (1 year and immediately before) and during the pandemic, defined as 1 March-31 May 2020. The prior 1-year control period (1 March-31 May 2019) was obtained to account for seasonal variation. FINDINGS/RESULTS:There was a significant decline in SAH hospitalisations, with 2044 admissions in the 3 months immediately before and 1585 admissions during the pandemic, representing a relative decline of 22.5% (95% CI -24.3% to -20.7%, p<0.0001). Embolisation of ruptured aneurysms declined with 1170-1035 procedures, respectively, representing an 11.5% (95%CI -13.5% to -9.8%, p=0.002) relative drop. Subgroup analysis was noted for aneurysmal SAH hospitalisation decline from 834 to 626 hospitalisations, a 24.9% relative decline (95% CI -28.0% to -22.1%, p<0.0001). A relative increase in ruptured aneurysm coiling was noted in low coiling volume hospitals of 41.1% (95% CI 32.3% to 50.6%, p=0.008) despite a decrease in SAH admissions in this tertile. INTERPRETATION/CONCLUSIONS:There was a relative decrease in the volume of SAH hospitalisations, aneurysmal SAH hospitalisations and ruptured aneurysm embolisations during the COVID-19 pandemic. These findings in SAH are consistent with a decrease in other emergencies, such as stroke and myocardial infarction.
PMCID:8006491
PMID: 33771936
ISSN: 2059-8696
CID: 4830292
Inhibition of the norepinephrine transporter to treat neurogenic orthostatic hypotension: is this the end of the story? [Comment]
PMID: 34757507
ISSN: 1619-1560
CID: 5285202
Association of asymptomatic hemorrhage after endovascular stroke treatment with outcomes
BACKGROUND:Intracerebral hemorrhage (ICH) occurs in ~20%-30% of stroke patients undergoing endovascular therapy (EVT). However, there is conflicting evidence regarding the effect of asymptomatic ICH (aICH) on post-EVT outcomes. We sought to evaluate the effect of aICH on immediate and 90-day post-EVT neurological outcomes. METHODS:In this post-hoc analysis of the multicenter, prospective Blood Pressure after Endovascular Therapy (BEST) study we identified subjects with ICH following EVT. This population was divided into no ICH, aICH, and symptomatic ICH (sICH). Associations with 90-day modified Rankin Scale (mRS) dichotomized by functional independence (0-2 vs 3-6) and early neurological recovery (ENR) were determined using univariate/multivariate logistic regression models. RESULTS:Of 485 patients enrolled in BEST, 446 had 90-day follow-up data available. 92 (20.6%) developed aICH, and 18 (4%) developed sICH. Compared with those without ICH, aICH was not associated with worse 90-day outcome or lower ENR (OR 0.84 [0.53-1.35], P=0.55, aOR 0.84 [0.48-1.44], P=0.53 for 90-day mRS 0-2; OR 0.77 [0.48-1.23], P=0.34, aOR 0.72 [0.43-1.22] for ENR). aICH was not associated with 90-day outcome or ENR in patients with mTICI ≥2 b (OR 0.78 [0.48-1.26], P=0.33 for 90-day mRS 0-2; OR 0.89 [0.69-1.12], P=0.15 for ENR). A higher proportion of patients with aICH had mTICI ≥2 b than those without ICH (97%vs 87%, P=0.01). CONCLUSIONS:aICH was not associated with worse outcomes in patients with large-vessel stroke treated with EVT. aICH was more frequent in patients with successful recanalization. Further validation of our findings in large cohort studies of EVT-treated patients is warranted.
PMID: 33558440
ISSN: 1759-8486
CID: 4779472
Bilateral Distance Partition of Periventricular and Deep White Matter Hyperintensities: Performance of the Method in the Aging Brain
RATIONALE AND OBJECTIVES/OBJECTIVE:Periventricular and deep white matter hyperintensities (WMHs) in the elderly have been reported with distinctive roles in the progression of cognitive decline and dementia. However, the definition of these two subregions of WMHs is arbitrary and varies across studies. Here, we evaluate three partition methods for WMH subregions, including two widely used conventional methods (CV & D10) and one novel method based on bilateral distance (BD). MATERIALS AND METHODS/METHODS:The three partition methods were assessed on the MRI scans of 60 subjects, with 20 normal control, 20 mild cognitive impairment, and 20 Alzheimer's disease (AD). Resulting WMH subregional volumes were (1) compared among different partition methods and subject groups, and (2) tested for clinical associations with cognition and dementia. Inter-rater, intrarater, and interscan reproducibility of WMHs volumes were tested on 12 randomly selected subjects from the 60. RESULTS:For all three partition methods, increased periventricular WMHs were found for AD subjects over normal control. For BD and D10, but not CV method, increased Periventricular WMHs were found for AD subjects over mild cognitive impairment. Significant correlations were found between PVWMHs and Mini-Mental State Examination, Montreal Cognitive Assessment, and Clinical Dementia Rating scores. Furthermore, PVWMHs under BD partition showed higher correlations than D10 and CV. High intrarater and interscan reproducibility (ICCA = 0.998 and 0.992 correspondingly) and substantial inter-rater reproducibility (ICCA = 0.886) were detected. CONCLUSION/CONCLUSIONS:Different WMH partition methods showed comparable diagnostic abilities. The proposed BD method showed advantages in quantifying PVWMH over conventional CV and D10 methods, in terms of higher consistency, larger contrast, and higher diagnosis accuracy. Furthermore, the PVWMH under BD partition showed stronger clinical correlations than conventional methods.
PMID: 33127308
ISSN: 1878-4046
CID: 4770722
Improved Bioavailability with Dry Powder Cannabidiol Inhalation: A Phase 1 Clinical Study
Oral cannabidiol (CBD) is approved by the Food and Drug Administration (FDA) to treat patients with Dravet and Lennox-Gastaut syndromes, and tuberous sclerosis complex. The therapeutic potential of oral CBD formulations is limited by extensive first-pass hepatic metabolism. Following oral administration, the inactive metabolite blood concentration is ∼40-fold higher than CBD. Inhalation bypasses the pharmacokinetic (PK) variability attributed to irregular gastrointestinal absorption and first-pass hepatic metabolism and may efficiently deliver CBD into systemic circulation. This phase 1 study compared the PK of a dry-powder inhaler (DPI) CBD formulation (10 mg; excipient containing 2.1 mg CBD) with an oral CBD solution (Epidiolex®, 50 mg) in healthy participants. Following a single dose of Epidiolex or DPI CBD (n=10 PK evaluable participants each), the maximum CBD concentration for the inhaled powder was 71-fold higher than that of Epidiolex while administering 24-fold less CBD. The mean time to reach maximum concentration was 3.8 minutes for the DPI CBD formulation compared with 122 minutes for Epidiolex. Both Epidiolex and DPI CBD were generally safe and well-tolerated. These data indicate that DPI CBD provided more rapid onset and increased bioavailability than oral CBD and support further investigations on the use of DPI CBD for acute indications.
PMID: 34400185
ISSN: 1520-6017
CID: 4998292
Adjunctive everolimus therapy for tuberous sclerosis complex-associated refractory seizures: Results from the postextension phase of EXIST-3
OBJECTIVE:Epilepsy is highly prevalent in patients with tuberous sclerosis complex (TSC). Everolimus showed higher efficacy than placebo for seizures in the primary analysis of the EXIST-3 study. Here, we present the long-term outcomes of everolimus at the end of the postextension phase (PEP; data cutoff date: October 25, 2017). METHODS:After completion of the extension phase, patients were invited to continue everolimus in the PEP with everolimus (targeted trough concentration = 5-15 ng/ml, investigator-judged). Efficacy assessments included changes in seizure status during the PEP collected at 12-week intervals as parent/caregiver-reported data through a structured questionnaire. RESULTS:Among 361 patients, 343 entered the extension phase and 249 entered the PEP. After 12 weeks in the PEP, 18.9% (46/244) of patients were seizure-free since the last visit of the extension phase and 64.8% (158/244) had a stable/improved seizure status. At 24 weeks, the corresponding percentages were 18.2% (42/231) and 64.5% (149/231). Among 244 patients, the response rate was 32.8% (80/244) during the 12-week maintenance period of the core phase and 63.9% (156/244) at the end of the extension phase. Of the 149 responders at the end of the extension phase, 70.5% were seizure-free or had stable/improved seizure status. Long-term efficacy data showed persistent responses were observed in 183 of 361 patients (50.7%); 63.9% of these patients had a response that lasted at least 48 weeks. The most frequent Grade 3-4 adverse events (≥2% incidence) reported throughout the study were pneumonia, status epilepticus, seizure, stomatitis, neutropenia, and gastroenteritis. Four patients died during the study. SIGNIFICANCE/CONCLUSIONS:The final analysis of EXIST-3 demonstrated the sustained efficacy of everolimus as adjunctive therapy in patients with TSC-associated treatment-refractory seizures, with a tolerable safety profile.
PMID: 34693520
ISSN: 1528-1167
CID: 5068242
Percutaneous transorbital direct puncture to obliterate a cavernous sinus dural arteriovenous fistula
Cavernous sinus dural arteriovenous fistulas (CS-DAVF) can have an indolent course, with insidious onset, but still showing a high likelihood of spontaneous resolution.1 Nevertheless, symptoms in a subset of patients evolve more rapidly, with malignant signs on imaging, warranting intervention.2 We report on a patient in his 40s presenting with redness and proptosis of the right eye, intermittent blurred vision and diplopia. Once ophthalmological examination revealed increased intraocular pressure and imaging showed cortical venous congestion, the decision was made to obliterate a CS-DAVF involving the posteromedial right cavernous sinus.Multiple arteries including branches of the ascending pharyngeal artery, occipital artery and bilateral meningohypophyseal trunks supplied the fistula. Once transarterial embolization was deemed unsafe and both inferior petrosal sinuses did not grant access to the right cavernous sinus, a direct puncture to the cavernous sinus was performed to successfully coil the involved compartments.3-5 The aid of DynaCT imaging and needle guidance software is emphasized (video 1).neurintsurg;neurintsurg-2020-017118v1/V1F1V1Video 1.
PMID: 33685982
ISSN: 1759-8486
CID: 4809172
COVID-19 and neuroinflammation: a literature review of relevant neuroimaging and CSF markers in central nervous system inflammatory disorders from SARS-COV2
BACKGROUND:The literature on neurological manifestations in COVID-19 patients has been rapidly increasing with the pandemic. However, data on CNS inflammatory disorders in COVID-19 are still evolving. We performed a literature review of CNS inflammatory disorders associated with coronavirus disease-2019 (COVID-19). METHODS:We screened all articles resulting from a search of PubMed, Google Scholar and Scopus, using the keywords; "SARS-CoV-2 and neurological complication", "SARS-CoV-2 and CNS Complication" looking for reports of transverse myelitis, longitudinally extensive transverse myelitis, neuromyelitis optica, myelitis, Myelin Oligodendrocyte Glycoprotein Antibody Disorder (MOGAD), Acute Disseminated Encephalomyelitis (ADEM), Acute Hemorrhagic Necrotizing Encephalitis/Acute Hemorrhagic Leukoencephalitis (AHNE/AHLE), Cytotoxic lesion of the Corpus Callosum/Mild Encephalopathy Reversible Splenium Lesion(CLOCC/MERS) and Optic neuritis published between December 01, 2019 and March 15, 2021. RESULTS:Our literature search revealed 43 patients meeting the diagnosis of myelitis, including Transverse Myelitis, ADEM, AHNE/AHLE or CLOCC/MERS and Optic neuritis. Acute myelitis was most commonly associated with non-severe COVID-19 and all reported cases of AHNE/AHLE had severe COVID-19 infection. Based on IDSA/ATS criteria of either requiring vasopressor for septic shock or mechanical ventilation, 49% (n = 18) patients were considered to have a severe COVID infection. There were 7 (n = 19%) fatalities. CONCLUSION/CONCLUSIONS:To our knowledge, this is among the first reviews that includes the clinical features, neuroimaging, CSF findings and outcomes in COVID-19-associated CNS inflammatory disorders. Our observational review study reveals that although rare, myelitis, ADEM, AHNE and CLOCC can be associated with COVID-19 infection. Further studies using MRI imaging and CSF analysis in early diagnosis and intervention of these disorders are warranted.
PMCID:8131883
PMID: 34009454
ISSN: 1432-1459
CID: 5843512
Author Correction: Dectin 1 activation on macrophages by galectin 9 promotes pancreatic carcinoma and peritumoral immune tolerance
PMID: 34845391
ISSN: 1546-170x
CID: 5065482
