Faculty Bibliography

BACKGROUND:Papilledema can be a manifestation of neurologic Lyme borreliosis (LB). The clinical manifestations and progression of these cases have not been comprehensively documented to date. We aimed to describe clinical and diagnostic features and to assess patient outcomes in cases of papilledema secondary to neurologic LB. METHODS:We searched MEDLINE, EMBASE, and the Cochrane Database from inception to August 2019. We did not restrict our search by study design or by publication date, status, or language. RESULTS:Twenty-eight studies describing 46 cases of papilledema secondary to neurologic LB were included. Common clinical features included cranial neuropathy (68%) and diplopia (61%). Most patients did not recall tick bite (71%) and were afebrile (74%). Brain imaging was normal in 64% cases. Cerebrospinal fluid analysis showed lymphocytic pleocytosis (77%). Initial treatment with intravenous ceftriaxone was given in 52% of cases and resulted in a 100% resolution rate. Concomitant treatment with acetazolamide resulted in favorable outcomes. CONCLUSIONS:For patients in endemic regions who describe symptoms suggestive of intracranial hypertension and papilledema, especially accompanied by facial nerve palsy and other cranial nerve palsies, underlying neurologic LB should be considered.

ABSTRACT/UNASSIGNED:This article discusses the optimal ways to document and code for outpatient evaluation and management (E/M) codes. Since the changes for Current Procedural Terminology (CPT) codes 99202-99215 were finalized for 2021, they have been modified by the Centers for Medicare & Medicaid Services (CMS) in their Medicare Physician Fee Schedule and by technical corrections issued on March 9, 2021. The 21st Century Cures Act mandated that patients can access their notes and test results immediately. These developments have transformed medical documentation and coding for outpatient E/M services. One year in, the authors have a better understanding of the subtleties of documenting and accurately determining levels of service for outpatient encounters using these new rules and regulations, and they share key insights gained by experience with the new system.

OBJECTIVE:The purpose of this study was to establish whether a past psychiatric history could play a role in the development of psychiatric treatment-emergent adverse events (PTEAEs) in patients randomized to perampanel (PER) or placebo. METHODS:The development of PTEAEs was compared between patients with/without a psychiatric history in a post hoc analysis from four randomized placebo-controlled trials (RPCTs) of PER (304/305/306/335) in patients with treatment-resistant focal epilepsy. RESULTS:Among the 2,187 patients enrolled in the RPCTs, 352 (16.1%) had a psychiatric history (PER n = 244; placebo n = 108), while 1835 patients (83.9%) did not (PER n = 1325; placebo n = 510). Compared to patients without a psychiatric history, those with a positive history reported more PTEAEs for both patients randomized to PER (11.8% vs. 29.9%, p < 0.01) or to placebo (9.2% vs. 19.4%, p < 0.01). The prevalence of PTEAEs was not higher among patients randomized to 2 mg and 4 mg/day doses than placebo in both those with and without psychiatric history. Rather, the higher prevalence rates were among subjects randomized to 8 mg (29.8%) and 12 mg (36.4%) PER doses in patients with a past psychiatric history. SIGNIFICANCE:A psychiatric history appears to increase the risk of PTEAEs in patients randomized to placebo and to PER at doses of 8 and 12 mg/day. It should be identified in all patients considered for treatment with PER, particularly when prescribed at doses above 4 mg/day.

BACKGROUND & AIMS/OBJECTIVE:Criteria defined by the European Association for the Study of the Liver (EASL) and Liver Imaging Reporting and Data System (LI-RADS) enable hepatocellular carcinoma (HCC) diagnosis based on imaging in cirrhosis. Non-cirrhotic patients require biopsy given the lower pre-test probability of HCC. The objective of our study was to assess the performance of EASL and LI-RADS criteria for the diagnosis of HCC in non-cirrhotic patients with chronic HBV infection. METHODS:This was a cross-sectional study performed at a referral center. We included all patients with HBV without cirrhosis with focal liver lesions who underwent contrast-enhanced CT or MRI at our clinic between 2005-2018. Studies were reviewed by 2 radiologists blinded to the diagnosis. RESULTS:We included 280 patients, median age was 56.8 (IQR 48.2-65.45) years and 223 (80%) were male. In 191 (79%) cases the lesion was found as a result of screening. Cirrhosis was excluded based on pathology in 252 (90%) cases. We assessed 338 nodules: 257 (76%) HCC, 40 (12%) non-HCC malignant lesions, and 41 (12%) benign lesions. EASL criteria and LR-5/LR-tumor-in-vein (TIV) categories had a 100% agreement in categorizing lesions as HCC, and 226 nodules (67%) were classified as HCCs. The sensitivity, specificity, positive predictive value, and negative predictive value were 82.1 (76.9-86.6), 81.5 (71.3-89.2), 93.4 (89.3-96.2), and 58.9 (49.2-68.1), respectively. When the pre-test probability of HCC is >70%, estimated as a PAGE-B score above 9, and EASL or LR-5/LR-TIV criteria are met, post-test probability would be >90%. CONCLUSIONS:EASL criteria and LR-5/LR-TIV categories show a positive predictive value in patients with HBV without cirrhosis that is comparable to that seen in patients with cirrhosis. These criteria can be used when the pre-test probability of HCC is >70%. LAY SUMMARY/BACKGROUND:Current guidelines recommend performing a biopsy to confirm the diagnosis of presumed hepatocellular carcinoma (HCC) in patients without cirrhosis. We showed that specific imaging criteria had a 100% agreement for categorizing lesions as HCC, with a positive predictive value of 93.4%. These imaging criteria could be used to diagnose HCC in HBV patients without cirrhosis with a pre-test probability of HCC of ≥70%, avoiding the need for a liver biopsy.

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.

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.

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.

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.

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.