Browsing by Author "Kranz, Peter G"

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    Cerebral air embolism from angioinvasive cavitary aspergillosis.
    (Case Rep Neurol Med, 2014) Lin, Chen; Barrio, George A; Hurwitz, Lynne M; Kranz, Peter G
    Background. Nontraumatic cerebral air embolism cases are rare. We report a case of an air embolism resulting in cerebral infarction related to angioinvasive cavitary aspergillosis. To our knowledge, there have been no previous reports associating these two conditions together. Case Presentation. A 32-year-old female was admitted for treatment of acute lymphoblastic leukemia (ALL). Her hospital course was complicated by pulmonary aspergillosis. On hospital day 55, she acutely developed severe global aphasia with right hemiplegia. A CT and CT-angiogram of her head and neck were obtained demonstrating intravascular air emboli within the left middle cerebral artery (MCA) branches. She was emergently taken for hyperbaric oxygen therapy (HBOT). Evaluation for origin of the air embolus revealed an air focus along the left lower pulmonary vein. Over the course of 48 hours, her symptoms significantly improved. Conclusion. This unique case details an immunocompromised patient with pulmonary aspergillosis cavitary lesions that invaded into a pulmonary vein and caused a cerebral air embolism. With cerebral air embolisms, the acute treatment option differs from the typical ischemic stroke pathway and the provider should consider emergent HBOT. This case highlights the importance of considering atypical causes of acute ischemic stroke.
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    CN-105 in Participants with Acute Supratentorial Intracerebral Hemorrhage (CATCH) Trial.
    (Neurocritical care, 2021-08-23) James, Michael L; Troy, Jesse; Nowacki, Nathaniel; Komisarow, Jordan; Swisher, Christa B; Tucker, Kristi; Hatton, Kevin; Babi, Marc A; Worrall, Bradford B; Andrews, Charles; Woo, Daniel; Kranz, Peter G; Lascola, Christopher; Maughan, Maureen; Laskowitz, Daniel T; CATCH Investigators

    Background

    Endogenous apolipoprotein (apo) E mediates neuroinflammatory responses and recovery after brain injury. Exogenously administered apoE-mimetic peptides effectively penetrate the central nervous system compartment and downregulate acute inflammation. CN-105 is a novel apoE-mimetic pentapeptide with excellent evidence of functional and histological improvement in preclinical models of intracerebral hemorrhage (ICH). The CN-105 in participants with Acute supraTentorial intraCerebral Hemorrhage (CATCH) trial is a first-in-disease-state multicenter open-label trial evaluating safety and feasability of CN-105 administration in patients with acute primary supratentorial ICH.

    Methods

    Eligible patients were aged 30-80 years, had confirmed primary supratentorial ICH, and were able to intiate CN-105 administration (1.0 mg/kg every 6 h for 72 h) within 12 h of symptom onset. A priori defined safety end points, including hematoma volume, pharmacokinetics, and 30-day neurological outcomes, were analyzed. For clinical outcomes, CATCH participants were compared 1:1 with a closely matched contemporary ICH cohort through random selection. Hematoma volumes determined from computed tomography images on days 0, 1, 2, and 5 and ordinal modified Rankin Scale score at 30 days after ICH were compared.

    Results

    In 38 participants enrolled across six study sites in the United States, adverse events occurred at an expected rate without increase in hematoma expansion or neurological deterioration. CN-105 treatment had an odds ratio (95% confidence interval) of 2.69 (1.31-5.51) for lower 30-day modified Rankin Scale score, after adjustment for ICH score, sex, and race/ethnicity, as compared with a matched contemporary cohort.

    Conclusions

    CN-105 administration represents an excellent translational candidate for treatment of acute ICH because of its safety, dosing feasibility, favorable pharmacokinetics, and possible improvement in neurological recovery.
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    Cross-sectional CT Assessment of the Extent of Injectate Spread at CT Fluoroscopy-guided Cervical Epidural Interlaminar Steroid Injections.
    (Radiology, 2019-07-16) Amrhein, Timothy J; Bozdogan, Erol; Vekaria, Sunit; Patel, Prasad; Lerebours, Reginald; Luo, Sheng; Kranz, Peter G
    Background Previous studies analyzed contrast agent spread during cervical interlaminar epidural steroid injections (CILESIs) by using planar fluoroscopy and reported wide variance of the rate of spread to the ventral epidural space (VES). Cross-sectional CT allows for direct viewing of contrast agent in the VES, providing improved spread assessment and thereby informing needle placement decisions when targeting pain generators. Purpose To determine the extent of injectate spread at CT fluoroscopy-guided CILESI, with particular attention to the VES and bilateral neuroforamina, by using cross-sectional CT. Materials and Methods This study reviewed 83 consecutive CT fluoroscopy-guided CILESIs at which a postprocedural cervical spine CT was performed (June 2016 to December 2017). All procedures used the same injectate (2 mL corticosteroid, 3 mL contrast agent). Postprocedural CT scans were reviewed for the presence of contrast within the VES, dorsal epidural space, ipsilateral neuroforamen, and contralateral neuroforamen in every cervical interlaminar level. Descriptive data are presented as frequencies or means. McNemar tests or hierarchical logistic models were used to assess associations between covariates and contrast agent spread to particular locations. Results The study cohort included 73 individual patients (59% women; 43 of 73) (mean patient age, 57.6 years ± 11.5 [standard deviation]). Mean number of levels of cranial spread were 0.6 level for VES, 1.9 levels for contralateral neuroforamen, 2.1 levels for ipsilateral neuroforamen, and 3 levels for dorsal epidural space. No VES spread in any level was found with 35% (29 of 83) of injections. VES spread was more likely to occur in the level of needle placement (43%; 36 of 83) than in other interlaminar levels (19.5%; 97 of 498; P < .001). Spread was more likely to occur in the neuroforamen ipsilateral to the needle approach compared with contralateral (P < .001). Conclusion Cervical interlaminar epidural steroid injections have injectate spreads with a mean of less than one level cranially in the ventral epidural space (VES) and approximately two levels in the neuroforamen. VES spread occurs more frequently at the level of needle placement and within the ipsilateral neuroforamen. © RSNA, 2019.
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    Gender and age interact to affect early outcome after intracerebral hemorrhage.
    (PLoS One, 2013) Umeano, Odera; Phillips-Bute, Barbara; Hailey, Claire E; Sun, Wei; Gray, Marisa C; Roulhac-Wilson, Briana; McDonagh, David L; Kranz, Peter G; Laskowitz, Daniel T; James, Michael L
    BACKGROUND: Intracerebral hemorrhage (ICH) is a common and devastating form of cerebrovascular disease. In ICH, gender differences in outcomes remain relatively understudied but have been examined in other neurological emergencies. Further, a potential effect of age and gender on outcomes after ICH has not been explored. This study was designed to test the hypothesis that age and gender interact to modify neurological outcomes after ICH. METHODS: Adult patients admitted with spontaneous primary supratentorial ICH from July 2007 through April 2010 were assessed via retrospective analysis of an existing stroke database at Duke University. Univariate analysis of collected variables was used to compare gender and outcome. Unfavorable outcome was defined as discharge to hospice or death. Using multivariate regression, the combined effect of age and gender on outcome after ICH was analyzed. RESULTS: In this study population, women were younger (61.1+14.5 versus 65.8+17.3 years, p=0.03) and more likely to have a history of substance abuse (35% versus 8.9%, p<0.0001) compared to men. Multivariable models demonstrated that advancing age had a greater effect on predicting discharge outcome in women compared to men (p=0.02). For younger patients, female sex was protective; however, at ages greater than 60 years, female sex was a risk factor for discharge to hospice or death. CONCLUSION: While independently associated with discharge to hospice or death after ICH, the interaction effect between gender and age demonstrated significantly stronger correlation with early outcome after ICH in a single center cohort. Prospective study is required to verify these findings.
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    Looking beyond the exome: a phenotype-first approach to molecular diagnostic resolution in rare and undiagnosed diseases.
    (Genetics in medicine : official journal of the American College of Medical Genetics, 2018-04) Pena, Loren DM; Jiang, Yong-Hui; Schoch, Kelly; Spillmann, Rebecca C; Walley, Nicole; Stong, Nicholas; Rapisardo Horn, Sarah; Sullivan, Jennifer A; McConkie-Rosell, Allyn; Kansagra, Sujay; Smith, Edward C; El-Dairi, Mays; Bellet, Jane; Keels, Martha Ann; Jasien, Joan; Kranz, Peter G; Noel, Richard; Nagaraj, Shashi K; Lark, Robert K; Wechsler, Daniel SG; Del Gaudio, Daniela; Leung, Marco L; Hendon, Laura G; Parker, Collette C; Jones, Kelly L; Undiagnosed Diseases Network Members; Goldstein, David B; Shashi, Vandana
    PurposeTo describe examples of missed pathogenic variants on whole-exome sequencing (WES) and the importance of deep phenotyping for further diagnostic testing.MethodsGuided by phenotypic information, three children with negative WES underwent targeted single-gene testing.ResultsIndividual 1 had a clinical diagnosis consistent with infantile systemic hyalinosis, although WES and a next-generation sequencing (NGS)-based ANTXR2 test were negative. Sanger sequencing of ANTXR2 revealed a homozygous single base pair insertion, previously missed by the WES variant caller software. Individual 2 had neurodevelopmental regression and cerebellar atrophy, with no diagnosis on WES. New clinical findings prompted Sanger sequencing and copy number testing of PLA2G6. A novel homozygous deletion of the noncoding exon 1 (not included in the WES capture kit) was detected, with extension into the promoter, confirming the clinical suspicion of infantile neuroaxonal dystrophy. Individual 3 had progressive ataxia, spasticity, and magnetic resonance image changes of vanishing white matter leukoencephalopathy. An NGS leukodystrophy gene panel and WES showed a heterozygous pathogenic variant in EIF2B5; no deletions/duplications were detected. Sanger sequencing of EIF2B5 showed a frameshift indel, probably missed owing to failure of alignment.ConclusionThese cases illustrate potential pitfalls of WES/NGS testing and the importance of phenotype-guided molecular testing in yielding diagnoses.
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    Myelography Using Energy-Integrating Detector CT Versus Photon-Counting Detector CT for Detection of CSF-Venous Fistulas in Patients With Spontaneous Intracranial Hypotension.
    (AJR. American journal of roentgenology, 2024-01) Schwartz, Fides R; Kranz, Peter G; Malinzak, Michael D; Cox, David N; Ria, Francesco; McCabe, Cindy; Harrawood, Brian; Leithe, Linda G; Samei, Ehsan; Amrhein, Timothy J
    Background: CSF-venous fistulas (CVFs) are an increasingly recognized cause of spontaneous intracranial hypotension (SIH) that are often diminutive in size and exceedingly difficult to detect by conventional imaging. Objective: This study's objective was to compare EID-CT myelography and PCD-CT myelography in terms of image quality and diagnostic performance for detecting CVFs in patients with SIH. Methods: This retrospective study included 38 patients (15 men, 23 women; mean age, 55±10 years) with SIH who underwent both clinically indicated EID-CT myelography (slice thickness, 0.625 mm) and PCD-CT myelography (slice thickness, 0.2 mm; performed in ultrahigh-resolution mode) to assess for CSF leak. Three blinded radiologists reviewed examinations in random order, assessing image noise, discernibility of spinal nerve root sleeves, and overall image quality using 0-100 scales (100=highest quality), and recording locations of CVFs. Definite CVFs were defined as CVFs described in CT myelography reports using unequivocal language and showing attenuation >70 HU. Results: For all readers, PCD-CT myelography, in comparison with EID-CT myelography, showed higher image noise (reader 1: 69±19 vs 38±15; reader 2: 59±9 vs 49±13; reader 3: 57±13 vs 43±15), higher nerve root sleeve discernibility (reader 1: 84±19 vs 30±14; reader 2: 84±19 vs 70±19; reader 3: 60±13 vs 52±12), and higher overall image quality (reader 1: 84±21 vs 40±15; reader 2: 81±10 vs 72±20; reader 3: 58±11 vs 53±11) (all p<.05). Eleven patients had a definite CVF. Sensitivity and specificity for detection of definite CVF for EID-CT myelography and PCD-CT myelography for reader 1 were 45% and 96% versus 64% and 85; for reader 2 were 36% and 100% versus 55% and 96%; and for reader 3 were 45% and 100% versus 55% and 93%. For all readers, PCD-CT myelography, in comparison with EID-CT myelography, showed significantly higher sensitivity (all p<.05), without significant difference in specificity (all p>.05). Conclusion: In comparison with EID-CT myelography, PCD-CT myelography yielded significantly improved image quality with significantly higher sensitivity for CVFs without significant loss of specificity. Clinical Impact: The findings support a potential role of PCD-CT myelography in facilitating earlier diagnosis and targeted treatment of SIH, avoiding high morbidity during potentially prolonged diagnostic workups.
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    Reorganization and stability for motor and language areas using cortical stimulation: case example and review of the literature.
    (Brain sciences, 2013-11) Serafini, Sandra; Komisarow, Jordan M; Gallentine, William; Mikati, Mohamad A; Bonner, Melanie J; Kranz, Peter G; Haglund, Michael M; Grant, Gerald
    The cerebral organization of language in epilepsy patients has been studied with invasive procedures such as Wada testing and electrical cortical stimulation mapping and more recently with noninvasive neuroimaging techniques, such as functional MRI. In the setting of a chronic seizure disorder, clinical variables have been shown to contribute to cerebral language reorganization underscoring the need for language lateralization and localization procedures. We present a 14-year-old pediatric patient with a refractory epilepsy disorder who underwent two neurosurgical resections of a left frontal epileptic focus separated by a year. He was mapped extraoperatively through a subdural grid using cortical stimulation to preserve motor and language functions. The clinical history and extensive workup prior to surgery is discussed as well as the opportunity to compare the cortical maps for language, motor, and sensory function before each resection. Reorganization in cortical tongue sensory areas was seen concomitant with a new zone of ictal and interictal activity in the previous tongue sensory area. Detailed neuropsychological data is presented before and after any surgical intervention to hypothesize about the extent of reorganization between epochs. We conclude that intrahemispheric cortical plasticity does occur following frontal lobe resective surgery in a teenager with medically refractory seizures.
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    The microRNA processor DROSHA is a candidate gene for a severe progressive neurological disorder.
    (Human molecular genetics, 2022-04-11) Barish, Scott; Senturk, Mumine; Schoch, Kelly; Minogue, Amanda L; Lopergolo, Diego; Fallerini, Chiara; Harland, Jake; Seemann, Jacob H; Stong, Nicholas; Kranz, Peter G; Kansagra, Sujay; Mikati, Mohamad A; Jasien, Joan; El-Dairi, Mays; Galluzzi, Paolo; Undiagnosed Diseases Network; Ariani, Francesca; Renieri, Alessandra; Mari, Francesca; Wangler, Michael F; Arur, Swathi; Jiang, Yong-Hui; Yamamoto, Shinya; Shashi, Vandana; Bellen, Hugo J
    DROSHA encodes a ribonuclease that is a subunit of the Microprocessor complex and is involved in the first step of microRNA (miRNA) biogenesis. To date, DROSHA has not yet been associated with a Mendelian disease. Here we describe two individuals with profound intellectual disability, epilepsy, white matter atrophy, microcephaly, and dysmorphic features, who carry damaging de novo heterozygous variants in DROSHA. DROSHA is constrained for missense variants and moderately intolerant to loss of function (o/e = 0.24). The loss of the fruit fly ortholog drosha causes developmental arrest and death in third instar larvae, a severe reduction in brain size, and loss of imaginal discs in the larva. Loss of drosha in eye clones causes small and rough eyes in adult flies. One of the identified DROSHA variants (p.Asp1219Gly) behaves as a strong loss-of-function allele in flies, while another variant (p.Arg1342Trp) is less damaging in our assays. In worms, a knock-in that mimics the p.Asp1219Gly variant at a worm equivalent residue causes loss of miRNA expression and heterochronicity, a phenotype characteristic of the loss of miRNA. Together, our data show that the DROSHA variants found in the individuals presented here are damaging based on functional studies in model organisms and likely underlie the severe phenotype involving the nervous system.