Publications by authors named "Kristen O Riley"

73 Publications

An unusual cause of shunt failure requiring multidisciplinary treatment.

Clin Case Rep 2021 Apr 24;9(4):2465-2466. Epub 2021 Feb 24.

Department of Neurosurgery University of Alabama at Birmingham Birmingham AL USA.

Rarer etiologies of shunt malfunction may be difficult to detect, can present insidiously, and often require a multidisciplinary approach to safely and effectively address.
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http://dx.doi.org/10.1002/ccr3.3655DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8077442PMC
April 2021

Control and Toxicity in Melanoma Versus Other Brain Metastases in Response to Combined Radiosurgery and PD-(L)1 Immune Checkpoint Inhibition.

Adv Radiat Oncol 2021 Jan-Feb;6(1):100561. Epub 2020 Sep 16.

Department of Radiation Oncology, Department of Internal Medicine, University of Alabama at Birmingham, Birmingham, Alabama.

Purpose: Prior studies have mixed conclusions about the efficacy and central nervous system (CNS) toxicity profile of combining radiosurgery with anti-programed cell death 1 (PD-1) immune checkpoint inhibition (ICI) for brain metastases. This study evaluates the safety and efficacy of combined radiosurgery and anti-PD-1 ICI for melanoma, non-small cell lung cancer (NSCLC), and renal cell carcinoma (RCC) brain metastases (BM).

Methods And Materials: Forty-one patients with 153 radiation naïve melanoma BM and 33 patients with 118 BM of NSCLC and RCC origin from 2014 through 2019 received radiosurgery and either anti PD-1 receptor inhibition or anti PD-L1 inhibition targeting the PD-1 ligand with less than 4 months separating either therapy. Similar to Radiation Therapy Oncology Group 9005, high-grade CNS toxicity was defined as irreversible grade 3 or any grade 4/5 neurologic event. Salvage resection revealing necrosis and viable tumor was considered grade 4 toxicity and local failure. An increase in greatest cross-sectional diameter of 25% on contrasted magnetic resonance imaging was designated as a local failure.

Results: Median follow-up was 10 months (range, 1-41 months). Local control was estimated to be 90.3% at 1 year. Distant control was 38.8% at 1 year, and neither local nor distant control were significantly influenced by limiting steroids to the day of treatment ( = .55, .52 respectively). One-year freedom from high-grade toxicity was 90.4% for patients and 94.6% for tumors. Though melanoma accounted for 41 (55%) patients and 153 (56%) tumors, it accounted for all high-grade toxicities ( = .03). These patients had some combination of high tumor burden, aggressive steroid taper, and treatment with ipilimumab.

Conclusions: Stereotactic radiosurgery combined with anti-PD-1 ICI appears to result in a high rate of local tumor control and a low rate of high-grade CNS toxicity, comparable to historical series with radiosurgery alone. High-grade toxicity is more likely in melanoma than RCC and NSCLC. Coming prospective studies will shed light on further questions about treatment timing, steroids, and response.
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http://dx.doi.org/10.1016/j.adro.2020.08.017DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7897762PMC
September 2020

Transition From Manual to Automated Planning and Delivery of Volumetric Modulated Arc Therapy Stereotactic Radiosurgery: Clinical, Dosimetric, and Quality Assurance Results.

Pract Radiat Oncol 2021 Mar-Apr;11(2):e163-e171. Epub 2021 Feb 23.

Department of Radiation Oncology, The University of Alabama at Birmingham, Birmingham, Alabama.

Purpose: Properly planned single isocenter volumetric modulated arc therapy (VMAT) radiosurgery plans exhibit high quality and efficiency. We report here the largest clinical experience to date, to our knowledge, comparing manual planning with a new automated platform designed to standardize and simplify radiosurgery planning and delivery processes.

Methods: We treated 693 patients with single isocenter VMAT radiosurgical plans generated by either our conventional manual (mVMAT) or a recently implemented automated (HyperArc) technique. All plans targeted the gross tumor volume without margin. Radiochromic film was used for patient-specific quality assurance (PSQA). We evaluated local control and toxicity data for a subgroup of 107 patients having 377 metastatic tumors that were treated with HyperArc.

Results: The median Radiation Therapy Oncology Group (RTOG) conformity index was 1.14 and was not different between the 2 techniques. The median Paddick gradient index was 5.42 for HyperArc versus 7.09 for mVMAT (P < .001). The median mean brain doses were 4.6% and 5.1% for HyperArc and mVMAT, respectively (P = .04). The PSQA for both techniques met clinical criteria, but 97% of the HyperArc plans satisfied the gamma tolerance limit recommended by the American Association of Physicists in Medicine Task Group No. 218, compared with 94% of the mVMAT plans (P = .02). The median treatment-planning times were not significantly different. The median treatment times were 10.5 and 11.4 minutes for HyperArc and mVMAT, respectively (P < .001). The Kaplan-Meier estimate of local control was 90.1% at 1 year.

Conclusions: HyperArc produces high-quality radiosurgical plans that are at least as good as mVMAT plans created by an expert manual planner with easier planning and more efficient delivery workflow. A less experienced planner can produce very high-quality radiosurgical plans even for patients with more than 10 targets. The use of a single-isocenter technique for multiple targets with no PTV margin did not compromise clinical outcomes, and 1-year local control for treated targets remained congruent with historical series.
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http://dx.doi.org/10.1016/j.prro.2020.10.013DOI Listing
August 2021

THE NOVEL USE OF STEREOTACTIC RADIOTHERAPY FOR REMNANT ADRENAL TISSUE IN NELSON SYNDROME.

AACE Clin Case Rep 2020 Jan-Feb;6(1):e33-e36. Epub 2020 Nov 6.

Objective: Recurrent Cushing disease (CD) is a rare complication that occurs in patients who have undergone bilateral adrenalectomy (BLA). We report a case of recurrent CD in a patient with Nelson syndrome and adrenalectomy due to remnant adrenal tissue, and a novel treatment strategy using stereotactic body radiation therapy (SBRT) to the adrenal glands.

Methods: We report a case of recurrent CD in a woman with Nelson syndrome and adrenalectomy and describe her clinical course and management. We also include a literature review of CD management and adrenal radiation.

Results: The patient had persistent pituitary CD despite pituitary surgery and radiosurgery and underwent BLA. She developed recurrent CD due to a remnant adrenal gland post adrenalectomy. She then underwent SBRT to both adrenal beds to treat the remnant adrenal tissue. Her serum cortisol dropped rapidly after adrenal radiation and she experienced minimal side effects. She has been in remission for over 2 years.

Conclusion: This is the first reported case of recurrent CD in a patient post adrenalectomy that was successfully treated with SBRT to the remnant adrenal tissue.
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http://dx.doi.org/10.4158/ACCR-2019-0333DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7279778PMC
November 2020

Surface guided imaging during stereotactic radiosurgery with automated delivery.

J Appl Clin Med Phys 2020 Dec 23;21(12):90-95. Epub 2020 Oct 23.

Department of Radiation Oncology, University of Alabama - Birmingham, Birmingham, AL, USA.

Purpose: To report on the use of surface guided imaging during frameless intracranial stereotactic radiotherapy with automated delivery via HyperArc (Varian Medical Systems, Palo Alto, CA).

Methods: All patients received intracranial radiotherapy with HyperArc and were monitored for intrafraction motion by the AlignRT® (VisionRT, London, UK) surface imaging (SI) system. Immobilization was with the Encompass (Qfix, Avondale, PA) aquaplast mask device. AlignRT® log files were correlated with trajectory log files to correlate treatment parameters with SI reported offsets. SI reported offsets were correlated with gantry angle and analyzed for performance issues at non-zero couch angles and during camera-pod blockage during gantry motion. Demographics in the treatment management system were used to identify race and determine if differences in SI reported offsets are due to skin tone settings.

Results: A total of 981 fractions were monitored over 14 months and 819 were analyzed. The median AlignRT® reported motion from beginning to the end of treatment was 0.24 mm. The median offset before beam on at non-zero couch angles was 0.55 mm. During gantry motion when camera pods are blocked, the median magnitude was below 1 mm. Median magnitude of offsets at non-zero couch angles was not found to be significantly different for patients stratified by race.

Conclusions: Surface image guidance is a viable alternative to scheduled mid-treatment imaging for monitoring intrafraction motion during stereotactic radiosurgery with automated delivery.
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http://dx.doi.org/10.1002/acm2.13066DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7769383PMC
December 2020

Systematic review of anterior congenital cephaloceles: open vs endoscopic repair.

Int Forum Allergy Rhinol 2020 12 27;10(12):1334-1336. Epub 2020 Sep 27.

Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.

Background: Anterior cephaloceles are rare congenital malformations that have historically been corrected via open approaches. Although the advent of endoscopic endonasal surgery has provided a minimally invasive and theoretically less morbid approach to the anterior skull base, whether endoscopic approaches provide superior treatment outcomes to open techniques has yet to be elucidated. The objective of this study was to systematically review the available literature regarding presentation and outcomes of open vs endoscopic repair of congenital anterior cephaloceles.

Methods: A systematic review of the PubMed, Embase, CINAHL, and Cochrane databases was performed on January 15, 2020, to identify studies from the past 50 years reporting cases of congenital anterior cephaloceles. Data on gender, age at operation, imaging modality, cephalocele location, operative approach, and intra- and postoperative complications were collected.

Results: Nonduplicated data (153 articles) consisted of 781 patients with congenital anterior encephaloceles. Surgical outcomes were reported in 349 patients (222 open approaches, 127 endoscopic approaches), with an average age of 4.6 years. There was a 1.3:1 male-to-female ratio. Clinical presentation included nasal obstruction (n = 154), hypertelorism (n = 106), and cleft lip/palate (n = 100). Defects were classified as sincipital (n = 479) or basal (n = 257), with 45 patients broadly classified as anterior. The number of complications experienced per operation was 0.13 for endoscopic and 0.44 for open approaches (p < 0.0001). Mortality was significantly lower for the endoscopic group compared with patients treated with open surgery (0.008 vs 0.05, p < 0.05).

Conclusion: Endoscopic repair of congenital anterior cephaloceles resulted in decreased postoperative complications and mortality compared with open approaches. ©2020 ARSAAOA, LLC.
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http://dx.doi.org/10.1002/alr.22701DOI Listing
December 2020

An Expedited Intracranial Pressure Monitoring Protocol Following Spontaneous CSF Leak Repair.

Laryngoscope 2021 02 14;131(2):E408-E412. Epub 2020 Aug 14.

Department of Otolaryngology - Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, Alabama, U.S.A.

Objective: Spontaneous cerebrospinal fluid (CSF) leaks represent a unique subset of skull base pathology and require distinctive management. Perioperative evaluation and management of intracranial hypertension are essential in preventing further erosion of the skull base and development of recurrent leak. The objective of this study is to evaluate the safety and utility of an expedited protocol for recording and managing intracranial hypertension following endoscopic repair of spontaneous CSF leaks.

Methods: Prospectively collected data was reviewed in patients undergoing endoscopic repair of spontaneous CSF leaks between January 2017 and March 2020. A standard intracranial pressure monitoring protocol was compared to an expedited protocol (EP), and data regarding the two groups was compared for leak location, short-term success of skull base repair, complications, hospital length of stay, and cost-based analysis.

Results: Fifty-five patients (standard protocol, n = 28 vs. EP, n = 27) were included in the study. Leak location was similar between cohorts, with the lateral recess being the most common locations in both groups (37.9% vs. 40.6%; P = .90). Postoperative complications (3.6% vs. 7.4%; P = .53) and ventriculoperitoneal shunt rate (32.1% vs. 22.2%; P = .41) were similar among cohorts. There was no difference in lumbar drain complications (0% vs. 7.4%; P = .14) or recurrent leak (7.1% vs. 0%; P = .16). Length of stay was shorter in the EP group [median(interquartile range): 3(1) vs. 2 (1); P < .01]. Total hospital charges were similar between groups (median (USD/$1,000): 83.57 ± 49.58 vs. 83.93 ± 46.11; P = .18).

Conclusion: An expedited monitoring protocol shortened hospital stay without increased risk of complications.

Level Of Evidence: III Laryngoscope, 131:E408-E412, 2021.
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http://dx.doi.org/10.1002/lary.28929DOI Listing
February 2021

Anticoagulant Medications and Operative Subdural Hematomas: A Retrospective Cohort Study Evaluating Reoperation Rates.

World Neurosurg 2020 11 22;143:e294-e302. Epub 2020 Jul 22.

Neuroscience and Rehabilitation Institute, Orlando Health, Orlando, Florida, USA.

Background: Anticoagulant therapy is common and complicates the operative management of acute and mixed-density subdural hematomas (SDHs). The risk of reoperation inferred by anticoagulant (AC) medication and the ability of reversal agents to reduce hemorrhagic complications in patients presenting with AC-associated SDHs are not fully understood.

Methods: Data were collected for 288 consecutive patients treated with craniotomy or craniectomy for evacuation of an acute or mixed-density SDH between 2012 and 2017 at 2 academic institutions. Primary end points were reoperation within 30 days and functional outcome at discharge. Groups were compared based on AC use. Logistic regression models were used to identify predictors of reoperation and functional outcome at discharge.

Results: Forty-six patients on ACs and 242 with no AC history were analyzed. All patients on AC underwent AC reversal before hematoma evacuation. Reoperation rates between groups were not significantly different (10.9% vs. 12.4%; P = 1.00); however, time to reoperation was significantly shorter in those on ACs (0.8 ± 1.1 days vs. 6.8 ± 10.4 days; P = 0.04). Aspirin use was independently associated with the need for reoperation (odds ratio, 3.05; confidence interval, 1.30-7.19; P = 0.01). Patients taking ACs were significantly older, had more medical comorbidities and were more likely to have a higher modified Rankin Scale score at discharge.

Conclusions: Anticoagulant use was not associated with an increased reoperation rate, suggesting that reversal of AC may have eliminated the hemorrhagic risk conferred by these medications. Patients on ACs were significantly older, harbored more medical comorbidities, and had a worse functional outcome at discharge.
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http://dx.doi.org/10.1016/j.wneu.2020.07.105DOI Listing
November 2020

Preoperative radiographic and clinical factors associated with the visualization of intraoperative cerebrospinal fluid during endoscopic transsphenoidal resection of pituitary adenomas.

Surg Neurol Int 2020 4;11:59. Epub 2020 Apr 4.

Departments of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama.

Background: Intraoperative visualization of cerebrospinal fluid (CSF) during endoscopic endonasal resection of skull base tumors is the most common factor contributing to the development of postoperative CSF leaks. No previous studies have solely evaluated preoperative factors contributing to intraoperative CSF visualization. The purpose of this study was to identify preoperative factors predictive of intraoperative CSF visualization.

Methods: Retrospective review of patients who underwent transsphenoidal resection of pituitary adenomas was conducted. Clinical and radiographic variables were compared for those who had CSF visualized to those who did not. Nominal logistic regression models were built to determine predictive variables.

Results: Two hundred and sixty patients were included in the study. All significant demographic and radiographic variables on univariate analysis were included in multivariate analysis. Two multivariate models were built, as tumor height and supraclinoid extension were collinear. The first model, which considered tumor height, found that extension into the third ventricle carried a 4.60-fold greater risk of CSF visualization ( = 0.005). Increasing tumor height showed a stepwise, linear increase in risk; tumors >3 cm carried a 19.02-fold greater risk of CSF visualization ( = 0.003). The second model, which considered supraclinoid tumor extension, demonstrated that extension into the third ventricle carried a 4.38-fold increase in risk for CSF visualization ( = 0.010). Supraclinoid extension showed a stepwise, linear increase in intraoperative CSF risk; tumors with >2 cm of extension carried a 9.26-fold increase in risk ( = 0.017).

Conclusion: Our findings demonstrate that tumor height, extension into the third ventricle, and extension above the clinoids are predictive of intraoperative CSF visualization.
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http://dx.doi.org/10.25259/SNI_24_2020DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7193202PMC
April 2020

Robot-assisted stereoelectroencephalography exploration of the limbic thalamus in human focal epilepsy: implantation technique and complications in the first 24 patients.

Neurosurg Focus 2020 04;48(4):E2

1Department of Neurology.

Objective: Despite numerous imaging studies highlighting the importance of the thalamus in a patient's surgical prognosis, human electrophysiological studies involving the limbic thalamic nuclei are limited. The objective of this study was to evaluate the safety and accuracy of robot-assisted stereotactic electrode placement in the limbic thalamic nuclei of patients with suspected temporal lobe epilepsy (TLE).

Methods: After providing informed consent, 24 adults with drug-resistant, suspected TLE undergoing evaluation with stereoelectroencephalography (SEEG) were enrolled in the prospective study. The trajectory of one electrode planned for clinical sampling of the operculoinsular cortex was modified to extend it to the thalamus, thereby preventing the need for additional electrode placement for research. The anterior nucleus of the thalamus (ANT) (n = 13) and the medial group of thalamic nuclei (MED) (n = 11), including the mediodorsal and centromedian nuclei, were targeted. The postimplantation CT scan was coregistered to the preoperative MR image, and Morel's thalamic atlas was used to confirm the accuracy of implantation.

Results: Ten (77%) of 13 patients in the ANT group and 10 (91%) of 11 patients in the MED group had electrodes accurately placed in the thalamic nuclei. None of the patients had a thalamic hemorrhage. However, trace asymptomatic hemorrhages at the cortical-level entry site were noted in 20.8% of patients, who did not require additional surgical intervention. SEEG data from all the patients were interpretable and analyzable. The trajectories for the ANT implant differed slightly from those of the MED group at the entry point-i.e., the precentral gyrus in the former and the postcentral gyrus in the latter.

Conclusions: Using judiciously planned robot-assisted SEEG, the authors demonstrate the safety of electrophysiological sampling from various thalamic nuclei for research recordings, presenting a technique that avoids implanting additional depth electrodes or compromising clinical care. With these results, we propose that if patients are fully informed of the risks involved, there are potential benefits of gaining mechanistic insights to seizure genesis, which may help to develop neuromodulation therapies.
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http://dx.doi.org/10.3171/2020.1.FOCUS19887DOI Listing
April 2020

Focal Management of Large Brain Metastases and Risk of Leptomeningeal Disease.

Adv Radiat Oncol 2020 Jan-Feb;5(1):34-42. Epub 2019 Aug 5.

Department of Radiation Oncology, University of Alabama at Birmingham, Birmingham, Alabama.

Purpose: Surgery is often used for large or symptomatic brain metastases but is associated with risk of developing leptomeningeal dissemination. Emerging data suggest that fractionated stereotactic radiation therapy (FSRT) is an effective management strategy in large brain metastases. We sought to retrospectively compare leptomeningeal disease (LMD) and local control (LC) rates for patients treated with surgical resection followed by radiosurgery (S + SRS) versus FSRT alone.

Methods And Materials: We identified all patients with a brain metastasis ≥3 cm in diameter treated from 2004 to 2017 with S + SRS or FSRT alone (25 or 30 Gy in 5 fractions) who had follow-up imaging. LMD was defined as focal or diffuse leptomeningeal enhancement that was >5 mm from the index metastasis. Categorical baseline characteristics were compared with the χ test. LMD and LC rates were evaluated by the Kaplan-Meier (KM) method, with the log-rank test used to compare subgroups.

Results: A total of 125 patients were identified, including 82 and 43 in the S + SRS and FSRT alone groups, respectively. Median pretreatment Graded Prognostic Assessment in the S + SRS and FSRT groups was 2.5 and 1.5, respectively ( < .001). Median follow-up was 7 months. The KM estimate of 12-month LMD rate in the S + SRS and FSRT groups was 45% and 19%, respectively ( = .048). The KM estimate of 12-month local control in the S + SRS and FSRT groups was 70% and 69%, respectively ( = .753). The 12-month KM estimate of grade ≥3 toxicity was 1.4% in S + SRS group versus 6.3% in the FSRT alone group ( = .248). After adjusting for graded prognostic assessment (GPA), no overall survival difference was observed between groups ( = .257).

Conclusions: Surgery is appropriate for certain brain metastases, but S + SRS may increase LMD risk compared with FSRT alone. Because S + SRS and FSRT seem to have similar LC, FSRT may be a viable alternative to S + SRS in select patients with large brain metastases.
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http://dx.doi.org/10.1016/j.adro.2019.07.016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7004932PMC
August 2019

Optimizing therapies for neurobehavioral comorbidities of epilepsy using chronic ambulatory electrocorticography.

Epilepsy Behav 2020 01 2;102:106814. Epub 2019 Dec 2.

Department of Neurology, University of Alabama at Birmingham, AL, United States of America. Electronic address:

There is an unmet need to improve therapy for neuropsychiatric comorbidities that are highly prevalent in persons with epilepsy (PWE). However, diagnosing and monitoring the neurobehavioral symptoms is challenging as their presentation can overlap with seizures. In this retrospective study, we report the advantage of chronic ambulatory electrocorticography (ECoG) from implanted Responsive Neurostimulator System (RNS®) in characterizing these psychosomatic paroxysms as a possible ictal, postictal, or interictal phenomenon and how the diagnosis guided the therapy choices. Five out of 21 patients with RNS had neuropsychiatric symptoms (panic attack, psychosis, conversion, and somatization disorders) that overlapped with their seizure semiology and were found to benefit from the use of RNS ECoG data by timely diagnosing and titrating targeted therapies. The cases illustrate the use of RNS ECoG data in diagnosing and improving the management of comorbidities in PWE. The ability to access RNS ECoG data and correlate it with patient symptoms is unique among available therapeutic options for PWE.
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http://dx.doi.org/10.1016/j.yebeh.2019.106814DOI Listing
January 2020

Long-term seizure freedom following intracranial sEEG monitoring: Therapeutic benefit of a diagnostic technique.

Epilepsy Behav Rep 2019 5;12:100345. Epub 2019 Nov 5.

Department of Neurology, University of Alabama at Birmingham, AL, United States of America.

Patients with treatment-resistant epilepsy often require surgery. It is very rare that patients with TRE can have sustained seizure freedom spontaneously, without undergoing further resection or neuro-modulation after invasive monitoring with sEEG. Of the 78 TRE cases monitored over last 5 years, we identified three patients who became seizure-free following sEEG monitoring without undergoing further resection or neuro-modulation. Seizure-freedom after sEEG is possible even without further intervention. In cases where seizures after the completion of the invasive monitoring are not observed, a longer observation period following electrode explantation prior to planned neuro-modulation or resection is warranted. This could be due to the disruption of the cortical-subcortical epileptogenic network due to focal area of tissue damage along and around the electrode tract.
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http://dx.doi.org/10.1016/j.ebr.2019.100345DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6883308PMC
November 2019

Spectral organization of focal seizures within the thalamotemporal network.

Ann Clin Transl Neurol 2019 09 30;6(9):1836-1848. Epub 2019 Aug 30.

Department of Neurology, University of Alabama at Birmingham, Birmingham, Alabama.

Objective: To investigate dynamic changes in neural activity between the anterior nucleus of the thalamus (ANT) and the seizure onset zone (SOZ) in patients with drug-resistant temporal lobe epilepsy (TLE) based on anatomic location, seizure subtype, and state of vigilance (SOV).

Methods: Eleven patients undergoing stereoelectroencephalography for seizure localization were recruited prospectively for local field potential (LFP) recording directly from the ANT. The SOZ was identified using line length and epileptogenicity index. Changes in power spectral density (PSD) were compared between the two anatomic sites as seizures (N = 53) transitioned from interictal baseline to the posttermination stage.

Results: At baseline, the thalamic LFPs were significantly lower and distinct from the SOZ with the presence of higher power in the fast ripple band (P < 0.001). Temporal changes in ictal power of neural activity within ANT mimic those of the SOZ, are increased significantly at seizure onset (P < 0.05), and are distinct for seizures that impaired awareness or that secondarily generalized (P < 0.05). The onset of seizure was preceded by a decrease in the mean power spectral density (PSD) in ANT and SOZ (P < 0.05). Neural activity correlated with different states of vigilance at seizure onset within the ANT but not in the SOZ (P = 0.005).

Interpretation: The ANT can be recruited at the onset of mesial temporal lobe seizures, and the recruitment pattern differs with seizure subtypes. Furthermore, changes in neural dynamics precede seizure onset and are widespread to involve temporo-thalamic regions, thereby providing an opportunity to intervene early with closed-loop DBS.
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http://dx.doi.org/10.1002/acn3.50880DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6764631PMC
September 2019

Early ictal recruitment of midline thalamus in mesial temporal lobe epilepsy.

Ann Clin Transl Neurol 2019 08 5;6(8):1552-1558. Epub 2019 Jul 5.

Department of Neurology, University of Alabama at Birmingham, Alabama.

The causal role of midline thalamus in the initiation and early organization of mesial temporal lobe seizures is studied. Three patients undergoing stereoelectroencephalography were enrolled for the placement of an additional depth electrode targeting the midline thalamus. The midline thalamus was recruited in all three patients at varying points of seizure initiation (0-13 sec) and propagation (9-60 sec). Stimulation of either thalamus or hippocampus induced similar habitual seizures. Seizure-induced in the hippocampus rapidly recruited the thalamus. Evoked potentials demonstrated stronger connectivity from the hippocampus to the thalamus than in the opposite direction. The midline thalamus can be within the seizure initiation and symptomatogenic circuits.
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http://dx.doi.org/10.1002/acn3.50835DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6689686PMC
August 2019

Factors Associated With Ventriculoperitoneal Shunt Placement in Patients With Cryptococcal Meningitis.

Open Forum Infect Dis 2019 Jun 20;6(6):ofz241. Epub 2019 May 20.

Department of Internal Medicine, Division of Infectious Diseases, University of Alabama at Birmingham.

Objective: Increased intracranial pressure (ICP) is an important complication of cryptococcal meningitis (CM) and impacts morbidity and mortality. Factors associated with permanent ventriculoperitoneal (VP) shunt placement are poorly characterized.

Method: We conducted a retrospective cohort study of patients with CM at the University of Alabama at Birmingham from 1996 through 2015. Characteristics of patients at time of CM diagnosis who did and did not receive a VP shunt were compared with use of the 2-group chi-square test or Fisher exact test for categorical variables and the 2-group test for continuous variables. Stepwise logistic regression analysis was used to determine predictors of shunt placement.

Results: Of 422 patients with cryptococcosis, 257 (60.9%) had CM. Mean age was 47.7 years, 71.6% were male, and 44.4% were African American. The most common underlying conditions were HIV (42.4%), solid organ transplantation (29.6%), and corticosteroid use (34.2%). Forty-four (17.1%) received a VP shunt a median of 17 days (range, 1-320 days) post-diagnosis. By multivariable analysis, baseline opening pressure >30 cm HO (OR, 9.4; 95% CI, 3.0, 28.8; < .0001), being a normal host (OR, 6.3; 95% CI, 1.5, 26.1; = .011) and hydrocephalus (OR, 4.9, 95% CI, 1.3, 17.9); = .017) were associated with increased odds of shunting (Table 2). In contrast, age (OR, 0.96; 95% CI, 0.92, 0.99; = .037) and male gender (OR, 0.18; 95% CI, 0.06, 0.55; = .023) were associated with decreased odds of shunting.

Conclusions: Identification of factors at time of CM diagnosis associated with need for permanent VP shunt placement may allow for earlier, more aggressive treatment and potentially improve outcomes associated with increased ICP from cryptococcal meningitis.
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http://dx.doi.org/10.1093/ofid/ofz241DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6565380PMC
June 2019

Lateral nasal wall extension of the nasoseptal flap for skull-base and medial orbital wall defects.

Int Forum Allergy Rhinol 2019 09 7;9(9):1041-1045. Epub 2019 Jun 7.

Department of Otolaryngology-Head and Neck Surgery, University of Alabama at Birmingham, Birmingham, AL.

Background: Sinonasal and skull-base tumors that previously required open resection can often be completely resected via an endonasal approach. The nasoseptal flap (NSF) is the workhorse vascularized tissue flap for the endoscopic reconstruction of large skull-base defects from tumor resections. The objective of the current article is to describe a novel modification of the NSF for simultaneous reconstruction of skull-base and medial orbital wall defects.

Methods: An extension of the standard NSF to include mucosa of the lateral nasal wall was developed for closure of simultaneous skull-base and medial orbital wall defects. Outcomes including successful cerebrospinal fluid (CSF) leak closure, orbital edema, and postoperative cosmesis are reported. Eyelid edema was characterized according to the Surgeon Periorbital Rating of Edema and Ecchymosis (SPREE) scale.

Results: Three patients underwent reconstruction using the modified NSF (average age 75 years). The average defect size of the skull base was 3.6 ± 0.1 cm by 2.3 ± 0.2 cm. The average defect size of the medial orbit was 2.7 ± 0.1 cm by 2.6 ± 0.1 cm. All defects were successfully covered intraoperatively using the lateral nasal wall extension of the NSF. Two patients developed mild eyelid edema, whereas 1 individual had no noticeable swelling (SPREE classification 2, 2, and 1). All patients were successfully sealed at last clinical follow up (average 28 weeks).

Conclusion: The modification of the NSF described here provides excellent coverage for reconstruction of large anterior skull-base defects and simultaneous medial orbital wall defects.
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http://dx.doi.org/10.1002/alr.22364DOI Listing
September 2019

Ictogenesis during sEEG evaluation after acute intracranial hemorrhage.

Epilepsy Behav Case Rep 2019 7;11:115-119. Epub 2019 Mar 7.

Department of Neurology, University of Alabama at Birmingham, AL, United States of America.

We present a unique case of a patient with drug-resistant focal epilepsy undergoing stereoelectroencephalography (sEEG) who developed an acute posttraumatic intracranial hemorrhage during monitoring, first detected by changes on sEEG. Our case demonstrates the evolution of electrographic changes at the time of initial hemorrhage to the development of ictal activity. We conducted spectral analysis of the sEEG data to illustrate the transition from an interictal to ictal state. Initially, delta power increased in the region of acute hemorrhage, followed by sustained regional reduction in frequency variability. Our findings provide further information on the development of epileptiform activity in acute hemorrhage.
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http://dx.doi.org/10.1016/j.ebcr.2019.02.001DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6434162PMC
March 2019

The centromedian nucleus: Anatomy, physiology, and clinical implications.

J Clin Neurosci 2019 May 28;63:1-7. Epub 2019 Feb 28.

Department of Neurology, University of Alabama at Birmingham, Birmingham, AL, United States.

Of all the truncothalamic nuclei, the centromedian-parafascicular nuclei complex (CM-Pf) is the largest and is considered the prototypic thalamic projection system. Located among the caudal intralaminar thalamic nuclei, the CM-Pf been described by Jones as "the forgotten components of the great loop of connections joining the cerebral cortex via the basal ganglia". The CM, located lateral relative to the Pf, is a major source of direct input to the striatum and also has connections to other, distinct region of the basal ganglia as well as the brainstem and cortex. Functionally, the CM participates in sensorimotor coordination, cognition (e.g. attention, arousal), and pain processing. The role of CM as 'gate control' function by propagating only salient stimuli during attention-demanding tasks has been proposed. Given its rich connectivity and diverse physiologic role, recent studies have explored the CM as potential target for neuromodulation therapy for Tourette syndrome, Parkinson's disease, generalized epilepsy, intractable neuropathic pain, and in restoring consciousness. This comprehensive review summarizes the structural and functional anatomy of the CM and its physiologic role with a focus on clinical implications.
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http://dx.doi.org/10.1016/j.jocn.2019.01.050DOI Listing
May 2019

Antiplatelet Medication and Operative Subdural Hematomas: A Retrospective Cohort Study Evaluating Reoperation Rates.

World Neurosurg 2019 05 5;125:e671-e677. Epub 2019 Feb 5.

Department of Neurosurgery, Geisinger, Danville, Pennsylvania, USA; Research Institute of Neurointervention, Paracelsus Medical University, Salzburg, Austria.

Background: Antiplatelet therapy is common and complicates the operative management of subdural hematomas (SDH). The risk of reoperation inferred by antiplatelet medication and the ability of platelet transfusion to reduce hemorrhagic complications in patients presenting with antiplatelet associated SDHs are poorly defined.

Methods: We performed a retrospective review of consecutive patients treated with craniotomy or craniectomy for evacuation of an acute or mixed-density SDH between 2012 and 2017 at 2 academic institutions. Exclusion criteria included anticoagulant therapy, thrombocytopenia, and/or international normalized ratio >1.3. Clinical and radiographic data were collected; primary endpoint was reoperation within 30 days. Logistic regression models were used to identify predictors of reoperation.

Results: A total of 195 patients were included: 86 patients on antiplatelet medication and 109 with no antithrombotic history. Overall, 24 (12.3%) of patients required a reoperation. Reoperation rate in patients on antiplatelet medication was not significantly different than those not on antithrombotics (14.0% vs. 11.0%, P = 0.53). Patients taking antiplatelet medication were significantly older, more likely to have medical comorbidities, and more likely to receive preoperative platelet transfusion (36.0% vs. 3.7%, P < 0.001). Of patients taking antiplatelet medications, there was no difference in reoperation rate between those patients receiving preoperative platelet transfusion and those not receiving transfusion (16.1% vs. 12.7%, P = 0.75).

Conclusions: Antiplatelet medication was not a significant predictor of reoperation following evacuation of an acute or mixed-density SDH. In patients on antiplatelet medication, preoperative platelet transfusion did not reduce reoperation rates.
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http://dx.doi.org/10.1016/j.wneu.2019.01.151DOI Listing
May 2019

Predictors of Nasoseptal Flap Use After Endoscopic Transsphenoidal Pituitary Mass Resection.

World Neurosurg 2018 Dec 30. Epub 2018 Dec 30.

Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Objective: The pedicled nasoseptal flap (NSF) is the widely accepted reconstructive technique of choice for repair of larger skull base defects after endoscopic endonasal approaches. There is a dearth of literature examining the decision-making process regarding flap harvest. The objective of this study is to evaluate preoperative characteristics that predict the use of NSF reconstruction after endoscopic transsphenoidal resection of pituitary tumors.

Methods: In this retrospective case control study, demographic, clinical, imaging, and procedural details were gathered on all patients undergoing endoscopic transsphenoidal pituitary adenoma resection at a single academic center since January 2009. Characteristics were compared for patients receiving an NSF and those not undergoing NSF repair. A multivariate model that best predicted the use of an NSF was built and a risk score was developed.

Results: Two hundred thirty-eight patients were included, and 39 underwent NSF placement. Tumor size and anatomic characteristics were the predominant factors that significantly differed between cases and controls. Patients with transsellar tumor extension had 6.3 higher odds of requiring NSF, each millimeter increase in tumor height on coronal T1 magnetic resonance imaging increased the odds of NSF use by 1.2. The flap risk score (FRS) is calculated by adding tumor height (mm) to 6 if there is transsellar extension. At an FRS of >35, the FRS is 87% specific and 85% sensitive for flap placement.

Conclusions: Preoperative imaging characteristics can predict NSF use. The FRS can be applied by surgical teams and referring physicians to determine which patients are more likely to undergo NSF repair.
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http://dx.doi.org/10.1016/j.wneu.2018.12.097DOI Listing
December 2018

Modulation of neural oscillations by vagus nerve stimulation in posttraumatic multifocal epilepsy: case report.

J Neurosurg 2018 Nov 1:1-7. Epub 2018 Nov 1.

2Neurology; and.

The putative mechanism of vagus nerve stimulation (VNS) for medically refractory epilepsy is desynchronization of hippocampal and thalamocortical circuitry; however, the nature of the dose-response relationship and temporal dynamics is poorly understood. For greater elucidation, a study in a nonepileptic rat model was previously conducted and showed that rapid-cycle (RC) VNS achieved superior desynchrony compared to standard-cycle (SC) VNS. Here, the authors report on the first in-human analysis of the neuromodulatory dose-response effects of VNS in a patient with posttraumatic, independent, bilateral mesial temporal lobe epilepsy refractory to medications and SC-VNS who was referred as a potential candidate for a responsive neurostimulation device. During stereotactic electroencephalography (SEEG) recordings, the VNS device was initially turned off, then changed to SC-VNS and then RC-VNS settings. Spectral analysis revealed a global reduction of power in the theta (4-8 Hz) and alpha (8-15 Hz) bands with both SC- and RC-VNS compared to the stimulation off setting (p < 0.001). Furthermore, in the alpha band, both SC- and RC-VNS were associated with greater global desynchrony compared to the off setting (p < 0.001); and, specifically, in the bilateral epileptogenic hippocampi, RC-VNS further reduced spectral power compared to SC-VNS (p < 0.001). The dose-response and temporal effects suggest that VNS modulates regional and global dynamics differently.
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http://dx.doi.org/10.3171/2018.6.JNS18735DOI Listing
November 2018

Long-Term Survival After Transformation of an Adrenocorticotropic Hormone-Secreting Pituitary Macroadenoma to a Silent Corticotroph Pituitary Carcinoma.

World Neurosurg 2019 Feb 14;122:417-423. Epub 2018 Nov 14.

Department of Neurosurgery, University of Alabama at Birmingham, Birmingham, Alabama, USA.

Background: Pituitary carcinomas are rare and aggressive neoplasms that despite current treatment regimens continue to have a poor prognosis. Adrenocorticotrophic hormone pituitary tumors have been shown to alter their clinical manifestations with conversion to Cushing disease and silent types.

Case Description: The purpose of this paper is to present the first documented case of an adrenocorticotrophic hormone-secreting pituitary adenoma with Cushing disease that differentiated into a silent corticotroph pituitary carcinoma with metastases to distant sites in the central nervous system.

Conclusions: This patient was later treated with radiotherapy, temozolomide, and bevacizumab, with 8 years of progression-free survival.
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http://dx.doi.org/10.1016/j.wneu.2018.11.011DOI Listing
February 2019

In Response to In Reference to Intervention for Elevated Intracranial Pressure Improves Success Rate After Repair of Spontaneous Cerebrospinal Fluid Leaks.

Laryngoscope 2018 Sep 19. Epub 2018 Sep 19.

Department of Neurosurgery, University of Alabama Birmingham, Birmingham, Alabama, U.S.A.

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http://dx.doi.org/10.1002/lary.27139DOI Listing
September 2018

Auras localized to the temporal lobe disrupt verbal memory and learning - Causal evidence from direct electrical stimulation of the hippocampus.

Epilepsy Behav Case Rep 2018 3;10:99-101. Epub 2018 Aug 3.

Department of Neurology, University of Alabama at Birmingham, AL, United States of America.

Auras (focal aware seizure; FAS) are subjective ictal events with retained consciousness. Epileptiform activities can disrupt cognitive tasks, but studies are limited to seizures with impaired awareness. As a proof of concept, we examined the cognitive effects of direct electrical stimulation to the left hippocampus which induced a habitual FAS in a patient with left mesial temporal lobe epilepsy. During the induced habitual FAS, verbal memory performance declined significantly as compared to pre-stimulation testing. Tasks measuring auditory working memory and psychomotor processing speed were not affected by the stimulation. The study confirms that FAS can impair episodic verbal memory and learning.
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http://dx.doi.org/10.1016/j.ebcr.2018.07.006DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6120344PMC
August 2018

Automated detection of mesial temporal and temporoperisylvian seizures in the anterior thalamic nucleus.

Epilepsy Res 2018 10 23;146:17-20. Epub 2018 Jul 23.

Department of Neurology, University of Alabama at Birmingham, AL, United States; Epilepsy and Cognitive Neurophysiology Laboratory, University of Alabama at Birmingham, AL, United States. Electronic address:

Background And Purpose: Focal seizures can arise from coordinated activity across large-scale epileptic networks and propagate to regions that are not functionally altered but are recruited by epileptiform discharges. In preclinical models of focal epilepsy, the thalamus is recruited by cortical onset seizures, but it remains to be demonstrated in clinical studies. In this pilot study, the authors investigate whether seizures with onset within and outside the mesial temporal structures are detected in the anterior thalamus (ATN).

Methods: After written consent, three subjects with suspected temporal lobe epilepsy undergoing stereotactic electrode implantation were recruited prospectively for thalamocortical depth EEG recordings. Three seizure detection metrics (line length-LL, Laplace operator-Lap; Teager energy-TE) were studied within the seizure onset zone and ATN.

Results: The LL, Lap, and TE metrics detected 40 (95%) seizures each in the ATN before the behavioral manifestation. Rates of detection in the seizure onset zone were 40 (95%), 42 (100%), and 41 (98%), respectively. The mean detection latency in ATN from SOZ ranged from 0.25 to 5.17 s. Seizures were localized to amygdala-hippocampus, temporal pole, anterior insula and superior temporal gyrus.

Conclusions: The pilot study demonstrates that seizures in mesial temporal and temporal-plus epilepsies (i.e., temporoperisylvian) can be detected reliably in the ATN. Further studies are needed to validate these findings.
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http://dx.doi.org/10.1016/j.eplepsyres.2018.07.014DOI Listing
October 2018

Porcine small intestine submucosal grafts improve remucosalization and progenitor cell recruitment to sites of upper airway tissue remodeling.

Int Forum Allergy Rhinol 2018 10 1;8(10):1162-1168. Epub 2018 Jun 1.

Department of Otolaryngology-Head and Neck Surgery, University of Alabama Birmingham, Birmingham, AL.

Background: To better understand upper airway tissue regeneration, the exposed cartilage and bone at donor sites of tissue flaps may serve as in vivo "Petri dishes" for active wound healing. The pedicled nasoseptal flap (NSF) for skull-base reconstruction creates an exposed donor site within the nasal airway. The objective of this study is to evaluate whether grafting the donor site with a sinonasal repair cover graft is effective in promoting wound healing.

Methods: In this multicenter, prospective trial, subjects were randomized to intervention (graft) or control (no graft) intraoperatively after NSF elevation. Individuals were evaluated at 2, 6, and 12 weeks postintervention with endoscopic recordings. Videos were graded (Likert scale) by 3 otolaryngologists blinded to intervention on remucosalization, crusting, and edema. Scores were analyzed for interrater reliability and cohorts compared. Biopsy and immunohistochemistry at the leading edge of wound healing was performed in select cases.

Results: Twenty-one patients were randomized to intervention and 26 to control. Subjects receiving the graft had significantly greater overall remucosalization (p = 0.01) than controls over 12 weeks. Although crusting was less in the small intestine submucosa (SIS) group, this was not statistically significant (p = 0.08). There was no overall effect on nasal edema (p = 0.2). Immunohistochemistry demonstrated abundant upper airway basal cell progenitors in 2 intervention samples, suggesting that covering grafts may facilitate tissue proliferation via progenitor cell expansion.

Conclusion: This prospective, randomized, controlled trial indicates that a porcine SIS graft placed on exposed cartilage and bone within the upper airway confers improved remucosalization compared to current practice standards.
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http://dx.doi.org/10.1002/alr.22156DOI Listing
October 2018
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