Publications by authors named "Ashesh A Thaker"

12 Publications

  • Page 1 of 1

Persistent visual dysfunction following posterior reversible encephalopathy syndrome due to COVID-19: Case series and literature review.

Eur J Neurol 2021 10 29;28(10):3289-3302. Epub 2021 Jun 29.

Department of Ophthalmology, University of Colorado School of Medicine, Aurora, CO, USA.

Background And Purpose: The full spectrum of neurological sequelae in COVID-19 is beginning to emerge. SARS-CoV-2 has the potential to cause both direct and indirect brain vascular endothelial damage through infection and inflammation that may result in long-term neurological signs and symptoms. We sought to illuminate persistent neuro-ophthalmological deficits that may be seen following posterior reversible encephalopathy syndrome (PRES) due to COVID-19.

Methods: We identified three individuals with PRES due to COVID-19 in our hospital system. One patient was identified on presentation to our neuro-ophthalmology clinic. The other patients were identified through internal records search. These cases were compared to published reports of PRES in COVID-19 identified through systematic literature search of PubMed/LitCOVID.

Results: All three patients were hospitalized with severe COVID-19 and developed altered mental status with new onset seizures that led to the recognition of PRES through diagnostic imaging. During recovery, two patients had persistent visual dysfunction including visual field deficits. One patient also experienced hallucinatory palinopsia and visual hallucinations. Literature search identified 32 other cases of PRES in the context of COVID-19. Visual disturbances were described in 14 cases (40%), with only seven cases (50%) reporting full recovery by the time of publication.

Conclusions: As we learn about enduring neurological complications of COVID-19, it is possible that complications may be underrecognized and underreported. Understanding the range of complications can help in postcare evaluation and management changes in the critical care setting to potentially allow intervention before persistent deficits occur due to COVID-19.
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http://dx.doi.org/10.1111/ene.14965DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8444757PMC
October 2021

New-onset seizures in adults: Low diagnostic yield of gadolinium contrast in initial brain MRI evaluation.

J Neuroimaging 2021 Sep 10;31(5):874-878. Epub 2021 Jun 10.

Department of Radiology, University of Colorado Hospital, Aurora, Colorado, USA.

Background And Purpose: The diagnostic utility of contrast MR-imaging in adult new-onset seizures without clinically suspected neoplasia or infection is not well defined in the literature. Imaging guidelines consider both contrast and noncontrast MR-imaging examinations appropriate in this clinical scenario. The purpose of this study was to evaluate the utility of contrast MR-sequences in evaluation of seizure in patients without suspicion for neoplasia or infection.

Methods: Imaging and clinical data were reviewed for 103 consecutive patients admitted for phase-1 seizure monitoring with the following criteria: (1) MRI-brain performed with/without intravenous contrast; (2) no clinical suspicion for central nervous system (CNS) infection; and (3) no history of CNS neoplasia, or suspected metastatic disease. Readers designated cases as lesional or nonlesional. Lesional cases were further categorized as either visualized on noncontrast sequences only, contrast sequences only, or both.

Results: 29/103 (28%) patients had epileptogenic lesions, 74/103 (72%) were nonlesional studies. 29/29 (100%) lesional abnormalities were detected on noncontrast sequences (sensitivity 100% [95 confidence interval (CI): 88-100], specificity 100% [95 CI: 95-100]). 23/29 (79.3%) lesional cases were visualized on both noncontrast and postcontrast sequences. 6/29 (20.7%) were visualized only on noncontrast sequences. No lesional cases were detected exclusively on postcontrast MR sequences. With an observed nonlesional extraneous contrast MR-imaging rate of 72%, estimated excess cost of contrast MR-imaging per 1000 patients using Medicare data was $103,680 USD.

Conclusions: Contrast MR-imaging has limited diagnostic utility in initial screening of adult new-onset seizure patients without clinically suspected neoplasia or infection. More judicious use of contrast MR-imaging in this patient population may reduce unnecessary exposure to gadolinium and lower associated healthcare costs.
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http://dx.doi.org/10.1111/jon.12897DOI Listing
September 2021

Coronal Gradient Echo MRI to Visualize the Zona Incerta for Deep Brain Stimulation Targeting in Parkinson's Disease.

Stereotact Funct Neurosurg 2021 26;99(5):443-450. Epub 2021 Apr 26.

Department of Neurology, University of Colorado Anschutz Medical Campus, Aurora, Colorado, USA.

Introduction: Deep brain stimulation of the zona incerta is effective at treating tremor and other forms of parkinsonism. However, the structure is not well visualized with standard MRI protocols making direct surgical targeting unfeasible and contributing to inconsistent clinical outcomes. In this study, we applied coronal gradient echo MRI to directly visualize the rostral zona incerta in Parkinson's disease patients to improve targeting for deep brain stimulation.

Methods: We conducted a prospective study to optimize and evaluate an MRI sequence to visualize the rostral zona incerta in patients with Parkinson's disease (n = 31) and other movement disorders (n = 13). We performed a contrast-to-noise ratio analysis of specific regions of interest to quantitatively assess visual discrimination of relevant deep brain structures in the optimized MRI sequence. Regions of interest were independently assessed by 2 neuroradiologists, and interrater reliability was assessed.

Results: Rostral zona incerta and subthalamic nucleus were well delineated in our 5.5-min MRI sequence, indicated by excellent interrater agreement between neuroradiologists for region-of-interest measurements (>0.90 intraclass coefficient). Mean contrast-to-noise ratio was high for both rostral zona incerta (6.39 ± 3.37) and subthalamic nucleus (17.27 ± 5.61) relative to adjacent white matter. There was no significant difference between mean signal intensities or contrast-to-noise ratio for Parkinson's and non-Parkinson's patients for either structure.

Discussion/conclusion: Our optimized coronal gradient echo MRI sequence delineates subcortical structures relevant to traditional and novel deep brain stimulation targets, including the zona incerta, with high contrast-to-noise. Future studies will prospectively apply this sequence to surgical planning and postimplantation outcomes.
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http://dx.doi.org/10.1159/000515772DOI Listing
October 2021

Astrogliosis and episodic memory in late life: higher GFAP is related to worse memory and white matter microstructure in healthy aging and Alzheimer's disease.

Neurobiol Aging 2021 07 26;103:68-77. Epub 2021 Feb 26.

Department of Neurology, University of Colorado Alzheimer's & Cognition Center, Linda Crnic Institute for Down Syndrome, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.

Astrocytes play a formative role in memory consolidation during physiological conditions; when dysregulated, astrocytes release glial fibrillary acidic protein (GFAP), which has been linked with negative memory outcomes in animal studies. We examined the association between blood GFAP, memory, and white matter (WM) integrity, accounting for blood markers of AD pathology (i.e., Aβ42) and neurodegeneration (i.e., total tau; neurofilament light chain) in 114 older adults (asymptomatic, n = 69; MCI/AD dementia, n = 45). Higher levels of GFAP were associated with lower memory scores (p < 0.0001), such that for 1 SD increase in mean GFAP values, the memory composite score decreased on average by 0.49 (Standard error = 0.071). These results remained significant after controlling for diagnostic status and AD-related blood biomarkers. Higher GFAP was also related to lower WM integrity in regions vulnerable to AD pathology; however, WM integrity did not account for the association between GFAP and memory. Study findings suggest that higher blood levels of a marker of astrogliosis may reflect impoverished memory functions and white matter health, independent of markers of amyloid or neurodegeneration.
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http://dx.doi.org/10.1016/j.neurobiolaging.2021.02.012DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8313091PMC
July 2021

Safety and efficacy of sargramostim (GM-CSF) in the treatment of Alzheimer's disease.

Alzheimers Dement (N Y) 2021 24;7(1):e12158. Epub 2021 Mar 24.

Department of Neurology University of Colorado School of Medicine Aurora Colorado USA.

Introduction: Inflammatory markers have long been observed in the brain, cerebrospinal fluid (CSF), and plasma of Alzheimer's disease (AD) patients, suggesting that inflammation contributes to AD and might be a therapeutic target. However, non-steroidal anti-inflammatory drug trials in AD and mild cognitive impairment (MCI) failed to show benefit. Our previous work seeking to understand why people with the inflammatory disease rheumatoid arthritis are protected from AD found that short-term treatment of transgenic AD mice with the pro-inflammatory cytokine granulocyte-macrophage colony-stimulating factor (GM-CSF) led to an increase in activated microglia, a 50% reduction in amyloid load, an increase in synaptic area, and improvement in spatial memory to normal. These results called into question the consensus view that inflammation is solely detrimental in AD. Here, we tested our hypothesis that modulation of the innate immune system might similarly be used to treat AD in humans by investigating the ability of GM-CSF/sargramostim to safely ameliorate AD symptoms/pathology.

Methods: A randomized, double-blind, placebo-controlled trial was conducted in mild-to-moderate AD participants (NCT01409915). Treatments (20 participants/group) occurred 5 days/week for 3 weeks plus two follow-up (FU) visits (FU1 at 45 days and FU2 at 90 days) with neurological, neuropsychological, blood biomarker, and imaging assessments.

Results: Sargramostim treatment expectedly changed innate immune system markers, with no drug-related serious adverse events or amyloid-related imaging abnormalities. At end of treatment (EOT), the Mini-Mental State Examination score of the sargramostim group increased compared to baseline ( = .0074) and compared to placebo ( = .0370); the treatment effect persisted at FU1 ( = .0272). Plasma markers of amyloid beta (Aβ40 [decreased in AD]) increased 10% ( = .0105); plasma markers of neurodegeneration (total tau and UCH-L1) decreased 24% ( = .0174) and 42% ( = .0019), respectively, after sargramostim treatment compared to placebo.

Discussion: The innate immune system is a viable target for therapeutic intervention in AD. An extended treatment trial testing the long-term safety and efficacy of GM-CSF/sargramostim in AD is warranted.
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http://dx.doi.org/10.1002/trc2.12158DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7988877PMC
March 2021

Quantitative FDG PET asymmetry features predict long-term seizure recurrence in refractory epilepsy.

Epilepsy Behav 2021 03 21;116:107714. Epub 2021 Jan 21.

Center for Neuroengineering and Therapeutics, University of Pennsylvania, 240 Skirkanich Hall, 210 S 33rd St, Philadelphia, PA 19104, United States; Department of Neurology, Hospital of the University of Pennsylvania, 3400 Spruce St, 3 West Gates Bldg, Philadelphia, PA 19104, United States. Electronic address:

Objective: Fluorodeoxyglucose-positron emission tomography (FDG-PET) is an established, independent, strong predictor of surgical outcome in refractory epilepsy. In this study, we explored the added value of quantitative [F]FDG-PET features combined with clinical variables, including electroencephalography (EEG), [F]FDG-PET, and magnetic resonance imaging (MRI) qualitative interpretations, to predict long-term seizure recurrence (mean post-op follow-up of 5.85 ± 3.77 years).

Methods: Machine learning predictive models of surgical outcome were created using a random forest classifier trained on quantitative features in 89 patients with drug-refractory temporal lobe epilepsy evaluated at the Hospital of the University of Pennsylvania epilepsy surgery program (2003-2016). Quantitative features were calculated from asymmetry features derived from image processing using Advanced Normalization Tools (ANTs).

Results: The best-performing model used quantification and had an out-of-bag accuracy of 0.71 in identifying patients with seizure recurrence (Engel IB or worse) which outperformed that using qualitative clinical data by 10%. This model is shared through open-source software for research use. In addition, several asymmetry features in temporal and extratemporal regions that were significantly associated with seizure freedom are identified for future study.

Significance: Complex quantitative [F]FDG-PET imaging features can predict seizure recurrence in patients with refractory temporal lobe epilepsy. These initial retrospective results in a cohort with long-term follow-up suggest that using quantitative imaging features from regions in the epileptogenic network can inform the clinical decision-making process.
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http://dx.doi.org/10.1016/j.yebeh.2020.107714DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC8344068PMC
March 2021

Frontiers in Neuroscience Imaging: Whole-Body PET.

PET Clin 2021 Jan 5;16(1):137-146. Epub 2020 Nov 5.

Division of Nuclear Medicine and Clinical Molecular Imaging, Perelman School of Medicine at the University of Pennsylvania, 3400 Spruce Street, 1 Silverstein, Philadelphia, PA 19104, USA. Electronic address:

Since its inception, PET imaging of the nervous system and neuropsychiatric disease has focused on the brain. Although this has resulted in many important contributions to basic science and clinical medicine, PET has not been used to explore nervous system physiology and disease throughout the remainder of the body. Our understanding of neurologic disorders has also changed during this period, and we are beginning to realize that many neuropsychiatric diseases manifest throughout the entire body. Thus, whole-body PET imaging with the Explorer instrument represents an exciting tool to address important questions in pathophysiology and develop novel pharmacologic strategies.
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http://dx.doi.org/10.1016/j.cpet.2020.09.014DOI Listing
January 2021

The predictive value of preoperative apparent diffusion coefficient (ADC) for facial nerve outcomes after vestibular schwannoma resection: clinical study.

Acta Neurochir (Wien) 2020 08 21;162(8):1995-2005. Epub 2020 May 21.

Department of Neurosurgery, University of Colorado School of Medicine, Aurora, CO, 80045, USA.

Object: Diffusion MRI has been used to predict intraoperative consistency of tumors. Apparent diffusion coefficient (ADC) has shown predictive value as an imaging biomarker in many CNS tumors but has not been studied in a large cohort of patients with vestibular schwannoma. In this study, we examine the utility of ADC as a predictive biomarker for intraoperative tumor characteristics and postoperative facial nerve outcome.

Methods: A retrospective review of patients who underwent vestibular schwannoma resection at our institution from 2008 to 2018 yielded 87 patients, of which 72 met inclusion criteria. Operative reports and clinical records were reviewed for clinical data; MRI data were interpreted in a blinded fashion for qualitative and quantitative biomarkers, including tumor ADC.

Results: Mean tumor ADC values did not predict intraoperative consistency or adherence (p = 0.63). Adherent tumors were associated with worse facial nerve outcomes (p = 0.003). Regression tree analysis identified 3 ADC categories with statistically different facial nerve outcomes. The categories identified were ADC < 1006.04 × 10 mms; ADC 1006.04-1563.93 × 10 mms and ADC ≥ 1563.94 × 10 mms. Postoperative and final House-Brackmann (HB) scores were significantly higher in the intermediate ADC group (2.3, p = 0.0038). HB outcomes were similar between the group with ADC < 1006.04 × 10 mms and ≥ 1563.94 × 10 mms (1.3 vs 1.3).

Conclusions: Middle-range preoperative ADC in vestibular schwannoma suggests a less favorable postoperative HB score. Preoperative measurement of ADC in vestibular schwannoma may provide additional information regarding prognostication of facial nerve outcomes.
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http://dx.doi.org/10.1007/s00701-020-04338-1DOI Listing
August 2020

Beyond the embolus: "do not miss" diffusion abnormalities of ischaemic and non-ischaemic neurological disease.

Insights Imaging 2017 Dec 6;8(6):573-580. Epub 2017 Oct 6.

Department of Radiology, University of Colorado School of Medicine, Aurora, CO, 80045, USA.

Given the rapid evolution and technological advances in the diagnosis and treatment of acute ischaemic stroke (AIS), including the proliferation of comprehensive stroke centres and increasing emphasis on interventional stroke therapies, the need for prompt recognition of stroke due to acute large vessel occlusion has received significant attention in the recent literature. Diffusion-weighted imaging (DWI) is the gold standard for the diagnosis of acute ischaemic stroke, as images appear positive within minutes of ischaemic injury, and a high signal-to-noise ratio enables even punctate infarcts to be readily detected. DWI lesions resulting from a single arterial embolic occlusion or steno-occlusive lesion classically lateralise and conform to a specific arterial territory. When there is a central embolic source (e.g. left atrial thrombus), embolic infarcts are often found in multiple vascular territories. However, ischaemic disease arising from aetiologies other than arterial occlusion will often not conform to an arterial territory. Furthermore, there are several important entities unrelated to ischaemic disease that can present with abnormal DWI and which should not be confused with infarct. This pictorial review explores the scope and typical DWI findings of select neurologic conditions beyond acute arterial occlusion, which should not be missed or misinterpreted.

Teaching Points: • DWI abnormalities due to acute arterial occlusion must be promptly identified. • DWI abnormalities not due to arterial occlusion will often not conform to an arterial territory. • Several important non-ischaemic entities can present on DWI and should not be confused with infarct.
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http://dx.doi.org/10.1007/s13244-017-0574-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5707221PMC
December 2017

Natalizumab-induced progressive multifocal leukoencephalopathy.

Clin Nucl Med 2014 Jul;39(7):e365-6

From the Department of *Radiology; and †Neurology, Hospital of the University of Pennsylvania, Philadelphia, PA.

A 55-year-old woman with known relapsing-remitting multiple sclerosis (RRMS) on natalizumab (Tysabri®) for 3 years was admitted to the hospital with worsening word-finding difficulties and gait instability. Neurologic examination revealed right hemianopia, right arm hemiplegia, right-sided sensory loss, and global aphasia. The patient underwent MRI and PET imaging with concurrent electroencephalogram. She was subsequently diagnosed with natalizumab-induced progressive multifocal leukoencephalopathy (PML) and treated with plasmapheresis, intravenous immunoglobulin, and high-dose intravenous steroids. Steroids were continued over a 3-month hospital course and tapered upon discharge. Speech, arm strength, and ambulation have since improved.
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http://dx.doi.org/10.1097/RLU.0000000000000238DOI Listing
July 2014

Ectopic functioning adrenocortical oncocytic adenoma (oncocytoma) with myelolipoma causing virilization.

Case Rep Pathol 2012 10;2012:326418. Epub 2012 Oct 10.

Department of Pathology and Laboratory Medicine, The Hospital of the University of Pennsylvania, Philadelphia, PA 19104, USA.

Functioning adrenal adenomas are well-described entities that can rarely occur outside the adrenal gland in the ectopic adrenal tissue. Similarly, myelolipoma is an another benign lesion of the adrenal tissue which can rarely occur outside the adrenal gland. We report the first case of a testosterone producing an extra-adrenal adrenocortical oncocytoma accompanied by a myelolipoma. The patient presented with virilization and elevated androgen levels. Imaging revealed a retroperitoneal mass, which histologically consisted of oncocytes and intermingled myelolipoma. Postoperative androgen levels decreased to normal. The tumor cells were strongly positive for inhibin and Melan-A, supporting the adrenal origin. This case demonstrates a diagnostic challenge in which correlation with histology, immunohistochemistry, and serum endocrine studies led to the final diagnosis.
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http://dx.doi.org/10.1155/2012/326418DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3474228PMC
October 2012

Combination therapy of radiofrequency ablation and bevacizumab monitored with power Doppler ultrasound in a murine model of hepatocellular carcinoma.

Int J Hyperthermia 2012 8;28(8):766-75. Epub 2012 Oct 8.

Center for Interventional Oncology, Radiology and Imaging Sciences, Clinical Center, National Cancer Institute, National Institutes of Health, Bethesda, MD 20892, USA.

Purpose: The purpose of this study was to monitor tumour blood flow with power Doppler ultrasound following antiangiogenic therapy with bevacizumab in order to optimally time the application of radiofrequency (RF) ablation to increase ablation diameter.

Materials And Methods: Athymic nude mice bearing human hepatocellular carcinoma xenografts were treated with bevacizumab and imaged daily with power Doppler ultrasound to quantify tumour blood flow. Mice were treated with RF ablation alone or in combination with bevacizumab at the optimal time, as determined by ultrasound. Ablation diameter was measured with histology and tumour microvascular density was calculated with immunohistochemistry. A computational thermal model of RF ablation was used to estimate ablation volume.

Results: A maximum reduction of 27.8 ± 8.6% in tumour blood flow occurred on day 2 following antiangiogenic therapy, while control tumours increased 29.3 ± 17.1% (p < 0.05). Tumour microvascular density was similarly reduced by 45.1 ± 5.9% on day 2 following antiangiogenic therapy. Histology demonstrated a 13.6 ± 5.6% increase in ablation diameter (40 ± 21% increase in volume) consistent with a computational model.

Conclusion: Quantitative power Doppler ultrasound is a useful biomarker to monitor tumour blood flow following antiangiogenic treatment and to guide the application of RF ablation as a drug plus device combination therapy.
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http://dx.doi.org/10.3109/02656736.2012.724517DOI Listing
April 2013
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