Publications by authors named "Ethan G Brown"

20 Publications

  • Page 1 of 1

The TOPAZ study: a home-based trial of zoledronic acid to prevent fractures in neurodegenerative parkinsonism.

NPJ Parkinsons Dis 2021 Mar 1;7(1):16. Epub 2021 Mar 1.

Department of Medicine, Duke University School of Medicine, VA Medical Center, Durham, NC, USA.

The Trial of Parkinson's And Zoledronic acid (TOPAZ, https://clinicaltrials.gov/ct2/show/NCT03924414 ) is a unique collaboration between experts in movement disorders and osteoporosis to test the efficacy of zoledronic acid, an FDA-approved parenteral treatment for osteoporosis, for fracture prevention in people with neurodegenerative parkinsonism. Aiming to enroll 3,500 participants age 65 years or older, TOPAZ is one of the largest randomized, placebo-controlled clinical trials ever attempted in parkinsonism. The feasibility of TOPAZ is enhanced by its design as a U.S.- wide home-based trial without geographical limits. Participants receive information from multiple sources, including specialty practices, support groups and websites. Conducting TOPAZ in participants' homes takes advantage of online consent technology, the capacity to confirm diagnosis using telemedicine and the availability of research nursing to provide screening and parenteral therapy in homes. Home-based clinical research may provide an efficient, convenient, less expensive method that opens participation in clinical trials to almost anyone with parkinsonism.
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http://dx.doi.org/10.1038/s41531-021-00162-1DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7921548PMC
March 2021

DBS targeting for essential tremor using intersectional dentato-rubro-thalamic tractography and direct proton density visualization of the VIM: technical note on 2 cases.

J Neurosurg 2021 Jan 15:1-9. Epub 2021 Jan 15.

1Department of Neurological Surgery, Weill Institute for Neurosciences, University of California, San Francisco.

Objective: Direct visualization of the ventral intermediate nucleus (VIM) of the thalamus on standard MRI sequences remains elusive. Therefore, deep brain stimulation (DBS) surgery for essential tremor (ET) indirectly targets the VIM using atlas-derived consensus coordinates and requires awake intraoperative testing to confirm clinical benefits. The objective of this study was to evaluate the utility of proton density (PD)-weighted MRI and tractography of the intersecting dentato-rubro-thalamic tract (DRTT) for direct "intersectional" targeting of the VIM in ET.

Methods: DBS targets were selected by identifying the VIM on PD-weighted images relative to the DRTT in 2 patients with ET. Tremor reduction was confirmed with intraoperative clinical testing. Intended target coordinates based on the direct intersectional targeting technique were compared with consensus coordinates obtained with indirect targeting. Pre- and postoperative tremor scores were assessed using the Fahn-Tolosa-Marin tremor rating scale (TRS).

Results: Planned DBS coordinates based on direct versus indirect targeting of the VIM differed in both the anteroposterior (range 0 to 2.3) and lateral (range -0.7 to 1) directions. For 1 patient, indirect targeting-without PD-weighted visualization of the VIM and DRTT-would have likely resulted in suboptimal electrode placement within the VIM. At the 3-month follow-up, both patients demonstrated significant improvement in tremor symptoms subjectively and according to the TRS (case 1: 68%, case 2: 72%).

Conclusions: Direct intersectional targeting of the VIM using PD-weighted imaging and DRTT tractography is a feasible method for DBS placement in patients with ET. These advanced targeting techniques can supplement awake intraoperative testing or be used independently in asleep cases to improve surgical efficiency and confidence.
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http://dx.doi.org/10.3171/2020.8.JNS201378DOI Listing
January 2021

Modulation of the Microbiome in Parkinson's Disease: Diet, Drug, Stool Transplant, and Beyond.

Neurotherapeutics 2020 10 9;17(4):1406-1417. Epub 2020 Oct 9.

Division of Movement Disorders and Neuromodulation, Weill Institute of Neurology, University of California, San Francisco, CA, USA.

The gastrointestinal microbiome is altered in Parkinson's disease and likely plays a key role in its pathophysiology, affecting symptoms and response to therapy and perhaps modifying progression or even disease initiation. Gut dysbiosis therefore has a significant potential as a therapeutic target in Parkinson's disease, a condition elusive to disease-modifying therapy thus far. The gastrointestinal environment hosts a complex ecology, and efforts to modulate the relative abundance or function of established microorganisms are still in their infancy. Still, these techniques are being rapidly developed and have important implications for our understanding of Parkinson's disease. Currently, modulation of the microbiome can be achieved through non-pharmacologic means such as diet, pharmacologically through probiotic, prebiotic, or antibiotic use and procedurally through fecal transplant. Novel techniques being explored include the use of small molecules or genetically engineered organisms, with vast potential. Here, we review how some of these approaches have been used to date, important areas of ongoing research, and how microbiome modulation may play a role in the clinical management of Parkinson's disease in the future.
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http://dx.doi.org/10.1007/s13311-020-00942-2DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7851230PMC
October 2020

The Effect of the COVID-19 Pandemic on People with Parkinson's Disease.

J Parkinsons Dis 2020 ;10(4):1365-1377

Department of Neurology, Weill Institute for the Neurosciences, University of California San Francisco, & San Francisco VA Health Care System, San Francisco, CA, USA.

Background: The effect of the COVID-19 pandemic on people with Parkinson's disease (PD) is poorly understood.

Objective: To rapidly identify areas of need and improve care in people with PD during the COVID-19 pandemic, we deployed a survey to assess COVID-19 symptoms and the pandemic's effect among those with and without COVID-19.

Methods: People with and without PD participating in the online study Fox Insight (FI) were invited to complete a survey between April 23 and May 23, 2020. Among people reporting COVID-19 diagnoses, we compared symptoms and outcomes in people with and without PD. Among people not reporting COVID-19, we assessed access to healthcare and services and PD symptoms.

Results: 7,209/9,762 active FI users responded (approximately 74% response rate), 5,429 people with PD and 1,452 without PD. COVID-19 diagnoses were reported by 51 people with and 26 without PD. Complications were more frequent in people with longer PD duration. People with PD and COVID-19 experienced new or worsening motor (63%) and nonmotor (75%) symptoms. People with PD not diagnosed with COVID-19 reported disrupted medical care (64%), exercise (21%), and social activities (57%), and worsened motor (43%) and non-motor (52%) symptoms. Disruptions were more common for those living alone, with lower income and non-White race.

Conclusions: The COVID-19 pandemic is associated with wide-ranging effects on people with PD, and certain groups may be at particular risk. FI provides a rapid, patient-centered means to assess these effects and identify needs that can be used to improve the health of people with PD.
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http://dx.doi.org/10.3233/JPD-202249DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7683050PMC
November 2020

Medical education in movement disorders during the COVID-19 pandemic.

Parkinsonism Relat Disord 2020 08 15;77:11-12. Epub 2020 Jun 15.

Department of Neurology, University of California, San Francisco, United States.

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http://dx.doi.org/10.1016/j.parkreldis.2020.06.013DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7295506PMC
August 2020

The Visual Word Form Area compensates for auditory working memory dysfunction in schizophrenia.

Sci Rep 2020 06 1;10(1):8881. Epub 2020 Jun 1.

Department of Radiology and Biomedical Imaging, University of California, San Francisco, San Francisco, CA, United States.

Auditory working memory impairments feature prominently in schizophrenia. However, the existence of altered and perhaps compensatory neural dynamics, sub-serving auditory working memory, remains largely unexplored. We compared the dynamics of induced high gamma power (iHGP) across cortex in humans during speech-sound working memory in individuals with schizophrenia (SZ) and healthy comparison subjects (HC) using magnetoencephalography (MEG). SZ showed similar task performance to HC while utilizing different brain regions. During encoding of speech sounds, SZ lacked the correlation of iHGP with task performance in posterior superior temporal gyrus (STGp) that was observed in healthy subjects. Instead, SZ recruited the visual word form area (VWFA) during both stimulus encoding and response preparation. Importantly, VWFA activity during encoding correlated with the magnitude of SZ hallucinations, task performance and an independent measure of verbal working memory. These findings suggest that VWFA plasticity is harnessed to compensate for STGp dysfunction in schizophrenia patients with hallucinations.
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http://dx.doi.org/10.1038/s41598-020-63962-0DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7264140PMC
June 2020

Cerebellar Deep Brain Stimulation for Acquired Hemidystonia.

Mov Disord Clin Pract 2020 Feb 8;7(2):188-193. Epub 2020 Jan 8.

Movement Disorders and Neuromodulation Center, Department of Neurology University of California San Francisco San Francisco California USA.

Background: The cerebellum's role in dystonia is increasingly recognized. Dystonia can be a disabling and refractory condition; deep brain stimulation can help many patients, but it is traditionally less effective in acquired dystonia. New surgical targets would be instrumental in providing treatment options and understanding dystonia further.

Objective: To evaluate the efficacy of deep brain stimulation of the cerebellum in acquired dystonia.

Methods: We report our management of a 37-year-old woman with severe left arm and leg dystonia, a complication of an ischemic stroke in childhood. She had already had 2 thalamotomies with only transient benefit. These procedures, in addition to her initial stroke that had damaged the basal ganglia, left traditional deep brain stimulation targets unavailable.

Results: After implantation of bilateral deep cerebellar nuclei, dystonia improved with a 40% reduction in severity on scales and subjective reports of improved posturing, gait, and pain. This improvement has been maintained for almost 2 years after implantation.

Conclusion: Cerebellar stimulation has potential for therapeutic benefit in acquired dystonia and should be further explored.
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http://dx.doi.org/10.1002/mdc3.12876DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7011833PMC
February 2020

Traumatic brain injury and α-synuclein: Proceed with caution.

Neurology 2020 02 28;94(8):335-336. Epub 2020 Jan 28.

From the University of California, San Francisco.

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http://dx.doi.org/10.1212/WNL.0000000000008991DOI Listing
February 2020

Intervention-specific patterns of cortical function plasticity during auditory encoding in people with schizophrenia.

Schizophr Res 2020 01 21;215:241-249. Epub 2019 Oct 21.

Department of Radiology and Biomedical Imaging, University of California San Francisco, United States; UCB-UCSF Graduate Program in Bioengineering, University of California, Berkeley, United States.

Schizophrenia is a neurocognitive illness characterized by behavioral and neural impairments in both early auditory processing and higher order verbal working memory. Previously we have shown intervention-specific cognitive performance improvements with computerized, targeted training of auditory processing (AT) when compared to a computer games (CG) control intervention that emphasized visual processing. To investigate spatiotemporal changes in patterns of neural activity specific to the AT intervention, the current study used magnetoencephalography (MEG) imaging to derive induced high gamma band oscillations (HGO) during auditory encoding, before and after 50 h (∼10 weeks) of exposure to either the AT or CG intervention. During stimulus encoding, AT intervention-specific changes in high gamma activity occurred in left middle frontal and left middle-superior temporal cortices. In contrast, CG intervention-specific changes were observed in right medial frontal and supramarginal gyri during stimulus encoding, and in bilateral temporal cortices during response preparation. These data reveal that, in schizophrenia, intensive exposure to either training of auditory processing or exposure to visuospatial activities produces significant but complementary patterns of cortical function plasticity within a distributed fronto-temporal network. These results underscore the importance of delineating the specific neuroplastic effects of targeted behavioral interventions to ensure desired neurophysiological changes and avoid unintended consequences on neural system functioning.
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http://dx.doi.org/10.1016/j.schres.2019.10.022DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7035971PMC
January 2020

Mendel and urate: Acid test or random noise?

Parkinsonism Relat Disord 2018 08 7;53:1-3. Epub 2018 Aug 7.

Department of Neurology, University of California - San Francisco, San Francisco, CA, USA; Department of Neurology, Weil Institute for Neurosciences, University of California - San Francisco, San Francisco, CA, USA; Parkinson's Disease Research, Education and Clinical Center, San Francisco Veterans Affairs Health Care System, San Francisco, CA, USA. Electronic address:

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http://dx.doi.org/10.1016/j.parkreldis.2018.08.005DOI Listing
August 2018

Evaluation of a multicomponent pathway to address inpatient delirium on a neurosciences ward.

BMC Health Serv Res 2018 02 12;18(1):106. Epub 2018 Feb 12.

Department of Neurology, University of California, San Francisco, CA, USA.

Background: Delirium is a frequent and detrimental complication of inpatient hospitalization. Multicomponent intervention in selected groups has been shown to prevent and treat delirium, though little data exists on the effect of intervention in neurological patients. We studied the efficacy of a multicomponent delirium care pathway implemented on a largely neurology and neurosurgery hospital ward among unselected patients.

Methods: We incorporated a multicomponent delirium care pathway into the workflow of a university hospital for patients older than 50 years. The pathway involved risk-stratification for development of delirium, delirium screening, and non-pharmacologic behavioral prevention and intervention. We then retrospectively reviewed admissions before and after implementation of the care pathway. Our primary endpoint was incidence of delirium; secondary endpoints included delirium days, length of stay, restraint use, readmission rates, and discharge disposition.

Results: Seven hundred ninety eight admissions from before the delirium care pathway went into effect and 797 admissions from afterwards were reviewed. Baseline characteristics between groups were similar. Delirium incidence between the two groups did not change (7.0% before vs 7.2% after, p = 0.89). Length of stay among delirious patients significantly decreased after implementation of the delirium care pathway (9.60 before vs 7.06 after, β = - 0.16, adjusted p-value = 0.001).

Conclusion: Implementation of a delirium care pathway on a neurosciences ward was not associated with changes in the rate of delirium development, though length of stay among delirious patients decreased. In a largely neurologic population, multicomponent intervention to prevent and treat delirium may not change delirium incidence, but may be effective in mitigating delirium complications.
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http://dx.doi.org/10.1186/s12913-018-2906-3DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC5809949PMC
February 2018

Impaired Cognition and the Risk of Parkinson Disease: Trouble in Mind.

JAMA Neurol 2017 12;74(12):1398-1400

Movement Disorders and Neuromodulation Center, Department of Neurology, University of California, San Francisco.

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http://dx.doi.org/10.1001/jamaneurol.2017.1474DOI Listing
December 2017

Predicting inpatient delirium: The AWOL delirium risk-stratification score in clinical practice.

Geriatr Nurs 2017 Nov - Dec;38(6):567-572. Epub 2017 May 19.

Department of Neurology, University of California, San Francisco, USA. Electronic address:

Inpatient delirium improves with multicomponent interventions by hospital staff, though the resources needed are often limited. Risk-stratification to predict delirium is a useful first step to help triage resources, but the performance of risk-stratification as part of a functioning multicomponent pathway has not been assessed. We retrospectively studied the performance of a validated delirium prediction rule, the AWOL score, as a part of a multicomponent delirium care pathway in practice on a university hospital ward. We reviewed the hospitalizations of patients 50 years or older for evidence of delirium and extracted the AWOL score from nursing documentation (n = 347). The area under the receiver operating characteristic curve (AUC) was 0.83 (95% CI 0.77-0.89) for all cases and 0.73 (95% CI 0.60-0.85) when cases of prevalent delirium were removed. Involving minimal additional assessment, this nursing-based risk stratification score performed well as part of a multicomponent delirium care pathway.
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http://dx.doi.org/10.1016/j.gerinurse.2017.04.006DOI Listing
February 2018

Confirmed case of levamisole-associated multifocal inflammatory leukoencephalopathy in a cocaine user.

J Neuroimmunol 2017 04 2;305:128-130. Epub 2017 Feb 2.

University of California, San Francisco, Department of Neurology, San Francisco, CA, USA.

Levamisole is a common adulterant in cocaine and has previously been associated with a variety of serious complications including multifocal inflammatory leukoencephalopathy (MIL). There have been several reports of MIL in patients taking cocaine and, though suspected, the presence of levamisole was not confirmed. We present a case of a 63-year-old woman presenting with stupor and spastic quadraparesis found to have urine positive for cocaine and levamisole. An MRI brain revealed innumerable FLAIR hyperintensities with restricted diffusion and incomplete ring-enhancement. This is the first case to confirm the presence of levamisole in a patient with MIL associated with cocaine use.
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http://dx.doi.org/10.1016/j.jneuroim.2017.01.018DOI Listing
April 2017

The Contribution of the Corpus Callosum to Language Lateralization.

J Neurosci 2016 Apr;36(16):4522-33

Department of Radiology and Biomedical Imaging,

Unlabelled: The development of hemispheric lateralization for language is poorly understood. In one hypothesis, early asymmetric gene expression assigns language to the left hemisphere. In an alternate view, language is represented a priori in both hemispheres and lateralization emerges via cross-hemispheric communication through the corpus callosum. To address this second hypothesis, we capitalized on the high temporal and spatial resolution of magnetoencephalographic imaging to measure cortical activity during language processing, speech preparation, and speech execution in 25 participants with agenesis of the corpus callosum (AgCC) and 21 matched neurotypical individuals. In contrast to strongly lateralized left hemisphere activations for language in neurotypical controls, participants with complete or partial AgCC exhibited bilateral hemispheric activations in both auditory or visually driven language tasks, with complete AgCC participants showing significantly more right hemisphere activations than controls or than individuals with partial AgCC. In AgCC individuals, language laterality positively correlated with verbal IQ. These findings suggest that the corpus callosum helps to drive language lateralization.

Significance Statement: The role that corpus callosum development has on the hemispheric specialization of language is poorly understood. Here, we used magnetoencephalographic imaging during linguistic tests (verb generation, picture naming) to test for hemispheric dominance in patients with agenesis of the corpus callosum (AgCC) and found reduced laterality (i.e., greater likelihood of bilaterality or right hemisphere dominance) in this cohort compared with controls, especially in patients with complete agenesis. Laterality was positively correlated with behavioral measures of verbal intelligence. These findings provide support for the hypothesis that the callosum aids in functional specialization throughout neural development and that the loss of this mechanism correlates with impairments in verbal performance.
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http://dx.doi.org/10.1523/JNEUROSCI.3850-14.2016DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4837685PMC
April 2016

Moving Beyond Metabolic Encephalopathy: An Update on Delirium Prevention, Workup, and Management.

Semin Neurol 2015 Dec 23;35(6):646-55. Epub 2015 Nov 23.

Department of Neurology, University of California, San Francisco, California.

Delirium is a condition that frequently complicates hospitalization and consists of an acute decline in orientation and attention, often accompanied by other cognitive changes. Delirium is tied to multiple detrimental outcomes both in the short and long term, including cognitive and functional decline, inpatient complications, and mortality. Postoperative, elderly medical, and critical care patients have been identified as populations at particular risk. In this review, the authors discuss current theories on pathophysiology, recommended workup, and evidence-based prevention and management of inpatient delirium. In general, instituting a system of active screening of at-risk populations and nonpharmacologic interventions for prevention and treatment seems to be the most effective method of addressing delirium. More research is needed to clarify the etiology of delirium and develop safe therapeutic options that address the underlying pathophysiology.
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http://dx.doi.org/10.1055/s-0035-1564685DOI Listing
December 2015

Auditory Cortical Plasticity Drives Training-Induced Cognitive Changes in Schizophrenia.

Schizophr Bull 2016 Jan 6;42(1):220-8. Epub 2015 Jul 6.

Northern California Institute for Research and Education (NCIRE), San Francisco Veterans' Affairs Medical Center, San Francisco, CA; Department of Psychiatry, University of California, San Francisco, San Francisco, CA;

Schizophrenia is characterized by dysfunction in basic auditory processing, as well as higher-order operations of verbal learning and executive functions. We investigated whether targeted cognitive training of auditory processing improves neural responses to speech stimuli, and how these changes relate to higher-order cognitive functions. Patients with schizophrenia performed an auditory syllable identification task during magnetoencephalography before and after 50 hours of either targeted cognitive training or a computer games control. Healthy comparison subjects were assessed at baseline and after a 10 week no-contact interval. Prior to training, patients (N = 34) showed reduced M100 response in primary auditory cortex relative to healthy participants (N = 13). At reassessment, only the targeted cognitive training patient group (N = 18) exhibited increased M100 responses. Additionally, this group showed increased induced high gamma band activity within left dorsolateral prefrontal cortex immediately after stimulus presentation, and later in bilateral temporal cortices. Training-related changes in neural activity correlated with changes in executive function scores but not verbal learning and memory. These data suggest that computerized cognitive training that targets auditory and verbal learning operations enhances both sensory responses in auditory cortex as well as engagement of prefrontal regions, as indexed during an auditory processing task with low demands on working memory. This neural circuit enhancement is in turn associated with better executive function but not verbal memory.
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http://dx.doi.org/10.1093/schbul/sbv087DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4681549PMC
January 2016

Immediate Hemorrhagic Transformation After Intravenous Tissue-Type Plasminogen Activator Injection in 2 Cocaine Users.

Stroke 2015 Jul 28;46(7):e167-9. Epub 2015 Apr 28.

From the Department of Neurology, University of California, San Francisco (M.O.B., E.G.B., N.S.S., J.C.H.); and Department of Neurology, San Francisco General Hospital, CA (N.S.S., J.C.H.).

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http://dx.doi.org/10.1161/STROKEAHA.115.008687DOI Listing
July 2015

Rescuing the physical exam.

Wilderness Environ Med 2010 Jun 22;21(2):172-3. Epub 2009 Dec 22.

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http://dx.doi.org/10.1016/j.wem.2009.12.013DOI Listing
June 2010
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