Browsing by Author "Adler, Charles H."

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    Feasibility and Safety of Multicenter Tissue and Biofluid Sampling for α-Synuclein in Parkinson's Disease: The Systemic Synuclein Sampling Study (S4)
    (IOS Press, 2018) Chahine, Lana M.; Beach, Thomas G.; Seedorff, Nicholas; Caspell-Garcia, Chelsea; Coffey, Christopher S.; Brumm, Michael; Adler, Charles H.; Serrano, Geidy E.; Linder, Carly; Mosovsky, Sherri; Foroud, Tatiana; Riss, Holly; Ecklund, Dixie; Seibyl, John; Jennings, Danna; Arnedo, Vanessa; Riley, Lindsey; Dave, K.D.; Mollenhauer, Brit; SystemicSynuclein Sampling study; Medical and Molecular Genetics, School of Medicine
    BACKGROUND: α-synuclein is a lead Parkinson's disease (PD) biomarker. There are conflicting reports regarding accuracy of α-synuclein in different tissues and biofluids as a PD biomarker, and the within-subject anatomical distribution of α-synuclein is not well described. The Systemic Synuclein Sampling Study (S4) aims to address these gaps in knowledge. The S4 is a multicenter, cross-sectional, observational study evaluating α-synuclein in multiple tissues and biofluids in PD and healthy controls (HC). OBJECTIVE: To describe the baseline characteristics of the S4 cohort and safety and feasibility of this study. METHODS: Participants underwent motor and non-motor clinical assessments, dopamine transporter SPECT, biofluid collection (cerebrospinal fluid, saliva, and blood), and tissue biopsies (skin, sigmoid colon, and submandibular gland). Biopsy adequacy was determined based on presence of adequate target tissue. Tissue sections were stained with the 5C12 monoclonal antibody against unmodified α-synuclein. All specimens were acquired and processed in a standardized manner. Adverse events were systematically recorded. RESULTS: The final cohort consists of 82 participants (61 PD, 21 HC). In 68 subjects (83%), all types of specimens were obtained but only 50 (61%) of subjects had all specimens both collected and evaluable for α-synuclein. Mild adverse events were common, especially for submandibular gland biopsy, but only 1 severe adverse event occurred. CONCLUSION: Multicenter tissue and biofluid sampling for α-synuclein is feasible and generally safe. S4 will inform understanding of the concurrent distribution of α-synuclein pathology and biomarkers in biofluids and peripheral nervous system in PD.
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    National Institute of Neurological Disorders and Stroke Consensus Diagnostic Criteria for Traumatic Encephalopathy Syndrome
    (Wolters Kluwer, 2021) Katz, Douglas I.; Bernick, Charles; Dodick, David W.; Mez, Jesse; Mariani, Megan L.; Adler, Charles H.; Alosco, Michael L.; Balcer, Laura J.; Banks, Sarah J.; Barr, William B.; Brody, David L.; Cantu, Robert C.; Dams-O’Connor, Kristen; Geda, Yonas E.; Jordan, Barry D.; McAllister, Thomas W.; Peskind, Elaine R.; Petersen, Ronald C.; Wethe, Jennifer V.; Zafonte, Ross D.; Foley, Éimear M.; Babcock, Debra J.; Koroshetz, Walter J.; Tripodis, Yorghos; McKee, Ann C.; Shenton, Martha E.; Cummings, Jeffrey L.; Reiman, Eric M.; Stern, Robert A.; Psychiatry, School of Medicine
    Objective: To develop evidence-informed, expert consensus research diagnostic criteria for traumatic encephalopathy syndrome (TES), the clinical disorder associated with neuropathologically diagnosed chronic traumatic encephalopathy (CTE). Methods: A panel of 20 expert clinician-scientists in neurology, neuropsychology, psychiatry, neurosurgery, and physical medicine and rehabilitation, from 11 academic institutions, participated in a modified Delphi procedure to achieve consensus, initiated at the First National Institute of Neurological Disorders and Stroke Consensus Workshop to Define the Diagnostic Criteria for TES, April, 2019. Before consensus, panelists reviewed evidence from all published cases of CTE with neuropathologic confirmation, and they examined the predictive validity data on clinical features in relation to CTE pathology from a large clinicopathologic study (n = 298). Results: Consensus was achieved in 4 rounds of the Delphi procedure. Diagnosis of TES requires (1) substantial exposure to repetitive head impacts (RHIs) from contact sports, military service, or other causes; (2) core clinical features of cognitive impairment (in episodic memory and/or executive functioning) and/or neurobehavioral dysregulation; (3) a progressive course; and (4) that the clinical features are not fully accounted for by any other neurologic, psychiatric, or medical conditions. For those meeting criteria for TES, functional dependence is graded on 5 levels, ranging from independent to severe dementia. A provisional level of certainty for CTE pathology is determined based on specific RHI exposure thresholds, core clinical features, functional status, and additional supportive features, including delayed onset, motor signs, and psychiatric features. Conclusions: New consensus diagnostic criteria for TES were developed with a primary goal of facilitating future CTE research. These criteria will be revised as updated clinical and pathologic information and in vivo biomarkers become available.