{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,20]],"date-time":"2026-10-20T15:30:34Z","timestamp":1792510234243,"version":"4.5.0"},"reference-count":49,"publisher":"Oxford University Press (OUP)","issue":"1","license":[{"start":{"date-parts":[[2024,2,21]],"date-time":"2024-02-21T00:00:00Z","timestamp":1708473600000},"content-version":"vor","delay-in-days":55,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"MINDlink Foundation"},{"DOI":"10.13039\/100028898","name":"Raynor Cerebellum Project","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100028898","id-type":"DOI","asserted-by":"publisher"}]},{"name":"Ms. Mary Jo Reston"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2023,12,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n               <jats:p>Definitive diagnosis of multiple system atrophy of the cerebellar type (MSA-C) is challenging. We hypothesized that rates of change of pons and middle cerebellar peduncle diameters on MRI would be unique to MSA-C and serve as diagnostic biomarkers. We defined the normative data for anterior\u2013posterior pons and transverse middle cerebellar peduncle diameters on brain MRI in healthy controls, performed diameter\u2013volume correlations and measured intra- and inter-rater reliability. We studied an Exploratory cohort (2002\u20132014) of 88 MSA-C and 78 other cerebellar ataxia patients, and a Validation cohort (2015\u20132021) of 49 MSA-C, 13 multiple system atrophy of the parkinsonian type (MSA-P), 99 other cerebellar ataxia patients and 314 non-ataxia patients. We measured anterior\u2013posterior pons and middle cerebellar peduncle diameters on baseline and subsequent MRIs, and correlated results with Brief Ataxia Rating Scale scores. We assessed midbrain:pons and middle cerebellar peduncle:pons ratios over time. The normative anterior\u2013posterior pons diameter was 23.6 \u00b1 1.6\u2005mm, and middle cerebellar peduncle diameter 16.4 \u00b1 1.4\u2005mm. Pons diameter correlated with volume, r = 0.94, P &amp;lt; 0.0001. The anterior\u2013posterior pons and middle cerebellar peduncle measures were smaller at first scan in MSA-C compared to all other ataxias; anterior\u2013posterior pons diameter: Exploratory, 19.3 \u00b1 2.6\u2005mm versus 20.7 \u00b1 2.6\u2005mm, Validation, 19.9 \u00b1 2.1\u2005mm versus 21.1 \u00b1 2.1\u2005mm; middle cerebellar peduncle transverse diameter, Exploratory, 12.0 \u00b1 2.6\u2005mm versus 14.3 \u00b12.1\u2005mm, Validation, 13.6 \u00b1 2.1\u2005mm versus 15.1 \u00b1 1.8\u2005mm, all P &amp;lt; 0.001. The anterior\u2013posterior pons and middle cerebellar peduncle rates of change were faster in MSA-C than in all other ataxias; anterior\u2013posterior pons diameter rates of change: Exploratory, \u22120.87 \u00b1 0.04\u2005mm\/year versus \u22120.09 \u00b1 0.02\u2005mm\/year, Validation, \u22120.89 \u00b1 0.48\u2005mm\/year versus \u22120.10 \u00b1 0.21\u2005mm\/year; middle cerebellar peduncle transverse diameter rates of change: Exploratory, \u22120.84 \u00b1 0.05\u2005mm\/year versus \u22120.08 \u00b1 0.02\u2005mm\/year, Validation, \u22120.94 \u00b1 0.64\u2005mm\/year versus \u22120.11 \u00b1 0.27\u2005mm\/year, all values P &amp;lt; 0.0001. Anterior\u2013posterior pons and middle cerebellar peduncle diameters were indistinguishable between Possible, Probable and Definite MSA-C. The rate of anterior\u2013posterior pons atrophy was linear, correlating with ataxia severity. Using a lower threshold anterior\u2013posterior pons diameter decrease of \u22120.4\u2005mm\/year to balance sensitivity and specificity, area under the curve analysis discriminating MSA-C from other ataxias was 0.94, yielding sensitivity 0.92 and specificity 0.87. For the middle cerebellar peduncle, with threshold decline \u22120.5\u2005mm\/year, area under the curve was 0.90 yielding sensitivity 0.85 and specificity 0.79. The midbrain:pons ratio increased progressively in MSA-C, whereas the middle cerebellar peduncle:pons ratio was almost unchanged. Anterior\u2013posterior pons and middle cerebellar peduncle diameters were smaller in MSA-C than in MSA-P, P &amp;lt; 0.001. We conclude from this 20-year longitudinal clinical and imaging study that anterior\u2013posterior pons and middle cerebellar peduncle diameters are phenotypic imaging biomarkers of MSA-C. In the correct clinical context, an anterior\u2013posterior pons and transverse middle cerebellar peduncle diameter decline of \u223c0.8\u2005mm\/year is sufficient for and diagnostic of MSA-C.<\/jats:p>","DOI":"10.1093\/braincomms\/fcae019","type":"journal-article","created":{"date-parts":[[2024,2,19]],"date-time":"2024-02-19T21:56:04Z","timestamp":1708379764000},"source":"Crossref","is-referenced-by-count":9,"title":["Rates of change of pons and middle cerebellar peduncle diameters are diagnostic of multiple system atrophy of the cerebellar type"],"prefix":"10.1093","volume":"6","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-4727-192X","authenticated-orcid":false,"given":"Christopher D","family":"Stephen","sequence":"first","affiliation":[{"name":"Ataxia Center, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114 , USA"},{"name":"Cognitive Behavioral Neurology Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114 , 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USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jason P","family":"MacMore","sequence":"additional","affiliation":[{"name":"Ataxia Center, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114 , USA"},{"name":"Cognitive Behavioral Neurology Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114 , USA"},{"name":"Laboratory for Neuroanatomy and Cerebellar Neurobiology, Department of Neurology, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114 , USA"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-0706-5125","authenticated-orcid":false,"given":"Jeremy D","family":"Schmahmann","sequence":"additional","affiliation":[{"name":"Ataxia Center, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114 , USA"},{"name":"Cognitive Behavioral Neurology Unit, Massachusetts General Hospital and Harvard Medical School , Boston, MA 02114 , 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