Progressive Ataxia and Palatal Tremor: Two Autopsy Cases of a Novel Tauopathy Andrew F. Gao, MD, 1 Achinoam Faust-Socher, MD, 2 Maryam Al-Murshed, MD, 3 Marc R. Del Bigio, MD, PhD, 4,5 Anthony E. Lang, MD, 2,6 and David G. Munoz, MD, MSc 1,7 * 1 Department of Laboratory Medicine and Pathobiology, University of Toronto, Toronto, ON, Canada 2 Morton and Gloria Shulman Movement Disorders Centre, Toronto Western Hospital, Toronto, ON, Canada 3 Department of Laboratory Medicine and Pathology, University Health Network, Toronto, ON, Canada 4 Diagnostic Services Manitoba, Winnipeg, MB, Canada 5 Department of Pathology, University of Manitoba, Winnipeg, MB, Canada 6 Division of Neurology, Dept. of Medicine, University of Toronto, Toronto, ON, Canada 7 Department of Laboratory Medicine, St. Michael’s Hospital, Toronto, ON, Canada ABSTRACT: Background: Sporadic progressive ataxia and palatal tremor is a rare syndrome characterized by mid- to late-adult-onset symptomatic palatal tremor and slowly progressive cerebellar ataxia. To date, there has been only one autopsy report, which described a novel 4-repeat tauopathy with hypertrophic olivary degen- eration and tau-positive inclusions in olivary neurons and dystrophic neuritic processes termed glomeruloid bodies. We report on 2 additional autopsy cases. Methods: Sections from selected paraffin-embedded brain regions were stained with hematoxylin and eosin/ Luxol fast blue and processed for phosphorylated tau, 3-repeat tau, 4-repeat tau, neurofilament, glial fibrillary acid protein, phosphorylated a-synuclein, phosphory- lated TAR DNA-binding protein 43, beta-amyloid, and p62 immunohistochemistry. Results: Two male patients were aged 74 and 64 years at onset. Both had clinical findings consistent with progres- sive ataxia and palatal tremor and T2 hyperintensity in the bilateral olives on MRI. Pathological findings included bilateral hypertrophic olivary degeneration accompanied by glomeruloid bodies, 3-repeat and 4-repeat tau-positive neuronal inclusions in the olive, and additional tauopathy in the midbrain, pons, and thalamus. Cerebellar cortical degeneration was extensive, but involvement of the den- tate was minimal. P62-positive, but tau- and TAR DNA- binding protein 43–negative, inclusions in the cerebellum of 1 case was also a feature. Conclusions: Whereas our findings are largely in keep- ing with the previously published case report, we found a more extensive and mixed 3/4-repeat tauopathy and additional cerebellar p62 pathology, highlighting our incomplete understanding of the pathogenesis of this disease. VC 2017 International Parkinson and Movement Disorder Society Key Words: ataxia; palatal tremor; PAPT; tauopathy; hypertrophic olivary degeneration Progressive ataxia and palatal tremor (PAPT) is a subtype of symptomatic palatal tremor (SPT), the latter associated with lesions of the brainstem or cere- bellum (within the dentato-rubro-olivary pathway [DROP] or Guillain-Mollaret triangle). 1,2 In contrast to other forms of SPT, in PAPT, ataxia progresses and is not usually the result of a monophasic illness. PAPT can be divided into familial and sporadic forms. Familial causes include Alexander’s disease, polymer- ase gamma mutations, spinocerebellar ataxia type 20, and GM2 gangliosidosis. 3-7 Sporadic PAPT is a poorly understood progressive neurodegenerative disorder with onset in mid to late adulthood. 8 Clinical features include palatal tremor (often incidental), visual disturbance, gait and limb ataxia, dysarthria, dyspha- gia, and other noncerebellar/brainstem associated symptoms, such as autonomic involvement. Brain MRI findings include increased signal intensity on ------------------------------------------------------------ *Correspondence to: Dr. David G. Munoz, Department of Laboratory Medicine, St. Michael’s Hospital, Room 2CC-097, 30 Bond Street, Toronto, ON, Canada, M5B 1W8; E-mail: munozd@smh.ca Relevant conflicts of interest/financial disclosures: Nothing to report. Full financial disclosures and author roles may be found in the online ver- sion of this article. Received: 26 January 2017; Revised: 15 April 2017; Accepted: 14 May 2017 Published online 00 Month 2017 in Wiley Online Library (wileyonlinelibrary.com). DOI: 10.1002/mds.27074 RESEARCH ARTICLE Movement Disorders, Vol. 00, No. 00, 2017 1