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Progressive Supranuclear Palsy and Primary Lateral Sclerosis Secondary Neurocase The Neural Basis of Cognition ISSN: 1355-4794 (Print) 1465-3656 (Online) Journal homepage: https://www.tandfonline.com/loi/nncs20 Progressive supranuclear palsy and primary lateral sclerosis secondary to globular glial tauopathy: a case report and a practical theoretical framework for the clinical prediction of this rare pathological entity Andy J. Liu, Jessica E. Chang, Georges Naasan, Adam L. Boxer, Bruce L. Miller & Salvatore Spina To cite this article: Andy J. Liu, Jessica E. Chang, Georges Naasan, Adam L. Boxer, Bruce L. Miller & Salvatore Spina (2020): Progressive supranuclear palsy and primary lateral sclerosis secondary to globular glial tauopathy: a case report and a practical theoretical framework for the clinical prediction of this rare pathological entity, Neurocase, DOI: 10.1080/13554794.2020.1732427 To link to this article: https://doi.org/10.1080/13554794.2020.1732427 Published online: 23 Feb 2020. Submit your article to this journal Article views: 19 View related articles View Crossmark data Full Terms & Conditions of access and use can be found at https://www.tandfonline.com/action/journalInformation?journalCode=nncs20 NEUROCASE https://doi.org/10.1080/13554794.2020.1732427 Progressive supranuclear palsy and primary lateral sclerosis secondary to globular glial tauopathy: a case report and a practical theoretical framework for the clinical prediction of this rare pathological entity Andy J. Liua, Jessica E. Changb, Georges Naasana, Adam L. Boxera, Bruce L. Millera and Salvatore Spinaa aMemory and Aging Center, Department of Neurology, University of California San Francisco, San Francisco, CA, USA; bDepartment of Psychological Services, San Francisco Veterans Affairs Medical Center, San Francisco, CA, USA ABSTRACT ARTICLE HISTORY Globular glial tauopathy (GGT) is a rare 4-repeat tauopathy characterized by the accumulation of tau Received 28 May 2019 globular inclusions in astrocytes and oligodendrocytes. Several clinical phenotypes have been associated Accepted 12 February 2020 ffi with GGT, making the prediction of this rare pathological entity di cult. We report the case of a patient KEYWORDS with eye-movement abnormalities and gait instability, reminiscent of progressive supranuclear palsy- Globular glial tauopathy; Richardson’s syndrome (PSP-RS), who later developed upper motor neuron symptoms suggestive of primary lateral sclerosis; primary lateral sclerosis (PLS). Neuropathological assessment revealed GGT type III pathology. frontotemporal dementia; A theoretical framework is proposed to help clinicians predict GGT in subjects with coexistent features progressive supranuclear of PSP-RS and PLS. palsy; neuropathology Introduction GGT which includes bvFTD, nonfluent variant PPA, semantic variant PPA, and primary lateral sclerosis (PLS) among others, Frontotemporal lobar degenerations (FTLDs) are neurodegen- together with a variable extent of extrapyramidal motor fea- erative diseases predominately affecting the frontal and tem- tures (Ahmed et al., 2013;Burrelletal.,2016;Ferreretal.,2014; poral lobes of the brain, associated with progressive changes in Graff-Radford et al., 2016;Kimetal.,2017; Zarranz et al., 2005). behavior, language, and executive function. Patients may Subsequently, predicting a neuropathological diagnosis of develop motor deficits consistent with parkinsonism and/or GGT based on clinical manifestations proves challenging. In motor neuron disease (Bang, Spina, & Miller, 2015). FTLDs are addition, prediction of pathology could be particularly diffi- classified into neuropathological subtypes according to the cult in patients with PLS, because of the shared selective main protein that accumulates in the brain of affected indivi- vulnerabilityofthemotorcortexandcorticospinaltractsin duals, the three most common of which are TDP-43, tau, and GGT, PSP, and motor neuron disease (MND) secondary to TDP- FUS, as well as on the basis of the cellular and morphological 43 pathology (Ahmed et al., 2013; Josephs et al., 2006; characteristics of these inclusions (Mackenzie et al., 2011). FTLD Neumann et al., 2006). may present clinically as behavioral variant frontotemporal PLS is a clinical syndrome under the umbrella spectrum of dementia (bvFTD), primary progressive aphasia (PPA), cortico- motor neuron diseases, characterized by early predominant basal syndrome, and progressive supranuclear palsy (PSP). upper motor neuron degeneration with weakness, spasticity, Because of the extensive anatomical, pathological, and clinical and absence of symptoms of lower motor neuron degeneration overlap between the various FTLD subtypes, the prediction of during the first four years of disease course (Gordon et al., a specific neuropathological substrate in vivo, given any clinical 2006). The definition of PLS as a distinct clinicopathological presentation, remains complex (Perry et al., 2017). entity from amyotrophic lateral sclerosis (ALS) is controversial, Globular glial tauopathy (GGT) is a rare FTLD subtype char- since a large proportion of PLS patients eventually develop acterized by the presence of tau-immunoreactive (tau-ir) glob- signs of LMN disease later in the disease course. Nevertheless, ular inclusions in astrocytes and oligodendrocytes. The a clinical diagnosis of PLS may be predictive of a slow disease inclusions are composed by hyperphosphorylated tau iso- progression (D’Amico et al., 2013). forms containing four microtubule-binding domain repeats, We report the case of a patient who developed clinical making GGT a 4-repeat (4 R)-tauopathy (Ahmed et al., 2013). features suggestive of both PSP Richardson’s syndrome (PSP- GGT is more commonly observed as a sporadic disease, RS) and PLS, and had GGT pathology on autopsy. We discuss in though cases associated with mutations in the microtubule- detail the aspects of his clinical presentation and highlight associated protein (MAPT) taugenehavebeenreported(Ferrer those features that might have helped to predict his underlying et al., 2014;Taciketal.,2015, 2017; Zarranz et al., 2005). pathology in vivo. We propose a theoretical framework to Pathologically, GGT is classified into three distinct subtypes facilitate the antemortem recognition of this rare pathological (Ahmed et al., 2013). This neuropathological variability con- entity in patients with FTD syndromes. stitutes the basis of the heterogeneous clinical presentation of CONTACT Salvatore Spina [email protected] © 2020 Informa UK Limited, trading as Taylor & Francis Group 2 A. J. LIU ET AL. Case presentation experienced a near-drowning accident at the age of 12. He never smoked or used illicit drugs and occasionally drank alco- An 83-year-old right-handed man presented to the UCSF hol. He suffered multiple head traumas due to falls beginning at Memory and Aging Center clinic with 6 years of progressive the age of 78. His family history was remarkable for his father imbalance and falls. At age 77, he reported difficulties with who died of an intracranial aneurysmal bleed at the age of 59. vision and gait instability. One year later, he developed bilateral His mother and two of his brothers died of cancer. foot drop and cramps in his legs. Later that same year, he began complaining of right arm weakness and difficulties with fine movements, and began falling approximately once a month. At Neuropsychological testing age 81, he complained of weakness in the right leg, dysphagia, and dysarthria, and developed a facial stare. He began falling Formal neuropsychological testing (Kramer et al., 2003) at age fi once a week and started using a walker. A year later, he was 84 (Table 1), revealed signi cant multiple-domain cognitive ffi hospitalized after a fall and began using a wheelchair. By the impairment. Language di culties were observed. His speech “ ” age of 83, he was no longer able to write or use utensils. He had had a musical quality. Several phonological and paraphasic developed dystonia and involuntary movements of the right errors on formal testing of repetition were noted. Verbal agility arm. Behavioral and cognitive changes developed contextually was markedly impaired, and there was evidence of word- fi ffi to the motor deficits and included impulsivity, diminished nding di culties and mild semantic loss. Performance on judgment, difficulties with thought expression, grammar and tests of memory showed poor learning, and delayed recall in spelling, and dysprosody. the average range. On executive function testing, he was prone Neurological examination at age 83 showed a procerus sign to errors and loss of set. Visuospatial and constructional skills fi and hypomimia. Speech was characterized by frequent phone- were impacted by motor de cits. Clinical dementia rating (CDR) mic distortions and paraphasic errors. Square wave jerks were score was 0.5. The patient repeated neuropsychological testing present along with delayed saccade initiation and slow velo- 8 months later. At that time, his speech had further deterio- cities on horizontal gaze, and diminished vertical gaze ampli- rated to the point that he was only able to communicate fi tude. Muscle tone was increased axially in an extrapyramidal through nodding or knocking on the table. A modi ed trail fashion, in the right upper extremity with combined pyramidal and extrapyramidal features, and at the right lower extremity Table 1. Neuropsychological performance at baseline and 8-month follow-up. with extrapyramidal feature. Fine movements of the right hand Expected score, mean were impaired, but segmental strength was otherwise full and Neuropsychological
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