Language impairment associated with prognosis in progressive supranuclear palsy
Indira García‐CorderoMohsen HadianEce BayramFederico Rodríguez‐PorcelChristopher D. StephenAlexander PantelyatJay M. IyerTao XieAdam L. BoxerDouglas D. GunzlerMarian L. DaleNikolaus R. McFarlandKyurim KangMatthew SwanAnne‐Marie WillsAnthony E. LangMaria Carmela Tartaglia
0
Citation
0
Reference
10
Related Paper
Abstract:
Abstract Background Language impairment is common in progressive supranuclear palsy (PSP) and is often overlooked due to the severity of the motor symptoms. We investigated whether language can be used to predict PSP prognosis. Methods One hundred‐forty‐six patients with a diagnosis of possible or probable PSP from the Tilavonemab (ABBV‐8E12) clinical trial were evaluated at baseline and week 32 using the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS), the PSP rating scale (PSPRS) and the Schwab and England Activities of Daily Living Scale (SEADL). Percentage of change was calculated for each measure. Using correlations, we evaluated relationships between all RBANS‐subscores (language, attention, memory and visuoconstructional), the PSPRS and SEADL scores at baseline; p‐values were FDR corrected. Linear regression analyses were performed between the RBANS‐language, RBANS‐delayed‐memory and RBANS‐executive at baseline and the percentage of change over time. Grey matter volumes were extracted from three regions of interest based on language (bilateral temporal poles and inferior frontal gyri), executive (bilateral dorsolateral and superior frontal gyri and frontal pole) and memory (bilateral hippocampus, inferior, middle and superior temporal gyri) areas. Results Mean age of PSP patients: 68.8 years (49‐86 years), 57 (39%) females. The RBANS language, executive and delayed memory scores at baseline were positively correlated with each other and with visuoconstructional and immediate memory score (all p<0.05). Only the RBANS‐language score at baseline predicted percentage of change in PSPRS (B = ‐0.63, p = 0.003). The percentage of change in the RBANS‐language score was predicted by the RBANS‐language at baseline (B = ‐0.59, p<0.001). Lower age at baseline was associated with a worsening in language score over time (B = 0.51, p = 0.009). Language grey matter volume was associated with the change in RBANS‐language score (B = 0.01, p = 0.02). Conclusions language impairment at baseline, in contrast to memory and executive functions, was predictive of functional decline as measured by PSPRS. Atrophy in language areas at baseline predicted language decline. Language impairment may be an independent prognostic factor in PSP. *Based on research using data from AbbVie that has been made available through Vivli, Inc. Vivli has not contributed to or approved, and is not in any way responsible for, the contents of this publication.In the current study we explored the relationship between neurometabolites measured by proton magnetic resonance spectroscopy (1H-MRS) and cognitive ability assessed with a battery of neuropsychological tests. Forty-five participants were recruited from the local college community, and examined utilizing neuropsychological testing and 1H-MRS. Our central finding was that N-acetylaspartate (NAA) was associated with overall neuropsychological performance (F(1,42) = 23.16, p < 0.0001], r2 = 0.35. We found an even stronger association between timed neuropsychological measures and NAA (F(1,42) = 31.15, p < 0.0001], r = 0.43. These results reveal the specific relationship of NAA to neuropsychological functioning in normal human brain. The current observations in healthy individuals are consistent with the hypothesis that variability in NAA levels and neuropsychological performance may be related to mitochondrial function.
Proton magnetic resonance
Neuropsychological test
Cite
Citations (88)
Diagnostic criteria for progressive supranuclear palsy (PSP) include midbrain atrophy in MRI and hypometabolism in [
Cite
Citations (0)
Abstract To better understand the pathological and phenotypic heterogeneity of progressive supranuclear palsy and the links between the two, we applied a novel unsupervised machine learning algorithm (Subtype and Stage Inference) to the largest MRI data set to date of people with clinically diagnosed progressive supranuclear palsy (including progressive supranuclear palsy–Richardson and variant progressive supranuclear palsy syndromes). Our cohort is comprised of 426 progressive supranuclear palsy cases, of which 367 had at least one follow-up scan, and 290 controls. Of the progressive supranuclear palsy cases, 357 were clinically diagnosed with progressive supranuclear palsy–Richardson, 52 with a progressive supranuclear palsy–cortical variant (progressive supranuclear palsy–frontal, progressive supranuclear palsy–speech/language, or progressive supranuclear palsy–corticobasal), and 17 with a progressive supranuclear palsy–subcortical variant (progressive supranuclear palsy–parkinsonism or progressive supranuclear palsy–progressive gait freezing). Subtype and Stage Inference was applied to volumetric MRI features extracted from baseline structural (T1-weighted) MRI scans and then used to subtype and stage follow-up scans. The subtypes and stages at follow-up were used to validate the longitudinal consistency of subtype and stage assignments. We further compared the clinical phenotypes of each subtype to gain insight into the relationship between progressive supranuclear palsy pathology, atrophy patterns, and clinical presentation. The data supported two subtypes, each with a distinct progression of atrophy: a ‘subcortical’ subtype, in which early atrophy was most prominent in the brainstem, ventral diencephalon, superior cerebellar peduncles, and the dentate nucleus, and a ‘cortical’ subtype, in which there was early atrophy in the frontal lobes and the insula alongside brainstem atrophy. There was a strong association between clinical diagnosis and the Subtype and Stage Inference subtype with 82% of progressive supranuclear palsy–subcortical cases and 81% of progressive supranuclear palsy–Richardson cases assigned to the subcortical subtype and 82% of progressive supranuclear palsy–cortical cases assigned to the cortical subtype. The increasing stage was associated with worsening clinical scores, whilst the ‘subcortical’ subtype was associated with worse clinical severity scores compared to the ‘cortical subtype’ (progressive supranuclear palsy rating scale and Unified Parkinson’s Disease Rating Scale). Validation experiments showed that subtype assignment was longitudinally stable (95% of scans were assigned to the same subtype at follow-up) and individual staging was longitudinally consistent with 90% remaining at the same stage or progressing to a later stage at follow-up. In summary, we applied Subtype and Stage Inference to structural MRI data and empirically identified two distinct subtypes of spatiotemporal atrophy in progressive supranuclear palsy. These image-based subtypes were differentially enriched for progressive supranuclear palsy clinical syndromes and showed different clinical characteristics. Being able to accurately subtype and stage progressive supranuclear palsy patients at baseline has important implications for screening patients on entry to clinical trials, as well as tracking disease progression.
Corticobasal degeneration
Cite
Citations (13)
My dad and progressive supranuclear palsy (PSP)
Cite
Citations (0)
When the 2017 Movement Disorders Society Criteria for progressive supranuclear palsy is applied, patients may appear to have multiple phenotypes. The maximum allocation extinction rules were developed to provide a consistent method for applying the criteria and reaching a single diagnostic label. In this study, we apply both to a neuropathologic cohort of progressive supranuclear palsy and other parkinsonian conditions.An autopsy cohort of 54 patients with progressive supranuclear palsy and 56 patients with other neuropathologic diseases was selected. Clinical data were retrospectively abstracted, and the diagnostic criteria for progressive supranuclear palsy were applied. All possible phenotypes applicable were listed and maximum allocation extinction rules were applied to assess reduction in the number of phenotypes ascribed per patient.In the progressive supranuclear palsy group, 52 patients met the criteria for multiple phenotypes, with an average of 7 phenotypes per patient. In the nonprogressive supranuclear palsy group, all 56 patients had features of more than one phenotype, up to 3 per patient. After application of maximum allocation extinction rules, the majority of the patients in both groups had a single predominant phenotype. Freezing of gait, supranuclear gaze palsy, and frontal behavioral syndrome were more common in the progressive supranuclear palsy group.The diagnostic criteria for progressive supranuclear palsy identify many clinical features, thereby leading to assignment of multiple phenotypes per patient. We demonstrate that the maximum allocation extinction rules can effectively lead to a single consensus phenotype, maintaining a uniform diagnostic label for clinical and research applications.
Movement Disorders
Cite
Citations (15)
Progressive supranuclear palsy is one of the causes of atypical parkinsonian syndrome. We present the case of an 83-year-old patient with typical symptomatology suggesting progressive supranuclear palsy with characteristic imaging.
Cite
Citations (0)
Cite
Citations (0)
Cite
Citations (6)
ABSTRACT Background The Movement Disorder Society diagnostic criteria for progressive supranuclear palsy introduced the diagnostic certainty level “suggestive of progressive supranuclear palsy” for clinical conditions with subtle signs, suggestive of the disease. This category aims at the early identification of patients, in whom the diagnosis may be confirmed as the disease evolves. Objective To assess the diagnostic performance of the defined clinical conditions suggestive of progressive supranuclear palsy in an autopsy‐confirmed cohort. Methods Diagnostic performance of the criteria was analyzed based on retrospective clinical data of 204 autopsy‐confirmed patients with progressive supranuclear palsy and 216 patients with other neurological diseases. Results The conditions suggestive of progressive supranuclear palsy strongly increased the sensitivity compared to the National Institute of Neurological Disorders and Stroke and Society for Progressive Supranuclear Palsy criteria. Within the first year after symptom onset, 40% of patients with definite progressive supranuclear palsy fulfilled criteria for suggestive of progressive supranuclear palsy. Two‐thirds of patients suggestive of progressive supranuclear palsy evolved into probable progressive supranuclear palsy after an average of 3.6 years. Application of the criteria for suggestive of progressive supranuclear palsy reduced the average time to diagnosis from 3.8 to 2.2 years. Conclusions Clinical conditions suggestive of progressive supranuclear palsy allow earlier identification of patients likely to evolve into clinically possible or probable progressive supranuclear and to have underlying progressive supranuclear palsy pathology. Further work needs to establish the specificity and positive predictive value of this category in real‐life clinical settings, and to develop specific biomarkers that enhance their diagnostic accuracy in early disease stages. © 2020 The Authors. Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society
Pseudobulbar palsy
Cite
Citations (32)