Probable Progressive Supranuclear Palsy Research Articles

Ethnic background and distribution of clinical phenotypes in patients with probable progressive supranuclear palsy

BackgroundProgressive Supranuclear Palsy (PSP) is a sporadic neurodegenerative disease without a clear geographic prevalence. Cohorts studied in the UK and India showed no higher prevalence of atypical parkinsonism in South Asian patients. We describe the ethnic and racial background of PSP patients in the Greater Toronto Area (GTA), Canada. MethodsA prospective observational study of patients with clinically probable PSP evaluated at the dedicated Rossy PSP program. Demographic and clinical data were collected at baseline including PSP phenotype. Results were compared with the latest demographic information from the greater Toronto area. ResultsOf the 197 patients screened, 135 had probable PSP and resided within the GTA. The mean age at visit was 71.1 years, disease duration 4.4 years, and disease severity moderate. Compared to our catchment area, there was a higher proportion of patients with a South Asian origin and a lower proportion of patients from East and Southeastern Asia and Africa. A secondary analysis using population census data limited to individuals greater than 65 confirmed the significantly higher representation of South Asians in our clinic but found no differences for other racial and ethnic origins. ConclusionEvaluation of this Toronto cohort found a greater than expected proportion of affected individuals with South Asian ethnic and racial origin. Despite limitations, our results suggest the possibility of a racial and ethnic predisposition to PSP. Further studies are needed to confirm and to address potential associated risk factors, and genome-environmental interactions.

Monash-Alfred protocol for assessment of atypical parkinsonian syndromes (MAP-APS)

IntroductionAtypical parkinsonian syndromes (APS) are rare neurodegenerative syndromes for which parkinsonism is one significant feature. APS includes progressive supranuclear palsy (PSP), multiple system atrophy (MSA) and corticobasal syndrome (CBS). The...

Remote at-home wearable-based gait assessments in Progressive Supranuclear Palsy compared to Parkinson’s Disease

BackgroundWearable sensors can differentiate Progressive Supranuclear Palsy (PSP) from Parkinson’s Disease (PD) in laboratory settings but have not been tested in remote settings.ObjectivesTo compare gait and balance in PSP and PD remotely using wearable-based assessments.MethodsParticipants with probable PSP or probable/clinically established PD with reliable caregivers, still able to ambulate 10 feet unassisted, were recruited, enrolled, and consented remotely and instructed by video conference to operate a study-specific tablet solution (BioDigit Home ™) and to wear three inertial sensors (LEGSys™, BioSensics LLC, Newton, MA USA) while performing the Timed Up and Go, 5 × sit-to-stand, and 2-min walk tests. PSPRS and MDS-UPDRS scores were collected virtually or during routine clinical visits.ResultsBetween November, 2021- November, 2022, 27 participants were screened of whom 3 were excluded because of technological difficulties. Eleven PSP and 12 PD participants enrolled, of whom 10 from each group had complete analyzable data. Demographics were well-matched (PSP mean age = 67.6 ± 1.3 years, 40% female; PD mean age = 70.3 ± 1.8 years, 40% female) while disease duration was significantly shorter in PSP (PSP 14 ± 3.5 months vs PD 87.9 ± 16.9 months). Gait parameters showed significant group differences with effect sizes ranging from d = 1.0 to 2.27. Gait speed was significantly slower in PSP: 0.45 ± 0.06 m/s vs. 0.79 ± 0.06 m/s in PD (d = 1.78, p < 0.001).ConclusionOur study demonstrates the feasibility of measuring gait in PSP and PD remotely using wearable sensors. The study provides insight into digital biomarkers for both neurodegenerative diseases.Trial registrationClinicalTrials.gov Identifier: NCT04753320, first posted Febuary 15, 2021.

Brain FDG-PET correlates of saccadic disorders in early PSP.

New diagnostic criteria of Progressive Supranuclear Palsy (PSP) have highlighted the interest of Eye Movement Records (EMR) at the early stage of the disease. To investigate the metabolic brain correlates of ocular motor dysfunction using [18F] Fluorodeoxyglucose Positron Emission Tomography (FDG-PET) in early PSP. Retrospective observational descriptive study on longitudinal data with patients who underwent EMR and FDG-PET at the stage of suggestive and possible PSP according to Movement Disorders Society criteria. Longitudinal follow-up enables to confirm diagnosis of probable PSP. Using the Statistical Parametric Mapping software, we performed whole-brain voxel-based correlations between oculomotor variables and FDG-PET metabolism. Thirty-seven patients with early PSP who fulfilled criteria of probable PSP during the follow-up were included. Decrease in the gain of vertical saccades correlated with reduced metabolism in Superior Colliculi (SC). We also found a positive correlation between mean velocity of horizontal saccades and SC metabolism as well as dorsal nuclei in the pons. Finally, increase in horizontal saccades latencies correlated with decrease of posterior parietal metabolism. These findings suggest the early involvement of SC in saccadic dysfunction in the course of PSP.

Imaging Criteria for the Diagnosis of Progressive Supranuclear Palsy: Supportive or Mandatory?

We present the case of a 54-year-old male, without any significant medical history, who insidiously developed speech disturbances and walking difficulties, accompanied by backward falls. The symptoms progressively worsened over time. The patient was initially diagnosed with Parkinson's disease; however, he failed to respond to standard therapy with Levodopa. He came to our attention for worsening postural instability and binocular diplopia. A neurological exam was highly suggestive of a Parkinson-plus disease, most likely progressive supranuclear gaze palsy. Brain MRI was performed and revealed moderate midbrain atrophy with the characteristic "hummingbird" and "Mickey mouse" signs. An increased MR parkinsonism index was also noted. Based on all clinical and paraclinical data, a diagnosis of probable progressive supranuclear palsy was established. We review the main imaging features of this disease and their current role in diagnosis.

Differences Among Native Hawaiian, Asian, and White Patients with Progressive Supranuclear Palsy.

Most studies of progressive supranuclear palsy (PSP) have been conducted in White populations. The objective of this study was to identify whether differences exist for patients with PSP among Whites, East Asians (EAs), and Native Hawaiians/Pacific Islanders (NHPIs) in Hawaii. We conducted a single-center, retrospective study of patients meeting Movement Disorder Society probable PSP criteria (2006-2021). Data variables included age of onset and diagnosis, comorbidities, and survival rate. Variables were compared across groups using Fisher's exact test, Kruskal-Wallis rank sum test, and log-rank tests. A total of 94 (59 EAs, 9 NHPIs, 16 Whites, and 10 Others) patients were identified. Mean age ± standard deviation (in years) of symptom onset/diagnosis were both youngest in NHPIs (64.0 ± 7.2/66.3 ± 8.0) followed by Whites (70.8 ± 7.6/73.9 ± 7.8), then EAs (75.9 ± 8.2/79.2 ± 8.3) (P < 0.001). Median survival from diagnosis was significantly lower (P < 0.05) in NHPIs (2 years) compared with EAs (4 years) and Whites (6 years). There may be racial disparities for PSP, and studies are needed to identify genetic, environmental, and socioeconomic contributions. © 2023 International Parkinson and Movement Disorder Society.

Longitudinal study of Progressive Supranuclear Palsy (PSP) using remote at-home multi-modal digital assessments and wearable devices (S51.002)

<h3>Objective:</h3> To measure Progressive Supranuclear Palsy (PSP) progression remotely in participants’ homes using wearable sensors, digital speech and cognitive assessments. <h3>Background:</h3> There are limited studies using technology to objectively measure disease progression in PSP and no studies using wearable technology in participants’ homes. We hypothesized that remote, objective, quantitative measures of disease progression will facilitate clinical trials and help spur development of new therapies for PSP. <h3>Design/Methods:</h3> Patients with clinically probable PSP by MDS 2017 criteria able to ambulate ≥10 feet unassisted were recruited at Massachusetts General Hospital and Johns Hopkins from November 2021 through September, 2022 and followed virtually monthly for 1 year. Motor assessments performed monthly wearing LEGSys™ and BalanSense™ (BioSensics LLC, Newton, MA USA) devices included: balance assessments, 5x sit-to-stand, 3-meter timed up and go, and 2-minute walk tests. Participants wore PAMSys™ (BioSensics LLC) pendant sensors for 1 year to measure physical activity, walking parameters, postural transitions, and falls during daily activities. Digital cognitive and speech assessments performed using the BioDigit Home™ (BioSensics LLC) tablet every 3 months included: Color Trails, Conflicting Instructions, Go/No-Go, Forward and Backward Digit Span. The PSP Rating Scale (PSPRS), MoCA, PSP-QoL and CBFS were collected virtually every 3 months or in-person. <h3>Results:</h3> As of October 2022, 11 PSP participants were enrolled. By April 2023, 7 participants will have completed 12 months of follow-up. One participant was unable to complete virtual assessments due to lack of caregiver support and 3 participants could not perform walking tasks after 6 months. Walking parameters, postural duration and transition times correlated strongly with disease progression as measured using the PSPRS and PSP-QoL. Instrumented gait measures correlated with activity levels. <h3>Conclusions:</h3> Our study demonstrates the feasibility of remote longitudinal measurement of PSP progression in participants’ homes using wearable devices and digital assessments. The study identifies possible digital biomarkers of PSP progression. <b>Disclosure:</b> Miss Sharma has nothing to disclose. Ms. Hall has received research support from National Institutes of Health. Miss Cole has nothing to disclose. Mr. Casado has received personal compensation for serving as an employee of BioSensics LLC. Dr. Mishra has received personal compensation for serving as an employee of Biosensics. Dr. Vaziri has received personal compensation for serving as an employee of Biosensics. Dr. Pantelyat has received personal compensation for serving as an employee of MedRhythms, Inc.. Dr. Pantelyat has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for MedRhythms, Inc.. Dr. Pantelyat has received personal compensation in the range of $10,000-$49,999 for serving as an Expert Witness for Kelly &amp; Ignoffo Law Group. The institution of Dr. Pantelyat has received research support from NIH/NIA. Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Accordant, a CVS/Caremark company. Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Sanofi/Genzyme. The institution of Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Ono Pharmaceuticals. The institution of Dr. Wills has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Amylyx. Dr. Wills has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Parkinson’s Foundation. The institution of Dr. Wills has received research support from Parkinson’s Foundation. The institution of Dr. Wills has received research support from Biogen. The institution of Dr. Wills has received research support from Roche/Genentech. The institution of Dr. Wills has received research support from BioSensics.

Clinical, cognitive, and morphometric profiles of progressive supranuclear palsy phenotypes

The International Parkinson’s and Movement Disorder Society (MDS) criteria for progressive supranuclear palsy (PSP) have broadened the clinical spectrum of the disease and established phenotypic characterization according to the predominant manifestation at onset. The objective of this study is to describe clinical/cognitive and imaging features of a monocentric cohort of PSP patients, highlighting different patterns of functional disability according to the assigned phenotype. We retrospectively reviewed clinical/imaging data of 53 PSP patients diagnosed with probable PSP according to the MDS criteria and 40 age/sex-matched healthy controls (HCs). Neurological/neuropsychological assessments were performed using standardized scales, as well as comprehensive magnetic resonance imaging (MRI) morphometric measurements. In our cohort, there were 24/53 PSP-RS (Richardson’s syndrome), 13/53 PSP-P (Parkinsonism), 7/53 PSP-PGF (Progressive gait freezing), and 9/53 PSP-Cog (Cognitive impairment). PSP-Cog presented the worst motor profiles, the highest percentages of dementia and impaired functional autonomy; 4/9 PSP-Cog and 2/7 PSP-PGF died. PSP-P had the lowest motor/cognitive burden. All MRI parameters had good discriminative efficacy vs. HCs, with P/M 2.0 discriminating PSP-PGF from PSP-RS and PSP-Cog. We highlighted discrete clinical and imaging patterns that best characterize different PSP phenotypes. PSP-Cog and PSP-PGF/RS manifest greater incidence of dementia and motor disability, respectively, while PSP-P has a more benign course. The identification of different phenotypes may be the expression of different progression patterns requiring tailored approaches in terms of follow-up and treatment. These findings support the concept of discrete patterns of Tau pathology within the PSP spectrum and encourage research for phenotype-specific outcome measures.

Higher prevalence of idiopathic normal pressure hydrocephalus-like MRI features in progressive supranuclear palsy: An imaging reminder of atypical parkinsonism.

The classic triad of idiopathic normal pressure hydrocephalus (NPH) encompass gait disturbance, cognitive impairment, and urinary incontinence. These symptoms overlap with parkinsonism but with distinct treatment. Lacking applicable differentiation also hampers the prediction to therapeutic response. Here, we try to clarify this issue among different Parkinsonian syndromes and propose some innovative thinking while approaching a patient with parkinsonism and hydrocephalus concomitantly. Twenty-four patients with clinical probable multiple system atrophy (MSA), 34 with probable progressive supranuclear palsy (PSP), and 58 with sex- and age-matched Parkinson's disease (PD) were enrolled. Evans' index (EI), callosal angle (CA), antero-posterior (AP) diameterof the midbrain, length of the midbrain tegmentum diameter (MBTegm ), and disproportionately enlarged subarachnoid space hydrocephalus (DESH) were evaluated using the conventional MRI. Logistic regression was applied to identify the independent variables in hydrocephalus. Patients with PSP had higher mean EI than those with MSA and PD. Around 38.2% of patients with PSP had accompanied hydrocephalus (EI>0.3). Parkinsonism subtypes (PD, MSA, or PSP), AP diameterof the midbrain, and MBTegm were significantly different among patients with and without hydrocephalus. After regression analysis, parkinsonism subtype stood out to be the most key risk factor of hydrocephalus. The comparison between patients with PSP with and without hydrocephalus did not disclose specific clinical characteristics or risk factors. This study demonstrates that the presence of NPH-like MRI features is much higher in PSP patients, and this tendency is decided upon the determination of parkinsonism subtype. Sharing pathophysiological characteristics in these two diseases is implied. More diagnostic tools are needed to better differentiate the two diseases and decide the treatment. To closely observe hydrocephalic parkinsonism patients and well inform the possible limited shunting benefits if PSP core features appear, will be more pivotal and practical at present clinical practice.

Rapidly Progressive Corticobasal Degeneration Mimicking Brainstem Encephalitis.

Corticobasal degeneration (CBD) may have a rapidly progressive (RP) clinical course, mimicking other neurological conditions. To describe a neuropathologically proven case of RP-CBD in a patient initially diagnosed with immune-mediated brainstem encephalitis. Retrospective data collection from electronic records and authorized video material. A 51-year-old man presented with bilateral ptosis, diplopia, and dysphagia. The diagnostic workup was negative for myasthenic syndromes. He progressively developed cognitive dysfunction with frontal release signs and asymmetric parkinsonism. Cerebrospinal fluid evaluation revealed 4 leukocytes/uL, 0.32 g/L proteins, 0.85 g/L glucose, and absent oligoclonal bands. Weakly positive anti-PNMA2 (Ma2/Ta) antibodies were present, and magnetic resonance imaging showed a T2 hyperintensity involving the midbrain and pons. Based on these features, the diagnosis of immune-mediated brainstem encephalitis was considered. The patient did not improve after several cycles of methylprednisolone, intravenous immunoglobulin, and plasma exchange. At 1 year after onset, he developed horizontal and vertical gaze limitation and worsening of the parkinsonism and cognitive dysfunction. By age 53, he was severely disabled, requiring percutaneous gastrostomy for feeding. Anti-IgLON5 was negative. He fulfilled the clinical criteria for probable progressive supranuclear palsy. He died from pneumonia at age 54. The neuropathological examination revealed a 4-repeat tauopathy with features of CBD with extensive involvement of the brainstem. RP-CBD may resemble brainstem encephalitis. The severity of brainstem and upper spinal cord pathology in the postmortem examination correlated with the clinical and imaging features.

Interplay of tau and functional network connectivity in progressive supranuclear palsy: a [18F]PI-2620 PET/MRI study.

Progressive supranuclear palsy (PSP) is primary 4-repeat tauopathy. Evidence spanning from imaging studies indicate aberrant connectivity in PSPs. Our goal was to assess functional connectivity network alterations in PSP patients and the potential link between regional tau-burden and network-level functional connectivity using the next-generation tau PET tracer [18F]PI-2620 and resting-state functional MRI (fMRI). Twenty-four probable PSP patients (70.9 ± 6.9years, 13 female), including 14 Richardson syndrome (RS) and 10 non-RS phenotypes, underwent [18F]PI-2620 PET/MRI imaging. Distribution volume ratios (DVRs) were estimated using non-invasive pharmacokinetic modeling. Resting-state fMRI was also acquired in these patients as well as in thirteen older non-AD MCI reference group (64 ± 9years, 4 female). The functional network was constructed using 141 by 141 region-to-region functional connectivity metrics (RRC) and network-based statistic was carried out (connection threshold p < 0.001, cluster threshold pFDR < 0.05). In total, 9870 functional connections were analyzed. PSPs compared to aged non-AD MCI reference group expressed aberrant connectivity evidenced by the significant NBS network consisting of 89 ROIs and 118 connections among them (NBS mass 4226, pFDR < 0.05). Tau load in the right globus pallidus externus (GPe) and left dentate nucleus (DN) showed significant effects on functional network connectivity. The network linked with increased tau load in the right GPe was associated with hyperconnectivity of low-range intra-opercular connections (NBS mass 356, pFDR < 0.05), while the network linked with increased tau load in the left cerebellar DN was associated with cerebellar hyperconnectivity and cortico-cerebellar hypoconnectivity (NBS mass 517, pFDR < 0.05). PSP patients show altered functional connectivity. Network incorporating deep gray matter structures demonstrate hypoconnectivity, cerebellum hyperconnectivity, while cortico-cortical connections show variable changes. Tau load in the right GPe and left DN is associated with functional networks which strengthen low-scale intra-opercular and intra-cerebellar connections and weaken opercular-cerebellar connections. These findings support the concept of tau load-dependent functional network changes in PSP, by that providing evidence for downstream effects of neuropathology on brain functionality in this primary tauopathy.

In vivo imaging of tau deposition in Alzheimer's disease using both [18F]-THK5317 and [18F]-S16: A pilot human study.

ObjectiveTo evaluate the effectiveness of a new tracer (S)-1-(4-(6-(dimethylamino)quinoxalin-2-yl)phenoxy)-3-fluoropropan-2-ol ([18F]-S16), in distinguishing patients with AD from HCs.MethodsPaired [18F]-S16 and [18F]-THK5317 scans were acquired in five patients with AD, six HCs, one subject with a semantic variant of primary progressive aphasia (sv-PPA) and one subject with probable progressive supranuclear palsy (PSP). Dynamic PET scanning was performed over 90 min after injection of the tracers. Standardized uptake values (SUV) and cortical-to-cerebellum standardized uptake value ratios (SUVRs) were used for tau deposition semi-quantization. A voxel-based analysis was employed to assess the uptake difference between populations.Results[18F]-S16 exhibited excellent blood-brain-barrier penetration. AD patients showed increased cortical [18F]-THK5317 and [18F]-S16 binding. Compared to HCs, AD patients showed significantly increased cortical [18F]-S16 uptake in the bilateral occipital cortex, posterior cingulated cortex/precuneus, and lateral frontal cortex. Notable [18F]-S16 uptake was observed in the basal ganglia and brainstem compared to the neocortex. A substantial [18F]-S16 signal was detected in the basal ganglia and midbrain in a patient with probable PSP and in the bilateral anterior temporal cortex in a sv-PPA patient.Conclusion[18F]-S16 might be of help to detect tau protein in vivo.

Genetics of progressive supranuclear palsy in a Chinese population

BackgroundGenetics plays an important role in progressive supranuclear palsy (PSP) and remains poorly understood. A detailed literature search identified 19 PSP-associated genes: MAPT, LRRK2, LRP10, DCTN1, GRN, NPC1, PARK, TARDBP, TBK1, BSN, GBA, STX6, EIF2AK3, MOBP, DUSP10, SLCO1A2, RUNX2, CXCR4, and APOE. To date, genetic studies on PSP have focused on Caucasian population. The gaps in PSP genetic study on East Asian populations need to be filled. MethodsExon and flanking regions of the PSP-associated genes were sequenced in 104 patients with PSP and 488 healthy controls. Common variant-based association analysis and gene-based association tests of rare variants were performed using PLINK 1.9 and the sequence kernel association test-optimal, respectively. Additionally, the association of APOE and MAPT genotypes with PSP was evaluated. The above association analyses were repeated among probable PSP patients. Finally, PLINK 1.9 was used to test variants associated with the onset age of PSP. ResultsA rare non-pathogenic variant of MAPT (c.425C > T,p.A142V) was detected in a PSP patient. No common variants were significantly associated with PSP. In both the rare-variant and the rare-damaging-variant groups, the combined effect for GBA reached statistical significance (p = 1.43 × 10−3, p = 4.98 × 10−4). The result between APOE, MAPT genotypes and PSP risk were inconsistent across all PSP group and probably PSP group. ConclusionsThe pathogenic variant in MAPT were uncommon in PSP patients. Moreover, GBA gene was likely to increase the risk of PSP, and GBA-associated diseases were beyond α-synucleinopathies. The association between APOE, MAPT and PSP is still unclear among the non-Caucasian population.

The Non-motor Symptoms, Disability Progression, and Survival Analysis of Atypical Parkinsonism: Case Series from Eastern India and Brief Review of Literature

Objective The objectives of this study are (1) to describe the non-motor profile, the motor disability progression, and survival analysis of atypical parkinsonism in a tertiary care hospital of eastern India and (2) to elucidate the neurocircuitry and the putative substrates responsible for non-motor manifestations. Methods In this prospective observational study, patients were diagnosed based on Consensus Criteria for Progressive Supranuclear Palsy (PSP), The Fourth Consensus Report of the Dementia with Lewy Body (DLBD) Consortium 2017, The Autonomic Neuroscience 2018 Criteria for Multiple System Atrophy (MSA), and Armstrong 2013 Criteria for Corticobasal Degeneration (CBD). Disease severity was assessed at baseline and 6 months of follow-up using the Unified Parkinson's Disease Rating Scales (UPDRS). For PSP and MSA, the PSP-Clinical Deficits Scale (PSP-CDS) and the Unified MSA Rating Scale (UMSARS), respectively, were used. Cox regression analysis and the hazard ratio were calculated. Results Out of 27 patients, the diagnosis was probable PSP in 12, probable MSA in 7, probable CBD in 5, and probable DLBD in 3. Non-motor symptoms were highly prevalent across all subtypes. Motor disability progression as assessed by UPDRS parts 2 and 3 showed significant deterioration over 6-month follow-up across all groups ( p < 0.05). Disease progression assessed by PSP-CDS and UMSARS over 6 months was significant ( p < 0.05). One PSP and two MSA patients died during a 6-month follow-up period. The hazard ratio in MSA was 3.5 (95% confidence interval: 0.31–0.38) with p = 0.306. Conclusion Atypical parkinsonian disorders are rare, and usually more severe than idiopathic parkinsonism. As no definitive treatment is available, symptomatic management involving a multidisciplinary team approach must be prioritized.

Difficulties in differential diagnosis of chronic tick-borne encephalitis and progressive supranuclear palsy

The article presents two clinical cases of 51 and 57-year-old patients living in regions endemic for tick-borne encephalitis in which the differential diagnosis between progressive supranuclear palsy (PSP) and the extremely rare parkinsonian variant of chronic tick-borne encephalitis (CTBE) resulted in a diagnostic challenge. In both cases there was a clinical presentation of progressive symmetric levodopa-resistant parkinsonism with vertical gaze palsy, cognitive impairment of the executive type, frontal lobe signs, focal dystonia and in one case — early onset of postural instability, which corresponds to the diagnosis of probable PSP. The parkinsonian variant of CTBE was supported by the lack of tick-borne encephalitis virus IgG-antibodies negativity in the blood for several years, intrathecal oligoclonal antibody synthesis in one patient, the absence of typical neuroimaging signs of PSP, and delayed disease onset after a tick bite. Difficulties in diagnosis and possible mechanisms of the pathogenesis of primary progressive CTBE, as well as the similarity of the clinical and pathomorphological presentation of PSP, von Economo encephalitis lethargica, and postencephalitic parkinsonism are discussed.

Unusual progressive supranuclear palsy: A case report

Introduction: Progressive supranuclear palsy (PSP) is a rare brain condition. It is predominantly a sporadic disease that occurs between 45 and 75 years of age, typically after the age of 40. We herein report a presentation of PSP in a 35-year-old male patient. Observation: A 35-year-old man progressively presented gait disturbances with postural instability leading to falls. On examination: Akineto-rigid parkinsonian syndrome (PS), primarily axial, associated with vertical gaze palsy, head backwards tilt and postural instability without tremor. There was a slight frontal syndrome, irritability and dysphagia. The biological assessment (autoimmunity, copper and CSF testing) was correct. Brain MRI of the onset [figure1] did not show mesencephalic atrophy, nor signal abnormalities of overload disorders (Wilson's disease (WD), neuroferritinopathy). The patient underwent a therapeutic test (L-dopa 300 mg/d) over three months, without significant improvement. We then added ropinirole, rivastigmine and paroxetine. Despite the given therapeutics, no remarkable changes were noticed. Discussion: PSP is the most common phenotype of parkinsonism after Parkinson’s disease (PD). Its prevalence estimated to be 5–7 cases /100 000 with peak occurrence at age 63 and no cases recorded before the age of 40. Although neuropathology is the gold standard for diagnosing definite PSP, certain clinical features, such as vertical supranuclear palsy evident in our patient are highly sensitive and specific. It is frequently seen in PSP and has strong relevance. A combination of clinical characteristics with high specificity is used to diagnose probable PSP. Vertical gaze palsy, pseudobulbar palsy, axial rigidity, falls and cognitive dysfunction are PSP’s clinical hallmarks. Our patient clinical presentation strongly suggested probable PSP with Richardson’s syndrome (PSP-RS), which is the commonest PSP presentations. In front of this atypical and sporadic PS, WD was ruled out as well as other differential diagnoses (anti-DPPX encephalitis). A control brain MRI is planned to look for possible midbrain atrophy that may not be found at the disease’s start. The patient clinical features are evocative arguments of the diagnosis, although the onset at the age of 35 is atypical and original. Conclusion: The onset of PSP after the age of 40 is one of the diagnostic requirements so far, however, early presentation should be considered.

Teaching Video NeuroImage: Tongue Tremor as a Presenting Feature of Progressive Supranuclear Palsy.

A 76-year-old man was referred to neurology by speech and language therapy after video fluoroscopy showed oropharyngeal dysphagia, aspiration, and tongue tremor (Video 1). He had presented with 6 months of progressive dysphagia, dysarthria, weight loss, and falls. Examination revealed akinetic rigidity, vertical supranuclear gaze palsy, slowed saccades, dysarthrophonia, and tongue tremor without palatal, jaw, or limb tremor. We diagnosed probable progressive supranuclear palsy (PSP). He did not respond to levodopa (400 mg/d). On a follow-up assessment 27 months later, the tremor persisted (Video 1). Tremor, usually upper limb, occurs in 42% of PSP cases.1 Isolated tongue tremor is a rare feature of PSP.1,2

The Overlap in Neuroimaging Findings Between Idiopathic Normal Pressure Hydrocephalus and Progressive Supranuclear Palsy.

The neuroimaging findings of brain stem atrophy resembling progressive supranuclear palsy (PSP) radiology are common in idiopathic normal pressure hydrocephalus (iNPH) subjects. Besides, recent studies report the existence of iNPH-like MRI findings in PSP subjects. We aimed to comparatively investigate the neuroimaging indices of iNPH and PSP in our patient groups in a detailed methodology. Ultimately, 19 probable PSP patients and 18 patients with a definite diagnosis of iNPH were enrolled. The subjects were recruited retrospectively from those who had been admitted between 2017 and 2021 to the Movement Disorders Polyclinic and the Neurosurgery Clinic of the Diskapi Yildirim Beyazit Training and Education Hospital. MRI-based DESH score, Evans index, and the callosal angle (CA) have been calculated in all the individuals. Besides, quantitative MRI parameters of PSP were evaluated in every subject. Statistical analyses were performed using IBM SPSS Statistics 26. The comparative analyses regarding the radiological parameters of PSP did not reveal any difference between patient groups. On the other hand, the comparisons of the neuroimaging parameters of iNPH, yielded differences in the CA, CA score, and the total DESH score. However, the ROC curve analyses did not reveal a discriminative power at a value of "very good" or "excellent" in any of the indices. We found that the neuroimaging features of iNPH and PSP highly overlapped between these patient groups. These results may provide indirect evidence regarding the coexistence of PSP and iNPH pathophysiology that has been deliberated in several recent reports.

Feasibility of short imaging protocols for [18F]PI‐2620 tau‐PET in progressive supranuclear palsy

AbstractBackgroundDynamic 60‐minute positron‐emission‐tomography (PET) imaging with the novel tau radiotracer [18F]PI‐2620 facilitated accurate discrimination between patients with progressive supranuclear palsy (PSP) and healthy controls (HCs). We now aimed to investigate if shorter acquisition and static time windows of [18F]PI‐2620 tau‐PET can be used for imaging of patients with PSP.MethodWe evaluated 37 patients at five different centers with probable or possible PSP Richardson syndrome (PSP‐RS) together with ten HCs. [18F]PI‐2620 PET was performed by a dynamic 60 minute scan. Distribution volume ratios (DVRs, multilinear reference tissue model 2, cerebellar reference) were calculated using full and truncated scan durations (0‐60, 0‐50, 0‐40, 0‐30, and 0‐20 minutes p.i.). Standardized uptake value ratios (SUVrs, cerebellar reference) were obtained from static imaging windows with 20 minutes duration (20‐40, 30‐50, and 40‐60 minutes p.i.). All DVR and SUVr data were compared with regard to their potential to discriminate patients with PSP‐RS from HCs in predefined subcortical and cortical target regions (effect size, receiver operating area under the curve (AUC), multi‐region classifier). Finally, we tested if shorter [18F]PI‐2620 PET imaging can also be applied to patients with Alzheimer’s disease (n=11).ResultThe effect size of 0‐50 and 0‐40 DVR was equivalent to 0‐60 DVR (averaged Cohen’s d: 1.22 and 1.16 vs. 1.26), whereas the performance dropped for 0‐30 or 0‐20 DVR. The 20‐40 SUVr indicated the best performance of all short static acquisition windows (averaged Cohen’s d: 0.99). The globus pallidus internus discriminated patients with PSP and healthy controls at a similarly high level for 0‐60 DVR (AUC: 0.96), 0‐40 DVR (AUC: 0.96), and 20‐40 SUVr (AUC: 0.94). The multi‐region classifier sensitivity of these time windows was consistently 86%. 0‐40 DVR showed similar performance in Alzheimer’s disease when compared to 0‐60 DVR.ConclusionShort dynamic acquisition and static imaging windows can be used for [18F]PI‐2620 PET imaging of PSP. 0‐40 minute dynamic scanning offers the best balance between accuracy and economic scanning and is may also be suitable for [18F]PI‐2620 PET imaging of Alzheimer’s disease.

InVivo 18F-Flortaucipir PET Does Not Accurately Support the Staging of Progressive Supranuclear Palsy.

Progressive Supranuclear Palsy (PSP) is a neurodegenerative disorder characterised by neuro-glial tau pathology. A new staging system for PSP pathology at post-mortem has been described and validated. We used a data-driven approach to test whether post-mortem pathological staging in PSP can be reproduced in vivo with 18F-flortaucipir PET.MethodsN=42 patients with probable PSP and N=39 controls underwent 18F-flortaucipir PET. Conditional inference tree analyses on regional binding potential values identified absent/present pathology thresholds to define in vivo staging. Following the staging system for PSP pathology, the combination of absent/present values across all regions was evaluated to assign each participant to in vivo stages. Analysis of variance was applied to analyse differences among means of disease severity between stages. In vivo staging was compared with post-mortem staging in N=9 patients who also had post-mortem confirmation of the diagnosis and stage.ResultsStage assignment was estimable in 41 patients: N=10 patients were classified in stage I/II, N=26 in stage III/IV, N=5 in stage V/VI, while N=1 was not classifiable. An explorative sub-staging identified N=2 patients in stage I, N=8 in stage II, N=9 in stage III, N=17 in stage IV and N=5 in stage V. However, the nominal 18F-flortaucipir derived stage was not associated with clinical severity and was not indicative of pathology staging at post-mortem.Conclusion18F-flortaucipir PET in vivo does not correspond to neuropathological staging in PSP. This analytic approach, seeking to mirror in vivo the neuropathology staging with PET-to-autopsy correlational analyses might enable in vivo staging with next-generation PET tracers for tau, but further evidence and comparison with post-mortem data are needed.