Diagnostic Criteria For Progressive Supranuclear Palsy Research Articles

Dopa-responsive Rest Tremor Preceding Tachyphemia in Progressive Supranuclear Palsy: A Case Report.

Progressive supranuclear palsy (PSP) is characterized by progressive postural instability, falls, and supranuclear vertical gaze abnormalities. In this report, we present the case of a 71-year-old woman with dopa-responsive rest tremor followed by tachyphemia and postural instability. She initially presented with dopa-responsive slowness and tremor in the right hand. Two years later, she developed speech difficulties (tachyphemia) and a propensity for falls. Based on the diagnostic criteria for PSP, the patient was diagnosed with probable PSP-RS. The clinical manifestations observed in our patient are unique and are considered important for illustrating a broad spectrum of PSP syndrome.

Environmental Risk Factors for Progressive Supranuclear Palsy.

Typically, progressive supranuclear palsy (PSP) is clinically characterized by slow vertical saccades or supranuclear gaze palsy, levodopa-resistant parkinsonism with predominant axial symptoms, and cognitive executive impairment. Over the past decades, various PSP phenotypes, including PSP with predominant parkinsonism, PSP with corticobasal syndrome, PSP with progressive gait freezing, and PSP with predominant frontal dysfunction, have been identified from pathologically confirmed cases. Expanding knowledge led to new diagnostic criteria for PSP that with increased disease awareness led to increased PSP prevalence estimates. The identification of environmental and modifiable risk factors creates an opportunity to intervene and delay the onset of PSP or slow disease progression. To date, despite the increasing number of publications assessing risk factors for PSP, few articles have focused on environmental and lifestyle risk factors for this disorder. In this article, we reviewed the literature investigating the relationship between PSP and several environmental and other modifiable lifestyle risk factors. In our review, we found that exposures to toxins related to diet, metals, well water, and hypertension were associated with increased PSP risk. In contrast, higher education and statins may be protective. Further case-control studies are encouraged to determine the exact role of these factors in the etiopathogenesis of PSP, which in turn would inform strategies to prevent and reduce the burden of PSP.

Diagnosis Across the Spectrum of Progressive Supranuclear Palsy and Corticobasal Syndrome

Atypical parkinsonian syndromes (APS), including progressive supranuclear palsy (PSP), corticobasal syndrome (CBS), and multiple system atrophy (MSA), may be difficult to distinguish in early stages and are often misdiagnosed as Parkinson disease (PD). The diagnostic criteria for PSP have been updated to encompass a range of clinical subtypes but have not been prospectively studied. To define the distinguishing features of PSP and CBS subtypes and to assess their usefulness in facilitating early diagnosis and separation from PD. This cohort study recruited patients with APS and PD from movement disorder clinics across the United Kingdom from September 1, 2015, through December 1, 2018. Patients with APS were stratified into the following groups: those with Richardson syndrome (PSP-RS), PSP-subcortical (including PSP-parkinsonism and progressive gait freezing subtypes), PSP-cortical (including PSP-frontal and PSP-CBS overlap subtypes), MSA-parkinsonism, MSA-cerebellar, CBS-Alzheimer disease (CBS-AD), and CBS-non-AD. Data were analyzed from February 1, through May 1, 2019. Baseline group comparisons used (1) clinical trajectory; (2) cognitive screening scales; (3) serum neurofilament light chain (NF-L) levels; (4) TRIM11, ApoE, and MAPT genotypes; and (5) volumetric magnetic resonance imaging measures. A total of 222 patients with APS (101 with PSP, 55 with MSA, 40 with CBS, and 26 indeterminate) were recruited (129 [58.1%] male; mean [SD] age at recruitment, 68.3 [8.7] years). Age-matched control participants (n = 76) and patients with PD (n = 1967) were included for comparison. Concordance between the antemortem clinical and pathologic diagnoses was achieved in 12 of 13 patients with PSP and CBS (92.3%) undergoing postmortem evaluation. Applying the Movement Disorder Society PSP diagnostic criteria almost doubled the number of patients diagnosed with PSP from 58 to 101. Forty-nine of 101 patients with reclassified PSP (48.5%) did not have the classic PSP-RS subtype. Patients in the PSP-subcortical group had a longer diagnostic latency and a more benign clinical trajectory than those in PSP-RS and PSP-cortical groups. The PSP-subcortical group was distinguished from PSP-cortical and PSP-RS groups by cortical volumetric magnetic resonance imaging measures (area under the curve [AUC], 0.84-0.89), cognitive profile (AUC, 0.80-0.83), serum NF-L level (AUC, 0.75-0.83), and TRIM11 rs564309 genotype. Midbrain atrophy was a common feature of all PSP groups. Eight of 17 patients with CBS (47.1%) undergoing cerebrospinal fluid analysis were identified as having the CBS-AD subtype. Patients in the CBS-AD group had a longer diagnostic latency, relatively benign clinical trajectory, greater cognitive impairment, and higher APOE-ε4 allele frequency than those in the CBS-non-AD group (AUC, 0.80-0.87; P < .05). Serum NF-L levels distinguished PD from all PSP and CBS cases combined (AUC, 0.80; P < .05). These findings suggest that studies focusing on the PSP-RS subtype are likely to miss a large number of patients with underlying PSP tau pathology. Analysis of cerebrospinal fluid defined a distinct CBS-AD subtype. The PSP and CBS subtypes have distinct characteristics that may enhance their early diagnosis.

PB 10 Identifying an imaging biomarker for progressive supranuclear palsy – a combined gray &amp; white matter meta-analysis using ALE and SDM

Background Progressive supranuclear palsy (PSP) is an atypical parkinsonian syndrome. PSP is described by clinical features of vertical gaze palsy and postural instability. Even though midbrain atrophy has been suggested as a hallmark of the disease, it has not been validated systematically so far. Methods To identify disease-specific regional atrophy in PSP, we conducted a systematic and quantitative meta-analysis on structural magnetic resonance imaging (MRI) data. Based on strict inclusion criteria 18 studies were identified in PubMed including 315 patients compared with 393 healthy controls. For analysis, the included studies were separated into studies investigating either gray or white matter atrophy. Ensuring consistent results, we used a unique approach by combining two widely used meta-analytical algorithms. The results of anatomical likelihood estimation (ALE) and Seed-basedDMapping (SDM) were superimposed in a conjunction analysis. Results The analysis of gray matter revealed that clusters in the bilateral thalamus, bilateral anterior insulae, midbrain and bilateral caudate nuclei were consistently identified as effected by both methods, SDM and ALE ( Fig. 1 ). White matter analyses revealed consistent atrophy in the bilateral superior cerebellar pedunculi, cerebral pedunculi, and midbrain. Discussion In light of previous meta-analyses investigating neurodegenerative diseases, our meta- analyses identify atrophy in the gray matter in the midbrain and in the white matter in the cerebral/cerebellar pedunculi and midbrain as disease-specific in PSP. Atrophy in these brain regions is suggested to be incorporated into new revised diagnostic criteria for PSP. The study design enabled high validity and statistical power. We combined two meta-analytic techniques, combined analyses in white and gray matter, and included the biggest cohort of PSP patients to date.

The Brainstem: Anatomy, Assessment, and Clinical Syndromes

Cover and Figure 1. The internal anatomy of the brainstem is presented in a simplified, color-coded format. Cover. The approximate locations and extents of nuclei that are important sources for a particular neurotransmitter are colorcoded onto a sagittal magnetic resonance image. Figure 1. The approximate locations and extent of major tracts and nuclei are colorcoded onto simplified axial illustrations of brainstem sections (left panel). The most common pattern of arterial territories is also presented (right panel). All illustrations are oriented in the radiographic perspective.

Differentiation of atypical Parkinson syndrome and delineation from idiopathic Parkinson syndrome with routine magnetic resonance tomography

Atrophy of frontal lobe, midbrain, pons, and cerebellum was studied in 16 patients with progressive supranuclear palsy (PSP), 14 with multiple system atrophy of striatonigral type (MSA-P), 20 with idiopathic Parkinson's disease (IPS), and 12 age-matched healthy controls using axial T2-weighted MR images (1.5 Teslar). With <16 mm, the PSP group showed significantly lower anteroposterior midbrain diameters than the IPS, MSA-P, and control groups. We conclude that measurement of the anteroposterior diameter of the midbrain with axial T2-weighted MRI is a useful feature and should be incorporated into the diagnostic criteria for PSP. In addition to the typical slit hyperintensity in margin of putamen and decreased signal intensity in dorsolateral putamen, we found cerebellar atrophy in 64% of patients with MSA-P. Before now, this was considered a typical sign of multiple system atrophy of cerebellar type (MSA-C). The use of this feature in the differential diagnosis of both types of multiple system atrophy is debatable.

The prevalence of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome) in the UK.

We performed a study to estimate the point prevalence of progressive supranuclear palsy (PSP) in the UK at national, regional and community levels. A 'Russian doll' design was used in which the population denominator for each of the three studies was successively smaller, whilst the method of case ascertainment became increasingly more rigorous. The NINDS-SPSP (National Institute of Neurological Disorders and the Society for Progressive Supranuclear Palsy) diagnostic criteria for PSP were applied throughout the study for case definition. The national study identified cases using passive referral mechanisms [e.g. the British Neurological Surveillance Unit (BNSU), PSP (Europe) Association patient register]. We identified 577 cases of PSP, giving a national prevalence estimate of 1.0 per 100 000 [95% confidence interval (CI) 0.9-1.1]. The North of England regional study used active 'multiple source' case ascertainment from a collaborative network of neurologists and non-neurologists. We identified 80 cases of PSP in this study, giving a crude and age-adjusted prevalence of 3.1 (95% CI 2.4-3.8) and 2.4 (1.9-3.0) per 100 000, respectively. Of these 80 cases, 51 patients (65%) were referred initially to non-neurologists and 10 patients (13%) had not seen a neurologist at any stage of their illness. The proportion of female cases was significantly greater in the regional than in the national study (61% versus 44%; P < 0.02). Cases referred to non-neurologists were significantly older than those referred to neurologists in the regional study (median age 73 versus 69.5 years; P < 0.01). Patients in the community study were identified via diagnostic and therapeutic registers from a representative sample of general practices in Newcastle upon Tyne. We identified 17 cases of PSP, yielding crude and age-adjusted prevalences of 6.5 (95% CI 3.4-9.7) and 5.0 (95% CI 2.5-7.5) per 100 000, respectively. Seven of the 17 cases (41%) had not previously been diagnosed as PSP. This study suggests that PSP is more common than previously considered, is commonly misdiagnosed and that the majority of cases are not initially referred to neurologists. The study also confirms the importance of active and detailed case ascertainment in ensuring reliable prevalence estimates.