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

BACKGROUND: Most studies of progressive supranuclear palsy (PSP) have been conducted in White populations. OBJECTIVE: 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. METHODS: 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. RESULTS: 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). CONCLUSIONS: 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.

Prevalence of Progressive Supranuclear Palsy and Corticobasal Syndrome in Scotland.

INTRODUCTION: We estimated the point prevalence of progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) at regional and national levels in Scotland, UK, as there are few high-quality prevalence studies of these conditions. METHODS: Nationally, multiple methods of case ascertainment were used including clinician and nurse specialist referral, searches of ICD-10 diagnostic coding in routinely collected electronic health data (Scottish Morbidity Record), and patient self-referral. In one region, we also searched GP databases and unselected hospital correspondence. Cases were verified by clinical examination or medical record review. National and regional total and age-sex-stratified crude prevalence rates on December 31, 2018, were calculated. RESULTS: The regional crude point prevalence was 4.28 per 100,000 (95% CI 2.90, 6.31) for PSP and 2.05 per 100,000 (95% CI 1.17, 3.59) for CBS. The national crude prevalence rates were lower due to the greater reliance on passive case ascertainment. There were no clear sex differences. At a national level, the peak crude prevalence rate for both PSP and CBS was in the 70-79 age group. DISCUSSION: The prevalence rates of PSP and CBS were similar to previous estimates with little change over the past 20 years.

Seizure prevalence in neurodegenerative diseases-a study of autopsy proven cases.

BACKGROUND AND PURPOSE: Knowledge about the seizure prevalence in the whole symptomatic course, from disease onset to death, in neurodegenerative diseases (ND) is lacking. Therefore, the aim was to investigate seizure prevalence and associated clinical implications in neuropathologically diagnosed ND. METHODS: Clinical records of cases from the Neurobiobank Munich, Germany, were analyzed. Neuropathological diagnoses of the assessed cases included Alzheimer disease (AD), corticobasal degeneration (CBD), frontotemporal lobar degeneration (FTLD), Lewy body disease (LBD), multiple system atrophy (MSA) and progressive supranuclear palsy (PSP). Seizure prevalence during the whole symptomatic disease phase was assessed and compared amongst ND. Associations between first clinical symptom and seizure prevalence and between seizures and disease duration were examined. RESULTS: In all, 454 patients with neuropathologically diagnosed ND and with available and meaningful clinical records were investigated (AD, n = 144; LBD, n = 103; PSP, n = 93; FTLD, n = 53; MSA, n = 36; CBD, n = 25). Seizure prevalence was 31.3% for AD, 20.0% for CBD, 12.6% for LBD, 11.3% for FTLD, 8.3% for MSA and 7.5% for PSP. Seizure prevalence was significantly higher in AD compared to FTLD (p = 0.005), LBD (p = 0.001), MSA (p = 0.005) and PSP (p < 0.001). No other significant differences regarding seizure prevalence were found between the studied ND. Cognitive first symptoms in ND were associated with an increased seizure prevalence (21.1% vs. 11.0% in patients without cognitive first symptoms) and motor first symptoms with a decreased seizure prevalence (10.3% vs. 20.5% in patients without motor first symptoms). Seizures were associated with a longer disease duration in MSA (12.3 vs. 7.0 years in patients without seizures; p = 0.017). CONCLUSIONS: Seizures are a clinically relevant comorbidity in ND, particularly in AD. Knowledge of the first clinical symptom in ND may allow for estimation of seizure risk.

Prevalence and associated factors of frailty and sarcopenia in multiple system atrophy and progressive supranuclear palsy: a cross-sectional study.

OBJECTIVE: To investigate the prevalence of, and clinicodemographic factors associated with, frailty and sarcopenia in patients with multiple system atrophy or progressive supranuclear palsy. METHODS: A total of 264 participants were recruited in this study. Demographic and clinical data were collected through structured interviews. Frailty was assessed with the clinical frailty scale (CFS), and sarcopenia was assessed with the simple five-item scoring questionnaire (SARC-F). RESULTS: The prevalence of frailty and sarcopenia was 48.57% and 35.71% in multiple system atrophy, and 51.09% and 39.13% in progressive supranuclear palsy. Multiple system atrophy patients with frailty or sarcopenia were more likely to be female and have longer disease duration, greater motor impairment, greater non-motor burden, and lower life quality. In multiple system atrophy, frailty was associated with reduced motor function and sarcopenia was associated with female sex, reduced motor function, and orthostatic hypotension. Progressive supranuclear palsy patients with frailty or sarcopenia had more severe motor impairment and non-motor burden, longer disease duration, and lower life quality. In progressive supranuclear palsy, frailty was associated with mentation and gait/midline symptoms, while sarcopenia was associated with reduced daily activity and severe gait/midline symptoms. CONCLUSION: Frailty and sarcopenia may be more common among patients with multiple system atrophy or progressive supranuclear palsy than among the general population, and they are associated with more severe forms of the two diseases. Prospective studies are necessary to clarify causal relationships between frailty/sarcopenia and clinical manifestations of multiple system atrophy and progressive supranuclear palsy.

First symptom guides diagnosis and prognosis in neurodegenerative diseases-a retrospective study of autopsy proven cases.

BACKGROUND AND PURPOSE: Clinical diagnostic criteria for neurodegenerative diseases have been framed based on clinical phenomenology. However, systematic knowledge about the first reported clinical symptoms in neurodegenerative diseases is lacking. Therefore, the aim was to determine the prevalence and clinical implications of the first clinical symptom (FS) as assessed by medical history in neuropathologically proven neurodegenerative diseases. METHODS: Neuropathological diagnoses from the Neurobiobank Munich, Germany, were matched with clinical records for analyses of the diagnostic and prognostic values of FSs. RESULTS: In all, 301 patients with the neuropathological diagnoses Alzheimer disease (AD), progressive supranuclear palsy (PSP), frontotemporal lobar degeneration (FTLD), Lewy body disease (LBD) including the neuropathologically indistinguishable clinical phenotypes Parkinson disease and dementia with Lewy bodies, multiple system atrophy (MSA) and corticobasal degeneration (CBD) were studied. Memory disturbance was the most common FS in AD (34%), FTLD (19%) and LBD (26%), gait disturbance in PSP (35%) and MSA (27%) and aphasia and personality changes in CBD (20%, respectively). In a model adjusting for prevalence in the general population, AD was predicted by memory disturbance in 79.0%, aphasia in 97.2%, personality changes in 96.0% and by cognitive disturbance in 99.0%. Gait disturbance and tremor predicted LBD in 54.6% and 97.3%, coordination disturbance MSA in 59.4% and dysarthria FTLD in 73.0%. Cognitive FSs were associated with longer survival in AD (12.0 vs. 5.3 years; p < 0.001) and FTLD (8.2 vs. 4.1 years; p = 0.005) and motor FSs with shorter survival in PSP (7.2 vs. 9.7; p = 0.048). CONCLUSIONS: Assessing FSs in neurodegenerative diseases may be beneficial for accuracy of diagnosis and prognosis and thereby may improve clinical care and precision of study recruitment.

"Parkinson's disease" on the way to progressive supranuclear palsy: a review on PSP-parkinsonism.

Progressive supranuclear palsy (PSP) is a progressive atypical parkinsonian syndrome characterised by postural instability, supranuclear ophthalmoplegia, dysarthria, dysphagia, executive dysfunction and other features. This clinical presentation represents the classic PSP-Richardson syndrome (PSP-RS). However, several other clinical subtypes have been recognised, including PSP-parkinsonism (PSP-P), probably the second most common PSP variant. Unlike PSP-RS, PSP-P often presents with an asymmetric onset, tremor and a moderate initial response to levodopa, especially during the first years of the disease, thus resembling Parkinson's disease (PD). It runs a more favourable course, but over time, PSP-P may evolve clinically into PSP-RS. Therefore, it may seem that PSP-P stands clinically between PD and PSP. There are several peculiarities that can distinguish PSP-P from these entities. As there is lack of systematic reviews on PSP-P in the literature, we decided to summarise all the necessary data about the epidemiology, clinical picture, neuroimaging, genetics and other aspects of this PSP variant in order to provide complete information for the reader.

Pain in neurodegenerative diseases with atypical parkinsonism: a systematic review on prevalence, clinical presentation, and findings from experimental studies.

Parkinson's disease-related pain has increasingly been investigated in research studies. Still, only a few studies have addressed the prevalence and clinical characteristics of pain in neurodegenerative disorders with atypical parkinsonism. The existing evidence, although scarce, suggests that, similarly as in Parkinson's disease, individuals with neurodegenerative diseases with atypical parkinsonism might be predisposed to the development of persistent pain. Today, as the global population is aging and we face an epidemic of neurodegenerative disorders, under-treated pain is taking a great toll on an ever-rising number of people. Here, we provide an up-to-date review of the current knowledge on the prevalence of pain, its clinical features, and findings from experimental studies that might signpost altered pain processing in the most prevalent neurodegenerative disorders with atypical parkinsonism: multiple system atrophy, progressive supranuclear palsy, corticobasal syndrome, frontotemporal dementia, and dementia with Lewy bodies. Finally, we point out the current gaps and unmet needs that future research studies should focus on. Large-scale, high-quality clinical trials, coupled with pre-clinical research, are urgently needed to reveal the exact pathophysiological mechanisms underpinning heightened pain and pave the path for mechanistically-driven analgesic interventions to be developed, ultimately leading to an improvement in the quality of life of individuals with neurodegenerative disorders.

Copathology in Progressive Supranuclear Palsy: Does It Matter?

BACKGROUND: The influence of concomitant brain pathologies on the progression rate in PSP is unclear. OBJECTIVES: To analyze the frequency and severity of copathologies and their impact on the progression in PSP. METHODS: We analyzed clinic-pathological features of 101 PSP patients. Diagnoses and stages of copathologies were established according to standardized criteria, including Alzheimer's disease-related pathology, argyrophilic grains, Lewy-related pathology, transactive response DNA-binding protein 43 pathology, fused in sarcoma pathology, cerebral amyloid angiopathy, and small vessel disease. Demographic data and major clinical milestones (frequency and latency to onset) were extracted from patients' files. RESULTS: Only 8% of 101 patients presented with pure PSP pathology without any copathology. Alzheimer's disease-related pathology was the most frequent (84%), followed by argyrophilic grains (58%), both occurring as single copathology or in combination with other proteinopathies or cerebrovascular disease. Lewy-related and transactive response DNA-binding protein 43 copathology occurred rarely (8% and 6%, respectively). Fused in sarcoma-positive cases were not found. While being common, copathology was mostly mild in severity, with the exception of frequently widespread argyrophilic grains. Small vessel disease was also frequent (65%). Cerebral amyloid angiopathy occurred only in the presence of Alzheimer's disease-related changes (25%). The copathologies did not have major impact on prevalence and time frame of major disease milestones. CONCLUSIONS: In PSP, concomitant neurodegenerative proteinopathies or cerebrovascular diseases are frequent, but generally mild in severity. Our data confirmed that four repeat tau is still the most relevant target for PSP, whereas the impact of copathologies on progression rate appears to be of less importance. This is relevant information for the development of disease-modifying therapies. © 2020 The Authors. Movement Disorders published by Wiley Periodicals, Inc. on behalf of International Parkinson and Movement Disorder Society.

Progressive Supranuclear Palsy and Statin Use.

INTRODUCTION: Statins were proposed to be neuroprotective; however, the effects are unknown in progressive supranuclear palsy (PSP), a pure tauopathy. METHODS: Data of 284 PSP cases and 284 age-matched, sex-matched, and race-matched controls were obtained from the environmental and genetic PSP (ENGENE-PSP) study. Cases were evaluated with the PSP Rating Scale, Unified Parkinson's Disease Rating Scale, Mattis Dementia Rating Scale, and Neuropsychiatric Inventory. Statin associations with PSP risk, onset age, and disease features were analyzed. RESULTS: Univariate models showed lower PSP risk for type 1 statin users (simvastatin, lovastatin, pravastatin). After adjusting for confounding variables, statin use and lower PSP risk association remained only at a trend level. For PSP cases, type 1 statins were associated with 1-year older onset age; type 2 statins (atorvastatin, rosuvastatin) were associated with the lower PSP Rating Scale and Unified Parkinson's Disease Rating Scale. CONCLUSION: Statins may have inverse associations with PSP risk and motor impairment. Randomized prospective studies are required to confirm this effect. © 2020 International Parkinson and Movement Disorder Society.

Lifetime exposure to estrogen and progressive supranuclear palsy: Environmental and Genetic PSP study.

BACKGROUND: Studies suggesting a protective effect of estrogen in neurodegenerative diseases prompted us to investigate this relationship in progressive supranuclear palsy (PSP). METHODS: This case-control study evaluated the self-reported reproductive characteristics and estrogen of 150 women with PSP and 150 age-matched female controls who participated in the Environmental Genetic-PSP study. Conditional logistic regression models were generated to examine associations of PSP with estrogen. RESULTS: There was no association between years of estrogen exposure duration and PSP. There was a suggestion of an inverse association between composite estrogen score and PSP that did not reach statistical significance (P = .06). Any exposure to estrogen replacement therapy halved the risk of PSP (odds ratio = 0.52; 95% confidence interval = 0.30-0.92; P = .03). Among PSP cases, earlier age at menarche was associated with better performance on Hoehn and Yahr stage (ß = -0.60; SE = 0.26; P = .02) and Unified Parkinson's Disease Rating Scale II score (ß = -5.19; SE = 2.48; P = .04) at clinical examination. CONCLUSIONS: This case-control study suggests a protective role of lifetime estrogen exposure in PSP. Future studies will be needed to confirm this association. © 2018 International Parkinson and Movement Disorder Society.

Clinicopathologic discrepancies in a population-based incidence study of parkinsonism in olmsted county: 1991-2010.

OBJECTIVE: The purpose of this study was to examine the discrepancies between the clinical diagnosis of parkinsonism and neuropathological findings in a population-based cohort with parkinsonian disorders. BACKGROUND: The specific clinical diagnosis of parkinsonism is challenging, and definite confirmation requires neuropathological evaluation. Currently, autopsies are seldom performed, and most brain autopsies represent atypical or diagnostically unresolved cases. METHODS: We used a defined population-based incidence cohort with clinical parkinsonism (n = 669) from the Rochester Epidemiology Project in Olmsted County, Minnesota, 1991-2010. We reviewed reports of all patients who underwent neuropathologic examination at autopsy (n = 60; 9%) and applied consensus pathologic guidelines for neurodegenerative disease diagnosis. RESULTS: Among the 60 patients examined pathologically, the median time from the last recorded clinical diagnosis to death was 7 years (range from 2 to 17 years). Clinical-pathological concordance was found in 52 cases (86.7%), whereas 8 (13.3%) had a clinical-pathological discrepancy. Four patients with a clinical diagnosis of idiopathic Parkinson's disease had no pathological evidence of Lewy bodies or α-synucleinopathy; of these, pathological diagnoses were Alzheimer's disease (2 cases), progressive supranuclear palsy (1 case), and vascular parkinsonism (1 case). Two patients with clinical diagnoses of "dementia with Lewy bodies" and one patient with an "unspecified parkinsonism" had a pathological diagnosis of Alzheimer's disease without concomitant α-synuclein lesions. One patient with clinically diagnosed "progressive supranuclear palsy" had indeterminate pathological findings without α-synuclein or Aß- or tau-immunoreactive lesions at autopsy. CONCLUSIONS: Overall, the clinical diagnoses of parkinsonian subtypes had good concordance with pathological confirmation (86.7%). However, clinical-pathological discrepancies were documented in 13.3%. © 2017 International Parkinson and Movement Disorder Society.

Distribution and characteristics of transactive response DNA binding protein 43 kDa pathology in progressive supranuclear palsy.

BACKGROUND: This study aimed to determine the frequency of transactive response DNA binding protein 43 kDa pathology in PSP, the clinical features of patients with this pathology, and genetic risk factors for it. METHODS: Hippocampal sections were screened with immunohistochemistry for transactive response DNA binding protein 43 kDa in 945 PSP cases. A subset of 261 cases that were negative in hippocampus was screened in the amygdala. The density and disruption of this pathology, as well as regional tau burden, and clinical and genetic characteristics were analyzed. RESULTS: We observed transactive response DNA binding protein 43 kDa pathology in 47 cases in the hippocampus and an additional 9 cases that only affected the amygdala. Hippocampal sclerosis was the strongest risk factor, followed by Alzheimer's disease pathology, argyrophilic grain disease, and older age at death. Five stages of transactive response DNA binding protein 43 kDa pathology were identified in PSP: Stage A had pathology only in the amygdala (16%); stage I had pathology confined to the hippocampus and entorhinal cortex (9%); stage II included both regions of stage A and I (38%); stage III spread further to medial occipitotemporal gyrus (20%); and stage IV had pathology in the dorsolateral frontal lobe (18%). Anatomical areas vulnerable to PSP pathology had varying degrees of this pathology in stage II and later. PSP with transactive response DNA binding protein 43 kDa pathology were older at disease onset and had lower median MMSE scores; however, the latter was driven by concurrent pathologies. CONCLUSIONS: Distribution and clinical characteristics of transactive response DNA binding protein 43 kDa pathology in PSP were influenced by concurrent pathologies. This is the first study to observe that PSP-vulnerable regions are also susceptible to this non-tau pathology. © 2016 International Parkinson and Movement Disorder Society.

Cerebellar ataxia in progressive supranuclear palsy: An autopsy study of PSP-C.

BACKGROUND: Cerebellar ataxia is an exclusion criterion for the clinical diagnosis of progressive supranuclear palsy, but a variant with predominant cerebellar ataxia has been reported. The aims of this study were to estimate the frequency of progressive supranuclear palsy with predominant cerebellar ataxia in an autopsy series from the United States and to compare clinical, pathologic, and genetic differences between progressive supranuclear palsy with and without predominant cerebellar ataxia. METHOD: We selected 100 consecutive patients with pathologically confirmed progressive supranuclear palsy who had been evaluated at the Mayo Clinic (referred to as the Mayo Clinic patient series) from our brain bank database (N = 1085). We next enriched in cases likely to have cerebellar ataxia by searching the remaining 985 cases for (1) an antemortem diagnosis of multiple system atrophy or (2) neuropathologic evidence of prominent degeneration of the cerebellum or cerebellar afferent nuclei. Subsequently, clinical, pathologic, and genetic features were compared between the two groups. RESULTS: One patient in the Mayo Clinic patient series (1%) met criteria for progressive supranuclear palsy with predominant cerebellar ataxia and had both cerebellar and mild midbrain atrophy on MRI. Four patients were identified with the targeted search. Four of the five patients were clinically misdiagnosed as multiple system atrophy. The severity of tau-related pathology and cerebellar degeneration were not different between the two groups. No differences were detected in tau genotypes. CONCLUSION: Although our data cannot provide definitive information about how to make an accurate clinical diagnosis, they should serve to raise awareness of progressive supranuclear palsy with predominant cerebellar ataxia in the differential diagnosis of multiple system atrophy. © 2016 Movement Disorder Society.

Environmental and occupational risk factors for progressive supranuclear palsy: Case-control study.

BACKGROUND: The cause of progressive supranuclear palsy (PSP) is largely unknown. Based on evidence for impaired mitochondrial activity in PSP, we hypothesized that the disease may be related to exposure to environmental toxins, some of which are mitochondrial inhibitors. METHODS: This multicenter case-control study included 284 incident PSP cases of 350 cases and 284 age-, sex-, and race-matched controls primarily from the same geographical areas. All subjects were administered standardized interviews to obtain data on demographics, residential history, and lifetime occupational history. An industrial hygienist and a toxicologist unaware of case status assessed occupational histories to estimate past exposure to metals, pesticides, organic solvents, and other chemicals. RESULTS: Cases and controls were similar on demographic factors. In unadjusted analyses, PSP was associated with lower education, lower income, more smoking pack-years, more years of drinking well water, more years living on a farm, more years living 1 mile from an agricultural region, more transportation jobs, and more jobs with exposure to metals in general. However, in adjusted models, only more years of drinking well water was significantly associated with PSP. There was an inverse association with having a college degree. CONCLUSIONS: We did not find evidence for a specific causative chemical exposure; higher number of years of drinking well water is a risk factor for PSP. This result remained significant after adjusting for income, smoking, education and occupational exposures. This is the first case-control study to demonstrate PSP is associated with environmental factors. © 2016 International Parkinson and Movement Disorder Society.

Effectiveness of risk minimization measures for cabergoline-induced cardiac valve fibrosis in clinical practice in Italy.

On June 2008, the European Medicines Agency (EMA) introduced changes to the Summary of Product Characteristics (SPC) for cabergoline and pergolide, to reduce the risk of cardiac valvulopathy in users of these drugs. To assess the effectiveness of EMA recommendations in Italian clinical practice, we retrospectively reviewed medical charts of patients with degenerative Parkinsonism treated with cabergoline in three large Italian clinics between January 2006 and June 2012. The prevalence and the severity of cardiac valve regurgitation were assessed in patients who stopped cabergoline therapy prior to June 2008 or continued therapy after that date. In addition, the proportion of patients undergoing echocardiographic examination in each cohort was evaluated. A total of 61 patients were available for evaluation. The proportion of patients who underwent a baseline echocardiographic examination increased from 64 % in the period before the 2008 SPC changes to 71 % among those who continued treatment after that date. However, only 18 and 29 % of patients underwent at least two echocardiographic examinations during the pre-SPC and cross-SPC change period, respectively. No severe cardiac valve regurgitation was documented in any of the study patients using cabergoline either prior or after 26th June 2008. Our findings show that the 2008 changes to the SPC resulted in an increase in physicians' awareness of cabergoline-induced valvulopathy risk in Italy. However, only a small percentage of patients underwent serial echocardiography. Further efforts are needed to achieve better compliance with the prescribing guidelines for cabergoline treated patients in clinical practice.

Progressive supra-nuclear palsy: frequency of cardinal extrapyramidal features at first presentation.

OBJECTIVES: Cardinal extrapyramidal features of progressive supranuclear palsy (PSP) help in clinically differentiating this condition from Parkinson's disease and other Parkinsonian syndromes. However, not all extrapyramidal features may be initially present, thus posing a difficulty in early diagnosis. We studied their frequency at the time of first presentation. METHODS: Patients diagnosed clinically with PSP using the National Institute for Neurological Disorders and Society for PSP (NINDS/SPSP) criteria and seen between August 2010 and April 2013 were examined for the presence, 'presence with deviation' or absence of six extrapyramidal features: axial rigidity, symmetry, extended posture, backward falls, absence of tremors and lack of levodopa response. RESULTS: Twenty-eight patients (mean (SD) age 64.86 (9.72) years; 16 (57%) men) met the inclusion criteria. Of these, 14% had all six extrapyramidal features associated with PSP, 39% had five, 29% had four, 14% had three and 4% had two. The most frequent extrapyramidal sign was axial rigidity (68%). Axial plus peripheral rigidity was found in 18% of patients and peripheral rigidity alone in 14%. Extrapyramidal features were symmetrical in 29% and asymmetrical beyond 1 year in 29%. Body posture was extended in 46% and flexed in 21%. Backward falls were found in 50% and forward falls in 11%. Pill-rolling tremors were observed in 29%. Response to levodopa therapy was poor in 21% and good beyond 6 months in 39%. CONCLUSIONS: Only 14% of PSP patients present with all six cardinal extrapyramidal features. Also, deviations from standard descriptions are common in the initial stages of disease.

Progressive supranuclear palsy.

Progressive supranuclear palsy is a disorder of tau protein aggregation. Its clinical spectrum is now known to be wider than originally described, with a phenotype resembling Parkinson disease accounting for a third of cases. However, at least half of the patients with PSP exhibit the classic bradykinesia with disproportionate postural instability, erect posture with nuchal rigidity, frontal behavioral and cognitive changes, vertical gaze palsy, and other disabling brainstem deficits. Nonmendelian genetic risk factors exist, but PSP is almost entirely sporadic, with a prevalence of five to six persons per 100,000, mean onset age of 63, and median survival of 7 years. Clinical diagnostic criteria with excellent specificity and a clinical rating scale sensitive to progression are available. Diagnosis remains clinical, although magnetic resonance imaging and cerebrospinal fluid measures are showing promise as early-stage screening tools. Multiple candidate neuroprotective medications have proven ineffective to date. Treatment remains supportive, although coenzyme Q-10 has shown preliminary symptomatic efficacy and levodopa may provide transient, modest benefit.

Familial progressive supranuclear palsy: a literature review.

BACKGROUND: Many genes/loci associated with Parkinsonian disorders have been identified. However, the genetic causes for a number of familial forms of Parkinsonian disorders remain to be elucidated. OBJECTIVE: It was the aim of this paper to review the familial progressive supranuclear palsy (PSP) cases without any known gene mutations published in the English literature. METHODS: We searched the PubMed database for reports of familial PSP cases without known mutations. RESULTS: We found 19 PSP families. The mean age at onset was approximately 60 years, and the mean disease duration was about 8 years. Parkinsonism and ophthalmoplegia were most frequently reported, and a vast majority of patients manifested with these two symptoms. Other symptoms such as falls, postural instability and pyramidal signs were also common. A small subset of patients transiently responded to L-dopa therapy. CONCLUSION: There is an increasing number of reported familial PSP. A recently performed genome-wide association study indicated genetic factors for this condition. Furthermore, clinical, pathological and genetic investigations will open new avenues to the discovery of causative genes and new therapeutics for PSP.

The comorbidity and co-medication profile of patients with progressive supranuclear palsy.

BACKGROUND: Progressive supranuclear palsy (PSP) is usually diagnosed in elderly. Currently, little is known about comorbidities and the co-medication in these patients. OBJECTIVES: To explore the pattern of comorbidities and co-medication in PSP patients according to the known different phenotypes and in comparison with patients without neurodegenerative disease. METHODS: Cross-sectional data of PSP and patients without neurodegenerative diseases (non-ND) were collected from three German multicenter observational studies (DescribePSP, ProPSP and DANCER). The prevalence of comorbidities according to WHO ICD-10 classification and the prevalence of drugs administered according to WHO ATC system were analyzed. Potential drug-drug interactions were evaluated using AiDKlinik®. RESULTS: In total, 335 PSP and 275 non-ND patients were included in this analysis. The prevalence of diseases of the circulatory and the nervous system was higher in PSP at first level of ICD-10. Dorsopathies, diabetes mellitus, other nutritional deficiencies and polyneuropathies were more frequent in PSP at second level of ICD-10. In particular, the summed prevalence of cardiovascular and cerebrovascular diseases was higher in PSP patients. More drugs were administered in the PSP group leading to a greater percentage of patients with polypharmacy. Accordingly, the prevalence of potential drug-drug interactions was higher in PSP patients, especially severe and moderate interactions. CONCLUSIONS: PSP patients possess a characteristic profile of comorbidities, particularly diabetes and cardiovascular diseases. The eminent burden of comorbidities and resulting polypharmacy should be carefully considered when treating PSP patients.

Gray matter atrophy in progressive supranuclear palsy: meta-analysis of voxel-based morphometry studies.

Voxel-based morphometry (VBM) studies have provided cumulative evidence of gray matter (GM) atrophy in patients with progressive supranuclear palsy (PSP) relative to healthy controls (HC). However, not all findings have been entirely concordant. Herein, we performed a quantitative meta-analysis study in order to consistently quantify GM anomalies in PSP. We conducted a systematic search for VBM studies of PSP patients and HC using PubMed and Embase databases from January 2000 to May 2012. Meta-analysis of these VBM studies was performed using a newly improved voxel-based meta-analytic technique, effect-size signed differential mapping. A total of 9 cross-sectional VBM studies that involved 143 PSP patients and 216 HC subjects met the inclusion criteria. Considerable regional GM volume decrease was detected in the thalamus, basal ganglia, midbrain, insular cortex, and frontal cortex. These findings remained largely unchanged following jackknife sensitivity analyses. The present meta-analysis provided evidence of PSP-specific GM atrophy. This finding might help contribute to our understanding of the neurobiological basis underlying PSP.