Atypical Parkinsonian Syndromes: Tauopathies

2017 ◽  
Author(s):  
Hee Kyung Park ◽  
Irene Litvan
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Corticobasal Degeneration ◽  
Parkinsonian Syndromes ◽  
Disease Modifying Therapies ◽  
Experimental Therapies ◽  
Parkinsonian Disorders ◽  
Abnormal Accumulation ◽  
Genetic Features ◽  
Basic Concepts ◽  
Atypical Parkinsonian Disorders

Atypical parkinsonian disorders, which include two common proteinopathies, tauopathies and α-synucleinopathies, are clinically characterized by a progressive parkinsonism that typically does not respond to levodopa therapy and usually associates with early postural instability, falls, and other atypical features not observed in Parkinson disease. Tauopathies refer to neurodegenerative diseases in which there is an abnormal accumulation of hyperphosphorylated tau. The most frequent tauopathies are progressive supranuclear palsy and corticobasal degeneration. Better recognition of the expanding phenotypes of these disorders has led to the development of new diagnostic criteria. Furthermore, better knowledge about the pathogenesis (cell-to-cell transmission of pathologic tau) has resulted in advances in novel disease-modifying therapies that target tau. This review addresses the basic concepts of and recent issues in tauopathies, including their clinical phenotypes, genetic features, biomarkers, and novel experimental therapies.  Key words: atypical parkinsonian disorders, corticobasal degeneration, progressive supranuclear palsy, proteinopathies, tauopathies 

Atypical Parkinsonian Syndromes: Tauopathies

2017 ◽  
Author(s):  
Hee Kyung Park ◽  
Irene Litvan
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Corticobasal Degeneration ◽  
Parkinsonian Syndromes ◽  
Disease Modifying Therapies ◽  
Experimental Therapies ◽  
Parkinsonian Disorders ◽  
Abnormal Accumulation ◽  
Genetic Features ◽  
Basic Concepts ◽  
Atypical Parkinsonian Disorders

Atypical parkinsonian disorders, which include two common proteinopathies, tauopathies and α-synucleinopathies, are clinically characterized by a progressive parkinsonism that typically does not respond to levodopa therapy and usually associates with early postural instability, falls, and other atypical features not observed in Parkinson disease. Tauopathies refer to neurodegenerative diseases in which there is an abnormal accumulation of hyperphosphorylated tau. The most frequent tauopathies are progressive supranuclear palsy and corticobasal degeneration. Better recognition of the expanding phenotypes of these disorders has led to the development of new diagnostic criteria. Furthermore, better knowledge about the pathogenesis (cell-to-cell transmission of pathologic tau) has resulted in advances in novel disease-modifying therapies that target tau. This review addresses the basic concepts of and recent issues in tauopathies, including their clinical phenotypes, genetic features, biomarkers, and novel experimental therapies.  Key words: atypical parkinsonian disorders, corticobasal degeneration, progressive supranuclear palsy, proteinopathies, tauopathies 

scholarly journals Tauopathies: One Disease or Many?

2011 ◽  
Vol 38 (4) ◽  
pp. 547-556 ◽  
Author(s):  
Manon Bouchard ◽  
Oksana Suchowersky
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Tau Protein ◽  
Clinical Result ◽  
Frontotemporal Lobar Degeneration ◽  
Disease Process ◽  
Corticobasal Degeneration ◽  
Pathological Lesions ◽  
Abnormal Accumulation ◽  
Genetic Features ◽  
The Brain

Tauopathies are a group of disorders that have in common abnormal accumulation of tau protein in the brain. Although the different tauopathies have long been considered to be separate diseases, it is now clear that progressive supranuclear palsy, corticobasal degeneration and some forms of tau-positive frontotemporal lobar degeneration share clinical, pathological and genetic features. The important overlap between these disorders suggest they may represent different phenotypes of a single disease process, the clinical result depending on the topography of pathological lesions as well as other unknown factors.

scholarly journals Therapeutic Application of rTMS in Atypical Parkinsonian Disorders

2021 ◽  
Vol 2021 ◽  
pp. 1-12
Author(s):  
Chrysi Petsani ◽  
Athina-Maria Aloizou ◽  
Vasileios Siokas ◽  
Lambros Messinis ◽  
Eleni Peristeri ◽  
...  
Keyword(s):  
Repetitive Transcranial Magnetic Stimulation ◽  
Alternative Therapy ◽  
Lewy Bodies ◽  
Corticobasal Degeneration ◽  
Double Blind ◽  
Beneficial Effects ◽  
Disease Modifying Therapies ◽  
Parkinsonian Disorders ◽  
Preliminary Phase ◽  
Atypical Parkinsonian Disorders

The terms atypical parkinsonian disorders (APDs) and Parkinson plus syndromes are mainly used to describe the four major entities of sporadic neuronal multisystem degeneration: progressive supranuclear palsy (PSP), corticobasal degeneration (CBD), multiple system atrophy (MSA), and dementia with Lewy bodies (LBD). APDs are characterized by a variety of symptoms and a lack of disease modifying therapies; their treatment thus remains mainly symptomatic. Brain stimulation via repetitive transcranial magnetic stimulation (rTMS) is a safe and noninvasive intervention using a magnetic coil, and it is considered an alternative therapy in various neuropsychiatric pathologies. In this paper, we review the available studies that investigate the efficacy of rTMS in the treatment of these APDs and Parkinson plus syndromes. Τhe majority of the studies have shown beneficial effects on motor and nonmotor symptoms, but research is still at a preliminary phase, with large, double-blind studies lacking in the literature.

scholarly journals Mechanisms of Neurodegeneration in Various Forms of Parkinsonism—Similarities and Differences

Cells ◽  
2021 ◽  
Vol 10 (3) ◽  
pp. 656
Author(s):  
Dariusz Koziorowski ◽  
Monika Figura ◽  
Łukasz M. Milanowski ◽  
Stanisław Szlufik ◽  
Piotr Alster ◽  
...  
Keyword(s):  
Neurodegenerative Diseases ◽  
Tau Protein ◽  
Protein Gene ◽  
Clinical Presentation ◽  
Neuronal Loss ◽  
Corticobasal Degeneration ◽  
Inflammatory Factors ◽  
Parkinsonian Disorders ◽  
Genetic Features ◽  
The Brain

Parkinson's disease (PD), dementia with Lewy body (DLB), progressive supranuclear palsy (PSP), corticobasal degeneration (CBD) and multiple system atrophy (MSA) belong to a group of neurodegenerative diseases called parkinsonian syndromes. They share several clinical, neuropathological and genetic features. Neurodegenerative diseases are characterized by the progressive dysfunction of specific populations of neurons, determining clinical presentation. Neuronal loss is associated with extra- and intracellular accumulation of misfolded proteins. The parkinsonian diseases affect distinct areas of the brain. PD and MSA belong to a group of synucleinopathies that are characterized by the presence of fibrillary aggregates of α-synuclein protein in the cytoplasm of selected populations of neurons and glial cells. PSP is a tauopathy associated with the pathological aggregation of the microtubule associated tau protein. Although PD is common in the world's aging population and has been extensively studied, the exact mechanisms of the neurodegeneration are still not fully understood. Growing evidence indicates that parkinsonian disorders to some extent share a genetic background, with two key components identified so far: the microtubule associated tau protein gene (MAPT) and the α-synuclein gene (SNCA). The main pathways of parkinsonian neurodegeneration described in the literature are the protein and mitochondrial pathways. The factors that lead to neurodegeneration are primarily environmental toxins, inflammatory factors, oxidative stress and traumatic brain injury.

scholarly journals The Value of GRE, ADC and Routine MRI in Distinguishing Parkinsonian Disorders

2013 ◽  
Vol 40 (3) ◽  
pp. 389-402 ◽  
Author(s):  
Pettarusp M. Wadia ◽  
Peter Howard ◽  
Manuel Q. Ribeirro ◽  
Jennifer Robblee ◽  
Abena Asante ◽  
...  
Keyword(s):  
Medical Records ◽  
Corticobasal Degeneration ◽  
Cellular Damage ◽  
Middle Cerebellar Peduncle ◽  
Clinical Criteria ◽  
Parkinsonian Syndromes ◽  
Parkinsonian Disorders ◽  
Apparent Diffusion ◽  
Adc Values ◽  
Cerebellar Peduncle

Objectives:To study different radiological signs and sequences including apparent diffusion coefficient (ADC) and gradient echo (GRE) to differentiate degenerative parkinsonian syndromes.Background:Multiple system atrophy (MSA), Parkinson's disease (PD), progressive supranuclear palsy (PSP) and corticobasal degeneration (CbD) differ in the pattern of neurodegeneration and cellular damage. Measuring the ADC, GRE sequences for paramagnetic substances and simple anatomical assessments have been reported individually to assist in separating some of these disorders, but have not been compared.Methods:brain MRIs from May 2002 to February 2008 were retrospectively evaluated by raters blinded to the clinical diagnosis for predefined MRI signs on T1, T2 and GRE sequences. ADC values were quantitatively measured. Medical records were objectively analyzed using standard clinical criteria for different parkinsonian syndromes.Results:195 cases comprising of 61 PD, 15 MSA-P, 7 MSA-C, 21 PSP, 6 Corticobasal syndrome, 21 not fitting criteria and 64 controls were evaluated. 73% of patients with MSA-P had hypointensity of the putamen (compared to the pallidum) on GRE. The specificity of this sign to diagnose MSA-P was 90% versus PD and 76% versus PSP. When GRE hypointensity was combined with atrophy of the putamen the specificity improved to 98% (versus PD) and 95% (versus PSP) without altering the sensitivity. The ADC values were significantly higher in the middle cerebellar peduncle in cases with MSA-C versus controls, PD and PSP (p<0.001).Conclusions:The combination of hypointensity and atrophy of the putamen on GRE is useful in differentiating MSA-P from other parkinsonian syndromes.

scholarly journals Midbrain Pons Ratio- A Diagnostic Tool for Progressive Supranuclear Palsy

2020 ◽  
Author(s):  
Mappilaveetil Sayed Jabir ◽  
Anjamparuthikal Aboobakar Haris
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Clinical Features ◽  
Corticobasal Degeneration ◽  
Cross Sectional Study ◽  
Cross Sectional ◽  
Course Of Illness ◽  
Medical College ◽  
Parkinsonian Syndromes ◽  
The Mean ◽  
Magnetic Resonance Imaging Mri

Introduction: Progressive Supranuclear Palsy (PSP) is a Parkinsonism plus syndrome. PSP has different clinical features, it is unresponsive to levodopa and have poor prognosis compared to classical Parkinson’s Disease (PD). However, in clinical practice accurate diagnosis of parkinsonian syndromes are difficult especially when the patient presents early during the course of illness. Diagnosis of each condition is important since it affects patient’s management, rehabilitation and prognosis. Magnetic Resonance Imaging (MRI) is especially useful tool in parkinsonian syndromes, since it identifies changes produced by the neurodegeneration. Rostral midbrain atrophy is seen in PSP. Midbrain pons ratio helps to identify the atrophy involving midbrain, thus helps in differentiating PSP from other causes of parkinsonism. Aim: To investigate the utility of midbrain diameter and midbrain pons ratio in mid-sagittal sections of MRI for differentiation of PSP from other neurodegenerative parkinsonism. Materials and Methods: This was a cross-sectional study conducted in Department of Neurology, Government Medical College, Kottayam, Kerala, India. Of all the patients who presented with clinical features of Parkinsonism, 124 patients who met the inclusion criteria were selected for the study. Comparison was made between the values obtained in clinically diagnosed patients with PSP (n=30), PD (n=30), Multiple System Atrophy (MSA) (n=30), Corticobasal Degeneration (CBD) (n=4) and normal Controls (n=30). These patients underwent MRI and the mid-sagittal T1 weighted MRI images were obtained; the diameter of midbrain and pontine base as well as midbrain-to-pons ratio was calculated. Quantitative analysis of five groups were done using Analysis of Variance (ANOVA) with post-hoc Tukey correction. Results: Mean age of patients in PSP was 59.47±3.86 years. The mean midbrain diameter was found to be lower in PSP, measuring 7.8±0.83 mm (p<0.001) with reduction of the midbrain-to-pons ratio. The mean midbrain pons ratio was found to be lower in PSP, measuring 0.45±0.03 in comparison with the other parkinsonian syndromes (p<0.001). Conclusion: Midbrain pons ratio and midbrain diameter in MRI is a simple measurement for differentiating PSP from other degenerative parkinsonian syndromes.

Bladder dysfunction in IPD and atypical Parkinsonian disorders – pathophysiology and treatment

2005 ◽  
Vol 32 (06) ◽  
Author(s):  
K Winge ◽  
H Stimpel ◽  
KK Nielsen ◽  
L Friberg ◽  
L Werdelin
Keyword(s):  
Bladder Dysfunction ◽  
Parkinsonian Disorders ◽  
Atypical Parkinsonian Disorders

scholarly journals A molecular pathology, neurobiology, biochemical, genetic and neuroimaging study of progressive apraxia of speech

2021 ◽  
Vol 12 (1) ◽  
Author(s):  
Keith A. Josephs ◽  
Joseph R. Duffy ◽  
Heather M. Clark ◽  
Rene L. Utianski ◽  
Edythe A. Strand ◽  
...  
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Molecular Pathology ◽  
Age At Onset ◽  
Haplotype Frequency ◽  
Corticobasal Degeneration ◽  
Apraxia Of Speech ◽  
Speech Characteristics ◽  
Biochemical Genetic ◽  
Neuroimaging Study ◽  
Longitudinal Imaging

AbstractProgressive apraxia of speech is a neurodegenerative syndrome affecting spoken communication. Molecular pathology, biochemistry, genetics, and longitudinal imaging were investigated in 32 autopsy-confirmed patients with progressive apraxia of speech who were followed over 10 years. Corticobasal degeneration and progressive supranuclear palsy (4R-tauopathies) were the most common underlying pathologies. Perceptually distinct speech characteristics, combined with age-at-onset, predicted specific 4R-tauopathy; phonetic subtype and younger age predicted corticobasal degeneration, and prosodic subtype and older age predicted progressive supranuclear palsy. Phonetic and prosodic subtypes showed differing relationships within the cortico-striato-pallido-nigro-luysial network. Biochemical analysis revealed no distinct differences in aggregated 4R-tau while tau H1 haplotype frequency (69%) was lower compared to 1000+ autopsy-confirmed 4R-tauopathies. Corticobasal degeneration patients had faster rates of decline, greater cortical degeneration, and shorter illness duration than progressive supranuclear palsy. These findings help define the pathobiology of progressive apraxia of speech and may have consequences for development of 4R-tau targeting treatment.

scholarly journals Cerebrospinal Fluid α-Synuclein Species in Cognitive and Movements Disorders

2021 ◽  
Vol 11 (1) ◽  
pp. 119
Author(s):  
Vasilios C. Constantinides ◽  
Nour K. Majbour ◽  
George P. Paraskevas ◽  
Ilham Abdi ◽  
Bared Safieh-Garabedian ◽  
...  
Keyword(s):  
Cerebrospinal Fluid ◽  
Multiple System Atrophy ◽  
Progressive Supranuclear Palsy ◽  
Movement Disorders ◽  
Corticobasal Degeneration ◽  
Healthy Controls ◽  
Frontotemporal Degeneration ◽  
Blood Contamination ◽  
Dementia Patients ◽  
Specificity And Sensitivity

Total CSF α-synuclein (t-α-syn), phosphorylated α-syn (pS129-α-syn) and α-syn oligomers (o-α-syn) have been studied as candidate biomarkers for synucleinopathies, with suboptimal specificity and sensitivity in the differentiation from healthy controls. Studies of α-syn species in patients with other underlying pathologies are lacking. The aim of this study was to investigate possible alterations in CSF α-syn species in a cohort of patients with diverse underlying pathologies. A total of 135 patients were included, comprising Parkinson’s disease (PD; n = 13), multiple system atrophy (MSA; n = 9), progressive supranuclear palsy (PSP; n = 13), corticobasal degeneration (CBD; n = 9), Alzheimer’s disease (AD; n = 51), frontotemporal degeneration (FTD; n = 26) and vascular dementia patients (VD; n = 14). PD patients exhibited higher pS129-α-syn/α-syn ratios compared to FTD (p = 0.045), after exclusion of samples with CSF blood contamination. When comparing movement disorders (i.e., MSA vs. PD vs. PSP vs. CBD), MSA patients had lower α-syn levels compared to CBD (p = 0.024). Patients with a synucleinopathy (PD and MSA) exhibited lower t-α-syn levels (p = 0.002; cut-off value: ≤865 pg/mL; sensitivity: 95%, specificity: 69%) and higher pS129-/t-α-syn ratios (p = 0.020; cut-off value: ≥0.122; sensitivity: 71%, specificity: 77%) compared to patients with tauopathies (PSP and CBD). There are no significant α-syn species alterations in non-synucleinopathies.

scholarly journals Clinical features differentiating patients with postmortem confirmed progressive supranuclear palsy and corticobasal degeneration

1999 ◽  
Vol 246 (S2) ◽  
pp. II1-II5 ◽  
Author(s):  
I. Litvan ◽  
D. A. Grimes ◽  
A. E. Lang ◽  
J. Jankovic ◽  
A. McKee ◽  
...  
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Clinical Features ◽  
Corticobasal Degeneration
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