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

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.

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Differential Diagnosis of Parkinsonism

Canadian Journal of Neurological Sciences / Journal Canadien des Sciences Neurologiques ◽

10.1017/s0317167100000020 ◽

1999 ◽

Vol 26 (S2) ◽

pp. S1-S4 ◽

Cited By ~ 5

Author(s):

A. Jon Stoessl ◽

Jean Rivest

Keyword(s):

Differential Diagnosis ◽

Multiple System Atrophy ◽

Progressive Supranuclear Palsy ◽

Essential Tremor ◽

Clinical Features ◽

Lewy Body ◽

Lewy Body Disease ◽

Corticobasal Degeneration ◽

Diffuse Lewy Body Disease ◽

Degenerative Disorders

The diagnosis of Parkinson's disease is predominantly clinical, based on a combination of the cardinal features of tremor, bradykinesia and rigidity. The differential essentially lies between other conditions resulting in tremor, of which essential tremor is the commonest, and other akinetic-rigid syndromes. These include progressive supranuclear palsy, multiple system atrophy, toxins and other degenerative disorders, including diffuse Lewy body disease and corticobasal degeneration. The key clinical features of these disorders and a practical diagnostic approach are briefly reviewed in this article.

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

Nature Communications ◽

10.1038/s41467-021-23687-8 ◽

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.

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Cerebrospinal Fluid α-Synuclein Species in Cognitive and Movements Disorders

Brain Sciences ◽

10.3390/brainsci11010119 ◽

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.

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