BACKGROUND: Reports evaluating the efficacy of transcranial sonography (TCS) for the differential diagnosis of Parkinson disease (PD) and other movement disorders in China are scarce. Therefore, this study aimed to assess the application of TCS for the differential diagnosis of PD, multiple system atrophy (MSA), progressive supranuclear palsy (PSP), and essential tremor (ET) in Chinese individuals. METHODS: From 2017 to 2019, 500 inpatients treated at the Department of Dyskinesia, Beijing Tiantan Hospital, Capital Medical University underwent routine transcranial ultrasound examination. The cross-sections at the midbrain and thalamus levels were scanned, and the incidence rates of substantia nigra (SN) positivity and the incidence rates of lenticular hyperechoic area were recorded. The echo of the SN was manually measured. RESULTS: Of the 500 patients, 125 were excluded due to poor signal in temporal window sound transmission. Among the 375 individuals with good temporal window sound transmission, 200 were diagnosed with PD, 90 with ET, 50 with MSA, and 35 with PSP. The incidence rates of SN positivity differed significantly among the four patient groups (χ2 = 121.061, P < 0.001). Between-group comparisons were performed, and the PD group showed a higher SN positivity rate than the ET (χ2 = 94.898, P < 0.017), MSA (χ2 = 57.619, P < 0.017), and PSP (χ2 = 37.687, P < 0.017) groups. SN positivity showed a good diagnostic value for differentiating PD from the other three movement diseases, collectively or individually. The incidences of lenticular hyperechoic area significantly differed among the four patient groups (χ2 = 38.904, P < 0.001). Next, between-group comparisons were performed. The lenticular hyperechoic area was higher in the PD group than in the ET (χ2 = 6.714, P < 0.017) and MSA (χ2 = 18.680, P < 0.017) groups but lower than that in the PSP group (χ2 = 0.679, P > 0.017). CONCLUSION SN positivity could effectively differentiate PD from ET, PSP, and MSA in a Chinese population.
Diagnosis, Differential ; Humans ; Multiple System Atrophy/diagnostic imaging* ; Parkinson Disease/diagnostic imaging* ; Substantia Nigra/diagnostic imaging* ; Supranuclear Palsy, Progressive

OBJECTIVE: Multiple System Atrophy (MSA) and progressive supranuclear palsy (PSP) are rapidly progressive forms of degenerative Parkinsonism. The difficulties of diagnosing MSA and PSP in their early stages may lead to delayed referral to appropriate specialists and distress to patients, as well as delaying symptomatic treatment and participation in clinical trials. This work aimed to describe the symptoms that patients with MSA and PSP developed and plot their emergence relative to final diagnosis using a median onset in months. METHODS: Forty-seven patients from the United Kingdom with MSA or PSP diagnosed by a movement disorder specialist were interviewed with carers or relatives to establish milestone onset. This was corroborated using clinical notes and letters. RESULTS: In the MSA cohort (n = 23), autonomic symptoms (median 5.5 months before diagnosis) and falls (median 1 month before diagnosis) were the two clinical milestones which occurred before diagnosis. In the PSP cohort (n = 24), falling was the only milestone which occurred before diagnosis (median of 18.5 months). CONCLUSION: This study shows that PSP patients experience falling more than a year and a half an average before receiving a diagnosis and although MSA patients also tended to fall, this was much closer to the time of diagnosis. Further work with larger cohorts may illustrate whether these preliminary findings can be generalised to guide diagnosis and management.
Accidental Falls ; Advance Care Planning ; Caregivers ; Cohort Studies ; Delayed Diagnosis ; Diagnosis ; Great Britain ; Humans ; Movement Disorders ; Multiple System Atrophy ; Parkinsonian Disorders ; Referral and Consultation ; Retrospective Studies ; Specialization ; Supranuclear Palsy, Progressive

OBJECTIVE: The provisional diagnosis of progressive supranuclear palsy (PSP) depends on a combination of typical clinical features and specific MRI findings, such as atrophy of the tegmentum in the midbrain. Atrophy of the superior cerebellar peduncle (SCP) distinguishes PSP from other types of parkinsonism. Histological factors affect the conventional fluid-attenuated inversion recovery (FLAIR) signals, such as the extent of neuronal loss and gliosis. METHODS: We investigated patients with PSP to verify the percentage of patients with various PSP phenotypes presenting a high signal intensity in the SCP. Three interviewers, who were not informed about the clinical data, visually inspected the presence or absence of a high signal intensity in the SCP on the FLAIR images. We measured the pixel value in the SCP of each patient. Clinical characteristics were evaluated using the Mann-Whitney test, followed by the χ² test. RESULTS: Ten of the 51 patients with PSP showed a high signal intensity in the SCP on FLAIR MRI. Higher pixel values were observed within the SCP of patients with a high signal intensity in the SCP than in patients without a high signal intensity (p < 0.001). The sensitivity and specificity of the high signal intensity in the SCP of patients with PSP was 19.6% and 100%, respectively. This finding was more frequently observed in patients with PSP with Richardson's syndrome (PSP-RS) (25.7%) than other phenotypes (6.2%). CONCLUSION: The high signal intensity in the SCP on FLAIR MRI might be an effective diagnostic tool for PSP-RS.
Atrophy ; Diagnosis ; Gliosis ; Humans ; Magnetic Resonance Imaging ; Mesencephalon ; Neurodegenerative Diseases ; Neurons ; Parkinsonian Disorders ; Phenotype ; Sensitivity and Specificity ; Supranuclear Palsy, Progressive

The pathological features of Alzheimer's disease are senile plaques which are aggregates of β-amyloid peptides and neurofibrillary tangles in the brain. Neurofibrillary tangles are aggregates of hyperphosphorylated tau proteins, and these induce various other neurodegenerative diseases, such as progressive supranuclear palsy, corticobasal degeneration, frontotemporal lobar degeneration, frontotemporal dementia and parkinsonism linked to chromosome 17 (FTDP-17), and chronic traumatic encephalopathy. In the case of Alzheimer's disease, the measurement of neurofibrillary tangles associated with cognitive decline is suitable for differential diagnosis, disease progression assessment, and to monitor the effects of therapeutic treatment. This review discusses considerations for the development of tau ligands for imaging and summarizes the results of the first-in-human and preclinical studies of the tau tracers that have been developed thus far. The development of tau ligands for imaging studies will be helpful for differential diagnosis and for the development of therapeutic treatments for tauopathies including Alzheimer's disease.
Alzheimer Disease ; Brain ; Brain Injury, Chronic ; Chromosomes, Human, Pair 17 ; Diagnosis, Differential ; Disease Progression ; Frontotemporal Dementia ; Frontotemporal Lobar Degeneration ; Ligands ; Neurodegenerative Diseases ; Neurofibrillary Tangles ; Parkinsonian Disorders ; Peptides ; Plaque, Amyloid ; Supranuclear Palsy, Progressive ; tau Proteins ; Tauopathies

In recent years, several radiotracers that selectively bind to pathological tau proteins have been developed. Evidence is emerging that binding patterns of in vivo tau positron emission tomography (PET) studies in Alzheimer's disease (AD) patients closely resemble the distribution patterns of known neurofibrillary tangle pathology, with the extent of tracer binding reflecting the clinical and pathological progression of AD. In Lewy body diseases (LBD), tau PET imaging has clearly revealed cortical tau burden with a distribution pattern distinct from AD and increased cortical binding within the LBD spectrum. In progressive supranuclear palsy, the globus pallidus and midbrain have shown increased binding most prominently. Tau PET patterns in patients with corticobasal syndrome are characterized by asymmetrical uptake in the motor cortex and underlying white matter, as well as in the basal ganglia. Even in the patients with multiple system atrophy, which is basically a synucleinopathy, ¹⁸F-flortaucipir, a widely used tau PET tracer, also binds to the atrophic posterior putamen, possibly due to off-target binding. These distinct patterns of tau-selective radiotracer binding in the various degenerative parkinsonisms suggest its utility as a potential imaging biomarker for the differential diagnosis of parkinsonisms.
Alzheimer Disease ; Basal Ganglia ; Diagnosis, Differential ; Electrons ; Globus Pallidus ; Humans ; Lewy Bodies ; Mesencephalon ; Motor Cortex ; Multiple System Atrophy ; Neurofibrillary Tangles ; Parkinsonian Disorders ; Pathology ; Positron-Emission Tomography ; Putamen ; Supranuclear Palsy, Progressive ; tau Proteins ; White Matter

Progressive supranuclear palsy (PSP) with predominant cerebellar ataxia (PSP-C) is a rare phenotype of PSP. The clinical and radiological features of this disorder remain poorly characterized. Through a retrospective case series, we aim to characterize the clinical and radiological features of PSP-C. Four patients with PSP-C were identified: patients who presented with prominent cerebellar dysfunction that disappeared with the progression of the disease. Supranuclear gaze palsy occurred at a mean of 2.0 ± 2.3 years after the onset of ataxia. Mild cerebellar volume loss and midbrain atrophy were detected on brain imaging, which are supportive of a diagnosis of PSP. Videos are presented illustrating the co-existence of cerebellar signs and supranuclear gaze palsy and the disappearance of cerebellar signs with disease progression. Better recognition and the development of validated diagnostic criteria would aid in the antemortem recognition of this rare condition.
Ataxia ; Atrophy ; Cerebellar Ataxia* ; Cerebellar Diseases ; Diagnosis ; Disease Progression ; Humans ; Mesencephalon ; Neuroimaging ; Paralysis* ; Phenotype ; Retrospective Studies ; Supranuclear Palsy, Progressive

BACKGROUND AND PURPOSE: Various magnetic resonance (MR) measurements have been proposed to aid in differentiating between progressive supranuclear palsy (PSP) and idiopathic Parkinson's disease (IPD); however, these methods have not been compared directly. The aim of this study was to determine which measurement method exhibits the highest power to differentiate between PSP and IPD. METHODS: Brain MR images from 82 IPD and 29 PSP patients were analyzed retrospectively. T1-weighted 3D volumetric axial images, or sagittal images reconstructed from those axial images were examined. MR measurements included the length from the interpeduncular fossa to the center of the cerebral aqueduct at the mid-mammillary-body level, adjusted according to the anterior commissure-posterior commissure length (MB(Tegm)), the ratio of the midbrain area to the pons area (M/P ratio) as measured by both Oba's method (Oba M/P) and Cosottini's method (Cosottini M/P), and a modified MR parkinsonism index (mMRPI). RESULTS: Receiver operating characteristic (ROC) analysis indicated that the areas under the ROC curves (AUCs) exceeded 0.70, with a high intrarater reliability for all MR measurement methods. ROC analyses of four MR measurements yielded AUCs of 0.69-0.76. At the cutoff value with the highest Youden index, mMRPI had the highest sensitivity, while Oba M/P offered the highest specificity. A comparison of the ROC analyses revealed that MB(Tegm) was superior to mMRPI in differentiating PSP from IPD (p=0.049). There was no difference in discriminating power among Oba M/P, Cosottini M/P, and MB(Tegm). CONCLUSIONS: Simple measurements of MB(Tegm) on axial MR images at the mid-mammillary-body level are comparable to measurements of the M/P ratio with regard to their ability to discriminate PSP from IPD.
Area Under Curve ; Brain ; Cerebral Aqueduct ; Diagnosis, Differential* ; Humans ; Magnetic Resonance Imaging ; Mesencephalon* ; Neuroimaging ; Parkinson Disease* ; Parkinsonian Disorders ; Pons ; Retrospective Studies ; ROC Curve ; Sensitivity and Specificity ; Supranuclear Palsy, Progressive*

We report a patient with progressive supranuclear palsy (PSP) with his serial photographs before the onset of ocular symptoms and after the onset with two year intervals. These photographs show his progressive eyeball deviations toward complete exotropia. There were no effective voluntary eyeball movements, Bell's phenomenon, doll's eye movements, and vestibulo-ocular reflexes. These signs indicate the involvement of the oculomotor nuclear complex by the disease. We suggest that PSP may cause not only 'supranuclear' but also 'nuclear' complete ophthalmoplegia with exodeviation of the eyes.
Aged ; Exotropia/diagnosis ; Eye Movements ; Humans ; Magnetic Resonance Imaging ; Male ; Ophthalmoplegia/*diagnosis ; Supranuclear Palsy, Progressive/*diagnosis ; Time Factors ; Vision, Binocular

Imaging of the dopamine transporter (DAT) provides a marker for the integrity of presynaptic nigrostriatal dopaminergic system. DAT density is reduced in Parkinson disease, multiple system atrophy, and progressive supranuclear palsy. In patients with suspicious parkinsonism, normal DAT imaging suggests an alternative diagnosis such as essential tremor, vascular parkinsonism, or drug-induced parkinsonism. DAT imaging is a useful tool to aid clinician's differential diagnosis in parkinsonism.
Diagnosis ; Diagnosis, Differential ; Dopamine Plasma Membrane Transport Proteins* ; Dopamine* ; Essential Tremor ; Humans ; Multiple System Atrophy ; Parkinson Disease ; Parkinsonian Disorders ; Supranuclear Palsy, Progressive

Parkinson's disease is one of the most frequent neurodegenerative diseases, which mainly affects the elderly. Parkinson's disease is often difficult to differentiate from atypical parkinson diorder such as progressive supranuclear palsy, multiple system atrophy, dementia with Lewy body, and corticobasal ganglionic degeneration, based on the clinical findings because of the similarity of phenotypes and lack of diagnostic markers. The accurate diagnosis of Parkinson's disease and atypical Parkinson disorders is not only important for deciding on treatment regimens and providing prognosis, but also it is critical for studies designed to investigate etiology and pathogenesis of parkinsonism and to develop new therapeutic strategies. Although degeneration of the nigrostriatal dopamine system results in marked loss of striatal dopamine content in most of the diseases causing parkinsonism, pathologic studies revealed different topographies of the neuronal cell loss in Parkisonism. Since the regional cerebral glucose metabolism is a marker of integrated local synaptic activity and as such is sensitive to both direct neuronal/synaptic damage and secondary functional disruption at synapses distant from the primary site of pathology, an assessment of the regional cerebral glucose metabolism with F-18 FDG PET is useful in the differential diagnosis of parkinsonism and evaluating the pathophysiology of parkisonism.
Aged ; Dementia ; Diagnosis ; Diagnosis, Differential ; Dopamine ; Ganglion Cysts ; Glucose ; Humans ; Lewy Bodies ; Metabolism ; Multiple System Atrophy ; Neurodegenerative Diseases ; Neurons ; Parkinson Disease ; Parkinsonian Disorders* ; Pathology ; Phenotype ; Prognosis ; Supranuclear Palsy, Progressive ; Synapses