scholarly journals Safety and Effectiveness of Cell Therapy in Neurodegenerative Diseases: Take-Home Messages From a Pilot Feasibility Phase I Study of Progressive Supranuclear Palsy

2021 ◽  
Vol 15 ◽  
Author(s):  
Rosaria Giordano ◽  
Margherita Canesi ◽  
Maurizio Isalberti ◽  
Giovanni Marfia ◽  
Rolando Campanella ◽  
...  
Keyword(s):  
Adverse Events ◽  
Neurodegenerative Diseases ◽  
Progressive Supranuclear Palsy ◽  
Rating Scales ◽  
Photon Emission ◽  
Blood Levels ◽  
Emission Computed Tomography ◽  
Size Estimation ◽  
Phase Ii Trials ◽  
Severe Adverse Events

Mesenchymal stromal cells (MSCs) are multipotent cells with anti-inflammatory properties. Here we tested the safety of MSCs in patients with progressive supranuclear palsy (PSP; ClinicalTrials.gov: NCT01824121; Eudract No. 2011-004051-39). Seven patients were treated. To improve the safety, protocol adjustments were made during the performance of the study. The objectives of our work were: (1) to assess the safety of MSCs and (2) to identify critical issues in cell therapies for neurodegenerative diseases. Autologous MSCs from the bone marrow of PSP patients were administered through the internal carotid arteries. 1-year survival and number of severe adverse events were considered as safety endpoints. Clinical rating scales, neuropsychological assessments, gait and posture analysis, single-photon emission computed tomography, positron emission tomography, and brain magnetic resonance (BMR) were performed at different follow-up times. Peripheral blood levels of inflammatory cytokines were measured before and after cell infusion. Six of the seven treated patients were living 1 year after cell infusion. Asymptomatic spotty lesions were observed at BMR after 24 h in six of the seven treated patients. The last patient in the preliminary cohort (Case 5) exhibited transiently symptomatic BMR ischemic alterations. No severe adverse events were recorded in the last two treated patients. Interleukin-8 serum concentrations decreased in three patients (Case 2, 3, and 4). An adaptive study design, appropriate and up-to-date efficacy measures, adequate sample size estimation, and, possibly, the use of a cellular and/or allogeneic cell sources may help in performing phase II trials in the field.

scholarly journals The Use of [99mTc]-HM-PAO in the Diagnosis of Primary Degenerative Dementia

1988 ◽  
Vol 8 (1_suppl) ◽  
pp. S123-S126 ◽  
Author(s):  
H. J. Testa ◽  
J. S. Snowden ◽  
D. Neary ◽  
R. A. Shields ◽  
A. W. I. Burjan ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Progressive Supranuclear Palsy ◽  
Frontal Lobe ◽  
Single Photon ◽  
Photon Emission ◽  
Cerebral Atrophy ◽  
Emission Computed Tomography ◽  
Clinical Value ◽  
Diagnosis Of Dementia

The clinical value of single photon emission computed tomography (SPECT) in the differential diagnosis of dementia due to cerebral atrophy was evaluated by comparing the pattern of distribution [99mTc]–HM-PAO in three dementing conditions. Imaging was carried out in 26 patients with suspected Alzheimer's disease, 14 with dementia of the frontal-lobe type, and 13 with progressive supranuclear palsy. Images were evaluated and reported without knowledge of clinical diagnosis with respect to regions of reduced uptake of tracer. Reduced uptake in the posterior cerebral hemispheres was characteristic of Alzheimer's disease, while selective anterior hemisphere abnormalities characterized both dementia of the frontal-lobe type and progressive supranuclear palsy. The latter conditions could be distinguished on the basis of the appearance of integrity of the rim of the frontal cortex. The technique has an important role in the differentiation of degenerative dementias.

Combined Use of 123i-fp-cit Spect and 123i-mibg Scintigraphy for Differentiation of Progressive Supranuclear Palsy Subtypes and Parkinson's Disease

2020 ◽  
Author(s):  
Keita Sakurai ◽  
Shohei Inui ◽  
Yufuko Saito ◽  
Satoko Sakakibara ◽  
Rina Hashimoto ◽  
...  
Keyword(s):  
Parkinson’S Disease ◽  
Parkinson's Disease ◽  
Progressive Supranuclear Palsy ◽  
Single Photon ◽  
Photon Emission ◽  
Washout Rate ◽  
Emission Computed Tomography ◽  
Mibg Scintigraphy ◽  
Adaptive Boosting ◽  
Specific Binding Ratio

Abstract Background:This study was undertaken to investigate the utility of 123I-ioflupane (123I-FP-CIT) single photon emission computed tomography (SPECT), 123I-metaiodobenzylguanidine (123I-MIBG) scintigraphy and both of these to differentiate among progressive supranuclear palsy (PSP), including typical cases and other subtypes, and Parkinson’s disease (PD).Methods: Twenty-five patients with typical PSP (Richardson's syndrome; PSP-RS), 14 atypical ones (PSP-variants; PSP-V) and 42 PD who underwent both 23I-FP-CIT SPECT and 123I-MIBG scintigraphy within short intervals were enrolled. Specific binding ratio (SBR) of the striatum and midbrain and anteroposterior and asymmetry ratio of the striatal SBR on 123I-FP-CIT SPECT and heart-to-mediastinum (H/M) ratio and washout rate (WR) on 123I-MIBG scintigraphy were used as quantitative measures. The classifier performance based on adaptive boosting was evaluated using five-fold cross-validation for these measures.Results: Midbrain SBR and the striatal anteroposterior ratio were statistically lower in PSP-RS than PD. On the other hand, there were no significant differences in any other quantitative measures among PSP-RS, PSP-V and PD. Striatal and midbrain SBRs and anteroposterior ratio of PSP-V were approximately in-between those of PSP-RS and PD. PD showed the lowest early and delayed H/M ratios and highest WR of any group. The combination of 123I-FP-CIT and 123I-MIBG was useful in discriminating PSP-RS and PSP-V from PD, while 123I-FP-CIT was superior to 123I-MIBG in differentiating PSP-RS from PSP-V.Conclusion: The combination of 123I-FP-CIT SPECT and 123I-MIBG scintigraphy, rather than either alone, may be a useful differential diagnostic tool to differentiate patients with PSP-RS, PSP-V and PD.

Report of an International Workshop to Standardize Response Criteria for Non-Hodgkin's Lymphomas

1999 ◽  
Vol 17 (4) ◽  
pp. 1244-1244 ◽  
Author(s):  
Bruce D. Cheson ◽  
Sandra J. Horning ◽  
Bertr Coiffier ◽  
Margaret A. Shipp ◽  
Richard I. Fisher ◽  
...  
Keyword(s):  
Clinical Trials ◽  
Photon Emission ◽  
Large Cell ◽  
Phase Iii ◽  
Computer Assisted ◽  
Emission Computed Tomography ◽  
Transverse Diameter ◽  
Phase Ii Trials ◽  
Valuable Adjunct ◽  
Hodgkin's Lymphomas

ABSTRACT: Standardized guidelines for response assessment are needed to ensure comparability among clinical trials in non-Hodgkin's lymphomas (NHL). To achieve this, two meetings were convened among United States and international lymphoma experts representing medical hematology/oncology, radiology, radiation oncology, and pathology to review currently used response definitions and to develop a uniform set of criteria for assessing response in clinical trials. The criteria that were developed include anatomic definitions of response, with normal lymph node size after treatment of 1.5 cm in the longest transverse diameter by computer-assisted tomography scan. A designation of complete response/unconfirmed was adopted to include patients with a greater than 75% reduction in tumor size after therapy but with a residual mass, to include patients—especially those with large-cell NHL—who may not have residual disease. Single-photon emission computed tomography gallium scans are encouraged as a valuable adjunct to assessment of patients with large-cell NHL, but such scans require appropriate expertise. Flow cytometric, cytogenetic, and molecular studies are not currently included in response definitions. Response rates may be the most important objective in phase II trials where the activity of a new agent is important and may provide support for approval by regulatory agencies. However, the goals of most phase III trials are to identify therapies that will prolong the progression-free survival, if not the overall survival, of the treated patients. We hope that these guidelines will serve to improve communication among investigators and comparability among clinical trials until clinically relevant laboratory and imaging studies are identified and become more widely available.

scholarly journals Word-Retrieval in Two Cases of Progressive Supranuclear Palsy

1997 ◽  
Vol 10 (1) ◽  
pp. 31-41 ◽  
Author(s):  
Jennifer M. Gurd ◽  
John R. Hodges
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Single Photon ◽  
Photon Emission ◽  
Word Retrieval ◽  
Emission Computed Tomography ◽  
Word Finding ◽  
Neuropsychological Investigation ◽  
Scan Data ◽  
Motor Effects

In this paper, we describe the detailed neuropsychological investigation of two cases of progressive supranuclear palsy (PSP) and demonstrate word-finding difficulties associated with pervasive problems in word-retrieval. The pattern of deficits resembles that seen in Parkinson’s Disease (PD) but is more severe, even in very mild PSP, and appears less amenable to cue facilitation. Performance on a variety of word-production tasks is compared, and experimental controls for motor effects on performance are included. The role of stimulus cues in speeded word-finding is addressed experimentally, as are central executive influences on task performance. This combines with functional brain-scan data from single photon emission computed tomography (SPECT) which shows reduced frontal perfusion in one of the two cases.

scholarly journals The Role of Frontal Assessment Battery and Frontal Lobe Single-Photon Emission Computed Tomography in the Differential Diagnosis of Progressive Supranuclear Palsy Variants and Corticobasal Syndrome—A Pilot Study

2021 ◽  
Vol 12 ◽  
Author(s):  
Piotr Alster ◽  
Bartosz Migda ◽  
Natalia Madetko ◽  
Karolina Duszyńska-Wąs ◽  
Agnieszka Drzewińska ◽  
...  
Keyword(s):  
Computed Tomography ◽  
Differential Diagnosis ◽  
Progressive Supranuclear Palsy ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Frontal Assessment Battery ◽  
Single Photon Emission ◽  
Single Photon Emission Computed ◽  
Photon Emission Computed Tomography

Progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) are clinical syndromes classified as atypical parkinsonism. Due to their overlapping symptomatology, recent research shows the necessity of finding new methods of examination of these clinical entities. PSP is a heterogenic disease. PSP Richardson-Steele Syndrome (PSP-RS) and parkinsonism predominant (PSP-P) are the most common clinical variants of progressive supranuclear palsy syndrome. The different clinical course and life expectancy of PSP-RS and PSP-P stress the need of efficient examination in the early stages. The aim of the study was to evaluate the possible feasibility of the combined use of frontal assessment battery (FAB) and single-photon emission computed tomography (SPECT) in the differentiation of PSP-RS, PSP-P, and CBS. The findings show that FAB may be interpreted as a possible supplementary tool in the differential diagnosis of PSP-P and PSP-RS. The differences in SPECT are less pronounced. The study does not show any advantages of performing combined frontal SPECT and FAB in the differential examination of PSP and CBS. Moreover, PSP-RS and CBS, in a detailed evaluation of the frontal lobe, do not show any significant differences. This is a relatively small study which, however, highlights the relevant features of clinical examination of these rare entities.

scholarly journals Cerebral Hypoperfusion in Progressive Supranuclear Palsy (PSP) and Corticobasal Syndrome (CBS)

2019 ◽  
Author(s):  
Piotr Alster ◽  
Michał Nieciecki ◽  
Dariusz Koziorowski ◽  
Ingeborga Charzyńska ◽  
Leszek Królicki ◽  
...  
Keyword(s):  
Progressive Supranuclear Palsy ◽  
Single Photon ◽  
Contemporary Literature ◽  
Photon Emission ◽  
Clinical Manifestations ◽  
Corticobasal Syndrome ◽  
Cerebral Hypoperfusion ◽  
Emission Computed Tomography ◽  
Extended Analysis ◽  
Photon Emission Computed Tomography

Abstract Background: Perfusion single photon emission computed tomography (SPECT) as a method of examination of progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS) as its clinical manifestation was not extensively analyzed in contemporary literature. Recent criteria of PSP and CBS do not describe this method of examination as primary or additional. The aim of this work is to present whether SPECT HMPAO can be a method of examination possibly differentiating the diseases. Methods: 21 patients with PSP. and 14 patients with CBS were examined using SPECT HMPAO. Extended analysis was done in the context of regions of interest affected by significant average hypoperfusion (>2 standard deviations). Differences between the diseases where subsequently evaluated using U-Mann-Whitney test. Results: Results confirmed significant differences (p<0,05) within the left and right thalamus, Hypoperfusion of this region was observed in both of the diseases. Conclusion: Relatively small differences of hypoperfusion in the indicated regions led to a conclusion that PSP and CBS should not be differentiated using SPECT HMPAO. The overlapping of clinical manifestations and locations of hypoperfusion leads to a question whether the diseases should be interpreted as separate entities or variants of the same disease.

scholarly journals Neuroimaging techniques for diagnosing Alzheimer’s disease and cerebrovascular diseases with cognitive impairment

2019 ◽  
Vol 11 (3S) ◽  
pp. 18-25 ◽  
Author(s):  
I. V. Litvinenko ◽  
A. Yu. Emelin ◽  
V. Yu. Lobzin ◽  
K. A. Kolmakova
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Impairment ◽  
Magnetic Resonance ◽  
Rating Scales ◽  
Single Photon ◽  
Photon Emission ◽  
Emission Computed Tomography ◽  
Resonance Spectroscopy ◽  
Neuroimaging Techniques

The paper provides data on current neuroimaging techniques for diagnosing Alzheimer’s disease and vascular cognitive impairment (CN). Structural neuroimaging methods can identify potentially treatable diseases leading to dementia and assess the magnitude and localization of atrophic and cerebrovascular changes in brain tissue. Particular attention is paid to the specific signs of Alzheimer’s disease: to the visual assessment of sections and the use of various rating scales (GCA, MTA, Koedam). Vascular changes that are most significant for the development of CI are considered. A new approach to diagnosing CI is presented, by taking into account the biomarkers of amyloidosis, tauopathy, neurodegeneration, and cerebrovascular damage. The results of the authors’ own investigations using positron emission tomography, single photon emission computed tomography, magnetic resonance spectroscopy, and functional magnetic resonance imaging at rest allow these techniques to be recommended for the early diagnosis of CI of different genesis.

scholarly journals Brain SPECT as a Biomarker of Neurodegeneration in Dementia in the Era of Molecular Imaging: Still a Valid Option?

2021 ◽  
Vol 12 ◽  
Author(s):  
Rodolfo Ferrando ◽  
Andres Damian
Keyword(s):  
Neurodegenerative Diseases ◽  
Single Photon ◽  
Photon Emission ◽  
High Sensitivity ◽  
Emission Computed Tomography ◽  
Middle Income ◽  
Middle Income Countries ◽  
Leading Role ◽  
Positron Emission ◽  
Additional Costs

Biomarkers are playing a progressively leading role in both clinical practice and scientific research in dementia. Although amyloid and tau biomarkers have gained ground in the clinical community in recent years, neurodegeneration biomarkers continue to play a key role due to their ability to identify different patterns of brain involvement that sign the transition between asymptomatic and symptomatic stages of the disease with high sensitivity and specificity. Both 18F-FDG positron emission tomography (PET) and perfusion single photon emission computed tomography (SPECT) have proved useful to reveal the functional alterations underlying various neurodegenerative diseases. Although the focus of nuclear neuroimaging has shifted to PET, the lower cost and wider availability of SPECT make it a still valid alternative for the study of patients with dementia. This review discusses the principles of both techniques, compares their diagnostic performance for the diagnosis of neurodegenerative diseases and highlights the role of SPECT to characterize patients from low- and middle-income countries, where special care of additional costs is particularly needed to meet the new recommendations for the diagnosis and characterization of patients with dementia.

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