Parkinsonismi FDG-PET e parkinsonismi Valentina Berti Dipartimento di Scienze Biomediche, Sperimentali e Cliniche Sez. Medicina Nucleare Università degli Studi di Firenze
History 140 PubMed: FDG AND parkinsonism 120 100 80 60 40 20 0 1980-1989 1990-1999 2000-2009 2010-2014
Clinical differentiation of parkisonian syndromes can be challenging Neuroimaging contributes to the correct diagnosis of parkinsonism Dopaminergic system imaging is recommended by international guidelines, but no/low accuracy in differential diagnosis FDG-PET Good accuracy in the differential diagnosis of parkinsonisms Correlation with clinical symptoms Correlation with pathological alterations
Parkinsonisms - Pathology α-synucleinopathies α-synuclein structural protein localized primarily in synaptic terminals and involved in synaptic plasticity Parkinson s disease - PD Parkinson s disease dementia PDD Dementia with Lewy bodies - DLB Multisystemic atrophy Tauopathies Tau protein microtubule-associated protein involved in axonal transport Progressive Supranuclear Palsy Corticobasal Degeneration/Syndrome
Parkinson s disease - PD Parkinson s disease dementia PDD Dementia with Lewy bodies - DLB Multisystemic Atrophy Progressive Supranuclear Palsy Cortico-basal syndrome / Cortico-basal Degeneration - CBS
PD Brain pathology α-synuclein-immunopositive Lewy neurites and Lewy bodies Braak staging of Lewy body pathology I. Medulla oblongata (Dorsal IX/X motor and anterior olfactory nucleus) II. Medulla oblongata and pontine tegmentum (caudal raphe nuclei, gigantocellular reticular nucleus, and coeruleus subcoeruleus complex) III.Midbrain (pars compacta substantia nigra) IV.Mesocortex (transentorhinal region) V.Neocortex (high order sensory association and prefrontal areas) VI.Neocortex (first order sensory association areas and premotor areas)
PD - FDG-PET pattern NL PD PD-early Widespread mild to severe cortical hypometabolism Parieto-temporo-occipital regions Frontal lobes Relative sparing of striata, thalamus, cerebellum PD-advanced
PD - FDG-PET pattern Key point Relative sparing of striata PD - early R
PD motor symptoms UPDRS III CMRGlu bilateral premotor cortex Putaminal dopaminergic deficit CMRGlu dorso-lateral prefrontal cortex premotor cortex anterior prefrontal cortex orbitofrontal cortex
PD cognitive symptoms Executive dysfunction: anterior cingulate cortex dorso-lateral prefrontal cortex orbito-frontal cortex Executive dysfunction: Dorso-lateral prefrontal cortex PCC Caudate nucleus dopaminergic deficit: anterior cingulate cortex dorso-lateral prefrontal cortex orbito-frontal cortex
PD cognitive pattern
From PD to PDD Hypometabolic cortical areas frequently observed in nondemented PD correspond to those in PDD and DLB FDG-PET findings in patients with PD without dementia span a spectrum from normality to pronounced posterior cortical and sometimes frontal hypometabolism as observed in patients with PDD Meyer et al. Current Opinion in Neurology 2014
PDD vs controls PD vs controls
From PD to PDD PD-MCI PD-MCI vs PD-nMCI PD-MCI vs controls Hypometabolism Prefrontal Cortex Superior and Inferior Parietal Cortex Associative Occipital Cortex
From PD to PDD PD-MCI Overall pattern of hypometabolism is similar in PDD and PD-MCI However, metabolic deficits were significantly more severe in PDD
From PD to PDD PD-MCI PDD: vs PDCN: extensive bilateral areas of reduced FDG uptake in the frontal, parietal, occipital and temporal lobes and in the posterior cingulate cortex; vs PDMCI: lower metabolism mainly in posterior brain areas (parietal, occipital and temporal lobes) than PD-MCI patients, and also, albeit to a lesser extent, in the right frontal lobe PD-MCI: vs PDCN: mild hypometabolism in the left frontal lobe and to a lesser extent in the left parietal lobe Garcia-Garcia et al. Eur J Nucl Med Mol Imaging 2012
PD-MCI, PDD cognitive symptoms regional glucose metabolism correlated with executive, memory, language and visuospatial functions Executive function: parietal, frontal and occipitotemporal junction; Memory: temporal and parietal regions; Visuospatial function: posterior areas (occipitoparietal and temporal) uptake; Language: anterior areas mainly the frontal lobe Garcia-Garcia et al. Eur J Nucl Med Mol Imaging 2012
From PDD to DLB Both PDD and DLB: widespread lateral frontal, temporoparietal and occipital hypometabolism PDD vs DLB: metabolic differences appear to be minor, if any
DLB metabolic pattern Congruence with Cortical cholinergic dysfunction Cognitive impairment Meyer et al. Current Opinion in Neurology 2014
DLB metabolic correlations Correlation between MMSE and regional FDG uptake in DLB lateral frontal, temporal and parietal association cortices cingulate gyrus and precuneus caudate nucleus no significant correlation is found in occipital cortex, in line with the finding that occipital hypometabolism may be observed well before and unrelated to cognitive impairment Meyer et al. Current Opinion in Neurology 2014
Conversion from PD to PDD Converters to PDD Baseline: significant hypometabolism in posterior cingulate, occipital cortex and caudate nucleus 2-year follow-up: widespread metabolic decline in association cortices, posterior cingulate, hippocampus and thalamus Primary visual cortex hypometabolism was also observed in cognitively stable PD patients.
Conversion to DLB Converters to DLB: hypometabolism in the parietal and the lateral occipital cortex compared to non-converters.
Parkinson s disease - PD Parkinson s disease dementia PDD Dementia with Lewy bodies - DLB Multisystemic Atrophy Progressive Supranuclear Palsy Cortico-basal syndrome / Cortico-basal Degeneration - CBS
MSA - Brain pathology MSA-C Predominant cerebellar ataxia MSA-P Parkinsonian clinical phenotype OPCA inferior olivary nucleus, pontine nuclei, cerebellar hemispheres and vermis SND substantia nigra (SbN), putamen, caudate nucleus and globus pallidus abnormal α-synuclein positive glial cytoplasmic inclusions in oligodendrocytes
MSA FDG-PET pattern NL MSA consistent with MSA neuropathological features Degenerative changes in: Striata (putamen < caudate) Cerebellum Brainstem More advenced stages: Frontal lobes Parietal lobes Occipital lobes basal ganglia (putamen and globus pallidus) cerebellum (cerebellar Purkinje cells) brainstem (substantia nigra, locus ceruleus, dorsal vagal nuclei, vestibular nuclei, inferior olives, and pontine nuclei) Hypometabolic pattern - reflects the loss of neurons and synaptic connections in these sites
MSA FDG-PET pattern R L
MSA motor symptoms ATAXIA negative CMRGlu CEREBELLUM
MSA Clinicometabolic correlation PARKINSONISM negative CMRglu STRIATUM AUTONOMIC DYSFUNCTION negative CMRglu THALAMUS
Tauopathies Neurodegenerative parkinsonism with disturbances in tau protein handling PSP and CBD similarities with frontotemporal dementia overlap in pathology with Alzheimer s disease
Parkinson s disease - PD Parkinson s disease dementia PDD Dementia with Lewy bodies - DLB Multisystemic Atrophy Progressive Supranuclear Palsy Cortico-basal syndrome / Cortico-basal Degeneration - CBS
PSP - Brain pathology Tau-positive star-shaped astrocytic tufts and neurofibrillary tangles
PSP FDG-PET pattern NL PSP consistent with Richardson's syndrome neuropathological features Subcortical Striata (caudate<putamen) Thalamus Brainstem Hypometabolism reflects the loss of neurons and synaptic connections in these sites Cortical Frontal lobe ACC Medial frontal cortex Neuropathologic alterations and neuronal loss in frontal lobes Functional deprivation of the frontal lobe due to pallidal degeneration
PSP FDG-PET pattern R L Statistical maps of hypometabolism from Teune et al. Mov Disord 2010
PSP FDG-PET pattern Midbrain hypometabolism Pimple sign focal area of midbrain hypometabolism on statistical maps of FDG-PET scans in some patients with PSP-Richardson s syndrome associated with midbrain atrophy helpful in differentiating PSP-RS from CBS and MSA definite pimple sign : high specificity (100%), low sensitivity (29%) possible or definite pimple sign : sensitivity of 79%
Atypical PSP FDG-PET pattern PSP-P Striata Thalamus Frontal lobe RS PSP-P
Atypical PSP FDG-PET pattern PSP-PAGF Midbrain Frontal lobe RS PAGF
PSP Clinicometabolic correlation COGNITIVE DEFICIT DISEASE DURATION positive negative CMRglu FRONTAL cortex MOTOR SYMPTOMS negative CMRglu CAUDATE NUCLEUS THALAMUS
Parkinson s disease - PD Parkinson s disease dementia PDD Dementia with Lewy bodies - DLB Multisystemic Atrophy Progressive Supranuclear Palsy Cortico-basal syndrome / Cortico-basal Degeneration - CBS
CBS - Brain pathology ballooned neurons and characteristic glial pathology, including tau-positive astrocytic plaques Same pathology Different clinical syndromes Same clinical syndrome Different pathologies
CBS FDG-PET pattern NL CBS ASYMMETRICAL DISTRIBUTION Hypometabolism contralateral to the clinically most affected side CORTICAL Frontal lobe Parieto-temporal regions SUBCORTICAL Striata (putamen=caudate) Thalamus
CBS FDG-PET pattern ASYMMETRICAL DISTRIBUTION Hypometabolism contralateral to the clinically most affected side CORTICAL Frontal lobe Parieto-temporal regions SUBCORTICAL Striata (putamen=caudate) Thalamus
Ad Interim Summary NL Disease-specific metabolic pattern in FDG-PET PD PDD DLB MSA Sparing (relative hypermetabolism) of putamen/pallidum and, possibly, thalamus and cerebellum Hypometabolism of occipital, temporoparietal and frontal cortices Hypometabolism of putamen, pons and/or cerebellum PSP CBS Hypometabolism of midline frontal, upper brainstem, thalamus and caudate nucleus Asymmetric hypometabolism of cortical and subcortical regions (striatum and thalamus), including parietal, primary sensorimotor, midline frontal and premotor cortices
PD vs atypical parkinsonisms Accuracy 95% MSA diagnosis Sensitivity 76.9% Specificity 96.9% PSP diagnosis Sensitivity 73.9% Specificity 95.2% CBD diagnosis Sensitivity 75.0% Specificity 91.7%
Juh et al.eur J Radiology 2004 Kwon et al. Eur J Neurol 2008 Baudrexel et al. Mov Disord 2014 FDG-PET in parkinsonism Differential diagnosis PD Sparing of the striata vs MSA Hypometabolism Occipital lobe and visual cortex Discriminating regions Putamen, pons vs PSP Occipital lobe Midbrain, midline frontal, thalamus
Juh et al.eur J Radiology 2004 Kwon et al. Eur J Neurol 2008 Baudrexel et al. Mov Disord 2014 FDG-PET in parkinsonism Differential diagnosis MSA Accuracy: 82-96% vs PD Hypometabolism Putamen (posterior>anterior), pons, cerebellum Discriminating regions Putamen, pons vs PSP Pons Midbrain, cingulated gyrus, pons
Juh et al.eur J Radiology 2004 Kwon et al. Eur J Neurol 2008 Baudrexel et al. Mov Disord 2014 FDG-PET in parkinsonism Differential diagnosis PSP vs PD vs MSA Hypometabolism Cingulated gyrus, caudate nucleus, thalamus and midbrain Cingulated gyrus, thalamus and midbrain Discriminating regions Midbrain, cingulated gyrus, thalamus Midbrain, cingulated gyrus, pons
Conclusion FDG-PET: Differential diagnosis Clinical variants Clinico-pathological correlation Thank you