A disease-specific metabolic brain network associated with corticobasal degeneration

Abstract

Corticobasal degeneration is an uncommon parkinsonian variant condition that is diagnosed mainly on clinical examination. To facilitate the differential diagnosis of this disorder, we used metabolic brain imaging to characterize a specific network that can be used to discriminate corticobasal degeneration from other atypical parkinsonian syndromes. Ten non-demented patients (eight females/two males; age 73.9 ± 5.7 years) underwent metabolic brain imaging with (18)F-fluorodeoxyglucose positron emission tomography for atypical parkinsonism. These individuals were diagnosed clinically with probable corticobasal degeneration. This diagnosis was confirmed in the three subjects who additionally underwent post-mortem examination. Ten age-matched healthy subjects (five females/five males; age 71.7 ± 6.7 years) served as controls for the imaging studies. Spatial covariance analysis was applied to scan data from the combined group to identify a significant corticobasal degeneration-related metabolic pattern that discriminated (P < 0.001) the patients from the healthy control group. This pattern was characterized by bilateral, asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus. These pattern-related changes were greater in magnitude in the cerebral hemisphere opposite the more clinically affected body side. The presence of this corticobasal degeneration-related metabolic topography was confirmed in two independent testing sets of patient and control scans, with elevated pattern expression (P < 0.001) in both disease groups relative to corresponding normal values. We next determined whether prospectively computed expression values for this pattern accurately discriminated corticobasal degeneration from multiple system atrophy and progressive supranuclear palsy (the two most common atypical parkinsonian syndromes) on a single case basis. Based upon this measure, corticobasal degeneration was successfully distinguished from multiple system atrophy (P < 0.001) but not progressive supranuclear palsy, presumably because of the overlap (∼ 24%) that existed between the corticobasal degeneration- and the progressive supranuclear palsy-related metabolic topographies. Nonetheless, excellent discrimination between these disease entities was achieved by computing hemispheric asymmetry scores for the corticobasal degeneration-related pattern on a prospective single scan basis. Indeed, a logistic algorithm based on the asymmetry scores combined with separately computed expression values for a previously validated progressive supranuclear palsy-related pattern provided excellent specificity (corticobasal degeneration: 92.7%; progressive supranuclear palsy: 94.1%) in classifying 58 testing subjects. In conclusion, corticobasal degeneration is associated with a reproducible disease-related metabolic covariance pattern that may help to distinguish this disorder from other atypical parkinsonian syndromes.

Cognitive dysfunction in corticobasal degeneration

“…Although asymmetric metabolic reductions involving frontal and parietal cortex, thalamus, and caudate nucleus are not specific for CBD diagnosis 40 , one study hypothesized that parietal hypometabolism may be a distinctive feature 41 . Additionally, targeted methods such as SPECT and PET assessing striatal dopaminergic activity, and techniques focused on specific markers, such as tau protein, are of growing interest.…”

Nuclear Medicine Applications in Movement Disorders

“…Buna karşılık, MSA'da bazal gangliada ve serebellumda hipometabolizma izlenir ve bu tutulum farklılığı sayesinde MSA ile PH'nin ayırıcı tanısı yapılabilir (1,21,35,39,41). Beyin FDG PET görüntüleme bulgularına dayanan tanısal sınıflandırma kesin klinik tanı ile %90 oranında örtüşmekte ve nörodejeneratif parkinsonizm nedenleri (PH, MSA, PSP ve LCD) %90 oranında ayırt edilebilmektedir (21,22,35,40). Parkinsonizm sendromlarında beyin FDG PET görüntüleme saptanan anormal bulguların yaygınlığı ve derecesi klinik bulgular ile genellikle korelasyon gösterir (1,3,19,23,24,30,34,35,39,49,50,51,52).…”

“…Serebellumda hipometabolizma olması parkinsonizm ayırıcı tanısında yer alan diğer nörodejeneratif hastalıklarda gözlenmemesi nedeniyle MSA'nın ayırıcı tanısına yardımcı özgül bir bulgudur (39). Benzer biçimde MSA'da bazal gangliada tutulumun bilateral olması, asimetrik bazal ganglia tutulumu gözlenen KBD ile ayırıcı tanı bakımından yardımcı bir özelliktir (39,40).…”

“…KBD ise tipik olarak asimetrik başlangıçlı, nadir görülen nörodejeneratif bir hastalık olup, hastalarda klinik olarak akineto-rijid sendrom, distoni, miyoklonus, apraksi, kortikal duyu kaybı ve yabancı el sendromu gibi bulgular vardır (56). KBD hastalarında vücudun en çok etkilenen tarafının karşı tarafındaki serebral hemisferde daha belirgin olmak üzere asimetrik bilateral kaudat ve talamik çekirdek tutulumu; parietal lobda, orta frontal ve singulat girusta kortikal hipometabolizma bulguları izlenir (3,21,37,39,40). Ancak her ikisi de beyinde anormal tau (4R-taupati) birikimleri ile karakterize olan PSP ve KBD, metabolik tutulum biçimi bakımından da benzerlik gösterebilir (58).…”

“…Ancak her ikisi de beyinde anormal tau (4R-taupati) birikimleri ile karakterize olan PSP ve KBD, metabolik tutulum biçimi bakımından da benzerlik gösterebilir (58). Bu durumda metabolik tutulum bakımından hemisferik asimetrinin sayısal olarak gösterilmesi PSP ve KBD hastalarının ayırıcı tanısını iyileştirmektedir (40,58).…”