 |
|
Patterns of Brain Atrophy That Differentiate Corticobasal Degeneration Syndrome From Progressive Supranuclear Palsy
Adam L. Boxer, MD, PhD;
Michael D. Geschwind, MD, PhD;
Nataliya Belfor, PhD;
Maria Luisa Gorno-Tempini, MD, PhD;
Guido F. Schauer, BSc;
Bruce L. Miller, MD;
Michael W. Weiner, MD;
Howard J. Rosen, MD
Arch Neurol. 2006;63:81-86.
ABSTRACT
| |
Background Progressive brain atrophy is associated with the corticobasal degeneration syndrome (CBDS) and progressive supranuclear palsy (PSP). Regional differences in brain atrophy may reflect the clinical features of disease.
Objective To quantify the structural neuroanatomical differences between CBDS and PSP.
Design A survey of neurologic deficits was conducted in all patients. Voxel-based morphometry was used to quantify structural neuroanatomical differences on magnetic resonance images in each subject group.
Setting University hospital dementia clinic.
Participants Fourteen patients who met clinical research criteria for CBD and 15 patients who met clinical research criteria for PSP, who were matched for severity of disease, age, and functional status, and 80 age-matched control subjects.
Main Outcome Measures Statistically significant differences in regional gray and white matter volume, after multiple comparisons correction, between groups of subjects.
Results The patients with CBDS displayed an asymmetric (left > right) pattern of brain atrophy that involved the bilateral premotor cortex, superior parietal lobules, and striatum. Progressive supranuclear palsy was associated with atrophy of the midbrain, pons, thalamus, and striatum, with minimal involvement of the frontal cortex. Midbrain structures were more atrophied in PSP than in CBD, whereas dorsal frontal and parietal cortices were more atrophied in CBD than in PSP. The degree of atrophy of the midbrain and pontine tegmentum and the left frontal eye field differentiated the 2 patient groups with 93% accuracy.
Conclusions Distinct patterns of brain atrophy exist in CBDS and PSP that can be used to differentiate the 2 diseases. Assessments of brain atrophy in these disorders should be focused on cortical and brainstem ocular motor control areas.
INTRODUCTION
The corticobasal degeneration syndrome (CBDS) and progressive supranuclear palsy (PSP) are genetically related but pathologically distinct causes of progressive motor dysfunction and dementia. Because both diseases cause atypical parkinsonism that is not responsive to levodopa treatment, PSP and CBDS may be confused during life.1 As new therapies are developed to treat tauopathies such as CBDS and PSP, improved methods of antemortem diagnosis will be necessary to effectively target treatments to those individuals who are most likely to benefit.
Although both disorders lead to deposits of the same isoform of the protein tau (4R) in neurons and glia, in pathologically diagnosed CBD tau deposits are in the form of cortical ballooned neurons, astrocytic plaques, and coiled bodies, whereas in PSP subcortical globose neurofibrillary tangles and tufted astrocytes are found.2 At autopsy, the degree of brain atrophy is markedly more severe in CBD than in PSP in individuals with similar disease severity.3 Consistent with these findings, studies of brain atrophy in living patients with CBD and PSP show that differences in the degree of cortical and midbrain atrophy observed on structural magnetic resonance imaging (MRI) help to differentiate the 2 disorders.4-5 The prior studies that compared the neuroimaging features of PSP and CBD used region-of-interest–based approaches, which could not identify specific regions within the major cerebral lobes and brainstem that were differentially atrophied in the 2 disorders.
The clinical features of PSP and CBDS suggest specific cortical and subcortical patterns of atrophy in each of the 2 disorders. Eye movement control is severely impaired by CBDS and PSP, and quantitative eye movement measurements suggest that abnormalities in the velocity and latency of saccades can differentiate clinically defined cases of PSP from CBDS.6 The pattern of histopathologic findings in PSP has led to the hypothesis that damage to structures within the dorsal midbrain underlies the early and prominent vertical saccade slowing in PSP.7 In contrast, studies of patients with cortical lesions suggest that the increased latency of saccades in CBDS reflects damage to cortical eye fields.8 On the basis of these findings, we hypothesized that damage to cortical and brainstem ocular motor control regions would be measurable in living patients with CBDS and PSP as atrophy of the frontal eye fields in CBDS and the dorsal midbrain and pons in PSP. To test this hypothesis, we used voxel-based morphometry (VBM),9 an unbiased quantitative MRI analysis method with higher spatial resolution than the methods previously used, to compare regional atrophy in CBD and PSP.
METHODS
STUDY PARTICIPANTS
A total of 109 individuals participated in the study: 80 control subjects, 15 patients with PSP, and 14 patients with CBDS. Informed consent was obtained for all components of the study. All PSP patients met the National Institute of Neurological Disorders and Stroke–Society for Progressive Supranuclear Palsy criteria for probable PSP.10 Briefly, these include (1) a gradually progressive disorder with onset at the age of 40 years or later and (2) vertical supranuclear gaze palsy and prominent postural instability within the first year of disease onset. The following features were required for a diagnosis of probable CBDS: (1) a slowly progressive course, (2) asymmetric limb or axial rigidity, present without reinforcement, (3) aphasia, visuospatial impairment or neglect, or apraxia, and (4) dystonia, myoclonus, cortical sensory loss, or alien limb phenomenon. All participants underwent MRI. The MRIs were not used in diagnostic decision making for definition of groups.
CLINICAL RATINGS
Patients’ medical records were reviewed by one of the authors (A.L.B). Neurologists’ spontaneous reports of clinical findings were recorded as present if mentioned in a clinic medical record up to and/or within 3 months of the MRI. All patients were rated on the Clinical Dementia Rating scale,11 the modified Hoehn and Yahr scale,12 and the Schwaab and England Activities of Daily Living Scale.13 The Hoehn and Yahr scale and Schwaab and England scale scores were calculated based on detailed neurologists’ reports from the patients’ clinical medical records. General intellectual function was assessed using the Mini-Mental State Examination (MMSE).14
MAGNETIC RESONANCE IMAGING
Images were obtained at the San Francisco Veterans Affairs Magnetic Resonance Unit. The T1-weighted (magnetization-prepared rapid gradient echo) MRIs were obtained on a 1.5-T Magnetom VISION system (Siemens Inc, Iselin, NJ). The structural MRI sequence used in our study was identical to that described in a previous study.15
VOXEL-BASED MORPHOMETRY
Images were preprocessed and statistically analyzed with the SPM2 software package (http://www.fil.ion.ucl.ac.uk/spm), using standard procedures.9 To improve image spatial preprocessing, the "optimized" 2-step procedure was applied.16 A customized gray matter template, constructed by normalizing segmented gray matter images from 40 of the healthy control images (mean age, 66 years; 20 men and 20 women; 30 with full neurologic and neuropsychological evaluations) to the SPM2 gray matter template, was used for spatial normalization. Gray and white matter voxel values were multiplied by the jacobian determinants derived from the spatial normalization step to preserve the initial volumes. Images were spatially smoothed with a 12-mm full width at half maximum isotropic gaussian kernel. Total intracranial volume was used as a confounding covariate in an analysis of covariance. Age and sex for each study participant were entered into the design matrix as nuisance variables. A statistical threshold of P<.05 at the voxel level, corrected for multiple comparisons (familywise error), was accepted for the main contrasts.
To examine the patterns of atrophy specific to each patient group, the following contrasts were performed: (1) PSP patients vs controls: the areas of gray and white matter loss in the PSP patients relative to the controls were examined (PSP < controls); (2) CBDS patients vs controls: the areas of gray and white matter loss in the CBDS patients relative to the controls were examined (CBDS patients < controls); (3) PSP patients vs CBDS patients: the areas of gray and white matter loss in the PSP patients relative to the CBD patients were examined (PSP patients < CBDS patients); (4) CBDS patients vs PSP patients: the areas of gray matter and loss in the CBDS patients relative to the PSP patients were examined (CBDS patients < PSP patients).
Localization of areas of significant cortical and subcortical gray matter loss was accomplished by superimposing the regions of significant atrophy on the averaged T1-weighted image used to create the template for spatial normalization and visual comparison with the cerebral atlases.17-18 Regions of atrophy are reported in Montreal Neurological Institute coordinates.
PATIENT CLASSIFICATION
Gray and white matter concentrations from voxels found to be most significantly different among groups in any of the 4 VBM contrasts were entered into a stepwise discriminant function analysis to identify which regions of atrophy best discriminated between the 2 patient groups. Statistical analysis was accomplished using the SPSS software package (version 10.0.5 for Windows, SPSS Inc, Chicago, Ill).
RESULTS
CLINICAL FINDINGS
No differences were identified in age, education, or disease duration between the 2 patient groups (Table 1). There were more men than women in the PSP group but not in the CBD or control group. The CBD group was more impaired on the MMSE than the PSP group (P = .05; 2-tailed t test). Despite the difference in MMSE score, no difference was identified in functional status between the 2 patient groups on the Clinical Dementia Rating, the Hoehn and Yahr scale, and the Schwaab and England functional scales (Table 2).
|
|
|
|
Table 1. Demographics for Patients and Controls*
|
|
|
|
|
|
|
Table 2. Functional and Motor Ratings in Patient Groups*
|
|
|
Dystonia (P = .001), limb apraxia (P<.001), apraxia of speech (P = .004), myoclonus (P = .02), and cortical sensory deficits (P<.001) were present in a greater number of the CBD patients than PSP patients ( 2 test; Table 3). Slow saccades (P = .001), vertical gaze limitation (P<.001), square wave jerks (P = .001), axial rigidity (P<.001), and falls (P = .001) were reported more frequently in the PSP group than in the CBD group. No significant difference were identified in the prevalence of limb rigidity, alien limb phenomenon, tremor, dysarthria, and subjective response to levodopa between the 2 patient groups.
|
|
|
|
Table 3. Motor Findings and Symptoms at Time of Magnetic Resonance Imaging*
|
|
|
NEUROIMAGING ANALYSIS OF REGIONAL BRAIN ATROPHY
CBD Patients vs Controls
Multiple regions of gray and white matter loss were identified in the frontal and parietal cortex and the basal ganglia when the 14 CBDS patients were compared with the 80 control subjects using VBM (Figure 1A, Table 4). There was an asymmetric pattern of cortical atrophy, with greater left-sided than right-sided involvement (Figure 1A, row 1). Bilaterally, the CBDS patients had volume loss relative to controls in the premotor cortex (Figure 1A, red) and frontal subcortical white matter (Figure 1A, yellow). Within this region, the most significant area of atrophy was bilaterally at the junction of the superior frontal sulci and the precentral sulci (Figure 1A, row 2), a region thought to contain the frontal eye fields.19 The left superior parietal cortex, posterior cingulate cortex, and occipital cortex also showed significant gray matter loss relative to controls. Subcortically, significant gray matter loss was identified, involving the caudate and putamen nuclei.
|
|
|
|
Figure 1. Regions of brain atrophy in patients with corticobasal degeneration syndrome (CBDS) and progressive supranuclear palsy (PSP) relative to controls. Voxel-based morphometry–identified regions of decreased gray and white matter volume relative to 80 age-matched control subjects in CBD and PSP patients are displayed on a normal adult brain template (P<.05, corrected). A, CBD patients vs controls. B, PSP patients vs controls. Row 1 shows the regions of significant gray matter loss rendered on a healthy subject’s brain. Row 2 shows regions of significant gray (displayed in red) and white (displayed in yellow) matter loss relative to controls at the following Montreal Neurological Institute (MNI) coordinates: x = –33, y = –4, and z = 49. Row 3 shows regions of significant gray (displayed in red) and white (displayed in yellow) matter loss relative to controls at the following MNI coordinates: x = 5, y = –15, and z = –8. A indicates anterior; P, posterior.
|
|
|
|
|
|
|
Table 4. Regions of Brain Atrophy in Corticobasal Degeneration and Progressive Supranuclear Palsy Relative to Controls and to Each Other
|
|
|
PSP Patients vs Controls
The most significant areas of atrophy observed in the 15 PSP patients relative to controls were in the midbrain and pons (Figure 1B, Table 4). In the midbrain, multiple voxels within a region that encompassed the medial longitudinal fasciculus and the nucleus of cranial nerve III, the central mesencephalic reticular formation, and the decussation of the superior cerebellar peduncles were significantly atrophied (Figure 1B, row 3). In the pons, a dorsal region, including the nucleus of cranial nerve VI, and portions of the parapontine reticular formation showed volume loss (Figure 1B, row 3; Table 4). The left caudate and right thalamus were also atrophied relative to controls. Bilaterally, there were small areas of gray matter loss (Figure 1B, row 2, red) in the frontal opercular cortex and white matter loss (Figure 1B, row 2, yellow) in the frontal, periventricular regions.
Direct Comparisons of Patient Groups
When the degree of gray and white matter loss was directly compared in the 2 patient groups, the CBDS group had more atrophy in the left frontal eye field and left superior parietal lobule than the PSP group (Table 4). In contrast, the PSP group displayed more atrophy than the CBDS group in the midbrain, in a region encompassing the central mesencephalic reticular formation, the nucleus of cranial nerve III, and the rostral portion of the medial longitudinal fasciculus (Table 4).
Patient Classification
To determine which regions of atrophy best differentiated the 2 patient groups, the gray or white matter concentration at each voxel listed in Table 4 was entered into a stepwise discriminant function analysis. The degree of atrophy in 3 brain regions, the midbrain tegmentum, the dorsal pons, and the left frontal eye field, differentiated the CBDS patients from the PSP patients with 93% accuracy (Figure 2). One patient in each clinically defined patient group was misclassified as belonging to the other patient group by the neuroimaging criteria. Standardized canonical discriminant function coefficients for the 3 brain regions were 0.578 (midbrain tegmentum), 0.517 (pontine tegmentum), and –0.815 (frontal eye field).
|
|
|
|
Figure 2. Magnitude of brain atrophy in regions that discriminate corticobasal degeneration syndrome (CBDS) from progressive supranuclear palsy (PSP). Brain volume (arbitrary units) from the voxel-based morphometry analysis is displayed for each patient at the 3 brain regions found to best discriminate the 2 patient groups. Dorsal midbrain volume is shown at the following Montreal Neurological Institute coordinates: x = 5, y = –15, and z = –8. Dorsal pons coordinates are x = –1, y = –36, and z = –43. Left frontal cortex coordinates are x = –27, y = 4, and z = 54. Two patients were incorrectly classified by the discriminate function.
|
|
|
COMMENT
This is the first study to use voxel-based methods to directly compare brain atrophy patterns in CBDS and PSP patients and thus provides much greater neuroanatomical detail than previous brain imaging studies of these 2 disorders. This study demonstrates that the most significant differences in brain atrophy in CBDS and PSP patients with similar disease severity occur in regions involved in eye movement control. Consistent with our hypothesis, CBDS patients showed more atrophy of the left dorsal frontal and parietal structures than PSP patients in the vicinity of the frontal and parietal eye fields. Conversely, PSP patients displayed more atrophy of the midbrain structures, in the region of the oculomotor nucleus and central mesencephalic reticular formation, than CBD patients. Compared with controls, both disorders were associated with atrophy of the basal ganglia structures; however, CBD patients displayed prominent cortical volume loss, whereas PSP patients showed the most atrophy in the rostral brainstem. The degree of atrophy of these brain regions accurately differentiated patients with CBDS from those with PSP.
COMPARISON WITH PATHOLOGIC STUDIES OF CBD AND PSP
This study extends the findings of a recent autopsy comparison of brain atrophy between CBD and PSP, which demonstrated a greater degree of cortical atrophy in CBD than PSP,3 to show that the same differences in brain anatomy are appreciable during life at an intermediate stage of disease severity in patients with typical clinical presentations of the 2 disorders. The patterns of brain atrophy observed in our study are also highly consistent with the anatomical distribution of tau protein deposits in PSP and CBD. In CBD, we found that the most prominent region of atrophy was in the left superior frontal gyrus, which at autopsy usually contains the highest concentrations of ballooned neurons.2 In PSP, we found that the most prominent regions of brain atrophy were in the dorsal midbrain and pontine regions, which contain the ocular motor nuclei, and at autopsy consistently have high concentrations of neurofibrillary tangles.20 We were also able to document significant atrophy of the superior cerebellar peduncles (especially in the region of their decussation) in the PSP group, a neuroimaging finding suggested by a recent neuropathologic study.21
COMPARISON WITH PREVIOUS NEUROIMAGING STUDIES OF CBD AND PSP
The patterns of brain atrophy that were observed in our study of CBDS and PSP are consistent with previous MRI-based studies of brain atrophy in these disorders.4-5 Our data extend the results of a recent region-of-interest MRI analysis of pathologically confirmed cases of PSP and CBD.4 Consistent with this study, we demonstrated greater brainstem atrophy in PSP than in CBDS and greater cortical atrophy in CBDS than in PSP. The use of a voxel-by-voxel analysis of brain atrophy in our study allowed for much greater anatomical detail with similar accuracy in classification of patients based on fewer anatomical measurements. Specifically, we were able to identify regions within the frontal and parietal cortical regions where atrophy differentiates CBDS from PSP. The regions identified are important for the cortical control of eye movement, making this imaging finding concordant with a major aspect of the clinical presentation in CBD. Although a similar pattern has been demonstrated in autopsy studies, this type of specificity has not previously been demonstrated in vivo. In contrast to the region-of-interest MRI analysis,4 which suggested a symmetric pattern of cortical atrophy in CBD, we identified an asymmetric pattern of cortical atrophy in the CBD group. This finding is nearly identical to the pattern of resting cerebral hypometabolism noted on statistical parametric maps of positron emission tomograms with 18fluorodeoxyglucose of patients with CBDS22 and subjective ratings of atrophy in CBD.5
CLINICAL-ANATOMICAL RELATIONSHIPS IN PSP AND CBD
From the earliest descriptions of PSP and CBD, it has been recognized that the control of eye movements is severely impaired by both disorders,20, 23 and their distinctive saccade abnormalities can differentiate patients in each group.6 Our neuroimaging analysis demonstrated that the most significant areas of atrophy in both patient groups relative to controls were in brain regions involved in ocular motor control. In CBD, the intersection of the superior frontal sulcus and precentral sulcus, a region identified by functional MRI as the frontal eye field, was significantly atrophied relative to controls and PSP patients.19 In PSP, the dorsal midbrain and pons, regions involved in basic aspects of ocular motor control,7 were most atrophied. Thus, our results provide a potential neuroanatomical basis for saccade abnormalities associated with CBD and PSP. Further studies that correlate quantitative measures of saccades with regional brain atrophy are needed to test this hypothetical basis for CBD- and PSP-associated eye movement abnormalities.
AUTHOR INFORMATION
Correspondence: Adam L. Boxer, MD, PhD, Memory and Aging Center, Department of Neurology, University of California, San Francisco, Box 1207, San Francisco, CA 94143-1207 (aboxer{at}memory.ucsf.edu).
Accepted for Publication: August 23, 2005.
Author Contributions: Study concept and design: Boxer, Geschwind, and Rosen. Acquisition of data: Boxer, Geschwind, Gorno-Tempini, Schauer, Miller, Weiner, and Rosen. Analysis and interpretation of data: Boxer, Geschwind, Belfor, and Gorno-Tempini. Drafting of the manuscript: Boxer, Geschwind, Belfor, Gorno-Tempini, and Schauer. Critical revision of the manuscript for important intellectual content: Boxer, Geschwind, Miller, Weiner, and Rosen. Statistical analysis: Boxer, Belfor, Gorno-Tempini, and Rosen. Obtained funding: Boxer, Miller, Weiner, and Rosen. Administrative, technical, and material support: Weiner. Study supervision: Boxer, Miller, and Rosen.
Funding/Support: This study was supported by grant K23 NS48855 (Dr Boxer) from the National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, Md; the John Douglas French Foundation, Los Angeles, Calif; grant NIH AG19724 (Dr Miller) from the National Institutes of Health; a National Institutes of Health Alzheimer’s Disease Research Center grant; the Hillblom Foundation, Petaluma, Calif; the State of California; and the McBean Foundation, San Mateo, Calif.
Author Affiliations: Memory and Aging Center, Department of Neurology, University of California, San Francisco (Drs Boxer, Geschwind, Belfor, Gorno-Tempini, Miller, and Rosen and Mr Schauer); and Magnetic Resonance Spectroscopy Unit, San Francisco Veterans Administration Hospital (Drs Boxer and Weiner).
REFERENCES
| |
1. Boeve BF, Lang AE, Litvan I. Corticobasal degeneration and its relationship to progressive supranuclear palsy and frontotemporal dementia. Ann Neurol. 2003;54(suppl 5):S15-S19.
FULL TEXT
| PUBMED
2. Dickson DW. Neuropathologic differentiation of progressive supranuclear palsy and corticobasal degeneration. J Neurol. 1999;246(suppl 2):II6-II15.
PUBMED
3. Schofield EC, Caine D, Kril JJ, Cordato NJ, Halliday GM. Staging disease severity in movement disorder tauopathies: brain atrophy separates progressive supranuclear palsy from corticobasal degeneration. Mov Disord. 2004;20:34-39.4. Groschel K, Hauser TK, Luft A, et al. Magnetic resonance imaging-based volumetry differentiates progressive supranuclear palsy from corticobasal degeneration. Neuroimage. 2004;21:714-724.
FULL TEXT
|
ISI
| PUBMED
5. Soliveri P, Monza D, Paridi D, et al. Cognitive and magnetic resonance imaging aspects of corticobasal degeneration and progressive supranuclear palsy. Neurology. 1999;53:502-507.
FREE FULL TEXT
6. Rivaud-Pechoux S, Vidailhet M, Gallouedec G, Litvan I, Gaymard B, Pierrot-Deseilligny C. Longitudinal ocular motor study in corticobasal degeneration and progressive supranuclear palsy. Neurology. 2000;54:1029-1032.
FREE FULL TEXT
7. Bhidayasiri R, Riley DE, Somers JT, Lerner AJ, Buttner-Ennever JA, Leigh RJ. Pathophysiology of slow vertical saccades in progressive supranuclear palsy. Neurology. 2001;57:2070-2077.
FREE FULL TEXT
8. Pierrot-Deseilligny C, Gautier JC, Loron P. Acquired ocular motor apraxia due to bilateral frontoparietal infarcts. Ann Neurol. 1988;23:199-202.
FULL TEXT
|
ISI
| PUBMED
9. Ashburner J, Friston KJ. Voxel-based morphometry—the methods. Neuroimage. 2000;11:805-821.
FULL TEXT
|
ISI
| PUBMED
10. Litvan I, Agid Y, Calne D, et al. Clinical research criteria for the diagnosis of progressive supranuclear palsy (Steele-Richardson-Olszewski syndrome): report of the NINDS-SPSP International Workshop. Neurology. 1996;47:1-9.
ISI
| PUBMED
11. Morris JC. The Clinical Dementia Rating (CDR): current version and scoring rules. Neurology. 1993;43:2412-2414.
FREE FULL TEXT
12. Hoehn MM, Yahr MD. Parkinsonism: onset, progression and mortality. Neurology. 1967;17:427-442.
FREE FULL TEXT
13. Schwab RS, England AC. projection technique for evaluating surgery in Parkinson’s disease. In: Gillingham FS, Donaldson MC, eds. Third Symposium on Parkinson’s Disease Research. Edinburgh, Scotland: ES Livingston; 1969.14. Folstein MF, Folstein SE, McHugh PR. "Mini-mental state": a practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res. 1975;12:189-198.
FULL TEXT
|
ISI
| PUBMED
15. Du AT, Schuff N, Zhu XP, et al. Atrophy rates of entorhinal cortex in AD and normal aging. Neurology. 2003;60:481-486.
FREE FULL TEXT
16. Good CD, Johnsrude IS, Ashburner J, Henson RN, Friston KJ, Frackowiak RS. Voxel-based morphometric study of ageing in 465 normal adult human brains. Neuroimage. 2001;14:21-36.
FULL TEXT
|
ISI
| PUBMED
17. Duvornoy HM. The Human Brain: Surface, Three-dimensional Sectional Anatomy With MRI, and Blood Supply. New York, NY: Springer-Verlag Wein; 1999.18. DeArmond SJ, Fusco MM, Dewey MM. Structure of the Human Brain: A Photographic Atlas. New York, NY: Oxford University Press; 1989.19. Rosano C, Krisky CM, Welling JS, et al. Pursuit and saccadic eye movement subregions in human frontal eye field: a high-resolution fMRI investigation. Cereb Cortex. 2002;12:107-115.
FREE FULL TEXT
20. Steele JC, Richardson JC, Olszewski J. Progressive supranuclear palsy: a heterogeneous degeneration involving the brain stem, basal ganglia and cerebellum with vertical gaze and pseudobulbar palsy, nuchal dystonia and dementia. Arch Neurol. 1964;10:333-359.
FREE FULL TEXT
21. Tsuboi Y, Slowinski J, Josephs KA, Honer WG, Wszolek ZK, Dickson DW. Atrophy of superior cerebellar peduncle in progressive supranuclear palsy. Neurology. 2003;60:1766-1769.
FREE FULL TEXT
22. Peigneux P, Salmon E, Garraux G, et al. Neural and cognitive bases of upper limb apraxia in corticobasal degeneration. Neurology. 2001;57:1259-1268.
FREE FULL TEXT
23. Rebeiz JJ, Kolodny EH, Richardson EP Jr. Corticodentatonigral degeneration with neuronal achromasia: a progressive disorder of late adult life. Trans Am Neurol Assoc. 1967;92:23-26.
PUBMED
 CiteULike  Connotea  Del.icio.us  Digg  Reddit  Technorati  Twitter
What's this?
THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES
|
Distinct anatomical subtypes of the behavioural variant of frontotemporal dementia: a cluster analysis study
Whitwell et al.
Brain 2009;132:2932-2946.
ABSTRACT
| FULL TEXT
Association of Ideomotor Apraxia With Frontal Gray Matter Volume Loss in Corticobasal Syndrome
Huey et al.
Arch Neurol 2009;66:1274-1280.
ABSTRACT
| FULL TEXT
Diffusion Tensor Imaging Shows Different Topographic Involvement of the Thalamus in Progressive Supranuclear Palsy and Corticobasal Degeneration
Erbetta et al.
Am. J. Neuroradiol. 2009;30:1482-1487.
ABSTRACT
| FULL TEXT
Tau forms in CSF as a reliable biomarker for progressive supranuclear palsy
Borroni et al.
Neurology 2008;71:1796-1803.
ABSTRACT
| FULL TEXT
Diffusion-weighted brain imaging study of patients with clinical diagnosis of corticobasal degeneration, progressive supranuclear palsy and Parkinson's disease
Rizzo et al.
Brain 2008;131:2690-2700.
ABSTRACT
| FULL TEXT
White Matter Changes in Corticobasal Degeneration Syndrome and Correlation With Limb Apraxia
Borroni et al.
Arch Neurol 2008;65:796-801.
ABSTRACT
| FULL TEXT
Oculomotor function in frontotemporal lobar degeneration, related disorders and Alzheimer's disease
Garbutt et al.
Brain 2008;131:1268-1281.
ABSTRACT
| FULL TEXT
Corticobasal syndrome and primary progressive aphasia as manifestations of LRRK2 gene mutations
Chen-Plotkin et al.
Neurology 2008;70:521-527.
ABSTRACT
| FULL TEXT
Distinct MRI Atrophy Patterns in Autopsy-Proven Alzheimer's Disease and Frontotemporal Lobar Degeneration
Rabinovici et al.
AM J ALZHEIMERS DIS OTHER DEMEN 2008;22:474-488.
ABSTRACT
Deformation-Based Morphometry Reveals Brain Atrophy in Frontotemporal Dementia
Cardenas et al.
Arch Neurol 2007;64:873-877.
ABSTRACT
| FULL TEXT
Rates of cerebral atrophy differ in different degenerative pathologies
Whitwell et al.
Brain 2007;130:1148-1158.
ABSTRACT
| FULL TEXT
Loss of insight in frontotemporal dementia, corticobasal degeneration and progressive supranuclear palsy
O'Keeffe et al.
Brain 2007;130:753-764.
ABSTRACT
| FULL TEXT
Mixing pro- and antisaccades in patients with parkinsonian syndromes
Rivaud-Pechoux et al.
Brain 2007;130:256-264.
ABSTRACT
| FULL TEXT
Structural anatomy of empathy in neurodegenerative disease
Rankin et al.
Brain 2006;129:2945-2956.
ABSTRACT
| FULL TEXT
|
