Rates of brain atrophy and clinical decline over 6 and 12-month intervals in PSP: determining sample size for treatment trials

Imaging biomarkers are useful outcome measures in treatment trials. We compared sample size estimates for future treatment trials performed over 6 or 12-months in progressive supranuclear palsy using both imaging and clinical measures. We recruited 16 probable progressive supranuclear palsy patients that underwent baseline, 6 and 12-month brain scans, and 16 age-matched controls with serial scans. Disease severity was measured at each time-point using the progressive supranuclear palsy rating scale. Rates of ventricular expansion and rates of atrophy of the whole brain, superior frontal lobe, thalamus, caudate and midbrain were calculated. Rates of atrophy and clinical decline were used to calculate sample sizes required to power placebo-controlled treatment trials over 6 and 12-months. Rates of whole brain, thalamus and midbrain atrophy, and ventricular expansion, were increased over 6 and 12-months in progressive supranuclear palsy compared to controls. The progressive supranuclear palsy rating scale increased by 9 points over 6-months, and 18 points over 12-months. The smallest sample size estimates for treatment trials over 6-months were achieved using rate of midbrain atrophy, followed by rate of whole brain atrophy and ventricular expansion. Sample size estimates were further reduced over 12-month intervals. Sample size estimates for the progressive supranuclear palsy rating scale were worse than imaging measures over 6-months, but comparable over 12-months. Atrophy and clinical decline can be detected over 6-months in progressive supranuclear palsy. Sample size estimates suggest that treatment trials could be performed over this interval, with rate of midbrain atrophy providing the best outcome measure.     

Cortical atrophy differentiates Richardson's syndrome from the parkinsonian form of progressive supranuclear palsy

To determine whether brain atrophy differs between the two subtypes of progressive supranuclear palsy (PSP), Richardson's syndrome (PSP‐RS), and PSP parkinsonism (PSP‐P), and whether such atrophy directly relates to clinical deficits and the severity of tau deposition. We compared 24 pathologically confirmed PSP cases (17 PSP‐RS and 7 PSP‐P) with 22 controls from a Sydney brain donor program. Volume loss was analyzed in 29 anatomically discrete brain regions using a validated point‐counting technique, and tau–immunoreactive neurons, astrocytes and oligodendrocytes/threads semiquantified. Correlations between the two pathological measures and the presence or absence of cardinal PSP symptoms were investigated. Cortical atrophy was more severe in PSP‐RS than PSP‐P and affected more frontal lobe regions (frontal pole, inferior frontal gyrus). The supramarginal gyrus was atrophic in both subtypes. Additionally, atrophy of the internal globus pallidus, amygdala, and thalamus was more severe in PSP‐RS. As expected, more severe frontal lobe tau pathology differentiated PSP‐RS from PSP‐P. No correlations were found between the degree of atrophy and severity of tau pathology in any region assessed, or between the severity of atrophy or tau pathology and the presence or absence of cardinal PSP symptoms. Our study shows that thalamocortical atrophy is a defining feature of PSP‐RS, but this atrophy does not correlate with the presence of any specific cardinal clinical feature. Interestingly, there is a disassociation between tau pathology and atrophy in the brain regions affected in PSP‐RS that requires further investigation. © 2010 Movement Disorder Society     

Patterns of brain atrophy that differentiate corticobasal degeneration syndrome from progressive supranuclear palsy

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.     

Brain perfusion differences in Parkinsonian disorders

We aimed to objectively examine the brain perfusion differences between PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy. ^99mTc ethylcysteinate dimer single‐photon emission CT (SPECT) was performed in 28 patients with PD, 12 with Parkinson variant of multiple system atrophy, 19 with progressive supranuclear palsy, and 17 age‐ and sex‐matched control subjects. A voxel‐by‐voxel group analysis, using statistical parametric mapping 8, was performed to detect the differences of regional cerebral blood flow among three diseases and control groups. Regional cerebral blood flow was measured using the noninvasive Patlak plot method and calculated using a fully automated region of interest technique. Progressive supranuclear palsy showed decreased regional cerebral blood flow in the cingulate gyrus and thalamus, whereas Parkinson variant of multiple system atrophy showed decreased regional cerebral blood flow in the cerebellum, compared with other patients and controls. Regional cerebral blood flow in the thalamus could be used to discriminate progressive supranuclear palsy from other diseases and control subjects with high sensitivity. These findings suggest that parkinsonian disorders, such as PD, Parkinson variant of multiple system atrophy, and progressive supranuclear palsy show a distinct SPECT pattern in the frontal cortex, thalamus, and cerebellum. Moreover, the measurements of regional cerebral blood flow in the thalamus and cerebellum may be helpful in screening for the differential diagnosis of parkinsonian syndrome. © 2011 Movement Disorder Society     

Gray matter correlates of behavioral severity in progressive supranuclear palsy

Background: Behavioral changes occur in progressive supranuclear palsy. This study aimed to identify the anatomic correlate of behavioral severity in progressive supranuclear palsy. Methods: We performed standardized tests of behavioral severity (Frontal Behavioral Inventory), cognitive severity (Mini‐Mental State Examination), motor severity (Movement Disorder Society‐sponsored revision of the Unified Parkinson's Disease Rating Scale Part III), and a 3.0‐T volumetric head magnetic resonance imaging scan in 18 prospectively recruited subjects meeting National Institute of Neurological Diseases and Stroke‐Society of Progressive Supranuclear Palsy criteria for probable progressive supranuclear palsy. Atlas‐based parcellation was utilized to obtain regional gray matter volumes of frontal, temporal, and parietal lobe, and caudate and putamen, and voxel‐based morphometry was used to assess voxel‐level gray matter loss. We performed correlation analyses between total Frontal Behavioral Inventory score and gray matter volume, as well as assessed gray matter volume across three groups defined according to behavioral severity (mild, moderate, and severe) based on total Frontal Behavioral Inventory score. Results: Specific behaviors, with the exception of apathy that occurred in 83% of the subjects, were relatively infrequent. There was no association between Frontal Behavioral Inventory and cognitive or motor severity. Regions of the frontal lobe, particularly, the lateral posterior frontal cortex, significantly correlated with the total Frontal Behavioral Inventory score when using both regional volume and voxel‐level analyses. The groupwise analyses also supported these findings. The presence of apathy correlated with atrophy of the putamen. Discussion: Behavioral severity in progressive supranuclear palsy appears to be associated with volume loss of frontostriatal regions, in particular, lateral posterior frontal lobe and putamen. © 2011 Movement Disorder Society     

Atrophy of the corpus callosum,cognitive impairment,and cortical hypometabolism in progressive supranuclear palsy

Recent studies disclosed neurofibrillary degeneration in layer 3 of the association cortex in patients with progressive supranuclear palsy. This lesion may be associated with corpus callosum atrophy and may impair the function of cortical regions indispensable for complex cognitive activity. To investigate whether corpus callosum atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, we studied 10 patients with progressive supranuclear palsy using magnetic resonance imaging and positron emission tomography with fluorodeoxyglucose as a tracer. Compared with 23 age-matched control subjects, the patients had significantly decreased callosal area-skull area ratios, with anterior predominance of the degree of atrophy. The corpus callosum atrophy was accompanied by a decreased mean cortical glucose metabolic rate, predominantly in the frontal region of the cortex, and poor performance on the picture arrangement subtest of the Wechsler Adult Intelligence Scale and the verbal fluency task. We conclude that corpus callosum atrophy with anterior predominance is present in progressive supranuclear palsy, and that this atrophy is associated with cognitive impairment and cerebral cortical hypometabolism, especially in the frontal cortical region. Corpus callosum atrophy may reflect the pathological changes in the cerebral cortex, accentuated in the frontal region, that contribute to the development of frontal lobe dysfunction in this disease.     

The in vivo distribution of brain tissue loss in Richardson’s syndrome and PSP‐parkinsonism: a VBM‐DARTEL study

In this study, we wished to test, using magnetic resonance imaging and voxel‐based morphometry (VBM), whether specific cortical and subcortical patterns of brain grey (GM) and white matter (WM) tissue loss can be detected in patients with Richardson’s syndrome (PSP‐RS) and progressive supranuclear palsy‐parkinsonism (PSP‐P), and possibly account for their clinical heterogeneity. Twenty patients with PSP, classified as PSP‐RS (10 patients) or PSP‐P (10 patients), and 24 healthy controls were studied. The Statistical Parametric Mapping (SPM5) and the Diffeomorphic Anatomical Registration using Exponentiated Lie algebra method were used to perform a VBM analysis. Compared with controls, both patient groups showed GM loss in the central midbrain, cerebellar lobes, caudate nuclei, frontotemporal cortices and right hippocampus. WM loss was detected in both conditions in the midbrain, left superior cerebellar peduncle, internal capsulae, and left premotor and bilateral prefrontal regions. Compared with PSP‐P, patients with PSP‐RS showed additional regions of GM loss in the midbrain, left cerebellar lobe and dentate nuclei. PSP‐RS was also associated with a more severe WM loss in the midbrain, internal capsulae, and orbitofrontal, prefrontal and precentral/premotor regions, bilaterally. Patients with PSP‐P showed a more pronounced GM loss only in the frontal cortex, bilaterally. This study shows that, albeit the overall pattern of brain atrophy associated with PSP appears remarkably consistent across the spectrum of clinical features recorded in life, major anatomical differences between these two conditions do exist. Such a different topographical distribution of tissue damage may account for the clinical differences between PSP‐RS and PSP‐P.     

Clinical and cognitive correlations of regional gray matter atrophy in progressive supranuclear palsy

BackgroundProgressive supranuclear palsy is the most common neurodegenerative bradykinetic-rigid syndrome after Parkinson's disease. Several volumetric studies have revealed a widespread cortical and subcortical gray matter atrophy, however the correlations between the pattern of gray matter loss and clinical-cognitive features have been poorly investigated.MethodsBy using 3-T magnetic-resonance imaging and voxel-based morphometry we compared gray matter volume in 15 patients with progressive supranuclear palsy, 15 patients with Parkinson's disease and 15 healthy controls. All patients underwent a clinical and neuropsychological evaluation.ResultsIn agreement with previous studies, patients with progressive supranuclear palsy, compared to patients with Parkinson's disease and healthy controls, showed a reduced gray matter volume in several cortical and subcortical areas including cerebellum, frontal, temporal and parahippocampal cortical structures. We did not find any significant gray matter volume changes when comparing patients with Parkinson's disease vs healthy controls. Among different significant correlations between motor-cognitive features and gray matter loss, we detected a significant correlation between fronto-cerebellar gray matter atrophy and executive cognitive impairment in patients with progressive supranuclear palsy.ConclusionsOur findings confirm that gray matter loss in patients with progressive supranuclear palsy involves several brain areas and suggest that cerebellar atrophy may play a role in the pathogenesis of cognitive dysfunction in patients with progressive supranuclear palsy due to a disruption of its modulation on executive functions.     

Voxel based morphometry reveals a distinct pattern of frontal atrophy in progressive supranuclear palsy

BACKGROUND: Frontal lobe atrophy is a well known neuropathological feature of progressive supranuclear palsy (PSP), accompanied by characteristic neuropsychological deficits. OBJECTIVE: To determine subregional frontal lobe atrophy patterns in patients with PSP using voxel based morphometry (VBM). METHODS: VBM is an observer unbiased volumetry which allows the investigation of the entire brain. An optimised protocol for normalisation, segmentation, and correction for volume changes in preprocessing was used. Grey matter, white matter, and cerebrospinal fluid (CSF) partitions in 12 patients with probable PSP were compared with 12 healthy controls matched for age and sex. RESULTS: In PSP patients, the following cortical areas were decreased in volume (p(corr)<0.05): the prefrontal cortex, predominantly the medial frontal gyri and a cluster in the left lateral middle frontal gyrus; the insular region including the frontal opercula; both supplementary motor areas; and the left medio-temporal area (V5). White matter comparisons revealed a volume reduction in both frontotemporal regions and the mesencephalon. Analysis of the CSF compartment showed no significant regional changes between the groups. CONCLUSIONS: Frontal atrophy in PSP predominantly involves mesio-frontal targets of striatal projections. This atrophy pattern probably accounts for cardinal PSP associated behavioural deficits.     

Longitudinal atrophy characterization of cortical and subcortical gray matter in Huntington’s disease patients

Huntington's disease (HD) is an inherited neurodegenerative disease with clinical manifestations that involve motor, cognitive and psychiatric deficits. Cross‐sectional magnetic resonance imaging (MRI) studies have described the main cortical and subcortical macrostructural atrophy of HD. However, longitudinal studies characterizing progressive atrophy are lacking. This study aimed to describe the cortical and subcortical gray matter atrophy using complementary volumetric and surface‐based MRI analyses in a cohort of seventeen early HD patients in a cross‐sectional and longitudinal analysis and to correlate the longitudinal volumetric atrophy with the functional decline using several clinical measures. A group of seventeen healthy individuals was included as controls. After obtaining structural MRIs, volumetric analyses were performed in 36 cortical and 7 subcortical regions of interest per hemisphere and surface‐based analyses were performed in the whole cortex, caudate, putamen and thalamus. Cross‐sectional cortical surface‐based and volumetric analyses showed significant decreases in frontoparietal and temporo‐occipital cortices, while subcortical volumetric analysis showed significant decreases in all subcortical structures except the hippocampus. The longitudinal surface‐based analysis showed widespread cortical thinning with volumetric decreases in the superior frontal lobe, while a subcortical volumetric decrease occurred in the caudate, putamen and thalamus with shape deformation on the anterior, medial and dorsal side. Functional capacity and motor status decline correlated with caudate progressive atrophy, while cognitive decline correlated with left superior frontal and right paracentral progressive atrophy. These results provide new insights into progressive volumetric and surface‐based morphometric atrophy of gray matter in HD.     

进行性核上性麻痹与多系统萎缩的头部MRI和FDG-PET比较

目的对比研究进行性核上性麻痹(PSP)与多系统萎缩(MSA)的脑干MRI表现和头部葡萄糖代谢特征。方法对11例PSP患者、37例MSA患者和43例健康对照进行头部MRI平扫检查,并计算MRI正中矢状面T1加权像上中脑截面面积,其中5例PSP和19例MSA进行了18F-FDG PET检查。结果(1)MRI:11例PSP正中矢状位T1加权像均可见中脑上缘平坦或凹陷表现,呈"蜂鸟征",而MSA患者和健康对照组未见上述表现。37例MSA患者中有34例轴位T2加权像桥脑可见"十字征"样长T2异常信号。PSP患者正中矢状位T1加权像上中脑截面面积分别低于MSA组和健康对照组(P<0.01)。(2)PET:PSP组主要表现为对称性额叶低代谢;MSA组主要表现为额、顶、颞叶普遍低代谢,纹状体对称性代谢降低,丘脑代谢高于纹状体。结论PSP中脑MRI特征和头部葡萄糖代谢特征与MSA和健康对照有明确差异,有助于PSP与MSA的鉴别诊断。     

Rigidity and dorsiflexion of the neck in progressive supranuclear palsy and the interstitial nucleus of Cajal.

Rigidity and dorsiflexion of the neck are typical signs in progressive supranuclear palsy, but the responsible areas in the brain are unknown. To examine whether bilateral lesions of the interstitial nucleus of Cajal (INC) in the midbrain tegmentum contribute to the signs of patients with progressive supranuclear palsy, we have made bilateral INC lesions in cats and tried to correlate these studies with clinical and pathological data, including our case of progressive supranuclear palsy. Bilateral INC lesioned cats showed dorsiflexion of the neck and impairment of vertical eye movement, similar to progressive supranuclear palsy patients. Analysis of the previous clinical-pathological studies and our case have shown that dorsiflexion of the neck in progressive supranuclear palsy patients was correlated more with INC lesions than lesions of the basal ganglia.     

Tideglusib reduces progression of brain atrophy in progressive supranuclear palsy in a randomized trial

It is believed that glycogen synthase kinase‐3 hyperphosphorylates tau protein in progressive supranuclear palsy (PSP). The Tau Restoration on PSP (TAUROS) trial assessed the glycogen synthase kinase‐3 inhibitor tideglusib as potential treatment. For the magnetic resonance imaging (MRI) substudy reported here, we assessed the progression of brain atrophy. TAUROS was a multinational, phase 2, double‐blind, placebo‐controlled trial in patients with mild‐to‐moderate PSP who were treated with oral tideglusib (600 mg or 800 mg daily) or with placebo for 1 year. A subset of patients underwent baseline and 52‐week MRI. Automated, observer‐independent, atlas‐based, and mask‐based volumetry was done on high‐resolution, T1‐weighted, three‐dimensional data. For primary outcomes, progression of atrophy was compared both globally (brain, cerebrum) and regionally (third ventricle, midbrain, pons) between the active and placebo groups (Bonferroni correction). For secondary outcomes, 15 additional brain structures were explored (Benjamini & Yekutieli correction). In total, MRIs from 37 patient were studied (placebo group, N = 9; tideglusib 600 mg group, N = 19; tideglusib 800 mg group, N = 9). The groups compared well in their demographic characteristics. Clinical results showed no effect of tideglusib over placebo. Progression of atrophy was significantly lower in the active group than in the placebo group for the brain (mean ± standard error of the mean: ?1.3% ± 1.4% vs. ?3.1% ± 2.3%, respectively), cerebrum (?1.3% ± 1.5% vs. ?3.2% ± 2.1%, respectively), parietal lobe (?1.6% ± 1.9% vs. ?4.1% ± 3.0%, respectively), and occipital lobe (?0.3% ± 1.8% vs. ?2.7% ± 3.2%, respectively). A trend toward reduced atrophy also was observed in the frontal lobe, hippocampus, caudate nucleus, midbrain, and brainstem. In patients with PSP, tideglusib reduced the progression of atrophy in the whole brain, particularly in the parietal and occipital lobes. © 2014 International Parkinson and Movement Disorder Society     

Progressive supranuclear palsy syndrome presenting as progressive nonfluent aphasia: A neuropsychological and neuroimaging analysis

There is currently considerable interest in the clinical spectrum of progressive nonfluent aphasia (PNFA) and progressive supranuclear palsy (PSP) and the intersection of these two entities. Here, we undertook a detailed prospective clinical, neuropsychological, and neuroimaging analysis of 14 consecutive patients presenting with PNFA to identify cases meeting clinical criteria for PSP. These patients had further detailed assessment of extrapyramidal and oculomotor functions. All patients had high‐resolution MR brain volumetry and a cortical thickness analysis was undertaken on the brain images. Four patients presenting with PNFA subsequently developed features of a PSP syndrome, including a typical oculomotor palsy. The neuropsychological profile in these cases was similar to other patients with PNFA, however, with more marked reduction in propositional speech, fewer speech errors, less marked impairment of literacy skills but more severe associated deficits of episodic memory and praxis. These PSP‐PNFA cases had less prominent midbrain atrophy but more marked prefrontal atrophy than a comparison group of five patients with pathologically confirmed PSP without PNFA and more prominent midbrain atrophy but less marked perisylvian atrophy than other PNFA cases. In summary, although the PSP‐PNFA syndrome overlaps with PNFA without PSP, certain neuropsychological and neuroanatomical differences may help predict the development of a PSP syndrome. © 2010 Movement Disorder Society     

Pick’s disease with Pick bodies combined with progressive supranuclear palsy without tuft‐shaped astrocytes: A clinical,neuroradiologic and pathological study of an autopsied case

We report clinical, neuroradiologic features, and neuropathologic findings of a 76‐year‐old man with coexistent Pick’s disease and progressive supranuclear palsy. The patient presented with loss of recent memory, abnormal behavior and change in personality at the age of 60. The symptoms were progressive. Three years later, repetitive or compulsive behavior became prominent. About 9 years after onset, he had difficulty moving and became bed‐ridden because of a fracture of his left leg. His condition gradually deteriorated and he developed mutism and became vegetative. The patient died from pneumonia 16 years after the onset of symptoms. Serial MRI scans showed progressive cortex atrophy, especially in the bilateral frontal and temporal lobes. Macroscopic inspection showed severe atrophy of the whole brain, including cerebrum, brainstem and cerebellum. Microscopic observations showed extensive superficial spongiosis and severe neuronal loss with gliosis in the second and third cortical layers in the frontal, temporal and parietal cortex. There were Pick cells and argyrophilic Pick bodies, which were tau‐ and ubiquitin‐positive in neurons of layers II–III of the above‐mentioned cortex. Numerous argyrophilic Pick bodies were observed in the hippocampus, especially in the dentate fascia. In addition, moderate to severe loss of neurons was found with gliosis and a lot of Gallyas/tau‐positive globus neurofibrillary tangles in the caudate nucleus, globus pallidus, thalamus, substantia nigra, locus coeruleus and dentate nucleus. Numerous thorned‐astrocytes and coiled bodies but no‐tuft shaped astrocytes were noted in the basal ganglion, brainstem and cerebellar white matter. In conclusion, these histopathological features were compatible with classical Pick’s disease and coexistence with progressive supranuclear palsy without tuft‐shaped astrocytes.     

Regional brain atrophy in progressive supranuclear palsy and Lewy body disease

There have been no previous three-dimensional volumetric studies of regional brain atrophy in patients with pathologically confirmed progressive supranuclear palsy (PSP). Postmortem cortical and subcortical volumes were compared with neuropathology in 9 patients with PSP, 15 patients with Parkinson's disease, 10 patients with dementia with Lewy bodies, and 23 controls. Cases with the neuritic pathology of Alzheimer's disease were excluded. The topography of brain atrophy differed according to clinicopathological phenotype. Patients with Parkinson's disease had atrophy confined to the amygdala. Atrophy of the frontal lobe was found in both PSP and dementia with Lewy bodies and correlated with increasing neurofibrillary tangle or Lewy body densities, respectively. Patients with PSP could be differentiated by their marked atrophy of the internal globus pallidus. Further analysis of variance revealed that trends for greater frontal lobe atrophy correlated with clinical dementia in PSP, whereas both greater frontal and hippocampal atrophy and higher densities of Lewy bodies and Lewy neurites correlated with clinical dementia in cases with Lewy bodies. The present study provides evidence for selective regional atrophy that correlates with the underlying pathology of PSP and Lewy body disease.     

Neurite orientation dispersion and density imaging (NODDI) and free‐water imaging in Parkinsonism

Neurite orientation dispersion and density imaging (NODDI) uses a three‐compartment model to probe brain tissue microstructure, whereas free‐water (FW) imaging models two‐compartments. It is unknown if NODDI detects more disease‐specific effects related to neurodegeneration in Parkinson's disease (PD) and atypical Parkinsonism. We acquired multi‐ and single‐shell diffusion imaging at 3 Tesla across two sites. NODDI (using multi‐shell; isotropic volume [Viso]; intracellular volume [Vic]; orientation dispersion [ODI]) and FW imaging (using single‐shell; FW; free‐water corrected fractional anisotropy [FAt]) were compared with 44 PD, 21 multiple system atrophy Parkinsonian variant (MSAp), 26 progressive supranuclear palsy (PSP), and 24 healthy control subjects in the basal ganglia, midbrain/thalamus, cerebellum, and corpus callosum. There was elevated Viso in posterior substantia nigra across Parkinsonisms, and Viso, Vic, and ODI were altered in MSAp and PSP in the striatum, globus pallidus, midbrain, thalamus, cerebellum, and corpus callosum relative to controls. The mean effect size across regions for Viso was 0.163, ODI 0.131, Vic 0.122, FW 0.359, and FAt 0.125, with extracellular compartments having the greatest effect size. A key question addressed was if these techniques discriminate PD and atypical Parkinsonism. Both NODDI (AUC: 0.945) and FW imaging (AUC: 0.969) had high accuracy, with no significant difference between models. This study provides new evidence that NODDI and FW imaging offer similar discriminability between PD and atypical Parkinsonism, and FW had higher effect sizes for detecting Parkinsonism within regions across the basal ganglia and cerebellum.     

Regional brain volumes distinguish PSP, MSA-P, and PD: MRI-based clinico-radiological correlations.

Progressive supranuclear palsy (PSP) and multiple system atrophy (MSA) are neurodegenerative disorders, each with a prevalence of around 5 per 100,000. Regional brain atrophy patterns differ in the two disorders, however, and magnetic resonance imaging is sometimes helpful in distinguishing them in the later stages. We measured whole brain and regional volumes, including cerebellum, pons, midbrain, superior cerebellar peduncle (SCP), and ventricular volumes as well as frontal and posterior-inferior cerebral regions in 18 subjects with PSP, 9 with MSA-P (parkinsonian phenotype), 9 with Parkinson's disease (PD), and 18 healthy controls. Associations between these volumes, cognitive profiles, and clinical measures of disease severity and motor disability were assessed. Mean midbrain volume was 30% smaller in PSP than in PD or controls (P < 0.001) and 15% smaller than in MSA-P (P = 0.009). The mean SCP volume in PSP was 30% smaller than in MSA-P, PD, or controls (P < 0.001). Mean cerebellar volumes in MSA-P were 20% smaller than in controls and PD and 18% smaller than in PSP (P = 0.01). Mean pontine volume in MSA-P was 30% smaller than in PD or controls (P < 0.001) and 25% smaller than in PSP (P = 0.01). Motor disability was most strongly associated with midbrain volume, and more severe executive dysfunction was associated with reduced frontal volume. These distinct patterns of cortical and subcortical atrophy, when considered together rather than independently, better differentiate PSP and MSA-P from each other and also from healthy controls.     

进行性核上性麻痹的临床特点以及MRI和PET-CT分析

目的总结临床诊断为进行性核上性麻痹(PSP)病例,分析PSP的临床特点以及MRI和PET-CT表现,以探索PSP的诊断及治疗方法。方法回顾性分析5例PSP患者的临床资料,总结该病的MRI和PET-CT表现及临床特点。结果 5例患者均呈慢性隐匿性起病,进行性加重,中晚期出现核上性凝视麻痹、头后仰、轴性肌张力增高、动作迟缓和反复跌倒。头颅MRI可见中脑萎缩明显,脚间池扩大,中脑和脑桥长轴的垂直线比值在0.35~0.43区间,脑桥与中脑的面积比值在0.10~0.15区间,5例患者磁共振帕金森综合征指数(MRPI)均13.55。PET-CT示双侧额叶、中脑、丘脑、纹状体等部位可有不同程度的葡萄糖代谢减低,5例患者均有双侧纹状体多巴胺代谢减低。唑吡坦对患者运动障碍改善似有帮助。结论 PSP的诊断仍以临床表现为主,影像学特异性改变有助诊断。目前尚无确切有效的治疗。     

Cognitive deficits in progressive supranuclear palsy, Parkinson's disease, and multiple system atrophy in tests sensitive to frontal lobe dysfunction.

Groups of patients with idiopathic Parkinson's disease, multiple system atrophy, and progressive supranuclear palsy or Steele-Richardson-Olszewski syndrome, matched for overall clinical disability, were compared using three computerised cognitive tests previously shown to be sensitive to frontal lobe dysfunction. On a test of planning based on the Tower of London task, all three groups were impaired, but in different ways. The groups with palsy and Parkinson's disease were slower in the measure of initial thinking time, whereas the group with multiple system atrophy was only slower in a measure of thinking time subsequent to the first move, resembling patients with frontal lobe damage. On a test of spatial working memory, each group showed deficits relative to their matched control groups, but the three groups differed in their strategy for dealing with this task. On a test of attentional set shifting, each group was again impaired, mainly at the extradimensional shifting stage, but the group with Steele-Richardson-Olszewski syndrome exhibited the greatest deficit. The results are compared with previous findings in patients with Alzheimer's disease or frontal lobe damage. It is concluded that these basal ganglia disorders share a distinctive pattern of cognitive deficits on tests of frontal lobe dysfunction, but there are differences in the exact nature of the impairments, in comparison not only with frontal lobe damage but also with one another.