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BACKGROUND: Stepwise functional connectivity (SFC) detects whole-brain functional couplings of a selected region of interest at increasing link-step topological distances. OBJECTIVE: This study applied SFC to test the hypothesis that stepwise architecture propagating from the disease epicenter would shape patterns of brain atrophy in patients with progressive supranuclear palsy-Richardson's syndrome (PSP-RS). METHODS: Thirty-six patients with PSP-RS and 44 age-matched healthy control subjects underwent brain magnetic resonance imaging on a 3-T scanner. The disease epicenter was defined as the peak of atrophy observed in an independent cohort of 13 cases with postmortem confirmation of PSP pathology and used as seed region for SFC analysis. First, we explored SFC rearrangements in patients with PSP-RS, as compared with age-matched control subjects. Subsequently, we tested SFC architecture propagating from the disease epicenter as a determinant of brain atrophy distribution. RESULTS: The disease epicenter was identified in the left midbrain tegmental region. Compared with age-matched control subjects, patients with PSP-RS showed progressively widespread decreased SFC of the midbrain with striatal and cerebellar regions through direct connections and sensorimotor cortical regions through indirect connections. A correlation was found between average link-step distance from the left midbrain in healthy subjects and brain volumes in patients with PSP-RS (r = 0.38, P < 0.001). CONCLUSIONS: This study provides comprehensive insights into the topology of functional network rearrangements in PSP-RS and demonstrates that the brain architectural topology, as described by SFC propagating from the disease epicenter, shapes the pattern of atrophic changes in PSP-RS. Our findings support the view of a network-based pathology propagation in this primary tauopathy. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
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Progressive supranuclear palsy (PSP) is a rare, rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. Caring for a partner or relative who suffers from PSP entails a strenuous and demanding task, usually lasting for years that affects carers' everyday life routines and emotional and social well-being. The 26-item Parkinsonism Carers QoL (PQoL Carer) is a self-administered, concise instrument evaluating the quality of life of caregivers of patients with atypical parkinsonism (both PSP and multiple system atrophy). Here, the PQoL Carer was translated into Italian and validated in 162 carers of PSP patients (54.3% women; mean age (standard deviation), 62.4 (15.4)) diagnosed according to the Movement Disorder Society criteria and recruited in 16 third-level movement disorders centers participating in the Neurecanet project. The mean PQoL total score was 40.66 ± 19.46. The internal consistency was excellent (Cronbach's alpha = 0.941); corrected item-total correlation was > 0.40 for all the items. A correlation with other health-related quality of life measures as well as with behavioral assessments was shown suggesting adequate convergent validity of the scale. PQoL also correlated with patients' severity of disease. The discriminant validity of the scale was evidenced by its capacity to differentiate between carers with varying levels of self-reported health (p < 0.001). In conclusion, the Italian version of the PQoL Carer is an easy, consistent, and valid tool for the assessment of the quality of life in carers of PSP patients.
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Cuidadores/psicología , Psicometría/instrumentación , Calidad de Vida/psicología , Encuestas y Cuestionarios , Adulto , Anciano , Femenino , Humanos , Italia , Masculino , Persona de Mediana Edad , Trastornos Parkinsonianos/etiología , Parálisis Supranuclear Progresiva/complicaciones , TraducciónRESUMEN
BACKGROUND: Progressive supranuclear palsy (PSP) is a rare rapidly progressive, neurodegenerative disease characterized by falls and ocular movement disturbances. The use of health-related quality of life (HR-QoL) measures allows assessing changes in health status induced by therapeutic interventions or disease progress in neurodegenerative diseases. The PSP-QoL is a 45-item, self-administered questionnaire designed to evaluate HR-QoL in PSP. METHODS AND RESULTS: Here, the PSP-QoL was translated into Italian and validated in 190 PSP (96 women and 94 men; mean age ± standard deviation, 72 ± 6.5; mean disease duration, 4.2 ± 2.3) patients diagnosed according to the Movement Disorder Society criteria and recruited in 16 third level movement disorders centers participating in the Neurecanet project. The mean PSP-QoL total score was 77.8 ± 37 (physical subscore, 46.5 ± 18.7; mental subscore, 33.6 ± 19.2). The internal consistency was high (Cronbach's alpha = 0.954); corrected item-total correlation was > 0.40 for the majority of items. The significant and moderate correlation of the PSP-QoL with other HR-QoL measures as well as with motor and disability assessments indicated adequate convergent validity of the scale. Gender and geographic location presented a significant impact on the PSP-QoL in our sample with women and patients from the South of Italy scoring higher than their counterparts. CONCLUSION: In conclusion, the Italian version of the PSP-QoL is an easy, reliable and valid tool for assessment of HR-QoL in PSP.
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Psicometría/normas , Calidad de Vida , Parálisis Supranuclear Progresiva/diagnóstico , Anciano , Anciano de 80 o más Años , Femenino , Humanos , Italia , Masculino , Psicometría/instrumentación , Reproducibilidad de los Resultados , AutoinformeRESUMEN
Purpose To investigate the structural brain connectome in patients with Parkinson disease (PD) and mild cognitive impairment (MCI) and in patients with PD without MCI. Materials and Methods This prospective study was approved by the local ethics committees, and written informed consent was obtained from all subjects prior to enrollment. The individual structural brain connectome of 170 patients with PD (54 with MCI, 116 without MCI) and 41 healthy control subjects was obtained by using deterministic diffusion-tensor tractography. A network-based statistic was used to assess structural connectivity differences among groups. Results Patients with PD and MCI had global network alterations when compared with both control subjects and patients with PD without MCI (range, P = .004 to P = .048). Relative to control subjects, patients with PD and MCI had a large basal ganglia and frontoparietal network with decreased fractional anisotropy (FA) in the right hemisphere and a subnetwork with increased mean diffusivity (MD) involving similar regions bilaterally (P < .01). When compared with patients with PD without MCI, those with PD and MCI had a network with decreased FA, including basal ganglia and frontotemporoparietal regions bilaterally (P < .05). Similar findings were obtained by adjusting for motor disability (P < .05, permutation-corrected P = .06). At P < .01, patients with PD and MCI did not show network alterations relative to patients with PD without MCI. Network FA and MD values were used to differentiate patients with PD and MCI from healthy control subjects and patients with PD without MCI with fair to good accuracy (cross-validated area under the receiver operating characteristic curve [principal + secondary connected components] range, 0.75-0.85). Conclusion A disruption of structural connections between brain areas forming a network contributes to determine an altered information integration and organization and thus cognitive deficits in patients with PD. These results provide novel information concerning the structural substrates of MCI in patients with PD and may offer markers that can be used to differentiate between patients with PD and MCI and patients with PD without MCI. © RSNA, 2016 Online supplemental material is available for this article.
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Encéfalo/patología , Disfunción Cognitiva/patología , Conectoma/métodos , Imagen de Difusión Tensora/métodos , Enfermedad de Parkinson/patología , Sustancia Blanca/patología , Adulto , Anciano , Anciano de 80 o más Años , Encéfalo/diagnóstico por imagen , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/etiología , Femenino , Humanos , Interpretación de Imagen Asistida por Computador/métodos , Masculino , Persona de Mediana Edad , Red Nerviosa/diagnóstico por imagen , Red Nerviosa/patología , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/etiología , Reproducibilidad de los Resultados , Sensibilidad y Especificidad , Sustancia Blanca/diagnóstico por imagenRESUMEN
Magnetic resonance imaging (MRI) is playing an increasingly important role in the study of neurodegenerative diseases, delineating the structural and functional alterations determined by these conditions. Advanced MRI techniques are of special interest for their potential to characterize the signature of each neurodegenerative condition and aid both the diagnostic process and the monitoring of disease progression. This aspect will become crucial when disease-modifying (personalized) therapies will be established. MRI techniques are very diverse and go from the visual inspection of MRI scans to more complex approaches, such as manual and automatic volume measurements, diffusion tensor MRI, and functional MRI. All these techniques allow us to investigate the different features of neurodegeneration. In this review, we summarize the most recent advances concerning the use of MRI in some of the most important neurodegenerative conditions, putting an emphasis on the advanced techniques.
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Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética/métodos , Enfermedades Neurodegenerativas/diagnóstico por imagen , Encéfalo/patología , Progresión de la Enfermedad , Humanos , Enfermedades Neurodegenerativas/patologíaRESUMEN
The anterior temporal lobes (ATL) have been implicated in a range of cognitive functions including auditory and visual perception, language, semantic knowledge, and social-emotional processing. However, the anatomical relationships between the ATLs and the broader cortical networks that subserve these functions have not been fully elucidated. Using diffusion tensor imaging (DTI) and probabilistic tractography, we tested the hypothesis that functional segregation of information in the ATLs is reflected by distinct patterns of structural connectivity to regions outside the ATLs. We performed a parcellation of the ATLs bilaterally based on the degree of connectivity of each voxel with eight ipsilateral target regions known to be involved in various cognitive networks. Six discrete segments within each ATL showed preferential connectivity to one of the ipsilateral target regions, via four major fiber tracts (uncinate, inferior longitudinal, middle longitudinal, and arcuate fasciculi). Two noteworthy interhemispheric differences were observed: connections between the ATL and orbito-frontal areas were stronger in the right hemisphere, while the consistency of the connection between the ATL and the inferior frontal gyrus through the arcuate fasciculus was greater in the left hemisphere. Our findings support the hypothesis that distinct regions within the ATLs have anatomical connections to different cognitive networks. Hum Brain Mapp 37:2210-2222, 2016. © 2016 Wiley Periodicals, Inc.
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Imagen de Difusión por Resonancia Magnética , Lóbulo Temporal/diagnóstico por imagen , Anciano , Mapeo Encefálico , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Vías Nerviosas/diagnóstico por imagenRESUMEN
OBJECTIVE: To identify overlapping and unique grey (GM) and white matter (WM) signatures within the frontotemporal lobar degeneration (FTLD) continuum, and discriminate likely FTLD-TAU and FTLD-TDP patients using structural and diffusion tensor (DT) magnetic resonance imaging (MRI). METHODS: T1-weighted and DT MRI were collected from 121 subjects: 35 motor neuron disease (MND), 14 behavioral variant of frontotemporal dementia, 12 semantic and 11 nonfluent primary progressive aphasia, 21 progressive supranuclear palsy syndrome patients, and 28 healthy controls. Patterns of GM atrophy were established using voxel-based morphometry. Tract-based spatial statistics was used to perform a WM voxelwise analysis of mean diffusivity and fractional anisotropy. RESULTS: In all clinical FTLD phenotypes, the pattern of WM damage was more distributed than that of GM atrophy. All patient groups, with the exception of MND cases with a pure motor syndrome, shared a focal GM atrophy centered around the dorsolateral and medial frontal cortex and a largely overlapping pattern of WM damage involving the genu and body of the corpus callosum and ventral frontotemporal and dorsal frontoparietal WM pathways. Surrounding this common area, phenotype (symptom)-specific GM and WM regions of damage were found in each group. CONCLUSIONS: In the FTLD spectrum, WM disruption is more severe than GM damage. Frontal cortex and WM pathways represent the common target of neurodegeneration in these conditions. The topographic pattern of damage supports a "prion-like" protein propagation through WM connections as underlying mechanism of the stereotyped progression of FTLD.
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Degeneración Lobar Frontotemporal/patología , Sustancia Gris/patología , Imagen por Resonancia Magnética/métodos , Enfermedad de la Neurona Motora/patología , Parálisis Supranuclear Progresiva/patología , Sustancia Blanca/patología , Adulto , Anciano , Anciano de 80 o más Años , Atrofia/patología , Imagen de Difusión Tensora/métodos , Femenino , Demencia Frontotemporal/patología , Humanos , Masculino , Persona de Mediana Edad , Afasia Progresiva Primaria no Fluente/patologíaRESUMEN
PURPOSE: To test a multimodal magnetic resonance (MR) imaging-based approach composed of cortical thickness and white matter (WM) damage metrics to discriminate between variants of primary progressive aphasia (PPA) that are nonfluent and/or agrammatic (NFVPPA) and semantic (SVPPA). MATERIALS AND METHODS: This study was approved by the local ethics committees on human studies, and written informed consent from all patients was obtained before their enrollment. T1-weighted and diffusion-tensor (DT) MR images were obtained from 13 NFVPPA patients, 13 SVPPA patients, and 23 healthy control participants. Cortical thickness and DT MR imaging indices from the long-associative and interhemispheric WM tracts were obtained. A random forest (RF) analysis was used to identify the image features associated with each clinical syndrome. Individual patient classification was performed by using receiver operator characteristic curve analysis with cortical thickness, DT MR imaging, and a combination of the two modalities. RESULTS RF analysis showed that the best markers to differentiate the two PPA variants at an individual patient level among cortical thickness and DT MR imaging metrics were diffusivity abnormalities of the left inferior longitudinal and uncinate fasciculi and cortical thickness measures of the left temporal pole and inferior frontal gyrus. A combination of cortical thickness and DT MR imaging measures (the so-called gray-matter-and-WM model) was able to distinguish patients with NFVPPA and SVPPA with the following classification pattern: area under the curve, 0.91; accuracy, 0.89; sensitivity, 0.92; specificity, 0.85. Leave-one-out analysis demonstrated that the gray matter and WM model is more robust than the single MR modality models to distinguish PPA variants (accuracy was 0.86, 0.73, and 0.68 for the gray matter and WM model, the gray matter-only model, and the WM-only model, respectively). CONCLUSION: A combination of structural and DT MR imaging metrics may provide a quantitative procedure to distinguish NFVPPA and SVPPA patients at an individual patient level. The discrimination accuracies obtained suggest that the gray matter and WM model is potentially relevant for the differential diagnosis of the PPA variants in clinical practice.
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Afasia Progresiva Primaria/clasificación , Afasia Progresiva Primaria/patología , Corteza Cerebral/patología , Imagen de Difusión Tensora , Imagen por Resonancia Magnética , Anciano , Diagnóstico Diferencial , Femenino , Humanos , Masculino , Persona de Mediana EdadRESUMEN
BACKGROUND: Thrombolysis is often withheld from acute ischemic stroke patients presenting with mild symptoms; however, up to 40% of these patients end up with a poor outcome when left untreated. Since there is lack of consensus on the definition of minor symptoms, we aimed at addressing this issue by looking for features that would better predict functional outcomes at 3 months. METHODS: Among all acute ischemic stroke patients admitted to our Stroke Unit (n = 1,229), we selected a cohort of patients who arrived within 24 hours from symptoms onset, with baseline NIHSS ≤6, not treated with thrombolysis (n = 304). Epidemiological data, comorbidities, radiological features and clinical presentation (NIHSS items) were collected to identify predictors of outcome. Our cohort was tested against minor stroke definitions selected from the literature and a newly proposed one. RESULTS: Three months after stroke onset, 97 patients (31.9%) had mRS ≥ 2. Independent predictors of poor outcome were age (OR 0.97 [95% CI 0.95-9.99]) and baseline NIHSS score (OR 0.79 [95% CI 0.67-0.94]), while cardioembolic aetiology was negatively associated (OR 3.29 [95% CI 1.51-7.14]). Items of NIHSS associated with poor outcome were impairment of right motor arm (OR 0.49 [95% CI 0.27-0.91]) or the involvement of any of the motor items (OR 0.69 [95% CI 0.48-0.99]). The definition of minor stroke as NIHSS ≤3 and the new proposed definition had the highest sensitivity and accuracy and were independent predictors of outcome. CONCLUSIONS: Our study confirmed that in spite of a low NIHSS score, one third of patients had poor outcome. As already described, age and NIHSS score remained independent predictors of poor outcome even in mild stroke. Also, motor impairment appeared a major determinant of poor outcome. The new proposed definition of minor stroke featured the NIHSS score and the NIHSS items that better predicted functional outcome. Awareness that even minor stroke can yield to poor outcome should sensitize patients to arrive early to the ED and neurologists to administer rt-PA.
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Isquemia Encefálica/tratamiento farmacológico , Evaluación de la Discapacidad , Fibrinolíticos/uso terapéutico , Accidente Cerebrovascular/tratamiento farmacológico , Activador de Tejido Plasminógeno/uso terapéutico , Adulto , Anciano , Anciano de 80 o más Años , Isquemia Encefálica/diagnóstico , Femenino , Humanos , Masculino , Persona de Mediana Edad , Accidente Cerebrovascular/diagnóstico , Terapia Trombolítica/métodos , Resultado del TratamientoRESUMEN
Using diffusion tensor (DT) magnetic resonance imaging (MRI), damage to brain intrahemispheric and interhemispheric connections was assessed in 26 sporadic primary lateral sclerosis (PLS) patients compared with 28 sporadic amyotrophic lateral sclerosis (ALS) patients with similar disability and 35 healthy controls. DT MRI diagnostic accuracy in distinguishing the two motor neuron disease (MND) variants was tested. PLS and ALS patients showed a distributed pattern of abnormalities of the motor system, including the corticospinal tracts and corpus callosum (CC). PLS versus ALS patients showed a more severe damage to the motor CC fibers and subcortical white matter (WM) underlying the primary motor cortices. Both patient groups showed an extra-motor damage, which was more severe in PLS. This did not appear to be driven by longer disease duration in PLS. In PLS patients, damage to the CC mid-body correlated with the severity of upper motor neuron clinical burden. CC fractional anisotropy values had the highest accuracy in distinguishing PLS from controls and ALS. PLS and ALS share an overlapped pattern of WM abnormalities. This underscores that PLS, despite its distinct clinical phenotype and long survival, still lies within the wider MND spectrum. Whether CC diffusivity may be a novel marker to increase confidence in an early diagnostic separation of PLS from ALS still needs to be investigated.
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Esclerosis Amiotrófica Lateral/patología , Encéfalo/patología , Enfermedad de la Neurona Motora/patología , Adulto , Anciano , Esclerosis Amiotrófica Lateral/diagnóstico , Anisotropía , Diagnóstico por Computador , Diagnóstico Diferencial , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana Edad , Enfermedad de la Neurona Motora/diagnóstico , Vías Nerviosas/patologíaRESUMEN
Primary progressive aphasia is a clinical syndrome that encompasses three major phenotypes: non-fluent/agrammatic, semantic and logopenic. These clinical entities have been associated with characteristic patterns of focal grey matter atrophy in left posterior frontoinsular, anterior temporal and left temporoparietal regions, respectively. Recently, network-level dysfunction has been hypothesized but research to date has focused largely on studying grey matter damage. The aim of this study was to assess the integrity of white matter tracts in the different primary progressive aphasia subtypes. We used diffusion tensor imaging in 48 individuals: nine non-fluent, nine semantic, nine logopenic and 21 age-matched controls. Probabilistic tractography was used to identify bilateral inferior longitudinal (anterior, middle, posterior) and uncinate fasciculi (referred to as the ventral pathway); and the superior longitudinal fasciculus segmented into its frontosupramarginal, frontoangular, frontotemporal and temporoparietal components, (referred to as the dorsal pathway). We compared the tracts' mean fractional anisotropy, axial, radial and mean diffusivities for each tract in the different diagnostic categories. The most prominent white matter changes were found in the dorsal pathways in non-fluent patients, in the two ventral pathways and the temporal components of the dorsal pathways in semantic variant, and in the temporoparietal component of the dorsal bundles in logopenic patients. Each of the primary progressive aphasia variants showed different patterns of diffusion tensor metrics alterations: non-fluent patients showed the greatest changes in fractional anisotropy and radial and mean diffusivities; semantic variant patients had severe changes in all metrics; and logopenic patients had the least white matter damage, mainly involving diffusivity, with fractional anisotropy altered only in the temporoparietal component of the dorsal pathway. This study demonstrates that both careful dissection of the main language tracts and consideration of all diffusion tensor metrics are necessary to characterize the white matter changes that occur in the variants of primary progressive aphasia. These results highlight the potential value of diffusion tensor imaging as a new tool in the multimodal diagnostic evaluation of primary progressive aphasia.
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Afasia Progresiva Primaria/patología , Encéfalo/patología , Fibras Nerviosas Mielínicas/patología , Red Nerviosa/patología , Anciano , Afasia Progresiva Primaria/psicología , Atrofia , Mapeo Encefálico , Imagen de Difusión Tensora , Femenino , Humanos , Masculino , Persona de Mediana Edad , Pruebas NeuropsicológicasRESUMEN
BACKGROUND: Diffusion tensor magnetic resonance imaging tractography allows quantification of in vivo white matter tract damage. METHODS: Using tractography, diffusion tensor magnetic resonance imaging metrics were obtained from the superior and middle cerebellar peduncles and major cerebral white matter tracts in 5 patients with progressive supranuclear palsy and 13 controls. RESULTS: Patients showed severe intrinsic damage to the superior cerebellar peduncle, corpus callosum, and cingulum bilaterally. Only decreased axial diffusivity was found in the left middle cerebellar peduncle. CONCLUSIONS: Diffusion tensor magnetic resonance imaging tractography holds promise for providing accurate in vivo cartography of progressive supranuclear palsy tissue damage.
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Encéfalo/patología , Imagen de Difusión por Resonancia Magnética , Parálisis Supranuclear Progresiva/diagnóstico , Anciano , Mapeo Encefálico , Femenino , Humanos , Procesamiento de Imagen Asistido por Computador/métodos , Masculino , Estadísticas no ParamétricasRESUMEN
BACKGROUND: Parkinson's disease (PD) is the second most common neurodegenerative disorder, affecting both motor and non-motor systems. Deep brain stimulation of the subthalamic nucleus (STN-DBS) has been an approved treatment for PD for more than 30 years, but few data are available regarding its long-term effectiveness. OBJECTIVE: The aim of this study is to evaluate patients' outcome, both from a motor and non-motor perspective, 9 to 14 years after DBS implantation. We have investigated patients with advanced PD and treated with STN-DBS, in relation to key clinical features of PD. METHODS: 18 patients were assessed both retrospectively and prospectively. They underwent motor examination, neuropsychological evaluation and questionnaires on the quality of life, preoperatively, as well as 1, 9 and 14 years after DBS surgery. All patients were implanted with STN-DBS at San Raffaele Hospital between 2004 and 2010. RESULTS: 13 males and five females underwent DBS implantation with a mean PD duration of 11 years. Stimulation significantly improved med-off/stim-on condition up to 9 years, compared to the preoperative off state, and med-on/stim-on condition at 14 years, compared to med-on/stim-off state. Long term improvement specifically involved tremor and rigidity, as well as dopaminergic daily dose. At the same time, STN-DBS had no long-lasting effect on axial symptoms and cognitive functions. CONCLUSIONS: STN-DBS remains an effective therapy for advanced PD, also over the years. Despite the underlying progression of the disease, this treatment extends the period in which the overall quality of life is still acceptable.
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Estimulación Encefálica Profunda , Enfermedad de Parkinson , Núcleo Subtalámico , Femenino , Estudios de Seguimiento , Humanos , Masculino , Enfermedad de Parkinson/terapia , Calidad de Vida , Estudios Retrospectivos , Resultado del TratamientoRESUMEN
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.
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Atrofia/patología , Mapeo Encefálico/métodos , Encéfalo/patología , Imagen por Resonancia Magnética/métodos , Trastornos Parkinsonianos/patología , Parálisis Supranuclear Progresiva/patología , Anciano , Anciano de 80 o más Años , Encéfalo/anatomía & histología , Femenino , Humanos , Masculino , Persona de Mediana Edad , SíndromeRESUMEN
OBJECTIVE: To determine frequency and type of cognitive disorders in cross-sectional analysis of a Parkinson's disease (PD) cohort, and explore its relations to motor symptoms, modifiable vascular risk factors and white matter lesions (WML) volume. METHODS: In a group of 133 PD patients, mild cognitive impairment (PD-MCI) and dementia (PDD) were diagnosed according to Movement Disorders Society Task Force criteria (level 2 for PD-MCI). Detailed motor measurements were applied, including rigidity, axial, bradykinesia, tremor and postural instability gait disorders (PIGD) scores. Vascular risk was estimated by the Framingham General Cardiovascular Disease risk scoring algorithm and WML volume was measured for whole brain and frontal lobe. RESULTS: Sixty-one (46.9%) patients fulfilled criteria for PD-MCI, and 23 (17.7%) for PDD. Non-amnestic multiple domain MCI was most frequent (52% of PD-MCI patients). Motor scores were significantly higher in cognitively impaired patients, but only axial score discriminated between MCI and dementia. High vascular risk was related to impaired cognition, bradykinesia, axial, PIGD and freezing of gait (FOG) score, while whole brain WML volume was associated with PDD, FOG and attention deficits. Furthermore, high vascular risk was identified as a potential predictor of both MCI and dementia in PD. Additionally, age and bradykinesia score were independently associated with PD-MCI and age, axial score and whole brain WML volume with PDD. CONCLUSION: Cognitive disorders in PD are associated with more severe, predominantly axial motor deficits and increased, but partly modifiable vascular burden, thus opening a possibility for development of preventive strategies in PD.
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Enfermedades Cardiovasculares/complicaciones , Disfunción Cognitiva/complicaciones , Demencia/complicaciones , Trastornos del Movimiento/complicaciones , Enfermedad de Parkinson/complicaciones , Anciano , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Enfermedades Cardiovasculares/diagnóstico por imagen , Enfermedades Cardiovasculares/fisiopatología , Cognición , Disfunción Cognitiva/diagnóstico por imagen , Disfunción Cognitiva/fisiopatología , Estudios de Cohortes , Estudios Transversales , Demencia/diagnóstico por imagen , Demencia/fisiopatología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Trastornos del Movimiento/diagnóstico por imagen , Trastornos del Movimiento/fisiopatología , Tamaño de los Órganos , Enfermedad de Parkinson/diagnóstico por imagen , Enfermedad de Parkinson/fisiopatología , Enfermedad de Parkinson/psicología , Factores de Riesgo , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patologíaRESUMEN
Several studies provide information useful to our understanding of restless legs syndrome (RLS), using various imaging techniques to investigate different aspects putatively involved in the pathophysiology of RLS, although there are discrepancies between these findings. The majority of magnetic resonance imaging (MRI) studies using iron-sensitive sequences supports the presence of a diffuse, but regionally variable low brain-iron content, mainly at the level of the substantia nigra, but there is increasing evidence of reduced iron levels in the thalamus. Positron emission tomography (PET) and single positron emission computed tomography (SPECT) findings mainly support dysfunction of dopaminergic pathways involving not only the nigrostriatal but also mesolimbic pathways. None or variable brain structural or microstructural abnormalities have been reported in RLS patients; reports are slightly more consistent concerning levels of white matter. Most of the reported changes were in regions belonging to sensorimotor and limbic/nociceptive networks. Functional MRI studies have demonstrated activation or connectivity changes in the same networks. The thalamus, which includes different sensorimotor and limbic/nociceptive networks, appears to have lower iron content, metabolic abnormalities, dopaminergic dysfunction, and changes in activation and functional connectivity. Summarizing these findings, the primary change could be the reduction of brain iron content, which leads to dysfunction of mesolimbic and nigrostriatal dopaminergic pathways, and in turn to a dysregulation of limbic and sensorimotor networks. Future studies in RLS should evaluate the actual causal relationship among these findings, better investigate the role of neurotransmitters other than dopamine, focus on brain networks by connectivity analysis, and test the reversibility of the different imaging findings following therapy.
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Encéfalo/diagnóstico por imagen , Síndrome de las Piernas Inquietas/diagnóstico por imagen , Animales , Encéfalo/fisiopatología , Humanos , Vías Nerviosas/diagnóstico por imagen , Vías Nerviosas/fisiopatología , Neuroimagen , Síndrome de las Piernas Inquietas/fisiopatologíaRESUMEN
Non-cognitive features including personality changes are increasingly recognized in the three PPA variants (semantic-svPPA, non fluent-nfvPPA, and logopenic-lvPPA). However, differences in emotion processing among the PPA variants and its association with white matter tracts are unknown. We compared emotion detection across the three PPA variants and healthy controls (HC), and related them to white matter tract integrity and cortical degeneration. Personality traits in the PPA group were also examined in relation to white matter tracts. Thirty-three patients with svPPA, nfvPPA, lvPPA, and 32 HC underwent neuropsychological assessment, emotion evaluation task (EET), and MRI scan. Patients' study partners were interviewed on the Clinical Dementia Rating Scale (CDR) and completed an interpersonal traits assessment, the Interpersonal Adjective Scale (IAS). Diffusion tensor imaging of uncinate fasciculus (UF), superior longitudinal fasciculus (SLF) and inferior longitudinal fasciculus (ILF), and voxel-based morphometry to derive gray matter volumes for orbitofrontal cortex (OFC), anterior temporal lobe (ATL) regions were performed. In addition, gray matter volumes of white matter tract-associated regions were also calculated: inferior frontal gyrus (IFG), posterior temporal lobe (PTL), inferior parietal lobe (IPL) and occipital lobe (OL). ANCOVA was used to compare EET performance. Partial correlation and multivariate linear regression were conducted to examine association between EET and neuroanatomical regions affected in PPA. All three variants of PPA performed significantly worse than HC on EET, and the svPPA group was least accurate at recognizing emotions. Performance on EET was related to the right UF, SLF, and ILF integrity. Regression analysis revealed EET performance primarily relates to the right UF integrity. The IAS subdomain, cold-hearted, was also associated with right UF integrity. Disease-specific emotion recognition and personality changes occur in the three PPA variants and are likely associated with disease-specific neuroanatomical changes. Loss of white matter integrity contributes as significantly as focal atrophy in behavioral changes in PPA.
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Afasia Progresiva Primaria/patología , Afasia Progresiva Primaria/fisiopatología , Corteza Cerebral/patología , Imagen de Difusión Tensora/métodos , Emociones/fisiología , Expresión Facial , Personalidad/fisiología , Percepción Social , Sustancia Blanca/patología , Anciano , Afasia Progresiva Primaria/diagnóstico por imagen , Atrofia/patología , Corteza Cerebral/diagnóstico por imagen , Reconocimiento Facial/fisiología , Femenino , Humanos , Masculino , Persona de Mediana Edad , Sustancia Blanca/diagnóstico por imagenRESUMEN
INTRODUCTION: The pathophysiology of spasmodic dysphonia is poorly understood. This study evaluated patterns of cortical morphology, basal ganglia, and white matter microstructural alterations in patients with spasmodic dysphonia relative to healthy controls. METHODS: T1-weighted and diffusion tensor magnetic resonance imaging (MRI) scans were obtained from 13 spasmodic dysphonia patients and 30 controls. Tract-based spatial statistics was applied to compare diffusion tensor MRI indices (i.e., mean, radial and axial diffusivities, and fractional anisotropy) between groups on a voxel-by-voxel basis. Cortical measures were analyzed using surface-based morphometry. Basal ganglia were segmented on T1-weighted images, and volumes and diffusion tensor MRI metrics of nuclei were measured. RESULTS: Relative to controls, patients with spasmodic dysphonia showed increased cortical surface area of the primary somatosensory cortex bilaterally in a region consistent with the buccal sensory representation, as well as right primary motor cortex, left superior temporal, supramarginal and superior frontal gyri. A decreased cortical area was found in the rolandic operculum bilaterally, left superior/inferior parietal and lingual gyri, as well as in the right angular gyrus. Compared to controls, spasmodic dysphonia patients showed increased diffusivities and decreased fractional anisotropy of the corpus callosum and major white matter tracts, in the right hemisphere. Altered diffusion tensor MRI measures were found in the right caudate and putamen nuclei with no volumetric changes. CONCLUSIONS: Multi-level alterations in voice-controlling networks, that included regions devoted not only to sensorimotor integration, motor preparation and motor execution, but also processing of auditory and visual information during speech, might have a role in the pathophysiology of spasmodic dysphonia.
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Encéfalo/patología , Disfonía/patología , Adulto , Anciano , Anisotropía , Imagen de Difusión por Resonancia Magnética , Femenino , Humanos , Interpretación de Imagen Asistida por Computador , Masculino , Persona de Mediana Edad , Imagen Multimodal , Neuroimagen/métodosRESUMEN
Little is known about the longitudinal changes of brain damage in patients with sporadic nonfluent/agrammatic variant of primary progressive aphasia (nfvPPA) and in progranulin (GRN) mutation carriers. This study reports the clinical and MRI longitudinal data of a patient with nfvPPA carrying GRN Cys157LysfsX97 mutation (GRN+). Voxel-based morphometry, tensor-based morphometry and diffusion tensor MRI were applied to evaluate gray matter (GM) and white matter (WM) changes over three years. The prominent clinical feature was motor speech impairment associated with only mild agrammatism. MRI demonstrated a progressive and severe GM atrophy of inferior fronto-insular-temporo-parietal regions with focal damage to frontotemporal and frontoparietal WM connections. This is the first report of longitudinal MRI data in a nfvPPA- GRN+ patient and this report offers new insights into the pathophysiology of the disease.