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1.
J Neurol ; 2020 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-32388831

RESUMO

OBJECTIVE: To describe 123I-FP-CIT (DAT scan) SPECT findings in progressive apraxia of speech (PAOS) patients and to compare those findings with progressive supranuclear palsy (PSP) and corticobasal syndrome (CBS). BACKGROUND: PAOS is a neurodegenerative syndrome in which patients present with apraxia of speech, a motor speech disorder affecting programming and planning of speech. Patients with PAOS predictably develop Parkinsonism. DAT scan is a neuroimaging tool that assesses the integrity of presynaptic dopamine transporters in striatum and is usually abnormal in PSP and CBS. METHODS: As part of an NIH-funded grant, we performed a DAT scan on 17 PAOS patients early in the disease course. DaTQUANT software was used to quantify uptake in the left and right caudate and anterior/posterior putamen, with striatum to background ratios (SBRs). The PAOS cohort was compared to 15 PSP and 8 CBS patients. RESULTS: Five PAOS patients (29%) showed abnormalities in at least one striatal region on DAT scan. When the five PAOS patients with abnormal DAT were compared to the PSP and CBS patients, the only difference observed was lower uptake in the posterior putamen in PSP (p = 0.03). There were no differences is putamen/caudate ratio or in symmetry of uptake, across all groups. There was also no difference in MDS-UPDRS-III scores between PAOS patients with and without abnormal DAT scans (p = 0.56). CONCLUSIONS: Abnormal DAT scan is observed early in the disease course in approximately 30% of PAOS patients, with striatal abnormalities similar to those in PSP and CBS.

2.
Parkinsonism Relat Disord ; 73: 19-22, 2020 04.
Artigo em Inglês | MEDLINE | ID: mdl-32203914

RESUMO

INTRODUCTION: To determine whether vitamin B12 level at Parkinson's disease (PD) diagnosis predicts time to develop dementia. METHODS: We utilized a population-based cohort of Parkinsonism patients to examine the relationship between serum vitamin B12 at the time of PD diagnosis and dementia risk. Receiver operating curves were calculated for vitamin B12 cutoffs maximizing sensitivity and specificity for determining who developed dementia. Time from Parkinsonism diagnosis to dementia, death, or censoring was calculated utilizing Kaplan-Meier analysis and Cox-proportional hazard models. RESULTS: PD patients who did not develop dementia had higher baseline levels of vitamin B12 at PD diagnosis (648.5 ng/L vs 452 ng/L, p < 0.05) than those who developed dementia. Dementia risk was significantly lower in the 3rd tertile compared with 2nd tertile and trended towards significance compared to the 1st tertile. Each 100 unit increase in vitamin B12 level had a hazard ratio of 0.31 (95% CI 0.44-0.95) for future dementia (p < 0.05). Vitamin B12 cutoff of <587 ng/L was 87% sensitive and 70% specific (AUC 0.79, 95% CI 0.60-0.98) distinguishing patients with dementia. PD patients with vitamin B12 levels <587 ng/L were 5.4 times more likely to develop dementia, with 50% having dementia within 5 years of PD diagnosis compared with 11% in those with a vitamin B12 level of ≥587 ng/L (p < 0.05). CONCLUSION: Higher levels of serum vitamin B12 at PD diagnosis correlate with lower risk of future dementia. The role of vitamin B12 in the development of dementia among PD patients deserves further evaluation.

3.
Neuroimage Clin ; 25: 102152, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31935638

RESUMO

BACKGROUND AND PURPOSE: Progressive supranuclear palsy (PSP) is a neurodegenerative tauopathy that is associated with different clinical variants, including PSP-Richardson's syndrome (PSP-RS), PSP-parkinsonism (PSP-P), PSP-corticobasal syndrome (PSP-CBS), PSP-frontal (PSP-F), PSP-progressive gait freezing (PSP-PGF) and PSP-speech/language (PSP-SL). While PSP-RS has been well-characterized on neuroimaging, the characteristics of the other atypical variants are less well defined and it is unknown how they compare to each other or relate to neuropathology. We aimed to assess and compare regional atrophy on MRI and [18F]flortaucipir uptake on PET across PSP variants. MATERIALS AND METHODS: 105 PSP patients (53 PSP-RS, 23 PSP-SL, 12 PSP-P, 8 PSP-CBS, 5 PSP-F and 4 PSP-PGF) underwent volumetric MRI, with 59 of these also undergoing flortaucipir PET. Voxel-level and region-level analyses were performed comparing PSP variants to 30 controls and to each other. Semi-quantitative tau burden measurements were also performed in 21 patients with autopsy-confirmed PSP. RESULTS: All variants showed evidence for atrophy or increased flortaucipir uptake in striatum, globus pallidus and thalamus. Superior cerebellar peduncle volume loss was only observed in PSP-RS, PSP-CBS and PSP-F. Volume loss in the frontal lobes was observed in PSP-SL, PSP-CBS and PSP-F, with these variants also showing highest cortical tau burden at autopsy. The PSP-P and PSP-PGF variants showed more restricted patterns of neurodegeneration predominantly involving striatum, globus pallidus, subthalamic nucleus and thalamus. The PSP-SL variant showed greater volume loss and flortaucipir uptake in supplementary motor area and motor cortex compared to all other variants, but showed less involvement of subthalamic nucleus and midbrain. Compared to PSP-RS, PSP-P had larger midbrain volume and greater flortaucipir uptake in putamen. CONCLUSION: The PSP variants have different patterns of involvement of subcortical circuitry, perhaps suggesting different patterns of disease spread through the brain. These findings will be important in the development of appropriate neuroimaging biomarkers for the different PSP variants.

4.
Neurocrit Care ; 32(1): 286-294, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31732848

RESUMO

Immune response against neuronal and glial cell surface and cytosolic antigens is an important cause of encephalitis. It may be triggered by activation of the immune system in response to an infection (para-infectious), cancer (paraneoplastic), or due to a patient's tendency toward autoimmunity. Antibodies directed toward neuronal cell surface antigens are directly pathogenic, whereas antibodies with intracellular targets may become pathogenic if the antigen is transiently exposed to the cell surface or via activation of cytotoxic T cells. Immune-mediated encephalitis is well recognized and may require intensive care due to status epilepticus, need for invasive ventilation, or dysautonomia. Patients with immune-mediated encephalitis may become critically ill and display clinically complex and challenging to treat movement disorders in over 80% of the cases (Zhang et al. in Neurocrit Care 29(2):264-272, 2018). Treatment options include immunotherapy and symptomatic agents affecting dopamine or acetylcholine neurotransmission. There has been no prior published guidance for management of these movement disorders for the intensivist. Herein, we discuss the immune-mediated encephalitis most likely to cause critical illness, clinical features and mechanisms of movement disorders and propose a management algorithm.

5.
Dysphagia ; 2019 Nov 01.
Artigo em Inglês | MEDLINE | ID: mdl-31676923

RESUMO

Progressive supranuclear palsy (PSP) is the most common Parkinson-Plus syndrome and is associated with early onset of dysphagia relative to Parkinson Disease. The current study contributes to the growing understanding of swallowing dysfunction in PSP by describing oropharyngeal swallowing characteristics in a large prospective cohort of participants with PSP employing a nationally standardized videofluoroscopy protocol and a disease severity scale developed expressly for PSP. Participants were 51 adults diagnosed with PSP. Each participant underwent a clinical interview and standardized videofluorographic assessment. Swallowing function was characterized with the Modified Barium Swallow Impairment Scale (MBSImP) and Penetration-Aspiration Scale (PAS). Variables of interest were participant-reported difficulties with liquids and/or solids; overall impression score for each of the 17 individual MBSImP components, as well as Oral Total Sum and Pharyngeal Total Sum; and PAS. Data were described with median interquartile range, counts, and proportions. Spearman's rank correlations were calculated between MBSImP scores and participant-reported indices, FOIS, and PSP Rating Scale. Approximately two-thirds of participants reported difficulties with liquids, solids, or both, although fewer than 15% reported modifying consistencies. Videofluorographic findings included predominant oral phase impairments, including back and forth rocking motion of the tongue, delayed initiation of the pharyngeal swallow, and oral residue. Pharyngeal phase impairments were relatively infrequent and comparatively mild, with the exception of reduced tongue base retraction contributing to pharyngeal residue, and mildly disrupted laryngeal vestibule closure. Disease severity correlated significantly with oral (r = .0.42, p = .0.002) and pharyngeal (r = 0.41, p = .0.003) total sum scores as well as with the oral phase components of oral transport (r = .0.33, p = .0.02) and initiation of the pharyngeal swallow (r = .0.38, p = .0.007), and PAS for thin liquids (r = .0.44, p = .0.001). The PSP Rating Scale was not more strongly correlated with swallowing impairment than has been reported for other disease severity rating scales. Dysphagia is a common complaint of patients with PSP. The current findings corroborate and expand upon those reported in the literature, detailing relatively more frequent and more severe oral phase impairments and relatively spared hyolaryngeal excursion. Further research is needed to characterize the progression of dysphagia in PSP and to determine whether dysphagia varies in character or in rate of progression across variants of PSP.

6.
Mov Disord Clin Pract ; 6(6): 436-439, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31392243

RESUMO

Objectives: When the 2017 Movement Disorders Society Criteria for progressive supranuclear palsy is applied, patients may appear to have multiple phenotypes. The maximum allocation extinction rules were developed to provide a consistent method for applying the criteria and reaching a single diagnostic label. In this study, we apply both to a neuropathologic cohort of progressive supranuclear palsy and other parkinsonian conditions. Methods: An autopsy cohort of 54 patients with progressive supranuclear palsy and 56 patients with other neuropathologic diseases was selected. Clinical data were retrospectively abstracted, and the diagnostic criteria for progressive supranuclear palsy were applied. All possible phenotypes applicable were listed and maximum allocation extinction rules were applied to assess reduction in the number of phenotypes ascribed per patient. Results: In the progressive supranuclear palsy group, 52 patients met the criteria for multiple phenotypes, with an average of 7 phenotypes per patient. In the nonprogressive supranuclear palsy group, all 56 patients had features of more than one phenotype, up to 3 per patient. After application of maximum allocation extinction rules, the majority of the patients in both groups had a single predominant phenotype. Freezing of gait, supranuclear gaze palsy, and frontal behavioral syndrome were more common in the progressive supranuclear palsy group. Conclusions: The diagnostic criteria for progressive supranuclear palsy identify many clinical features, thereby leading to assignment of multiple phenotypes per patient. We demonstrate that the maximum allocation extinction rules can effectively lead to a single consensus phenotype, maintaining a uniform diagnostic label for clinical and research applications.

7.
Mov Disord Clin Pract ; 6(6): 452-461, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-31392246

RESUMO

Background: The Movement Disorder Society clinical criteria for progressive supranuclear palsy (PSP) provide a framework for assessing the presence/severity of clinical symptoms and define a speech/language variant of PSP. Objectives: To evaluate the clinical criteria in a cohort of speech/language patients with longitudinal follow-up. Methods: A total of 52 patients presenting with progressive apraxia of speech and/or agrammatic aphasia were followed longitudinally for up to 6 visits with clinical assessments and magnetic resonance imaging. We assessed oculomotor, postural instability, and akinesia diagnostic levels and determined whether patients met criteria for possible PSP-speech/language or probable PSP at each visit. Kaplan-Meier curves assessed time-to-event probabilities according to age. Statistical parametric mapping and midbrain volume were assessed according to disease progression. Results: Few PSP symptoms were observed early in the disease, with oculomotor abnormalities and falls first observed 2 years after onset. Falls were more common than vertical supranuclear gaze palsy. Bradykinesia and rigidity commonly developed but axial was rarely greater than appendicular rigidity. During follow-up, 54% met criteria for possible PSP-speech/language, 38% for probable PSP-Richardson's syndrome, and 38% for probable PSP-parkinsonism, most commonly 6 to 6.9 years after onset. The probability of developing PSP was greater when onset was at an age older than 70 years. Patients who progressed to probable PSP had more parkinsonism and oculomotor impairment at baseline and greater midbrain atrophy when compared with those who did not develop probable PSP. Conclusions: Symptoms typical of PSP commonly develop in patients presenting with a progressive speech/language disorder. Older age appears to be an important prognostic factor in these patients.

8.
Parkinsonism Relat Disord ; 66: 56-61, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31279635

RESUMO

Progressive supranuclear palsy is characterized primarily by 4R tau inclusions, atrophy in the brainstem and basal ganglia, and neurodegeneration along the dentatorubrothalamic tract, which are measurable in vivo using flortaucipir PET, T1-weighted MRI, and MRI with diffusion tensor imaging (DTI). However, little is known about how these processes relate to each other. The aim of this study was to investigate multimodal associations between flortaucipir PET uptake, tissue volume loss on structural MRI and white matter tract disruption on DTI. Thirty-four patients with progressive supranuclear palsy and 29 normal controls underwent flortaucipir PET, MRI and DTI. Voxel-wise comparison was performed between patients and controls. Sparse canonical correlations analysis was applied on regional measurements of flortaucipir uptake, tissue volume, fractional anisotropy and mean diffusivity of the PSP population. Pearson's correlation coefficients were assessed across modalities on the regions identified by the sparse canonical correlation analyses. Sparse canonical correlation analyses identified associations between elevated flortaucipir uptake in the cerebellar dentate, red nucleus and subthalamic nucleus and decreased volume in the same regions, and decreased fractional anisotropy and increased mean diffusivity in tracts including the superior cerebellar peduncle, sagittal striatum and posterior corona radiata. Furthermore, decreased fractional anisotropy and increased mean diffusivity in the body of the corpus callosum and anterior and superior corona radiata were related to volume loss in the frontal lobe. Tau uptake measured by flortaucipir PET appears to be related to the neurodegenerative process of progressive supranuclear palsy, including reduced tissue volume and white matter tract degeneration.

11.
Semin Neurol ; 39(2): 264-273, 2019 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-30925618

RESUMO

Tauopathies are rare neurodegenerative disorders related to microtubule-associated protein tau, which functions to stabilize microtubules. Pathological changes caused by overexpression or hyperphosphorylation of tau lead to the disengagement of tau from microtubules and accumulation of toxic intracellular inclusions. Tau pathology is the underlying mechanism for several sporadic and genetic disorders. These are collectively known as tauopathies. Each tauopathy is differentiated from others by its neuropathological features such as the presence of specific isoforms of tau, type of cellular inclusions, and the regions of the brain affected. Neuropathological features, with a few exceptions however, do not correspond to distinct clinical phenotypes. There is considerable phenotypic overlap between the different tauopathies. Interaction between tau and other protein inclusions further alters the clinical phenotype.Recent advances in the development of tau biomarkers, especially the development of tau radioligands used in positron emission tomography neuroimaging, and a better understanding of biology and pathology of tau are important first steps toward the ultimate goal of accurate diagnosis and disease modification in tauopathies.


Assuntos
Tauopatias/diagnóstico , Humanos , Tauopatias/metabolismo , Tauopatias/patologia , Tauopatias/terapia
12.
Mov Disord ; 34(8): 1144-1153, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-30726566

RESUMO

BACKGROUND: In 2017, the International Parkinson and Movement Disorder Society put forward new clinical criteria for the diagnosis of PSP, recognizing diverse PSP phenotypes. In this study, we compared the sensitivity and specificity of the new criteria with the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria at different times. METHODS: Patients with clinical parkinsonism, clinical and/or neuropathological diagnosis of PSP, were identified from the Society for Progressive Supranuclear Palsy brain bank. All patients had neuropathologic diagnoses and detailed clinical examination performed by a neurologist at 1 of the 3 Mayo Clinic sites, in Florida, Arizona, and Minnesota. Clinical symptoms and signs were abstracted retrospectively in a blinded fashion and used to determine whether patients met either diagnostic criterion. Patients were divided into early and late disease stage groups using a 3-year cutoff. RESULTS: A total of 129 patients were included, of whom 66 had PSP pathology (51%). The remainder had other neurodegenerative diseases. The overall sensitivity of the International Parkinson and Movement Disorder Society criteria was 87.9%, compared with 45.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy criteria, whereas the specificity of the International Parkinson and Movement Disorder Society probable PSP criteria was 85.7%, compared with 90.5% for the National Institutes of Neurological Disease and Society for Progressive Supranuclear Palsy. Individual patients were noted to have features of multiple PSP phenotypes. CONCLUSION: The International Parkinson and Movement Disorder Society criteria recognize several phenotypes of progressive supranuclear palsy and hence have higher sensitivity than the previous criteria. © 2019 International Parkinson and Movement Disorder Society.

13.
Cureus ; 10(9): e3290, 2018 Sep 12.
Artigo em Inglês | MEDLINE | ID: mdl-30443460

RESUMO

The Zika Virus (ZIKV) has been slowly becoming an epidemic in different parts of the world. Since its discovery in 1947, there have been numerous outbreaks affecting many different populations. Currently, there is an ongoing threat of ZIKV in Latin America and the United States of America. ZIKV is mainly spread by the Aedes aegypti mosquito and causes non-specific symptoms such as fever, myalgia, and generalized weakness. In addition to these symptoms, it has been noted the ZIKV is capable of causing associated conditions in adults, particularly in pregnant women as well as in newborns via vertical transmission. These manifestations include microcephaly, lissencephaly, ventriculomegaly, optic neuropathy, and congenital glaucoma, arthralgia, maculopapular rash, and cardiovascular anomalies such as atrial fibrillation. It is important to understand the reason for this specific set of associated conditions that emerge with ZIKV. This paper aims to identify the manifestations of ZIKV in adults and neonates in detail and attempts to understand the pathophysiology behind each one.

14.
Cureus ; 10(8): e3158, 2018 Aug 17.
Artigo em Inglês | MEDLINE | ID: mdl-30349765

RESUMO

Background Plasma uric acid has been shown to be associated with an increased risk of hypertension, cardiovascular disease, chronic kidney disease, insulin resistance, and metabolic syndrome. Conflicting data regarding plasma uric acid levels in type 2 diabetes mellitus and their role in the development and progression of diabetic complications have been observed by many studies. The present study aimed to evaluate plasma uric acid levels in type 2 diabetic patients and to determine the effects of hypoglycemic drugs and pharmacologic insulin on plasma uric acid concentration. Subjects and methods The study included 162 type 2 diabetic patients divided into three groups (insulin taking group (N=58), glibenclamide taking group (N=40), and metformin taking group (N=64), and 47 normal healthy controls. A questionnaire that included variables such as age, sex, duration of disease, and body mass index (BMI) were answered by all the participants. Blood samples were collected and estimated for serum uric acid (SUA), fasting blood sugar (FBS), and glycated hemoglobin (HbA1c) using standard methods and the data were statistically analyzed. Results Diabetic patients showed a significant increase in serum uric acid, fasting blood sugar, glycated hemoglobin, and body mass index when compared to control subjects. The serum uric acid levels of metformin and glibenclamide taking groups were significantly higher than the control group. The difference of serum uric concentration between the insulin taking group and both the control and metformin groups was statistically non-significant. On the other hand, obese diabetics showed a significantly higher serum uric acid than overweight and lean diabetics. Furthermore, serum uric acid had a significant strong positive correlation with body mass index. Conclusion Type 2 diabetes mellitus (T2DM) is associated with high serum uric acid levels. Hypoglycemic drugs and pharmacologic insulin do not have a large impact on SUA concentration, but obesity seems to be the primary determinant of SUA levels in T2DM patients. The condition of diabetes may have a direct effect on the oxidation of the purine nucleotides resulting in the increased uric acid (UA) levels. In addition, hyperinsulinemia could lead to hyperuricemia by increasing the rate of xanthine oxidase synthesis. There is a strong relationship between T2DM and obesity with high uric acid levels.

15.
Cureus ; 10(7): e3030, 2018 Jul 23.
Artigo em Inglês | MEDLINE | ID: mdl-30254819

RESUMO

Type 2 diabetes mellitus (T2DM) has high morbidity and results in increased risk of mortality mainly due to cardiovascular diseases. Different factors have been found to be responsible for the increased prevalence of coronary artery disease (CAD) in T2DM. One of these factors includes raised serum levels of lipoprotein(a) (Lp(a)). The present study was designed to evaluate the association of Lp(a) levels with T2DM in Libyan patients and find the degree of association between Lp(a), glycemic control, insulin, and lipid profile. The study included 100 T2DM patients, recruited from the Benghazi Center for Diagnosis and Treatment of Diabetes, and 30 apparently healthy age and sex-matched individuals, to serve as controls. All participants completed a questionnaire to obtain clinical information and medical history. Blood samples were collected and analyzed for Lp(a), fasting blood glucose (FBS), HbA1c, insulin, total cholesterol (TC), triglycerides (TAG), low-density lipoprotein c (LDL-c), and high-density lipoprotein c (HDL-c). The results from the comparison between the control and experimental groups showed that Lp(a) was significantly higher in diabetic patients. It showed the positive correlation with TC and LDL-c. On the contrary, it showed no significant correlations with glycemic control parameters nor insulin, TAG, HDL-c, body mass index (BMI), and blood pressor (BP). Cardiovascular disease (CVD) risk in type 2 diabetic patients could be dependent on risk factors other than LDL-c, which may not be an independent risk factor for the development and progression of atherogenesis in T2DM. Lp(a) may be a new metabolic syndrome risk factor, and it may be useful as a cardiovascular risk biomarker in future clinical practice.

16.
Neurol Clin Pract ; 8(3): 240-248, 2018 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-30105164

RESUMO

Background: We sought to determine the etiologies, diagnostic testing, and management of a retrospective cohort of patients with camptocormia evaluated at a single center. Methods: We reviewed medical records of all adult patients evaluated at Mayo Clinic Rochester with a diagnosis of camptocormia from 2000 to 2014. Demographic and clinical data were abstracted and analyzed. Results: There were 276 patients (58.0% male), with mean age at presentation of 68.6 (±12.7) years. An etiology was identified in 98.2%. The most common etiologies were idiopathic Parkinson disease (22.5%), idiopathic axial myopathy (14.1%), and degenerative joint disease without fixed deformity (13.0%). We also identified several rare causes of camptocormia. Investigations included spine imaging, needle and surface EMG, and muscle biopsy. Most patients received physical therapy and orthotic support with limited benefit. Limited improvement of camptocormia was seen where a treatable etiology was identified. Conclusions: An etiology can be identified in almost all cases of camptocormia. Most cases are due to 3 common disorders: Parkinson disease, axial myopathy, and degenerative joint disease. A diagnostic and treatment algorithm is proposed.

18.
Expert Rev Neurother ; 18(7): 603-616, 2018 07.
Artigo em Inglês | MEDLINE | ID: mdl-29902389

RESUMO

INTRODUCTION: Progressive supranuclear palsy (PSP) is associated with microtubule-associated protein tau dysfunction. Originally thought to result in a syndrome of atypical Parkinsonism, vertical supranuclear gaze palsy, and cognitive impairment, several additional phenotypic manifestations of PSP pathology have been described over the last 20 years. Furthermore, prototypical PSP features may develop late, making early diagnosis challenging. Areas covered: An in-depth view of emerging knowledge in the field of PSP. Advances in clinicopathologic correlation, blood, cerebrospinal, and more importantly neuroimaging biomarkers are discussed in light of the 2017 PSP diagnostic criteria by the Movement Disorders Society Study Group. Discoveries related to molecular pathogenesis have enabled development of disease-modifying therapies for PSP, many of which are currently under investigation. Expert commentary: Despite remarkable growth in our knowledge of tauopathies like PSP, early and accurate clinical prediction of PSP neuropathology remains challenging. Clinical phenotypes overlap, and biomarkers are nonspecific. There is a pressing need for disease-specific biomarkers that enable timely identification of patients and biomarker-driven investigation of disease-modifying therapies.


Assuntos
Paralisia Supranuclear Progressiva/diagnóstico , Biomarcadores , Humanos , Neuroimagem , Fenótipo , Paralisia Supranuclear Progressiva/epidemiologia , Paralisia Supranuclear Progressiva/fisiopatologia , Paralisia Supranuclear Progressiva/terapia , Proteínas tau/fisiologia
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