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BACKGROUND AND PURPOSE: Alterations of the Basilar Artery (BA) anatomy have been suggested as a possible Magnetic Resonance Angiography (MRA) feature of Fabry Disease (FD). Nonetheless, no information about their clinical or pathophysiological correlates is available, limiting our comprehension of the real impact of vessel remodeling in FD. MATERIALS AND METHODS: Brain MRIs of 53 FD subjects (40.7±12.4 years, M/F=23/30) were collected in this single center study. Mean BA diameter and its Tortuosity Index (TI) were calculated on MRA. Possible correlations between these metrics and clinical, laboratory and advanced imaging variables of the posterior circulation were tested. In a subgroup of 20 subjects, a two-year clinical and imaging follow-up was available, with possible longitudinal changes of these metrics and their ability in predicting clinical scores that were also probed. RESULTS: No significant association was found between MRA metrics and any clinical, laboratory or advanced imaging variable (ρ values ranging from -0.006 to 0.32). At the follow-up examination, no changes were observed over time for mean BA diameter (p = 0.84) and TI (p = 0.70). Finally, baseline MRA variables failed to predict the clinical status of FD patients at follow-up (p=0.42 and 0.66, respectively). CONCLUSIONS: Alterations of BA in FD lack of any significant association with clinical, laboratory or advanced imaging findings collected in this study. Furthermore, this lack of correlation seems constant over time, suggesting their stability over time. Taken together, all these results suggest that the role of BA dolichoectasia in FD should be reconsidered. ABBREVIATIONS: CNS = Central Nervous System; FASTEX = FAbry STabilization indEX; FD = Fabry Disease; Gb3 = Globotriaosylceramide; LysoGb3 = globotriaosylsphingosine; MSSI = Mainz Severity Score Index.
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Anderson-Fabry disease (AFD) is a genetic sphingolipidosis involving virtually the entire body. Among its manifestation, the involvement of the central and peripheral nervous system is frequent. In recent decades, it has become evident that, besides cerebrovascular damage, a pure neuronal phenotype of AFD exists in the central nervous system, which is supported by clinical, pathological, and neuroimaging data. This neurodegenerative phenotype is often clinically characterized by an extrapyramidal component similar to the one seen in prodromal Parkinson's disease (PD). We analyzed the biological, clinical pathological, and neuroimaging data supporting this phenotype recently proposed in the literature. Moreover, we compared the neurodegenerative PD phenotype of AFD with a classical monogenic vascular disease responsible for vascular parkinsonism and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy (CADASIL). A substantial difference in the clinical and neuroimaging features of neurodegenerative and vascular parkinsonism phenotypes emerged, with AFD being potentially responsible for both forms of the extrapyramidal involvement, and CADASIL mainly associated with the vascular subtype. The available studies share some limitations regarding both patients' information and neurological and genetic investigations. Further studies are needed to clarify the potential association between AFD and extrapyramidal manifestations.
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Enfermedad de Fabry , Fenotipo , Humanos , Enfermedad de Fabry/genética , Enfermedad de Fabry/patología , Enfermedad de Fabry/complicaciones , Trastornos Parkinsonianos/genética , Trastornos Parkinsonianos/diagnóstico por imagen , Trastornos Parkinsonianos/patología , CADASIL/genética , CADASIL/patologíaRESUMEN
BACKGROUND: Autosomal recessive spastic ataxia of Charlevoix-Saguenay (ARSACS) and hereditary spastic paraplegia type 7 (SPG7) represent the most common genotypes of spastic ataxia (SPAX). To date, their magnetic resonance imaging (MRI) features have only been described qualitatively, and a pure neuroradiological differential diagnosis between these two conditions is difficult to achieve. OBJECTIVES: To test the performance of MRI measures to discriminate between ARSACS and SPG7 (as an index of common SPAX disease). METHODS: In this prospective multicenter study, 3D-T1-weighted images of 59 ARSACS (35.4 ± 10.3 years, M/F = 33/26) and 78 SPG7 (54.8 ± 10.3 years, M/F = 51/27) patients of the PROSPAX Consortium were analyzed, together with 30 controls (45.9 ± 16.9 years, M/F = 15/15). Different linear and surface measures were evaluated. A receiver operating characteristic analysis was performed, calculating area under the curve (AUC) and corresponding diagnostic accuracy parameters. RESULTS: The pons area proved to be the only metric increased exclusively in ARSACS patients (P = 0.02). Other different measures were reduced in ARSACS and SPG7 compared with controls (all with P ≤ 0.005). A cut-off value equal to 1.67 of the pons-to-superior vermis area ratio proved to have the highest AUC (0.98, diagnostic accuracy 93%, sensitivity 97%) in discriminating between ARSACS and SPG7. CONCLUSIONS: Evaluation of the pons-to-superior vermis area ratio can discriminate ARSACS from other SPAX patients, as exemplified here by SPG7. Hence, we hereby propose this ratio as the Magnetic Resonance Index for the Assessment and Recognition of patients harboring SACS mutations (MRI-ARSACS), a novel diagnostic tool able to identify ARSACS patients and useful for discriminating ARSACS from other SPAX patients undergoing MRI. © 2024 International Parkinson and Movement Disorder Society.
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BACKGROUND: Autosomal Recessive Spastic Ataxia of Charlevoix-Saguenay (ARSACS) and Spastic Paraplegia Type 7 (SPG7) are paradigmatic spastic ataxias (SPAX) with suggested white matter (WM) involvement. Aim of this work was to thoroughly disentangle the degree of WM involvement in these conditions, evaluating both macrostructure and microstructure via the analysis of diffusion MRI (dMRI) data. MATERIAL AND METHODS: In this multi-center prospective study, ARSACS and SPG7 patients and Healthy Controls (HC) were enrolled, all undergoing a standardized dMRI protocol and a clinimetrics evaluation including the Scale for the Assessment and Rating of Ataxia (SARA). Differences in terms of WM volume or global microstructural WM metrics were probed, as well as the possible occurrence of a spatially defined microstructural WM involvement via voxel-wise analyses, and its correlation with patients' clinical status. RESULTS: Data of 37 ARSACS (M/F = 21/16; 33.4 ± 12.4 years), 37 SPG7 (M/F = 24/13; 55.7 ± 10.7 years), and 29 HC (M/F = 13/16; 42.1 ± 17.2 years) were analyzed. While in SPG7, only a mild mean microstructural damage was found compared to HC, ARSACS patients present a severe WM involvement, with a reduced global volume (p < 0.001), an alteration of all microstructural metrics (all with p < 0.001), without a spatially defined pattern of damage but with a prominent involvement of commissural fibers. Finally, in ARSACS, a correlation between microstructural damage and SARA scores was found (p = 0.004). CONCLUSION: In ARSACS, but not SPG7 patients, we observed a complex and multi-faced involvement of brain WM, with a clinically meaningful widespread loss of axonal and dendritic integrity, secondary demyelination and, overall, a reduction in cellularity and volume.
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Espasticidad Muscular , Ataxias Espinocerebelosas , Sustancia Blanca , Humanos , Masculino , Femenino , Adulto , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/patología , Persona de Mediana Edad , Ataxias Espinocerebelosas/diagnóstico por imagen , Ataxias Espinocerebelosas/patología , Espasticidad Muscular/diagnóstico por imagen , Espasticidad Muscular/patología , Adulto Joven , Estudios Prospectivos , Anciano , Paraplejía Espástica Hereditaria/diagnóstico por imagen , Paraplejía Espástica Hereditaria/patología , Imagen de Difusión por Resonancia Magnética , Encéfalo/diagnóstico por imagen , Encéfalo/patología , Imagen por Resonancia Magnética , Discapacidad Intelectual , Atrofia ÓpticaRESUMEN
PURPOSE: How to measure brain globotriaosylceramide (Gb3) accumulation in Fabry Disease (FD) patients in-vivo is still an open challenge. The objective of this study is to provide a quantitative, non-invasive demonstration of this phenomenon using quantitative MRI (qMRI). METHODS: In this retrospective, monocentric cross-sectional study conducted from November 2015 to July 2018, FD patients and healthy controls (HC) underwent an MRI scan with a relaxometry protocol to compute longitudinal relaxation rate (R1) maps to evaluate gray (GM) and white matter (WM) lipid accumulation. In a subgroup of 22 FD patients, clinical (FAbry STabilization indEX -FASTEX- score) and biochemical (residual α-galactosidase activity) variables were correlated with MRI data. Quantitative maps were analyzed at both global ("bulk" analysis) and regional ("voxel-wise" analysis) levels. RESULTS: Data were obtained from 42 FD patients (mean age = 42.4 ± 12.9, M/F = 16/26) and 49 HC (mean age = 42.3 ± 16.3, M/F = 28/21). Compared to HC, FD patients showed a widespread increase in R1 values encompassing both GM (pFWE = 0.02) and WM (pFWE = 0.02) structures. While no correlations were found between increased R1 values and FASTEX score, a significant negative correlation emerged between residual enzymatic activity levels and R1 values in GM (r = -0.57, p = 0.008) and WM (r = -0.49, p = 0.03). CONCLUSIONS: We demonstrated the feasibility and clinical relevance of non-invasively assessing cerebral Gb3 accumulation in FD using MRI. R1 mapping might be used as an in-vivo quantitative neuroimaging biomarker in FD patients.
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Enfermedad de Fabry , Imagen por Resonancia Magnética , Trihexosilceramidas , Humanos , Enfermedad de Fabry/diagnóstico por imagen , Enfermedad de Fabry/metabolismo , Masculino , Femenino , Adulto , Imagen por Resonancia Magnética/métodos , Trihexosilceramidas/metabolismo , Estudios Transversales , Estudios Retrospectivos , Estudios de Casos y Controles , Encéfalo/diagnóstico por imagen , Encéfalo/metabolismo , Persona de Mediana Edad , Sustancia Blanca/diagnóstico por imagen , Sustancia Blanca/metabolismoRESUMEN
The complexity in diagnosing hereditary degenerative ataxias lies not only in their rarity, but also in the variety of different genetic conditions that can determine sometimes similar and overlapping clinical findings. In this light, Magnetic Resonance Imaging (MRI) plays a key role in the evaluation of these conditions, being a fundamental diagnostic tool needed not only to exclude other causes determining the observed clinical phenotype, but also to proper guide to an adequate genetic testing. Here, we propose an MRI-based diagnostic algorithm named CHARON (Characterization of Hereditary Ataxias Relying On Neuroimaging), to help in disentangling among the numerous, and apparently very similar, hereditary degenerative ataxias. Being conceived from a neuroradiological standpoint, it is based primarily on an accurate evaluation of the observed MRI findings, with the first and most important being the pattern of cerebellar atrophy. Along with the evaluation of the presence, or absence, of additional signal changes and/or supratentorial involvement, CHARON allows for the identification of a small groups of ataxias sharing similar imaging features. The integration of additional MRI findings, demographic, clinical and laboratory data allow then for the identification of typical, and in some cases pathognomonic, phenotypes of hereditary ataxias.
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While neurological manifestations are core features of Fabry disease (FD), quantitative neuroimaging biomarkers allowing to measure brain involvement are lacking. We used deep learning and the brain-age paradigm to assess whether FD patients' brains appear older than normal and to validate brain-predicted age difference (brain-PAD) as a possible disease severity biomarker. MRI scans of FD patients and healthy controls (HCs) from a single Institution were, retrospectively, studied. The Fabry stabilization index (FASTEX) was recorded as a measure of disease severity. Using minimally preprocessed 3D T1-weighted brain scans of healthy subjects from eight publicly available sources (N = 2160; mean age = 33 years [range 4-86]), we trained a model predicting chronological age based on a DenseNet architecture and used it to generate brain-age predictions in the internal cohort. Within a linear modeling framework, brain-PAD was tested for age/sex-adjusted associations with diagnostic group (FD vs. HC), FASTEX score, and both global and voxel-level neuroimaging measures. We studied 52 FD patients (40.6 ± 12.6 years; 28F) and 58 HC (38.4 ± 13.4 years; 28F). The brain-age model achieved accurate out-of-sample performance (mean absolute error = 4.01 years, R2 = .90). FD patients had significantly higher brain-PAD than HC (estimated marginal means: 3.1 vs. -0.1, p = .01). Brain-PAD was associated with FASTEX score (B = 0.10, p = .02), brain parenchymal fraction (B = -153.50, p = .001), white matter hyperintensities load (B = 0.85, p = .01), and tissue volume reduction throughout the brain. We demonstrated that FD patients' brains appear older than normal. Brain-PAD correlates with FD-related multi-organ damage and is influenced by both global brain volume and white matter hyperintensities, offering a comprehensive biomarker of (neurological) disease severity.
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Aprendizaje Profundo , Enfermedad de Fabry , Leucoaraiosis , Humanos , Preescolar , Niño , Adolescente , Adulto Joven , Adulto , Persona de Mediana Edad , Anciano , Anciano de 80 o más Años , Enfermedad de Fabry/diagnóstico por imagen , Estudios Retrospectivos , Encéfalo/diagnóstico por imagen , Imagen por Resonancia Magnética , BiomarcadoresRESUMEN
OBJECTIVES: In the neuroradiological work-up of Multiple Sclerosis (MS), the detection of "black holes" (BH) represent an information of undeniable importance. Nevertheless, different sequences can be used in clinical practice to evaluate BH in MS. Aim of this study was to investigate the possible impact of different sequences, resolutions, and levels of expertise on the intra- and inter-rater reliability identification of BH in MS. METHODS: Brain MRI scans of 85 MS patients (M/F = 22/63; mean age = 36.0 ± 10.2 years) were evaluated in this prospective single-center study. The acquisition protocol included a 3 mm SE-T1w sequence, a 1 mm 3D-GrE-T1w sequence from which a resliced 3 mm sequence was also obtained. Images were evaluated independently by two readers of different expertise at baseline and after a wash-out period of 30 days. The intraclass correlation coefficient (ICC) was calculated as an index of intra and inter-reader reliability. RESULTS: For both readers, the intra-reader ICC analysis showed that the 3 mm SE-T1w and 3 mm resliced GrE-T1w images achieved an excellent performance (both with an ICC ≥ 0.95), while 1 mm 3D-GrE-T1w scans achieved a moderate one (ICC < 0.90). The inter-reader analysis showed that each of the three sequences achieved a moderate performance (all ICCs < 0.90). CONCLUSIONS: The 1 mm 3D-GrE-T1w sequence seems to be prone to a greater intra-reader variability compared to the 3 mm SE-T1w, with this effect being driven by the higher spatial resolution of the first sequence. To ensure reliability levels comparable with the standard SE-T1w in BH count, an assessment on a 3 mm resliced GrE-T1w sequence should be recommended.
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Imagen por Resonancia Magnética , Esclerosis Múltiple , Humanos , Esclerosis Múltiple/diagnóstico por imagen , Femenino , Imagen por Resonancia Magnética/métodos , Masculino , Adulto , Estudios Prospectivos , Reproducibilidad de los Resultados , Competencia Clínica , Interpretación de Imagen Asistida por Computador/métodos , Variaciones Dependientes del Observador , Imagenología Tridimensional/métodos , Aumento de la Imagen/métodos , Persona de Mediana EdadRESUMEN
The association of cerebellar ataxia and hypogonadism occurs in a heterogeneous group of disorders, caused by different genetic mutations often associated with a recessive inheritance. In these patients, magnetic resonance imaging (MRI) plays a pivotal role in the diagnostic workflow, with a variable involvement of the cerebellar cortex, alone or in combination with other brain structures. Neuroimaging involvement of the pituitary gland is also variable. Here, we provide an overview of the main clinical and conventional brain and pituitary gland MRI imaging findings of the most common genetic mutations associated with the clinical phenotype of ataxia and hypogonadism, with the aim of helping neuroradiologists in the identification of these disorders.
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Ataxia Cerebelosa , Hipogonadismo , Humanos , Ataxia Cerebelosa/diagnóstico por imagen , Ataxia Cerebelosa/genética , Ataxia Cerebelosa/complicaciones , Hipogonadismo/diagnóstico por imagen , Hipogonadismo/genética , Encéfalo/diagnóstico por imagen , Hipófisis/diagnóstico por imagen , Imagen por Resonancia MagnéticaRESUMEN
Recent advances in machine learning and artificial intelligence technology have ensured automated evaluation of medical images. As a result, quantifiable diagnostic and prognostic biomarkers have been created. We discuss radiomics applications for the head and neck region in this paper. Molecular characterization, categorization, prognosis and therapy recommendation are given special consideration. In a narrative manner, we outline the fundamental technological principles, the overall idea and usual workflow of radiomic analysis and what seem to be the present and potential challenges in normal clinical practice. Clinical oncology intends for all of this to ensure informed decision support for personalized and useful cancer treatment. Head and neck cancers present a unique set of diagnostic and therapeutic challenges. These challenges are brought on by the complicated anatomy and heterogeneity of the area under investigation. Radiomics has the potential to address these barriers. Future research must be interdisciplinary and focus on the study of certain oncologic functions and outcomes, with external validation and multi-institutional cooperation in order to achieve this.
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The sellar region represents a complex anatomical area, composed of multiple structures of different embryological derivation, including the skull base and the pituitary gland, along with vascular, nervous, and meningeal structures. Masses arising in this region include benign and malignant lesions arising from the pituitary gland itself, but also from vestigial embryological residues or surrounding tissues, that may require different therapeutic approaches. While assessing sellar region masses, the combination of clinical presentation and imaging features is fundamental to define hypotheses about their nature. MR represents the imaging modality of choice, providing information about the site of the lesion, its imaging features, and relation with adjacent structures, while CT is useful to confirm the presence of lesion calcifications or to reveal tumor invasion of bony structures. The aim of this pictorial review is to provide an overview of the common neoplasms and tumor-like conditions of the sellar region, according to the 2021 WHO Classification of Tumors of the Central Nervous System (fifth edition), with an emphasis on the radiologic-pathologic correlation. After a brief introduction on the anatomy of this region and the imaging and pathological techniques currently used, the most relevant MRI characteristics, clinical findings, and pathological data, including histologic and molecular features, will be shown and discussed, with the aim of facilitating an appropriate differential diagnosis among these entities.
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Neoplasias Hipofisarias , Humanos , Neoplasias Hipofisarias/diagnóstico por imagen , Neoplasias Hipofisarias/patología , Silla Turca/diagnóstico por imagen , Hipófisis , Imagen por Resonancia Magnética/métodos , Organización Mundial de la SaludRESUMEN
CONTEXT: Subclinical hypothyroidism (SH) is associated with some abnormalities in primary and secondary hemostasis. OBJECTIVE: The objective of the study was to evaluate changes in primary and secondary hemostasis induced by levothyroxine (L-T4) treatment in SH patients. DESIGN: This was a prospective cohort study with a 6-month follow-up. STUDY SETTING: Outpatients were referred to "Federico II" University of Naples. PATIENTS: Subjects with a SH without previous/ongoing L-T4 therapy participated in the study. MAIN OUTCOME MEASURE: Changes in major hemostatic/fibrinolytic variables and platelet reactivity [mean platelet volume (MPV), arachidonic acid (AA), or ADP concentrations inducing a ≥ 50% irreversible aggregation (AC-50%)] in SH patients before and after a 6-month L-T4 treatment. RESULTS: At baseline, 41 SH patients showed higher levels of factor VII activity (123.9 ± 20.4 vs 107.7 ± 12.2, P < .001), plasminogen activator inhibitor-1 (33.6 ± 13.9 vs 22.5 ± 5.74, P < .001) and tissue plasminogen activator (5.56 ± 2.22 vs 4.75 ± 1.61, P = .010), with lower levels of D-dimer (220.3 ± 67.1 vs 252.1 ± 72.4, P = .017) compared with healthy controls. SH patients also showed a higher MPV (9.92 ± 1.15 vs 8.9 ± 0.9, P < .001) and AC-50% to AA (0.18 ± 0.12 vs 0.36 ± 0.10, P < .001) and to ADP (1.5 ± 0.6 vs 1.9 ± 1.3, P = .024). After a 6-month L-T4 therapy, a reduction of factor VII activity (from 123.9 ± 20.4 to 102.6 ± 14.3, P < .001), plasminogen activator inhibitor-1 (33.6 ± 13.9 to 19.4 ± 7.6, P < .001), and tissue plasminogen activator (5.56 ± 2.22 to 1.91 ± 4:43, P = .002) was found in SH subjects, with a marginal increase in D-dimer (from 220.3 ± 67.1 to 245.2 ± 103.1, P = .053). AC-50% to AA (from 0.18 ± 0.12 to 0.54 ± 0.3, P < .001) and to ADP (from 1.5 ± 0.6 to 1.86 ± 0.3, P = .042) were reduced, paralleled by a significant reduction of MPV (from 9.92 ± 1.15 to 9.10 ± 1.23, P = .016). CONCLUSIONS: SH patients exhibit a prothrombotic status, which is reverted by a 6-month L-T4 treatment.
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Hemostasis/efectos de los fármacos , Hipotiroidismo/sangre , Hipotiroidismo/tratamiento farmacológico , Tiroxina/farmacología , Tiroxina/uso terapéutico , Adulto , Enfermedades Asintomáticas , Femenino , Fibrinólisis/efectos de los fármacos , Estudios de Seguimiento , Humanos , Hipotiroidismo/complicaciones , Masculino , Volúmen Plaquetario Medio , Persona de Mediana Edad , Agregación Plaquetaria/efectos de los fármacosRESUMEN
Folic acid supplementation is the mainstay treatment of hyperhomocysteinemia (HHcy). However, no recommendations are currently available in regard to the optimal replacement therapy. Therefore, this prospective study hypothesized that a cyclic schedule (1 month of therapy followed by 2 months of withdrawal) of 5-methyltetrahydrofolate (5-MTHF) would reduce plasma levels of fasting total homocysteine (tHcy) in patients with mild/moderate HHcy. Patients with a new diagnosis of mild/moderate HHcy were evaluated for the methylenetetrahydrofolate reductase genotype and the presence of major features of metabolic syndrome. All enrolled subjects received a cyclic 5-MTHF oral supplementation and were reevaluated after each treatment cycle for a total of 2 years. In the 246 enrolled subjects, a significant reduction of tHcy levels occurred after the first cycle of treatment (from 31.6 ± 13.6 to 14.4 ± 5.77 µmol/L, P < .001) and during the whole 2-year follow-up (from 31.6 ± 13.6 to 12.18 ± 3.03 µmol/L, P < .001). The values of tHcy returned to reference range in 117 subjects (51.3%) after the first cycle and in 198 (86.8%) during the follow-up. The risk of failure in tHcy level normalization was increased in patients with metabolic syndrome (hazard ratio [HR], 3.49; 95% confidence interval [CI], 1.46-8.36), higher baseline tHcy levels (HR, 1.045; 95% CI, 1.018-1.073), or methylenetetrahydrofolate reductase homozygous mutation (HR, 6.59; 95% CI, 2.64-16.4). This study clearly shows that a cyclic schedule (1 month of therapy followed by 2 months of withdrawal) of 5-MTHF supplementation is able to significantly reduce tHcy levels in patients with mild/moderate HHcy.