Striatonigral involvement in Fabry Disease: A quantitative and volumetric Magnetic Resonance Imaging study

Russo, Camilla; Pontillo, Giuseppe; Pisani, Antonio; Saccà, Francesco; Riccio, Eleonora; Macera, Antonio; Rusconi, Giovanni; Stanzione, Arnaldo; Borrelli, Pasquale; Morra, Vincenzo Brescia; Tedeschi, Enrico; Brunetti, Arturo; Cocozza, Sirio; Palma, Giuseppe

doi:10.1016/j.parkreldis.2018.07.011

Cited by 13 publications

(11 citation statements)

References 30 publications

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“…Poorer motor performance compared with age-matched HC has been described in FD patients, mainly involving functional domains (e.g., gait and hand speed) related to the extrapyramidal system [3]. Along with the evidence from ex vivo studies of pathologic Gb3 accumulation in different neuronal populations including the substantia nigra [23,24], recent neuroimaging studies demonstrated the occurrence of neurodegenerative phenomena in two of the main hubs within the cortico-striatal-thalamo-cortical motor loop (i.e., striatum and substantia nigra), as well as functional disconnection between the motor cortex and the basal ganglia in this condition [5,6]. In conjunction with these previous evidences, our results may support the hypothesis of a primary neurodegenerative damage of the extrapyramidal system, occurring at least in part independently from micro-and macro-vascular pathologies.…”

Section: Discussionmentioning

confidence: 96%

“…Furthermore, the lack of clinical data also needs to be acknowledged as a limitation of our study. However, even if theoretically the correlation with clinical measures of motor impairment could have helped to elucidate the functional meaning of the observed WM alterations, it is known that neurological alterations in FD patients are mild [3] and thus hardly relate to findings of advanced brain MRI techniques [5,6].…”

Section: Discussionmentioning

confidence: 99%

“…Indeed, an alteration of the corticostriatal pathway has been described in FD patients, and a reduced functional connectivity between the motor cortex and the striatum has been described in this condition [5]. An additional evidence of the involvement of the extrapyramidal pathway in FD has been demonstrated in a recent study showing the presence of susceptibility and volumetric alterations affecting two of the main relay stations of the extrapyramidal system, namely the striatum and the substantia nigra [6].…”

Section: Introductionmentioning

confidence: 95%

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Microstructural damage of the cortico-striatal and thalamo-cortical fibers in Fabry disease: a diffusion MRI tractometry study

et al. 2020

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Purpose Recent evidences have suggested the possible presence of an involvement of the extrapyramidal system in Fabry disease (FD), a rare X-linked lysosomal storage disorder. We aimed to investigate the microstructural integrity of the main tracts of the cortico-striatal-thalamo-cortical loop in FD patients. Methods Forty-seven FD patients (mean age = 42.3 ± 16.3 years, M/F = 28/21) and 49 healthy controls (mean age = 42.3 ± 13.1 years, M/F = 19/28) were enrolled in this study. Fractional anisotropy (FA), axial (AD), radial (RD), and mean diffusivity (MD) maps were computed for each subject, and connectomes were built using a standard atlas. Diffusion metrics and connectomes were then combined to carry on a diffusion MRI tractometry analysis. The main afferent and efferent pathways of the cortico-striatal-thalamo-cortical loop (namely, bundles connecting the precentral gyrus (PreCG) with the striatum and the thalamus) were evaluated. Results We found the presence of a microstructural involvement of cortico-striatal-thalamo-cortical loop in FD patients, predominantly affecting the left side. In particular, we found significant lower mean FA values of the left cortico-striatal fibers (p = 0.001), coupled to higher MD (p = 0.001) and RD (p < 0.001) values, as well as higher MD (p = 0.01) and RD (p = 0.01) values at the level of the thalamo-cortical fibers. Conclusion We confirmed the presence of an alteration of the extrapyramidal system in FD patients, in line with recent evidences suggesting the presence of brain changes as a possible reflection of the subtle motor symptoms present in this condition. Our results suggest that, along with functional changes, microstructural damage of this pathway is also present in FD patients.

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Section: Discussionmentioning

confidence: 96%

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 95%

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Microstructural damage of the cortico-striatal and thalamo-cortical fibers in Fabry disease: a diffusion MRI tractometry study

et al. 2020

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“…94,98,99 A recent study also demonstrated an increase in susceptibility values of the SN and striatum in susceptibility weighted imaging (SWI) sequences, coupled to a reduced volume of the SN only. 99 A presynaptic dopaminergic deficit has been demonstrated in those who underwent a functional dopaminergic imaging, either a DaTscan or a fluorodopa positron emission tomography (PET) scan. 94,97 Treatment Parkinsonian features show a mild to moderate response to treatment with L-dopa.…”

Section: Clinical Presentationmentioning

confidence: 99%

X‐Linked Parkinsonism: Phenotypic and Genetic Heterogeneity

et al. 2021

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A BS TRACT: X-linked parkinsonism encompasses rare heterogeneous disorders mainly inherited as a recessive trait, therefore being more prevalent in males. Recent developments have revealed a complex underlying panorama, including a spectrum of disorders in which parkinsonism is variably associated with additional neurological and non-neurological signs. In particular, a childhoodonset encephalopathy with epilepsy and/or cognitive disability is the most common feature. Their genetic basis is also heterogeneous, with many causative genes and different mutation types ranging from "classical" coding variants to intronic repeat expansions. In this review, we provide an updated overview of the phenotypic and genetic spectrum of the most relevant X-linked parkinsonian syndromes, namely X-linked dystonia-parkinsonism (XDP, Lubag disease), fragile X-associated tremor/ataxia syndrome (FXTAS), beta-propeller protein-associated neurodegeneration (BPAN, NBIA/PARK-WDR45), Fabry disease, Waisman syndrome, methyl CpG-binding protein 2 (MeCP2) spectrum disorder, phosphoglycerate kinase-1 deficiency syndrome (PGK1) and X-linked parkinsonism and spasticity (XPDS). All clinical and radiological features reported in the literature have been reviewed. Epilepsy occasionally represents the symptom of onset, predating parkinsonism even by a few years; action tremor is another common feature along with akinetic-rigid parkinsonism. A focus on the genetic background and its pathophysiological implications is provided. The pathogenesis of these disorders ranges from well-defined metabolic alterations (PGK1) to non-specific lysosomal dysfunctions (XPDS) and vesicular trafficking alterations (Waisman syndrome). However, in other cases it still remains poorly defined. Recognition of the phenotypic and genetic heterogeneity of X-linked parkinsonism has important implications for diagnosis, management, and genetic counseling.

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“…In addition, α-Gal activity was significantly lower in the serum of PD patients compared to parkinsonian syndrome [ 39 ]. Finally, reduced nigral volume (suggesting neurodegeneration in this region) correlating with increased susceptibility of this region was observed in Fabry disease patients [ 40 ].…”

Section: Associations Between Lsds and Pdmentioning

confidence: 99%

Lysosomal Storage Disorders Shed Light on Lysosomal Dysfunction in Parkinson’s Disease

Blumenreich

Barav

Jenkins

et al. 2020

IJMS

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The lysosome is a central player in the cell, acting as a clearing house for macromolecular degradation, but also plays a critical role in a variety of additional metabolic and regulatory processes. The lysosome has recently attracted the attention of neurobiologists and neurologists since a number of neurological diseases involve a lysosomal component. Among these is Parkinson’s disease (PD). While heterozygous and homozygous mutations in GBA1 are the highest genetic risk factor for PD, studies performed over the past decade have suggested that lysosomal loss of function is likely involved in PD pathology, since a significant percent of PD patients have a mutation in one or more genes that cause a lysosomal storage disease (LSD). Although the mechanistic connection between the lysosome and PD remains somewhat enigmatic, significant evidence is accumulating that lysosomal dysfunction plays a central role in PD pathophysiology. Thus, lysosomal dysfunction, resulting from mutations in lysosomal genes, may enhance the accumulation of α-synuclein in the brain, which may result in the earlier development of PD.

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Striatonigral involvement in Fabry Disease: A quantitative and volumetric Magnetic Resonance Imaging study

Cited by 13 publications

References 30 publications

Microstructural damage of the cortico-striatal and thalamo-cortical fibers in Fabry disease: a diffusion MRI tractometry study

Microstructural damage of the cortico-striatal and thalamo-cortical fibers in Fabry disease: a diffusion MRI tractometry study

X‐Linked Parkinsonism: Phenotypic and Genetic Heterogeneity

Lysosomal Storage Disorders Shed Light on Lysosomal Dysfunction in Parkinson’s Disease

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